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Sample records for injury dramatically improves

  1. Dramatic Cataplexy Improvement Following Right Parietal Surgery

    PubMed Central

    Fam, David J.; Shammi, Prathiba; Mainprize, Todd G.; Murray, Brian J.

    2015-01-01

    This is the case of a 34-year-old woman with severe narcolepsy with cataplexy who experienced a dramatic reduction in cataplexy symptoms after resection of a right parietal astrocytoma. The patient underwent detailed neurological exam, neuropsychological testing, polysomnography and multiple sleep latency testing following surgery. Citation: Fam DJ, Shammi P, Mainprize TG, Murray BJ. Dramatic cataplexy improvement following right parietal surgery. J Clin Sleep Med 2015;11(7):829–830. PMID:25902819

  2. Dramatic Improvements to Feature Based Stereo

    NASA Technical Reports Server (NTRS)

    Smelyansky, V. N.; Morris, R. D.; Kuehnel, F. O.; Maluf, D. A.; Cheeseman, P.

    2004-01-01

    The camera registration extracted from feature based stereo is usually considered sufficient to accurately localize the 3D points. However, for natural scenes the feature localization is not as precise as in man-made environments. This results in small camera registration errors. We show that even very small registration errors result in large errors in dense surface reconstruction. We describe a method for registering entire images to the inaccurate surface model. This gives small, but crucially important improvements to the camera parameters. The new registration gives dramatically better dense surface reconstruction.

  3. Dramatically Improve How and Where Academic Content Is Taught

    ERIC Educational Resources Information Center

    Hyslop, Alisha

    2007-01-01

    The fourth recommendation in ACTE's high school reform position statement is to dramatically improve how and where academic content is taught. Even as advanced academic course-taking and high school graduation requirements have increased, student achievement on national benchmarks has remained flat, and college remediation rates continue to…

  4. Dramatic Improvements in Beach Water Quality Following Gull Removal

    EPA Science Inventory

    Gulls are often cited as important contributors of fecal contamination to surface waters, and some recreational beaches have used gull control measures to improve microbial water quality. In this study, gulls were chased from a Lake Michigan beach using specially trained dogs, a...

  5. SAFETY IMPROVES DRAMATICALLY IN FLUOR HANFORD SOIL AND GROUNDWATER REMEDIATION PROJECT

    SciTech Connect

    GERBER MS

    2007-12-05

    This paper describes dramatic improvements in the safety record of the Soil and Groundwater Remediation Project (SGRP) at the Hanford Site in southeast Washington state over the past four years. During a period of enormous growth in project work and scope, contractor Fluor Hanford reduced injuries, accidents, and other safety-related incidents and enhanced a safety culture that earned the SGRP Star Status in the Department of Energy's (DOE's) Voluntary Protection Program (VPP) in 2007. This paper outlines the complex and multi-faceted work of Fluor Hanford's SGRP and details the steps taken by the project's Field Operations and Safety organizations to improve safety. Holding field safety meetings and walkdowns, broadening safety inspections, organizing employee safety councils, intensively flowing down safety requirements to subcontractors, and adopting other methods to achieve remarkable improvement in safety are discussed. The roles of management, labor and subcontractors are detailed. Finally, SGRP's safety improvements are discussed within the context of overall safety enhancements made by Fluor Hanford in the company's 11 years of managing nuclear waste cleanup at the Hanford Site.

  6. Safety Improves Dramatically In Fluor Hanford Soil and Groundwater Remediation Project

    SciTech Connect

    Foster, A.L.; Gerber, M.S.; VonBargen, B.H.

    2008-07-01

    This paper describes dramatic improvements in the safety record of the Soil and Groundwater Remediation Project (SGRP) at the Hanford Site in southeast Washington state over the past four years. During a period of enormous growth in project work and scope, contractor Fluor Hanford reduced injuries, accidents, and other safety-related incidents and enhanced a safety culture that earned the SGRP Star Status in the Department of Energy's (DOE's) Voluntary Protection Program (VPP) in 2007. This paper outlines the complex and multi-faceted work of Fluor Hanford's SGRP and details the steps taken by the project's Field Operations and Safety organizations to improve safety. Holding field safety meetings and walk-downs, broadening safety inspections, organizing employee safety councils, intensively flowing down safety requirements to subcontractors, and adopting other methods to achieve remarkable improvement in safety are discussed. The roles of management, labor and subcontractors are detailed. Finally, SGRP's safety improvements are discussed within the context of overall safety enhancements made by Fluor Hanford in the company's 11 years of managing nuclear waste cleanup at the Hanford Site. (authors)

  7. Publications on Peripheral Nerve Injuries during World War I: A Dramatic Increase in Knowledge.

    PubMed

    Koehler, Peter J

    2016-01-01

    Publications from French (Jules Tinel and Chiriachitza Athanassio-Bénisty), English (James Purves-Stewart, Arthur Henry Evans and Hartley Sidney Carter), German (Otfrid Foerster and Hermann Oppenheim) and American (Charles Harrison Frazier and Byron Stookey) physicians from both sides of the front during World War I (WWI) contributed to a dramatic increase in knowledge about peripheral nerve injuries. Silas Weir Mitchell's original experience with respect to these injuries, and particularly causalgia, during the American Civil War was further expanded in Europe during WWI. Following the translation of one of his books, he was referred to mainly by French physicians. During WWI, several French books were in turn translated into English, which influenced American physicians, as was observed in the case of Byron Stookey. The establishment of neurological centres played an important role in the concentration of experience and knowledge. Several eponyms originated during this period (including the Hoffmann-Tinel sign and the Froment sign). Electrodiagnostic tools were increasingly used. PMID:27035152

  8. DRAMATIC IMPROVEMENTS IN CAUSTIC-SIDE SOLVENT EXTRACTION OF CESIUM THROUGH MORE EFFICIENT STRIPPING

    SciTech Connect

    Delmau, Laetitia Helene; Bazelaire, Eve; Bonnesen, Peter V; Engle, Nancy L; Gorbunova, Maryna; Haverlock, Tamara; Moyer, Bruce A; Ensor, Dale; Meadors, Viola M; Harmon, Ben; Bartsch, Richard A.; Surowiec, Malgorzata A.; Zhou, Hui

    2008-01-01

    Dramatic potential improvements to the chemistry of the Caustic-Side Solvent Extraction (CSSX) process are presented as related to enhancement of cesium stripping. The current process for removing cesium from the alkaline high-level waste (HLW) at the USDOE Savannah River Site employs acidic scrub and strip stages and shows remarkable extraction and selectivity properties for cesium. It was determined that cesium stripping can be greatly improved with caustic or near-neutral stages using sodium hydroxide and boric acid as scrub and strip solutions, respectively. Improvements can also be achieved by appending pH-sensitive functional groups to the calix[4]arene-crown-6 extractant. Addition of a proton-ionizable group to the calixarene frame leads to a dramatic "pH swing" of up to 6 orders of magnitude change in cesium distribution ratio.

  9. Unexpected, dramatic improvement in atrioventricular conduction during pacemaker implantation for apparent complete heart block.

    PubMed

    Dizon, Jose'; Wang, Huijian; Biviano, Angelo; Garan, Hasan

    2007-09-01

    We describe the case of a 29-year-old man with complete heart block after aortic and mitral valve surgery for bacterial endocarditis. Prior to pacemaker implantation, the patient had sinus bradycardia with third degree atrioventricular (AV) block. During testing of the atrial lead, the patient manifested intact AV conduction with a constant PR interval, which was robust up to 120 beats/min. This case represents a dramatic example of unexpected, improved AV conduction, perhaps a result of loss of Phase IV block. PMID:17725759

  10. Dramatic improvements in toughness in poly(lactide-co-glycolide) nanocomposites.

    PubMed

    Xu, Wei; Raychowdhury, Subhendu; Jiang, David D; Retsos, Haris; Giannelis, Emmanuel P

    2008-05-01

    Poly(lactide-co-glycolide) (PLG), a biocompatible and biodegradable polymer, is dramatically toughened by adding small amounts of surface modified clay nanoparticles. The elongation during tensile tests increases from 7% for the pure polymer to 210% for the nanocomposite, accompanied with a modest increase in modulus. In contrast, PLG nanocomposites based on fumed silica treated with hexamethyldisilazane show only modest improvements in toughness. Electron microscopy, X-ray scattering, rheometry, and dielectric relaxation spectroscopy are used to investigate the toughening mechanism. Multiple crazing occurs in the clay nanocomposite after yielding. Small angle X-ray scattering studies show significant orientation of the clay nanoparticles along the tensile stress direction during deformation. The clay nanocomposites show a new, slow relaxation mode, most likely due to interfacial adsorbption of PLG chains on the surface of the clay nanoparticles. The dramatic increase in toughness is attributed to physical crosslinks introduced by the clay nanoparticles, a mechanism absent in the PLG/silica nanocomposites. The physical crosslinks increase the brittle fracture strength of the polymer and, consequently, trigger a toughening mechanism via multiple crazing and shear yielding. PMID:18398925

  11. Emulating a crowded intracellular environment in vitro dramatically improves RT-PCR performance

    SciTech Connect

    Lareu, Ricky R.; Harve, Karthik S.; Raghunath, Michael

    2007-11-09

    The polymerase chain reaction's (PCR) phenomenal success in advancing fields as diverse as Medicine, Agriculture, Conservation, or Paleontology is based on the ability of using isolated prokaryotic thermostable DNA polymerases in vitro to copy DNA irrespective of origin. This process occurs intracellularly and has evolved to function efficiently under crowded conditions, namely in an environment packed with macromolecules. However, current in vitro practice ignores this important biophysical parameter of life. In order to more closely emulate conditions of intracellular biochemistry in vitro we added inert macromolecules into reverse transcription (RT) and PCR. We show dramatic improvements in all parameters of RT-PCR including 8- to 10-fold greater sensitivity, enhanced polymerase processivity, higher specific amplicon yield, greater primer annealing and specificity, and enhanced DNA polymerase thermal stability. The faster and more efficient reaction kinetics was a consequence of the cumulative molecular and thermodynamic effects of the excluded volume effect created by macromolecular crowding.

  12. Dramatic improvement of crystals of large RNAs by cation replacement and dehydration

    PubMed Central

    Zhang, Jinwei; Ferré-D’Amare, Adrian R.

    2014-01-01

    Summary Compared to globular proteins, RNAs with complex three-dimensional folds are characterized by poorly differentiated molecular surfaces dominated by backbone phosphates, sparse tertiary contacts stabilizing global architecture, and conformational flexibility. The resulting generally poor order of crystals of large RNAs and their complexes frequently hampers crystallographic structure determination. We describe and rationalize a post-crystallization treatment strategy that exploits the importance of solvation and counterions for RNA folding. Replacement of Li+ and Mg2+ needed for growth of crystals of a tRNA-riboswitch-protein co-crystal with Sr2+, coupled with dehydration, dramatically improved the resolution limit (8.5 to 3.2 Å) and data quality, enabling structure determination. The soft Sr2+ ion forms numerous stabilizing intermolecular contacts. Comparison of pre- and post-treatment structures reveals how RNA assemblies redistribute as quasi-rigid bodies to yield improved crystal packing. Cation exchange complements previously reported post-crystallization dehydration of protein crystals, and represents a potentially general strategy for improving crystals of large RNAs. PMID:25185828

  13. Dramatic improvement of crystals of large RNAs by cation replacement and dehydration.

    PubMed

    Zhang, Jinwei; Ferré-D'Amaré, Adrian R

    2014-09-01

    Compared to globular proteins, RNAs with complex 3D folds are characterized by poorly differentiated molecular surfaces dominated by backbone phosphates, sparse tertiary contacts stabilizing global architecture, and conformational flexibility. The resulting generally poor order of crystals of large RNAs and their complexes frequently hampers crystallographic structure determination. We describe and rationalize a postcrystallization treatment strategy that exploits the importance of solvation and counterions for RNA folding. Replacement of Li(+) and Mg(2+) needed for growth of crystals of a tRNA-riboswitch-protein complex with Sr(2+), coupled with dehydration, dramatically improved the resolution limit (8.5-3.2 Å) and data quality, enabling structure determination. The soft Sr(2+) ion forms numerous stabilizing intermolecular contacts. Comparison of pre- and posttreatment structures reveals how RNA assemblies redistribute as quasi-rigid bodies to yield improved crystal packing. Cation exchange complements previously reported postcrystallization dehydration of protein crystals and represents a potentially general strategy for improving crystals of large RNAs. PMID:25185828

  14. Use of microsecond current prepulse for dramatic improvements of wire array Z-pinch implosion

    NASA Astrophysics Data System (ADS)

    Calamy, H.; Lassalle, F.; Loyen, A.; Zucchini, F.; Chittenden, J. P.; Hamann, F.; Maury, P.; Georges, A.; Bedoch, J. P.; Morell, A.

    2008-01-01

    The Sphinx machine [F. Lassalle et al., "Status on the SPHINX machine based on the 1microsecond LTD technology"] based on microsecond linear transformer driver (LTD) technology is used to implode an aluminium wire array with an outer diameter up to 140mm and maximum current from 3.5to5MA. 700to800ns implosion Z-pinch experiments are performed on this driver essentially with aluminium. Best results obtained before the improvement described in this paper were 1-3TW radial total power, 100-300kJ total yield, and 20-30kJ energy above 1keV. An auxiliary generator was added to the Sphinx machine in order to allow a multi microsecond current to be injected through the wire array load before the start of the main current. Amplitude and duration of this current prepulse are adjustable, with maxima ˜10kA and 50μs. This prepulse dramatically changes the ablation phase leading to an improvement of the axial homogeneity of both the implosion and the final radiating column. Total power was multiplied by a factor of 6, total yield by a factor of 2.5 with a reproducible behavior. This paper presents experimental results, magnetohydrodynamic simulations, and analysis of the effect of such a long current prepulse.

  15. Use of microsecond current prepulse for dramatic improvements of wire array Z-pinch implosion

    SciTech Connect

    Calamy, H.; Lassalle, F.; Loyen, A.; Zucchini, F.; Chittenden, J. P.; Hamann, F.; Maury, P.; Georges, A.; Bedoch, J. P.; Morell, A.

    2008-01-15

    The Sphinx machine [F. Lassalle et al., 'Status on the SPHINX machine based on the 1microsecond LTD technology'] based on microsecond linear transformer driver (LTD) technology is used to implode an aluminium wire array with an outer diameter up to 140 mm and maximum current from 3.5 to 5 MA. 700 to 800 ns implosion Z-pinch experiments are performed on this driver essentially with aluminium. Best results obtained before the improvement described in this paper were 1-3 TW radial total power, 100-300 kJ total yield, and 20-30 kJ energy above 1 keV. An auxiliary generator was added to the Sphinx machine in order to allow a multi microsecond current to be injected through the wire array load before the start of the main current. Amplitude and duration of this current prepulse are adjustable, with maxima {approx}10 kA and 50 {mu}s. This prepulse dramatically changes the ablation phase leading to an improvement of the axial homogeneity of both the implosion and the final radiating column. Total power was multiplied by a factor of 6, total yield by a factor of 2.5 with a reproducible behavior. This paper presents experimental results, magnetohydrodynamic simulations, and analysis of the effect of such a long current prepulse.

  16. Dramatic improvement of anti-SS-A/Ro-associated interstitial lung disease after immunosuppressive treatment.

    PubMed

    Paola, Caramaschi; Giuliana, Festi; Giovanni, Orsolini; Cristian, Caimmi; Domenico, Biasi

    2016-07-01

    The aim of the study was to report three patients affected by interstitial lung disease associated with positive anti-SS-A/Ro autoantibody who showed a dramatic improvement after immunosuppressive treatment. Medical charts were reviewed to obtain clinical data, laboratory parameters, lung function tests, high-resolution computed tomography results and response to immunosuppressive treatment. The three patients showed a clinical picture of a lung-dominant connective tissue disease characterized by a sudden onset with dyspnea, cough and subtle extrathoracic features together with positive anti-SS-A/Ro antibody and weak titer antinuclear antibodies. All three patients responded favorably to immunosuppressive therapy: Two cases were treated with a combination of corticosteroid and cyclophosphamide followed by mycophenolate mofetil; in the third patient, clinical benefit was obtained after rituximab was added to corticosteroid and immunosuppressant drug. In spite of an abrupt onset with significant lung function impairment, all three patients had a favorable clinical response to immunosuppressive therapy. This report may be useful in making therapeutic decisions in case of interstitial lung disease associated with anti-SS-A antibody. PMID:27021338

  17. Correcting Inadequate Model Snow Process Descriptions Dramatically Improves Mountain Hydrology Simulations

    NASA Astrophysics Data System (ADS)

    Pomeroy, J. W.; Fang, X.

    2014-12-01

    The vast effort in hydrology devoted to parameter calibration as a means to improve model performance assumes that the models concerned are not fundamentally wrong. By focussing on finding optimal parameter sets and ascribing poor model performance to parameter or data uncertainty, these efforts may fail to consider the need to improve models with more intelligent descriptions of hydrological processes. To test this hypothesis, a flexible physically based hydrological model including a full suite of snow hydrology processes as well as warm season, hillslope and groundwater hydrology was applied to Marmot Creek Research Basin, Canadian Rocky Mountains where excellent driving meteorology and basin biophysical descriptions exist. Model parameters were set from values found in the basin or from similar environments; no parameters were calibrated. The model was tested against snow surveys and streamflow observations. The model used algorithms that describe snow redistribution, sublimation and forest canopy effects on snowmelt and evaporative processes that are rarely implemented in hydrological models. To investigate the contribution of these processes to model predictive capability, the model was "falsified" by deleting parameterisations for forest canopy snow mass and energy, blowing snow, intercepted rain evaporation, and sublimation. Model falsification by ignoring forest canopy processes contributed to a large increase in SWE errors for forested portions of the research basin with RMSE increasing from 19 to 55 mm and mean bias (MB) increasing from 0.004 to 0.62. In the alpine tundra portion, removing blowing processes resulted in an increase in model SWE MB from 0.04 to 2.55 on north-facing slopes and -0.006 to -0.48 on south-facing slopes. Eliminating these algorithms degraded streamflow prediction with the Nash Sutcliffe efficiency dropping from 0.58 to 0.22 and MB increasing from 0.01 to 0.09. These results show dramatic model improvements by including snow

  18. [A case of progressive supranuclear palsy dramatically improved with L-threo-3,4-dihydroxyphenylserine].

    PubMed

    Maruyama, T; Tamaru, F; Yamagisawa, N

    1992-06-01

    We report a 67-year-old female with progressive supranuclear palsy (PSP) who dramatically improved when given L-threo-3,4-dihydroxyphenylserine (L-DOPS). This patient developed dysarthria, lack of facial expression, and slowness at age 64. She was admitted to a local hospital, diagnosed as having parkinsonism and treated with antiparkinsonian drugs. Despite this treatment, she had difficulty in turning over in bed and standing up from a seat, and began to fall backward at age 65. One year later, she had trouble in walking due to frequent falls and became bedridden. The patient was admitted to our hospital in July 1991 under treatment with 20 mg/200 mg of carbidopa/L-dopa and 4 mg of trihexyphenydyl hydrochloride per day. Neurological examination revealed masked face, pseudobulbar palsy, and dystonic rigidity of the neck and upper trunk. Eye movements were normal except for impaired vertical saccades and convergence inability. Deep tendon reflexes were generally brisk and the plantar responses were flexor bilaterally. Tests of pulsion showed that her postural reflex was markedly disturbed, especially in retropulsion. Her gait showed severe unsteadiness. Neuropsychological tests showed intellectual impairment, frontal lobe dysfunction, and memory disturbance. Computed tomography showed an atrophic midbrain with prominent enlargement of ambient and quadrigeminal plate cisterns. Single photon emission computed tomography (SPECT) using 123-I-isopropyl-iodoamphetamine demonstrated marked frontal hypoperfusion. L-DOPS was administered at a dose of 100 mg per day and gradually increased up to 600 mg per day over a period of five weeks, while carbidopa/L-dopa and trihexyphenidyl hydrochloride were continued as on admission.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1424339

  19. Sustainable improvements in injury surveillance in Ghana

    PubMed Central

    Adofo, Koranteng; Donkor, Peter; Afukaar, Francis; Boateng, Kofi Adomako; Mock, Charles

    2015-01-01

    Introduction The mortuary is an important foundation for injury surveillance. However, mortuary data are incomplete in many developing countries. Methods The KATH mortuary handles most injury deaths for Kumasi, Ghana. During 1994–5, many cases in KATH’s mortuary logbooks had missing information deaths. A low-cost pilot program was adopted to improve recording of injury deaths. During 1996–9, 633 deaths/year were recorded. Results Project sustainability assessment in 2006 showed that reporting was high, with 773 cases per year. Data quality was standard with similar percents of missing values for key variables compared with the pilot period. Supplemental data constituting 20% was obtained from the ICU, for which data recording in the mortuary was incomplete. Conclusion Low-cost improvements can lead to improved mortuary reporting of injury deaths. Collation of data from multiple sources remains a problem at KATH. Improved organization and training could remedy the situation. PMID:20467961

  20. Sustainable improvements in injury surveillance in Ghana.

    PubMed

    Adofo, Koranteng; Donkor, Peter; Boateng, Kofi A; Afukaar, Francis; Mock, Charles

    2010-06-01

    The mortuary is an important foundation for injury surveillance. However, mortuary data are incomplete in many developing countries. The Komfo Anokye Teaching Hospital (KATH) mortuary handles most injury deaths for Kumasi, Ghana. During 1994-1995, many cases in KATH's mortuary logbooks had missing information deaths. A low-cost pilot programme was adopted to improve recording of injury deaths. During 1996-1999, 633 deaths per year were recorded. Project sustainability assessment in 2006 showed that reporting was high, with 773 cases per year. Data quality was standard with similar per cents of missing values for key variables compared with the pilot period. Supplemental data constituting 20% was obtained from the intensive care unit, for which data recording in the mortuary was incomplete. Low-cost improvements can lead to improved mortuary reporting of injury deaths. Collation of data from multiple sources remains a problem at KATH. Improved organisation and training could remedy the situation. PMID:20467961

  1. Dramatic Science

    ERIC Educational Resources Information Center

    McGregor, Debbie; Precious, Wendy

    2010-01-01

    The setting: the science classroom. The characters: you and your students. The scene: Your students acting out scientific discoveries, modeling a frog's life cycle, mimicking the transition from liquid to solid. This is "dramatic science", a teaching approach that uses acting techniques to explore and develop young children's ideas about science.…

  2. Paclitaxel improves outcome from traumatic brain injury

    PubMed Central

    Cross, Donna J.; Garwin, Gregory G.; Cline, Marcella M.; Richards, Todd L.; Yarnykh, Vasily; Mourad, Pierre D.; Ho, Rodney J.Y.; Minoshima, Satoshi

    2016-01-01

    Pharmacologic interventions for traumatic brain injury (TBI) hold promise to improve outcome. The purpose of this study was to determine if the microtubule stabilizing therapeutic paclitaxel used for more than 20 years in chemotherapy would improve outcome after TBI. We assessed neurological outcome in mice that received direct application of paclitaxel to brain injury from controlled cortical impact (CCI). Magnetic resonance imaging was used to assess injury-related morphological changes. Catwalk Gait analysis showed significant improvement in the paclitaxel group on a variety of parameters compared to the saline group. MRI analysis revealed that paclitaxel treatment resulted in significantly reduced edema volume at site-of-injury (11.92 ± 3.0 and 8.86 ± 2.2 mm3 for saline vs. paclitaxel respectively, as determined by T2-weighted analysis; p ≤ 0.05), and significantly increased myelin tissue preservation (9.45 ± 0.4 vs. 8.95 ± 0.3, p ≤ 0.05). Our findings indicate that paclitaxel treatment resulted in improvement of neurological outcome and MR imaging biomarkers of injury. These results could have a significant impact on therapeutic developments to treat traumatic brain injury. PMID:26086366

  3. Dramatic improvement of severe cryptococcosis-induced immune reconstitution syndrome with adalimumab in a renal transplant recipient.

    PubMed

    Scemla, A; Gerber, S; Duquesne, A; Parize, P; Martinez, F; Anglicheau, D; Snanoudj, R; Zuber, M; Bougnoux, M-E; Legendre, C; Lortholary, O

    2015-02-01

    In solid organ transplant recipients, immune reconstitution inflammatory syndrome (IRIS) is a rare complication of cryptococcosis, which may require steroids in its most severe forms. Here, we report the case of a renal transplant recipient who developed severe cryptococcal meningitis-associated IRIS 1 week after immunosuppression reduction. High-dose steroids failed to improve the disease. Finally, a recombinant human monoclonal tumor necrosis factor-α (TNF-α) antagonist, adalimumab, was prescribed, and the patient rapidly experienced dramatic neurological improvement. No IRIS relapse occurred within 14 months following adalimumab discontinuation. PMID:25611999

  4. Dramatic Teaching for Dramatic Learning

    ERIC Educational Resources Information Center

    Graves, Julie

    2010-01-01

    Ressler's "Dramatic Changes" is a powerful guide for anyone brave enough to create a space for young people to discuss sexual orientation and gender identity. Her accessible style and tangible suggestions describe a creative and educationally sound approach to supporting youth in thoughtfully wrestling with one of the most controversial social…

  5. [Severe apathy following head injury: improvement with Selegiline treatment].

    PubMed

    Moutaouakil, F; El Otmani, H; Fadel, H; Slassi, I

    2009-12-01

    Apathy is defined as reduced goal-directed behavior due to lack of motivation. Traumatic brain injury is a frequent cause. Drugs activating the dopaminergic system provide variable benefit. A 30-year-old patient was the victim of a severe head injury with frontal bruise at the age of 15. At the request of his family, he consulted for a 7-year history that included a lack of initiative and the inability to generate behavior spontaneously, contrasting with the ability to execute behaviors on command. He also presented indifference, major emotional disruption without sadness, pessimism, and other depressive signs. The examination found a severe apathetic syndrome confirmed by specific scales with a mild impairment of executive functions and without depressive syndrome. Encephalic MRI showed atrophy of the whole prefrontal cerebral cortex. The patient was treated with bromocriptine, which he did not tolerate, then with Selegiline at 15 mg per day, which dramatically improved his symptoms. Apathy occurs frequently after traumatic brain injury, in 23-71% of patients according to the authors. The pathophysiology of apathy has been described in anatomical terms as related to disruption of frontal-subcortical pathways. The biochemical hypothesis postulates a disruption in dopaminergic activity. The use of dopaminergic agents usually improves cases similar to our patient. Apathy is frequent following head injury, warranting a search for systematic causes. Since it increases dopaminergic activity, Selegiline is well worth trying in these patients. PMID:19084243

  6. Nanocellulose-based Translucent Diffuser for Optoelectronic Device Applications with Dramatic Improvement of Light Coupling.

    PubMed

    Wu, Wei; Tassi, Nancy G; Zhu, Hongli; Fang, Zhiqiang; Hu, Liangbing

    2015-12-01

    Nanocellulose is a biogenerated and biorenewable organic material. Using a process based on 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)/NaClO/NaBr system, a highly translucent and light-diffusive film consisting of many layers of nanocellulose fibers and wood pulp microfibers was made. The film demonstrates a combination of large optical transmittance of ∼90% and tunable diffuse transmission of up to ∼78% across the visible and near-infrared spectra. The detailed characterizations of the film indicate the combination of high optical transmittance and haze is due to the film's large packing density and microstructured surface. The superior optical properties make the film a translucent light diffuser and applicable for improving the efficiencies of optoelectronic devices such as thin-film silicon solar cells and organic light-emitting devices. PMID:26572592

  7. Dramatic enhancement of genome editing by CRISPR/Cas9 through improved guide RNA design.

    PubMed

    Farboud, Behnom; Meyer, Barbara J

    2015-04-01

    Success with genome editing by the RNA-programmed nuclease Cas9 has been limited by the inability to predict effective guide RNAs and DNA target sites. Not all guide RNAs have been successful, and even those that were, varied widely in their efficacy. Here we describe and validate a strategy for Caenorhabditis elegans that reliably achieved a high frequency of genome editing for all targets tested in vivo. The key innovation was to design guide RNAs with a GG motif at the 3' end of their target-specific sequences. All guides designed using this simple principle induced a high frequency of targeted mutagenesis via nonhomologous end joining (NHEJ) and a high frequency of precise DNA integration from exogenous DNA templates via homology-directed repair (HDR). Related guide RNAs having the GG motif shifted by only three nucleotides showed severely reduced or no genome editing. We also combined the 3' GG guide improvement with a co-CRISPR/co-conversion approach. For this co-conversion scheme, animals were only screened for genome editing at designated targets if they exhibited a dominant phenotype caused by Cas9-dependent editing of an unrelated target. Combining the two strategies further enhanced the ease of mutant recovery, thereby providing a powerful means to obtain desired genetic changes in an otherwise unaltered genome. PMID:25695951

  8. Dramatic Enhancement of Genome Editing by CRISPR/Cas9 Through Improved Guide RNA Design

    PubMed Central

    Farboud, Behnom; Meyer, Barbara J.

    2015-01-01

    Success with genome editing by the RNA-programmed nuclease Cas9 has been limited by the inability to predict effective guide RNAs and DNA target sites. Not all guide RNAs have been successful, and even those that were, varied widely in their efficacy. Here we describe and validate a strategy for Caenorhabditis elegans that reliably achieved a high frequency of genome editing for all targets tested in vivo. The key innovation was to design guide RNAs with a GG motif at the 3′ end of their target-specific sequences. All guides designed using this simple principle induced a high frequency of targeted mutagenesis via nonhomologous end joining (NHEJ) and a high frequency of precise DNA integration from exogenous DNA templates via homology-directed repair (HDR). Related guide RNAs having the GG motif shifted by only three nucleotides showed severely reduced or no genome editing. We also combined the 3′ GG guide improvement with a co-CRISPR/co-conversion approach. For this co-conversion scheme, animals were only screened for genome editing at designated targets if they exhibited a dominant phenotype caused by Cas9-dependent editing of an unrelated target. Combining the two strategies further enhanced the ease of mutant recovery, thereby providing a powerful means to obtain desired genetic changes in an otherwise unaltered genome. PMID:25695951

  9. Dramatic Improvement of Crystal Quality for Low-temperature-grown Rabbit Muscle Aldolase

    SciTech Connect

    Park, H.; Rangarajan, E; Sygusch, J; Izard, T

    2010-01-01

    Rabbit muscle aldolase (RMA) was crystallized in complex with the low-complexity domain (LC4) of sorting nexin 9. Monoclinic crystals were obtained at room temperature that displayed large mosaicity and poor X-ray diffraction. However, orthorhombic RMA-LC4 crystals grown at 277 K under similar conditions exhibited low mosaicity, allowing data collection to 2.2 {angstrom} Bragg spacing and structure determination. It was concluded that the improvement of crystal quality as indicated by the higher resolution of the new RMA-LC4 complex crystals was a consequence of the introduction of new lattice contacts at lower temperature. The lattice contacts corresponded to an increased number of interactions between high-entropy side chains that mitigate the lattice strain incurred upon cryocooling and accompanying mosaic spread increases. The thermodynamically unfavorable immobilization of high-entropy side chains used in lattice formation was compensated by an entropic increase in the bulk-solvent content owing to the greater solvent content of the crystal lattice.

  10. Extended reach drilling advancements dramatically improve performance on Bass Strait wells

    SciTech Connect

    Santostefano, V.; Krepp, A.N.

    1994-12-31

    Esso Australia Ltd. (EAL) has been drilling deviated wells in Bass Strait since 1968. Recent technological developments have been employed on the Mackerel Infill Drilling Project, that have significantly improved EAL`s ability to drill Long Reach (LR)/Extended Reach (ER) wells more economically and consistently. The more notable achievements have been: advancements in hole condition reporting, utilizing torque and drag monitoring; the successful use of non-rotating drillpipe rubbers to reduce surface torque to acceptable levels; deeper casing setting depths, to minimize torque and drag, and to reduce time-dependent hole problems; the use of inhibitive/encapsulating mud systems for control of reactive clays/shales; and use of wellbore stability modeling. These advancements have helped EAL to drill 50% greater meterage than was expected in 1993, at 16% lower cost per meter. This paper chronicles the engineering decisions behind these advancements, their applications in the field, the success/failure story on Mackerel to date, and how these developments have been incorporated in EAL`s future well planning.

  11. Thaliporphine derivative improves acute lung injury after traumatic brain injury.

    PubMed

    Chen, Gunng-Shinng; Huang, Kuo-Feng; Huang, Chien-Chu; Wang, Jia-Yi

    2015-01-01

    Acute lung injury (ALI) occurs frequently in patients with severe traumatic brain injury (TBI) and is associated with a poor clinical outcome. Aquaporins (AQPs), particularly AQP1 and AQP4, maintain water balances between the epithelial and microvascular domains of the lung. Since pulmonary edema (PE) usually occurs in the TBI-induced ALI patients, we investigated the effects of a thaliporphine derivative, TM-1, on the expression of AQPs and histological outcomes in the lung following TBI in rats. TM-1 administered (10 mg/kg, intraperitoneal injection) at 3 or 4 h after TBI significantly reduced the elevated mRNA expression and protein levels of AQP1 and AQP4 and diminished the wet/dry weight ratio, which reflects PE, in the lung at 8 and 24 h after TBI. Postinjury TM-1 administration also improved histopathological changes at 8 and 24 h after TBI. PE was accompanied with tissue pathological changes because a positive correlation between the lung injury score and the wet/dry weight ratio in the same animal was observed. Postinjury administration of TM-1 improved ALI and reduced PE at 8 and 24 h following TBI. The pulmonary-protective effect of TM-1 may be attributed to, at least in part, downregulation of AQP1 and AQP4 expression after TBI. PMID:25705683

  12. [A case of Wernicke-Korsakoff syndrome with dramatic improvement in consciousness immediately after intravenous infusion of thiamine].

    PubMed

    Kikuchi, A; Chida, K; Misu, T; Okita, N; Nomura, H; Konno, H; Takase, S; Takeda, A; Itoyama, Y

    2000-01-01

    A 68-year-old man was hospitalized on March 4, 1998 for disturbances in consciousness. In 1995, he had received proximal subtotal gastrectomy and reconstructive surgery of the jejunal interposition for gastric cancer. Thereafter he had been taking enough food without the habit of taking liquor. In October 1997, his short term memory was becoming gradually worse. On February 12, 1998, he suffered from numbness in the feet, and then dysphagia, unsteady gait, and diplopia developed gradually. On February 26, brain MRI showed no abnormalities. On March 3, he had a fever of 38.5 degrees C and his consciousness became unclear. Neurological examination revealed semi-coma, total ophthalmoplegia, and absence of doll's eye movement. Deep tendon reflexes were absent. The serum thiamine level was 9 ng/ml (normal range: 20-50). Brain MRI demonstrated symmetrical high intensity lesions in the periaqueductal area of the midbrain, dorsomedial nuclei of bilateral thalami, and vestibular nuclei. About 30 seconds after intravenous infusion of thiamine, his consciousness improved dramatically, but returned to semi-coma after about two minutes. Wernicke-Korsakoff syndrome usually occurs acutely. In the present case, however, the disease showed slow onset, chronic progression, and then rapid worsening after fever. Reconstructive surgery of the jejunal interposition might have caused the slow onset of Wernicke-Korsakoff syndrome, and fever might have facilitated the rapid progression of the disease. An immediate high concentration of thiamine modifies the kinetics of acetylcholine receptor ion channels, thereby maintaining wakefulness, and the level of consciousness may change dramatically. PMID:10689693

  13. A Rural School/Community: A Case Study of a Dramatic Turnaround & Its Implications for School Improvement.

    ERIC Educational Resources Information Center

    Carlson, Robert V.

    This paper presents a case study of a rural community exhibiting a dramatic turnaround in community support for a new school bond issue. Demographic change was partly responsible for the change in community attitudes, with two waves of immigration altering the long-term conservative orientation of this community. After a series of failed…

  14. Spinal Cord Injury

    MedlinePlus

    ... Dramatically Improves Function After Spinal Cord Injury in Rats May 2004 press release on an experimental treatment ... NINDS). Signaling Molecule Improves Nerve Cell Regeneration in Rats August 2002 news summary on a signaling molecule ...

  15. Microstructured fiber@HZSM-5 core-shell catalysts with dramatic selectivity and stability improvement for the methanol-to-propylene process.

    PubMed

    Wang, Xiangyu; Wen, Ming; Wang, Chunzheng; Ding, Jia; Sun, Ying; Liu, Ye; Lu, Yong

    2014-06-18

    We report a macroscopic stainless-steel-fiber@HZSM-5 core-shell catalyst by direct growth of 27 wt% HZSM-5 on a 3D microfibrous structure using 20 μm SS fibers, demonstrating dramatic selectivity and stability improvement in the MTP process. The unprecedented performance is due to the promotion of the olefin methylation/cracking cycle in methanol-to-hydrocarbon catalysis. PMID:24798420

  16. Reducing synuclein accumulation improves neuronal survival after spinal cord injury.

    PubMed

    Fogerson, Stephanie M; van Brummen, Alexandra J; Busch, David J; Allen, Scott R; Roychaudhuri, Robin; Banks, Susan M L; Klärner, Frank-Gerrit; Schrader, Thomas; Bitan, Gal; Morgan, Jennifer R

    2016-04-01

    Spinal cord injury causes neuronal death, limiting subsequent regeneration and recovery. Thus, there is a need to develop strategies for improving neuronal survival after injury. Relative to our understanding of axon regeneration, comparatively little is known about the mechanisms that promote the survival of damaged neurons. To address this, we took advantage of lamprey giant reticulospinal neurons whose large size permits detailed examination of post-injury molecular responses at the level of individual, identified cells. We report here that spinal cord injury caused a select subset of giant reticulospinal neurons to accumulate synuclein, a synaptic vesicle-associated protein best known for its atypical aggregation and causal role in neurodegeneration in Parkinson's and other diseases. Post-injury synuclein accumulation took the form of punctate aggregates throughout the somata and occurred selectively in dying neurons, but not in those that survived. In contrast, another synaptic vesicle protein, synaptotagmin, did not accumulate in response to injury. We further show that the post-injury synuclein accumulation was greatly attenuated after single dose application of either the "molecular tweezer" inhibitor, CLR01, or a translation-blocking synuclein morpholino. Consequently, reduction of synuclein accumulation not only improved neuronal survival, but also increased the number of axons in the spinal cord proximal and distal to the lesion. This study is the first to reveal that reducing synuclein accumulation is a novel strategy for improving neuronal survival after spinal cord injury. PMID:26854933

  17. Mechanistic Studies Lead to Dramatically Improved Reaction Conditions for the Cu-Catalyzed Asymmetric Hydroamination of Olefins.

    PubMed

    Bandar, Jeffrey S; Pirnot, Michael T; Buchwald, Stephen L

    2015-11-25

    Enantioselective copper(I) hydride (CuH)-catalyzed hydroamination has undergone significant development over the past several years. To gain a general understanding of the factors governing these reactions, kinetic and spectroscopic studies were performed on the CuH-catalyzed hydroamination of styrene. Reaction profile analysis, rate order assessment, and Hammett studies indicate that the turnover-limiting step is regeneration of the CuH catalyst by reaction with a silane, with a phosphine-ligated copper(I) benzoate as the catalyst resting state. Spectroscopic, electrospray ionization mass spectrometry, and nonlinear effect studies are consistent with a monomeric active catalyst. With this insight, targeted reagent optimization led to the development of an optimized protocol with an operationally simple setup (ligated copper(II) precatalyst, open to air) and short reaction times (<30 min). This improved protocol is amenable to a diverse range of alkene and alkyne substrate classes. PMID:26522837

  18. The contribution of research results to dramatic improvements in post-abortion care: Centre Hospitalier de Libreville, Gabon.

    PubMed

    Mayi-Tsonga, Sosthène; Assoumou, Pamphile; Olé, Boniface Sima; Ntamack, Jacques Bang; Meyé, Jean François; Souza, Maria Helena; Faúndes, Anibal

    2012-12-01

    In 2009, we published an article in RHM showing a large delay in provision of emergency obstetric care to women who died from unsafe abortion complications at the Centre Hospitalier de Libreville. The paper raised awareness among hospital and government authorities of a serious delay in timely treatment, and they supported the recommendation of the hospital's Maternal Mortality Committee to greatly reduce the delay and also improve the care of women with abortion complications. Training in manual vacuum aspiration (MVA) for uterine evacuation was introduced, for use by midwives as well as obstetrician-gynaecologists, with local anaesthesia. The mean delay in providing care to women with abortion complications in the 2008 findings was compared to data from the five months from 1 November 2011 through 31 March 2012. In 2008, all incomplete abortions were treated by physicians with dilatation & evacuation (D&C) or electric vacuum aspiration (EVA) with general anaesthesia. In 2011-12, two-thirds of women were treated with manual vacuum aspiration with local anaesthesia instead, one half of them by midwives. The mean delay between presentation and treatment was 18.0 hours in 2008 and 1.8 hours in 2011-12. The mean delay did not differ between women treated with MVA or D&C/EVA, nor if treated by midwives or physicians. PMID:23245404

  19. The PPAR gamma agonist Pioglitazone improves anatomical and locomotor recovery after rodent spinal cord injury

    PubMed Central

    McTigue, Dana M.; Tripathi, Richa; Wei, Ping; Lash, A. Todd

    2007-01-01

    Traumatic spinal cord injury (SCI) is accompanied by a dramatic inflammatory response, which escalates over the first week post-injury and is thought to contribute to secondary pathology after SCI. Peroxisome proliferator-activated receptors (PPAR) are widely expressed nuclear receptors whose activation has led to diminished pro-inflammatory cascades in several CNS disorders. Therefore, we examined the efficacy of the PPARγ agonist Pioglitazone in a rodent SCI model. Rats received a moderate mid-thoracic contusion and were randomly placed into groups receiving vehicle, low dose or high dose Pioglitazone. Drug or vehicle was injected i.p. at 15 min post-injury and then every 12h for the first 7d post-injury. Locomotor function was followed for 5 weeks using the BBB scale. BBB scores were greater in treated animals at 7d post-injury and significant improvements in BBB subscores were noted, including better toe clearance, earlier stepping and more parallel paw position. Stereological measurements throughout the lesion revealed a significant increase in rostral spared white matter in both Pioglitazone treatment groups. Spinal cords from the high dose group also had significantly more gray matter sparing and motor neurons rostral and caudal to epicenter. Thus, our results reveal that clinical treatment with Pioglitazone, an FDA-approved drug used currently for diabetes, may be a feasible and promising strategy for promoting anatomical and functional repair after SCI. PMID:17433295

  20. Improving hand hygiene after neurological injury.

    PubMed

    Duke, Lynsay; Gibbison, Lucy; McMahon, Victoria

    Caring for hands tightened by spasticity after stroke, brain injury or other neurological conditions can be challenging for care staff. Opening and cleaning the hand, managing pressure areas, cutting nails and reducing pain becomes more complex if muscles are tight and short. Hand hygiene is key for staff but literature on patients' hand and nail care is lacking, so specialist education and care planning may be needed to help staff ensure these activities are done well. This article outlines the importance of maintaining patients' hand hygiene, explores the barriers to providing effective care and discusses how they might be overcome. PMID:26665632

  1. A case of shoshin beriberi presenting as cardiogenic shock with diffuse ST-segment elevation, which dramatically improved after a single dose of thiamine.

