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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 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

  8. 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.

  9. 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

  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. 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

  5. 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

  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.

    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

  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

    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.

  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

    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

  18. 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

  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. 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

  11. 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

  12. 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

  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. 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)

  15. 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

  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. 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...

  19. 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

  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

    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

  4. 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

  5. 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

  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. 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

  10. 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

  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. 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

  15. 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

  16. 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

  17. 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.

  18. 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

  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. 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

  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. 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

  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. 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…

  18. 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,…

  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. 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

  2. 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

  3. 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

  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. 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...

  15. 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…

  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. 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…

  8. 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)

  9. 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…

  10. 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…

  11. 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…

  12. 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,…

  13. 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

  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. 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

  10. 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

  11. 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

  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. 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…

  8. 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.…

  9. 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

  10. 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)...

  11. 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…

  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. 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

  17. 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

  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. 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

  20. 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

  1. 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

  2. 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

  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. "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…

  14. 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…

  15. 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.…

  16. 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

  17. 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

  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. 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

  2. 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

  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. 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

  5. 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

  6. 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

  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. 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

  9. 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

  10. 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

  11. Suppression of acute proinflammatory cytokine and chemokine upregulation by post-injury administration of a novel small molecule improves long-term neurologic outcome in a mouse model of traumatic brain injury

    PubMed Central

    Lloyd, Eric; Somera-Molina, Kathleen; Van Eldik, Linda J; Watterson, D Martin; Wainwright, Mark S

    2008-01-01

    Background Traumatic brain injury (TBI) with its associated morbidity is a major area of unmet medical need that lacks effective therapies. TBI initiates a neuroinflammatory cascade characterized by activation of astrocytes and microglia, and increased production of immune mediators including proinflammatory cytokines and chemokines. This inflammatory response contributes both to the acute pathologic processes following TBI including cerebral edema, in addition to longer-term neuronal damage and cognitive impairment. However, activated glia also play a neuroprotective and reparative role in recovery from injury. Thus, potential therapeutic strategies targeting the neuroinflammatory cascade must use careful dosing considerations, such as amount of drug and timing of administration post injury, in order not to interfere with the reparative contribution of activated glia. Methods We tested the hypothesis that attenuation of the acute increase in proinflammatory cytokines and chemokines following TBI would decrease neurologic injury and improve functional neurologic outcome. We used the small molecule experimental therapeutic, Minozac (Mzc), to suppress TBI-induced up-regulation of glial activation and proinflammatory cytokines back towards basal levels. Mzc was administered in a clinically relevant time window post-injury in a murine closed-skull, cortical impact model of TBI. Mzc effects on the acute increase in brain cytokine and chemokine levels were measured as well as the effect on neuronal injury and neurobehavioral function. Results Administration of Mzc (5 mg/kg) at 3 h and 9 h post-TBI attenuates the acute increase in proinflammatory cytokine and chemokine levels, reduces astrocyte activation, and the longer term neurologic injury, and neurobehavioral deficits measured by Y maze performance over a 28-day recovery period. Mzc-treated animals also have no significant increase in brain water content (edema), a major cause of the neurologic morbidity associated

  12. D-cycloserine improves functional recovery and reinstates long-term potentiation (LTP) in a mouse model of closed head injury.

    PubMed

    Yaka, Rami; Biegon, Anat; Grigoriadis, Nikolaos; Simeonidou, Constantina; Grigoriadis, Savvas; Alexandrovich, Alexander G; Matzner, Henri; Schumann, Johanna; Trembovler, Victoria; Tsenter, Jeanna; Shohami, Esther

    2007-07-01

    Traumatic brain injury triggers a massive glutamate efflux, activation of NMDA receptor channels, and cell death. Recently, we reported that NMDA receptors in mice are down-regulated from hours to days following closed head injury (CHI), and treatment with NMDA improved recovery of motor and cognitive functions up to 14 d post-injury. Here we show that a single injection of a low dose of D-cycloserine (DCS), a partial NMDA receptor agonist, in CHI mice 24 h post-injury, resulted in a faster and greater recovery of motor and memory functions as assessed by neurological severity score and object recognition tests, respectively. Moreover, DCS treatment of CHI mice led to a significant improvement of hippocampal long-term potentiation (LTP) in the CA1 region that was completely blunted in CHI control mice. However, DCS did not improve CHI-induced impairment in synaptic glutamate release measured by paired pulse facilitation (PPF) ratio in hippocampal CA1 region. Finally, CHI-induced reduction of brain-derived neurotrophic factor (BDNF) was fully restored following DCS treatment. Since DCS is in clinical use for other indications, the present study offers a novel approach to treat human brain injury. PMID:17351125

  13. SB203580, a p38 mitogen-activated protein kinase inhibitor, fails to improve functional outcome following a moderate spinal cord injury in rat.

    PubMed

    Stirling, D P; Liu, J; Plunet, W; Steeves, J D; Tetzlaff, W

    2008-07-31

    We examined the spatial and temporal expression patterns of active p38 mitogen-activated protein kinase (MAPK), an important regulator of immune cell function, following spinal cord injury (SCI). We further assessed whether administration of SB203580, an inhibitor of p38 MAPK activity, would reduce inflammation, improve tissue sparing, and improve functional outcome after SCI. Adult Wistar rats were subjected to a T9/10 SCI contusion of moderate severity and killed at several time points after injury, whereas sham-injured (control) animals only received a laminectomy. In control animals, active p38 MAPK expression was primarily localized to resting microglia within the spinal cord. Over the first 24 h after SCI, a continuing increase in active p38 MAPK expression was evident in neutrophils and activated microglia (OX42+) surrounding the spinal lesion site. At 15 days post-injury, active p38 MAPK was localized to macrophages (ED1+) that now dominated the lesion site. In addition, active p38 MAPK was localized to macrophages within white matter fiber tracts undergoing degeneration, several segments rostral and caudal to the injury site, which persisted for at least 6 weeks. Overall, our results demonstrate that active p38 MAPK is increased within resident and invading immune cells after SCI contusion injury and, therefore, may be an important target to regulate the inflammatory cascade after SCI. However, intrathecal application of SB203580 failed to improve functional outcome after a moderate SCI contusion. PMID:18562123

  14. Liver Injury Indicating Fatty Liver but Not Serologic NASH Marker Improves under Metformin Treatment in Polycystic Ovary Syndrome

    PubMed Central

    Tan, Susanne; Vollmar, Nils; Benson, Sven; Sowa, Jan-Peter; Bechmann, Lars P.; Gerken, Guido; Fuhrer, Dagmar; Canbay, Ali

    2015-01-01

    Objective. Polycystic ovary syndrome (PCOS) is associated with obesity and insulin resistance (IR), key features of nonalcoholic steatohepatitis (NASH). Cytokeratin 18 fragments (M30) have been established as a serum marker for NASH. The insulin sensitizer metformin improves hepatic IR. This study evaluates the influence of MF on serologic NASH (sNASH) in patients with PCOS. Patients and Methods. In 89 patients, metabolic parameters, liver injury indicating fatty liver (LIFL), and M30 were assessed at baseline and after metformin treatment. Patients with initial IR were subdivided into dissolved (PCOS-exIR) and persistent IR (PCOS-PIR) after treatment and compared to an initially insulin sensitive PCOS group (PCOS-C). Results. Improvement of LIFL prevalence could be seen in PCOS-C and PCOS-exIR compared to PCOS-PIR (−19.4, resp., −12.0% versus 7.2%, Chi2 = 29.5, P < 0.001) without change in sNASH prevalence. In PCOS-PIR, ALT levels increased significantly accompanied by a nominal, nonsignificant M30 increase. Conclusions. Metformin improves LIFL in subgroups of patients with PCOS without influencing sNASH. This could either indicate a missing effect of metformin on NAFLD or slowed disease progression. Further studies are needed to elucidate NAFLD in the context of PCOS and potential therapeutic options. PMID:25873949

  15. Loop chiller plant design dramatically lowers chilled water costs

    SciTech Connect

    Hartman, T.