    PubMed

    Kim, Jihye; Park, Sooyun; Kim, Jun-Hyun; Kim, Sun Woong; Kang, Won Chan; Kim, Sun Jong

    2014-01-01

    Shoshin beriberi is a fulminant form of cardiac beriberi caused by thiamine deficiency. We report on a case of an 87-year-old man with shoshin beriberi presenting as cardiogenic shock with diffuse ST-segment elevation, which dramatically improved after thiamine administration. Because of the rarity of the occurrence, lack of diagnostic test and atypical presentation, diagnosing shoshin beriberi is challenging and requires a high index of clinical suspicion. Shoshin beriberi leads to rapid haemodynamic collapse and death. Therefore, clinicians should consider shoshin beriberi (or cardiac beriberi) as one of the differential diagnoses in patients with heart failure or cardiogenic shock. PMID:25625639

  2. Dramatic improvement in decompensated right heart failure due to severe tricuspid regurgitation following ligation of arteriovenous fistula in a renal transplant recipient.

    PubMed

    Rao, Nitesh; Worthley, Matthew; Disney, Patrick; Faull, Randall

    2014-03-01

    Arteriovenous (AV) fistulas with high blood flow rate are necessary for adequate hemodialysis, but they can also cause significant hemodynamic changes, including raised cardiac output, left ventricular hypertrophy and occasionally overt cardiac failure (Basile et al., Nephrol Dial Transplant, 23, 2008, 282; Unger et al., Am J Transplant, 4, 2004, 2038). We now report a case of rapid and dramatic improvement in symptomatic right heart failure due to severe tricuspid regurgitation following ligation of an arteriovenous fistula. Cardiac magnetic resonance imaging (MRI) performed before and after the ligation of fistula showed striking improvement in both the tricuspid regurgitation and right ventricular dimensions, with minimal impact on left ventricular mass, size, and function. PMID:24118598

  3. Creative Dramatics. Beginnings Workshop.

    ERIC Educational Resources Information Center

    Gabriel, Julia; Sidlovskaya, Olga; Stotter, Ruth; Haugen, Kirsten; Leithold, Naomi

    2000-01-01

    Presents five articles on using creative dramatics in early childhood education: (1) "Drama: A Rehearsal for Life" (Julia Gabriel); (2) "Fairy Tales Enhance Imagination and Creative Thinking" (Olga Sidlovskaya); (3) "Starting with a Story" (Ruth Stotter); (4) "Using Creative Dramatics to Include All Children" (Kirsten Haugen); and (5) "Helping…

  4. Creative Dramatics Handbook.

    ERIC Educational Resources Information Center

    Philadelphia School District, PA. Office of Early Childhood Programs.

    This handbook on creative dramatics at the elementary school level is primarily intended to assist the teacher who already has some training in creative dramatics. The handbook contains sections on (1) the philosophy and objectives of the program, including a discussion of an affective curriculum; (2) definitions of key concepts, including general…

  5. Novel diarylpyrimidines and diaryltriazines as potent HIV-1 NNRTIs with dramatically improved solubility: a patent evaluation of US20140378443A1.

    PubMed

    Huang, Boshi; Kang, Dongwei; Yang, Jiapei; Zhan, Peng; Liu, Xinyong

    2016-02-01

    Diarylpyrimidine and diaryltriazine derivatives, two representative structurally related classes of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with robust potencies against wild-type and several mutant strains of HIV-1, have attracted more and more attention in the last decade. However, they have been suffering from poor aqueous solubility. A series of novel diarylpyrimidines and diaryltriazines with solubilizing substituents attached to the central rings were reported as potent NNRTIs in the patent US20140378443A1. Some compounds exhibited potencies against wild-type HIV-1 which were comparable or even superior to those of dapivirine, etravirine and rilpivirine. In addition, dramatically enhanced solubilities were observed for these new compounds. Moreover, some structure optimization strategies for improving aqueous solubility are detailed in this review, providing new insights into development of next-generation NNRTIs endowed with favorable solubility. We anticipate that application of these strategies will ultimately lead to discovery of new anti-HIV drug candidates. PMID:26559996

  6. Hyperbaric oxygen therapy improves local microenvironment after spinal cord injury

    PubMed Central

    Wang, Yang; Zhang, Shuquan; Luo, Min; Li, Yajun

    2014-01-01

    Clinical studies have shown that hyperbaric oxygen therapy improves motor function in patients with spinal cord injury. In the present study, we explored the mechanisms associated with the recovery of neurological function after hyperbaric oxygen therapy in a rat model of spinal cord injury. We established an acute spinal cord injury model using a modification of the free-falling object method, and treated the animals with oxygen at 0.2 MPa for 45 minutes, 4 hours after injury. The treatment was administered four times per day, for 3 days. Compared with model rats that did not receive the treatment, rats exposed to hyperbaric oxygen had fewer apoptotic cells in spinal cord tissue, lower expression levels of aquaporin 4/9 mRNA and protein, and more NF-200 positive nerve fibers. Furthermore, they had smaller spinal cord cavities, rapid recovery of somatosensory and motor evoked potentials, and notably better recovery of hindlimb motor function than model rats. Our findings indicate that hyperbaric oxygen therapy reduces apoptosis, downregulates aquaporin 4/9 mRNA and protein expression in injured spinal cord tissue, improves the local microenvironment for nerve regeneration, and protects and repairs the spinal cord after injury. PMID:25657740

  7. CD36 deletion improves recovery from spinal cord injury

    PubMed Central

    Myers, Scott A.; Andres, Kariena R.; Hagg, Theo; Whittemore, Scott R.

    2014-01-01

    CD36 is a pleiotropic receptor involved in several pathophysiological conditions, including cerebral ischemia, neurovascular dysfunction and atherosclerosis, and recent reports implicate its involvement in the endoplasmic reticulum stress response (ERSR). We hypothesized that CD36 signaling contributes to the inflammation and microvascular dysfunction following spinal cord injury. Following contusive injury, CD36−/− mice demonstrated improved hindlimb functional recovery and greater white matter sparing than CD36+/+ mice. CD36−/− mice exhibited a reduced macrophage, but not neutrophil, infiltration into the injury epicenter. Fewer infiltrating macrophages were either apoptotic or positive for the ERSR marker, phospho-ATF4. CD36−/− mice also exhibited significant improvements in injury heterodomain vascularity and function. These microvessels accumulated less of the oxidized lipid product 4-hydroxy-trans-2-nonenal (4HNE) and exhibited a reduced ERSR, as detected by vascular phospho-ATF4, CHOP and CHAC-1 expression. In cultured primary endothelial cells, deletion of CD36 diminished 4HNE-induced phospho-ATF4 and CHOP expression. A reduction in phospho-eIF2α and subsequent increase in KDEL-positive, ER-localized proteins suggest that 4HNE-CD36 signaling facilitates the detection of misfolded proteins upstream of eIF2α phosphorylation, ultimately leading to CHOP-induced apoptosis. We conclude that CD36 deletion modestly, but significantly, improves functional recovery from spinal cord injury by enhancing vascular function and reducing macrophage infiltration. These phenotypes may, in part, stem from reduced ER stress-induced cell death within endothelial and macrophage cells following injury. PMID:24690303

  8. Hyperbaric oxygen therapy improves cognitive functioning after brain injury

    PubMed Central

    Liu, Su; Shen, Guangyu; Deng, Shukun; Wang, Xiubin; Wu, Qinfeng; Guo, Aisong

    2013-01-01

    Hyperbaric oxygen therapy has been widely applied and recognized in the treatment of brain injury; however, the correlation between the protective effect of hyperbaric oxygen therapy and changes of metabolites in the brain remains unclear. To investigate the effect and potential mechanism of hyperbaric oxygen therapy on cognitive functioning in rats, we established traumatic brain injury models using Feeney's free falling method. We treated rat models with hyperbaric oxygen therapy at 0.2 MPa for 60 minutes per day. The Morris water maze test for spatial navigation showed that the average escape latency was significantly prolonged and cognitive function decreased in rats with brain injury. After treatment with hyperbaric oxygen therapy for 1 and 2 weeks, the rats’ spatial learning and memory abilities were improved. Hydrogen proton magnetic resonance spectroscopy analysis showed that the N-acetylaspartate/creatine ratio in the hippocampal CA3 region was significantly increased at 1 week, and the N-acetylaspartate/choline ratio was significantly increased at 2 weeks after hyperbaric oxygen therapy. Nissl staining and immunohistochemical staining showed that the number of nerve cells and Nissl bodies in the hippocampal CA3 region was significantly increased, and glial fibrillary acidic protein positive cells were decreased after a 2-week hyperbaric oxygen therapy treatment. Our findings indicate that hyperbaric oxygen therapy significantly improves cognitive functioning in rats with traumatic brain injury, and the potential mechanism is mediated by metabolic changes and nerve cell restoration in the hippocampal CA3 region. PMID:25206655

  9. Treatment Protocols to Reduce Injury and Improve Stone Breakage in SWL

    NASA Astrophysics Data System (ADS)

    McAteer, James A.; Evan, Andrew P.; Connors, Bret A.; Pishchalnikov, Yuri A.; Williams, James C.; Lingeman, James E.

    2008-09-01

    Here we provide a capsule summary of key observations showing that adverse effects can be reduced and stone breakage outcomes can be improved by the choice of the treatment protocol used in SWL. The take home message is—technique in lithotripsy can be used to significant advantage. SW-rate is key, and so is the sequence of SW delivery. Patient studies have shown that stone breakage is significantly improved at 60SW/min compared to a rate of 120SW/min, and laboratory experiments with pigs show that acute SWL injury to the kidney can be reduced dramatically by further slowing the SW firing rate to 30SW/min. The sequence of SW administration has a profound effect on the kidney, and renal injury is significantly reduced when the treatment protocol incorporates a priming dose of SW's followed by a brief pause before treatment is resumed. Continued developments in lithotripsy technology are welcome and will hopefully lead to improved SWL systems. Current experience suggests, however, that technology is not a substitute for expert technique, and attention to the fundamentals of SW delivery is essential to achieve the best possible outcomes regardless of the lithotripter at hand.

  10. Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes

    PubMed Central

    2014-01-01

    Background Lysophosphatidic acid (LPA) is a bioactive phospholipid with a potentially causative role in neurotrauma. Blocking LPA signaling with the LPA-directed monoclonal antibody B3/Lpathomab is neuroprotective in the mouse spinal cord following injury. Findings Here we investigated the use of this agent in treatment of secondary brain damage consequent to traumatic brain injury (TBI). LPA was elevated in cerebrospinal fluid (CSF) of patients with TBI compared to controls. LPA levels were also elevated in a mouse controlled cortical impact (CCI) model of TBI and B3 significantly reduced lesion volume by both histological and MRI assessments. Diminished tissue damage coincided with lower brain IL-6 levels and improvement in functional outcomes. Conclusions This study presents a novel therapeutic approach for the treatment of TBI by blocking extracellular LPA signaling to minimize secondary brain damage and neurological dysfunction. PMID:24576351

  11. Inosine improves functional recovery after experimental traumatic brain injury.

    PubMed

    Dachir, Shlomit; Shabashov, Dalia; Trembovler, Victoria; Alexandrovich, Alexander G; Benowitz, Larry I; Shohami, Esther

    2014-03-25

    Despite years of research, no effective therapy is yet available for the treatment of traumatic brain injury (TBI). The most prevalent and debilitating features in survivors of TBI are cognitive deficits and motor dysfunction. A potential therapeutic method for improving the function of patients following TBI would be to restore, at least in part, plasticity to the CNS in a controlled way that would allow for the formation of compensatory circuits. Inosine, a naturally occurring purine nucleoside, has been shown to promote axon collateral growth in the corticospinal tract (CST) following stroke and focal TBI. In the present study, we investigated the effects of inosine on motor and cognitive deficits, CST sprouting, and expression of synaptic proteins in an experimental model of closed head injury (CHI). Treatment with inosine (100 mg/kg i.p. at 1, 24 and 48 h following CHI) improved outcome after TBI, significantly decreasing the neurological severity score (NSS, p<0.04 vs. saline), an aggregate measure of performance on several tasks. It improved non-spatial cognitive performance (object recognition, p<0.016 vs. saline) but had little effect on sensorimotor coordination (rotarod) and spatial cognitive functions (Y-maze). Inosine did not affect CST sprouting in the lumbar spinal cord but did restore levels of the growth-associated protein GAP-43 in the hippocampus, though not in the cerebral cortex. Our results suggest that inosine may improve functional outcome after TBI. PMID:24502983

  12. Muscle injuries and strategies for improving their repair.

    PubMed

    Laumonier, Thomas; Menetrey, Jacques

    2016-12-01

    Satellite cells are tissue resident muscle stem cells required for postnatal skeletal muscle growth and repair through replacement of damaged myofibers. Muscle regeneration is coordinated through different mechanisms, which imply cell-cell and cell-matrix interactions as well as extracellular secreted factors. Cellular dynamics during muscle regeneration are highly complex. Immune, fibrotic, vascular and myogenic cells appear with distinct temporal and spatial kinetics after muscle injury. Three main phases have been identified in the process of muscle regeneration; a destruction phase with the initial inflammatory response, a regeneration phase with activation and proliferation of satellite cells and a remodeling phase with maturation of the regenerated myofibers. Whereas relatively minor muscle injuries, such as strains, heal spontaneously, severe muscle injuries form fibrotic tissue that impairs muscle function and lead to muscle contracture and chronic pain. Current therapeutic approaches have limited effectiveness and optimal strategies for such lesions are not known yet. Various strategies, including growth factors injections, transplantation of muscle stem cells in combination or not with biological scaffolds, anti-fibrotic therapies and mechanical stimulation, may become therapeutic alternatives to improve functional muscle recovery. PMID:27447481

  13. Therapeutic intraspinal microstimulation improves forelimb function after cervical contusion injury

    NASA Astrophysics Data System (ADS)

    Kasten, M. R.; Sunshine, M. D.; Secrist, E. S.; Horner, P. J.; Moritz, C. T.

    2013-08-01

    Objective. Intraspinal microstimulation (ISMS) is a promising method for activating the spinal cord distal to an injury. The objectives of this study were to examine the ability of chronically implanted stimulating wires within the cervical spinal cord to (1) directly produce forelimb movements, and (2) assess whether ISMS stimulation could improve subsequent volitional control of paretic extremities following injury. Approach. We developed a technique for implanting intraspinal stimulating electrodes within the cervical spinal cord segments C6-T1 of Long-Evans rats. Beginning 4 weeks after a severe cervical contusion injury at C4-C5, animals in the treatment condition received therapeutic ISMS 7 hours/day, 5 days/week for the following 12 weeks. Main results. Over 12 weeks of therapeutic ISMS, stimulus-evoked forelimb movements were relatively stable. We also explored whether therapeutic ISMS promoted recovery of forelimb reaching movements. Animals receiving daily therapeutic ISMS performed significantly better than unstimulated animals during behavioural tests conducted without stimulation. Quantitative video analysis of forelimb movements showed that stimulated animals performed better in the movements reinforced by stimulation, including extending the elbow to advance the forelimb and opening the digits. While threshold current to elicit forelimb movement gradually increased over time, no differences were observed between chronically stimulated and unstimulated electrodes suggesting that no additional tissue damage was produced by the electrical stimulation. Significance. The results indicate that therapeutic intraspinal stimulation delivered via chronic microwire implants within the cervical spinal cord confers benefits extending beyond the period of stimulation, suggesting future strategies for neural devices to promote sustained recovery after injury.

  14. Attenuated traumatic axonal injury and improved functional outcome after traumatic brain injury in mice lacking Sarm1.

    PubMed

    Henninger, Nils; Bouley, James; Sikoglu, Elif M; An, Jiyan; Moore, Constance M; King, Jean A; Bowser, Robert; Freeman, Marc R; Brown, Robert H

    2016-04-01

    Axonal degeneration is a critical, early event in many acute and chronic neurological disorders. It has been consistently observed after traumatic brain injury, but whether axon degeneration is a driver of traumatic brain injury remains unclear. Molecular pathways underlying the pathology of traumatic brain injury have not been defined, and there is no efficacious treatment for traumatic brain injury. Here we show that mice lacking the mouse Toll receptor adaptorSarm1(sterile α/Armadillo/Toll-Interleukin receptor homology domain protein) gene, a key mediator of Wallerian degeneration, demonstrate multiple improved traumatic brain injury-associated phenotypes after injury in a closed-head mild traumatic brain injury model.Sarm1(-/-)mice developed fewer β-amyloid precursor protein aggregates in axons of the corpus callosum after traumatic brain injury as compared toSarm1(+/+)mice. Furthermore, mice lackingSarm1had reduced plasma concentrations of the phophorylated axonal neurofilament subunit H, indicating that axonal integrity is maintained after traumatic brain injury. Strikingly, whereas wild-type mice exibited a number of behavioural deficits after traumatic brain injury, we observed a strong, early preservation of neurological function inSarm1(-/-)animals. Finally, usingin vivoproton magnetic resonance spectroscopy we found tissue signatures consistent with substantially preserved neuronal energy metabolism inSarm1(-/-)mice compared to controls immediately following traumatic brain injury. Our results indicate that the SARM1-mediated prodegenerative pathway promotes pathogenesis in traumatic brain injury and suggest that anti-SARM1 therapeutics are a viable approach for preserving neurological function after traumatic brain injury. PMID:26912636

  15. Dramatic Developments in the Neurosciences Challenge Educators.

    ERIC Educational Resources Information Center

    Sylwester, Robert

    1986-01-01

    Recent dramatic developments in brain research and technology suggest that a comprehensive understanding of how the human brain works may soon be within reach. Just as the ability of the medical profession to treat patients improved dramatically with the advent of effective research skills and technology concerning the structure, biochemistry, and…

  16. CCR2 Deficiency Impairs Macrophage Infiltration and Improves Cognitive Function after Traumatic Brain Injury

    PubMed Central

    Niemi, Erene C.; Wang, Sarah H.; Lee, Chih Cheng; Bingham, Deborah; Zhang, Jiasheng; Cozen, Myrna L.; Charo, Israel; Huang, Eric J.; Liu, Jialing; Nakamura, Mary C.

    2014-01-01

    Abstract Traumatic brain injury (TBI) provokes inflammatory responses, including a dramatic rise in brain macrophages in the area of injury. The pathway(s) responsible for macrophage infiltration of the traumatically injured brain and the effects of macrophages on functional outcomes are not well understood. C-C-chemokine receptor 2 (CCR2) is known for directing monocytes to inflamed tissues. To assess the role of macrophages and CCR2 in TBI, we determined outcomes in CCR2-deficient (Ccr2−/−) mice in a controlled cortical impact model. We quantified brain myeloid cell numbers post-TBI by flow cytometry and found that Ccr2−/− mice had greatly reduced macrophage numbers (∼80–90% reduction) early post-TBI, compared with wild-type mice. Motor, locomotor, and cognitive outcomes were assessed. Lack of Ccr2 improved locomotor activity with less hyperactivity in open field testing, but did not affect anxiety levels or motor coordination on the rotarod three weeks after TBI. Importantly, Ccr2−/− mice demonstrated greater spatial learning and memory, compared with wild-type mice eight weeks after TBI. Although there was no difference in the volume of tissue loss, Ccr2−/− mice had significantly increased neuronal density in the CA1-CA3 regions of the hippocampus after TBI, compared with wild-type mice. These data demonstrate that Ccr2 directs the majority of macrophage homing to the brain early after TBI and indicates that Ccr2 may facilitate harmful responses. Lack of Ccr2 improves functional recovery and neuronal survival. These results suggest that therapeutic blockade of CCR2-dependent responses may improve outcomes following TBI. PMID:24806994

  17. Elbow ulnar collateral ligament injuries in athletes: Can we improve our outcomes?

    PubMed Central

    Redler, Lauren H; Degen, Ryan M; McDonald, Lucas S; Altchek, David W; Dines, Joshua S

    2016-01-01

    Injury to the ulnar collateral ligament (UCL) most commonly occurs in the overhead throwing athlete. Knowledge surrounding UCL injury pathomechanics continues to improve, leading to better preventative treatment strategies and rehabilitation programs. Conservative treatment strategies for partial injuries, improved operative techniques for reconstruction in complete tears, adjunctive treatments, as well as structured sport specific rehabilitation programs including resistive exercises for the entire upper extremity kinetic chain are all important factors in allowing for a return to throwing in competitive environments. In this review, we explore each of these factors and provide recommendations based on the available literature to improve outcomes in UCL injuries in athletes. PMID:27114930

  18. Elbow ulnar collateral ligament injuries in athletes: Can we improve our outcomes?

    PubMed

    Redler, Lauren H; Degen, Ryan M; McDonald, Lucas S; Altchek, David W; Dines, Joshua S

    2016-04-18

    Injury to the ulnar collateral ligament (UCL) most commonly occurs in the overhead throwing athlete. Knowledge surrounding UCL injury pathomechanics continues to improve, leading to better preventative treatment strategies and rehabilitation programs. Conservative treatment strategies for partial injuries, improved operative techniques for reconstruction in complete tears, adjunctive treatments, as well as structured sport specific rehabilitation programs including resistive exercises for the entire upper extremity kinetic chain are all important factors in allowing for a return to throwing in competitive environments. In this review, we explore each of these factors and provide recommendations based on the available literature to improve outcomes in UCL injuries in athletes. PMID:27114930

  19. Xenon improves neurological outcome and reduces secondary injury following trauma in an in vivo model of traumatic brain injury

    PubMed Central

    Luh, Clara; Gruss, Marco; Radyushkin, Konstantin; Hirnet, Tobias; Werner, Christian; Engelhard, Kristin; Franks, Nicholas P; Thal, Serge C; Dickinson, Robert

    2015-01-01

    Objectives To determine the neuroprotective efficacy of the inert gas xenon following traumatic brain injury, and to determine whether application of xenon has a clinically relevant therapeutic time window. Design Controlled animal study. Setting University research laboratory. Subjects Male C57BL/6N mice (n=196) Interventions 75% xenon, 50% xenon or 30% xenon, with 25% oxygen (balance nitrogen) treatment following mechanical brain lesion by controlled cortical impact. Measurements & Main Results Outcome following trauma was measured using: 1) functional neurological outcome score, 2) histological measurement of contusion volume, 3) analysis of locomotor function and gait. Our study shows that xenon-treatment improves outcome following traumatic brain injury. Neurological outcome scores were significantly (p<0.05) better in xenon-treated groups in the early phase (24 hours) and up to 4 days after injury. Contusion volume was significantly (p<0.05) reduced in the xenon-treated groups. Xenon treatment significantly (p<0.05) reduced contusion volume when xenon was given 15 minutes after injury or when treatment was delayed 1 hour or 3 hours after injury. Neurological outcome was significantly (p<0.05) improved when xenon treatment was given 15 minutes or 1 hour after injury. Improvements in locomotor function (p<0.05) were observed in the xenon-treated group, 1 month after trauma. Conclusions These results show for the first time that xenon improves neurological outcome and reduces contusion volume following traumatic brain injury in mice. In this model, xenon application has a therapeutic time window of up to at least 3 hours. These findings support the idea that xenon may be of benefit as a neuroprotective treatment in brain trauma patients. PMID:25188549

  20. Improving outcome of sensorimotor functions after traumatic spinal cord injury

    PubMed Central

    Dietz, Volker

    2016-01-01

    In the rehabilitation of a patient suffering a spinal cord injury (SCI), the exploitation of neuroplasticity is well established. It can be facilitated through the training of functional movements with technical assistance as needed and can improve outcome after an SCI. The success of such training in individuals with incomplete SCI critically depends on the presence of physiological proprioceptive input to the spinal cord leading to meaningful muscle activations during movement performances. Some actual preclinical approaches to restore function by compensating for the loss of descending input to spinal networks following complete/incomplete SCI are critically discussed in this report. Electrical and pharmacological stimulation of spinal neural networks is still in the experimental stage, and despite promising repair studies in animal models, translations to humans up to now have not been convincing. It is possible that a combination of techniques targeting the promotion of axonal regeneration is necessary to advance the restoration of function. In the future, refinement of animal models according to clinical conditions and requirements may contribute to greater translational success. PMID:27303641

  1. Improve Tracking of Workplace Injuries and Illnesses. Final rule.

    PubMed

    2016-05-12

    OSHA is issuing a final rule to revise its Recording and Reporting Occupational Injuries and Illnesses regulation. The final rule requires employers in certain industries to electronically submit to OSHA injury and illness data that employers are already required to keep under existing OSHA regulations. The frequency and content of these establishment-specific submissions is set out in the final rule and is dependent on the size and industry of the employer. OSHA intends to post the data from these submissions on a publicly accessible Web site. OSHA does not intend to post any information on the Web site that could be used to identify individual employees. The final rule also amends OSHA's recordkeeping regulation to update requirements on how employers inform employees to report work-related injuries and illnesses to their employer. The final rule requires employers to inform employees of their right to report work-related injuries and illnesses free from retaliation; clarifies the existing implicit requirement that an employer's procedure for reporting work-related injuries and illnesses must be reasonable and not deter or discourage employees from reporting; and incorporates the existing statutory prohibition on retaliating against employees for reporting work-related injuries or illnesses. The final rule also amends OSHA's existing recordkeeping regulation to clarify the rights of employees and their representatives to access the injury and illness records. PMID:27192734

  2. Combining BRAF inhibitor and anti PD-L1 antibody dramatically improves tumor regression and anti tumor immunity in an immunocompetent murine model of anaplastic thyroid cancer

    PubMed Central

    Borre, Pierre Vanden; Zurakowski, David; Kim, Yon Seon; Dennett, Kate Virginia; Amin, Salma; Freeman, Gordon James; Parangi, Sareh

    2016-01-01

    The interaction of programmed cell death-1 and its ligand is widely studied in cancer. Monoclonal antibodies blocking these molecules have had great success but little is known about them in thyroid cancer. We investigated the role of PD-L1 in thyroid cancer with respect to BRAF mutation and MAP kinase pathway activity and the effect of anti PD-L1 antibody therapy on tumor regression and intra-tumoral immune response alone or in combination with BRAF inhibitor (BRAFi). BRAFV600E cells showed significantly higher baseline expression of PD-L1 at mRNA and protein levels compared to BRAFWT cells. MEK inhibitor treatment resulted in a decrease of PD-L1 expression across all cell lines. BRAFi treatment decreased PD-L1 expression in BRAFV600E cells, but paradoxically increased its expression in BRAFWT cells. BRAFV600E mutated patients samples had a higher level of PD-L1 mRNA compared to BRAFWT (p=0.015). Immunocompetent mice (B6129SF1/J) implanted with syngeneic 3747 BRAFV600E/WT P53−/− murine tumor cells were randomized to control, PLX4720, anti PD-L1 antibody and their combination. In this model of aggressive thyroid cancer, control tumor volume reached 782.3±174.6mm3 at two weeks. The combination dramatically reduced tumor volume to 147.3±60.8, compared to PLX4720 (439.3±188.4 mm3, P=0.023) or PD-L1 antibody (716.7±62.1, P<0.001) alone. Immunohistochemistry analysis revealed intense CD8+ CTL infiltration and cytotoxicity and favorable CD8+:Treg ratio compared to each individual treatment. Our results show anti PD-L1 treatment potentiates the effect of BRAFi on tumor regression and intensifies anti tumor immune response in an immunocompetent model of ATC. Clinical trials of this therapeutic combination may be of benefit in patients with ATC. PMID:26943572

  3. [Occupational injury risk in the shoe industry: frequency, types of injuries and equipment involved, improvement interventions].

    PubMed

    Tognon, Ilaria Desirée

    2012-01-01

    The aim of the work has been to evaluate the risk of injuries connected to the use of machinery and work tools in the footwear industry. The analysis of the data related to injuries in the footwear industry, deduced from the registers of injuries collected in the investigated factories, shows that most accidents arise from the contact of the operator's hands with tools and machinery parts during their use. Risk factors generally include the inherent specific danger of some work tools and machines, the lack or inadequacy of safety devices, the obsolescence of the equipment, the imprudence and underestimation of risk. PMID:22697028

  4. Post-Injury Administration of Mitochondrial Uncouplers Increases Tissue Sparing and Improves Behavioral Outcome following Traumatic Brain Injury in Rodents.

    PubMed

    Pandya, Jignesh D; Pauly, James R; Nukala, Vidya N; Sebastian, Andrea H; Day, Kristen M; Korde, Amit S; Maragos, William F; Hall, Edward D; Sullivan, Patrick G

    2007-05-01

    Following experimental traumatic brain injury (TBI), a rapid and significant necrosis occurs at the site of injury which coincides with significant mitochondrial dysfunction. The present study is driven by the hypothesis that TBI-induced glutamate release increases mitochondrial Ca(2+)cycling/overload, ultimately leading to mitochondrial dysfunction. Based on this premise, mitochondrial uncoupling during the acute phases of TBI-induced excitotoxicity should reduce mitochondrial Ca(2+) uptake (cycling) and reactive oxygen species (ROS) production since both are mitochondrial membrane potential dependent. In the present study, we utilized a cortical impact model of TBI to assess the potential use of mitochondrial uncouplers (2,4-DNP, FCCP) as a neuroprotective therapy. Young adult male rats were intraperitoneally administered vehicle (DMSO), 2,4-DNP (5 mg/kg), or FCCP (2.5 mg/kg) at 5 min post-injury. All animals treated with the uncouplers demonstrated a significant reduction in the amount of cortical damage and behavioral improvement following TBI. In addition, mitochondria isolated from the injured cortex at 3 or 6 h post-injury demonstrated that treatment with the uncouplers significantly improved several parameters of mitochondrial bioenergetics. These results demonstrate that post-injury treatment with mitochondrial uncouplers significantly (p < 0.01) increases cortical tissue sparing ( approximately 12%) and significantly (p< 0.01) improves behavioral outcome following TBI. The mechanism of neuroprotection most likely involves the maintenance of mitochondrial homeostasis by reducing mitochondrial Ca(2+) loading and subsequent mitochondrial dysfunction. These results further implicate mitochondrial dysfunction as an early event in the pathophysiology of TBI and that targeting acute mitochondrial events can result in long-term neuroprotection and improve behavioral outcome following brain injury. PMID:17518535

  5. Sodium selenate reduces hyperphosphorylated tau and improves outcomes after traumatic brain injury.

    PubMed

    Shultz, Sandy R; Wright, David K; Zheng, Ping; Stuchbery, Ryan; Liu, Shi-Jie; Sashindranath, Maithili; Medcalf, Robert L; Johnston, Leigh A; Hovens, Christopher M; Jones, Nigel C; O'Brien, Terence J

    2015-05-01

    Traumatic brain injury is a common and serious neurodegenerative condition that lacks a pharmaceutical intervention to improve long-term outcome. Hyperphosphorylated tau is implicated in some of the consequences of traumatic brain injury and is a potential pharmacological target. Protein phosphatase 2A is a heterotrimeric protein that regulates key signalling pathways, and protein phosphatase 2A heterotrimers consisting of the PR55 B-subunit represent the major tau phosphatase in the brain. Here we investigated whether traumatic brain injury in rats and humans would induce changes in protein phosphatase 2A and phosphorylated tau, and whether treatment with sodium selenate-a potent PR55 activator-would reduce phosphorylated tau and improve traumatic brain injury outcomes in rats. Ninety young adult male Long-Evans rats were administered either a fluid percussion injury or sham-injury. A proportion of rats were killed at 2, 24, and 72 h post-injury to assess acute changes in protein phosphatase 2A and tau. Other rats were given either sodium selenate or saline-vehicle treatment that was continuously administered via subcutaneous osmotic pump for 12 weeks. Serial magnetic resonance imaging was acquired prior to, and at 1, 4, and 12 weeks post-injury to assess evolving structural brain damage and axonal injury. Behavioural impairments were assessed at 12 weeks post-injury. The results showed that traumatic brain injury in rats acutely reduced PR55 expression and protein phosphatase 2A activity, and increased the expression of phosphorylated tau and the ratio of phosphorylated tau to total tau. Similar findings were seen in post-mortem brain samples from acute human traumatic brain injury patients, although many did not reach statistical significance. Continuous sodium selenate treatment for 12 weeks after sham or fluid percussion injury in rats increased protein phosphatase 2A activity and PR55 expression, and reduced the ratio of phosphorylated tau to total tau

  6. Why were alternating-current-driven electrochemiluminescence properties from Ru(bpy)3(2+) dramatically improved by the addition of titanium dioxide nanoparticles?

    PubMed

    Tsuneyasu, Shota; Ichihara, Kazuki; Nakamura, Kazuki; Kobayashi, Norihisa

    2016-06-28

    Electrochemiluminescence (ECL) is a phenomenon in which light is emitted from the excited state of a redox-active material generated by electrochemical reactions. Among light-emitting devices, ECL devices have various advantages in terms of structure and ease of fabrication, and therefore, they are expected to be next-generation emitting devices. In this study, we introduced rutile-type titanium dioxide nanoparticles (TiO2 NPs) in a Ru(ii)-complex-based electrolyte to improve the emission properties of an alternating current (AC)-driven ECL device. The properties of the ECL device with TiO2 NPs were greatly improved (emission luminescence, 165 cd m(-2); half-life time, 1000 s) compared to a previously reported AC-driven ECL device without nanoparticles. To determine how TiO2 NPs helped in achieving high emission luminescence and long-term stability, we measured the optical and electrochemical properties of the Ru(bpy)3(2+)-based ECL solution in detail. The PL intensity of Ru(bpy)3(2+) was increased by adding TiO2 NPs, which indicated that the suppression of non-radiative quenching of the complex's excited states could improve the ECL intensity. With respect to the enhanced stability, electron transfers between Ru(bpy)3(2+) and TiO2 were suggested by detailed electrochemical measurements. These electron transfers occurred from the reduced Ru(bpy)3(2+) species to the TiO2, and subsequently, from the TiO2 to the oxidized Ru(bpy)3(2+) species. Such electron transfers are thought to improve the balance of the redox reactions in the ECL device, leading to long-term stability. PMID:27253475

  7. Optimization of the GAFF force field to describe liquid crystal molecules: the path to a dramatic improvement in transition temperature predictions.

    PubMed

    Boyd, Nicola Jane; Wilson, Mark R

    2015-10-14

    The physical properties and phase transitions of thermotropic liquid crystals are highly sensitive to small changes in chemical structure. However, these changes are challenging to model, as both the phase diagram and mesophase properties obtained from fully atomistic simulations are strongly dependent on the force field model employed, and the current generation of chemical force fields has not proved accurate enough to provide reliable predictions of transition temperatures for many liquid crystals. This paper presents a strategy for improving the nematic clearing point, TNI, in atomistic simulations, by systematic optimization of the General Amber Force Field (GAFF) for key mesogenic fragments. We show that with careful optimization of the parameters describing a series of liquid crystal fragment molecules, it is possible to transfer these parameters to larger liquid crystal molecules and make accurate predictions for nematic mesophase formation. This new force field, GAFF-LCFF, is used to predict the nematic-isotropic clearing point to within 5 °C for the nematogen 1,3-benzenedicarboxylic acid,1,3-bis(4-butylphenyl)ester, an improvement of 60 °C over the standard GAFF force field. PMID:26343382

  8. Surface modification of alignment layer by ultraviolet irradiation to dramatically improve the detection limit of liquid-crystal-based immunoassay for the cancer biomarker CA125

    NASA Astrophysics Data System (ADS)

    Su, Hui-Wen; Lee, Mon-Juan; Lee, Wei

    2015-05-01

    Liquid crystal (LC)-based biosensing has attracted much attention in recent years. We focus on improving the detection limit of LC-based immunoassay techniques by surface modification of the surfactant alignment layer consisting of dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride (DMOAP). The cancer biomarker CA125 was detected with an array of anti-CA125 antibodies immobilized on the ultraviolet (UV)-modified DMOAP monolayer. Compared with a pristine counterpart, UV irradiation enhanced the binding affinity of the CA125 antibody and reproducibility of immunodetection in which a detection limit of 0.01 ng/ml for the cancer biomarker CA125 was achieved. Additionally, the optical texture observed under a crossed polarized microscope was correlated with the analyte concentration. In a proof-of-concept experiment using CA125-spiked human serum as the analyte, specific binding between the CA125 antigen and the anti-CA125 antibody resulted in a distinct and concentration-dependent optical response despite the high background caused by nonspecific binding of other biomolecules in the human serum. Results from this study indicate that UV modification of the alignment layer, as well as detection with LCs of large birefringence, contributes to the enhanced performance of the label-free LC-based immunodetection, which may be considered a promising alternative to conventional label-based methods.

  9. Surface modification of alignment layer by ultraviolet irradiation to dramatically improve the detection limit of liquid-crystal-based immunoassay for the cancer biomarker CA125.

    PubMed

    Su, Hui-Wen; Lee, Mon-Juan; Lee, Wei

    2015-05-01

    Liquid crystal (LC)-based biosensing has attracted much attention in recent years. We focus on improving the detection limit of LC-based immunoassay techniques by surface modification of the surfactant alignment layer consisting of dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride (DMOAP). The cancer biomarker CA125 was detected with an array of anti-CA125 antibodies immobilized on the ultraviolet (UV)-modified DMOAP monolayer. Compared with a pristine counterpart, UV irradiation enhanced the binding affinity of the CA125 antibody and reproducibility of immunodetection in which a detection limit of 0.01 ng∕ml for the cancer biomarker CA125 was achieved. Additionally, the optical texture observed under a crossed polarized microscope was correlated with the analyte concentration. In a proof-of-concept experiment using CA125-spiked human serum as the analyte, specific binding between the CA125 antigen and the anti-CA125 antibody resulted in a distinct and concentration-dependent optical response despite the high background caused by nonspecific binding of other biomolecules in the human serum. Results from this study indicate that UVmodification of the alignment layer, as well as detection with LCs of large birefringence, contributes to the enhanced performance of the label-free LC-based immunodetection, which may be considered a promising alternative to conventional label-based methods. PMID:26000796

  10. Poly(2,5-dimercapto-1,3,4-thiadiazole) as a cathode for rechargeable lithium batteries with dramatically improved performance.

    PubMed

    Gao, Jie; Lowe, Michael A; Conte, Sean; Burkhardt, Stephen E; Abruña, Héctor D

    2012-07-01

    Organosulfur compounds with multiple thiol groups are promising for high gravimetric energy density electrochemical energy storage. We have synthesized a poly(2,5-dimercapto-1,3,4-thiadiazole) (PDMcT)/poly(3,4-ethylenedioxythiophene) (PEDOT) composite cathode for lithium-ion batteries with a new method and investigated its electrochemical behavior by charge/discharge cycles and cyclic voltammetry (CV) in an ether-based electrolyte. Based on a comparison of the electrochemical performance with a carbonate-based electrolyte, we found a much higher discharge capacity, but also a very attractive cycling performance of PDMcT by using a tetra(ethylene glycol) dimethyl ether (TEGDME)-based electrolyte. The first discharge capacity of the as-synthesized PDMcT/PEDOT composite approached 210 mAh g(-1) in the TEGDME-based electrolyte. CV results clearly show that the redox reactions of PDMcT are highly reversible in this TEGDME-based electrolyte. The reversible capacity remained around 120 mAh g(-1) after 20 charge/discharge cycles. With improved cycling performance and very low cost, PDMcT could become a very promising cathode material when combined with a TEGDME-based electrolyte. The poor capacity in the carbonate-based electrolyte is a consequence of the irreversible reaction of the DMcT monomer and dimer with the solvent, emphasizing the importance of electrolyte chemistry when studying molecular-based battery materials. PMID:22644940

  11. Rapid Surface Cooling by ThermoSuit System Dramatically Reduces Scar Size, Prevents Post-Infarction Adverse Left Ventricular Remodeling, and Improves Cardiac Function in Rats

    PubMed Central

    Dai, Wangde; Herring, Michael J; Hale, Sharon L; Kloner, Robert A

    2015-01-01

    Background The long-term effects of transient hypothermia by the non-invasive ThermoSuit apparatus on myocardial infarct (MI) scar size, left ventricular (LV) remodeling, and LV function were assessed in rat MI model. Methods and Results Rats were randomized to normothermic or hypothermic groups (n=14 in each group) and subjected to 30 minutes coronary artery occlusion and 6 weeks of reperfusion. For hypothermia therapy, rats were placed into the ThermoSuit apparatus at 2 minutes after the onset of coronary artery occlusion, were taken out of the apparatus when the core body temperature reached 32°C (in ≈8 minutes), and were then allowed to rewarm. After 6 weeks of recovery, rats treated with hypothermia demonstrated markedly reduced scar size (expressed as % of left ventricular area: hypothermia, 6.5±1.1%; normothermia, 19.4±1.7%; P=1.3×10−6); and thicker anterior LV wall (hypothermia, 1.57±0.09 mm; normothermia, 1.07±0.05 mm; P=3.4×10−5); decreased postmortem left ventricular volume (hypothermia, 0.45±0.04 mL; normothermia, 0.6±0.03 mL; P=0.028); and better LV fractional shortening by echocardiography (hypothermia, 37.2±2.8%; normothermia, 18.9±2.3%; P=0.0002) and LV ejection fraction by LV contrast ventriculography (hypothermia, 66.8±2.3%; normothermia, 56.0±2.0%; P=0.0014). Conclusions Rapid, transient non-invasive surface cooling with the ThermoSuit apparatus in the acute phase of MI decreased scar size by 66.5%, attenuated adverse post-infarct left ventricular dilation and remodeling, and improved cardiac function in the chronic phase of experimental MI. PMID:26116692

  12. Creative Dramatics in Early Childhood

    ERIC Educational Resources Information Center

    Mandelbaum, Jean

    1975-01-01

    Offers suggestions as to how teachers of nursery through second grade children might develop a creative dramatics program from elements that are already in the curriculum and in the children themselves. (Author/SDH)

  13. Patients With Isolated PCL Injuries Improve From Surgery as Much as Patients With ACL Injuries After 2 Years

    PubMed Central

    Owesen, Christian; Sivertsen, Einar Andreas; Engebretsen, Lars; Granan, Lars-Petter; Årøen, Asbjørn

    2015-01-01

    Background: Reports on outcome after posterior cruciate ligament (PCL) reconstruction often contain both isolated PCL and combined knee ligament injuries. This makes it difficult to conclude on the outcome after reconstruction of isolated PCL injuries. Purpose: To investigate the outcome after PCL reconstruction in patients with an isolated PCL injury and to compare this with the outcome of patients treated with reconstruction after isolated anterior cruciate ligament (ACL) injuries. Study Design: Cohort study; Level of evidence, 3. Methods: Seventy-one patients with an isolated PCL injury that was reconstructed surgically and who had registered in the Norwegian Knee Ligament Registry between 2004 and 2010 were included in this study. Patients with isolated ACL reconstructions (n = 9661) who had registered in the same period were included for comparison. Knee Injury and Osteoarthritis Outcome Score (KOOS) was used as the patient-reported outcome measure. Preoperative and 2-year postoperative KOOS scores were compared. Changes in KOOS score reported by the PCL patients were compared with changes reported by the ACL patients. Results: At the 2-year postoperative follow-up of the PCL-reconstructed patients, the patient-reported outcome was improved, measured by KOOS as follows: pain, 15.1 (95% CI, 8.5-21.8; P < .001); symptoms, 0.9 (95% CI, –6.6 to 8.3; P = .82); activities of daily living, 13.2 (95% CI, 6.6-13.9; P < .001); sports, 20.7 (95% CI, 11.8-29.4; P < .001); and quality of life, 26.6 (95% CI, 18.9-34.2; P < .001). According to the KOOS, the incremental improvements were similar for PCL and ACL patients. Time from injury to surgery was longer for the PCL patients compared with ACL patients (median, 21.5 vs 8.0 months; P < .001). Conclusion: Patients undergoing PCL reconstruction can expect the same improvements in KOOS score as patients undergoing ACL reconstruction. However, PCL patients start out with an inferior score on average and consequently end up

  14. Can targeting glutamate receptors with long-term heat acclimation improve outcomes following hypoxic injury?

    PubMed Central

    Ely, Brett R; Brunt, Vienna E; Minson, Christopher T

    2015-01-01

    Long-term heat acclimation appears to improve tolerance to hypoxic insults in various tissues, including brain, providing a promising avenue to improve functional outcomes following cerebrovascular events. Glutamate discharge is implicated in dysfunction following hypoxic stress and thus, targeting glutamate receptors with heat acclimation could improve cognitive outcomes following hypoxic injury. PMID:27227003

  15. Neuroprotective Strategies for Traumatic Brain Injury: Improving Clinical Translation

    PubMed Central

    Kabadi, Shruti V.; Faden, Alan I.

    2014-01-01

    Traumatic brain injury (TBI) induces secondary biochemical changes that contribute to delayed neuroinflammation, neuronal cell death, and neurological dysfunction. Attenuating such secondary injury has provided the conceptual basis for neuroprotective treatments. Despite strong experimental data, more than 30 clinical trials of neuroprotection in TBI patients have failed. In part, these failures likely reflect methodological differences between the clinical and animal studies, as well as inadequate pre-clinical evaluation and/or trial design problems. However, recent changes in experimental approach and advances in clinical trial methodology have raised the potential for successful clinical translation. Here we critically analyze the current limitations and translational opportunities for developing successful neuroprotective therapies for TBI. PMID:24445258

  16. Bone Marrow Mesenchymal Cells Improve Muscle Function in a Skeletal Muscle Re-Injury Model

    PubMed Central

    Ribeiro, Karla C.; Porto, Anderson; Peçanha, Ramon; Fortes, Fabio S. A.; Zapata-Sudo, Gisele; Campos-de-Carvalho, Antonio C.; Goldenberg, Regina C. S.; Werneck-de-Castro, João Pedro

    2015-01-01

    Skeletal muscle injury is the most common problem in orthopedic and sports medicine, and severe injury leads to fibrosis and muscle dysfunction. Conventional treatment for successive muscle injury is currently controversial, although new therapies, like cell therapy, seem to be promise. We developed a model of successive injuries in rat to evaluate the therapeutic potential of bone marrow mesenchymal cells (BMMC) injected directly into the injured muscle. Functional and histological assays were performed 14 and 28 days after the injury protocol by isometric tension recording and picrosirius/Hematoxilin & Eosin staining, respectively. We also evaluated the presence and the fate of BMMC on treated muscles; and muscle fiber regeneration. BMMC treatment increased maximal skeletal muscle contraction 14 and 28 days after muscle injury compared to non-treated group (4.5 ± 1.7 vs 2.5 ± 0.98 N/cm2, p<0.05 and 8.4 ± 2.3 vs. 5.7 ± 1.3 N/cm2, p<0.05 respectively). Furthermore, BMMC treatment increased muscle fiber cross-sectional area and the presence of mature muscle fiber 28 days after muscle injury. However, there was no difference in collagen deposition between groups. Immunoassays for cytoskeleton markers of skeletal and smooth muscle cells revealed an apparent integration of the BMMC within the muscle. These data suggest that BMMC transplantation accelerates and improves muscle function recovery in our extensive muscle re-injury model. PMID:26039243

  17. Does Cryotherapy Improve Outcomes With Soft Tissue Injury?

    PubMed Central

    Denegar, Craig R.

    2004-01-01

    Reference: Bleakley C, McDonough S, MacAuley D. The use of ice in the treatment of acute soft-tissue injury: a systematic review of randomized controlled trials. Am J Sport Med. 2004; 32:251–261. Clinical Question: What is the clinical evidence base for cryotherapy use? Data Sources: Studies were identified by using a computer-based literature search on a total of 8 databases: MEDLINE, Proquest, ISI Web of Science, Cumulative Index to Nursing and Allied Health (CINAHL) on Ovid, Allied and Complementary Medicine Database (AMED) on Ovid, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effectiveness, and Cochrane Controlled Trials Register (Central). This was supplemented with citation tracking of relevant primary and review articles. Search terms included surgery,orthopaedics,sports injury,soft tissue injury,sprains and strains,contusions,athletic injury,acute,compression, cryotherapy,ice,RICE, andcold. Study Selection: To be included in the review, each study had to fulfill the following conditions: be a randomized, controlled trial of human subjects; be published in English as a full paper; include patients recovering from acute soft tissue or orthopaedic surgical interventions who received cryotherapy in inpatient, outpatient, or home-based treatment, in isolation or in combination with placebo or other therapies; provide comparisons with no treatment, placebo, a different mode or protocol of cryotherapy, or other physiotherapeutic interventions; and have outcome measures that included function (subjective or objective), pain, swelling, or range of motion. Data Extraction: The study population, interventions, outcomes, follow-up, and reported results of the assessed trials were extracted and tabulated. The primary outcome measures were pain, swelling, and range of motion. Only 2 groups reported adequate data for return to normal function. All eligible articles were rated for methodologic quality using the PEDro scale. The

  18. Does Cryotherapy Improve Outcomes With Soft Tissue Injury?

    PubMed

    Hubbard, Tricia J; Denegar, Craig R

    2004-09-01

    REFERENCE: Bleakley C, McDonough S, MacAuley D. The use of ice in the treatment of acute soft-tissue injury: a systematic review of randomized controlled trials. Am J Sport Med. 2004; 32:251-261. CLINICAL QUESTION: What is the clinical evidence base for cryotherapy use? DATA SOURCES: Studies were identified by using a computer-based literature search on a total of 8 databases: MEDLINE, Proquest, ISI Web of Science, Cumulative Index to Nursing and Allied Health (CINAHL) on Ovid, Allied and Complementary Medicine Database (AMED) on Ovid, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effectiveness, and Cochrane Controlled Trials Register (Central). This was supplemented with citation tracking of relevant primary and review articles. Search terms included surgery,orthopaedics,sports injury,soft tissue injury,sprains and strains,contusions,athletic injury,acute,compression, cryotherapy,ice,RICE, andcold. STUDY SELECTION: To be included in the review, each study had to fulfill the following conditions: be a randomized, controlled trial of human subjects; be published in English as a full paper; include patients recovering from acute soft tissue or orthopaedic surgical interventions who received cryotherapy in inpatient, outpatient, or home-based treatment, in isolation or in combination with placebo or other therapies; provide comparisons with no treatment, placebo, a different mode or protocol of cryotherapy, or other physiotherapeutic interventions; and have outcome measures that included function (subjective or objective), pain, swelling, or range of motion. DATA EXTRACTION: The study population, interventions, outcomes, follow-up, and reported results of the assessed trials were extracted and tabulated. The primary outcome measures were pain, swelling, and range of motion. Only 2 groups reported adequate data for return to normal function. All eligible articles were rated for methodologic quality using the PEDro scale. The

  19. Chondroitinase gene therapy improves upper limb function following cervical contusion injury

    PubMed Central

    James, Nicholas D.; Shea, Jessie; Muir, Elizabeth M.; Verhaagen, Joost; Schneider, Bernard L.; Bradbury, Elizabeth J.

    2015-01-01

    Chondroitin sulphate proteoglycans (CSPGs) are known to be important contributors to the intensely inhibitory environment that prevents tissue repair and regeneration following spinal cord injury. The bacterial enzyme chondroitinase ABC (ChABC) degrades these inhibitory molecules and has repeatedly been shown to promote functional recovery in a number of spinal cord injury models. However, when used to treat more traumatic and clinically relevant spinal contusion injuries, findings with the ChABC enzyme have been inconsistent. We recently demonstrated that delivery of mammalian-compatible ChABC via gene therapy led to sustained and widespread digestion of CSPGs, resulting in significant functional repair of a moderate thoracic contusion injury in adult rats. Here we demonstrate that chondroitinase gene therapy significantly enhances upper limb function following cervical contusion injury, with improved forelimb ladder performance and grip strength as well as increased spinal conduction through the injury site and reduced lesion pathology. This is an important addition to our previous findings as improving upper limb function is a top priority for spinal injured patients. Additionally great importance is placed on replication in the spinal cord injury field. That chondroitinase gene therapy has now been shown to be efficacious in contusion models at either thoracic or cervical level is an important step in the further development of this promising therapeutic strategy towards the clinic. PMID:26044197

  20. Children's Voices through Dramatic Play.

    ERIC Educational Resources Information Center

    Sierra, Zayda

    Dramatic play provides children an excellent way to express their feelings and perceptions of the world that surrounds them. It is also an alternative way for researchers and teachers to capture, understand, and interpret children's voices because of the difficulties that children have in expressing ideas through oral and written language. While…

  1. Dramatic Techniques in ESL Instruction.

    ERIC Educational Resources Information Center

    Radin, Barbara

    Three techniques have been found to be helpful in using dramatic techniques to provide motivation, self-confidence, and self-esteem to students of English as a second language at Hostos Community College. Strategic interaction is a technique based on the open-ended scenario, in which students are free to respond to the problem presented in the…

  2. Kenneth Burke's Discovery of Dramatism.

    ERIC Educational Resources Information Center

    Feehan, Michael

    1979-01-01

    Discusses how "Twelve Propositions by Kenneth Burke on the Relation between Economics and Psychology" generates a new synthesis of Marx and Freud and foreshadows Burke's system of dramatism. His conception of self, the community, and communication come together in a serious argument for drama as a model of human relations. (JMF)

  3. Learning through Dramatic Story Presentation

    ERIC Educational Resources Information Center

    Tindall, Evie

    2012-01-01

    The use of story with dramatic presentation approaches produces an engaging and powerful instructional choice for today's adult ESL educators. Two engaging and timed-tested approaches are Reader's Theater and Tableau Vivant. Both provide English language learners with content tailored to their abilities in addition to numerable opportunities to…

  4. Health and Economic Benefits of Improved Injury Prevention and Trauma Care Worldwide

    PubMed Central

    Kotagal, Meera; Agarwal-Harding, Kiran J.; Mock, Charles; Quansah, Robert; Arreola-Risa, Carlos; Meara, John G.

    2014-01-01

    Objectives Injury is a significant source of morbidity and mortality worldwide, and often disproportionately affects younger, more productive members of society. While many have made the case for improved injury prevention and trauma care, health system development in low- and middle-income countries is often limited by resources. This study aims to determine the economic benefit of improved injury prevention and trauma care in low- and middle-income countries. Methods This study uses existing data on injury mortality worldwide from the 2010 Global Burden of Disease Study to estimate the number of lives that could be saved if injury mortality rates in low- and middle-income countries could be reduced to rates in high-income countries. Using economic modeling – through the human capital approach and the value of a statistical life approach – the study then demonstrates the associated economic benefit of these lives saved. Results 88 percent of injury-related deaths occur in low- and middle-income countries. If injury mortality rates in low- and middle-income countries were reduced to rates in high-income countries, 2,117,500 lives could be saved per year. This would result in between 49 million and 52 million disability adjusted life years averted per year, with discounting and age weighting. Using the human capital approach, the associated economic benefit of reducing mortality rates ranges from $245 to $261 billion with discounting and age weighting. Using the value of a statistical life approach, the benefit is between 758 and 786 billion dollars per year. Conclusions Reducing injury mortality in low- and middle-income countries could save over 2 million lives per year and provide significant economic benefit globally. Further investments in trauma care and injury prevention are needed. PMID:24626472

  5. The novel apolipoprotein E-based peptide COG1410 improves sensorimotor performance and reduces injury magnitude following cortical contusion injury.

    PubMed

    Hoane, Michael R; Pierce, Jeremy L; Holland, Michael A; Birky, Nicholas D; Dang, Tan; Vitek, Michael P; McKenna, Suzanne E

    2007-07-01

    It has previously been shown that small peptide molecules derived from the apolipoprotein E (ApoE) receptor binding region are anti-inflammatory in nature and can improve outcome following head injury. The present study evaluated the preclinical efficacy of COG1410, a small molecule ApoE-mimetic peptide (1410 daltons), following cortical contusion injury (CCI). Animals were prepared with a unilateral CCI of the sensorimotor cortex (SMC) or sham procedure. Thirty mins post-CCI the animals received i.v. infusions of 0.8 mg/kg COG1410, 0.4 mg/kg COG1410, or vehicle. Starting on day 2, the animals were tested on a battery of behavioral measures to assess sensorimotor (vibrissae-forelimb placing and forelimb use-asymmetry), and motor (tapered balance beam) performance. Administration of the 0.8 mg/kg dose of COG1410 significantly improved recovery on the vibrissae-forelimb and limb asymmetry tests. However, no facilitation was observed on the tapered beam. The low dose (0.4 mg/kg) of COG1410 did not show any significant differences compared to vehicle. Lesion analysis revealed that the 0.8 mg/kg dose of COG1410 significantly reduced the size of the injury cavity compared to the 0.4 mg/kg dose and vehicle. The 0.8 mg/kg dose also reduced the number of glial fibrillary acid protein (GFAP+) reactive cells in the injured cortex. These results suggest that a single dose of COG1410 facilitates behavioral recovery and provides neuroprotection in a dose and task-dependent manner. Thus, the continued clinical development of ApoE based therapeutics is warranted and could represent a novel strategy for the treatment of traumatic brain injuries. PMID:17610351

  6. Granulocyte colony-stimulating factor improves alternative activation of microglia under microenvironment of spinal cord injury.

    PubMed

    Guo, Y; Zhang, H; Yang, J; Liu, S; Bing, L; Gao, J; Hao, A

    2013-05-15

    Granulocyte colony-stimulating factor (G-CSF) was investigated in the present study to examine whether it could affect the activation status of microglia under microenvironment of spinal cord injury and provide a potential therapeutic treatment for spinal cord injury. We established mouse spinal cord hemisection model and injected recombinant human G-CSF (rhG-CSF) subcutaneously. The results demonstrated that G-CSF could recruit microglia to the injury site in the first 72h after spinal cord injury. Moreover, G-CSF inhibits the expression of pro-inflammatory factors and promotes the expression of neurotrophic factors. Additionally, G-CSF also increases the expression of markers of M2 macrophage and inhibits the expression of markers of M1 macrophage in BV2 microglia in vitro model, favoring the M2 polarization of microglia under the microenvironment of spinal cord hemisection. NFκB signal pathway was involved in G-CSF-induced polarization of BV2 microglia. As a conclusion, we suggested that administration of G-CSF within the first 72h after spinal cord injury might reduce early inflammation-induced detrimental effect and promote an anti-inflammatory response that favors repair via improving alternative activation of microglia. Administration of G-CSF in the acute phase of spinal cord injury may be a promising strategy in restorative therapy after spinal cord injury. PMID:23419550

  7. Spinal Cord Injury: How Can We Improve the Classification and Quantification of Its Severity and Prognosis?

    PubMed Central

    Krishna, Vibhor; Andrews, Hampton; Varma, Abhay; Mintzer, Jacobo

    2014-01-01

    Abstract The preservation of functional neural tissue after spinal cord injury (SCI) is the basis for spontaneous neurological recovery. Some injured patients in the acute phase have more potential for recovery than others. This fact is problematic for the construction of clinical trials because enrollment of subjects with variable recovery potential makes it difficult to detect effects, requires large sample sizes, and risks Type II errors. In addition, the current methods to assess injury and recovery are non-quantitative and not sensitive. It is likely that therapeutic combinations will be necessary to cause substantially improved function after SCI, thus we need highly sensitive techniques to evaluate changes in motor, sensory, autonomic and other functions. We review several emerging neurophysiological techniques with high sensitivity. Quantitative methods to evaluate residual tissue sparing after severe acute SCI have not entered widespread clinical use. This reduces the ability to correlate structural preservation with clinical outcome following SCI resulting in enrollment of subjects with varying patterns of tissue preservation and injury into clinical trials. We propose that the inclusion of additional measures of injury severity, pattern, and individual genetic characteristics may enable stratification in clinical trials to make the testing of therapeutic interventions more effective and efficient. New imaging techniques to assess tract injury and demyelination and methods to quantify tissue injury, inflammatory markers, and neuroglial biochemical changes may improve the evaluation of injury severity, and the correlation with neurological outcome, and measure the effects of treatment more robustly than is currently possible. The ability to test such a multimodality approach will require a high degree of collaboration between clinical and research centers and government research support. When the most informative of these assessments is determined, it may

  8. A Multidisciplinary Approach with Hyperbaric Oxygen Therapy Improve Outcome in Snake Bite Injuries

    PubMed Central

    Korambayil, Pradeoth Mukundan; Ambookan, Prashanth Varkey; Abraham, Siju Varghese; Ambalakat, Ajay

    2015-01-01

    Aim: Snakebite injuries are common in tropical India among those who are involved in outdoor activities. These injuries results in cellulitis, gangrene at the bite area, bleeding manifestations, compartment syndrome, regional lymphadenopathy, septicemia, hypotension, and disseminated intravascular coagulation (DIC) resulting in significant morbidity and mortality. The purpose of this study is to share our experience of multidisciplinary approach in the management of snakebite injuries of the extremities with various treatment modalities including hyperbaric oxygen (HBO) therapy, surgical debridement, and soft tissue reconstruction to provide an effective treatment for snake bite injuries. Methods: The study was conducted in the Department of Plastic Surgery, during the period October 2012–December 2014, wherein all the patients who were admitted with snakebite injuries were enrolled and the patients treated in plastic surgery department were included into the study. Out of total 766 patients, there were 323 patients treated with anti snake venom (ASV) and 29 died among the treated patients; 205 patients belonged to pediatric age group. Results: Out of 112 patients referred to Department of Plastic Surgery, 50 cases presented with cellulitis, 24 patients with compartment syndrome, and 38 patients were referred for the management of soft tissue cover over the extremities. Among 112 patients, 77 involved the lower extremity and 35 the upper extremity. Conclusion: Multidisciplinary approach including hyperbaric oxygen (HBO) therapy improves outcome in the management of snakebite injuries of the extremities. PMID:26862269

  9. Successful Mitigation of Delayed Intestinal Radiation Injury Using Pravastatin is not Associated with Acute Injury Improvement or Tumor Protection

    SciTech Connect

    Haydont, Valerie; Bourhis, Jean; Vozenin-Brotons, Marie-Catherine |. E-mail: vozenin@igr.fr

    2007-08-01

    Purpose: To investigate whether pravastatin mitigates delayed radiation-induced enteropathy in rats, by focusing on the effects of pravastatin on acute cell death and fibrosis according to connective tissue growth factor (CTGF) expression and collagen inhibition. Methods and Materials: Mitigation of delayed radiation-induced enteropathy was investigated in rats using pravastatin administered in drinking water (30 mg/kg/day) 3 days before and 14 days after irradiation. The ileum was irradiated locally after surgical exteriorization (X-rays, 19 Gy). Acute apoptosis, acute and late histologic alterations, and late CTGF and collagen deposition were monitored by semiquantitative immunohistochemistry and colorimetric staining (6 h, 3 days, 14 days, 15 weeks, and 26 weeks after irradiation). Pravastatin antitumor action was studied in HT-29, HeLa, and PC-3 cells by clonogenic cell survival assays and tumor growth delay experiments. Results: Pravastatin improved delayed radiation enteropathy in rats, whereas its benefit in acute and subacute injury remained limited (6 h, 3 days, and 14 days after irradiation). Delayed structural improvement was associated with decreased CTGF and collagen deposition but seemed unrelated to acute damage. Indeed, the early apoptotic index increased, and severe subacute structural damage occurred. Pravastatin elicited a differential effect, protecting normal intestine but not tumors from radiation injury. Conclusion: Pravastatin provides effective protection against delayed radiation enteropathy without interfering with the primary antitumor action of radiotherapy, suggesting that clinical transfer is feasible.

  10. Inhibition of intestinal epithelial apoptosis improves survival in a murine model of radiation combined injury.

    PubMed

    Jung, Enjae; Perrone, Erin E; Brahmamdan, Pavan; McDonough, Jacquelyn S; Leathersich, Ann M; Dominguez, Jessica A; Clark, Andrew T; Fox, Amy C; Dunne, W Michael; Hotchkiss, Richard S; Coopersmith, Craig M

    2013-01-01

    World conditions place large populations at risk from ionizing radiation (IR) from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy) followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA). While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01). Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01). These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target. PMID:24204769

  11. Improving myocardial injury, infarct size, and myocardial salvage in the era of primary PCI for STEMI.

    PubMed

    Ndrepepa, Gjin

    2015-06-01

    ST-segment elevation myocardial infarction (STEMI) is a major cause of mortality and disability worldwide. Reperfusion therapy by thrombolysis or primary percutaneous coronary intervention (PPCI) improves survival and quality of life in patients with STEMI. Despite the proven efficacy of timely reperfusion, mortality from STEMI remains high, particularly among patients with suboptimal reperfusion. Reperfusion injury following opening of occluded coronary arteries mitigates the efficacy of PPCI by further accentuating ischemic damage and increasing infarct size (IS). On the basis of experimental studies, it is assumed that nearly 50% of the final IS is because of the reperfusion injury. IS is a marker of ischemic damage and adequacy of reperfusion that is strongly related to mortality in reperfused patients with STEMI. Many therapeutic strategies including pharmacological and conditioning agents have been proven effective in reducing reperfusion injury and IS in preclinical research. Mechanistically, these agents act either by inhibiting reperfusion injury cascades or by activating cellular prosurvival pathways. Although most of these agents/strategies are at the experimental stage, some of them have been tested clinically in patients with STEMI. This review provides an update on key pharmacological agents and postconditioning used in the setting of PPCI to reduce reperfusion injury and IS. Despite intensive research, no strategy or intervention has been shown to prevent reperfusion injury or enhance myocardial salvage in a consistent manner in a clinical setting. A number of novel therapeutic strategies to reduce reperfusion injury in the setting of PPCI in patients with STEMI are currently under investigation. They will lead to a better understanding of reperfusion injury and to more efficient strategies for its prevention. PMID:25715338

  12. Improved regeneration after femoral nerve injury in mice lacking functional T- and B-lymphocytes.

    PubMed

    Mehanna, Ali; Szpotowicz, Emanuela; Schachner, Melitta; Jakovcevski, Igor

    2014-11-01

    The immune system plays important functional roles in regeneration after injury to the mammalian central and peripheral nervous systems. After damage to the peripheral nerve several types of immune cells, invade the nerve within hours after the injury. To gain insights into the contribution of T- and B-lymphocytes to recovery from injury we used the mouse femoral nerve injury paradigm. RAG2-/- mice lacking mature T- and B-lymphocytes due to deletion of the recombination activating gene 2 were subjected to resection and surgical reconstruction of the femoral nerve, with the wild-type mice of the same inbred genetic background serving as controls. According to single frame motion analyses, RAG2-/- mice showed better motor recovery in comparison to control mice at four and eight weeks after injury. Retrograde tracing of regrown/sprouted axons of spinal motoneurons showed increased numbers of correctly projecting motoneurons in the lumbar spinal cord of RAG2-/- mice compared with controls. Whereas there was no difference in the motoneuron soma size between genotypes, RAG2-/- mice displayed fewer cholinergic and inhibitory synaptic terminals around somata of spinal motoneurons both prior to and after injury, compared with wild-type mice. Extent of myelination of regrown axons in the motor branch of the femoral nerve measured as g-ratio was more extensive in RAG2-/- than in control mice eight weeks after injury. We conclude that activated T- and B-lymphocytes restrict motor recovery after femoral nerve injury, associated with the increased survival of motoneurons and improved remyelination. PMID:24967682

  13. Inhibition of Intestinal Epithelial Apoptosis Improves Survival in a Murine Model of Radiation Combined Injury

    PubMed Central

    Jung, Enjae; Perrone, Erin E.; Brahmamdan, Pavan; McDonough, Jacquelyn S.; Leathersich, Ann M.; Dominguez, Jessica A.; Clark, Andrew T.; Fox, Amy C.; Dunne, W. Michael; Hotchkiss, Richard S.; Coopersmith, Craig M.

    2013-01-01

    World conditions place large populations at risk from ionizing radiation (IR) from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy) followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA). While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01). Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01). These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target. PMID:24204769

  14. Intravenous Administration of Simvastatin Improves Cognitive Outcome following Severe Traumatic Brain Injury in Rats.

    PubMed

    Mountney, Andrea; Boutté, Angela M; Gilsdorf, Janice; Lu, Xi-Chun; Tortella, Frank C; Shear, Deborah A

    2016-08-15

    Simvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor commonly used to reduce serum cholesterol. The beneficial effects of oral simvastatin have been reported in pre-clinical models of traumatic brain injury (TBI). The current study was designed to evaluate the potential beneficial effects of simvastatin in a model of severe penetrating TBI using an intravenous (IV) route of administration. Rats were subjected to unilateral frontal penetrating ballistic-like brain injury (PBBI), and simvastatin was delivered intravenously at 30 min and 6 h post-injury and continued once daily for either 4 or 10 days post-PBBI. Motor function was assessed on the rotarod and cognitive performance was evaluated using the Morris water maze (MWM) task. Serum levels of inflammatory cytokines and the astrocytic biomarker, glial fibrillary acidic protein (GFAP), were quantified at 1 h, 4 h, and 24 h post-injury. Histopathological damage was assessed at the terminal end-point. Rotarod testing revealed significant motor deficits in all injury groups but no significant simvastatin-induced therapeutic benefits. All PBBI-injured animals showed cognitive impairment on the MWM test; however, 10-day simvastatin treatment mitigated these effects. Animals showed significantly improved latency to platform and retention scores, whereas the 4-day treatment regimen failed to produce any significant improvements. Biomarker and cytokine analysis showed that IV simvastatin significantly reduced GFAP, interleukin (IL)-1α, and IL-17 serum levels by 4.0-, 2.6-, and 7.0-fold, respectively, at 4 h post-injury. Collectively, our results demonstrate that IV simvastatin provides significant protection against injury-induced cognitive dysfunction and reduces TBI-specific biomarker levels. Further research is warranted to identify the optimal dose and therapeutic window for IV delivery of simvastatin in models of severe TBI. PMID:26542887

  15. The Dramatic Methods of Hans van Dam.

    ERIC Educational Resources Information Center

    van de Water, Manon

    1994-01-01

    Interprets for the American reader the untranslated dramatic methods of Hans van Dam, a leading drama theorist in the Netherlands. Discusses the functions of drama as a method, closed dramatic methods, open dramatic methods, and applying van Dam's methods. (SR)

  16. Cognitive Improvement after Mild Traumatic Brain Injury Measured with Functional Neuroimaging during the Acute Period

    PubMed Central

    Wylie, Glenn R.; Freeman, Kalev; Thomas, Alex; Shpaner, Marina; OKeefe, Michael; Watts, Richard; Naylor, Magdalena R.

    2015-01-01

    Functional neuroimaging studies in mild traumatic brain injury (mTBI) have been largely limited to patients with persistent post-concussive symptoms, utilizing images obtained months to years after the actual head trauma. We sought to distinguish acute and delayed effects of mild traumatic brain injury on working memory functional brain activation patterns < 72 hours after mild traumatic brain injury (mTBI) and again one-week later. We hypothesized that clinical and fMRI measures of working memory would be abnormal in symptomatic mTBI patients assessed < 72 hours after injury, with most patients showing clinical recovery (i.e., improvement in these measures) within 1 week after the initial assessment. We also hypothesized that increased memory workload at 1 week following injury would expose different cortical activation patterns in mTBI patients with persistent post-concussive symptoms, compared to those with full clinical recovery. We performed a prospective, cohort study of working memory in emergency department patients with isolated head injury and clinical diagnosis of concussion, compared to control subjects (both uninjured volunteers and emergency department patients with extremity injuries and no head trauma). The primary outcome of cognitive recovery was defined as resolution of reported cognitive impairment and quantified by scoring the subject’s reported cognitive post-concussive symptoms at 1 week. Secondary outcomes included additional post-concussive symptoms and neurocognitive testing results. We enrolled 46 subjects: 27 with mild TBI and 19 controls. The time of initial neuroimaging was 48 (+22 S.D.) hours after injury (time 1). At follow up (8.7, + 1.2 S.D., days after injury, time 2), 18 of mTBI subjects (64%) reported moderate to complete cognitive recovery, 8 of whom fully recovered between initial and follow-up imaging. fMRI changes from time 1 to time 2 showed an increase in posterior cingulate activation in the mTBI subjects compared to

  17. Cognitive Improvement after Mild Traumatic Brain Injury Measured with Functional Neuroimaging during the Acute Period.

    PubMed

    Wylie, Glenn R; Freeman, Kalev; Thomas, Alex; Shpaner, Marina; OKeefe, Michael; Watts, Richard; Naylor, Magdalena R

    2015-01-01

    Functional neuroimaging studies in mild traumatic brain injury (mTBI) have been largely limited to patients with persistent post-concussive symptoms, utilizing images obtained months to years after the actual head trauma. We sought to distinguish acute and delayed effects of mild traumatic brain injury on working memory functional brain activation patterns < 72 hours after mild traumatic brain injury (mTBI) and again one-week later. We hypothesized that clinical and fMRI measures of working memory would be abnormal in symptomatic mTBI patients assessed < 72 hours after injury, with most patients showing clinical recovery (i.e., improvement in these measures) within 1 week after the initial assessment. We also hypothesized that increased memory workload at 1 week following injury would expose different cortical activation patterns in mTBI patients with persistent post-concussive symptoms, compared to those with full clinical recovery. We performed a prospective, cohort study of working memory in emergency department patients with isolated head injury and clinical diagnosis of concussion, compared to control subjects (both uninjured volunteers and emergency department patients with extremity injuries and no head trauma). The primary outcome of cognitive recovery was defined as resolution of reported cognitive impairment and quantified by scoring the subject's reported cognitive post-concussive symptoms at 1 week. Secondary outcomes included additional post-concussive symptoms and neurocognitive testing results. We enrolled 46 subjects: 27 with mild TBI and 19 controls. The time of initial neuroimaging was 48 (+22 S.D.) hours after injury (time 1). At follow up (8.7, + 1.2 S.D., days after injury, time 2), 18 of mTBI subjects (64%) reported moderate to complete cognitive recovery, 8 of whom fully recovered between initial and follow-up imaging. fMRI changes from time 1 to time 2 showed an increase in posterior cingulate activation in the mTBI subjects compared to

  18. Improving Population Health by Incorporating Chronic Disease and Injury Prevention Into Value-Based Care Models.

    PubMed

    Petersen, Ruth; Rushing, Jill; Nelson, Sharon; Rhyne, Sharon

    2016-01-01

    Today's health system transformation provides a prime opportunity to leverage the capacity of public health to reduce the burden of chronic disease and injury, improve population health, and contain health care costs. Health care settings and organizations should support public health capacity as a key investment in population health. PMID:27422946

  19. 75 FR 28261 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Improved...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-20

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Improved Diagnostics for Lyme Borreliosis, Funding Opportunity... Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC) announces...

  20. Learning From No-Fault Treatment Injury Claims to Improve the Safety of Older Patients

    PubMed Central

    Wallis, Katharine Ann

    2015-01-01

    New Zealand’s treatment injury compensation claims data set provides an uncommon no-fault perspective of patient safety incidents. Analysis of primary care claims data confirmed medication as the leading threat to the safety of older patients in primary care and drew particular attention to the threat posed by antibiotics. For most injuries there was no suggestion of error. The no-fault perspective reveals the greatest threat to the safety of older patients in primary care to be, not error, but the risk posed by treatment itself. To improve patients’ safety, in addition to reducing error, clinicians need to reduce patients’ exposure to treatment risk, where appropriate. PMID:26371269

  1. S-nitrosothiol signaling regulates hepatogenesis and improves outcome following toxic liver injury

    PubMed Central

    Cox, Andrew G.; Saunders, Diane C.; Kelsey, Peter; Conway, Allie A.; Tesmenitsky, Yevgenia; Marchini, Julio F.; Brown, Kristin K.; Stamler, Jonathan S.; Colagiovanni, Dorothy B.; Rosenthal, Gary J.; Croce, Kevin J.; North, Trista E.; Goessling, Wolfram

    2014-01-01

    Summary Toxic liver injury is a leading cause of liver failure and death, due to the organ’s inability to regenerate amidst massive cell death, and few therapeutic options exist. The mechanisms coordinating damage protection and repair are poorly understood. Here, we show that S-nitrosothiols regulate liver growth during development and after injury in vivo: in zebrafish, NO enhanced liver formation independent of cGMP-mediated vasoactive effects. Following acetaminophen (APAP) exposure, inhibition of the enzymatic regulator, S-nitrosoglutathione reductase (GSNOR), minimized toxic liver damage, increased cell proliferation, and improved survival through sustained activation of the cytoprotective Nrf2 pathway. Preclinical studies of APAP injury in GSNOR-deficient mice confirmed conservation of hepatoprotective properties of S-nitrosothiol signaling across vertebrates; a GSNOR-specific inhibitor improved liver histology and acted together with the approved therapy N-acetylcysteine, to expand the therapeutic time window and improve outcome. These studies demonstrate that GSNOR inhibitors will be beneficial therapeutic candidates to treat liver injury. PMID:24388745

  2. Cerebral Malaria; Mechanisms Of Brain Injury And Strategies For Improved Neuro-Cognitive Outcome

    PubMed Central

    Idro, Richard; Marsh, Kevin; John, Chandy C; Newton, Charles RJ

    2011-01-01

    Cerebral malaria is the most severe neurological complication of infection with Plasmodium falciparum. With over 575,000 cases annually, children in sub-Saharan Africa are the most affected. Surviving patients have an increased risk of neurological and cognitive deficits, behavioral difficulties and epilepsy making cerebral malaria a leading cause of childhood neuro-disability in the region. The pathogenesis of neuro-cognitive sequelae is poorly understood: coma develops through multiple mechanisms and there may be several mechanisms of brain injury. It is unclear how an intravascular parasite causes such brain injury. Understanding these mechanisms is important to develop appropriate neuro-protective interventions. This paper examines possible mechanisms of brain injury in cerebral malaria, relating this to the pathogenesis of the disease and explores prospects for improved neuro-cognitive outcome. PMID:20606600

  3. A Combination Therapy of Nicotinamide and Progesterone Improves Functional Recovery following Traumatic Brain Injury

    PubMed Central

    Peterson, Todd C.; McConomy, Keith S.; Farin, Fred M.; Bammler, Theo K.; MacDonald, James W.; Kantor, Eric D.; Anderson, Gail D.

    2015-01-01

    Abstract Neuroprotection, recovery of function, and gene expression were evaluated in an animal model of traumatic brain injury (TBI) after a combination treatment of nicotinamide (NAM) and progesterone (Prog). Animals received a cortical contusion injury over the sensorimotor cortex, and were treated with either Vehicle, NAM, Prog, or a NAM/Prog combination for 72 h and compared with a craniotomy only (Sham) group. Animals were assessed in a battery of behavioral, sensory, and both fine and gross motor tasks, and given histological assessments at 24 h post-injury to determine lesion cavity size, degenerating neurons, and reactive astrocytes. Microarray-based transcriptional profiling was used to determine treatment-specific changes on gene expression. Our results confirm the beneficial effects of treatment with either NAM or Prog, demonstrating significant improvements in recovery of function and a reduction in lesion cavitation, degenerating neurons, and reactive astrocytes 24 h post-injury. The combination treatment of NAM and Prog led to a significant improvement in both neuroprotection at 24 h post-injury and recovery of function in sensorimotor related tasks when compared with individual treatments. The NAM/Prog-treated group was the only treatment group to show a significant reduction of cortical loss 24 h post-injury. The combination appears to affect inflammatory and immune processes, reducing expression of a significant number of genes in both pathways. Further preclinical trials using NAM and Prog as a combination treatment should be conducted to identify the window of opportunity, determine the optimal duration of treatment, and evaluate the combination in other pre-clinical models of TBI. PMID:25313690

  4. A Combination Therapy of Nicotinamide and Progesterone Improves Functional Recovery following Traumatic Brain Injury.

    PubMed

    Peterson, Todd C; Hoane, Michael R; McConomy, Keith S; Farin, Fred M; Bammler, Theo K; MacDonald, James W; Kantor, Eric D; Anderson, Gail D

    2015-06-01

    Neuroprotection, recovery of function, and gene expression were evaluated in an animal model of traumatic brain injury (TBI) after a combination treatment of nicotinamide (NAM) and progesterone (Prog). Animals received a cortical contusion injury over the sensorimotor cortex, and were treated with either Vehicle, NAM, Prog, or a NAM/Prog combination for 72 h and compared with a craniotomy only (Sham) group. Animals were assessed in a battery of behavioral, sensory, and both fine and gross motor tasks, and given histological assessments at 24 h post-injury to determine lesion cavity size, degenerating neurons, and reactive astrocytes. Microarray-based transcriptional profiling was used to determine treatment-specific changes on gene expression. Our results confirm the beneficial effects of treatment with either NAM or Prog, demonstrating significant improvements in recovery of function and a reduction in lesion cavitation, degenerating neurons, and reactive astrocytes 24 h post-injury. The combination treatment of NAM and Prog led to a significant improvement in both neuroprotection at 24 h post-injury and recovery of function in sensorimotor related tasks when compared with individual treatments. The NAM/Prog-treated group was the only treatment group to show a significant reduction of cortical loss 24 h post-injury. The combination appears to affect inflammatory and immune processes, reducing expression of a significant number of genes in both pathways. Further preclinical trials using NAM and Prog as a combination treatment should be conducted to identify the window of opportunity, determine the optimal duration of treatment, and evaluate the combination in other pre-clinical models of TBI. PMID:25313690

  5. Pyridoxamine reduces postinjury fibrosis and improves functional recovery after acute kidney injury.

    PubMed

    Skrypnyk, Nataliya I; Voziyan, Paul; Yang, Haichun; de Caestecker, Christian R; Theberge, Marie-Claude; Drouin, Mathieu; Hudson, Billy; Harris, Raymond C; de Caestecker, Mark P

    2016-08-01

    Acute kidney injury (AKI) is a common and independent risk factor for death and chronic kidney disease (CKD). Despite promising preclinical data, there is no evidence that antioxidants reduce the severity of injury, increase recovery, or prevent CKD in patients with AKI. Pyridoxamine (PM) is a structural analog of vitamin B6 that interferes with oxidative macromolecular damage via a number of different mechanisms and is in a phase 3 clinical efficacy trial to delay CKD progression in patients with diabetic kidney disease. Because oxidative stress is implicated as one of the main drivers of renal injury after AKI, the ability of PM to interfere with multiple aspects of oxidative damage may be favorable for AKI treatment. In these studies we therefore evaluated PM treatment in a mouse model of AKI. Pretreatment with PM caused a dose-dependent reduction in acute tubular injury, long-term postinjury fibrosis, as well as improved functional recovery after ischemia-reperfusion AKI (IR-AKI). This was associated with a dose-dependent reduction in the oxidative stress marker isofuran-to-F2-isoprostane ratio, indicating that PM reduces renal oxidative damage post-AKI. PM also reduced postinjury fibrosis when administered 24 h after the initiating injury, but this was not associated with improvement in functional recovery after IR-AKI. This is the first report showing that treatment with PM reduces short- and long-term injury, fibrosis, and renal functional recovery after IR-AKI. These preclinical findings suggest that PM, which has a favorable clinical safety profile, holds therapeutic promise for AKI and, most importantly, for prevention of adverse long-term outcomes after AKI. PMID:27194713

  6. Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury.