    1999-07-01

    Recent improvements in HVAC networking and speed control technologies, together with an improved understanding of the nature of cooling loads in buildings offer exciting opportunities for improving the energy efficiency of chiller plants. A new Loop chiller plant design has been developed that incorporates variable speed control on all plant components. Operation of this cooling plant is coordinated with the load it serves through a control network. This new approach has enormous advantages over traditional optimized plants. The two key advantages of these new Loop design chiller plants designs are: (1) Annual operating energy requirements are reduced by as much as 50% or more when compared to present state-of-the-art optimized chiller plants, and (2) A smaller sized and therefore less costly chiller plant can be designed to serve HVAC loads. The term Loop is employed to describe the technologies employed because the concept employs closed loop control by providing operational feedback from each point of use to the plant. The Loop concept also employs a single, series coupled chilled water loop for higher pumping and distribution efficiencies. This paper presents background and design theory and follows with a case study to introduce the new Loop design and operations concept. Specifics of an actual design are presented along with an explanation of how the principles can be applied economically to all new or existing chiller plant designs to achieve dramatic reductions in both construction costs and energy costs.

  16. Carvacrol together with TRPC1 elimination improve functional recovery after traumatic brain injury in mice.

    PubMed

    Peters, Maximilian; Trembovler, Victoria; Alexandrovich, Alexander; Parnas, Moshe; Birnbaumer, Lutz; Minke, Baruch; Shohami, Esther

    2012-12-10

    Death of Central Nervous System (CNS) neurons following traumatic brain injury (TBI) is a complex process arising from a combination of factors, many of which are still unknown. It has been found that inhibition of transient receptor potential (TRP) channels constitutes an effective strategy for preventing death of CNS neurons following TBI. TRP channels are classified into seven related subfamilies, most of which are Ca(2+) permeable and involved in many cellular functions, including neuronal cell death. We hypothesized that TRP channels of the TRPC subfamily may be involved in post-TBI pathophysiology and that the compound 5-isopropyl-2-methylphenol (carvacrol), by inhibition of TRP channels, may exert neuroprotective effect after TBI. To test these suppositions, carvacrol was given to mice after TBI and its effect on their functional recovery was followed for several weeks. Our results show that neurological recovery after TBI was significantly enhanced by application of carvacrol. To better define the type of the specific channel involved, the effect of carvacrol on the extent and speed of recovery after TBI was compared among mice lacking TRPC1, TRPC3, or TRPC5, relative to wild type controls. We found that neurological recovery after TBI was significantly enhanced by combining carvacrol with TRPC1 elimination, but not by the absence of TRPC3 or TRPC5, showing a synergistic effect between carvacrol application and TRPC1 elimination. We conclude that TRPC1-sensitive mechanisms are involved in TBI pathology, and that inhibition of this channel by carvacrol enhances recovery and should be considered for further studies in animal models and humans. PMID:22994850

  17. Slowing down after a mild traumatic brain injury: a strategy to improve cognitive task performance?

    PubMed

    Ozen, Lana J; Fernandes, Myra A

    2012-01-01

    Long-term persistent attention and memory difficulties following a mild traumatic brain injury (TBI) often go undetected on standard neuropsychological tests, despite complaints by mild TBI individuals. We conducted a visual Repetition Detection working memory task to digits, in which we manipulated task difficulty by increasing cognitive load, to identify subtle deficits long after a mild TBI. Twenty-six undergraduate students with a self-report of one mild TBI, which occurred at least 6 months prior, and 31 non-head-injured controls took part in the study. Participants were not informed until study completion that the study's purpose was to examine cognitive changes following a mild TBI, to reduce the influence of "diagnosis threat" on performance. Neuropsychological tasks did not differentiate the groups, though mild TBI participants reported higher state anxiety levels. On our working memory task, the mild TBI group took significantly longer to accurately detect repeated targets on our task, suggesting that slowed information processing is a long-term consequence of mild TBI. Accuracy was comparable in the low-load condition and, unexpectedly, mild TBI performance surpassed that of controls in the high-load condition. Temporal analysis of target identification suggested a strategy difference between groups: mild TBI participants made a significantly greater number of accurate responses following the target's offset, and significantly fewer erroneous distracter responses prior to target onset, compared with controls. Results suggest that long after a mild TBI, high-functioning young adults invoke a strategy of delaying their identification of targets in order to maintain, and facilitate, accuracy on cognitively demanding tasks. PMID:22068441

  18. Using Dramatic Events and Visualization Technology to Teach About Watersheds

    NASA Astrophysics Data System (ADS)

    Huth, A. K.; Hall, M. K.

    2008-12-01

    We developed a GIS-based, two-unit module about dynamic watersheds that uses spatial visualization tools, inquiry-based questioning, and eyewitness accounts of historical, dramatic events to teach students about the natural phenomenon of watershed evolution. The module puts into context the relationship between watersheds and human behavior. The centerpiece of Unit 1 is the Big Thompson watershed in Colorado and the flash flood that killed 145 people in 1976. Unit 2 is a case history of the Sabino Canyon watershed in Arizona, which was ravaged by wildfires in 2002 and 2003, as well as destructive debris flows in 2006. Students examine the causes and magnitude of each of these events, and how they changed landscapes and people. Both units use MyWorld GIS and Google Earth visualization software tools. A teacher workshop in summer 2008 revealed an increased understanding of watersheds and an improved comfort level using spatial visualization software after working with the module. Prior to the workshop, a survey demonstrated that fewer than 50 percent of the workshop participants knew the name of the watershed in which they lived. After the workshop, all teachers were able to conceptually define a watershed, identify the watershed in which they live, and describe hazards that would put a watershed and its communities at risk for dramatic changes. They also showed an increased awareness of seasonal variations in streamflow and made connections between these variations and the sources that generate streamflow in different watersheds. We expect similar results among high-school students who will field test these materials during the Fall 2008 semester.

  19. Suppressor of Cytokine Signaling-2 (SOCS2) Regulates the Microglial Response and Improves Functional Outcome after Traumatic Brain Injury in Mice.

    PubMed

    Basrai, Harleen S; Christie, Kimberly J; Turbic, Alisa; Bye, Nicole; Turnley, Ann M

    2016-01-01

    Traumatic brain injury (TBI) is frequently characterized by neuronal, axonal and myelin loss, reactive gliosis and neuroinflammation, often associated with functional deficits. Endogenous repair mechanisms include production of new neurons from precursor cells, but usually the new neurons fail to integrate and survive more than a few weeks. This is in part mediated by the toxic and inflammatory environment present in the injured brain which activates precursor cells to proliferate and differentiate but limits survival of the newborn progeny. Therefore, an understanding of mechanisms that regulate production and survival of newborn neurons and the neuroinflammatory response after brain injury may lead to therapeutic options to improve outcomes. Suppressor of Cytokine Signaling 2 (SOCS2) promotes hippocampal neurogenesis and survival of newborn neurons in the adult brain and regulates anti-inflammatory responses in the periphery, suggesting it may be a useful candidate to improve outcomes of TBI. In this study the functional and cellular responses of SOCS2 over-expressing transgenic (SOCS2Tg) mice were compared to wildtype littermates following mild or moderately severe TBI. Unlike wildtype controls, SOCS2Tg mice showed functional improvement on a ladder test, with a smaller lesion volume at 7d post injury and increased numbers of proliferative CD11b+ microglia/macrophages at 35d post-injury in the mild injury paradigm. At 7d post-moderately severe injury there was an increase in the area covered by cells expressing an anti-inflammatory M2 phenotype marker (CD206+) but no difference in cells with a pro-inflammatory M1 phenotype marker (CD16/32+). No effect of SOCS2 overexpression was observed in production or survival of newborn neurons, even in the presence of the neuroprotective agent erythropoietin (EPO). Therefore, SOCS2 may improve outcome of TBI in mice by regulating aspects of the neuroinflammatory response, promoting a more anti-inflammatory environment

  20. Suppressor of Cytokine Signaling-2 (SOCS2) Regulates the Microglial Response and Improves Functional Outcome after Traumatic Brain Injury in Mice

    PubMed Central

    Basrai, Harleen S.; Christie, Kimberly J.; Turbic, Alisa; Bye, Nicole; Turnley, Ann M.

    2016-01-01

    Traumatic brain injury (TBI) is frequently characterized by neuronal, axonal and myelin loss, reactive gliosis and neuroinflammation, often associated with functional deficits. Endogenous repair mechanisms include production of new neurons from precursor cells, but usually the new neurons fail to integrate and survive more than a few weeks. This is in part mediated by the toxic and inflammatory environment present in the injured brain which activates precursor cells to proliferate and differentiate but limits survival of the newborn progeny. Therefore, an understanding of mechanisms that regulate production and survival of newborn neurons and the neuroinflammatory response after brain injury may lead to therapeutic options to improve outcomes. Suppressor of Cytokine Signaling 2 (SOCS2) promotes hippocampal neurogenesis and survival of newborn neurons in the adult brain and regulates anti-inflammatory responses in the periphery, suggesting it may be a useful candidate to improve outcomes of TBI. In this study the functional and cellular responses of SOCS2 over-expressing transgenic (SOCS2Tg) mice were compared to wildtype littermates following mild or moderately severe TBI. Unlike wildtype controls, SOCS2Tg mice showed functional improvement on a ladder test, with a smaller lesion volume at 7d post injury and increased numbers of proliferative CD11b+ microglia/macrophages at 35d post-injury in the mild injury paradigm. At 7d post-moderately severe injury there was an increase in the area covered by cells expressing an anti-inflammatory M2 phenotype marker (CD206+) but no difference in cells with a pro-inflammatory M1 phenotype marker (CD16/32+). No effect of SOCS2 overexpression was observed in production or survival of newborn neurons, even in the presence of the neuroprotective agent erythropoietin (EPO). Therefore, SOCS2 may improve outcome of TBI in mice by regulating aspects of the neuroinflammatory response, promoting a more anti-inflammatory environment

  1. Neural Progenitor Cell Transplantation Promotes Neuroprotection, Enhances Hippocampal Neurogenesis, and Improves Cognitive Outcomes after Traumatic Brain Injury

    PubMed Central

    Blaya, Meghan O.; Tsoulfas, Pantelis; Bramlett, Helen M.; Dietrich, W. Dalton

    2014-01-01

    Transplantation of neural progenitor cells (NPCs) may be a potential treatment strategy for traumatic brain injury (TBI) due to their intrinsic advantages, including the secretion of neurotrophins. Neurotrophins are critical for neuronal survival and repair, but their clinical use is limited. In this study, we hypothesized that pericontusional transplantation of NPCs genetically modified to secrete a synthetic, human multineurotrophin (MNTS1) would overcome some of the limitations of traditional neurotrophin therapy. MNTS1 is a multifunctional neurotrophin that binds all three tropomyosin-related kinase (Trk) receptors, recapitulating the prosurvival activity of 3 endogenous mature neurotrophins. NPCs obtained from rat fetuses at E15 were transduced with lentiviral vectors containing MNTS1 and GFP constructs (MNTS1-NPCs) or fluorescent constructs alone (control GFP-NPCs). Adult rats received fluid percussion-induced TBI or sham surgery. Animals were transplanted 1 week later with control GFP-NPCs, MNTS1-NPCs, or injected with saline (vehicle). At five weeks, animals were evaluated for hippocampal-dependent spatial memory. Six weeks post surgery, we observed significant survival and neuronal differentiation of MNTS1-NPCs and injury-activated tropism towards contused regions. NPCs displayed processes that extended into several remote structures, including the hippocampus and contralateral cortex. Both GFP- and MNTS1-NPCs conferred significant preservation of pericontusional host tissues and enhanced hippocampal neurogenesis. NPC transplantation improved spatial memory capacity on the Morris water maze (MWM) task. Transplant recipients exhibited escape latencies approximately half that of injured vehicle controls. While we observed greater transplant survival and neuronal differentiation of MNTS1-NPCs, our collective findings suggest that MNTS1 may be superfluous in terms of preserving the cytoarchitecture and rescuing behavioral deficits given the lack of significant

  2. N-methyl-D-aspartate preconditioning improves short-term motor deficits outcome after mild traumatic brain injury in mice.

    PubMed

    Costa, Tayana; Constantino, Leandra C; Mendonça, Bruna P; Pereira, Josimar G; Herculano, Bruno; Tasca, Carla I; Boeck, Carina R

    2010-05-01

    Traumatic brain injury (TBI) causes impairment of fine motor functions in humans and nonhuman mammals that often persists for months after the injury occurs. Neuroprotective strategies for prevention of the sequelae of TBI and understanding the molecular mechanisms and cellular pathways are related to the glutamatergic system. It has been suggested that cellular damage subsequent to TBI is mediated by the excitatory neurotransmitters, glutamate and aspartate, through the excessive activation of the N-methyl-D-aspartate (NMDA) receptors. Thus, preconditioning with a low dose of NMDA was used as a strategy for protection against locomotor deficits observed after TBI in mice. Male adult mice CF-1 were preconditioned with NMDA (75 mg/kg) 24 hr before the TBI induction. Under anesthesia with O(2)/N(2)O (33%: 66%) inhalation, the animals were subjected to the experimental model of trauma that occurs by the impact of a 25 g weight on the skull. Sensorimotor gating was evaluated at 1.5, 6, or 24 hr after TBI induction by using footprint and rotarod tests. Cellular damage also was assessed 24 hr after occurrence of cortical trauma. Mice preconditioned with NMDA were protected against all motor deficits revealed by footprint tests, but not those observed in rotarod tasks. Although mice showed motor deficits after TBI, no cellular damage was observed. These data corroborate the hypothesis that glutamatergic excitotoxicity, especially via NMDA receptors, contributes to severity of trauma. They also point to a putative neuroprotective mechanism induced by a sublethal dose of NMDA to improve motor behavioral deficits after TBI. PMID:19998488

  3. A Systematic Review of Experimental Strategies Aimed at Improving Motor Function after Acute and Chronic Spinal Cord Injury.