    PubMed

    Wenger, Nikolaus; Moraud, Eduardo Martin; Gandar, Jerome; Musienko, Pavel; Capogrosso, Marco; Baud, Laetitia; Le Goff, Camille G; Barraud, Quentin; Pavlova, Natalia; Dominici, Nadia; Minev, Ivan R; Asboth, Leonie; Hirsch, Arthur; Duis, Simone; Kreider, Julie; Mortera, Andrea; Haverbeck, Oliver; Kraus, Silvio; Schmitz, Felix; DiGiovanna, Jack; van den Brand, Rubia; Bloch, Jocelyne; Detemple, Peter; Lacour, Stéphanie P; Bézard, Erwan; Micera, Silvestro; Courtine, Grégoire

    2016-02-01

    Electrical neuromodulation of lumbar segments improves motor control after spinal cord injury in animal models and humans. However, the physiological principles underlying the effect of this intervention remain poorly understood, which has limited the therapeutic approach to continuous stimulation applied to restricted spinal cord locations. Here we developed stimulation protocols that reproduce the natural dynamics of motoneuron activation during locomotion. For this, we computed the spatiotemporal activation pattern of muscle synergies during locomotion in healthy rats. Computer simulations identified optimal electrode locations to target each synergy through the recruitment of proprioceptive feedback circuits. This framework steered the design of spatially selective spinal implants and real-time control software that modulate extensor and flexor synergies with precise temporal resolution. Spatiotemporal neuromodulation therapies improved gait quality, weight-bearing capacity, endurance and skilled locomotion in several rodent models of spinal cord injury. These new concepts are directly translatable to strategies to improve motor control in humans. PMID:26779815

  7. Lameness and hock injuries improve on farms participating in an assessment program.

    PubMed

    Chapinal, N; Weary, D M; Collings, L; von Keyserlingk, M A G

    2014-12-01

    Lameness and hock injuries are recognized welfare and production problems in the dairy industry. The objective of this study was to describe changes in the prevalence of these ailments in 15 freestall herds in the Northeastern United States that participated in an on-farm assessment program. Prevalence was assessed in a high-producing pen in each herd. A confidential report was delivered to each of the farms showing prevalence in relation to other herds assessed within the same region. The average (±SD) period between visits was 11.5 ± 4.4 months (range, 8-25 months). The prevalence of lameness decreased in most herds after the first assessment (mean difference ± SE [range] = -17 ± 4 % [-43 to 6]). An even larger improvement was seen in the prevalence of hock injuries with all farms showing a decrease (-38 ± 6% [-1 to -87]). The degree of improvement observed at the second assessment was greatest for those farms that had higher lameness prevalence when first assessed, but this was not the case for hock injuries. The changes in prevalence of clinical lameness and overall hock lesions were, however, correlated (ρ = 0.62). These results suggest that monitoring and reporting the prevalence of lameness and hock injuries to farmers can motivate changes in facilities and management targeted to address these ailments. PMID:25447801

  8. Progesterone and vitamin D: improvement after traumatic brain injury in middle-aged rats

    PubMed Central

    Tang, Huiling; Hua, Fang; Wang, Jun; Sayeed, Iqbal; Wang, Xiaojing; Chen, Zhengjia; Yousuf, Seema; Atif, Fahim; Stein, Donald G.

    2013-01-01

    Progesterone (PROG) and vitamin D hormone (VDH) have both shown promise in treating traumatic brain injury (TBI). Both modulate apoptosis, inflammation, oxidative stress, and excitotoxicity. We investigated whether 21 days of VDH deficiency would alter cognitive behavior after TBI and whether combined PROG and VDH would improve behavioral and morphological outcomes more than either hormone alone in VDH-deficient middle-aged rats given bilateral contusions of the medial frontal cortex. PROG (16 mg/kg) and VDH (5 µg/kg) were injected intraperitoneally 1 hour post-injury. Eight additional doses of PROG were injected subcutaneously over 7 days post-injury. VDH deficiency itself did not significantly reduce baseline behavioral functions or aggravate impaired cognitive outcomes. Combination therapy showed moderate improvement in preserving spatial and reference memory but was not significantly better than PROG monotherapy. However, combination therapy significantly reduced neuronal loss and the proliferation of reactive astrocytes, and showed better efficacy compared to VDH or PROG alone in preventing MAP-2 degradation. VDH+PROG combination therapy may attenuate some of the potential long-term, subtle, pathophysiological consequences of brain injury in older subjects. PMID:23896206

  9. The unrecognized epidemic of blunt carotid arterial injuries: early diagnosis improves neurologic outcome.

    PubMed Central

    Biffl, W L; Moore, E E; Ryu, R K; Offner, P J; Novak, Z; Coldwell, D M; Franciose, R J; Burch, J M

    1998-01-01

    OBJECTIVE: To determine the benefit of screening for blunt carotid arterial injuries (BCI) in patients who are asymptomatic. SUMMARY BACKGROUND DATA: Blunt carotid arterial injuries have the potential for devastating complications. Published studies report 23% to 28% mortality rates, with 48% to 58% of survivors having permanent severe neurologic deficits. Most patients have neurologic deficits when the injury is diagnosed. The authors hypothesized that screening patients who are asymptomatic and instituting early therapy would improve neurologic outcome. METHODS: The Trauma Registry of the author's Level I Trauma Center identified patients with BCI from 1990 through 1997. Beginning in August 1996, the authors implemented a screening for BCI. Arteriography was used for diagnosis. Patients without specific contraindications were anticoagulated. Endovascular stents were deployed in the setting of pseudoaneurysms. RESULTS: Thirty-seven patients with BCI were identified among 15,331 blunt-trauma victims (0.24%). During the screening period, 25 patients were diagnosed with BCI among 2902 admissions (0.86%); 13 (52%) were asymptomatic. Overall, eight patients died, and seven of the survivors had permanent severe neurologic deficits. Excluding those dying of massive brain injury and patients admitted with coma and brain injury, mortality associated with BCI was 15%, with severe neurologic morbidity in 16% of survivors. The patients who were asymptomatic at diagnosis had a better neurologic outcome than those who were symptomatic. Symptomatic patients who were anticoagulated showed a trend toward greater neurologic improvement at the time of discharge than those who were not anticoagulated. CONCLUSIONS: Screening allows the identification of asymptomatic BCI and thereby facilitates early systemic anticoagulation, which is associated with improved neurologic outcome. The role of endovascular stents in the treatment of blunt traumatic pseudoaneurysms remains to be defined

  10. Exogenous lactate infusion improved neurocognitive function of patients with mild traumatic brain injury

    PubMed Central

    Bisri, Tatang; Utomo, Billy A.; Fuadi, Iwan

    2016-01-01

    Background: Many studies showed a better recovery of cognitive function after administration of exogenous lactate during moderate-severe traumatic brain injury. However, the study evaluating lactate effect on mild traumatic brain injury is still limited. Aims: To evaluate the effect of exogenous lactate on cognitive function in mild traumatic brain injury patients. Settings and Design: Prospective, single blind, randomized controlled study on 60 mild traumatic brain injury patients who were undergoing neurosurgery. Materials and Methods: Subjects were randomly assigned into hyperosmolar sodium lactate (HSL) group or hyperosmolar sodium chloride (HSS) group. Patients in each group received either intravenous infusion of HSL or NaCl 3% at 1.5 ml/KgBW within 15 min before neurosurgery. During the surgery, patients in both groups received maintenance infusion of NaCl 0.9% at 1.5 ml/KgBW/hour. Statistical Analysis: Cognitive function, as assessed by Mini-Mental State Examination (MMSE) score at 24 h, 30 and 90 days post-surgery, was analyzed by Anova repeated measures test. Results: The MMSE score improvement was significantly better in HSL group than HSS group (P < 0.001). In HSL group the MMSE score improved from 16.00 (13.75-18.00) at baseline to 21.00 (18.75-22.00); 25.00 (23.75-26.00); 28.00 (27.00-29.00) at 24 h, 30, 90 days post-surgery, respectively. In contrast, in HSS group the MMSE score almost unchanged at 24 h and only slightly increased at 30 and 90 days post-surgery. Conclusions: Hyperosmolar sodium lactate infusion during mild traumatic brain injury improved cognitive function better than sodium chloride 3%. PMID:27057222

  11. Sirtuin 3–dependent mitochondrial dynamic improvements protect against acute kidney injury

    PubMed Central

    Morigi, Marina; Perico, Luca; Rota, Cinzia; Longaretti, Lorena; Conti, Sara; Rottoli, Daniela; Novelli, Rubina; Remuzzi, Giuseppe; Benigni, Ariela

    2015-01-01

    Acute kidney injury (AKI) is a public health concern with an annual mortality rate that exceeds those of breast and prostate cancer, heart failure, and diabetes combined. Oxidative stress and mitochondrial damage are drivers of AKI-associated pathology; however, the pathways that mediate these events are poorly defined. Here, using a murine cisplatin-induced AKI model, we determined that both oxidative stress and mitochondrial damage are associated with reduced levels of renal sirtuin 3 (SIRT3). Treatment with the AMPK agonist AICAR or the antioxidant agent acetyl-l-carnitine (ALCAR) restored SIRT3 expression and activity, improved renal function, and decreased tubular injury in WT animals, but had no effect in Sirt3–/– mice. Moreover, Sirt3-deficient mice given cisplatin experienced more severe AKI than WT animals and died, and neither AICAR nor ALCAR treatment prevented death in Sirt3–/– AKI mice. In cultured human tubular cells, cisplatin reduced SIRT3, resulting in mitochondrial fragmentation, while restoration of SIRT3 with AICAR and ALCAR improved cisplatin-induced mitochondrial dysfunction. Together, our results indicate that SIRT3 is protective against AKI and suggest that enhancing SIRT3 to improve mitochondrial dynamics has potential as a strategy for improving outcomes of renal injury. PMID:25607838

  12. CD47 Blockade Reduces Ischemia Reperfusion Injury and Improves Outcomes in a Rat Kidney Transplant Model

    PubMed Central

    Lin, Yiing; Manning, Pamela T.; Jia, Jianluo; Gaut, Joseph P.; Xiao, Zhen-yu; Capoccia, Ben J.; Chen, Chun-Cheng; Hiebsch, Ronald R.; Upadhya, Gundumi; Mohanakumar, Thalachallour; Frazier, William A.; Chapman, William C.

    2016-01-01

    Background Ischemia/reperfusion injury (IRI) significantly contributes to delayed graft function and inflammation leading to graft loss. IRI is exacerbated by the thrombospondin-1/CD47 system through inhibition of nitric oxide signaling. We postulate that CD47 blockade and prevention of nitric oxide inhibition reduces IRI in organ transplantation. Methods We used a syngeneic rat renal transplantation model of IRI with bilaterally nephrectomized recipients to evaluate the effect of a CD47 monoclonal antibody (CD47mAb) on IRI. Donor kidneys were flushed with CD47mAb OX101 or an isotype-matched control immunoglobulin and stored at 4°C in UW solution for 6 hours prior to transplantation. Results CD47mAb perfusion of donor kidneys resulted in marked improvement in post-transplant survival, lower levels of serum creatinine, BUN, phosphorus and magnesium and less histologic evidence of injury. In contrast, control groups did not survive more than 5 days, had increased biochemical indicators of renal injury and exhibited severe pathological injury with tubular atrophy and necrosis. Recipients of CD47mAb-treated kidneys showed decreased levels of plasma biomarkers of renal injury including cystatin C, osteopontin, TIMP1, β2-microglobulin, VEGF-A and clusterin compared to the control group. Furthermore, laser Doppler assessment showed higher renal blood flow in the CD47mAb-treated kidneys. Conclusions These results provide strong evidence for the use of CD47 antibody-mediated blockade to reduce IRI and improve organ preservation for renal transplantation. PMID:24983310

  13. Improved outcomes in the non-operative management of liver injuries

    PubMed Central

    Saltzherr, Teun Peter; van der Vlies, Cees H; van Lienden, Krijn P; Beenen, Ludo F M; Ponsen, Kees Jan; van Gulik, Thomas M; Goslings, J Carel

    2011-01-01

    Objectives Non-operative management has become the treatment of choice in the majority of liver injuries. The aim of this study was to assess the changes in primary treatment and outcomes in a single Dutch Level 1 trauma centre with wide experience in angio-embolisation (AE). Methods The prospective trauma registry was retrospectively analysed for 7-year periods before (Period 1) and after (Period 2) the introduction of AE. The primary outcome was the failure rate of primary treatment defined as liver injury-related death or re-bleeding requiring radiologic or operative (re)interventions. Secondary outcomes were liver injury-related intra-abdominal complications. Results Despite an increase in high-grade liver injuries, the incidence of primary non-operative management more than doubled over the two periods, from 33% (20 of 61 cases) in Period 1 to 72% (84 of 116 cases) in Period 2 (P < 0.001). The failure rate of primary treatment in Period 1 was 18% (11/61), compared with 11% (13/116) in Period 2 (P = 0.21). Complication rates were 23% (14/61) and 16% (18/116) in Periods 1 and 2, respectively (P = 0.22). Liver-related mortality rates were 10% (6/61) and 3% (4/116) in Periods 1 and 2, respectively (P = 0.095). The increase in the frequency of non-operative management was even higher in high-grade injuries, in which outcomes were improved. In high-grade injuries in Periods 1 and 2, failure rates decreased from 45% (9/20) to 20% (11/55) (P = 0.041), liver-related mortality decreased from 30% (6/20) to 7% (4/55) (P = 0.019) and complication rates fell from 60% (12/20) to 27% (15/55) (P = 0.014). Liver infarction or necrosis and abscess formation seemed to occur more frequently with AE. Conclusions Overall, liver-related mortality, treatment failure and complication rates remained constant despite an increase in non-operative management. However, in high-grade injuries outcomes improved after the introduction of AE. PMID:21492335

  14. Ectopic Muscle Expression of Neurotrophic Factors Improves Recovery After Nerve Injury.

    PubMed

    Glat, Micaela Johanna; Benninger, Felix; Barhum, Yael; Ben-Zur, Tali; Kogan, Elena; Steiner, Israel; Yaffe, David; Offen, Daniel

    2016-01-01

    Sciatic nerve damage is a common medical problem. The main causes include direct trauma, prolonged external nerve compression, and pressure from disk herniation. Possible complications include leg numbness and the loss of motor control. In mild cases, conservative treatment is feasible. However, following severe injury, recovery may not be possible. Neuronal regeneration, survival, and maintenance can be achieved by neurotrophic factors (NTFs). In this study, we examined the potency of combining brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor-1 (IGF-1) on the recovery of motor neuron function after crush injury of the sciatic nerve. We show that combined NTF application increases the survival of motor neurons exposed to a hypoxic environment. The ectopic expression of NTFs in the injured muscle improves the recovery of the sciatic nerve after crush injury. A significantly faster recovery of compound muscle action potential (CMAP) amplitude and conduction velocity is observed after muscle injections of viral vectors expressing a mixture of the four NTF genes. Our findings suggest a rationale for using genetic treatment with a combination of NTF-expressing vectors, as a potential therapeutic approach for severe peripheral nerve injury. PMID:26385386

  15. Methylphenidate on Cognitive Improvement in Patients with Traumatic Brain Injury: A Meta-Analysis.

    PubMed

    Huang, Chi-Hsien; Huang, Chia-Chen; Sun, Cheuk-Kwan; Lin, Gong-Hong; Hou, Wen-Hsuan

    2016-01-01

    Although methylphenidate has been used as a neurostimulant to treat patients with attention deficit hyperactivity disorder, its therapeutic role in the psychomotor or cognitive recovery of patients with traumatic brain injuries (TBIs) in both intensive care and rehabilitation settings has not been adequately explored. To address this issue, this meta-analysis searched the available electronic databases using the key words "methylphenidate", "brain injuries", "head injuries", and "traumatic brain injury". Analysis of the ten double-blind RCTs demonstrated significant benefit in using methylphenidate for enhancing vigilance-associated attention (i.e., selective, sustained, and divided attention) in patients with TBIs (standardized mean difference: 0.45, 95% CI: 0.10 to 0.79), especially in sustained attention (standardized mean difference: 0.66, 95% CI: 0.22 to 1.10). However, no significant positive impact was noted on the facilitation of memory or processing speed. More studies on the efficacy and safety of methylphenidate for the cognitive improvement of patients with TBIs are warranted. PMID:26951094

  16. Salvianolic Acids Attenuate Rat Hippocampal Injury after Acute CO Poisoning by Improving Blood Flow Properties

    PubMed Central

    Guan, Li; Zhang, Yan-Lin; Li, Zong-Yang; Zhu, Ming-Xia; Yao, Wei-Juan; Zhao, Jin-Yuan

    2015-01-01

    Carbon monoxide (CO) poisoning causes the major injury and death due to poisoning worldwide. The most severe damage via CO poisoning is brain injury and mortality. Delayed encephalopathy after acute CO poisoning (DEACMP) occurs in forty percent of the survivors of acute CO exposure. But the pathological cause for DEACMP is not well understood. And the corresponding therapy is not well developed. In order to investigate the effects of salvianolic acid (SA) on brain injury caused by CO exposure from the view point of hemorheology, we employed a rat model and studied the dynamic of blood changes in the hemorheological and coagulative properties over acute CO exposure. Compared with the groups of CO and 20% mannitol + CO treatments, the severe hippocampal injury caused by acute CO exposure was prevented by SA treatment. These protective effects were associated with the retaining level of hematocrit (Hct), plasma viscosity, fibrinogen, whole blood viscosities and malondialdehyde (MDA) levels in red blood cells (RBCs). These results indicated that SA treatment could significantly improve the deformation of erythrocytes and prevent the damage caused by CO poisoning. Meanwhile, hemorheological indexes are good indicators for monitoring the pathological dynamic after acute CO poisoning. PMID:25705671

  17. PEG-PDLLA Micelle Treatment Improves Axonal Function of the Corpus Callosum following Traumatic Brain Injury

    PubMed Central

    Ping, Xingjie; Jiang, Kewen; Lee, Seung-Young; Cheng, Ji-Xing

    2014-01-01

    Abstract The initial pathological changes of diffuse axonal injury following traumatic brain injury (TBI) include membrane disruption and loss of ionic homeostasis, which further lead to dysfunction of axonal conduction and axon disconnection. Resealing the axolemma is therefore a potential therapeutic strategy for the early treatment of TBI. Monomethoxy poly (ethylene glycol)-poly (D, L–lactic acid) di-block copolymer micelles (mPEG-PDLLA) have been shown to restore depressed compound action potentials (CAPs) of spinal axons and promote functional recovery after spinal cord injury. Here, we evaluate the effect of the micelles on repairing the injured cortical axons following TBI. Adult mice subjected to controlled cortical impact (CCI) were treated with intravenous injection of the micelles at 0 h or 4 h after injury. Evoked CAPs were recorded from the corpus callosum of coronal cortical slices at 2 days after injury. The CCI caused significant decreases in the amplitudes of two CAP peaks that were respectively generated by the faster myelinated axons and slower unmyelinated axons. Micelle treatment at both 0 h and 4 h after CCI resulted in significant increases in both CAP peak amplitudes. Injection of fluorescent dye-labeled micelles revealed high fluorescent staining in cortical gray and white matters underneath the impact site. Labeling membrane-perforated neurons by injecting a membrane impermeable dye Texas Red-labeled dextran into lateral ventricles at 2 h post-CCI revealed that immediate micelle injection after CCI did not reduce the number of dye-stained cortical neurons and dentate granule cells of the hippocampus, indicating its ineffectiveness in repairing plasma membrane of neuronal somata. We conclude that intravenous administration of mPEG-PDLLA micelles immediately or at 4 h after TBI allows brain penetration via the compromised blood brain–barrier, and thereby improves the function of both myelinated and unmyelinated axons of the

  18. D-Cycloserine improves functional outcome after traumatic brain injury with wide therapeutic window

    SciTech Connect

    Adeleye, A.; Biegon, A.; Adeleye, A.; Shohami, E.; Nachman, D.; Alexandrovich, A.; Trembovler, V.; Yaka, R.; Shoshan, Y.; Dhawan, J.; Biegon, A.

    2009-12-01

    It has been long thought that hyperactivation of N-methyl-D-aspartate (NMDA) receptors underlies neurological decline after traumatic brain injury. However, all clinical trials with NMDA receptor antagonists failed. Since NMDA receptors are down-regulated from 4 h to 2 weeks after brain injury, activation at 24 h, rather than inhibition, of these receptors, was previously shown to be beneficial in mice. Here, we tested the therapeutic window, dose regimen and mechanism of action of the NMDA receptor partial agonist d-cycloserine (DCS) in traumatic brain injury. Male mice were subjected to trauma using a weight-drop model, and administered 10 mg/kg (i.p.) DCS or vehicle once (8, 16, 24, or 72 h) twice (24 and 48 h) or three times (24, 48 and 72 h). Functional recovery was assessed for up to 60 days, using a Neurological Severity Score that measures neurobehavioral parameters. In all groups in which treatment was begun at 24 or 72 h neurobehavioral function was significantly better than in the vehicle-treated groups. Additional doses, on days 2 and 3 did not further improve recovery. Mice treated at 8 h or 16 h post injury did not differ from the vehicle-treated controls. Co-administration of the NMDA receptor antagonist MK-801 completely blocked the protective effect of DCS given at 24 h. Infarct volume measured by 2,3,5-triphenyltetrazolium chloride staining at 48 h or by cresyl violet at 28 days was not affected by DCS treatment. Since DCS is used clinically for other indications, the present study offers a novel approach for treating human traumatic brain injury with a therapeutic window of at least 24 h.

  19. Combining Enriched Environment, Progesterone, and Embryonic Neural Stem Cell Therapy Improves Recovery after Brain Injury.

    PubMed

    Nudi, Evan T; Jacqmain, Justin; Dubbs, Kelsey; Geeck, Katalin; Salois, Garrick; Searles, Madeleine A; Smith, Jeffrey S

    2015-07-15

    Millions of persons every year are affected by traumatic brain injury (TBI), and currently no therapies have shown efficacy in improving outcomes clinically. Recent research has suggested that enriched environments (EE), embryonic neural stem cells (eNSC), and progesterone (PROG) improve functional outcomes after TBI, and further, several investigators have suggested that a polytherapuetic approach may have greater efficacy than a single therapy. The purpose of the current study was to determine if varying combinations of post-injury EE, progesterone therapy, or eNSC transplantation would improve functional outcomes over just a single therapy. A controlled cortical impact was performed in rats to create a lesion in the medial frontal cortex. The rats were then placed in either EE or standard environments and administered 10 mg/kg progesterone or vehicle injections 4 h post-injury and every 12 h for 72 h after the initial injection. Seven days after the surgery, rats were transplanted with either eNSCs or media. Rats were then tested on the open field test, Barnes maze, Morris water maze, and Rotor-Rod tasks. Improved functional outcomes were shown on a majority of the behavioral tasks in animals that received a combination of therapies. This effect was especially prominent with therapies that were combined with EE. Immunohistochemistry showed that the transplanted eNSCs survived, migrated, and displayed neural phenotypes. These data suggest that a poly-therapeutic approach after TBI improves functional recovery to a greater magnitude. Moreover, when polytherapies are combined with EE, the effects on recovery are enhanced, leading to greater recovery of function. PMID:25268854

  20. Dietary Docosahexaenoic Acid Improves Cognitive Function, Tissue Sparing, and Magnetic Resonance Imaging Indices of Edema and White Matter Injury in the Immature Rat after Traumatic Brain Injury.

    PubMed

    Schober, Michelle E; Requena, Daniela F; Abdullah, Osama M; Casper, T Charles; Beachy, Joanna; Malleske, Daniel; Pauly, James R

    2016-02-15

    Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children. Specific therapies to treat acute TBI are lacking. Cognitive impairment from TBI may be blunted by decreasing inflammation and oxidative damage after injury. Docosahexaenoic acid (DHA) decreases cognitive impairment, oxidative stress, and white matter injury in adult rats after TBI. Effects of DHA on cognitive outcome, oxidative stress, and white matter injury in the developing rat after experimental TBI are unknown. We hypothesized that DHA would decrease early inflammatory markers and oxidative stress, and improve cognitive, imaging and histologic outcomes in rat pups after controlled cortical impact (CCI). CCI or sham surgery was delivered to 17 d old male rat pups exposed to DHA or standard diet for the duration of the experiments. DHA was introduced into the dam diet the day before CCI to allow timely DHA delivery to the pre-weanling pups. Inflammatory cytokines and nitrates/nitrites were measured in the injured brains at post-injury Day (PID) 1 and PID2. Morris water maze (MWM) testing was performed at PID41-PID47. T2-weighted and diffusion tensor imaging studies were obtained at PID12 and PID28. Tissue sparing was calculated histologically at PID3 and PID50. DHA did not adversely affect rat survival or weight gain. DHA acutely decreased oxidative stress and increased anti-inflammatory interleukin 10 in CCI brains. DHA improved MWM performance and lesion volume late after injury. At PID12, DHA decreased T2-imaging measures of cerebral edema and decreased radial diffusivity, an index of white matter injury. DHA improved short- and long-term neurologic outcomes after CCI in the rat pup. Given its favorable safety profile, DHA is a promising candidate therapy for pediatric TBI. Further studies are needed to explore neuroprotective mechanisms of DHA after developmental TBI. PMID:26247583

  1. Ketogenic Diet Improves Forelimb Motor Function after Spinal Cord Injury in Rodents

    PubMed Central

    Streijger, Femke; Plunet, Ward T.; Lee, Jae H. T.; Liu, Jie; Lam, Clarrie K.; Park, Soeyun; Hilton, Brett J.; Fransen, Bas L.; Matheson, Keely A. J.; Assinck, Peggy; Kwon, Brian K.; Tetzlaff, Wolfram

    2013-01-01

    High fat, low carbohydrate ketogenic diets (KD) are validated non-pharmacological treatments for some forms of drug-resistant epilepsy. Ketones reduce neuronal excitation and promote neuroprotection. Here, we investigated the efficacy of KD as a treatment for acute cervical spinal cord injury (SCI) in rats. Starting 4 hours following C5 hemi-contusion injury animals were fed either a standard carbohydrate based diet or a KD formulation with lipid to carbohydrate plus protein ratio of 3:1. The forelimb functional recovery was evaluated for 14 weeks, followed by quantitative histopathology. Post-injury 3:1 KD treatment resulted in increased usage and range of motion of the affected forepaw. Furthermore, KD improved pellet retrieval with recovery of wrist and digit movements. Importantly, after returning to a standard diet after 12 weeks of KD treatment, the improved forelimb function remained stable. Histologically, the spinal cords of KD treated animals displayed smaller lesion areas and more grey matter sparing. In addition, KD treatment increased the number of glucose transporter-1 positive blood vessels in the lesion penumbra and monocarboxylate transporter-1 (MCT1) expression. Pharmacological inhibition of MCTs with 4-CIN (α-cyano-4-hydroxycinnamate) prevented the KD-induced neuroprotection after SCI, In conclusion, post-injury KD effectively promotes functional recovery and is neuroprotective after cervical SCI. These beneficial effects require the function of monocarboxylate transporters responsible for ketone uptake and link the observed neuroprotection directly to the function of ketones, which are known to exert neuroprotection by multiple mechanisms. Our data suggest that current clinical nutritional guidelines, which include relatively high carbohydrate contents, should be revisited. PMID:24223849

  2. Enhancing primary care for persons with spinal cord injury: More than improving physical accessibility.

    PubMed

    Milligan, James; Lee, Joseph

    2016-09-01

    In Ontario, Canada, legislation exists that mandates that all medical practices be fully accessible by 2025, in an effort to improve access to primary care for persons with physical disabilities. The simple removal of physical barriers may not guarantee improved access to appropriate care. In this clinical note, members of an interprofessional primary care-based Mobility Clinic reflect on opportunities to improve primary care beyond just better physical accessibility for persons with spinal cord injury (SCI). The importance of collaborations between funders, researchers, and clinicians are examined. Using a participatory action research model, the unique perspective of consumers and consumer networks are incorporated into the Mobility Clinic's clinical and research efforts to improve primary care for persons with SCI. PMID:26111044

  3. Improved Dysphagia After Decannulation of Tracheostomy in Patients With Brain Injuries

    PubMed Central

    Kim, Yong Kyun; Choi, Jung-Hwa; Yoon, Jeong-Gyu; Lee, Jang-Won

    2015-01-01

    Objective To investigate improved dysphagia after the decannulation of a tracheostomy in patients with brain injuries. Methods The subjects of this study are patients with brain injuries who were admitted to the Department of Rehabilitation Medicine in Myongji Hospital and who underwent a decannulation between 2012 and 2014. A video fluoroscopic swallowing study (VFSS) was performed in order to investigate whether the patients' dysphagia had improved. We measured the following 5 parameters: laryngeal elevation, pharyngeal transit time, post-swallow pharyngeal remnant, upper esophageal width, and semisolid aspiration. We analyzed the patients' results from VFSS performed one month before and one month after decannulation. All VFSS images were recorded using a camcorder running at 30 frames per second. An AutoCAD 2D screen was used to measure laryngeal elevation, post-swallow pharyngeal remnant, and upper esophageal width. Results In this study, a number of dysphagia symptoms improved after decannulation. Laryngeal elevation, pharyngeal transit time, and semisolid aspiration showed no statistically significant differences (p>0.05), however after decannulation, the post-swallow pharyngeal remnant (pre 37.41%±24.80%, post 21.02%±11.75%; p<0.001) and upper esophageal width (pre 3.57±1.93 mm, post 4.53±2.05 mm; p<0.001) showed statistically significant differences. Conclusion When decannulation is performed on patients with brain injuries who do not require a ventilator and who are able to independently excrete sputum, improved esophageal dysphagia can be expected. PMID:26605176

  4. Wharton's jelly transplantation improves neurologic function in a rat model of traumatic brain injury

    PubMed Central

    Cheng, Tian; Yang, Bo; Li, Dongpeng; Ma, Shanshan; Tian, Yi; Qu, Ruina; Zhang, Wenjin; Zhang, Yanting; Hu, Kai; Guan, Fangxia; Wang, Jian

    2015-01-01

    Traumatic brain injury (TBI), which can lead to disability, dysfunction, and even death, is a prominent health problem worldwide. Effective therapy for this serious and debilitating condition is needed. Human umbilical cord matrix, known as Wharton's jelly (WJ), provides a natural, interface scaffold that is enriched in mesenchymal stem cells. In this study, we tested the efficacy of WJ tissue transplantation in a weight drop model of TBI in rats. WJ tissue was cultured and transplanted into the injury site 24h after TBI. The modified neurologic severity score, body weight, brain edema, and lesion volume were evaluated at various time points after TBI. Cognitive behavior was assessed by the novel object recognition test and the Morris water maze test. Expression of brain-derived neurotrophic factor (BDNF) in the perilesional brain area was measured at day 14 after TBI. We found that WJ tissue transplantation lessened TBI-induced brain edema (day 3), reduced lesion volume (day 28), improved neurologic function (days 21 to 28), and promoted memory and cognitive recovery. Additionally, expression of BDNF mRNA and protein was higher in WJ tissue-treated rats than in sham-operated or vehicle-treated rats. These data suggest that WJ tissue transplantation can reduce TBI-induced brain injury and may have therapeutic potential for the treatment of TBI. PMID:25638565

  5. Voluntary Exercise Preconditioning Activates Multiple Antiapoptotic Mechanisms and Improves Neurological Recovery after Experimental Traumatic Brain Injury

    PubMed Central

    Zhao, Zaorui; Sabirzhanov, Boris; Wu, Junfang; Faden, Alan I.

    2015-01-01

    Abstract Physical activity can attenuate neuronal loss, reduce neuroinflammation, and facilitate recovery after brain injury. However, little is known about the mechanisms of exercise-induced neuroprotection after traumatic brain injury (TBI) or its modulation of post-traumatic neuronal cell death. Voluntary exercise, using a running wheel, was conducted for 4 weeks immediately preceding (preconditioning) moderate-level controlled cortical impact (CCI), a well-established experimental TBI model in mice. Compared to nonexercised controls, exercise preconditioning (pre-exercise) improved recovery of sensorimotor performance in the beam walk task, as well as cognitive/affective functions in the Morris water maze, novel object recognition, and tail-suspension tests. Further, pre-exercise reduced lesion size, attenuated neuronal loss in the hippocampus, cortex, and thalamus, and decreased microglial activation in the cortex. In addition, exercise preconditioning activated the brain-derived neurotrophic factor pathway before trauma and amplified the injury-dependent increase in heat shock protein 70 expression, thus attenuating key apoptotic pathways. The latter include reduction in CCI-induced up-regulation of proapoptotic B-cell lymphoma 2 (Bcl-2)-homology 3–only Bcl-2 family molecules (Bid, Puma), decreased mitochondria permeabilization with attenuated release of cytochrome c and apoptosis-inducing factor (AIF), reduced AIF translocation to the nucleus, and attenuated caspase activation. Given these neuroprotective actions, voluntary physical exercise may serve to limit the consequences of TBI. PMID:25419789

  6. Improving Client-Centered Brain Injury Rehabilitation Through Research-Based Theater

    PubMed Central

    Kontos, Pia C.; Miller, Karen-Lee; Gilbert, Julie E.; Mitchell, Gail J.; Colantonio, Angela; Keightley, Michelle L.; Cott, Cheryl

    2013-01-01

    Traumatic brain injury often results in physical, behavioral, and cognitive impairments perceived by health care practitioners to limit or exclude clients’ full participation in treatment decision making. We used qualitative methods to evaluate the short- and long-term impact of “After the Crash: A Play About Brain Injury”, a research-based drama designed to teach client-centered care principles to brain injury rehabilitation staff. We conducted interviews and observations with staff of two inpatient neurorehabilitation units in Ontario, Canada. Findings demonstrate the effectiveness of the play in influencing practice through the avoidance of medical jargon to improve clients’ understanding and participation in treatment; newfound appreciation for clients’ needs for emotional expression and sexual intimacy; increased involvement of family caregivers; and avoidance of staff discussions as if clients were unaware. These findings suggest that research-based drama can effect reflexivity, empathy, and practice change to facilitate a client-centered culture of practice in brain injury rehabilitation. PMID:22941919

  7. Improving self-efficacy in spinal cord injury patients through “design thinking" rehabilitation workshops

    PubMed Central

    Wolstenholme, Daniel; Downes, Tom; Leaver, Jackie; Partridge, Rebecca; Langley, Joseph

    2014-01-01

    Advances in surgical and medical management have significantly reduced the length of time that patients with spinal cord injury (SCI) have to stay in hospital, but has left patients with potentially less time to psychologically adjust. Following a pilot in 2012, this project was designed to test the effect of “design thinking” workshops on the self-efficacy of people undergoing rehabilitation following spinal injuries. Design thinking is about understanding the approaches and methods that designers use and then applying these to think creatively about problems and suggest ways to solve them. In this instance, design thinking is not about designing new products (although the approaches can be used to do this) but about developing a long term creative and explorative mind-set through skills such as lateral thinking, prototyping and verbal and visual communication. The principles of “design thinking” have underpinned design education and practice for many years, it is also recognised in business and innovation for example, but a literature review indicated that there was no evidence of it being used in rehabilitation or spinal injury settings. Twenty participants took part in the study; 13 (65%) were male and the average age was 37 years (range 16 to 72). Statistically significant improvements were seen for EQ-5D score (t = -3.13, p = 0.007) and Patient Activation Measure score (t = -3.85, p = 0.001). Other outcome measures improved but not statistically. There were no statistical effects on length of stay or readmission rates, but qualitative interviews indicated improved patient experience. PMID:27493735

  8. Biological Approaches to Improve Skeletal Muscle Healing after Injury and Disease

    PubMed Central

    Gharaibeh, Burhan; Chun-Lansinger, Yuri; Hagen, Tanya; Ingham, Sheila Jean McNeill; Wright, Vonda; Fu, Freddie; Huard, Johnny

    2015-01-01

    Skeletal muscle injury and repair are complex processes, including well-coordinated steps of degeneration, inflammation, regeneration, and fibrosis. We have reviewed the recent literature including studies by our group that describe how to modulate the processes of skeletal muscle repair and regeneration. Antiinflammatory drugs that target cyclooxy-genase-2 were found to hamper the skeletal muscle repair process. Muscle regeneration phase can be aided by growth factors, including insulin-like growth factor-1 and nerve growth factor, but these factors are typically short-lived, and thus more effective methods of delivery are needed. Skeletal muscle damage caused by traumatic injury or genetic diseases can benefit from cell therapy; however, the majority of transplanted muscle cells (myoblasts) are unable to survive the immune response and hypoxic conditions. Our group has isolated neonatal skeletal muscle derived stem cells (MDSCs) that appear to repair muscle tissue in a more effective manner than myoblasts, most likely due to their better resistance to oxidative stress. Enhancing antioxidant levels of MDSCs led to improved regenerative potential. It is becoming increasingly clear that stem cells tissue repair by direct differentiation and paracrine effects leading to neovascularization of injured site and chemoattraction of host cells. The factors invoked in paracrine action are still under investigation. Our group has found that angiotensin II receptor blocker (losartan) significantly reduces fibrotic tissue formation and improves repair of murine injured muscle. Based on these data, we have conducted a case study on two hamstring injury patients and found that losartan treatment was well tolerated and possibly improved recovery time. We believe this medication holds great promise to optimize muscle repair in humans. PMID:22457179

  9. Platelet-rich plasma treatment improves outcomes for chronic proximal hamstring injuries in an athletic population

    PubMed Central

    Fader, Ryan R.; Mitchell, Justin J.; Traub, Shaun; Nichols, Roger; Roper, Michelle; Mei Dan, Omer; McCarty, Eric C.

    2014-01-01

    Summary Background: chronic proximal hamstring tendinopathies is a disabling activity related condition. Currently, there is no well-accepted or extensively documented non-operative treatment option that provides consistently successful results. Purpose: to evaluate the efficacy of ultrasound guided platelet-rich plasma injections in treating chronic proximal hamstring tendinopathies. Methods: a total of 18 consecutive patients were retrospectively analyzed. All patients received a single injection of platelet rich plasma via ultra-sound guidance by a single radiologist. Outcome measures included a questionnaire evaluating previous treatments, visual analog scale (VAS) for pain, subjective improvement, history of injury, and return to activity. Results: the patient population included 12 females and 6 males. The average age at the time of the injection was 42.6 years (19–60). Provocative activities included running, biking, swimming. The average body mass index of patients was 22.9 (17.2–30.2). The average time of chronic pain prior to receiving the first injection was 32.6 months (6–120). All patients had attempted other forms of non-surgical treatment prior to entering the study. The average VAS pre-injection was 4.6 (0–8). Six months after the injection, 10/18 patients had 80% or greater improvement in their VAS. Overall, the average improvement was 63% (5–100). The only documented side effect was post-injection discomfort that resolved within seventy-two hours. Conclusion: chronic hamstring tendinopathy is a debilitating condition secondary to the pain, which limits an athlete’s ability to perform. For refractory cases of chronic insertional proximal hamstring injuries, platelet-rich plasma injections are safe and show benefit in the majority of patients in our study, allowing return to pre-injury activities. Study Design: Case series; Level of evidence, 4. PMID:25767784

  10. Improving self-efficacy in spinal cord injury patients through "design thinking" rehabilitation workshops.

    PubMed

    Wolstenholme, Daniel; Downes, Tom; Leaver, Jackie; Partridge, Rebecca; Langley, Joseph

    2014-01-01

    Advances in surgical and medical management have significantly reduced the length of time that patients with spinal cord injury (SCI) have to stay in hospital, but has left patients with potentially less time to psychologically adjust. Following a pilot in 2012, this project was designed to test the effect of "design thinking" workshops on the self-efficacy of people undergoing rehabilitation following spinal injuries. Design thinking is about understanding the approaches and methods that designers use and then applying these to think creatively about problems and suggest ways to solve them. In this instance, design thinking is not about designing new products (although the approaches can be used to do this) but about developing a long term creative and explorative mind-set through skills such as lateral thinking, prototyping and verbal and visual communication. The principles of "design thinking" have underpinned design education and practice for many years, it is also recognised in business and innovation for example, but a literature review indicated that there was no evidence of it being used in rehabilitation or spinal injury settings. Twenty participants took part in the study; 13 (65%) were male and the average age was 37 years (range 16 to 72). Statistically significant improvements were seen for EQ-5D score (t = -3.13, p = 0.007) and Patient Activation Measure score (t = -3.85, p = 0.001). Other outcome measures improved but not statistically. There were no statistical effects on length of stay or readmission rates, but qualitative interviews indicated improved patient experience. PMID:27493735

  11. Standardizing ICU management of pediatric traumatic brain injury is associated with improved outcomes at discharge.

    PubMed

    O'Lynnger, Thomas M; Shannon, Chevis N; Le, Truc M; Greeno, Amber; Chung, Dai; Lamb, Fred S; Wellons, John C

    2016-01-01

    OBJECT The goal of critical care in treating traumatic brain injury (TBI) is to reduce secondary brain injury by limiting cerebral ischemia and optimizing cerebral blood flow. The authors compared short-term outcomes as defined by discharge disposition and Glasgow Outcome Scale scores in children with TBI before and after the implementation of a protocol that standardized decision-making and interventions among neurosurgeons and pediatric intensivists. METHODS The authors performed a retrospective pre- and postprotocol study of 128 pediatric patients with severe TBI, as defined by Glasgow Coma Scale (GCS) scores < 8, admitted to a tertiary care center pediatric critical care unit between April 1, 2008, and May 31, 2014. The preprotocol group included 99 patients, and the postprotocol group included 29 patients. The primary outcome of interest was discharge disposition before and after protocol implementation, which took place on April 1, 2013. Ordered logistic regression was used to assess outcomes while accounting for injury severity and clinical parameters. Favorable discharge disposition included discharge home. Unfavorable discharge disposition included discharge to an inpatient facility or death. RESULTS Demographics were similar between the treatment periods, as was injury severity as assessed by GCS score (mean 5.43 preprotocol, mean 5.28 postprotocol; p = 0.67). The ordered logistic regression model demonstrated an odds ratio of 4.0 of increasingly favorable outcome in the postprotocol cohort (p = 0.007). Prior to protocol implementation, 63 patients (64%) had unfavorable discharge disposition and 36 patients (36%) had favorable discharge disposition. After protocol implementation, 9 patients (31%) had unfavorable disposition, while 20 patients (69%) had favorable disposition (p = 0.002). In the preprotocol group, 31 patients (31%) died while 6 patients (21%) died after protocol implementation (p = 0.04). CONCLUSIONS Discharge disposition and mortality

  12. Targeting the thrombin receptor modulates inflammation and astrogliosis to improve recovery after spinal cord injury.