    PubMed

    Gomes-Osman, Joyce; Cortes, Mar; Guest, James; Pascual-Leone, Alvaro

    2016-03-01

    While various approaches have been proposed in clinical trials aimed at improving motor function after spinal cord injury in humans, there is still limited information regarding the scope, methodological quality, and evidence associated with single-intervention and multi-intervention approaches. A systematic review performed using the PubMed search engine and the key words "spinal cord injury motor recovery" identified 1973 records, of which 39 were selected (18 from the search records and 21 from reference list inspection). Study phase ( clinicaltrials.org criteria) and methodological quality (Cochrane criteria) were assessed. Studies included proposed a broad range of single-intervention (encompassing cell therapies, pharmacology, electrical stimulation, rehabilitation) (encompassing cell therapies, pharmacology, electrical stimulation, rehabilitation) and multi-intervention approaches (that combined more than one strategy). The highest evidence level was for Phase III studies supporting the role of multi-intervention approaches that contained a rehabilitation component. Quality appraisal revealed that the percentage of selected studies classified with high risk of bias by Cochrane criteria was as follows: random sequence generation = 64%; allocation concealment = 77%; blinding of participants and personnel = 69%; blinding of outcome assessment = 64%; attrition = 44%; selective reporting = 44%. The current literature contains a high proportion of studies with a limited ability to measure efficacy in a valid manner because of low methodological strength in all items of the Cochrane risk of bias assessment. Recommendations to decrease bias are discussed and include increased methodological rigor in the study design and recruitment of study participants, and the use of electrophysiological and imaging measures that can assess functional integrity of the spinal cord (and may be sufficiently sensitive to detect changes that occur in response to therapeutic

  4. Neurologic music therapy improves executive function and emotional adjustment in traumatic brain injury rehabilitation.

    PubMed

    Thaut, Michael H; Gardiner, James C; Holmberg, Dawn; Horwitz, Javan; Kent, Luanne; Andrews, Garrett; Donelan, Beth; McIntosh, Gerald R

    2009-07-01

    This study examined the immediate effects of neurologic music therapy (NMT) on cognitive functioning and emotional adjustment with brain-injured persons. Four treatment sessions were held, during which participants were given a pre-test, participated in 30 min of NMT that focused on one aspect of rehabilitation (attention, memory, executive function, or emotional adjustment), which was followed by post-testing. Control participants engaged in a pre-test, 30 min of rest, and then a post-test. Treatment participants showed improvement in executive function and overall emotional adjustment, and lessening of depression, sensation seeking, and anxiety. Control participants improved in emotional adjustment and lessening of hostility, but showed decreases in measures of memory, positive affect, and sensation seeking. PMID:19673815

  5. Improvement in acupoint selection for acupuncture of nerves surrounding the injury site: electro-acupuncture with Governor vessel with local meridian acupoints.

    PubMed

    He, Guan-Heng; Ruan, Jing-Wen; Zeng, Yuan-Shan; Zhou, Xin; Ding, Ying; Zhou, Guang-Hui

    2015-01-01

    nerve injury. After a single session, the patient's motor nerve conduction velocity increased by 23.2%, indicating that electroacupuncture at Governor vessel acupoints has an immediate therapeutic effect on peripheral nerve injury. Our results indicate that Governor vessel and local meridian acupoints used simultaneously promote functional repair after peripheral nerve injury. The mechanism of action may arise from an improvement of the local microenvironment in injured nervous tissue, as well as immediate effects of Governor vessel and local meridian acupoint stimulation to ensure the continuity between the peripheral and central nervous systems. PMID:25788933

  6. Improved Protective Effect of Umbilical Cord Stem Cell Transplantation on Cisplatin-Induced Kidney Injury in Mice Pretreated with Antithymocyte Globulin

    PubMed Central

    Večerić-Haler, Željka; Erman, Andreja; Cerar, Anton; Motaln, Helena; Kološa, Katja; Lah Turnšek, Tamara; Sodin Šemrl, Snežna; Lakota, Katja; Mrak-Poljšak, Katjuša; Škrajnar, Špela; Kranjc, Simona; Arnol, Miha; Perše, Martina

    2016-01-01

    Mesenchymal stem cells (MSCs) are recognised as a promising tool to improve renal recovery in experimental models of cisplatin-induced acute kidney injury. However, these preclinical studies were performed on severely immunodeficient animals. Here, we investigated whether human umbilical cord derived MSC treatment could equally ameliorate acute kidney injury induced by cisplatin and prolong survival in mice with a normal immune system and those with a suppressed immune system by polyclonal antithymocyte globulin (ATG). We demonstrated that ATG pretreatment, when followed by MSC transplantation, significantly improved injured renal function parameters, as evidenced by decreased blood urea nitrogen and serum creatinine concentration, as well as improved renal morphology. This tissue restoration was also supported by increased survival of mice. The beneficial effects of ATG were associated with reduced level of inflammatory protein serum amyloid A3 and induced antioxidative expression of superoxide dismutase-1 (SOD-1), glutathione peroxidase (GPx), and hem oxygenase-1 (HO-1). Infused MSCs became localised predominantly in peritubular areas and acted to reduce renal cell death. In conclusion, these results show that ATG diminished in situ inflammation and oxidative stress associated with cisplatin-induced acute kidney injury, the effects that may provide more favourable microenvironment for MSC action, with consequential synergistic improvements in renal injury and animal survival as compared to MSC treatment alone. PMID:26880955

  7. Minicircle microporation-based non-viral gene delivery improved the targeting of mesenchymal stem cells to an injury site.

    PubMed

    Mun, Ji-Young; Shin, Keun Koo; Kwon, Ohsuk; Lim, Yong Taik; Oh, Doo-Byoung

    2016-09-01

    Genetic engineering approaches to improve the therapeutic potential of mesenchymal stem cells (MSCs) have been made by viral and non-viral gene delivery methods. Viral methods have severe limitations in clinical application because of potential oncogenic, pathogenic, and immunogenic risks, while non-viral methods have suffered from low transfection efficiency and transient weak expression as MSCs are hard-to-transfect cells. In this study, minicircle, which is a minimal expression vector free of bacterial sequences, was employed for MSC transfection as a non-viral gene delivery method. The conventional cationic liposome method was not effective for MSC transfection as it resulted in very low transfection efficiency (less than 5%). Microporation, a new electroporation method, greatly improved the transfection efficiency of minicircles by up to 66% in MSCs without any significant loss of cell viability. Furthermore, minicircle microporation generated much stronger and prolonged transgene expression compared with plasmid microporation. When MSCs microporated with minicircle harboring firefly luciferase gene were subcutaneously injected to mice, the bioluminescence continued for more than a week, whereas the bioluminescence of the MSCs induced by plasmid microporation rapidly decreased and disappeared in mice within three days. By minicircle microporation as a non-viral gene delivery, MSCs engineered to overexpress CXCR4 showed greatly increased homing ability toward an injury site as confirmed through in vivo bioluminescence imaging in mice. In summary, the engineering of MSCs through minicircle microporation is expected to enhance the therapeutic potential of MSCs in clinical applications. PMID:27315214

  8. Recipient Hyperbilirubinemia May Reduce Ischemia-Reperfusion Injury but Fails to Improve Outcome in Clinical Liver Transplantation

    PubMed Central

    Oltean, Mihai; Barrenäs, Christian; Martins, Paulo Ney; Herlenius, Gustaf; Gustafsson, Bengt; Friman, Styrbjörn; Bennet, William

    2016-01-01

    Background. Exogenous bilirubin may reduce experimental ischemia-reperfusion injury (IRI) due to its antioxidant properties. We studied if early graft exposure to high bilirubin levels in the recipient affects the early IRI and outcomes after liver transplantation (LTx). Methods. In 427 LTx patients, the AUROC curve based on bilirubin and AST at day 1 identified a cutoff of 2.04 mg/dL for the recipient pretransplant bilirubin. Recipients were grouped as having low (group L, n = 152) or high (group H, n = 275) bilirubin. Both groups had similar donor-related variables (age, preservation time, donor BMI > 28, and donor risk index (DRI)). Results. Alanine (ALT) and aspartate (AST) aminotransferase levels were higher in group L at day 1; ALT levels remained higher at day 2 in group L. LTx from high risk donors (DRI > 2) revealed a trend towards lower transaminases during the first two days after transplantation in group H. One month and 1-year patient survival were similar in groups L and H. High preoperative bilirubin did not affect the risk for early graft dysfunction (EGD), death, or graft loss during the first year after transplantation nor the incidence of acute rejection. LTx using donors with DRI > 2 resulted in similar rates of EGD in both groups. Conclusion. Increased bilirubin appears to reduce the early IRI after LTx yet this improvement was insufficient to improve the clinical outcome.

  9. Continuous nicotinamide administration improves behavioral recovery and reduces lesion size following bilateral frontal controlled cortical impact injury.

    PubMed

    Vonder Haar, Cole; Anderson, Gail D; Hoane, Michael R

    2011-10-31

    Previous research has demonstrated considerable preclinical efficacy of nicotinamide (NAM; vitamin B(3)) in animal models of TBI with systemic dosing at 50 and 500 mg/kg yielding improvements on sensory, motor, cognitive and histological measures. The current study aimed to utilize a more specific dosing paradigm in a clinically relevant delivery mechanism: continuously secreting subcutaneous pumps. A bilateral frontal controlled cortical impact (CCI) or sham surgery was performed and rats were treated with NAM (150 mg/kg day) or saline (1 ml/kg) pumps 30 min after CCI, continuing until seven days post-CCI. Rats were given a loading dose of NAM (50mg/kg) or saline (1 ml/kg) following pump implant. Rats received behavioral testing (bilateral tactile adhesive removal, locomotor placing task and Morris water maze) starting on day two post-CCI and were sacrificed at 31 days post-CCI and brains were stained to examine lesion size. NAM-treated rats had reductions in sensory, motor and cognitive behavioral deficits compared to vehicle-treated rats. Specifically, NAM-treated rats significantly improved on the bilateral tactile adhesive removal task, locomotor placing task and the reference memory paradigm of the Morris water maze. Lesion size was also significantly reduced in the NAM-treated group. The results from this study indicate that at the current dose, NAM produces beneficial effects on recovery from a bilateral frontal brain injury and that it may be a relevant compound to be explored in human studies. PMID:21704653

  10. Cortisol Supplement Combined with Psychotherapy and Citalopram Improves Depression Outcomes in Patients with Hypocortisolism after Traumatic Brain Injury

    PubMed Central

    Luo, Lanlan; Chai, Yan; Jiang, Rongcai; Chen, Xin; Yan, Tao

    2015-01-01

    Depression is one of the most prevalent psychiatric disorders in people with Traumatic brain injury (TBI). Depression after TBI is closely related with social and psychological factors and hypothalamic-pituitary -adrenal (HPA) axis dysfunction. However, there is a lack of evidence regarding effective treatment approaches for depression. A total of 68 patients with depression following closed TBI were recruited. Glasgow Coma Scale score (GCS) was employed to demonstrate the severity of neurological deficits and Glasgow Outcome Scale (GOS) was employed to measure functional outcome after TBI. The severity of depression was quantified using the Beck Depression Inventory-II (BDI-II) in line with DSM-IV. Citalopram and Prednisone were administered to subjects with normal cortisol levels or hypocortisolism separately, based on psychotherapeutic interventions. We investigated the relationship between degree of depression of TBI patients and the severity and progression of TBI with the therapeutic effects of Citalopram in combination with psychotherapeutic and Prednisone in depressed patients. There was no relationship between the severity of depression and the severity and progression of TBI. The basic treatment of psychotherapeutic interventions could partially relieve depressive symptoms. Combination of psychotherapeutic support and Citalopram significantly improved depressive symptoms in patients with normal cortisol levels, but not in hypocortisolic patients. Combination of Prednisone administration with psychotherapeutic treatment and Citalopram significantly improved depression outcome in hypocortisolic patients after TBI. Hypocortisolism after TBI may regulate depression. Combination of Prednisone with psychotherapeutic treatment and Citalopram may provide better therapeutic effects in depression patients with hypocortisolism after TBI. PMID:26618043

  11. Administration of low dose estrogen attenuates persistent inflammation, promotes angiogenesis, and improves locomotor function following chronic spinal cord injury in rats.

    PubMed

    Samantaray, Supriti; Das, Arabinda; Matzelle, Denise C; Yu, Shan P; Wei, Ling; Varma, Abhay; Ray, Swapan K; Banik, Naren L

    2016-05-01

    Spinal cord injury (SCI) causes loss of neurological function and, depending upon the severity of injury, may lead to paralysis. Currently, no FDA-approved pharmacotherapy is available for SCI. High-dose methylprednisolone is widely used, but this treatment is controversial. We have previously shown that low doses of estrogen reduces inflammation, attenuates cell death, and protects axon and myelin in SCI rats, but its effectiveness in recovery of function is not known. Therefore, the goal of this study was to investigate whether low doses of estrogen in post-SCI would reduce inflammation, protect cells and axons, and improve locomotor function during the chronic phase of injury. Injury (40 g.cm force) was induced at thoracic 10 in young adult male rats. Rats were treated with 10 or 100 μg 17β-estradiol (estrogen) for 7 days following SCI and compared with vehicle-treated injury and laminectomy (sham) controls. Histology (H&E staining), immunohistofluorescence, Doppler laser technique, and Western blotting were used to monitor tissue integrity, gliosis, blood flow, angiogenesis, the expression of angiogenic factors, axonal degeneration, and locomotor function (Basso, Beattie, and Bresnahan rating) following injury. To assess the progression of recovery, rats were sacrificed at 7, 14, or 42 days post injury. A reduction in glial reactivity, attenuation of axonal and myelin damage, protection of cells, increased expression of angiogenic factors and microvessel growth, and improved locomotor function were found following estrogen treatment compared with vehicle-treated SCI rats. These results suggest that treatment with a very low dose of estrogen has significant therapeutic implications for the improvement of locomotor function in chronic SCI. Experimental studies with low dose estrogen therapy in chronic spinal cord injury (SCI) demonstrated the potential for multi-active beneficial outcomes that could ameliorate the degenerative pathways in chronic SCI as

  12. Making History Come Alive: Dramatization in the Classroom.

    ERIC Educational Resources Information Center

    Drake, Frederick D.; Corbin, Denee

    1993-01-01

    Asserts that people of all ages love a story that involves heroes and villains and that a teacher can bridge the gap between political and social history through dramatization. Describes procedures for identifying appropriate topics for dramatization and encouraging student involvement. (CFR)

  13. Cognitive Psychology and Audience-Oriented Dramatic Theory.

    ERIC Educational Resources Information Center

    Bratt, David

    Cognitive psychology's most useful contribution to dramatic theory is the concept of schemata, or the mental structures that make up part of the perceptual cycle. In regard to an audience-oriented dramatic theory, this suggests that analysis of a script ought to identify the sorts of schemata that are to be aroused in the audience's minds and the…

  14. Dramatic Activities in Language Arts Classrooms: Resource Summary. ERIC Digest.

    ERIC Educational Resources Information Center

    Tatar, Sibel

    This digest reviews some of the related literature about the benefits of classroom drama activities and introduces a variety of resources to help educators incorporate dramatic activities in their language arts classrooms. The digest notes that although several terms have been used to refer to "classroom drama" such as creative dramatics,…

  15. Dramatic Arts in the Secondary School, MSA Curriculum Guide 6.

    ERIC Educational Resources Information Center

    Herman, Deldee M., Ed.; Ratliffe, Sharon A., Ed.