    PubMed

    Radulovic, Maja; Yoon, Hyesook; Wu, Jianmin; Mustafa, Karim; Scarisbrick, Isobel A

    2016-09-01

    The deregulation of serine protease activity is a common feature of neurological injury, but little is known regarding their mechanisms of action or whether they can be targeted to facilitate repair. In this study we demonstrate that the thrombin receptor (Protease Activated Receptor 1, (PAR1)) serves as a critical translator of the spinal cord injury (SCI) proteolytic microenvironment into a cascade of pro-inflammatory events that contribute to astrogliosis and functional decline. PAR1 knockout mice displayed improved locomotor recovery after SCI and reduced signatures of inflammation and astrogliosis, including expression of glial fibrillary acidic protein (GFAP), vimentin, and STAT3 signaling. SCI-associated elevations in pro-inflammatory cytokines such as IL-1β and IL-6 were also reduced in PAR1-/- mice and co-ordinate improvements in tissue sparing and preservation of NeuN-positive ventral horn neurons, and PKCγ corticospinal axons, were observed. PAR1 and its agonist's thrombin and neurosin were expressed by perilesional astrocytes and each agonist increased the production of IL-6 and STAT3 signaling in primary astrocyte cultures in a PAR1-dependent manner. In turn, IL-6-stimulated astrocytes increased expression of PAR1, thrombin, and neurosin, pointing to a model in which PAR1 activation contributes to increased astrogliosis by feedforward- and feedback-signaling dynamics. Collectively, these findings identify the thrombin receptor as a key mediator of inflammation and astrogliosis in the aftermath of SCI that can be targeted to reduce neurodegeneration and improve neurobehavioral recovery. PMID:27145117

  13. Autophagy Modulation by Lanthionine Ketimine Ethyl Ester Improves Long-Term Outcome after Central Fluid Percussion Injury in the Mouse.

    PubMed

    Hensley, Kenneth; Poteshkina, Aleksandra; Johnson, Ming F; Eslami, Pirooz; Gabbita, S Prasad; Hristov, Alexandar M; Venkova-Hristova, Kalina M; Harris-White, Marni E

    2016-08-15

    Diffuse axonal injury is recognized as a progressive and long-term consequence of traumatic brain injury. Axonal injury can have sustained negative consequences on neuronal functions such as anterograde and retrograde transport and cellular processes such as autophagy that depend on cytoarchitecture and axon integrity. These changes can lead to somatic atrophy and an inability to repair and promote plasticity. Obstruction of the autophagic process has been noted after brain injury, and rapamycin, a drug used to stimulate autophagy, has demonstrated positive effects in brain injury models. The optimization of drugs to promote beneficial autophagy without negative side effects could be used to attenuate traumatic brain injury and promote improved outcome. Lanthionine ketimine ethyl ester, a bioavailable derivative of a natural sulfur amino acid metabolite, has demonstrated effects on autophagy both in vitro and in vivo. Thirty minutes after a moderate central fluid percussion injury and throughout the survival period, lanthionine ketimine ethyl ester was administered, and mice were subsequently evaluated for learning and memory impairments and biochemical and histological changes over a 5-week period. Lanthionine ketimine ethyl ester, which we have shown previously to modulate autophagy markers and alleviate pathology and slow cognitive decline in the 3 × TgAD mouse model, spared cognition and pathology after central fluid percussion injury through a mechanism involving autophagy modulation. PMID:26530250

  14. Myelin Basic Protein Cleaves Cell Adhesion Molecule L1 and Improves Regeneration After Injury.

    PubMed

    Lutz, David; Kataria, Hardeep; Kleene, Ralf; Loers, Gabriele; Chaudhary, Harshita; Guseva, Daria; Wu, Bin; Jakovcevski, Igor; Schachner, Melitta

    2016-07-01

    Myelin basic protein (MBP) is a serine protease that cleaves neural cell adhesion molecule L1 and generates a transmembrane L1 fragment which facilitates L1-dependent functions in vitro, such as neurite outgrowth, neuronal cell migration and survival, myelination by Schwann cells as well as Schwann cell proliferation, migration, and process formation. Ablation and blocking of MBP or disruption of its proteolytic activity by mutation of a proteolytically active serine residue abolish L1-dependent cellular responses. In utero injection of adeno-associated virus encoding proteolytically active MBP into MBP-deficient shiverer mice normalizes differentiation, myelination, and synaptogenesis in the developing postnatal spinal cord, in contrast to proteolytically inactive MBP. Application of active MBP to the injured wild-type spinal cord and femoral nerve augments levels of a transmembrane L1 fragment, promotes remyelination, and improves functional recovery after injury. Application of MBP antibody impairs recovery. Virus-mediated expression of active MBP in the lesion site after spinal cord injury results in improved functional recovery, whereas injection of virus encoding proteolytically inactive MBP fails to do so. The present study provides evidence for a novel L1-mediated function of MBP in the developing spinal cord and in the injured adult mammalian nervous system that leads to enhanced recovery after acute trauma. PMID:26081148

  15. Assessing the socioeconomic impact of improved treatment of head and spinal cord injuries.

    PubMed

    Berkowitz, M

    1993-01-01

    Assessment of improved treatment of neurotrauma presents two basic challenges: 1) measurement of the medical effects of treatment, and 2) evaluation of these effects in socioeconomic terms. A nationwide survey was conducted in 1988 to estimate the prevalence of persons in the United States who suffered traumatic spinal cord injury and to calculate its economic consequences. Seven hundred fifty-eight persons weighted to be representative of the spinal cord injury population were interviewed. The prevalence rate was found to be 721 cases per million people. Conservative calculations for 1988 showed that the average direct costs per person were $103,000 for hospitalization and home modifications during the first 2 years postinjury and $14,000 per year thereafter for medical care. Losses in earnings and homemaker services averaged $12,726 per year. Total aggregate costs for 1 year were estimated at $5.6 billion. Lifetime costs for a representative person with complete paraplegia injured at age 33 were estimated to be $500,000. For a representative person with complete quadriplegia injured at age 27, these costs amounted to $1 million. These data can be used to estimate cost savings related to decreased disability resulting from improved treatment. PMID:8445206

  16. Evaluation of a complex, population-based injury claims management intervention for improving injury outcomes: study protocol

    PubMed Central

    Collie, Alex; Gabbe, Belinda; Fitzharris, Michael

    2015-01-01

    Introduction Injuries resulting from road traffic crashes are a substantial cause of disability and death worldwide. Injured persons receiving compensation have poorer recovery and return to work than those with non-compensable injury. Case or claims management is a critical component of injury compensation systems, and there is now evidence that claims management can have powerful positive impacts on recovery, but can also impede recovery or exacerbate mental health concerns in some injured people. This study seeks to evaluate the impact of a population-based injury claims management intervention in the State of Victoria, Australia, on the health of those injured in motor vehicle crashes, their experience of the compensation process, and the financial viability of the compensation system. Methods and analysis Evaluation of this complex intervention involves a series of linked but stand-alone research projects to assess the anticipated process changes, impacts and outcomes of the intervention over a 5-year time frame. Linkage and analysis of routine administrative and health system data is supplemented with a series of primary studies collecting new information. Additionally, a series of ‘action’ research projects will be undertaken to inform the implementation of the intervention. A program logic model designed by the state government Transport Accident Commission in conjunction with the research team provides the evaluation framework. Ethics and dissemination Relatively few studies have comprehensively examined the impact of compensation system processes on the health of injured persons, their satisfaction with systems processes, and impacts on the financial performance of the compensation scheme itself. The wholesale, population-based transformation of an injury claims management model is a rare opportunity to document impacts of system-level policy change on outcomes of injured persons. Findings will contribute to the evidence base of information on the

  17. Fifth Graders' Story Dramatizations during Literature Study.

    ERIC Educational Resources Information Center

    Siddall, Jeffery L.

    Dramatizations as a response activity during literature study provide a vehicle for students to use language, both verbal and nonverbal, in an educational context. A study focused on a group of five students who chose to use story dramatizations as one way to create their interpretations of the book, "The Slave Dancer" (Fox, 1973). The study,…

  18. Dramatic Play in Childhood: Rehearsal for Life.

    ERIC Educational Resources Information Center

    Koste, Virginia Glasgow

    The purpose of this book is to help parents and teachers recognize and understand dramatic play in childhood as a process whereby the child acts out human experience in an attempt to order, clarify, and understand it. Written by a person experienced in theatre and drama, the book considers the following aspects of dramatic play: the importance of…

  19. Burn injury diagnostic imaging device's accuracy improved by outlier detection and removal

    NASA Astrophysics Data System (ADS)

    Li, Weizhi; Mo, Weirong; Zhang, Xu; Lu, Yang; Squiers, John J.; Sellke, Eric W.; Fan, Wensheng; DiMaio, J. Michael; Thatcher, Jeffery E.

    2015-05-01

    Multispectral imaging (MSI) was implemented to develop a burn diagnostic device that will assist burn surgeons in planning and performing burn debridement surgery by classifying burn tissue. In order to build a burn classification model, training data that accurately represents the burn tissue is needed. Acquiring accurate training data is difficult, in part because the labeling of raw MSI data to the appropriate tissue classes is prone to errors. We hypothesized that these difficulties could be surmounted by removing outliers from the training dataset, leading to an improvement in the classification accuracy. A swine burn model was developed to build an initial MSI training database and study an algorithm's ability to classify clinically important tissues present in a burn injury. Once the ground-truth database was generated from the swine images, we then developed a multi-stage method based on Z-test and univariate analysis to detect and remove outliers from the training dataset. Using 10-fold cross validation, we compared the algorithm's accuracy when trained with and without the presence of outliers. The outlier detection and removal method reduced the variance of the training data from wavelength space, and test accuracy was improved from 63% to 76%. Establishing this simple method of conditioning for the training data improved the accuracy of the algorithm to match the current standard of care in burn injury assessment. Given that there are few burn surgeons and burn care facilities in the United States, this technology is expected to improve the standard of burn care for burn patients with less access to specialized facilities.

  20. Acetyl-L-Carnitine Treatment Following Spinal Cord Injury Improves Mitochondrial Function Correlated with Remarkable Tissue Sparing and Functional Recovery

    PubMed Central

    Patel, Samir P.; Sullivan, Patrick G.; Lyttle, Travis S.; Magnuson, David S. K.; Rabchevsky, Alexander G.

    2012-01-01

    We have recently documented that treatment with the alternative biofuel, acetyl-l-carnitine (ALC, 300 mg/kg), as late as 1 hr after T10 contusion spinal cord injury (SCI), significantly maintained mitochondrial function 24 hrs after injury. Here we report that following more severe contusion SCI centered on the L1/L2 segments that are postulated to contain lamina X neurons critical for locomotion (the “central pattern generator”), ALC treatment resulted in significant improvements in acute mitochondrial bioenergetics and long-term hindlimb function. While control-injured rats were only able to achieve slight movements of hindlimb joints, ALC-treated animals produced consistent weight-supported plantar steps one month after injury. Such landmark behavioral improvements were significantly correlated with increased tissue sparing of both gray and white matter proximal to the injury, as well as preservation of choline acetyltransferase (ChAT)-positive neurons in lamina X rostral to the injury site. These findings signify that functional improvements with ALC treatment are mediated, in part, by preserved locomotor circuitry rostral to upper lumbar contusion SCI. Based on beneficial effects of ALC on mitochondrial bioenergetics after injury, our collective evidence demonstrate that preventing mitochondrial dysfunction acutely “promotes” neuroprotection that may be associated with the milestone recovery of plantar, weight-supported stepping. PMID:22445934

  1. Docosahexaenoic Acid Pretreatment Confers Protection and Functional Improvements after Acute Spinal Cord Injury in Adult Rats

    PubMed Central

    Figueroa, Johnny D.; Cordero, Kathia; Baldeosingh, Keisha; Torrado, Aranza I.; Walker, Robert L.; Miranda, Jorge D.

    2012-01-01

    Abstract Currently, few interventions have been shown to successfully limit the progression of secondary damage events associated with the acute phase of spinal cord injury (SCI). Docosahexaenoic acid (DHA, C22:6 n-3) is neuroprotective when administered following SCI, but its potential as a pretreatment modality has not been addressed. This study used a novel DHA pretreatment experimental paradigm that targets acute cellular and molecular events during the first week after SCI in rats. We found that DHA pretreatment reduced functional deficits during the acute phase of injury, as shown by significant improvements in Basso-Beattie-Bresnahan (BBB) locomotor scores, and the detection of transcranial magnetic motor evoked potentials (tcMMEPs) compared to vehicle-pretreated animals. We demonstrated that, at 7 days post-injury, DHA pretreatment significantly increased the percentage of white matter sparing, and resulted in axonal preservation, compared to the vehicle injections. We found a significant increase in the survival of NG2+, APC+, and NeuN+ cells in the ventrolateral funiculus (VLF), dorsal corticospinal tract (dCST), and ventral horns, respectively. Interestingly, these DHA protective effects were observed despite the lack of inhibition of inflammatory markers for monocytes/macrophages and astrocytes, ED1/OX42 and GFAP, respectively. DHA pretreatment induced levels of Akt and cyclic AMP responsive element binding protein (CREB) mRNA and protein. This study shows for the first time that DHA pretreatment ameliorates functional deficits, and increases tissue sparing and precursor cell survival. Further, our data suggest that DHA-mediated activation of pro-survival/anti-apoptotic pathways may be independent of its anti-inflammatory effects. PMID:21970623

  2. An Intensive Locomotor Training Paradigm Improves Neuropathic Pain following Spinal Cord Compression Injury in Rats.

    PubMed

    Dugan, Elizabeth A; Sagen, Jacqueline

    2015-05-01

    Spinal cord injury (SCI) is often associated with both locomotor deficits and sensory dysfunction, including debilitating neuropathic pain. Unfortunately, current conventional pharmacological, physiological, or psychological treatments provide only marginal relief for more than two-thirds of patients, highlighting the need for improved treatment options. Locomotor training is often prescribed as an adjunct therapy for peripheral neuropathic pain but is rarely used to treat central neuropathic pain. The goal of this study was to evaluate the potential anti-nociceptive benefits of intensive locomotor training (ILT) on neuropathic pain consequent to traumatic SCI. Using a rodent SCI model for central neuropathic pain, ILT was initiated either 5 d after injury prior to development of neuropathic pain symptoms (the "prevention" group) or delayed until pain symptoms fully developed (∼3 weeks post-injury, the "reversal" group). The training protocol consisted of 5 d/week of a ramping protocol that started with 11 m/min for 5 min and increased in speed (+1 m/min/week) and time (1-4 minutes/week) to a maximum of two 20-min sessions/d at 15 m/min by the fourth week of training. ILT prevented and reversed the development of heat hyperalgesia and cold allodynia, as well as reversed developed tactile allodynia, suggesting analgesic benefits not seen with moderate levels of locomotor training. Further, the analgesic benefits of ILT persisted for several weeks once training had been stopped. The unique ability of an ILT protocol to produce robust and sustained anti-nociceptive effects, as assessed by three distinct outcome measures for below-level SCI neuropathic pain, suggests that this adjunct therapeutic approach has great promise in a comprehensive treatment strategy for SCI pain. PMID:25539034

  3. Docosahexaenoic acid pretreatment confers protection and functional improvements after acute spinal cord injury in adult rats.

    PubMed

    Figueroa, Johnny D; Cordero, Kathia; Baldeosingh, Keisha; Torrado, Aranza I; Walker, Robert L; Miranda, Jorge D; Leon, Marino De

    2012-02-10

    Currently, few interventions have been shown to successfully limit the progression of secondary damage events associated with the acute phase of spinal cord injury (SCI). Docosahexaenoic acid (DHA, C22:6 n-3) is neuroprotective when administered following SCI, but its potential as a pretreatment modality has not been addressed. This study used a novel DHA pretreatment experimental paradigm that targets acute cellular and molecular events during the first week after SCI in rats. We found that DHA pretreatment reduced functional deficits during the acute phase of injury, as shown by significant improvements in Basso-Beattie-Bresnahan (BBB) locomotor scores, and the detection of transcranial magnetic motor evoked potentials (tcMMEPs) compared to vehicle-pretreated animals. We demonstrated that, at 7 days post-injury, DHA pretreatment significantly increased the percentage of white matter sparing, and resulted in axonal preservation, compared to the vehicle injections. We found a significant increase in the survival of NG2+, APC+, and NeuN+ cells in the ventrolateral funiculus (VLF), dorsal corticospinal tract (dCST), and ventral horns, respectively. Interestingly, these DHA protective effects were observed despite the lack of inhibition of inflammatory markers for monocytes/macrophages and astrocytes, ED1/OX42 and GFAP, respectively. DHA pretreatment induced levels of Akt and cyclic AMP responsive element binding protein (CREB) mRNA and protein. This study shows for the first time that DHA pretreatment ameliorates functional deficits, and increases tissue sparing and precursor cell survival. Further, our data suggest that DHA-mediated activation of pro-survival/anti-apoptotic pathways may be independent of its anti-inflammatory effects. PMID:21970623

  4. Multiple nontuberculous scrofulodermas showing dramatic response to clarithromycin.

    PubMed

    Parimalam, Kumar; Senthil, G; Vinnarasan, M; Arumugakani, V; Amutha, B M; Lalitha, S; Swarna, S

    2015-01-01

    Atypical mycobacteria are distinct from the Mycobacterium tuberculosis. Mycobacterium chelonae, a non-pigment producing rapid grower, can be found in many cutaneous sites; infection occurs most commonly after skin trauma from surgery, injections, or minor injuries. In immune competent patients, the infection is more frequently localized as a cellulitis or a nodule, whereas, in the immunocompromised patient, dissemination (more than five lesions) can occur. Because the organism is resistant to antituberculous therapy, abscess can develop and follow a chronic, indolent course. We report a case of multiple scrofuloderma due to nontuberculous infection caused by M. chelonae showing dramatic response to clarithromycin. PMID:25657914

  5. Partial liquid ventilation improves lung function in ventilation-induced lung injury.

    PubMed

    Vazquez de Anda, G F; Lachmann, R A; Verbrugge, S J; Gommers, D; Haitsma, J J; Lachmann, B

    2001-07-01

    Disturbances in lung function and lung mechanics are present after ventilation with high peak inspiratory pressures (PIP) and low levels of positive end-expiratory pressure (PEEP). Therefore, the authors investigated whether partial liquid ventilation can re-establish lung function after ventilation-induced lung injury. Adult rats were exposed to high PIP without PEEP for 20 min. Thereafter, the animals were randomly divided into five groups. The first group was killed immediately after randomization and used as an untreated control. The second group received only sham treatment and ventilation, and three groups received treatment with perfluorocarbon (10 mL x kg(-1), 20 mL x kg(-1), and 20 ml x kg(-1) plus an additional 5 mL x kg(-1) after 1 h). The four groups were maintained on mechanical ventilation for a further 2-h observation period. Blood gases, lung mechanics, total protein concentration, minimal surface tension, and small/large surfactant aggregates ratio were determined. The results show that in ventilation-induced lung injury, partial liquid ventilation with different amounts of perflubron improves gas exchange and pulmonary function, when compared to a group of animals treated with standard respiratory care. These effects have been observed despite the presence of a high intra-alveolar protein concentration, especially in those groups treated with 10 and 20 mL of perflubron. The data suggest that replacement of perfluorocarbon, lost over time, is crucial to maintain the constant effects of partial liquid ventilation. PMID:11510811

  6. The Development of Macrophage-Mediated Cell Therapy to Improve Skeletal Muscle Function after Injury

    PubMed Central

    Rybalko, Viktoriya; Hsieh, Pei-Ling; Merscham-Banda, Melissa; Suggs, Laura J.; Farrar, Roger P.

    2015-01-01

    Skeletal muscle regeneration following acute injury is a multi-step process involving complex changes in tissue microenvironment. Macrophages (MPs) are one of the key cell types involved in orchestration and modulation of the repair process. Multiple studies highlight the essential role of MPs in the control of the myogenic program and inflammatory response during skeletal muscle regeneration. A variety of MP phenotypes have been identified and characterized in vitro as well as in vivo. As such, MPs hold great promise for cell-based therapies in the field of regenerative medicine. In this study we used bone-marrow derived in vitro LPS/IFN-y-induced M1 MPs to enhance functional muscle recovery after tourniquet-induced ischemia/reperfusion injury (TK-I/R). We detected a 15% improvement in specific tension and force normalized to mass after M1 (LPS/IFN-γ) MP transplantation 24 hours post-reperfusion. Interestingly, we found that M0 bone marrow-derived unpolarized MPs significantly impaired muscle function highlighting the complexity of temporally coordinated skeletal muscle regenerative program. Furthermore, we show that delivery of M1 (LPS/IFN-γ) MPs early in regeneration accelerates myofiber repair, decreases fibrotic tissue deposition and increases whole muscle IGF-I expression. PMID:26717325

  7. Pretreatment with mangafodipir improves liver graft tolerance to ischemia/reperfusion injury in rat.

    PubMed

    Ben Mosbah, Ismail; Mouchel, Yann; Pajaud, Julie; Ribault, Catherine; Lucas, Catherine; Laurent, Alexis; Boudjema, Karim; Morel, Fabrice; Corlu, Anne; Compagnon, Philippe

    2012-01-01

    Ischemia/reperfusion injury occurring during liver transplantation is mainly due to the generation of reactive oxygen species (ROS) upon revascularization. Thus, delivery of antioxidant enzymes might reduce the deleterious effects of ROS and improve liver graft initial function. Mangafodipir trisodium (MnDPDP), a contrast agent currently used in magnetic resonance imaging of the liver, has been shown to be endowed with powerful antioxidant properties. We hypothesized that MnDPDP could have a protective effect against liver ischemia reperfusion injury when administrated to the donor prior to harvesting. Livers from Sprague Dawley rats pretreated or not with MnDPDP were harvested and subsequently preserved for 24 h in Celsior® solution at 4°C. Organs were then perfused ex vivo for 120 min at 37°C with Krebs Henseleit solution. In MnDPDP (5 µmol/kg) group, we observed that ATP content was significantly higher at the end of the cold preservation period relative to untreated group. After reperfusion, livers from MnDPDP-treated rats showed better tissue integrity, less hepatocellular and endothelial cell injury. This was accompanied by larger amounts of bile production and higher ATP recovery as compared to untreated livers. The protective effect of MnDPDP was associated with a significant decrease of lipid peroxidation, mitochondrial damage, and apoptosis. Interestingly, MnDPDP-pretreated livers exhibited activation of Nfr2 and HIF-1α pathways resulting in a higher catalase and HO-1 activities. MnDPDP also increased total nitric oxide (NO) production which derived from higher expression of constitutive NO synthase and lower expression of inducible NO synthase. In conclusion, our results show that donor pretreatment with MnDPDP protects the rat liver graft from cold ischemia/reperfusion injury and demonstrate for the first time the potential interest of this molecule in the field of organ preservation. Since MnDPDP is safely used in liver imaging, this preservation

  8. Pretreatment with Mangafodipir Improves Liver Graft Tolerance to Ischemia/Reperfusion Injury in Rat

    PubMed Central

    Ben Mosbah, Ismail; Mouchel, Yann; Pajaud, Julie; Ribault, Catherine; Lucas, Catherine; Laurent, Alexis; Boudjema, Karim; Morel, Fabrice

    2012-01-01

    Ischemia/reperfusion injury occurring during liver transplantation is mainly due to the generation of reactive oxygen species (ROS) upon revascularization. Thus, delivery of antioxidant enzymes might reduce the deleterious effects of ROS and improve liver graft initial function. Mangafodipir trisodium (MnDPDP), a contrast agent currently used in magnetic resonance imaging of the liver, has been shown to be endowed with powerful antioxidant properties. We hypothesized that MnDPDP could have a protective effect against liver ischemia reperfusion injury when administrated to the donor prior to harvesting. Livers from Sprague Dawley rats pretreated or not with MnDPDP were harvested and subsequently preserved for 24 h in Celsior® solution at 4°C. Organs were then perfused ex vivo for 120 min at 37°C with Krebs Henseleit solution. In MnDPDP (5 µmol/kg) group, we observed that ATP content was significantly higher at the end of the cold preservation period relative to untreated group. After reperfusion, livers from MnDPDP-treated rats showed better tissue integrity, less hepatocellular and endothelial cell injury. This was accompanied by larger amounts of bile production and higher ATP recovery as compared to untreated livers. The protective effect of MnDPDP was associated with a significant decrease of lipid peroxidation, mitochondrial damage, and apoptosis. Interestingly, MnDPDP-pretreated livers exhibited activation of Nfr2 and HIF-1α pathways resulting in a higher catalase and HO-1 activities. MnDPDP also increased total nitric oxide (NO) production which derived from higher expression of constitutive NO synthase and lower expression of inducible NO synthase. In conclusion, our results show that donor pretreatment with MnDPDP protects the rat liver graft from cold ischemia/reperfusion injury and demonstrate for the first time the potential interest of this molecule in the field of organ preservation. Since MnDPDP is safely used in liver imaging, this preservation

  9. Acute Delivery of EphA4-Fc Improves Functional Recovery after Contusive Spinal Cord Injury in Rats

    PubMed Central

    Spanevello, Mark Damien; Tajouri, Sophie Ines; Mirciov, Cornel; Kurniawan, Nyoman; Pearse, Martin John; Fabri, Louis Jerry; Owczarek, Catherine Mary; Hardy, Matthew Philip; Bradford, Rebecca Anne; Ramunno, Melanie Louise; Turnley, Ann Maree; Ruitenberg, Marc Jan

    2013-01-01

    Abstract Blocking the action of inhibitory molecules at sites of central nervous system injury has been proposed as a strategy to promote axonal regeneration and functional recovery. We have previously shown that genetic deletion or competitive antagonism of EphA4 receptor activity promotes axonal regeneration and functional recovery in a mouse model of lateral hemisection spinal cord injury. Here we have assessed the effect of blocking EphA4 activation using the competitive antagonist EphA4-Fc in a rat model of thoracic contusive spinal cord injury. Using a ledged tapered balance beam and open-field testing, we observed significant improvements in recovery of locomotor function after EphA4-Fc treatment. Consistent with functional improvement, using high-resolution ex vivo magnetic resonance imaging at 16.4T, we found that rats treated with EphA4-Fc had a significantly increased cross-sectional area of the dorsal funiculus caudal to the injury epicenter compared with controls. Our findings indicate that EphA4-Fc promotes functional recovery following contusive spinal cord injury and provides further support for the therapeutic benefit of treatment with the competitive antagonist in acute cases of spinal cord injury. PMID:23557244

  10. Creative Drama: More Than Story Dramatization

    ERIC Educational Resources Information Center

    Stewig, John Warren

    1977-01-01

    Suggests that creative drama, including story dramatization, must include components such as rhythmic movement, pantomime, story improvisation, minimal situations, and teaching-in-role in order to produce educational benefits from a cohesive learning sequence. (MH)

  11. Cervical spinal cord injury: tailoring clinical trial endpoints to reflect meaningful functional improvements

    PubMed Central

    Bond, Lisa M.; McKerracher, Lisa

    2014-01-01

    Cervical spinal cord injury (SCI) results in partial to full paralysis of the upper and lower extremities. Traditional primary endpoints for acute SCI clinical trials are too broad to assess functional recovery in cervical subjects, raising the possibility of false positive outcomes in trials for cervical SCI. Endpoints focused on the recovery of hand and arm control (e.g., upper extremity motor score, motor level change) show the most potential for use as primary outcomes in upcoming trials of cervical SCI. As the field moves forward, the most reliable way to ensure meaningful clinical testing in cervical subjects may be the development of a composite primary endpoint that measures both neurological recovery and functional improvement. PMID:25317162

  12. Urinary Biomarkers Improve the Diagnosis of Intrinsic Acute Kidney Injury in Coronary Care Units

    PubMed Central

    Chang, Chih-Hsiang; Yang, Chia-Hung; Yang, Huang-Yu; Chen, Tien-Hsing; Lin, Chan-Yu; Chang, Su-Wei; Chen, Yi-Ting; Hung, Cheng-Chieh; Fang, Ji-Tseng; Yang, Chih-Wei; Chen, Yung-Chang

    2015-01-01

    Abstract Acute kidney injury (AKI) is associated with increased morbidity and mortality and is frequently encountered in coronary care units (CCUs). Its clinical presentation differs considerably from that of prerenal or intrinsic AKI. We used the biomarkers calprotectin and neutrophil gelatinase-associated lipocalin (NGAL) and compared their utility in predicting and differentiating intrinsic AKI. This was a prospective observational study conducted in a CCU of a tertiary care university hospital. Patients who exhibited any comorbidity and a kidney stressor were enrolled. Urinary samples of the enrolled patients collected between September 2012 and August 2013 were tested for calprotectin and NGAL. The definition of AKI was based on Kidney Disease Improving Global Outcomes classification. All prospective demographic, clinical, and laboratory data were evaluated as predictors of AKI. A total of 147 adult patients with a mean age of 67 years were investigated. AKI was diagnosed in 71 (50.3%) patients, whereas intrinsic AKI was diagnosed in 43 (60.5%) of them. Multivariate logistic regression analysis revealed urinary calprotectin and serum albumin as independent risk factors for intrinsic AKI. For predicting intrinsic AKI, both urinary NGAL and calprotectin displayed excellent areas under the receiver operating characteristic curve (AUROC) (0.918 and 0.946, respectively). A combination of these markers revealed an AUROC of 0.946. Our result revealed that calprotectin and NGAL had considerable discriminative powers for predicting intrinsic AKI in CCU patients. Accordingly, careful inspection for medication, choice of therapy, and early intervention in patients exhibiting increased biomarker levels might improve the outcomes of kidney injury. PMID:26448023

  13. OPERANT CONDITIONING OF A SPINAL REFLEX CAN IMPROVE LOCOMOTION AFTER SPINAL CORD INJURY IN HUMANS

    PubMed Central

    Thompson, Aiko K.; Pomerantz, Ferne; Wolpaw, Jonathan R.

    2013-01-01

    Operant conditioning protocols can modify the activity of specific spinal cord pathways and can thereby affect behaviors that use these pathways. To explore the therapeutic application of these protocols, we studied the impact of down-conditioning the soleus H-reflex in people with impaired locomotion caused by chronic incomplete spinal cord injury. After a baseline period in which soleus H-reflex size was measured and locomotion was assessed, subjects completed either 30 H-reflex down-conditioning sessions (DC subjects) or 30 sessions in which the H-reflex was simply measured (Unconditioned (UC) subjects), and locomotion was reassessed. Over the 30 sessions, the soleus H-reflex decreased in two-thirds of the DC subjects (a success rate similar to that in normal subjects) and remained smaller several months later. In these subjects, locomotion became faster and more symmetrical, and the modulation of EMG activity across the step-cycle increased bilaterally. Furthermore, beginning about halfway through the conditioning sessions, all of these subjects commented spontaneously that they were walking faster and farther in their daily lives, and several noted less clonus, easier stepping, and/or other improvements. The H-reflex did not decrease in the other DC subjects or in any of the UC subjects; and their locomotion did not improve. These results suggest that reflex conditioning protocols can enhance recovery of function after incomplete spinal cord injuries and possibly in other disorders as well. Because they are able to target specific spinal pathways, these protocols could be designed to address each individual’s particular deficits, and might thereby complement other rehabilitation methods. PMID:23392666

  14. Building Family and Community Demand for Dramatic Change in Schools

    ERIC Educational Resources Information Center

    Brinson, Dana; Steiner, Lucy

    2012-01-01

    District-led, dramatic change efforts in failing schools--including turnarounds and school closures--often face strong resistance from families and communities. Resistance may be based on years of tension and distrust between districts and communities, failed past school improvement efforts, or a lack of understanding about the chasm between a…

  15. Cotton domestication: Dramatic changes in a single cell

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding the nature of genetic changes underpinning plant domestication is critical for untangling the evolutionary history of crops and for improving modern cultivars. A recent study in cotton provides information about the effects of domestication, showing that dramatic genome-wide changes i...

  16. Autologous bone marrow mononuclear cells therapy attenuates activated microglial/macrophage response and improves spatial learning after traumatic brain injury

    PubMed Central

    Bedi, Supinder S.; Walker, Peter A.; Shah, Shinil K.; Jimenez, Fernando; Thomas, Chelsea P.; Smith, Philippa; Hetz, Robert A.; Xue, Hasen; Pati, Shibani; Dash, Pramod K.; Cox, Charles S.

    2014-01-01

    Background Autologous bone marrow-derived mononuclear cells (AMNC) have shown therapeutic promise for central nervous system insults such as stroke and traumatic brain injury (TBI). We hypothesized that intravenous injection of AMNC provides neuroprotection which leads to cognitive improvement after TBI. Methods A controlled cortical impact (CCI) rodent traumatic brain injury (TBI) model was used to examine blood-brain barrier permeability (BBB), neuronal and glial apoptosis and cognitive behavior. Two groups of rats underwent CCI with (CCI-Autologous) or without AMNC treatment (CCI-Alone), consisting of 2 million AMNC/kilogram body weight harvested from the tibia and intravenously injected 72 hr after injury. CCI-Alone animals underwent sham harvests and received vehicle injections. Results 96 hr after injury, AMNC significantly reduced the BBB permeability in injured animals, and there was an increase in apoptosis of pro-inflammatory activated microglia in the ipsilateral hippocampus. At 4 weeks after injury, we examined changes in spatial memory after TBI due to AMNC treatment. There was a significant improvement in probe testing of CCI-Autologous group in comparison to CCI-Alone in the Morris Water Maze paradigm. Conclusions Our data demonstrate that the intravenous injection of AMNC after TBI leads to neuroprotection by preserving early BBB integrity and increasing activated microglial apoptosis. In addition, AMNC also improves cognitive function. PMID:23928737

  17. Improving brain injury cognitive rehabilitation by personalized telerehabilitation services: Guttmann neuropersonal trainer.

    PubMed

    Solana, Javier; Cáceres, César; García-Molina, Alberto; Opisso, Eloy; Roig, Teresa; Tormos, José M; Gómez, Enrique J

    2015-01-01

    Cognitive rehabilitation aims to remediate or alleviate the cognitive deficits appearing after an episode of acquired brain injury (ABI). The purpose of this work is to describe the telerehabilitation platform called Guttmann Neuropersonal Trainer (GNPT) which provides new strategies for cognitive rehabilitation, improving efficiency and access to treatments, and to increase knowledge generation from the process. A cognitive rehabilitation process has been modeled to design and develop the system, which allows neuropsychologists to configure and schedule rehabilitation sessions, consisting of set of personalized computerized cognitive exercises grounded on neuroscience and plasticity principles. It provides remote continuous monitoring of patient's performance, by an asynchronous communication strategy. An automatic knowledge extraction method has been used to implement a decision support system, improving treatment customization. GNPT has been implemented in 27 rehabilitation centers and in 83 patients' homes, facilitating the access to the treatment. In total, 1660 patients have been treated. Usability and cost analysis methodologies have been applied to measure the efficiency in real clinical environments. The usability evaluation reveals a system usability score higher than 70 for all target users. The cost efficiency study results show a relation of 1-20 compared to face-to-face rehabilitation. GNPT enables brain-damaged patients to continue and further extend rehabilitation beyond the hospital, improving the efficiency of the rehabilitation process. It allows customized therapeutic plans, providing information to further development of clinical practice guidelines. PMID:25204001

  18. Whither the "Improvement Standard"? Coverage for Severe Brain Injury after Jimmo v. Sebelius.

    PubMed

    Fins, Joseph J; Wright, Megan S; Kraft, Claudia; Rogers, Alix; Romani, Marina B; Godwin, Samantha; Ulrich, Michael R

    2016-03-01

    As improvements in neuroscience have enabled a better understanding of disorders of consciousness as well as methods to treat them, a hurdle that has become all too prevalent is the denial of coverage for treatment and rehabilitation services. In 2011, a settlement emerged from a Vermont District Court case, Jimmo v. Sebelius, which was brought to stop the use of an "improvement standard" that required tangible progress over an identifiable period of time for Medicare coverage of services. While the use of this standard can have deleterious effects on those with many chronic conditions, it is especially burdensome for those in the minimally conscious state (MCS), where improvements are unpredictable and often not manifested through repeatable overt behaviors. Though the focus of this paper is on the challenges of brain injury and the minimally conscious state, which an estimated 100,000 to 200,000 individuals suffer from in the United States, the post-Jimmo arguments presented can and should have a broad impact as envisioned by the plaintiffs who brought the case on behalf of multiple advocacy groups representing patients with a range of chronic care conditions. PMID:27256134

  19. Improved and standardized method for assessing years lived with disability after injury

    PubMed Central

    Polinder, S; Lyons, RA; Lund, J; Ditsuwan, V; Prinsloo, M; Veerman, JL; van Beeck, EF

    2012-01-01

    Abstract Objective To develop a standardized method for calculating years lived with disability (YLD) after injury. Methods The method developed consists of obtaining data on injury cases seen in emergency departments as well as injury-related hospital admissions, using the EUROCOST system to link the injury cases to disability information and employing empirical data to describe functional outcomes in injured patients. Findings Overall, 87 weights and proportions for 27 injury diagnoses involving lifelong consequences were included in the method. Almost all of the injuries investigated (96–100%) could be assigned to EUROCOST categories. The mean number of YLD per case of injury varied with the country studied. Use of the novel method resulted in estimated burdens of injury that were 3 to 8 times higher, in terms of YLD, than the corresponding estimates produced using the conventional methods employed in global burden of disease studies, which employ disability-adjusted life years. Conclusion The novel method for calculating YLD after injury can be applied in different settings, overcomes some limitations of the method used to calculate the global burden of disease, and allows more accurate estimates of the population burden of injury. PMID:22807597

  20. Normalization of coagulopathy is associated with improved outcome after isolated traumatic brain injury.

    PubMed

    Epstein, Daniel S; Mitra, Biswadev; Cameron, Peter A; Fitzgerald, Mark; Rosenfeld, Jeffrey V

    2016-07-01

    Acute traumatic coagulopathy (ATC) has been reported in the setting of isolated traumatic brain injury (iTBI) and is associated with poor outcomes. We aimed to evaluate the effectiveness of procoagulant agents administered to patients with ATC and iTBI during resuscitation, hypothesizing that timely normalization of coagulopathy may be associated with a decrease in mortality. A retrospective review of the Alfred Hospital trauma registry, Australia, was conducted and patients with iTBI (head Abbreviated Injury Score [AIS] ⩾3 and all other body AIS <3) and coagulopathy (international normalized ratio ⩾1.3) were selected for analysis. Data on procoagulant agents used (fresh frozen plasma, platelets, cryoprecipitate, prothrombin complex concentrates, tranexamic acid, vitamin K) were extracted. Among patients who had achieved normalization of INR or survived beyond 24hours and were not taking oral anticoagulants, the association of normalization of INR and death at hospital discharge was analyzed using multivariable logistic regression analysis. There were 157 patients with ATC of whom 68 (43.3%) received procoagulant products within 24hours of presentation. The median time to delivery of first products was 182.5 (interquartile range [IQR] 115-375) minutes, and following administration of coagulants, time to normalization of INR was 605 (IQR 274-1146) minutes. Normalization of INR was independently associated with significantly lower mortality (adjusted odds ratio 0.10; 95% confidence interval 0.03-0.38). Normalization of INR was associated with improved mortality in patients with ATC in the setting of iTBI. As there was a substantial time lag between delivery of products and eventual normalization of coagulation, specific management of coagulopathy should be implemented as early as possible. PMID:26947341

  1. Conditional Sox9 ablation improves locomotor recovery after spinal cord injury by increasing reactive sprouting.

    PubMed

    McKillop, William M; York, Elisa M; Rubinger, Luc; Liu, Tony; Ossowski, Natalie M; Xu, Kathy; Hryciw, Todd; Brown, Arthur

    2016-09-01

    The absence of axonal regeneration after spinal cord injury (SCI) has been attributed to the up-regulation of axon-repelling molecules, such as chondroitin sulfate proteoglycans (CSPGs) present in the glial scar that forms post-SCI. We previously identified the transcription factor SOX9 as a key up-regulator of CSPG production and also demonstrated that conditional Sox9 ablation leads to decreased CSPG levels and improved recovery of hind limb function after SCI. We herein demonstrate increased neural input onto spinal neurons caudal to the lesion in spinal cord injured Sox9 conditional knock out mice as indicated by increased levels of the presynaptic markers synaptophysin and vesicular glutamate transporter 1 (VGLUT1) compared to controls. Axonal sparing, long-range axonal regeneration and reactive sprouting were investigated as possible explanations for the increase in neural inputs caudal to the lesion and for the improved locomotor outcomes in spinal cord-injured Sox9 conditional knock out mice. Whereas retrograde tract-tracing studies failed to reveal any evidence for increased axonal sparing or for long-range regeneration in the Sox9 conditional knock out mice, anterograde tract-tracing experiments demonstrated increased reactive sprouting caudal to the lesion after SCI. Finally we demonstrate that application of a broad spectrum MMP inhibitor to reduce CSPG degradation in Sox9 conditional knock out mice prevents the improvements in locomotor recovery observed in untreated Sox9 conditional knock out mice. These results suggest that improved recovery of locomotor function in Sox9 conditional knock out mice after SCI is due to increased reactive sprouting secondary to reduced CSPG levels distal to the lesion. PMID:27235933

  2. Injury prevention counselling to improve safety practices by parents in Mexico.

    PubMed Central

    Mock, Charles; Arreola-Risa, Carlos; Trevino-Perez, Rodolfo; Almazan-Saavedra, Victoria; Zozaya-Paz, Jaime E.; Gonzalez-Solis, Reynaldo; Simpson, Kate; Rodriguez-Romo, Laura; Hernandez-Torre, Martin H.