    This volume of the Michigan Speech Association curriculum guide is a revision of the 1968 edition (ED 026 389). The first eight units comprise a first semester course that emphasizes theatre history, dramatic structure, and dramatic criticism and theory. There are also units on presenting a one-act play, music in the theatre, and children's…

  16. CHRONIC UCL INJURY: A MULTIMODAL APPROACH TO CORRECTING ALTERED MECHANICS AND IMPROVING HEALING IN A COLLEGE ATHLETE— A CASE REPORT

    PubMed Central

    Patrick, Rachel; McGinty, Josh; Lucado, Ann; Collier, Beth

    2016-01-01

    ABSTRACT Background Ulnar collateral ligament (UCL) tears and associated Tommy Johns surgical intervention from excessive and poor quality pitching has increased immensely—with more college and professional pitchers undergoing the surgery in 2014 alone than in the 1990s as a whole.1 Faulty mechanics developed at young ages are often well-engrained by the late adolescent years and the minimal healing ability of the largely avascular UCL often leads to delayed safe return to sport.2 Purpose The purpose of this case study was to describe an innovative, multimodal approach to conservative management of a chronic UCL injury in a college-aged baseball pitcher. This innovative approach utilizes both contractile and non-contractile dry needling to enhance soft tissue healing combined with standard conservative treatment to decrease pain and improve sport performance as measured by the Disabilities of Arm, Shoulder and Hand (DASH), Numeric Pain Report Scale (NPRS), and return to sport. Study Design Retrospective Case Report Case Description A collegiate athlete presented to an outpatient orthopedic physical therapy clinic for treatment of UCL sprain approximately six weeks post-injury and platelet-rich plasma injection. Diagnostic testing revealed chronic ligamentous microtrauma. Impairments at evaluation included proximal stabilizing strength deficits, myofascial trigger points throughout the dominant upper extremity, improper pitching form, and inability to pitch in game conditions due to severe pain. Interventions included addressing strength deficits throughout the body, dry needling, and sport-specific biomechanical training with pitching form analysis and correction. Outcomes Conventional DASH and Sport-Specific scale on the DASH and the numeric pain rating scale improved beyond both the minimally clinically important difference and minimal detectable change over the 12 week treatment3,4 At 24-week follow up, conventional DASH scores decreased from 34.20% disability

  17. Deguelin Attenuates Reperfusion Injury and Improves Outcome after Orthotopic Lung Transplantation in the Rat

    PubMed Central

    Paulus, Patrick; Ockelmann, Pia; Tacke, Sabine; Karnowski, Nora; Ellinghaus, Peter; Scheller, Bertram; Holfeld, Johannes; Urbschat, Anja; Zacharowski, Kai

    2012-01-01

    The main goal of adequate organ preservation is to avoid further cellular metabolism during the phase of ischemia. However, modern preservation solutions do rarely achieve this target. In donor organs hypoxia and ischemia induce a broad spectrum of pathologic molecular mechanisms favoring primary graft dysfunction (PGD) after transplantation. Increased hypoxia-induced transcriptional activity leads to increased vascular permeability which in turn is the soil of a reperfusion edema and the enhancement of a pro-inflammatory response in the graft after reperfusion. We hypothesize that inhibition of the respiration chain in mitochondria and thus inhibition of the hypoxia induced mechanisms might reduce reperfusion edema and consecutively improve survival in vivo. In this study we demonstrate that the rotenoid Deguelin reduces the expression of hypoxia induced target genes, and especially VEGF-A, dose-dependently in hypoxic human lung derived cells. Furthermore, Deguelin significantly suppresses the mRNA expression of the HIF target genes VEGF-A, the pro-inflammatory CXCR4 and ICAM-1 in ischemic lungs vs. control lungs. After lung transplantation, the VEGF-A induced reperfusion-edema is significantly lower in Deguelin-treated animals than in controls. Deguelin-treated rats exhibit a significantly increased survival-rate after transplantation. Additionally, a downregulation of the pro-inflammatory molecules ICAM-1 and CXCR4 and an increase in the recruitment of immunomodulatory monocytes (CD163+ and CD68+) to the transplanted organ involving the IL4 pathway was observed. Therefore, we conclude that ischemic periods preceding reperfusion are mainly responsible for the increased vascular permeability via upregulation of VEGF. Together with this, the resulting endothelial dysfunction also enhances inflammation and consequently lung dysfunction. Deguelin significantly decreases a VEGF-A induced reperfusion edema, induces the recruitment of immunomodulatory monocytes and thus

  18. Prior regular exercise improves clinical outcome and reduces demyelination and axonal injury in experimental autoimmune encephalomyelitis.

    PubMed

    Bernardes, Danielle; Brambilla, Roberta; Bracchi-Ricard, Valerie; Karmally, Shaffiat; Dellarole, Anna; Carvalho-Tavares, Juliana; Bethea, John R

    2016-01-01

    Although previous studies have shown that forced exercise modulates inflammation and is therapeutic acutely for experimental autoimmune encephalomyelitis (EAE), the long-term benefits have not been evaluated. In this study, we investigated the effects of preconditioning exercise on the clinical and pathological progression of EAE. Female C57BL/6 mice were randomly assigned to either an exercised (Ex) or unexercised (UEx) group and all of them were induced for EAE. Mice in the Ex group had an attenuated clinical score relative to UEx mice throughout the study. At 42 dpi, flow cytometry analysis showed a significant reduction in B cells, CD4(+) T cells, and CD8(+) T cells infiltrating into the spinal cord in the Ex group compared to UEx. Ex mice also had a significant reduction in myelin damage with a corresponding increase in proteolipid protein expression. Finally, Ex mice had a significant reduction in axonal damage. Collectively, our study demonstrates for the first time that a prolonged and forced preconditioning protocol of exercise improves clinical outcome and attenuates pathological hallmarks of EAE at chronic disease. In this study, we show that a program of 6 weeks of preconditioning exercise promoted a significant reduction of cells infiltrating into the spinal cord, a significant reduction in myelin damage and a significant reduction in axonal damage in experimental autoimmune encephalomyelitis (EAE) mice at 42 dpi. Collectively, our study demonstrates for the first time that a preconditioning protocol of exercise improves clinical outcome and attenuates pathological hallmarks of EAE at chronic disease. PMID:26364732

  19. Deficits in Discrimination after Experimental Frontal Brain Injury Are Mediated by Motivation and Can Be Improved by Nicotinamide Administration

    PubMed Central

    Vonder Haar, Cole; Maass, William R.; Jacobs, Eric A.

    2014-01-01

    Abstract One of the largest challenges in experimental neurotrauma work is the development of models relevant to the human condition. This includes both creating similar pathophysiology as well as the generation of relevant behavioral deficits. Recent studies have shown that there is a large potential for the use of discrimination tasks in rats to detect injury-induced deficits. The literature on discrimination and TBI is still limited, however. The current study investigated motivational and motor factors that could potentially contribute to deficits in discrimination. In addition, the efficacy of a neuroprotective agent, nicotinamide, was assessed. Rats were trained on a discrimination task and motivation task, given a bilateral frontal controlled cortical impact TBI (+3.0 AP, 0.0 ML from bregma), and then reassessed. They were also assessed on motor ability and Morris water maze (MWM) performance. Experiment 1 showed that TBI resulted in large deficits in discrimination and motivation. No deficits were observed on gross motor measures; however, the vehicle group showed impairments in fine motor control. Both injured groups were impaired on the reference memory MWM, but only nicotinamide-treated rats were impaired on the working memory MWM. Nicotinamide administration improved performance on discrimination and motivation measures. Experiment 2 evaluated retraining on the discrimination task and suggested that motivation may be a large factor underlying discrimination deficits. Retrained rats improved considerably on the discrimination task. The tasks evaluated in this study demonstrate robust deficits and may improve the detection of pharmaceutical effects by being very sensitive to pervasive cognitive deficits that occur after frontal TBI. PMID:24934504

  20. Deficits in discrimination after experimental frontal brain injury are mediated by motivation and can be improved by nicotinamide administration.

    PubMed

    Vonder Haar, Cole; Maass, William R; Jacobs, Eric A; Hoane, Michael R

    2014-10-15

    One of the largest challenges in experimental neurotrauma work is the development of models relevant to the human condition. This includes both creating similar pathophysiology as well as the generation of relevant behavioral deficits. Recent studies have shown that there is a large potential for the use of discrimination tasks in rats to detect injury-induced deficits. The literature on discrimination and TBI is still limited, however. The current study investigated motivational and motor factors that could potentially contribute to deficits in discrimination. In addition, the efficacy of a neuroprotective agent, nicotinamide, was assessed. Rats were trained on a discrimination task and motivation task, given a bilateral frontal controlled cortical impact TBI (+3.0 AP, 0.0 ML from bregma), and then reassessed. They were also assessed on motor ability and Morris water maze (MWM) performance. Experiment 1 showed that TBI resulted in large deficits in discrimination and motivation. No deficits were observed on gross motor measures; however, the vehicle group showed impairments in fine motor control. Both injured groups were impaired on the reference memory MWM, but only nicotinamide-treated rats were impaired on the working memory MWM. Nicotinamide administration improved performance on discrimination and motivation measures. Experiment 2 evaluated retraining on the discrimination task and suggested that motivation may be a large factor underlying discrimination deficits. Retrained rats improved considerably on the discrimination task. The tasks evaluated in this study demonstrate robust deficits and may improve the detection of pharmaceutical effects by being very sensitive to pervasive cognitive deficits that occur after frontal TBI. PMID:24934504

  1. Urethral Injuries

    MedlinePlus

    ... Injuries Ureteral Injuries Urethral Injuries Injuries to the Penis and Scrotum Most urethral injuries occur in men. ... leakage of urine into the tissues of the penis, scrotum, abdominal wall, or perineum (the area between ...

  2. Ankle syndesmosis injuries.

    PubMed

    Peña, Fernando A; Coetzee, J Chris

    2006-03-01

    Physician awareness of ankle syndesmosis injuries is improving. The anatomy involved and the mechanism of injury are extremely relevant for the understanding and treatment of this type of injury. Examination under anesthesia may confirm the syndesmosis instability. Based on those findings, stabilization is the recommended approach. PMID:16564452

  3. Absence of Sema4D improves oligodendrocyte recovery after cerebral ischemia/reperfusion injury in mice.

    PubMed

    Wada, Takenobu; Sawano, Toshinori; Tanaka, Takashi; Furuyama, Tatsuo; Fukumoto, Moe; Yamaguchi, Wataru; Saino, Orie; Takeda, Yuichi; Kogo, Mikihiko; Matsuyama, Tomohiro; Inagaki, Shinobu

    2016-07-01

    Sema4D, originally identified as a negative regulator of axon guidance during development, is involved in various physiological and pathological responses. In this study, we evaluated the effect of Sema4D-deficiency on oligodendrocyte restoration after the cerebral ischemia/reperfusion using direct ligation of the middle cerebral artery followed by reperfusion. In both Sema4D(+/+) wild-type and Sema4D(-/-) null mutant mice, the peri-infarct area showed a decrease in the number of oligodendrocytes at 3 days post-reperfusion. Subsequently, the number of oligodendrocytes was observed to gradually recover in both groups. Sema4D-deficient mice, however, showed an enhanced recovery of oligodendrocytes and an upregulation of oligodendrocyte progenitor cells at days 14 and 28 of reperfusion. Cell proliferation identified by incorporation of bromodeoxyuridine was enhanced in Sema4D(-/-) mice from days 3 to 14 post-reperfusion compared to the Sema4D(+/+) mice. Furthermore, apoptotic cell death of oligodendrocytes was reduced at days 7 post-reperfusion in Sema4D(-/-) mice compared to Sema4D(+/+) mice. These findings indicate that enhanced proliferation of progenitor cells and survival of oligodendrocytes resulted in improved oligodendrocyte recovery in Sema4D(-/-) mice. This may provide a new approach for neurorestorative treatment in patients with stroke, which aims to manipulate endogenous oligodendrogenesis and thereby to promote brain repair after stroke. PMID:26752319

  4. SP-8203 shows neuroprotective effects and improves cognitive impairment in ischemic brain injury through NMDA receptor.

    PubMed

    Noh, Su-Jin; Lee, Jong Min; Lee, Ki Sung; Hong, Hyun Su; Lee, Chul Kyu; Cho, Il Hwan; Kim, Hye-Sun; Suh, Yoo-Hun

    2011-11-01

    The extracts of earth worms, Eisenia andrei, have been used as a therapeutic agent for stroke in the traditional medicine. It is also reported that the protease fraction separated from the extracts has strong anti-thrombotic activity. Besides anti-thrombotic actions, we found that SP-8203, N-[3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propyl]-N-{4-[3-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)propylamino]butyl}acetamide, derived from the extracts of earth worms blocked N-methyl-(D)-aspartate (NMDA) receptor-mediated excitotoxicity in a competitive manner. The neuroprotective effects of SP-8203 were attributable to prevention of Ca(2+) influx through NMDA receptors. The systemic administration of SP-8203 markedly reduced neuronal death following middle cerebral artery occlusion in rats. SP-8203 significantly improved spatial learning and memory in the water maze test. These results provided strong pharmacological basis for its potential therapeutic roles in cerebral ischemia. PMID:21835192

  5. Sodium selenate, a protein phosphatase 2A activator, mitigates hyperphosphorylated tau and improves repeated mild traumatic brain injury outcomes.

    PubMed

    Tan, Xin L; Wright, David K; Liu, Shijie; Hovens, Christopher; O'Brien, Terence J; Shultz, Sandy R

    2016-09-01

    Mild traumatic brain injuries may result in cumulative brain damage and neurodegenerative disease. To date, there is no pharmaceutical intervention known to prevent these consequences. Hyperphosphorylated tau has been associated in this process, and protein phosphatase 2A 55 kDa regulatory B subunit (PP2A/PR55) - the major tau phosphatase - is decreased after a brain insult. Sodium selenate up-regulates PP2A/PR55 and dephosphorylates tau, and may hold promise as a treatment in the mild brain injury setting. Here we investigated sodium selenate treatment in rats given repeated mild traumatic brain injuries. Rats were given three mild fluid percussion injuries or three sham-injuries, and treated with sodium selenate (1 mg/kg/day) or saline-vehicle for three months before undergoing behavioral testing, MRI, and post-mortem analysis of brain tissue. Repeated mild traumatic brain injuries increased the phosphorylation of tau and decreased PP2A/PR55, whilst inducing brain atrophy and cognitive and sensorimotor deficits. Sodium selenate treatment increased PP2A/PR55, and decreased tau phosphorylation, brain damage, and cognitive and motor impairments in rats given repeated mild traumatic brain injuries. Our findings implicate PP2A/PR55 and tau as important mechanisms in the pathophysiological aftermath of repeated mild brain traumas, and support sodium selenate as a novel and translatable treatment for these common injuries. PMID:27163189

  6. Evaluation of a Reading Comprehension Strategy Package to Improve Reading Comprehension of Adult College Students with Acquired Brain Injuries

    ERIC Educational Resources Information Center

    Griffiths, Gina G.