    2003-01-01

    OBJECTIVES: To evaluate the effectiveness of educational counselling programmes aimed at increasing parents' practice of childhood safety in Monterrey, Mexico, and to provide information aimed at helping to improve the effectiveness of future efforts in this field. METHODS: Three different counselling programmes were designed to meet the needs of the upper, middle and lower socioeconomic strata. Evaluation involved the use of baseline questionnaires on parents' existing safety-related practices for intervention and control groups and the administration of corresponding questionnaires after the programmes had been carried out. FINDINGS: Data were obtained on 1124 children before counselling took place and on 625 after it had been given. Overall safety scores (% safe responses) increased from 54% and 65% for the lower and upper socioeconomic strata, respectively, before counselling to 62% and 73% after counselling (P <0.001 for all groups). Improvements occurred both for activities that required caution and for activities that required the use of safety-related devices (e.g. helmets, car seats). However, scores for the use of such devices remained suboptimal even after counselling and there were wide discrepancies between the socioeconomic strata. The post-counselling scores for the use of safety-related devices were 55%, 38% and 19% for the upper, middle and lower socioeconomic strata, respectively. CONCLUSIONS: Brief educational interventions targeting parents' practice of childhood safety improved safe behaviours. Increased attention should be given to specific safety-related devices and to the safety of pedestrians. Educational efforts should be combined with other strategies for injury prevention, such as the use of legislation and the improvement of environmental conditions. PMID:14576891

  3. SPECT Perfusion Imaging Demonstrates Improvement of Traumatic Brain Injury With Transcranial Near-infrared Laser Phototherapy.

    PubMed

    Henderson, Theodore A; Morries, Larry D

    2015-01-01

    Traumatic brain injury (TBI) is a growing health concern affecting civilians and military personnel. Near-infrared (NIR) light has shown benefits in animal models and human trials for stroke and in animal models for TBI. Diodes emitting low-level NIR often have lacked therapeutic efficacy, perhaps failing to deliver sufficient radiant energy to the necessary depth. In this case report, a patient with moderate TBI documented in anatomical magnetic resonance imaging (MRI) and perfusion single-photon emission computed tomography (SPECT) received 20 NIR treatments in the course of 2 mo using a high-power NIR laser. Symptoms were monitored by clinical examination and a novel patient diary system specifically designed for this patient population. Clinical application of these levels of infrared energy for this patient with TBI yielded highly favorable outcomes with decreased depression, anxiety, headache, and insomnia, whereas cognition and quality of life improved. Neurological function appeared to improve based on changes in the SPECT by quantitative analysis. NIR in the power range of 10-15 W at 810 and 980 nm can safely and effectively treat chronic symptoms of TBI. PMID:26535475

  4. A sustained quality improvement program reduces nephrotoxic medication-associated acute kidney injury.

    PubMed

    Goldstein, Stuart L; Mottes, Theresa; Simpson, Kendria; Barclay, Cynthia; Muething, Stephen; Haslam, David B; Kirkendall, Eric S

    2016-07-01

    Exposure to nephrotoxic medication is among the most common causes of acute kidney injury (AKI) in hospitalized patients. Here we conducted a prospective quality improvement project implementing a systematic Electronic Health Record screening and decision support process (trigger) in our quaternary pediatric inpatient hospital. Eligible patients were noncritically ill hospitalized children receiving an intravenous aminoglycoside for more than 3 days or more than 3 nephrotoxins simultaneously (exposure) from September 2011 through March 2015. Pharmacists recommended daily serum creatinine monitoring in exposed patients after appearance on the trigger report and AKI was defined by the Kidney Disease Improving Global Outcomes AKI criteria. A total of 1749 patients accounted for 2358 separate hospital admissions during which a total of 3243 episodes of nephrotoxin exposure were identified with 170 patients (9.7%) experiencing 2 or more exposures. A total of 575 individual AKI episodes occurred over the 43-month study period. Overall, the exposure rate decreased by 38% (11.63-7.24 exposures/1000 patient days), and the AKI rate decreased by 64% (2.96-1.06 episodes/1000 patient days). Assuming initial baseline exposure rates would have persisted without our project implementation, we estimate 633 exposures and 398 AKI episodes were avoided. Thus, systematic surveillance for nephrotoxic medication exposure and near real-time AKI risk can lead to sustained reductions in avoidable harm. These interventions and outcomes are translatable to other pediatric and nonpediatric hospitalized settings. PMID:27217196

  5. Bone marrow mesenchymal stem cells combined with minocycline improve spinal cord injury in a rat model

    PubMed Central

    Chen, Dayong; Zeng, Wei; Fu, Yunfeng; Gao, Meng; Lv, Guohua

    2015-01-01

    The aims of this study were to assess that the effects of bone marrow mesenchymal stem cells (BMSCs) combination with minocycline improve spinal cord injury (SCI) in rat model. In the present study, the Wistar rats were randomly divided into five groups: control group, SCI group, BMSCs group, Minocycline group and BMSCs + minocycline group. Basso, Beattie and Bresnahan (BBB) test and MPO activity were used to assess the effect of combination therapy on locomotion and neutrophil infiltration. Inflammation factors, VEGF and BDNF expression, caspase-3 activation, phosphorylation-p38MAPK, proNGF, p75NTR and RhoA expressions were estimated using commercial kits or western blot, respectively. BBB scores were significantly increased and MPO activity was significantly undermined by combination therapy. In addition, combination therapy significantly decreased inflammation factors in SCI rats. Results from western blot showed that combination therapy significantly up-regulated the protein of VEGF and BDNF expression and down-regulated the protein of phosphorylation-p38MAPK, proNGF, p75NTR and RhoA expressions in SCI rats. Combination therapy stimulation also suppressed the caspase-3 activation in SCI rats. These results demonstrated that the effects of bone marrow mesenchymal stem cells combination with minocycline improve SCI in rat model. PMID:26722382

  6. Interactive virtual feedback improves gait motor imagery after spinal cord injury: An exploratory study

    PubMed Central

    Roosink, Meyke; Robitaille, Nicolas; Jackson, Philip L.; Bouyer, Laurent J.; Mercier, Catherine

    2016-01-01

    Purpose: Motor imagery can improve motor function and reduce pain. This is relevant to individuals with spinal cord injury (SCI) in whom motor dysfunction and neuropathic pain are prevalent. However, therapy efficacy could be dependent on motor imagery ability, and a clear understanding of how motor imagery might be facilitated is currently lacking. Thus, the aim of the present study was to assess the immediate effects of interactive virtual feedback on motor imagery performance after SCI. Methods: Nine individuals with a traumatic SCI participated in the experiment. Motor imagery tasks consisted of forward (i.e. simpler) and backward (i.e. more complex) walking while receiving interactive versus static virtual feedback. Motor imagery performance (vividness, effort and speed), neuropathic pain intensity and feasibility (immersion, distraction, side-effects) were assessed. Results: During interactive feedback trials, motor imagery vividness and speed were significantly higher and effort was significantly lower as compared static feedback trials. No change in neuropathic pain was observed. Adverse effects were minor, and immersion was reported to be good. Conclusions: This exploratory study showed that interactive virtual walking was feasible and facilitated motor imagery performance. The response to motor imagery interventions after SCI might be improved by using interactive virtual feedback. PMID:26890097

  7. Reducing Contrast-Induced Acute Kidney Injury Using a Regional Multicenter Quality Improvement Intervention

    PubMed Central

    Brown, Jeremiah R.; Solomon, Richard J.; Sarnak, Mark J.; McCullough, Peter A.; Splaine, Mark E.; Davies, Louise; Ross, Cathy S.; Dauerman, Harold L.; Stender, Janette L.; Conley, Sheila M.; Robb, John F.; Chaisson, Kristine; Boss, Richard; Lambert, Peggy; Goldberg, David J.; Lucier, Deborah; Fedele, Frank A.; Kellett, Mirle A.; Horton, Susan; Phillips, William J.; Downs, Cynthia; Wiseman, Alan; MacKenzie, Todd A.; Malenka, David J.

    2016-01-01

    Background Contrast-induced acute kidney injury (CI-AKI) is associated with increased morbidity and mortality following percutaneous coronary interventions (PCI) and is a patient safety objective of the National Quality Forum. However, no formal quality improvement program to prevent CI-AKI has been conducted. Therefore, we sought to determine if a six-year regional multi-center quality improvement intervention could reduce CI-AKI following PCI. Methods and Results We conducted a prospective multi-center quality improvement study to prevent CI-AKI (serum creatinine increase ≥0.3 mg/dL within 48 hours or ≥50% during hospitalization) among 21,067 non-emergent patients undergoing PCI at ten hospitals between 2007 and 2012. Six ‘intervention’ hospitals participated in the quality improvement intervention. Two hospitals with significantly lower baseline rates of CI-AKI, which served as “benchmark” sites and were used to develop the intervention and two hospitals not receiving the intervention were used as controls. Using time series analysis and multilevel poisson regression clustering to the hospital-level we calculated adjusted risk ratios (RR) for CI-AKI comparing the intervention period to baseline. Adjusted rates of CI-AKI were significantly reduced in hospitals receiving the intervention by 21% (RR 0.79; 95%CI: 0.67 to 0.93; p=0.005) for all patients and by 28% in patients with baseline eGFR<60 ml/min/1.73 m2 (RR 0.72; 95%CI: 0.56 to 0.91; p=0.007). Benchmark hospitals had no significant changes in CI-AKI. Key qualitative system factors associated with improvement included: multidisciplinary teams, limiting contrast volume, standardized fluid orders, intravenous fluid bolus, and patient education about oral hydration. Conclusions Simple cost-effective quality improvement interventions can prevent up to one in five CI-AKI events in patients with undergoing non-emergent PCI. PMID:25074372

  8. Back to Basics through Creative Dramatics.

    ERIC Educational Resources Information Center

    Rubin, Janet E.

    In the back to basics era, creative dramatics should still be used in the English classroom because it helps to develop the entire child. For some time, teaching strategies have been directed at the left brain, the hemisphere that deals with logical and linear functions. Recently, however, attention has been given to the right side of the brain,…

  9. Dramatizing Poetry in the Second Language Classroom

    ERIC Educational Resources Information Center

    Elting, Stephen; Firkins, Arthur

    2006-01-01

    Poetry performance is an approach to learning where students can use theatrical techniques to develop a response to the poem. This paper argues that ELL students can explore the aesthetic function of language and, more widely, develop confidence in using English as a communicative tool through the dramatization of poetry. We describe the process…

  10. Nietzsche contra Burke: The Melodrama in Dramatism.

    ERIC Educational Resources Information Center

    Desilet, Gregory

    1989-01-01

    Examines Kenneth Burke's and Friedrich Nietzsche's similar understanding of the hortatory nature of language-using, weighed against their radically differing conceptions of the negative, which allows a distinction between two genres of dramatism, and illustrates contrasting orientations toward symbolic activity in general. (SR)

  11. Introductory Dramatics Guide for Grade 9. (Revised).

    ERIC Educational Resources Information Center

    Montgomery County Board of Education, Rockville, MD.

    Based on the experiences of classroom teachers of theatre, the elective dramatics course described in this guide is designed to enhance ninth grade students' aesthetic awareness, social development, intellectual growth, and technical knowledge. Following a brief course description and overview, the guide presents complete instructions for seven…

  12. Dramatic Ways to Engage Every Student

    ERIC Educational Resources Information Center

    Dixon, Edmond J.

    2012-01-01

    The goal of all teaching should be to help students make neural connections--the basis for all learning. To do that, however, the student has to have engagement and cognition around the material to be learned. At its core, dramatic activities, even when they have nothing to do with performance, have a tremendous ability to foster these…

  13. The Psychodrama-Social Dramatics Separation.

    ERIC Educational Resources Information Center

    Klepac, Richard L.

    Social dramatics is a therapeutic and educational program that can act as a mirror to reflect images of the self in action with others. It is the modality for experiential learning to correct social dysfunction by providing models for imitation, opportunities to practice and develop individual forms from that model, and risk free environments for…

  14. Dietary Supplementation with Organoselenium Accelerates Recovery of Bladder Expression, but Does Not Improve Locomotor Function, following Spinal Cord Injury

    PubMed Central

    Meyer, Carolyn A.; Singh, Ranjana; Jones, Mackenzie T.; Yu, Chen-Guang; Power, Ronan F.; Geddes, James W.

    2016-01-01

    Selenium is an essential element required for activity of several antioxidant enzymes, including glutathione peroxidase. Because of the critical role of the antioxidant system in responding to traumatic events, we hypothesized that dietary selenium supplementation would enhance neuroprotection in a rodent model of spinal cord injury. Rats were maintained on either a control or selenium-enriched diet prior to, and following, injury. Dietary selenium supplementation, provided as selenized yeast added to normal rat chow, resulted in a doubling of selenium levels in the spinal cord. Dietary selenium reduced the time required for recovery of bladder function following thoracic spinal cord injury. However, this was not accompanied by improvement in locomotor function or tissue sparing. PMID:26824231

  15. Selective Inhibition of Alpha/Beta-Hydrolase Domain 6 Attenuates Neurodegeneration, Alleviates Blood Brain Barrier Breakdown, and Improves Functional Recovery in a Mouse Model of Traumatic Brain Injury

    PubMed Central

    Tchantchou, Flaubert

    2013-01-01

    Abstract 2-arachidonylglycerol (2-AG) is the most abundant endocannabinoid in the central nervous system and is elevated after brain injury. Because of its rapid hydrolysis, however, the compensatory and neuroprotective effect of 2-AG is short-lived. Although inhibition of monoacylglycerol lipase, a principal enzyme for 2-AG degradation, causes a robust increase of brain levels of 2-AG, it also leads to cannabinoid receptor desensitization and behavioral tolerance. Alpha/beta hydrolase domain 6 (ABHD6) is a novel 2-AG hydrolytic enzyme that accounts for a small portion of 2-AG hydrolysis, but its inhibition is believed to elevate the levels of 2-AG within the therapeutic window without causing side effect. Using a mouse model of traumatic brain injury (TBI), we found that post-insult chronic treatment with a selective ABHD6 inhibitor WWL70 improved motor coordination and working memory performance. WWL70 treatment reduced lesion volume in the cortex and neurodegeneration in the dendate gyrus. It also suppressed the expression of inducible nitric oxide synthase and cyclooxygenase-2 and enhanced the expression of arginase-1 in the ipsilateral cortex at 3 and 7 days post-TBI, suggesting microglia/macrophages shifted from M1 to M2 phenotypes after treatment. The blood-brain barrier dysfunction at 3 and 7 days post-TBI was dramatically reduced. Furthermore, the beneficial effects of WWL70 involved up-regulation and activation of cannabinoid type 1 and type 2 receptors and were attributable to the phosphorylation of the extracellular signal regulated kinase and the serine/threonine protein kinase AKT. This study indicates that the fine-tuning of 2-AG signaling by modulating ABHD6 activity can exert anti-inflammatory and neuroprotective effects in TBI. PMID:23151067

  16. Selective inhibition of alpha/beta-hydrolase domain 6 attenuates neurodegeneration, alleviates blood brain barrier breakdown, and improves functional recovery in a mouse model of traumatic brain injury.

    PubMed

    Tchantchou, Flaubert; Zhang, Yumin

    2013-04-01

    2-arachidonylglycerol (2-AG) is the most abundant endocannabinoid in the central nervous system and is elevated after brain injury. Because of its rapid hydrolysis, however, the compensatory and neuroprotective effect of 2-AG is short-lived. Although inhibition of monoacylglycerol lipase, a principal enzyme for 2-AG degradation, causes a robust increase of brain levels of 2-AG, it also leads to cannabinoid receptor desensitization and behavioral tolerance. Alpha/beta hydrolase domain 6 (ABHD6) is a novel 2-AG hydrolytic enzyme that accounts for a small portion of 2-AG hydrolysis, but its inhibition is believed to elevate the levels of 2-AG within the therapeutic window without causing side effect. Using a mouse model of traumatic brain injury (TBI), we found that post-insult chronic treatment with a selective ABHD6 inhibitor WWL70 improved motor coordination and working memory performance. WWL70 treatment reduced lesion volume in the cortex and neurodegeneration in the dendate gyrus. It also suppressed the expression of inducible nitric oxide synthase and cyclooxygenase-2 and enhanced the expression of arginase-1 in the ipsilateral cortex at 3 and 7 days post-TBI, suggesting microglia/macrophages shifted from M1 to M2 phenotypes after treatment. The blood-brain barrier dysfunction at 3 and 7 days post-TBI was dramatically reduced. Furthermore, the beneficial effects of WWL70 involved up-regulation and activation of cannabinoid type 1 and type 2 receptors and were attributable to the phosphorylation of the extracellular signal regulated kinase and the serine/threonine protein kinase AKT. This study indicates that the fine-tuning of 2-AG signaling by modulating ABHD6 activity can exert anti-inflammatory and neuroprotective effects in TBI. PMID:23151067

  17. Improving on Army Field Gauze for Lethal Vascular Injuries: Challenges in Dressing Development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accounting for half of all deaths, uncontrolled hemorrhage remains the leading cause of death on the battlefield. Gaining hemostatic control of lethal vascular injuries sustained in combat using topical agents remains a challenge. Recent animal testing using a lethal arterial injury model compared a...

  18. Equestrian injury is costly, disabling, and frequently preventable: the imperative for improved safety awareness.

    PubMed

    Guyton, Kristina; Houchen-Wise, Emily; Peck, Ellen; Mayberry, John

    2013-01-01

    Horse-related injury can be severe and disabling. We investigated the causes, severity, and costs of equestrian injury with the goal of injury prevention. A retrospective review of horse-related injuries from 2001 to 2008 identified 231 patients with a mean age of 38 years and a mean Injury Severity Score of 11 (range, 1 to 45). Mean length of stay was 5.5 days. Fifty-nine patients (25%) required 84 surgeries. Helmet use was 20 per cent and of the 172 patients not wearing a helmet while mounted, 38 per cent received potentially preventable head injuries. There were three deaths of which two were the result of intracranial hemorrhage in riders not wearing a helmet. Mean hospital charge was $29,800 for a total of $6.9 million. Ninety-one patients completed a survey regarding causation and disability. Thirty-four per cent reported wearing a helmet at the time of injury. Forty per cent reported that poor environmental factors contributed, 30 per cent reported poor horse and rider pairing, and 9 per cent reported equipment failure. Fifty-nine per cent reported long-term disabilities. Compared with the general population, respondents had diminution in their ability to perform usual daily activities associated with physical problems, diminution in social function, and higher bodily pain. We conclude that equestrian injury is costly, disabling, and frequently preventable. PMID:23317616

  19. gamma-Tocopherol nebulization by a lipid aerosolization device improves pulmonary function in sheep with burn and smoke inhalation injury.

    PubMed

    Hamahata, Atsumori; Enkhbaatar, Perenlei; Kraft, Edward R; Lange, Matthias; Leonard, Scott W; Traber, Maret G; Cox, Robert A; Schmalstieg, Frank C; Hawkins, Hal K; Whorton, Elbert B; Horvath, Eszter M; Szabo, Csaba; Traber, Lillian D; Herndon, David N; Traber, Daniel L

    2008-08-15

    Fire accident victims who sustain both thermal injury to skin and smoke inhalation have gross evidence of systemic and pulmonary oxidant damage and acute lung injury. We hypothesized that gamma-tocopherol (gT), a reactive O(2) and N(2) scavenger, when delivered into the airway, would attenuate lung injury induced by burn and smoke inhalation. Acute lung injury was induced in chronically prepared, anesthetized sheep by 40% total burn surface area, third-degree skin burn and smoke insufflation (48 breaths of cotton smoke, <40 degrees C). The study groups were: (1) Sham (not injured, flaxseed oil (FO)-nebulized, n=6); (2) SA-neb (injured, saline-nebulized, n=6); (3) FO-neb (injured, FO-nebulized, n=6); and (4) gT+FO-neb (injured, gT and FO-nebulized, n=6). Nebulization was started 1 h postinjury, and 24 ml of FO with or without gT (51 mg/ml) was delivered into airways over 47 h using our newly developed lipid aerosolization device (droplet size: 2.5-5 microm). The burn- and smoke inhalation-induced pathological changes seen in the saline group were attenuated by FO nebulization; gT addition further improved pulmonary function. Pulmonary gT delivery along with a FO source may be a novel effective treatment strategy in management of patients with acute lung injury. PMID:18503777

  20. Hydrogen sulfide improves cardiomyocytes electrical remodeling post ischemia/reperfusion injury in rats.

    PubMed

    Sun, Ying-Gang; Wang, Xin-Yan; Chen, Xiu; Shen, Cheng-Xing; Li, Yi-Gang

    2015-01-01

    Hydrogen sulfide (H2S), produced by cystanthionine-γ-lysase (CSE) in the cardiovascular system, is an endogenous gaseous mediator exerting pronounced physiological effects as the third gasotransmitter in addition to nitric oxide (NO) and carbon monoxide (CO). Accumulating evidence indicated that H2S could mediate the cardioprotective effects in myocardial ischemia model. Ventricular arrhythmia is the most important risk factor for cardiac mortality and sudden death after acute myocardial infarction (AMI). The potential impact of H2S on cardiomyocytes electrical remodeling post ischemic insult is not fully explored now. Present study investigated the role of H2S on cardiomyocytes electrical remodeling in rats with ischemia/reperfusion injury. H2S concentration was reduced and arrhythmia score was increased in this model. CSE mRNA level was also upregulated in the ischemic myocardium. Exposure to exogenous NaHS reduced the action potential duration (APD), inhibited L-type Ca(2+) channels and activated K(ATP) channels in cardiomyocytes isolated from ischemic myocardium Exogenous H2S application improves electrical remodeling in cardiomyocytes isolated from ischemic myocardium. These results indicated that reduced H2S level might be linked to ischemia/reperfusion induced arrhythmias. PMID:25755736

  1. Administration of α-Galactosylceramide Improves Adenine-Induced Renal Injury

    PubMed Central

    Aguiar, Cristhiane Favero; Naffah-de-Souza, Cristiane; Castoldi, Angela; Corrêa-Costa, Matheus; Braga, Tárcio T; Naka, Érika L; Amano, Mariane T; Abate, Débora T R S; Hiyane, Meire I; Cenedeze, Marcos A; Filho, Alvaro Pacheco e Silva; Câmara, Niels O S

    2015-01-01

    Natural killer T (NKT) cells are a subset of lymphocytes that reacts to glycolipids presented by CD1d. Invariant NKT cells (iNKT) correspond to >90% of the total population of NKTs and reacts to α-galactosylceramide (αGalCer). αGalCer promotes a complex mixture of Th1 and Th2 cytokines, as interferon (IFN)-γ and interleukin (IL)-4. NKT cells and IFN-γ are known to participate in some models of renal diseases, but further studies are still necessary to elucidate their mechanisms. The aim of our study was to analyze the participation of iNKT cells in an experimental model of tubule-interstitial nephritis. We used 8-wk-old C57BL/6j, Jα18KO and IFN-γKO mice. They were fed a 0.25% adenine diet for 10 d. Both adenine-fed wild-type (WT) and Jα18KO mice exhibited renal dysfunction, but adenine-fed Jα18KO mice presented higher expression of kidney injury molecule-1 (KIM-1), tumor necrosis factor (TNF)-α and type I collagen. To analyze the role of activated iNKT cells in our model, we administered αGalCer in WT mice during adenine ingestion. After αGalCer injection, we observed a significant reduction in serum creatinine, proinflammatory cytokines and renal fibrosis. However, this improvement in renal function was not observed in IFN-γKO mice after αGalCer treatment and adenine feeding, illustrating that this cytokine plays a role in our model. Our findings may suggest that IFN-γ production is one of the factors contributing to improved renal function after αGalCer administration. PMID:26101952

  2. TRPV4 inhibition counteracts edema and inflammation and improves pulmonary function and oxygen saturation in chemically induced acute lung injury

    PubMed Central

    Balakrishna, Shrilatha; Song, Weifeng; Achanta, Satyanarayana; Doran, Stephen F.; Liu, Boyi; Kaelberer, Melanie M.; Yu, Zhihong; Sui, Aiwei; Cheung, Mui; Leishman, Emma; Eidam, Hilary S.; Ye, Guosen; Willette, Robert N.; Thorneloe, Kevin S.; Bradshaw, Heather B.; Matalon, Sadis

    2014-01-01

    The treatment of acute lung injury caused by exposure to reactive chemicals remains challenging because of the lack of mechanism-based therapeutic approaches. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), an ion channel expressed in pulmonary tissues, is a crucial mediator of pressure-induced damage associated with ventilator-induced lung injury, heart failure, and infarction. Here, we examined the effects of two novel TRPV4 inhibitors in mice exposed to hydrochloric acid, mimicking acid exposure and acid aspiration injury, and to chlorine gas, a severe chemical threat with frequent exposures in domestic and occupational environments and in transportation accidents. Postexposure treatment with a TRPV4 inhibitor suppressed acid-induced pulmonary inflammation by diminishing neutrophils, macrophages, and associated chemokines and cytokines, while improving tissue pathology. These effects were recapitulated in TRPV4-deficient mice. TRPV4 inhibitors had similar anti-inflammatory effects in chlorine-exposed mice and inhibited vascular leakage, airway hyperreactivity, and increase in elastance, while improving blood oxygen saturation. In both models of lung injury we detected increased concentrations of N-acylamides, a class of endogenous TRP channel agonists. Taken together, we demonstrate that TRPV4 inhibitors are potent and efficacious countermeasures against severe chemical exposures, acting against exaggerated inflammatory responses, and protecting tissue barriers and cardiovascular function. PMID:24838754

  3. TRPV4 inhibition counteracts edema and inflammation and improves pulmonary function and oxygen saturation in chemically induced acute lung injury.

    PubMed

    Balakrishna, Shrilatha; Song, Weifeng; Achanta, Satyanarayana; Doran, Stephen F; Liu, Boyi; Kaelberer, Melanie M; Yu, Zhihong; Sui, Aiwei; Cheung, Mui; Leishman, Emma; Eidam, Hilary S; Ye, Guosen; Willette, Robert N; Thorneloe, Kevin S; Bradshaw, Heather B; Matalon, Sadis; Jordt, Sven-Eric

    2014-07-15

    The treatment of acute lung injury caused by exposure to reactive chemicals remains challenging because of the lack of mechanism-based therapeutic approaches. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), an ion channel expressed in pulmonary tissues, is a crucial mediator of pressure-induced damage associated with ventilator-induced lung injury, heart failure, and infarction. Here, we examined the effects of two novel TRPV4 inhibitors in mice exposed to hydrochloric acid, mimicking acid exposure and acid aspiration injury, and to chlorine gas, a severe chemical threat with frequent exposures in domestic and occupational environments and in transportation accidents. Postexposure treatment with a TRPV4 inhibitor suppressed acid-induced pulmonary inflammation by diminishing neutrophils, macrophages, and associated chemokines and cytokines, while improving tissue pathology. These effects were recapitulated in TRPV4-deficient mice. TRPV4 inhibitors had similar anti-inflammatory effects in chlorine-exposed mice and inhibited vascular leakage, airway hyperreactivity, and increase in elastance, while improving blood oxygen saturation. In both models of lung injury we detected increased concentrations of N-acylamides, a class of endogenous TRP channel agonists. Taken together, we demonstrate that TRPV4 inhibitors are potent and efficacious countermeasures against severe chemical exposures, acting against exaggerated inflammatory responses, and protecting tissue barriers and cardiovascular function. PMID:24838754

  4. Fluoxetine and vitamin C synergistically inhibits blood-spinal cord barrier disruption and improves functional recovery after spinal cord injury.

    PubMed

    Lee, Jee Y; Choi, Hae Y; Yune, Tae Y

    2016-10-01

    Recently we reported that fluoxetine (10 mg/kg) improves functional recovery by attenuating blood spinal cord barrier (BSCB) disruption after spinal cord injury (SCI). Here we investigated whether a low-dose of fluoxetine (1 mg/kg) and vitamin C (100 mg/kg), separately not possessing any protective effect, prevents BSCB disruption and improves functional recovery when combined. After a moderate contusion injury at T9 in rat, a low-dose of fluoxetine and vitamin C, or the combination of both was administered intraperitoneally immediately after SCI and further treated once a day for 14 d. Co-treatment with fluoxetine and vitamin C significantly attenuated BSCB permeability at 1 d after SCI. When only fluoxetine or vitamin C was treated after injury, however, there was no effect on BSCB disruption. Co-treatment with fluoxetine and vitamin C also significantly inhibited the expression and activation of MMP-9 at 8 h and 1 d after injury, respectively, and the infiltration of neutrophils (at 1 d) and macrophages (at 5 d) and the expression of inflammatory mediators (at 2 h, 6 h, 8 h or 24 h after injury) were significantly inhibited by co-treatment with fluoxetine and vitamin C. Furthermore, the combination of fluoxetine and vitamin C attenuated apoptotic cell death at 1 d and 5 d and improved locomotor function at 5 weeks after SCI. These results demonstrate the synergistic effect combination of low-dose fluoxetine and vitamin C on BSCB disruption after SCI and furthermore support the effectiveness of the combination treatment regimen for the management of acute SCI. PMID:27256500

  5. Care initiation area yields dramatic results.

    PubMed

    2009-03-01

    The ED at Gaston Memorial Hospital in Gastonia, NC, has achieved dramatic results in key department metrics with a Care Initiation Area (CIA) and a physician in triage. Here's how the ED arrived at this winning solution: Leadership was trained in and implemented the Kaizen method, which eliminates redundant or inefficient process steps. Simulation software helped determine additional space needed by analyzing arrival patterns and other key data. After only two days of meetings, new ideas were implemented and tested. PMID:19275059

  6. Dramatic reduction of culture time of Mycobacterium tuberculosis

    NASA Astrophysics Data System (ADS)

    Ghodbane, Ramzi; Raoult, Didier; Drancourt, Michel

    2014-02-01

    Mycobacterium tuberculosis culture, a critical technique for routine diagnosis of tuberculosis, takes more than two weeks. Here, step-by-step improvements in the protocol including a new medium, microaerophlic atmosphere or ascorbic-acid supplement and autofluorescence detection dramatically shortened this delay. In the best case, primary culture and rifampicin susceptibility testing were achieved in 72 hours when specimens were inoculated directly on the medium supplemented by antibiotic at the beginning of the culture.

  7. Rosiglitazone Affects Nitric Oxide Synthases and Improves Renal Outcome in a Rat Model of Severe Ischemia/Reperfusion Injury

    PubMed Central

    Betz, Boris; Schneider, Reinhard; Kress, Tobias; Schick, Martin Alexander; Wanner, Christoph; Sauvant, Christoph

    2012-01-01

    Background. Nitric oxide (NO)-signal transduction plays an important role in renal ischemia/reperfusion (I/R) injury. NO produced by endothelial NO-synthase (eNOS) has protective functions whereas NO from inducible NO-synthase (iNOS) induces impairment. Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor (PPAR)-γ agonist exerted beneficial effects after renal I/R injury, so we investigated whether this might be causally linked with NOS imbalance. Methods. RGZ (5 mg/kg) was administered i.p. to SD-rats (f) subjected to bilateral renal ischemia (60 min). Following 24 h of reperfusion, inulin- and PAH-clearance as well as PAH-net secretion were determined. Morphological alterations were graded by histopathological scoring. Plasma NOx-production was measured. eNOS and iNOS expression was analyzed by qPCR. Cleaved caspase 3 (CC3) was determined as an apoptosis indicator and ED1 as a marker of macrophage infiltration in renal tissue. Results. RGZ improves renal function after renal I/R injury (PAH-/inulin-clearance, PAH-net secretion) and reduces histomorphological injury. Additionally, RGZ reduces NOx plasma levels, ED-1 positive cell infiltration and CC3 expression. iNOS-mRNA is reduced whereas eNOS-mRNA is increased by RGZ. Conclusion. RGZ has protective properties after severe renal I/R injury. Alterations of the NO pathway regarding eNOS and iNOS could be an explanation of the underlying mechanism of RGZ protection in renal I/R injury. PMID:22448163

  8. Intravenous Transplantation of Mesenchymal Progenitors Distribute Solely to the Lungs and Improve Outcomes in Cervical Spinal Cord Injury.

    PubMed

    White, Seok Voon; Czisch, Chris E; Han, May H; Plant, Christine D; Harvey, Alan R; Plant, Giles W

    2016-07-01

    Cellular transplantation strategies utilizing intraspinal injection of mesenchymal progenitor cells (MPCs) have been reported as beneficial for spinal cord injuries. However, intraspinal injection is not only technically challenging, but requires invasive surgical procedures for patients. Therefore, we investigated the feasibility and potential benefits of noninvasive intravenous injection of MPCs in two models of cervical spinal cord injury, unilateral C5 contusion and complete unilateral C5 hemisection. MPCs isolated from green fluorescence protein (GFP)-luciferase transgenic mice compact bone (1 × 10(6) cells), or vehicle Hank's Buffered Saline Solution (HBSS), were intravenously injected via the tail vein at D1, D3, D7, D10, or D14. Transplanted MPCs were tracked via bioluminescence imaging. Live in vivo imaging data showed that intravenously injected MPCs accumulate in the lungs, confirmed by postmortem bioluminescence signal-irrespective of the time of injection or injury model. The results showed a rapid, positive modulation of the inflammatory response providing protection to the injured spinal cord tissue. Histological processing of the lungs showed GFP(+) cells evenly distributed around the alveoli. We propose that injected cells can act as cellular target decoys to an immune system primed by injury, thereby lessening the inflammatory response at the injury site. We also propose that intravenous injected MPCs modulate the immune system via the lungs through secreted immune mediators or contact interaction with peripheral organs. In conclusion, the timing of intravenous injection of MPCs is key to the success for improving function and tissue preservation following cervical spinal cord injury. Stem Cells 2016;34:1812-1825. PMID:26989838

  9. Eprosartan improves cardiac function in swine working heart model of ischemia-reperfusion injury

    PubMed Central

    Weymann, Alexander; Sabashnikov, Anton; Patil, Nikhil P.; Konertz, Wolfgang; Modersohn, Diethelm; Dohmen, Pascal M.

    2014-01-01

    Background Eprosartan is an angiotensin II receptor antagonist used as an antihypertensive. We sought to evaluate the regional effect of Eprosartan on postinfarct ventricular remodeling and myocardial function in an isolated swine working heart model of ischemia-reperfusion injury. Material/Methods 22 swine hearts were perfused with the Langendorff perfusion apparatus under standard experimental conditions. Myocardial ischemia was induced by a 10-min left anterior descending artery ligation. Hearts were reperfused with either saline (control group, n=11), or Eprosartan (treatment group, n=11). Left ventricular pressure (LVP) and regional heart parameters such as intramyocardial pressure (IMP), wall thickening rate (WTh), and pressure-length-loops (PLL) were measured at baseline and after 30 min of reperfusion. Results Measured parameters were statistically similar between the 2 groups at baseline. The administration of Eprosartan led to a significantly better recovery of IMP and WTh: 44.4±2.5 mmHg vs. 51.2±3.3 mmHg, p<0.001 and 3.8±0.4 μm vs. 4.4±0.3 μm, p=0.001, respectively. PLL were also significantly higher in the treatment group following reperfusion (21694±3259 units vs. 31267±3429 units, p<0.01). There was no difference in the LVP response to Eprosartan versus controls (63.6±3.0 mmHg vs. 62.5±3.1 mmHg, p=0.400). Conclusions Pre-treatment with Eprosartan is associated with a significant improvement in regional cardiac function under ischemic conditions. Pharmacological treatment with eprosartan may exert a direct cardioprotective effect on ischemic myocardium. PMID:24762635

  10. 1-Deoxynojirimycin Alleviates Liver Injury and Improves Hepatic Glucose Metabolism in db/db Mice.

    PubMed

    Liu, Qingpu; Li, Xuan; Li, Cunyu; Zheng, Yunfeng; Wang, Fang; Li, Hongyang; Peng, Guoping

    2016-01-01

    The present study investigated the effect of 1-Deoxynojirimycin (DNJ) on liver injury and hepatic glucose metabolism in db/db mice. Mice were divided into five groups: normal control, db/db control, DNJ-20 (DNJ 20 mg·kg(-1)·day(-1)), DNJ-40 (DNJ 40 mg·kg(-1)·day(-1)) and DNJ-80 (DNJ 80 mg·kg(-1)·day(-1)). All doses were treated intravenously by tail vein for four weeks. DNJ was observed to significantly reduce the levels of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and liver TG, as well as activities of serum alanine aminotransferase (ALT), and aspartate transaminase (AST); DNJ also alleviated macrovesicular steatosis and decreased tumor necrosis factor α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6) levels in liver tissue. Furthermore, DNJ treatment significantly increased hepatic glycogen content, the activities of hexokinase (HK), pyruvate kinase (PK) in liver tissue, and decreased the activities of glucose-6-phosphatase (G6Pase), glycogen phosphorylase (GP), and phosphoenolpyruvate carboxykinase (PEPCK). Moreover, DNJ increased the phosphorylation of phosphatidylinositol 3 kinase (PI3K) on p85, protein kinase B (PKB) on Ser473, glycogen synthase kinase 3β (GSK-3β) on Ser9, and inhibited phosphorylation of glycogen synthase (GS) on Ser645 in liver tissue of db/db mice. These results demonstrate that DNJ can increase hepatic insulin sensitivity via strengthening of the insulin-stimulated PKB/GSK-3β signal pathway and by modulating glucose metabolic enzymes in db/db mice. Moreover, DNJ also can improve lipid homeostasis and attenuate hepatic steatosis in db/db mice. PMID:26927057

  11. Wnt Agonist Attenuates Liver Injury and Improves Survival after Hepatic Ischemia/Reperfusion

    PubMed Central

    Kuncewitch, Michael; Yang, Weng-Lang; Molmenti, Ernesto; Nicastro, Jeffrey; Coppa, Gene F.; Wang, Ping

    2012-01-01

    The Wnt/β-catenin signaling pathway is well characterized in stem cell biology and plays a critical role in liver development, regeneration, and homeostasis. We hypothesized that pharmacological activation of Wnt signaling protects against hepatic ischemia/reperfusion (I/R) injury through its known proliferative and anti-apoptotic properties. Sprague-Dawley rats underwent 70% hepatic ischemia by microvascular clamping of the hilum of the left and median lobes of the liver for 90 min, followed by reperfusion. Wnt agonist (2-amino-4-[3,4-(methylenedioxy)benzylamino]-6-(3-methoxyphenyl)pyrimidine, 5 mg/kg BW) or vehicle (20% DMSO in saline) in 0.5 ml was injected intraperitoneally (i.p.) 1 h prior to ischemia or infused intravenously over 30 min right after ischemia. Blood and tissue samples from the pre-treated groups were collected 24 h after reperfusion, and a survival study was performed. Hepatic expression of β-catenin and its downstream target gene Axin2 were decreased after I/R while Wnt agonist restored their expression to sham levels. Wnt agonist blunted I/R-induced elevations of AST, ALT, and LDH and significantly improved the microarchitecture of the liver. The cell proliferation determined by Ki67 immunostaining significantly increased with Wnt agonist treatment and inflammatory cascades were dampened in Wnt agonist-treated animals, as demonstrated by attenuations in IL-6, myeloperoxdase, iNOS and nitrotyrosine. Wnt agonist also significantly decreased the amount of apoptosis, as evidenced by decreases in both TUNEL staining as well as caspase-3 activity levels. Finally, the 10-day survival rate was increased from 27% in the vehicle group to 73% in the pre-treated Wnt agonist group and 55% in the Wnt agonist post-ischemia treatment group. Thus, we propose that direct Wnt/β-catenin stimulation may represent a novel therapeutic approach in the treatment of hepatic I/R. PMID:23143067

  12. Matrine attenuates focal cerebral ischemic injury by improving antioxidant activity and inhibiting apoptosis in mice

    PubMed Central

    ZHAO, PENG; ZHOU, RU; ZHU, XIAO-YUN; HAO, YIN-JU; LI, NAN; WANG, JIE; NIU, YANG; SUN, TAO; LI, YU-XIANG; YU, JIAN-QIANG

    2015-01-01

    Matrine, an active constituent of the Chinese herb, Sophora flavescens Ait., and it is known for its antioxidant, anti-inflammatory and antitumor activities. It has been demonstrated that matrine exerts protective effects against heart failure by decreasing the expression of caspase-3 and Bax, and increasing Bcl-2 levels. In this study, we aimed to determine whether these protective effects of matrine can be applied to cerebral ischemia. Following 7 successive days of treatment with matrine (7.5, 15 and 30 mg/kg) and nimodipine (1 mg/kg) by intraperitoneal injection, male Institute of Cancer Research (ICR) mice were subjected to middle cerebral artery occlusion (MCAO). Following reperfusion, the neurobehavioral score and brain infarct volume were estimated, and morphological changes were analyzed by hematoxylin and eosin (H&E) staining and electron microscopy. The percentage of apoptotic neurons was determined by flow cytometry. The levels of oxidative stress were assessed by measuring the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), and the total antioxidant capacity (T-AOC). Western blot analysis and immunofluorescence staining were used to examine the expression of the apoptosis-related proteins, caspase-3, Bax and Bcl-2. Our results revealed that pre-treatment with matrine significantly decreased the infarct volume and improved the neurological scores. Matrine also reduced the percentage of apoptotic neurons and relieved neuronal morphological damage. Furthermore, matrine markedly decreased the MDA levels, and increased SOD, GSH-Px and CAT activity, and T-AOC. Western blot analysis and immunofluorescence staining revealed a marked decrease in caspase-3 expression and an increase in the Bcl-2/Bax ratio in the group pre-treated with matrine (30 mg/kg) as compared with the vehicle-treated group. The findings of the present study demonstrate that matrine exerts neuroprotective effects against

  13. Low-level laser irradiation improves functional recovery and nerve regeneration in sciatic nerve crush rat injury model.

    PubMed

    Wang, Chau-Zen; Chen, Yi-Jen; Wang, Yan-Hsiung; Yeh, Ming-Long; Huang, Mao-Hsiung; Ho, Mei-Ling; Liang, Jen-I; Chen, Chia-Hsin

    2014-01-01

    The development of noninvasive approaches to facilitate the regeneration of post-traumatic nerve injury is important for clinical rehabilitation. In this study, we investigated the effective dose of noninvasive 808-nm low-level laser therapy (LLLT) on sciatic nerve crush rat injury model. Thirty-six male Sprague Dawley rats were divided into 6 experimental groups: a normal group with or without 808-nm LLLT at 8 J/cm(2) and a sciatic nerve crush injury group with or without 808-nm LLLT at 3, 8 or 15 J/cm(2). Rats were given consecutive transcutaneous LLLT at the crush site and sacrificed 20 days after the crush injury. Functional assessments of nerve regeneration were analyzed using the sciatic functional index (SFI) and hindlimb range of motion (ROM). Nerve regeneration was investigated by measuring the myelin sheath thickness of the sciatic nerve using transmission electron microscopy (TEM) and by analyzing the expression of growth-associated protein 43 (GAP43) in sciatic nerve using western blot and immunofluorescence staining. We found that sciatic-injured rats that were irradiated with LLLT at both 3 and 8 J/cm(2) had significantly improved SFI but that a significant improvement of ROM was only found in rats with LLLT at 8 J/cm(2). Furthermore, the myelin sheath thickness and GAP43 expression levels were significantly enhanced in sciatic nerve-crushed rats receiving 808-nm LLLT at 3 and 8 J/cm(2). Taken together, these results suggest that 808-nm LLLT at a low energy density (3 J/cm(2) and 8 J/cm(2)) is capable of enhancing sciatic nerve regeneration following a crush injury. PMID:25119457

  14. Intravenous Infusion of Magnesium Chloride Improves Epicenter Blood Flow during the Acute Stage of Contusive Spinal Cord Injury in Rats

    PubMed Central

    Muradov, Johongir M.

    2013-01-01

    Abstract Vasospasm, hemorrhage, and loss of microvessels at the site of contusive or compressive spinal cord injury lead to infarction and initiate secondary degeneration. Here, we used intravenous injection of endothelial-binding lectin followed by histology to show that the number of perfused microvessels at the injury site is decreased by 80–90% as early as 20 min following a moderate T9 contusion in adult female rats. Hemorrhage within the spinal cord also was maximal at 20 min, consistent with its vasoconstrictive actions in the central nervous system (CNS). Microvascular blood flow recovered to up to 50% of normal volume in the injury penumbra by 6 h, but not at the epicenter. A comparison with an endothelial cell marker suggested that many microvessels fail to be reperfused up to 48 h post-injury. The ischemia was probably caused by vasospasm of vessels penetrating the parenchyma, because repeated Doppler measurements over the spinal cord showed a doubling of total blood flow over the first 12 h. Moreover, intravenous infusion of magnesium chloride, used clinically to treat CNS vasospasm, greatly improved the number of perfused microvessels at 24 and 48 h. The magnesium treatment seemed safe as it did not increase hemorrhage, despite the improved parenchymal blood flow. However, the treatment did not reduce acute microvessel, motor neuron or oligodendrocyte loss, and when infused for 7 days did not affect functional recovery or spared epicenter white matter over a 4 week period. These data suggest that microvascular blood flow can be restored with a clinically relevant treatment following spinal cord injury. PMID:23302047

  15. Wound Healing Immediately Post-Thermal Injury Is Improved by Fat and Adipose Derived Stem Cell Isografts

    PubMed Central

    Loder, Shawn; Peterson, Jonathan R.; Agarwal, Shailesh; Eboda, Oluwatobi; Brownley, Cameron; DeLaRosa, Sara; Ranganathan, Kavitha; Cederna, Paul; Wang, Stewart C.; Levi, Benjamin

    2014-01-01

    Objectives Patients with severe burns suffer functional, structural, and aesthetic complications. It is important to explore reconstructive options given that no ideal treatment exists. Transfer of adipose and adipose-derived stem cells (ASCs) has been shown to improve healing in various models. We hypothesize that use of fat isografts and/or ASCs will improve healing in a mouse model of burn injury. Methods Twenty 6–8 week old C57BL/6 male mice received a 30% surface area partial-thickness scald burn. Adipose tissue and ASCs from inguinal fat pads were harvested from a second group of C57BL/6 mice. Burned mice received 500μl subcutaneous injection at burn site of 1) processed adipose, 2) ASCs, 3) mixed adipose (adipose and ASCs), or 4) sham (saline) injection (n=5/group) on the first day post-injury. Mice were followed by serial photography until sacrifice at days 5 and 14. Wounds were assessed for burn depth and healing by Hematoxylin and Eosin (H&E) and immunohistochemistry. Results All treated groups showed improved healing over controls defined by decreased wound depth, area, and apoptotic activity. After 5 days, mice receiving ASCs or mixed adipose displayed a non-significant improvement in vascularization. No significant changes in proliferation were noted at 5 days. Conclusions Adipose isografts improve some early markers of healing post-burn injury. We demonstrate that addition of these grafts improve specific structural markers of healing. This improvement may be due to an increase in early wound vascularity post-graft. Further studies are needed to optimize use of fat or ASC grafts in acute and reconstructive surgery. PMID:25185931

  16. Injury surveillance in young athletes: a clinician's guide to sports injury literature.

    PubMed

    Goldberg, Andrea S; Moroz, Leslie; Smith, Angela; Ganley, Theodore

    2007-01-01

    As participation in junior, high-school and college sports has increased dramatically over the last three decades, sports injuries have increased commensurately. In the US alone, sports-related injuries account for 2.6 million visits to the emergency room made by children and young adults (aged 5-24 years). Injuries sustained by high-school athletes have resulted in 500000 doctor visits, 30000 hospitalisations and a total cost to the healthcare system of nearly 2 billion dollars per year. Sports injury surveillance studies have long formed the backbone of injury prevention research, serving to highlight the types and patterns of injury that merit further investigation. Injury surveillance studies have been integral in guiding rule changes, equipment improvement and training regimens that prevent injury. Despite findings that the methodology of injury surveillance studies may significantly influence the design and efficacy of preventative interventions, relatively few sources address epidemiological considerations involved in such studies. The purpose of this review is 3-fold. First, to perform a review of the current injury surveillance literature in order to identify key epidemiological and methodological issues that arise when reading or conducting an injury surveillance study. Second, to identify and describe how injury surveillance studies have addressed these issues. Third, to provide recommendations about the identified issues in order to guide clinicians in the interpretation of data presented in such studies. Searches of Ovid MEDLINE (1966-present) and PubMed were performed. Thirty-three descriptive and review articles addressing epidemiological and methodological considerations in injury surveillance were selected, as well as 54 cohort studies and studies with an experimental design. Data with respect to each study's treatment of the three epidemiological issues of interest were extracted and synthesised into a table. This review identifies the following

  17. Study protocol: The Improving Care of Acute Lung Injury Patients (ICAP) study

    PubMed Central

    Needham, Dale M; Dennison, Cheryl R; Dowdy, David W; Mendez-Tellez, Pedro A; Ciesla, Nancy; Desai, Sanjay V; Sevransky, Jonathan; Shanholtz, Carl; Scharfstein, Daniel; Herridge, Margaret S; Pronovost, Peter J

    2006-01-01

    Introduction The short-term mortality benefit of lower tidal volume ventilation (LTVV) for patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) has been demonstrated in a large, multi-center randomized trial. However, the impact of LTVV and other critical care therapies on the longer-term outcomes of ALI/ARDS survivors remains uncertain. The Improving Care of ALI Patients (ICAP) study is a multi-site, prospective cohort study that aims to evaluate the longer-term outcomes of ALI/ARDS survivors with a particular focus on the effect of LTVV and other critical care therapies. Methods Consecutive mechanically ventilated ALI/ARDS patients from 11 intensive care units (ICUs) at four hospitals in the city of Baltimore, MD, USA, will be enrolled in a prospective cohort study. Exposures (patient-based, clinical management, and ICU organizational) will be comprehensively collected both at baseline and throughout patients' ICU stay. Outcomes, including mortality, organ impairment, functional status, and quality of life, will be assessed with the use of standardized surveys and testing at 3, 6, 12, and 24 months after ALI/ARDS diagnosis. A multi-faceted retention strategy will be used to minimize participant loss to follow-up. Results On the basis of the historical incidence of ALI/ARDS at the study sites, we expect to enroll 520 patients over two years. This projected sample size is more than double that of any published study of long-term outcomes in ALI/ARDS survivors, providing 86% power to detect a relative mortality hazard of 0.70 in patients receiving higher versus lower exposure to LTVV. The projected sample size also provides sufficient power to evaluate the association between a variety of other exposure and outcome variables, including quality of life. Conclusion The ICAP study is a novel, prospective cohort study that will build on previous critical care research to improve our understanding of the longer-term impact of ALI/ARDS, LTVV and

  18. An experimentally determined evolutionary model dramatically improves phylogenetic fit.

    PubMed

    Bloom, Jesse D

    2014-08-01

    All modern approaches to molecular phylogenetics require a quantitative model for how genes evolve. Unfortunately, existing evolutionary models do not realistically represent the site-heterogeneous selection that governs actual sequence change. Attempts to remedy this problem have involved augmenting these models with a burgeoning number of free parameters. Here, I demonstrate an alternative: Experimental determination of a parameter-free evolutionary model via mutagenesis, functional selection, and deep sequencing. Using this strategy, I create an evolutionary model for influenza nucleoprotein that describes the gene phylogeny far better than existing models with dozens or even hundreds of free parameters. Emerging high-throughput experimental strategies such as the one employed here provide fundamentally new information that has the potential to transform the sensitivity of phylogenetic and genetic analyses. PMID:24859245

  19. The Results Fieldbook: Practical Strategies from Dramatically Improved Schools.

    ERIC Educational Resources Information Center

    Schmoker, Mike

    This book offers methods on how to cultivate and capture teacher expertise--one of the most grossly underused assets in education. These methods are simple and include goal-oriented, data-driven collaboration and ongoing assessment that can lead to an array of effective innovations and strategies to enhance school effectiveness. Five case-study…

  20. Normothermic machine perfusion reduces bile duct injury and improves biliary epithelial function in rat donor livers.

    PubMed

    Op den Dries, Sanna; Karimian, Negin; Westerkamp, Andrie C; Sutton, Michael E; Kuipers, Michiel; Wiersema-Buist, Janneke; Ottens, Petra J; Kuipers, Jeroen; Giepmans, Ben N; Leuvenink, Henri G D; Lisman, Ton; Porte, Robert J

    2016-07-01

    Bile duct injury may occur during liver procurement and transplantation, especially in livers from donation after circulatory death (DCD) donors. Normothermic machine perfusion (NMP) has been shown to reduce hepatic injury compared to static cold storage (SCS). However, it is unknown whether NMP provides better preservation of bile ducts. The aim of this study was to determine the impact of NMP on bile duct preservation in both DCD and non-DCD livers. DCD and non-DCD livers obtained from Lewis rats were preserved for 3 hours using either SCS or NMP, followed by 2 hours ex vivo reperfusion. Biomarkers of bile duct injury (gamma-glutamyltransferase and lactate dehydrogenase in bile) were lower in NMP-preserved livers compared to SCS-preserved livers. Biliary bicarbonate concentration, reflecting biliary epithelial function, was 2-fold higher in NMP-preserved livers (P < 0.01). In parallel with this, the pH of the bile was significantly higher in NMP-preserved livers (7.63 ± 0.02 and 7.74 ± 0.05 for non-DCD and DCD livers, respectively) compared with SCS-preserved livers (7.46 ± 0.02 and 7.49 ± 0.04 for non-DCD and DCD livers, respectively). Scanning and transmission electron microscopy of donor extrahepatic bile ducts demonstrated significantly decreased injury of the biliary epithelium of NMP-preserved donor livers (including the loss of lateral interdigitations and mitochondrial injury). Differences between NMP and SCS were most prominent in DCD livers. Compared to conventional SCS, NMP provides superior preservation of bile duct epithelial cell function and morphology, especially in DCD donor livers. By reducing biliary injury, NMP could have an important impact on the utilization of DCD livers and outcome after transplantation. Liver Transplantation 22 994-1005 2016 AASLD. PMID:26946466

  1. Fgf2 improves functional recovery—decreasing gliosis and increasing radial glia and neural progenitor cells after spinal cord injury

    PubMed Central

    Goldshmit, Yona; Frisca, Frisca; Pinto, Alexander R; Pébay, Alice; Tang, Jean-Kitty K Y; Siegel, Ashley L; Kaslin, Jan; Currie, Peter D

    2014-01-01

    Objectives A major impediment for recovery after mammalian spinal cord injury (SCI) is the glial scar formed by proliferating reactive astrocytes. Finding factors that may reduce glial scarring, increase neuronal survival, and promote neurite outgrowth are of major importance for improving the outcome after SCI. Exogenous fibroblast growth factor (Fgf) has been shown to decrease injury volume and improve functional outcome; however, the mechanisms by which this is mediated are still largely unknown. Methods In this study, Fgf2 was administered for 2 weeks in mice subcutaneously, starting 30 min after spinal cord hemisection. Results Fgf2 treatment decreased the expression of TNF-a at the lesion site, decreased monocyte/macrophage infiltration, and decreased gliosis. Fgf2 induced astrocytes to adopt a polarized morphology and increased expression of radial markers such as Pax6 and nestin. In addition, the levels of chondroitin sulfate proteoglycans (CSPGs), expressed by glia, were markedly decreased. Furthermore, Fgf2 treatment promotes the formation of parallel glial processes, “bridges,” at the lesion site that enable regenerating axons through the injury site. Additionally, Fgf2 treatment increased Sox2-expressing cells in the gray matter and neurogenesis around and at the lesion site. Importantly, these effects were correlated with enhanced functional recovery of the left paretic hind limb. Conclusions Thus, early pharmacological intervention with Fgf2 following SCI is neuroprotective and creates a proregenerative environment by the modulation of the glia response. PMID:24683512

  2. Inhibitor of neuronal nitric oxide synthase improves gas exchange in ventilator-induced lung injury after pneumonectomy

    PubMed Central

    2012-01-01

    Background Mechanical ventilation with high tidal volumes may cause ventilator-induced lung injury (VILI) and enhanced generation of nitric oxide (NO). We demonstrated in sheep that pneumonectomy followed by injurious ventilation promotes pulmonary edema. We wished both to test the hypothesis that neuronal NOS (nNOS), which is distributed in airway epithelial and neuronal tissues, could be involved in the pathogenesis of VILI and we also aimed at investigating the influence of an inhibitor of nNOS on the course of VILI after pneumonectomy. Methods Anesthetized sheep underwent right pneumonectomy, mechanical ventilation with tidal volumes (VT) of 6 mL/kg and FiO2 0.5, and were subsequently randomized to a protectively ventilated group (PROTV; n = 8) keeping VT and FiO2 unchanged, respiratory rate (RR) 25 inflations/min and PEEP 4 cm H2O for the following 8 hrs; an injuriously ventilated group with VT of 12 mL/kg, zero end-expiratory pressure, and FiO2 and RR unchanged (INJV; n = 8) and a group, which additionally received the inhibitor of nNOS, 7-nitroindazole (NI) 1.0 mg/kg/h intravenously from 2 hours after the commencement of injurious ventilation (INJV + NI; n = 8). We assessed respiratory, hemodynamic and volumetric variables, including both the extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI). We measured plasma nitrite/nitrate (NOx) levels and examined lung biopsies for lung injury score (LIS). Results Both the injuriously ventilated groups demonstrated a 2–3-fold rise in EVLWI and PVPI, with no significant effects of NI. In the INJV group, gas exchange deteriorated in parallel with emerging respiratory acidosis, but administration of NI antagonized the derangement of oxygenation and the respiratory acidosis significantly. NOx displayed no significant changes and NI exerted no significant effect on LIS in the INJV group. Conclusion Inhibition of nNOS improved gas exchange, but did not

  3. Hyperbaric Oxygen Therapy Can Improve Post Concussion Syndrome Years after Mild Traumatic Brain Injury - Randomized Prospective Trial

    PubMed Central

    Fishlev, Gregori; Bechor, Yair; Volkov, Olga; Bergan, Jacob; Friedman, Mony; Hoofien, Dan; Shlamkovitch, Nathan; Ben-Jacob, Eshel; Efrati, Shai

    2013-01-01

    Background Traumatic brain injury (TBI) is the leading cause of death and disability in the US. Approximately 70-90% of the TBI cases are classified as mild, and up to 25% of them will not recover and suffer chronic neurocognitive impairments. The main pathology in these cases involves diffuse brain injuries, which are hard to detect by anatomical imaging yet noticeable in metabolic imaging. The current study tested the effectiveness of Hyperbaric Oxygen Therapy (HBOT) in improving brain function and quality of life in mTBI patients suffering chronic neurocognitive impairments. Methods and Findings The trial population included 56 mTBI patients 1–5 years after injury with prolonged post-concussion syndrome (PCS). The HBOT effect was evaluated by means of prospective, randomized, crossover controlled trial: the patients were randomly assigned to treated or crossover groups. Patients in the treated group were evaluated at baseline and following 40 HBOT sessions; patients in the crossover group were evaluated three times: at baseline, following a 2-month control period of no treatment, and following subsequent 2-months of 40 HBOT sessions. The HBOT protocol included 40 treatment sessions (5 days/week), 60 minutes each, with 100% oxygen at 1.5 ATA. “Mindstreams” was used for cognitive evaluations, quality of life (QOL) was evaluated by the EQ-5D, and changes in brain activity were assessed by SPECT imaging. Significant improvements were demonstrated in cognitive function and QOL in both groups following HBOT but no significant improvement was observed following the control period. SPECT imaging revealed elevated brain activity in good agreement with the cognitive improvements. Conclusions HBOT can induce neuroplasticity leading to repair of chronically impaired brain functions and improved quality of life in mTBI patients with prolonged PCS at late chronic stage. Trial Registration ClinicalTrials.gov NCT00715052 PMID:24260334

  4. Pulsed focused ultrasound pretreatment improves mesenchymal stem cell efficacy in preventing and rescuing established acute kidney injury in mice

    PubMed Central

    Burks, Scott R.; Nguyen, Ben A.; Tebebi, Pamela A.; Kim, Saejeong J.; Bresler, Michele N.; Ziadloo, Ali; Street, Jonathan M.; Yuen, Peter S. T.; Star, Robert A.; Frank, Joseph A.

    2014-01-01

    Animal studies have shown that mesenchymal stem cell (MSC) infusions improve acute kidney injury (AKI) outcomes when administered early after ischemic/reperfusion injury or within 24hr after cisplatin administration. These findings have spurred several human clinical trials to prevent AKI. However, no specific therapy effectively treats clinically obvious AKI or rescues renal function once advanced injury is established. We investigated if noninvasive image-guided pulsed focused ultrasound (pFUS) could alter the kidney microenvironment to enhance homing of subsequently infused MSC. To examine the efficacy of pFUS-enhanced cell homing in disease, we targeted pFUS to kidneys to enhance MSC homing after cisplatin-induced AKI. We found that pFUS enhanced MSC homing at 1 day post-cisplatin, prior to renal functional deficits, and that enhanced homing improved outcomes of renal function, tubular cell death, and regeneration at 5 days post-cisplatin compared to MSC alone. We then investigated whether pFUS+MSC therapy could rescue established AKI. MSC alone at 3 days post-cisplatin, after renal functional deficits were obvious, significantly improved 7-day survival of animals. Survival was further improved using pFUS+MSC. MSC, alone or with pFUS, changed kidney macrophage phenotypes from M1 to M2. This study shows pFUS is a neoadjuvant approach to improve MSC homing to diseased organs. pFUS with MSC better prevents AKI than MSC alone and allows rescue therapy in established AKI, which currently has no meaningful therapeutic options. PMID:25640064

  5. Locomotor step training with body weight support improves respiratory motor function in individuals with chronic spinal cord injury

    PubMed Central

    de Paleville, Daniela Terson; McKay, William; Aslan, Sevda; Folz, Rodney; Sayenko, Dimitry; Ovechkin, Alexander V.

    2013-01-01

    This prospective case-controlled clinical study was undertaken to investigate to what extent the manually assisted treadmill stepping Locomotor Training with body weight support (LT) can change respiratory function in individuals with chronic Spinal Cord Injury (SCI). Pulmonary function outcomes (Forced Vital Capacity /FVC/, Forced Expiratory Volume one second /FEV1/, Maximum Inspiratory Pressure /PImax/, Maximum Expiratory Pressure /PEmax/) and surface electromyographic (sEMG) measures of respiratory muscles activity during respiratory taskswere obtained from eight individuals with chronic C3-T12 SCI before and after 62±10 (Mean ± SD) sessions of the LT. FVC, FEV1, PImax, PEmax, amount of overall sEMG activity and rate of motor unit recruitment were significantly increased after LT (p<0.05) These results suggest that these improvements induced by the LT are likely the result of neuroplastic changes in spinal neural circuitry responsible for the activation of respiratory muscles preserved after injury. PMID:23999001

  6. Soccer injury in the lower extremities.

    PubMed

    Wong, P; Hong, Y

    2005-08-01

    Information about soccer injuries is required to develop prevention and rehabilitation programmes. Most soccer injuries occur in the lower extremities. This type of injury is reviewed here. Definitions of injury, injury rate, injury percentage, mechanism of injury, anatomical region of injury, type of injury, and severity of injury are summarised. In each section, a description and summary of the data are provided. Finally, the limitations of the studies and suggestions to improve the investigation of soccer injuries are provided. PMID:16046325

  7. Can Stretching Prior to Exercise and Sports Improve Performance and Prevent Injury?

    ERIC Educational Resources Information Center

    Bracko, Michael R.

    2002-01-01

    Examines data from research on stretching as it relates to enhanced performance and injury prevention so that fitness, exercise, and sports performance professionals can make informed decisions about stretching programs for clients. The paper notes that stretching is a misunderstood component of fitness and sports training. Few studies show…

  8. Improving on army field gauze for lethal vascular injuries: a progress report

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Uncontrolled hemorrhage is the leading cause of death on the battlefield and second leading cause of death in civilian trauma. Recent animal testing using a lethal arterial injury model compared a variety of woven and non woven products with granular products, and found only one product (WoundStat)...

  9. Improving the Quality of Staff and Participant Interaction in an Acquired Brain Injury Organization

    ERIC Educational Resources Information Center

    Guercio, John M.; Dixon, Mark R.

    2010-01-01

    Weekly observations of direct-care staff in a facility for persons with brain injury yielded less than optimal interactional style with facility residents. Following an observational baseline, staff were asked to self-rate a 15-min video sample of their interaction behavior with participants on their unit. They were then asked to compare their…

  10. Atypical Antipsychotic Medication Improves Aggression, but Not Self-Injurious Behaviour, in Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Ruedrich, S. L.; Swales, T. P.; Rossvanes, C.; Diana, L.; Arkadiev, V.; Lim, K.

    2008-01-01

    Objective: Atypical antipsychotic medications have largely supplanted their typical counterparts, both for psychosis and for the treatment of aggression and/or self-injurious behaviour (SIB), in persons with intellectual disabilities (ID). However, with the exception of risperidone, little systematic research supports their use in such persons.…

  11. PPARδ agonist attenuates alcohol-induced hepatic insulin resistance and improves liver injury and repair

    PubMed Central

    Pang, Maoyin; de la Monte, Suzanne M.; Longato, Lisa; Tong, Ming; He, Jiman; Chaudhry, Rajeeve; Duan, Kevin; Ouh, Jiyun; Wands, Jack R.

    2009-01-01

    Background/Aims Chronic ethanol exposure impairs liver regeneration due to inhibition of insulin signaling and oxidative injury. PPAR agonists function as insulin sensitizers and anti-inflammatory agents. We investigated whether treatment with a PPARδ agonist could restore hepatic insulin sensitivity, survival signaling, and regenerative responses vis-a-vis chronic ethanol feeding. Methods Adult rats were fed isocaloric liquid diets containing 0% or 37% ethanol, and administered a PPARδ agonist by i.p. injection. We used liver tissue to examine histopathology, gene expression, oxidative stress, insulin signaling, and regenerative responses to 2/3 hepatectomy. Results Chronic ethanol feeding caused insulin resistance, increased oxidative stress, lipid peroxidation, DNA damage, and hepatocellular injury in liver. These effects were associated with reduced insulin receptor binding and affinity, impaired survival signaling through PI3K/Akt/GSK3β, and reduced expression of insulin responsive genes mediating energy metabolism and tissue remodeling. PPARδ agonist treatment reduced ethanol-mediated hepatic injury, oxidative stress, lipid peroxidation, and insulin resistance, increased signaling through PI3K/Akt/GSK3β, and enhanced the regenerative response to partial hepatectomy. Conclusions PPARδ agonist administration may attenuate the severity of chronic ethanol-induced liver injury and ethanol’s adverse effects on the hepatic repair by restoring insulin responsiveness, even in the context of continued high-level ethanol consumption. PMID:19398227

  12. A Day at the Improv.... The Assessment and Treatment of Musculoskeletal Injuries in the Backcountry.

    ERIC Educational Resources Information Center

    Cochran, Brent

    Outdoor leaders and those involved in personal outdoor adventure pursuits must be knowledgeable in the assessment, treatment, and prevention of musculoskeletal injuries in the backcountry. In the wilderness medicine setting, extended time periods of patient care, rugged terrain, severe environmental conditions, and limited resources create…

  13. Propranolol Improves Impaired Hepatic Phosphatidylinositol 3-Kinase/Akt Signaling after Burn Injury

    PubMed Central

    Brooks, Natasha C; Song, Juquan; Boehning, Darren; Kraft, Robert; Finnerty, Celeste C; Herndon, David N; Jeschke, Marc G

    2012-01-01

    Severe burn injury is associated with induction of the hepatic endoplasmic reticulum (ER) stress response. ER stress leads to activation of c-Jun N-terminal kinase (JNK), suppression of insulin receptor signaling via phosphorylation of insulin receptor substrate 1 and subsequent insulin resistance. Marked and sustained increases in catecholamines are prominent after a burn. Here, we show that administration of propranolol, a nonselective β1/2 adrenergic receptor antagonist, attenuates ER stress and JNK activation. Attenuation of ER stress by propranolol results in increased insulin sensitivity, as determined by activation of hepatic phosphatidylinositol 3-kinase and Akt. We conclude that catecholamine release is responsible for the ER stress response and impaired insulin receptor signaling after burn injury. PMID:22396018

  14. Post-treatment with the Combination of AICAR and Carnitine Improves Renal Function after Ischemia/Reperfusion Injury

    PubMed Central

    Idrovo, Juan-Pablo; Yang, Weng-Lang; Matsuda, Akihisa; Nicastro, Jeffrey; Coppa, Gene F.; Wang, Ping

    2011-01-01

    Renal ischemia/reperfusion (I/R) injury is a major clinical problem where main metabolic pathways are compromised and cellular homeostasis crashes after ATP depletion. Fatty acids are major energy source in the kidneys. Carnitine palmitoyltransferase I (CPT1), a mitochondrial membrane enzyme, utilizes carnitine to transport fatty acids to mitochondria for the process of β-oxidation and ATP generation. In addition, CPT1 activity is indirectly regulated by adenosine monophosphate (AMP)-activated protein kinase, which can be activated by 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR). We hypothesized that administration of carnitine and AICAR could reestablish the energetic balance after reperfusion and ameliorate renal I/R injury. Male adult rats were subjected to renal I/R by bilateral renal pedicle clamping for 60 min, followed by administration of saline (vehicle), carnitine (250 mg/kg BW), AICAR (30 mg/kg BW), or combination of both drugs. Blood and renal tissues were collected 24 h after reperfusion for various measurements. Renal carnitine levels decreased 53% after I/R. The combined treatment significantly increased CPT1 activity and ATP levels, and lowered renal malondialdehyde and serum TNF-α levels against the vehicle group. It led to improvement in renal morphology and histological damage score associated with diminution in serum creatinine, blood urea nitrogen, and aspartate aminotransferase levels. Moreover, the combined treatment significantly improved the survival rate in comparison to the vehicle group. In contrast, administration of either drug alone did not show a significant improvement in most of the measurements. In conclusion, enhancing energy metabolism by combination of carnitine and AICAR provides a novel modality to treat renal I/R injury. PMID:21841537

  15. Heat acclimation provides sustained improvement in functional recovery and attenuates apoptosis after traumatic brain injury.

    PubMed

    Umscheif, Gali; Umschwief, Gali; Shein, Na'ama A; Alexandrovich, Alexander G; Trembovler, Victoria; Horowitz, Michal; Shohami, Esther

    2010-03-01

    Heat acclimation (HA) offers functional neuroprotection in mice after traumatic brain injury (TBI). This study further characterizes endogenous neuroprotection acquired by HA (34+/-1 degrees C, 30 d) after TBI. We establish here the ability of HA to induce sustained functional benefits and to reduce activation of apoptotic pathways. Neurobehavioral recovery, assessed by the Neurological Severity Score, was greater in HA mice up to 8 days after injury as compared with normothermic controls (P<0.05) and lesion volume was also smaller in the HA group (P<0.05). Reduced apoptotic cell death in HA mice was confirmed using caspase-3 activity measurements and immunohistochemistry. To investigate the underlying molecular pathways, expression levels of intrinsic apoptotic pathway-related proteins were examined. HA mice displayed higher mitochondrial levels of antiapoptotic Bcl-xL, accompanied by lower proapoptotic Bad levels and decreased cytochrome c release, suggesting a higher apoptotic threshold. Taken together with our previous reports, indicating increased Akt phosphorylation and antioxidative capacity, alongside with reduced tumor necrosis alpha levels after TBI in HA animals, the current results support the involvement of an antiapoptotic effect in HA-induced neuroprotection. Current results warrant further study as TBI-induced apoptosis may persist over weeks after injury, possibly providing a target for belated therapeutic intervention. PMID:19904288

  16. Exercise-induced improvement in cognitive performance after traumatic brain-injury in rats is dependent on BDNF Activation

    PubMed Central

    Griesbach, Grace Sophia; Hovda, David Allen; Gomez-Pinilla, Fernando

    2009-01-01

    We have previously shown that voluntary exercise upregulates brain-derived neurotrophic factor (BDNF) within the hippocampus and is associated with an enhancement of cognitive recovery after a lateral fluid-percussion injury (FPI). In order to determine if BDNF is critical to this effect we used an immunoadhesin chimera (TrkB-IgG) that inactivates free BDNF. This BDNF inhibitor was administered to adult male rats two weeks after they had received a mild fluid percussion injury (FPI) or sham surgery. These animals were then housed with or without access to a running wheel (RW) from post-injury-day (PID) 14 to 20. On PID 21, rats were tested for spatial learning in a Morris Water Maze. Results showed that exercise counteracted the cognitive deficits associated with the injury. However this exercise-induced cognitive improvement was attenuated in the FPI-RW rats that were treated with TrkB-IgG. Molecules important for synaptic plasticity and learning were measured in a separate group of rats that were sacrificed immediately after exercise (PID 21). Western blot analyses showed that exercise increased the mature form of BDNF, synapsin I and cyclic-AMP response-element-binding protein (CREB) in the vehicle treated Sham-RW group. However, only the mature form of BDNF and CREB were increased in the vehicle treated FPI-RW group. Blocking BDNF (pre administration of TrkB-IgG) greatly reduced the molecular effects of exercise in that exercise-induced increases of BDNF, synapsin I and CREB were not observed. These studies provide evidence that BDNF has a major role in exercise's cognitive effects in traumatically injured brain. PMID:19555673

  17. Aqueous Date Fruit Efficiency as Preventing Traumatic Brain Deterioration and Improving Pathological Parameters after Traumatic Brain Injury in Male Rats

    PubMed Central

    Badeli, Hamze; Shahrokhi, Nader; KhoshNazar, Mahdieosadat; Asadi-Shekaari, Majid; Shabani, Mohammad; Eftekhar Vaghefi, Hassan; Khaksari, Mohammad; Basiri, Mohsen

    2016-01-01

    Objective Following traumatic brain injury, disruption of blood-brain-barrier and consequent brain edema are critical events which might lead to increasing intracranial pressure (ICP), and nerve damage. The current study assessed the effects of aqueous date fruit extract (ADFE) on the aforementioned parameters. Materials and Methods In this experimental study, diffused traumatic brain injury (TBI) was generated in adult male rats using Marmarou’s method. Experimental groups include two pre-treatment (oral ADFE, 4 and 8 mL/kg for 14 days), vehicle (distilled water, for 14 days) and sham groups. Brain edema and neuronal injury were measured 72 hours after TBI. Veterinary coma scale (VCS) and ICP were determined at -1, 4, 24, 48 and 72 hours after TBI. Differences among multiple groups were assessed using ANOVA. Turkey’s test was employed for the ANOVA post-hoc analysis. The criterion of statistical significance was sign at P<0.05. Results Brain water content in ADFE-treated groups was decreased in comparison with the TBI+vehicle group. VCS at 24, 48 and 72 hours after TBI showed a significant increase in ADFE groups in comparison with the TBI+vehicle group. ICP at 24, 48 and 72 hours after TBI, was decreased in ADFE groups, compared to the TBI+vehicle. Brain edema, ICP and neuronal injury were also decreased in ADFE group, but VCS was increased following on TBI. Conclusion ADFE pre-treatment demonstrated an efficient method for preventing traumatic brain deterioration and improving pathological parameters after TBI. PMID:27602324

  18. Maverick Comet Splits during Dramatic Outburst

    NASA Astrophysics Data System (ADS)

    1996-01-01

    New ESO Observations of P/Schwassmann-Wachmann 3 A few months ago, Periodic Comet Schwassmann-Wachmann 3 underwent a dramatic and completely unexpected, thousand-fold brightening. At that time, the cause for this interesting event was unknown. However, observations with the two largest ESO telescopes have now shown that the ``dirty snowball'' nucleus of this comet has recently split into at least four individual pieces [1]. There is little doubt that the outburst and the splitting event(s) are closely related and that the greatly increased dust and gas production is due to ``fresh'' material of the icy cometary nucleus becoming exposed to the surrounding space for the first time. A Comet with a Troubled History Comet Schwassmann-Wachmann 3 was discovered on May 2, 1930, on a photographic plate obtained at the Hamburg Observatory (Germany) by two astronomers at this institution, Arnold Schwassmann and Arthur Arno Wachmann. The subsequent observations showed that the comet moved in an elliptical orbit with a revolution period of somewhat more than 5 years. Great efforts were expended to observe the comet during the next returns, but it was not recovered until nearly 50 years and eight revolutions later, when its faint image was found of a plate obtained in August 1979 with a telescope at the Perth Observatory in Western Australia. It was missed in 1984, but was sighted again in 1989 and most recently in 1994. Thus this comet has only been observed during four out of thirteen approaches since 1930. While this may be partly due to a less advantageous location in the sky at some returns, it is also a strong indication that the comet behaves unpredictably and must have a quite variable brightness. For the sake of convenience this comet is often referred to as ``SW-3'' by professional astronomers. Recent orbital calculations have shown that it was inserted into the present, short-period orbit by the strong gravitational pull of Jupiter during several, relatively close

  19. Serotonin and Histamine Therapy Increases Tetanic Forces of Myoblasts, Reduces Muscle Injury, and Improves Grip Strength Performance of Dmdmdx Mice

    PubMed Central

    Lins, Jeremy; Lambert, Kristyn; Lazauski, Joan; Spaulding, James; McMichael, John

    2015-01-01

    Duchenne muscular dystrophy (DMD) is a recessive X-linked fatal disorder caused by a mutation in the dystrophin gene. Although several therapeutic approaches have been studied, none has led to substantial long-term effects in patients. The aim of this study was to test a serotonin and histamine (S&H) combination on human skeletal myoblasts and Dmdmdx mice for its effects on muscle strength and injury. Normal human bioartificial muscles (BAMs) were treated, and muscle tetanic forces and muscle injury tests were performed using the MyoForce Analysis System. Dmdmdx mice, the murine model of DMD, were administered serotonin, histamine, or S&H combination twice daily for 6 weeks, and functional performance tests were conducted once a week. The S&H combination treatment caused significant increases in tetanic forces at all time points and concentrations tested as compared to the saline controls. Dose response of the BAMs to the treatment demonstrated a significant increase in force generation at all concentrations compared to the controls after 3 to 4 days of drug treatment. The highest 3 concentrations had a significant effect on lowering contractile-induced injury as measured by a reduction in the release of adenylate kinase. Histamine-only and S&H treatments improved grip strength of Dmdmdx mice, whereas serotonin-only treatment resulted in no significant improvement in muscle strength. The results of this study indicate that S&H therapy might be a promising new strategy for muscular dystrophies and that the mechanism should be further investigated. PMID:26740813

  20. Co-staining for Keratins 8/18 plus Ubiquitin Improves Detection of Hepatocyte Injury in Nonalcoholic Fatty Liver Disease

    PubMed Central

    Guy, Cynthia D; Suzuki, Ayako; Burchette, James L; Brunt, Elizabeth M; Abdelmalek, Manal F; Cardona, Diana; McCall, Shannon J; Ünalp, Aynur; Belt, Patricia; Ferrell, Linda D; Diehl, Anna Mae

    2011-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a global health dilemma. The gold standard for diagnosis is liver biopsy. Ballooned hepatocytes (BH) are histologic manifestations of hepatocellular injury and are characteristic features of steatohepatitis (SH), the more severe form of NAFLD. Definitive histologic identification of BH on routine stains, however, can be difficult. Immunohistochemical (IHC) evidence for loss of the normal hepatocytic keratins 8/18 (K8/18) can serve as an objective marker of BH. We sought to explore the utility of a K8/18 plus ubiquitin (Ub) double IHC stain for the histologic evaluation of adult NAFLD. Double IHC staining for K8/18 and Ub was analyzed using 40 adult human NAFLD core liver biopsies. Ballooned hepatocytes lack K8/18 staining (KBH) as previously shown by others, but normal size hepatocytes with keratin loss (KH) are approximately five times greater in number than KBH. KBH, KH, and Ub deposits show a zonal distribution, are positively associated with each other, and are frequently found adjacent to or intermixed with fibrous matrix. All three lesions correlate with fibrosis stage and the H&E diagnosis of SH (all p values < 0.05). Compared to H&E staining, IHC staining improves the receiver operating characteristics curve for advanced fibrosis (0.77 vs. 0.83, 0.89, and 0.89 for KBH, KH, and Ub, respectively) because IHC is more sensitive and specific for fibrogenic hepatocellular injury than H&E staining. K8/18+Ub double IHC stain improves detection of hepatocyte injury in NAFLD. Thus, it may help differentiate NASH from NAFL. PMID:22036053

  1. Epidermal growth factor improves survival and prevents intestinal injury in a murine model of Pseudomonas aeruginosa pneumonia

    PubMed Central

    Dominguez, Jessica A.; Vithayathil, Paul J.; Khailova, Ludmila; Lawrance, Christopher P.; Samocha, Alexandr J.; Jung, Enjae; Leathersich, Ann M.; Dunne, W. Michael; Coopersmith, Craig M.

    2011-01-01

    Mortality from pneumonia is mediated, in part, through extrapulmonary causes. Epidermal growth factor (EGF) has broad cytoprotective effects, including potent restorative properties in the injured intestine. The purpose of this study was to determine the efficacy of EGF treatment following Pseudomonas aeruginosa pneumonia. FVB/N mice underwent intratracheal injection of either Pseudomonas aeruginosa or saline and were then randomized to receive either systemic EGF or vehicle beginning immediately or 24 hours after the onset of pneumonia. Systemic EGF decreased seven-day mortality from 65% to 10% when initiated immediately after the onset of pneumonia and to 27% when initiated 24 hours after the onset of pneumonia. Even though injury in pneumonia is initiated in the lungs, the survival advantage conferred by EGF was not associated with improvements in pulmonary pathology. In contrast, EGF prevented intestinal injury by reversing pneumonia-induced increases in intestinal epithelial apoptosis and decreases in intestinal proliferation and villus length. Systemic cytokines, kidney and liver function were unaffected by EGF therapy although EGF decreased pneumonia-induced splenocyte apoptosis. To determine whether the intestine was sufficient to account for extrapulmonary effects induced by EGF, a separate set of experiments were done using transgenic mice with enterocyte-specific overexpression of EGF (IFABP-EGF mice) which were compared to WT mice subjected to pneumonia. IFABP-EGF mice had improved survival compared to WT mice following pneumonia (50% vs. 28% respectively, p<0.05) and were protected from pneumonia-induced intestinal injury. Thus, EGF may be a potential adjunctive therapy for pneumonia, mediated in part by its effects on the intestine. PMID:21701422

  2. Epidermal growth factor improves survival and prevents intestinal injury in a murine model of pseudomonas aeruginosa pneumonia.

    PubMed

    Dominguez, Jessica A; Vithayathil, Paul J; Khailova, Ludmila; Lawrance, Christopher P; Samocha, Alexandr J; Jung, Enjae; Leathersich, Ann M; Dunne, W Michael; Coopersmith, Craig M

    2011-10-01

    Mortality from pneumonia is mediated, in part, through extrapulmonary causes. Epidermal growth factor (EGF) has broad cytoprotective effects, including potent restorative properties in the injured intestine. The purpose of this study was to determine the efficacy of EGF treatment following Pseudomonas aeruginosa pneumonia. FVB/N mice underwent intratracheal injection of either P. aeruginosa or saline and were then randomized to receive either systemic EGF or vehicle beginning immediately or 24 h after the onset of pneumonia. Systemic EGF decreased 7-day mortality from 65% to 10% when initiated immediately after the onset of pneumonia and to 27% when initiated 24 h after the onset of pneumonia. Even though injury in pneumonia is initiated in the lungs, the survival advantage conferred by EGF was not associated with improvements in pulmonary pathology. In contrast, EGF prevented intestinal injury by reversing pneumonia-induced increases in intestinal epithelial apoptosis and decreases in intestinal proliferation and villus length. Systemic cytokines and kidney and liver function were unaffected by EGF therapy, although EGF decreased pneumonia-induced splenocyte apoptosis. To determine whether the intestine was sufficient to account for extrapulmonary effects induced by EGF, a separate set of experiments was done using transgenic mice with enterocyte-specific overexpression of EGF (IFABP-EGF [intestinal fatty acid-binding protein linked to mouse EGF] mice), which were compared with wild-type mice subjected to pneumonia. IFABP-EGF mice had improved survival compared with wild-type mice following pneumonia (50% vs. 28%, respectively, P < 0.05) and were protected from pneumonia-induced intestinal injury. Thus, EGF may be a potential adjunctive therapy for pneumonia, mediated in part by its effects on the intestine. PMID:21701422

  3. Attenuating the Endoplasmic Reticulum Stress Response Improves Functional Recovery After Spinal Cord Injury

    PubMed Central

    OHRI, SUJATA SARASWAT; MADDIE, MELISSA A.; ZHAO, YONGMEI; QIU, MENGSHENG S.; HETMAN, MICHAL; WHITTEMORE, SCOTT R.

    2012-01-01

    Activation of the unfolded protein response (UPR) is involved in the pathogenesis of numerous CNS myelin abnormalities; yet, its direct role in traumatic spinal cord injury (SCI)-induced demyelination is not known. The UPR is an evolutionarily conserved cell defense mechanism initiated to restore endoplasmic reticulum homeostasis in response to various cellular stresses including infection, trauma, and oxidative damage. However, if uncompensated, the UPR triggers apoptotic cell death. We demonstrate that the three signaling branches of UPR including the PERK, ATF6, and IRE1α are rapidly initiated in a mouse model of contusive SCI specifically at the injury epicenter. Immunohistochemical analyses of the various UPR markers revealed that in neurons, the UPR appeared at 6 and 24-h post-SCI. In contrast, in oligodendrocytes and astroglia, UPR persisted at least for up to 3 days post-SCI. The UPR-associated proapoptotic transcriptional regulator CHOP was among the UPR markers upregulated in neurons and oligodendrocytes, but not in astrocytes, of traumatized mouse spinal cords. To directly analyze its role in SCI, WT and CHOP null mice received a moderate T9 contusive injury. Deletion of CHOP led to an overall attenuation of the UPR after contusive SCI. Furthermore, analyses of hindlimb locomotion demonstrated a significant functional recovery that correlated with an increase in white-matter sparing, transcript levels of myelin basic protein, and Claudin 11 and decreased oligodendrocyte apoptosis in CHOP null mice in contrast to WT animals. Thus, our study provides evidence that the UPR contributes to oligodendrocyte loss after traumatic SCI. PMID:21638341

  4. Hemojuvelin Modulates Iron Stress During Acute Kidney Injury: Improved by Furin Inhibitor

    PubMed Central

    Young, Guang-Huar; Huang, Tao-Min; Wu, Che-Hsiung; Lai, Chun-Fu; Hou, Chun-Cheng; Peng, Kang-Yung; Liang, Chan-Jung; Lin, Shuei-Liong; Chang, Shih-Chung; Tsai, Pi-Ru; Wu, Kwan-Dun

    2014-01-01

    Abstract Aims: Free iron plays an important role in the pathogenesis of acute kidney injury (AKI) via the formation of hydroxyl radicals. Systemic iron homeostasis is controlled by the hemojuvelin-hepcidin-ferroportin axis in the liver, but less is known about this role in AKI. Results: By proteomics, we identified a 42 kDa soluble hemojuvelin (sHJV), processed by furin protease from membrane-bound hemojuvelin (mHJV), in the urine during AKI after cardiac surgery. Biopsies from human and mouse specimens with AKI confirm that HJV is extensively increased in renal tubules. Iron overload enhanced the expression of hemojuvelin-hepcidin signaling pathway. The furin inhibitor (FI) decreases furin-mediated proteolytic cleavage of mHJV into sHJV and augments the mHJV/sHJV ratio after iron overload with hypoxia condition. The FI could reduce renal tubule apoptosis, stabilize hypoxic induced factor-1, prevent the accumulation of iron in the kidney, and further ameliorate ischemic-reperfusion injury. mHJV is associated with decreasing total kidney iron, secreting hepcidin, and promoting the degradation of ferroportin at AKI, whereas sHJV does the opposite. Innovation: This study suggests the ratio of mHJV/sHJV affects the iron deposition during acute kidney injury and sHJV could be an early biomarker of AKI. Conclusion: Our findings link endogenous HJV inextricably with renal iron homeostasis for the first time, add new significance to early predict AKI, and identify novel therapeutic targets to reduce the severity of AKI using the FI. Antioxid. Redox Signal. 20, 1181–1194. PMID:23901875

  5. Mesenchymal Stem Cell Graft Improves Recovery after Spinal Cord Injury in Adult Rats through Neurotrophic and Pro-Angiogenic Actions

    PubMed Central

    Botman, Olivier; Sid, Selim; Schoenen, Jean; Franzen, Rachelle

    2012-01-01

    Numerous strategies have been managed to improve functional recovery after spinal cord injury (SCI) but an optimal strategy doesn't exist yet. Actually, it is the complexity of the injured spinal cord pathophysiology that begets the multifactorial approaches assessed to favour tissue protection, axonal regrowth and functional recovery. In this context, it appears that mesenchymal stem cells (MSCs) could take an interesting part. The aim of this study is to graft MSCs after a spinal cord compression injury in adult rat to assess their effect on functional recovery and to highlight their mechanisms of action. We found that in intravenously grafted animals, MSCs induce, as early as 1 week after the graft, an improvement of their open field and grid navigation scores compared to control animals. At the histological analysis of their dissected spinal cord, no MSCs were found within the host despite their BrdU labelling performed before the graft, whatever the delay observed: 7, 14 or 21 days. However, a cytokine array performed on spinal cord extracts 3 days after MSC graft reveals a significant increase of NGF expression in the injured tissue. Also, a significant tissue sparing effect of MSC graft was observed. Finally, we also show that MSCs promote vascularisation, as the density of blood vessels within the lesioned area was higher in grafted rats. In conclusion, we bring here some new evidences that MSCs most likely act throughout their secretions and not via their own integration/differentiation within the host tissue. PMID:22745769

  6. Dramatic innovations in modern surgical subspecialties

    PubMed Central

    Ball, Chad G.; Sutherland, Francis; Kirkpatrick, Andrew W.; Dixon, Elijah; MacLean, Anthony R.; Mack, Lloyd A.; Feliciano, David V.; Rajani, Ravi R.; Karmy-Jones, Riyad; Buie, W. Donald; Temple, Walley J.; Rozycki, Grace S.; Simeone, Alan

    2010-01-01

    Innovation is defined as the introduction of something new, whether an idea, method or device. In this article, we describe the most important and innovative concepts and techniques that have advanced patient care within modern surgical subspecialties. We performed a systematic literature review and consulted academic subspecialty experts to evaluate recent changes in practice. The identified innovations included reduced blood loss and improved training in hepatobiliary surgery, total mesorectal excision and neoadjuvant therapies in colorectal surgery, prosthetic mesh in outpatient surgery, sentinel lymph node theory in surgical oncology, endovascular and wire-based skills in vascular and cardiovascular surgery, and the acceptance of abnormal anatomy through damage-control procedures in trauma and critical care. The common denominator among all subspecialties is an improvement in patient care manifested as a decrease in morbidity and mortality. Surgeons must continue to pursue innovative thinking, technological advances, improved training and systematic research. PMID:20858379

  7. Locomotor training improves reciprocal and nonreciprocal inhibitory control of soleus motoneurons in human spinal cord injury

    PubMed Central

    Smith, Andrew C.; Mummidisetty, Chaithanya K.

    2015-01-01

    Pathologic reorganization of spinal networks and activity-dependent plasticity are common neuronal adaptations after spinal cord injury (SCI) in humans. In this work, we examined changes of reciprocal Ia and nonreciprocal Ib inhibition after locomotor training in 16 people with chronic SCI. The soleus H-reflex depression following common peroneal nerve (CPN) and medial gastrocnemius (MG) nerve stimulation at short conditioning-test (C-T) intervals was assessed before and after training in the seated position and during stepping. The conditioned H reflexes were normalized to the unconditioned H reflex recorded during seated. During stepping, both H reflexes were normalized to the maximal M wave evoked at each bin of the step cycle. In the seated position, locomotor training replaced reciprocal facilitation with reciprocal inhibition in all subjects, and Ib facilitation was replaced by Ib inhibition in 13 out of 14 subjects. During stepping, reciprocal inhibition was decreased at early stance and increased at midswing in American Spinal Injury Association Impairment Scale C (AIS C) and was decreased at midstance and midswing phases in AIS D after training. Ib inhibition was decreased at early swing and increased at late swing in AIS C and was decreased at early stance phase in AIS D after training. The results of this study support that locomotor training alters postsynaptic actions of Ia and Ib inhibitory interneurons on soleus motoneurons at rest and during stepping and that such changes occur in cases with limited or absent supraspinal inputs. PMID:25609110

  8. Intravenous Multipotent Adult Progenitor Cell Therapy Attenuates Activated Microglial/Macrophage Response and Improves Spatial Learning After Traumatic Brain Injury

    PubMed Central

    Bedi, Supinder S.; Hetz, Robert; Thomas, Chelsea; Smith, Philippa; Olsen, Alex B.; Williams, Stephen; Xue, Hasen; Aroom, Kevin; Uray, Karen; Hamilton, Jason; Mays, Robert W.

    2013-01-01

    We previously demonstrated that the intravenous delivery of multipotent adult progenitor cells (MAPCs) after traumatic brain injury (TBI) in rodents provides neuroprotection by preserving the blood-brain barrier and systemically attenuating inflammation in the acute time frame following cell treatment; however, the long-term behavioral and anti-inflammatory effects of MAPC administration after TBI have yet to be explored. We hypothesized that the intravenous injection of MAPCs after TBI attenuates the inflammatory response (as measured by microglial morphology) and improves performance at motor tasks and spatial learning (Morris water maze [MWM]). MAPCs were administered intravenously 2 and 24 hours after a cortical contusion injury (CCI). We tested four groups at 120 days after TBI: sham (uninjured), injured but not treated (CCI), and injured and treated with one of two concentrations of MAPCs, either 2 million cells per kilogram (CCI-2) or 10 million cells per kilogram (CCI-10). CCI-10 rats showed significant improvement in left hind limb deficit on the balance beam. On the fifth day of MWM trials, CCI-10 animals showed a significant decrease in both latency to platform and distance traveled compared with CCI. Probe trials revealed a significant decrease in proximity measure in CCI-10 compared with CCI, suggesting improved memory retrieval. Neuroinflammation was quantified by enumerating activated microglia in the ipsilateral hippocampus. We observed a significant decrease in the number of activated microglia in the dentate gyrus in CCI-10 compared with CCI. Our results demonstrate that intravenous MAPC treatment after TBI in a rodent model offers long-term improvements in spatial learning as well as attenuation of neuroinflammation. PMID:24191266

  9. Improved differentiation of oligodendrocyte precursor cells and neurological function after spinal cord injury in rats by oscillating field stimulation.

    PubMed

    Jing, J-H; Qian, J; Zhu, N; Chou, W-B; Huang, X-J

    2015-09-10

    Oscillating field stimulation (OFS) has been used in attempts to treat spinal cord injury (SCI) and has been shown to improve remyelination after SCI in rats. However, some controversies regarding the effects of OFS have been presented in previous papers. Oligodendrocytes (OLs) are the main cell for remyelination and are derived from the differentiation of oligodendrocyte precursor cells (OPCs). To date, it has been unclear whether the differentiation of OPCs can be regulated by OFS. The goal of this study was to determine if OFS can improve the differentiation of OPCs and promote the recovery of neurological function after SCI in rats. Immature and mature OLs were observed in spinal cord slices through immunofluorescence staining. Levels of adenosine triphosphate (ATP) and the cytokine leukemia inhibitory factor (LIF) were detected by enzyme-linked immunosorbent assay (ELISA). Basso-Beattie-Bresnahan (BBB) scores and transcranial magnetic motor-evoked potentials (tcMMEPs) were used to evaluate the locomotor outcomes of rats after SCI. Our results showed a significant improvement in the differentiation of OPCs and the content of ATP and LIF in the injured spinal cord in the OFS group. Furthermore, BBB scores and tcMMEPs were significantly improved in the rats stimulated by OFS. These findings suggest that OFS can improve the differentiation of OPCs and promote the recovery of neurological function following SCI in rats. PMID:26166729

  10. Rat Urinary Osteopontin and Neutrophil Gelatinase-Associated Lipocalin Improve Certainty of Detecting Drug-Induced Kidney Injury.

    PubMed

    Phillips, Jonathan A; Holder, Daniel J; Ennulat, Daniela; Gautier, Jean-Charles; Sauer, John-Michael; Yang, Yi; McDuffie, Eric; Sonee, Manisha; Gu, Yi-Zhong; Troth, Sean P; Lynch, Karen; Hamlin, Diane; Peters, David G; Brees, Dominique; Walker, Elizabeth G

    2016-06-01

    Traditional kidney biomarkers are insensitive indicators of acute kidney injury, with meaningful changes occurring late in the course of injury. The aim of this work was to demonstrate the diagnostic potential of urinary osteopontin (OPN) and neutrophil gelatinase-associated lipocalin (NGAL) for drug-induced kidney injury (DIKI) in rats using data from a recent regulatory qualification submission of translational DIKI biomarkers and to compare performance of NGAL and OPN to five previously qualified DIKI urinary biomarkers. Data were compiled from 15 studies of 11 different pharmaceuticals contributed by Critical Path Institute's Predictive Safety Testing Consortium (PSTC) Nephrotoxicity Working Group (NWG). Rats were given doses known to cause DIKI or other target organ toxicity, and urinary levels of the candidate biomarkers were assessed relative to kidney histopathology and serum creatinine (sCr) and blood urea nitrogen (BUN).OPN and NGAL outperformed sCr and BUN in identifying DIKI manifested as renal tubular epithelial degeneration or necrosis. In addition, urinary OPN and NGAL, when used with sCr and BUN, increased the ability to detect renal tubular epithelial degeneration or necrosis. NGAL and OPN had comparable or improved performance relative to Kim-1, clusterin, albumin, total protein, and beta-2 microglobulin. Given these data, both urinary OPN and NGAL are appropriate for use with current methods for assessing nephrotoxicity to identify and monitor DIKI in regulatory toxicology studies in rats. These data also support exploratory use of urinary OPN and NGAL in safety monitoring strategies of early clinical trials to aid in the assurance of patient safety. PMID:27026710

  11. Improved Fracture Healing in Patients with Concomitant Traumatic Brain Injury: Proven or Not?

    PubMed Central

    Koopmans, Guido; Kobbe, Philipp; Poeze, Martijn; Andruszkow, Hagen; Brink, Peter R. G.; Pape, Hans-Christoph

    2015-01-01

    Over the last 3 decades, scientific evidence advocates an association between traumatic brain injury (TBI) and accelerated fracture healing. Multiple clinical and preclinical studies have shown an enhanced callus formation and an increased callus volume in patients, respectively, rats with concomitant TBI. Over time, different substances (cytokines, hormones, etc.) were in focus to elucidate the relationship between TBI and fracture healing. Until now, the mechanism behind this relationship is not fully clarified and a consensus on which substance plays the key role could not be attained in the literature. In this review, we will give an overview of current concepts and opinions on this topic published in the last decade and both clinical and pathophysiological theories will be discussed. PMID:25873754

  12. Enriched environment improves the cognitive effects from traumatic brain injury in mice.

    PubMed

    Schreiber, S; Lin, R; Haim, L; Baratz-Goldstien, R; Rubovitch, V; Vaisman, N; Pick, C G

    2014-09-01

    To date, there is yet no established effective treatment (medication or cognitive intervention) for post-traumatic brain injury (TBI) patients with chronic sequelae. Enriched environment (EE) has been recognized of importance in brain regulation, behaviour and physiology. Rodents reared in, or pre-exposed to EE, recovered better from brain insults. Using the concussive head trauma model of minimal TBI in mice, we evaluated the effect of transition to EE following a weight-drop (30g or 50g) induced mTBI on behavioural and cognitive parameters in mice in the Novel Object Recognition task, the Y- and the Elevated Plus mazes. In all assays, both mTBI groups (30g, 50g) housed in normal conditions were equally and significantly impaired 6 weeks post injury in comparison with the no-mTBI (p<0.001 and p<0.03, respectively) and the mTBI+EE groups (p<0.001 for the 30g, and p<0.017 for the 50g). No differences were found between the control and the EE mice. Two separate finding emerge: (1) the significantly positive effects of the placement in EE following mTBI, on the rehabilitative process of the tested behaviours in the affected mice; (2) the lack of difference between the groups of mice affected by 30g or by 50g. Further studies are needed in order to characterize the exact pathways involved in the positive effects of the EE on mice recovery from mTBI. Possible clinical implications indicate the importance of adapting correlates of EE to humans, i.e., prolonged and intensive physical activity - possibly combined with juggling training and intensive cognitive stimulation. PMID:24906196

  13. How To Use Creative Dramatics in the Classroom.

    ERIC Educational Resources Information Center

    Johnson, Andrew P.

    1998-01-01

    Provides specific steps and techniques for teaching and using creative dramatics in elementary school classrooms. Notes that creative dramatics address children's powerful emotions and imaginations, which children rely on to explore and understand the world. Discusses four necessary components of creative dramatics--structure, open-endedness, a…

  14. Creative Dramatics: The Perfect Tool for Gifted Students.

    ERIC Educational Resources Information Center

    Johnson, Andrew P.

    2000-01-01

    Discussion of the use of creative dramatics with gifted students considers the value of creative dramatics; components of creative dramatics (structure, open-endedness, a safe environment, and feedback); the actor's elements (voice, body, character or imagination, and group work). Specific exercises to develop the actor's elements are described.…

  15. "Play for Real": Understanding Middle School Children's Dramatic Play.

    ERIC Educational Resources Information Center

    Sierra, Zayda

    2000-01-01

    Summarizes a dissertation that examines the theory and practice of dramatic play among middle school children. Finds that they are still adept and interested in dramatic play. Discusses four components describing the nature and product of the dramatic process (social interactions, metacognitive strategies, ideational processes, and content of…

  16. Helium preconditioning protects the brain against hypoxia/ischemia injury via improving the neurovascular niche in a neonatal rat model.

    PubMed

    Li, Yi; Zhang, Peixi; Liu, Ying; Liu, Wenwu; Yin, Na

    2016-11-01

    This study aimed to investigate whether helium preconditioning (He-PC) is able to exert neuroprotective effects via improving focal neurovascular niche in a neonatal rat hypoxia/ischemia (HI) brain injury model. Seven day old rat pups were divided into control group, HI group and He-PC group. HI was induced by exposure to 8% oxygen for 90min one day after preconditioning with 70% helium-30% oxygen for three 5-min periods. At 3 and 7 days, the brain was collected for the detection of inflammation related factors (tumor necrosis factor α [TNF-α], interleukin-1β [IL-1β], IL-10) and growth/neurotrophic factors (brain-derived neurotrophic factor [BDNF], basic fibroblast growth factor [bFGF] and nerve growth factor [NGF]); at 7 days, neurobehaviors were evaluated, and the brain was collected for the detection of mRNA expression of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) by PCR, protein expression of angiogenesis related molecules (VEGF, Ang-1, Tie-2 and Flt-1) by Western blotting and microvessel density (MCD) by immunohistochemistry for vWF. Results showed He-PC was able to reduce TNF-α and IL-1β, further increase IL-10, BDNF, bFGF and NGF, elevate the mRNA expression of VEGF and Ang-1, increase the protein expression of VEGF, Ang-1, Tie-2 and Flt-1, promote angiogenesis and improve neurobehaviors as compared to HI group. These findings suggest that He-PC may improve the post-stroke neurovascular niche to exert neuroprotective effects on neonatal HI brain injury. PMID:27515290

  17. Dramatic Outburst Reveals Nearest Black Hole

    NASA Astrophysics Data System (ADS)

    2000-01-01

    Scientists have discovered the closest black hole yet, a mere 1,600 light years from Earth. Its discovery was heralded by four of the most dramatic rapid X-ray intensity changes ever seen from one star. Astronomers from the Massachusetts Institute of Technology (MIT) and the National Science Foundation's National Radio Astronomy Observatory (NRAO) announced their findings at the American Astronomical Society's meeting in Atlanta. The black hole in the constellation Sagittarius, along with a normal star dubbed V4641 Sgr, form a violent system that briefly flooded part of our Milky Way Galaxy with X-rays and ejected subatomic particles moving at nearly the speed of light one day last September. At the peak of its X-ray output, V4641 Sgr was the brightest X-ray emitter in the sky. Astronomers call this type of system an X-ray nova because it suddenly becomes a bright source of X-rays, but this object shows characteristics never seen in an X-ray nova. "V4641 Sgr turns on and off so fast that it seems to represent a new subclass of X-ray novae," said Donald A. Smith, postdoctoral associate in MIT's Center for Space Research. Smith worked on data from this object with MIT principal research scientist Ronald Remillard and NRAO astronomer Robert Hjellming. "In X-rays, the intensity rose by a factor of more than 1,000 in seven hours, then dropped by a factor of 100 in two hours," Remillard said. The radio emission was seen as an image of an expanding "jet" of particles shooting out from the binary system. After reaching a maximum, the radio intensity dropped by a factor of nearly 40 within two days. "Radio telescopes give us a quick glimpse of something moving at a fantastically high velocity," Hjellming said. Black holes harbor enormous gravitational force that can literally rip the gas away from a nearby star. This transfer of gas is visible in many forms of radiation. Both orbiting X-ray telescopes and ground-based radio and optical telescopes saw the outburst of V4641

  18. Endothelin receptor-A (ETa) inhibition fails to improve neonatal hypoxic-ischemic brain injury in rats.

    PubMed

    Khatibi, Nikan H; Lee, Lillian K; Zhou, Yilin; Chen, Wanqiu; Rolland, William; Fathali, Nancy; Martin, Robert; Applegate, Richard; Stier, Gary; Zhang, John H

    2011-01-01

    Cerebral hypoxia-ischemia (HI) is an important cause of mortality and disability in newborns. It is a result of insufficient oxygen and glucose circulation to the brain, initiating long-term cerebral damage and cell death. Emerging evidence suggests that endothelin receptor-A (ETA) activation can play an important role in mediating brain damage. In this study, we investigated the role of ETA receptor inhibition using ABT-627 in neonatal HI injured rats. Postnatal day 10 Sprague-Dawley rat pups (n=91) were assigned to the following groups: sham (n=28), HI (vehicle, n=32), and HI with ABT-627 at 3 mg/kg (n=31). The Rice-Vannucci model was used to induce ischemia by ligating the right common carotid artery, followed by a 2 h hypoxic episode using 8% oxygen in a 37°C chamber. Postoperative assessment was conducted at 48 h after injury and again at 4 weeks. At the acute time point, investigative markers included cerebral edema, infarction volume, and body weight change. Neurobehavioral testing was measured at 4 weeks post-injury. Our findings indicated that ABT-627 had no effect on the measured parameters. This study suggests that ETA receptor blockade using ABT-627 post-treatment fails to improve neurological outcomes in neonatal HI injured rats. PMID:21725757

  19. Intravenous administration of Honokiol provides neuroprotection and improves functional recovery after traumatic brain injury through cell cycle inhibition.

    PubMed

    Wang, Haiquan; Liao, Zhengbu; Sun, Xiaochuan; Shi, Quanhong; Huo, Gang; Xie, Yanfeng; Tang, Xiaolan; Zhi, Xinggang; Tang, Zhaohua

    2014-11-01

    Recently, increasing evidence has shown that cell cycle activation is a key factor of neuronal death and neurological dysfunction after traumatic brain injury (TBI). This study aims to investigate the effects of Honokiol, a cell cycle inhibitor, on attenuating the neuronal damage and facilitating functional recovery after TBI in rats, in an attempt to unveil its underlying molecular mechanisms in TBI. This study suggested that delayed intravenous administration of Honokiol could effectively ameliorate TBI-induced sensorimotor and cognitive dysfunctions. Meanwhile, Honokiol treatment could also reduce the lesion volume and increase the neuronal survival in the cortex and hippocampus. The neuronal degeneration and apoptosis in the cortex and hippocampus were further significantly attenuated by Honokiol treatment. In addition, the expression of cell cycle-related proteins, including cyclin D1, CDK4, pRb and E2F1, was significantly increased and endogenous cell cycle inhibitor p27 was markedly decreased at different time points after TBI. And these changes were significantly reversed by post-injury Honokiol treatment. Furthermore, the expression of some of the key cell cycle proteins such as cyclin D1 and E2F1 and the associated apoptosis in neurons were both remarkably attenuated by Honokiol treatment. These results show that delayed intravenous administration of Honokiol could effectively improve the functional recovery and attenuate the neuronal cell death, which is probably, at least in part, attributed to its role as a cell cycle inhibitior. This might give clues to developing attractive therapies for future clinical trials. PMID:24973706

  20. Endocannabinoid Degradation Inhibition Improves Neurobehavioral Function, Blood–Brain Barrier Integrity, and Neuroinflammation following Mild Traumatic Brain Injury

    PubMed Central

    Katz, Paige S.; Sulzer, Jesse K.; Impastato, Renata A.; Teng, Sophie X.; Rogers, Emily K.

    2015-01-01

    Abstract Traumatic brain injury (TBI) is an increasingly frequent and poorly understood condition lacking effective therapeutic strategies. Inflammation and oxidative stress (OS) are critical components of injury, and targeted interventions to reduce their contribution to injury should improve neurobehavioral recovery and outcomes. Recent evidence reveals potential protective, yet short-lived, effects of the endocannabinoids (ECs), 2-arachidonoyl glycerol (2-AG) and N-arachidonoyl-ethanolamine (AEA), on neuroinflammatory and OS processes after TBI. The aim of this study was to determine whether EC degradation inhibition after TBI would improve neurobehavioral recovery by reducing inflammatory and oxidative damage. Adult male Sprague-Dawley rats underwent a 5-mm left lateral craniotomy, and TBI was induced by lateral fluid percussion. TBI produced apnea (17±5 sec) and a delayed righting reflex (479±21 sec). Thirty minutes post-TBI, rats were randomized to receive intraperitoneal injections of vehicle (alcohol, emulphor, and saline; 1:1:18) or a selective inhibitor of 2-AG (JZL184, 16 mg/kg) or AEA (URB597, 0.3 mg/kg) degradation. At 24 h post-TBI, animals showed significant neurological and -behavioral impairment as well as disruption of blood–brain barrier (BBB) integrity. Improved neurological and -behavioral function was observed in JZL184-treated animals. BBB integrity was protected in both JZL184- and URB597-treated animals. No significant differences in ipsilateral cortex messenger RNA expression of interleukin (IL)-1β, IL-6, chemokine (C-C motif) ligand 2, tumor necrosis factor alpha, cyclooxygenase 2 (COX2), or nicotinamide adenine dinucleotide phosphate oxidase (NOX2) and protein expression of COX2 or NOX2 were observed across experimental groups. Astrocyte and microglia activation was significantly increased post-TBI, and treatment with JZL184 or URB597 blocked activation of both cell types. These findings suggest that EC degradation

  1. Comparison of training methods to improve walking in persons with chronic spinal cord injury: a randomized clinical trial

    PubMed Central

    Alexeeva, Natalia; Sames, Carol; Jacobs, Patrick L.; Hobday, Lori; DiStasio, Marcello M.; Mitchell, Sarah A.; Calancie, Blair

    2011-01-01

    Objective To compare two forms of device-specific training – body-weight-supported (BWS) ambulation on a fixed track (TRK) and BWS ambulation on a treadmill (TM) – to comprehensive physical therapy (PT) for improving walking speed in persons with chronic, motor-incomplete spinal cord injury (SCI). Methods Thirty-five adult subjects with a history of chronic SCI (>1 year; AIS ‘C’ or ‘D’) participated in a 13-week (1 hour/day; 3 days per week) training program. Subjects were randomized into one of the three training groups. Subjects in the two BWS groups trained without the benefit of additional input from a physical therapist or gait expert. For each training session, performance values and heart rate were monitored. Pre- and post-training maximal 10-m walking speed, balance, muscle strength, fitness, and quality of life were assessed in each subject. Results All three training groups showed significant improvement in maximal walking speed, muscle strength, and psychological well-being. A significant improvement in balance was seen for PT and TRK groups but not for subjects in the TM group. In all groups, post-training measures of fitness, functional independence, and perceived health and vitality were unchanged. Conclusions Our results demonstrate that persons with chronic, motor-incomplete SCI can improve walking ability and psychological well-being following a concentrated period of ambulation therapy, regardless of training method. Improvement in walking speed was associated with improved balance and muscle strength. In spite of the fact that we withheld any formal input of a physical therapist or gait expert from subjects in the device-specific training groups, these subjects did just as well as subjects receiving comprehensive PT for improving walking speed and strength. It is likely that further modest benefits would accrue to those subjects receiving a combination of device-specific training with input from a physical therapist or gait expert to

  2. Perceptual stability during dramatic changes in olfactory bulb activation maps and dramatic declines in activation amplitudes

    PubMed Central

    Homma, R.; Cohen, L. B.; Kosmidis, E. K.; Youngentob, S. L.

    2009-01-01

    We compared the concentration dependence of the ability of rats to identify odorants with the calcium signals in the nerve terminals of the olfactory receptor neurons. Although identification performance decreased with concentrations both above and below the training stimuli it remained well above random at all concentrations tested (between 0.0006% and 35% of saturated vapor). In contrast, the calcium signals in the same awake animals were much smaller than their maximum values at odorant concentrations less than 1% of saturated vapor. In addition, maps of activated glomeruli changed dramatically as odorant concentration was reduced. Thus perceptual stability exists in the face of dramatic changes in both the amplitude and the maps of the input to the olfactory bulb. The data for the concentration dependence of the response of the most sensitive glomeruli for each of five odorants was fitted with a Michaelis-Menten (Hill) equation. The fitted curves were extrapolated to odorant concentrations several orders of magnitude lower the smallest observed signals and suggest that the calcium response at low odorant concentrations is more than 1000 times smaller than the response at saturating odorant concentrations. We speculate that only a few spikes in olfactory sensory neurons may be sufficient for correct odorant identification. PMID:19291227

  3. Occupational injury prevention research: progress and priorities.

    PubMed

    Stout, N A; Linn, H I

    2002-12-01

    The twentieth century witnessed remarkable reductions in the number and rate of occupational fatalities and injuries. However, many preventable injuries and deaths still occur. Barriers to progress in occupational injury prevention are discussed, along with strategies for overcoming them. In mining, the frequency of death has dramatically declined over the century. The latest figures from the BLS indicate that less than 6000 worker deaths from injury occurred in 2000. Catastrophic events have prompted increased attention, resources, and action on workplace hazards and risks, resulting in sweeping changes, including new protective laws. Science based approaches to prevention have contributed to progress. Multidisciplinary collaboration among injury prevention researchers, and collaboration and cooperation among multiple sectors, have improved the relevance and application of injury prevention research and development. Barriers to further progress include lack of evaluation of the effectiveness of prevention strategies and technologies, including cost effectiveness; lack of widespread implementation of known, effective prevention; and lack of efficient transfer and implementation of prevention knowledge and products to the workplace. Evaluation and implementation of prevention efforts are most successfully achieved in partnership between researchers and the industry at risk, which requires outreach efforts on the part of the occupational research community. PMID:12460949

  4. Lobeline improves acute lung injury via nuclear factor-κB-signaling pathway and oxidative stress.

    PubMed

    Li, Kun-Cheng; Ho, Yu-Ling; Chen, Cing-Yu; Hsieh, Wen-Tsong; Chang, Yuan-Shiun; Huang, Guan-Jhong

    2016-05-01

    Acute lung injury (ALI) is a severe, life-threatening medical condition whose pathogenesis is linked to neutrophil infiltration of the lung. Activation and recruitment of neutrophils to the lung is mostly attributed to the production of chemokines NO, IL-6, for instance. This study aims to investigate lobeline ability in reducing NO production, and nitric oxide synthase (iNOs) expression. Lobeline was tested by inhibiting phosphorylation of mitogen-activated protein kinases (MAPKs), NF-κB and IκBα in LPS-stimulated RAW 264.7 cells. When RAW 264.7 macrophages were given lobeline with LPS, a significant concentration-dependent inhibition of NO production was detected. In vivo tests, mice were either treated with normal saline, 10mg/kg dexmethasone or 5, 10, 20mg/kg lobeline intraperitoneally, and after an hour, the administration of 5mg/kg of LPS was given intratracheally. External performance, cytokines, MAPK pathways and antioxidative enzymes (AOEs) were also carried out to evaluate the effects of these drugs. This is the first investigation in which lobeline was found to effectively inhibit acute lung edema, which may provide a potential target for treating ALI. Lobeline may utilize MAPKs pathways as well as AOEs activity to attenuate LPS-induced nonspecific pulmonary inflammation. PMID:26702732

  5. Inhibition of Epidermal Growth Factor Receptor Improves Myelination and Attenuates Tissue Damage of Spinal Cord Injury.

    PubMed

    Zhang, Si; Ju, Peijun; Tjandra, Editha; Yeap, Yeeshan; Owlanj, Hamed; Feng, Zhiwei

    2016-10-01

    Preventing demyelination and promoting remyelination of denuded axons are promising therapeutic strategies for spinal cord injury (SCI). Epidermal growth factor receptor (EGFR) inhibition was reported to benefit the neural functional recovery and the axon regeneration after SCI. However, its role in de- and remyelination of axons in injured spinal cord is unclear. In the present study, we evaluated the effects of EGFR inhibitor, PD168393 (PD), on the myelination in mouse contusive SCI model. We found that expression of myelin basic protein (MBP) in the injured spinal cords of PD treated mice was remarkably elevated. The density of glial precursor cells and oligodendrocytes (OLs) was increased and the cell apoptosis in lesions was attenuated after PD168393 treatment. Moreover, PD168393 treatment reduced both the numbers of OX42 + microglial cells and glial fibrillary acidic protein + astrocytes in damaged area of spinal cords. We thus conclude that the therapeutic effects of EGFR inhibition after SCI involves facilitating remyelination of the injured spinal cord, increasing of oligodendrocyte precursor cells and OLs, as well as suppressing the activation of astrocytes and microglia/macrophages. PMID:26883518

  6. Active-Arm Passive-Leg Exercise Improves Cardiovascular Function in Spinal Cord Injury.

    PubMed

    West, Christopher R; Currie, Katharine D; Gee, Cameron; Krassioukov, Andrei V; Borisoff, Jaimie

    2015-11-01

    In a 43-yr-old male subject with a chronic T3 AIS A spinal cord injury, the acute cardiorespiratory responses to active upper-extremity exercise alone and combined active-arm passive-leg exercise (AAPLE) were investigated, along with the cardiorespiratory, cardiac, vascular, and body composition responses to a 6-wk AAPLE interval training intervention. AAPLE elicited superior acute maximal cardiorespiratory responses compared with upper-extremity exercise alone. In response to a 6-wk interval training regimen, AAPLE caused a 25% increase in peak oxygen uptake, a 10% increase in resting stroke volume, and a 4-fold increase in brachial artery blood flow. Conversely, there were no changes in femoral arterial function, body composition, or bone mineral density in response to training. As a potential clinical intervention, AAPLE may be advantageous over other forms of currently available exercise, owing to the minimal setup time and cost involved and the nonreliance on specialized equipment that is required for other exercise modalities. PMID:26259052

  7. Microencapsulation improves inhibitory effects of transplanted olfactory ensheathing cells on pain after sciatic nerve injury

    PubMed Central

    Zhao, Hao; Yang, Bao-lin; Liu, Zeng-xu; Yu, Qing; Zhang, Wen-jun; Yuan, Keng; Zeng, Hui-hong; Zhu, Gao-chun; Liu, De-ming; Li, Qing

    2015-01-01

    Olfactory bulb tissue transplantation inhibits P2X2/3 receptor-mediated neuropathic pain. However, the olfactory bulb has a complex cellular composition, and the mechanism underlying the action of purified transplanted olfactory ensheathing cells (OECs) remains unclear. In the present study, we microencapsulated OECs in alginic acid, and transplanted free and microencapsulated OECs into the region surrounding the injured sciatic nerve in rat models of chronic constriction injury. We assessed mechanical nociception in the rat models 7 and 14 days after surgery by measuring paw withdrawal threshold, and examined P2X2/3 receptor expression in L4–5 dorsal root ganglia using immunohistochemistry. Rats that received free and microencapsulated OEC transplants showed greater withdrawal thresholds than untreated model rats, and weaker P2X2/3 receptor immunoreactivity in dorsal root ganglia. At 14 days, paw withdrawal threshold was much higher in the microencapsulated OEC-treated animals. Our results confirm that microencapsulated OEC transplantation suppresses P2X2/3 receptor expression in L4–5 dorsal root ganglia in rat models of neuropathic pain and reduces allodynia, and also suggest that transplantation of microencapsulated OECs is more effective than transplantation of free OECs for the treatment of neuropathic pain. PMID:26487865

  8. Evaluation of use of reading comprehension strategies to improve reading comprehension of adult college students with acquired brain injury.

    PubMed

    Griffiths, Gina G; Sohlberg, McKay Moore; Kirk, Cecilia; Fickas, Stephen; Biancarosa, Gina

    2016-01-01

    Adults with mild to moderate acquired brain injury (ABI) often pursue post-secondary or professional education after their injuries in order to enter or re-enter the job market. An increasing number of these adults report problems with reading-to-learn. The problem is particularly concerning given the growing population of adult survivors of ABI. Despite the rising need, empirical evaluation of reading comprehension interventions for adults with ABI is scarce. This study used a within-subject design to evaluate whether adult college students with ABI with no more than moderate cognitive impairments benefited from using reading comprehension strategies to improve comprehension of expository text. Integrating empirical support from the cognitive rehabilitation and special education literature, the researchers designed a multi-component reading comprehension strategy package. Participants read chapters from an introductory-level college anthropology textbook in two different conditions: strategy and no-strategy. The results indicated that reading comprehension strategy use was associated with recall of more correct information units in immediate and delayed free recall tasks; more efficient recall in the delayed free recall task; and increased accuracy recognising statements from a sentence verification task designed to reflect the local and global coherence of the text. The findings support further research into using reading comprehension strategies as an intervention approach for the adult ABI population. Future research needs include identifying how to match particular reading comprehension strategies to individuals, examining whether reading comprehension performance improves further through the incorporation of systematic training, and evaluating texts from a range of disciplines and genres. PMID:25712402

  9. Extensive cell migration, axon regeneration and improved function with polysialic acid-modified Schwann cells after spinal cord injury

    PubMed Central

    Ghosh, Mousumi; Tuesta, Luis M.; Puentes, Rocio; Patel, Samik; Melendez, Kiara; Maarouf, Abderrahman El; Rutishauser, Urs; Pearse, Damien Daniel

    2015-01-01

    Schwann cells (SC) implantation after spinal cord injury (SCI) promotes axonal regeneration, remyelination repair and functional recovery. Reparative efficacy, however, may be limited due to the inability of SCs to migrate outward from the lesion-implant site. Altering SC cell surface properties by over-expressing polysialic acid (PSA) has been shown to promote SC migration. In the current study, a SCI contusion was used to evaluate the migration, supraspinal axon growth support and functional recovery associated with polysialyltransferase (PST)-over-expressing SCs (PST-GFP SCs) or controls (GFP SCs). Compared to GFP SCs, which remained confined to the injection site at the injury center, PST-GFP SCs migrated across the lesion:host cord interface for distances of up to 4.4 mm within adjacent host tissue. In addition, with PST-GFP SCs, there was extensive serotonergic and corticospinal axon in-growth within the implants that was limited in the GFP SC controls. The enhanced migration of PST-GFP SCs was accompanied by significant growth of these axons caudal to lesion. Animals receiving PST-GFP SCs exhibited improved functional outcome, both in the open-field and on the gridwalk test, over modest improvements provided by GFP SC controls. The current study for the first time demonstrates that a lack of migration by SC may hinder their reparative benefits and that cell surface overexpression of PSA enhances the ability of implanted SCs to associate with and support the growth of corticospinal axons. These results provide further promise that PSA modified SCs will be a potent reparative approach for SCI. PMID:22460918

  10. Extensive cell migration, axon regeneration, and improved function with polysialic acid-modified Schwann cells after spinal cord injury.

    PubMed

    Ghosh, Mousumi; Tuesta, Luis M; Puentes, Rocio; Patel, Samik; Melendez, Kiara; El Maarouf, Abderrahman; Rutishauser, Urs; Pearse, Damien Daniel

    2012-05-01

    Schwann cell (SC) implantation after spinal cord injury (SCI) promotes axonal regeneration, remyelination repair, and functional recovery. Reparative efficacy, however, may be limited because of the inability of SCs to migrate outward from the lesion-implant site. Altering SC cell surface properties by overexpressing polysialic acid (PSA) has been shown to promote SC migration. In this study, a SCI contusion model was used to evaluate the migration, supraspinal axon growth support, and functional recovery associated with polysialyltransferase (PST)-overexpressing SCs [PST-green fluorescent protein (GFP) SCs] or controls (GFP SCs). Compared with GFP SCs, which remained confined to the injection site at the injury center, PST-GFP SCs migrated across the lesion:host cord interface for distances of up to 4.4 mm within adjacent host tissue. In addition, with PST-GFP SCs, there was extensive serotonergic and corticospinal axon in-growth within the implants that was limited in the GFP SC controls. The enhanced migration of PST-GFP SCs was accompanied by significant growth of these axons caudal to lesion. Animals receiving PST-GFP SCs exhibited improved functional outcome, both in the open-field and on the gridwalk test, beyond the modest improvements provided by GFP SC controls. This study for the first time demonstrates that a lack of migration by SCs may hinder their reparative benefits and that cell surface overexpression of PSA enhances the ability of implanted SCs to associate with and support the growth of corticospinal axons. These results provide further promise that PSA-modified SCs will be a potent reparative approach for SCI. © 2012 Wiley Periodicals, Inc. PMID:22460918