    2013-01-01

    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.…

  7. A Dunnione Compound MB12662 Improves Cisplatin-Induced Tissue Injury and Emesis

    PubMed Central

    Park, Dongsun; Jo, In Geun; Jang, Ja Young; Kwak, Tae Hwan; Yoo, Sang Ku; Jeon, Jeong Hee; Choi, Ehn-Kyoung; Joo, Seong Soo; Kim, Okjin; Kim, Yun-Bae

    2015-01-01

    The present study was aimed to investigate the effects of MB12662, a synthetic dunnione compound, on cisplatin-induced vomiting reflexes and intestinal, renal, immune system, and hematopoietic toxicities in ferrets and mice, respectively. Male ICR mice were orally administered MB12662 (5, 10, 25 or 50 mg/kg) for 10 days, during which intraperitoneally challenged with cisplatin (3.5 mg/kg) from day 4 to 7, and sacrificed on day 10 for the pathological examination. Male ferrets were orally administered MB12662 (25, 50 or 100 mg/kg) for 7 days, subcutaneously challenged with cisplatin (5 mg/kg), and monitored for vomiting reflexes and survival of the animals. Four-day injection of cisplatin (3.5 mg/kg) to mice caused body weight loss and degeneration and atrophy of intestinal villi, reducing villi/crypt ratio to a half level of control animals. Cisplatin also induced renal and hepatic toxicities, and depletion of splenocytes and bone marrow progenitor cells. The systemic toxicities including decreased villi/crypt ratio, immune system atrophy, splenocyte depletion, and decreased cellularity in bone marrow were improved by MB12662. Cisplatin (5 mg/kg) induced retching and emetic responses of ferrets, which were remarkably attenuated by MB12662 in a dose-dependent manner. All the ferrets pretreated with MB12662 survived the challenge of cisplatin, in comparison with 40% mortality in vehicle-treated animals, and blood parameters of nephrotoxicity and hepatotoxicity were markedly recovered. It is expected that MB12662 could be a candidate for the body protection against burden, including emesis, of chemotherapeutic agents. PMID:26336585

  8. Cholecalciferol (Vitamin D3) Improves Myelination and Recovery after Nerve Injury

    PubMed Central

    Chabas, Jean-Francois; Stephan, Delphine; Marqueste, Tanguy; Garcia, Stephane; Lavaut, Marie-Noelle; Nguyen, Catherine; Legre, Regis; Khrestchatisky, Michel

    2013-01-01

    Previously, we demonstrated i) that ergocalciferol (vitamin D2) increases axon diameter and potentiates nerve regeneration in a rat model of transected peripheral nerve and ii) that cholecalciferol (vitamin D3) improves breathing and hyper-reflexia in a rat model of paraplegia. However, before bringing this molecule to the clinic, it was of prime importance i) to assess which form – ergocalciferol versus cholecalciferol – and which dose were the most efficient and ii) to identify the molecular pathways activated by this pleiotropic molecule. The rat left peroneal nerve was cut out on a length of 10 mm and autografted in an inverted position. Animals were treated with either cholecalciferol or ergocalciferol, at the dose of 100 or 500 IU/kg/day, or excipient (Vehicle), and compared to unlesioned rats (Control). Functional recovery of hindlimb was measured weekly, during 12 weeks, using the peroneal functional index. Ventilatory, motor and sensitive responses of the regenerated axons were recorded and histological analysis was performed. In parallel, to identify the genes regulated by vitamin D in dorsal root ganglia and/or Schwann cells, we performed an in vitro transcriptome study. We observed that cholecalciferol is more efficient than ergocalciferol and, when delivered at a high dose (500 IU/kg/day), cholecalciferol induces a significant locomotor and electrophysiological recovery. We also demonstrated that cholecalciferol increases i) the number of preserved or newly formed axons in the proximal end, ii) the mean axon diameter in the distal end, and iii) neurite myelination in both distal and proximal ends. Finally, we found a modified expression of several genes involved in axogenesis and myelination, after 24 hours of vitamin supplementation. Our study is the first to demonstrate that vitamin D acts on myelination via the activation of several myelin-associated genes. It paves the way for future randomised controlled clinical trials for peripheral nerve or

  9. A Dunnione Compound MB12662 Improves Cisplatin-Induced Tissue Injury and Emesis.

    PubMed

    Park, Dongsun; Jo, In Geun; Jang, Ja Young; Kwak, Tae Hwan; Yoo, Sang Ku; Jeon, Jeong Hee; Choi, Ehn-Kyoung; Joo, Seong Soo; Kim, Okjin; Kim, Yun-Bae

    2015-09-01

    The present study was aimed to investigate the effects of MB12662, a synthetic dunnione compound, on cisplatin-induced vomiting reflexes and intestinal, renal, immune system, and hematopoietic toxicities in ferrets and mice, respectively. Male ICR mice were orally administered MB12662 (5, 10, 25 or 50 mg/kg) for 10 days, during which intraperitoneally challenged with cisplatin (3.5 mg/kg) from day 4 to 7, and sacrificed on day 10 for the pathological examination. Male ferrets were orally administered MB12662 (25, 50 or 100 mg/kg) for 7 days, subcutaneously challenged with cisplatin (5 mg/kg), and monitored for vomiting reflexes and survival of the animals. Four-day injection of cisplatin (3.5 mg/kg) to mice caused body weight loss and degeneration and atrophy of intestinal villi, reducing villi/crypt ratio to a half level of control animals. Cisplatin also induced renal and hepatic toxicities, and depletion of splenocytes and bone marrow progenitor cells. The systemic toxicities including decreased villi/crypt ratio, immune system atrophy, splenocyte depletion, and decreased cellularity in bone marrow were improved by MB12662. Cisplatin (5 mg/kg) induced retching and emetic responses of ferrets, which were remarkably attenuated by MB12662 in a dose-dependent manner. All the ferrets pretreated with MB12662 survived the challenge of cisplatin, in comparison with 40% mortality in vehicle-treated animals, and blood parameters of nephrotoxicity and hepatotoxicity were markedly recovered. It is expected that MB12662 could be a candidate for the body protection against burden, including emesis, of chemotherapeutic agents. PMID:26336585

  10. Nesfatin-1 improves oxidative skin injury in normoglycemic or hyperglycemic rats.

    PubMed

    Solmaz, Ali; Bahadır, Elif; Gülçiçek, Osman B; Yiğitbaş, Hakan; Çelik, Atilla; Karagöz, Ayça; Özsavcı, Derya; Şirvancı, Serap; Yeğen, Berrak Ç

    2016-04-01

    Hyperglycemia is one of the major causes of suppressed angiogenesis and impaired wound healing leading to chronic wounds. Nesfatin-1 a novel peptide was reported to have antioxidant and anti-apoptotic properties. This study is aimed to investigate the potential healing-promoting effects of nesfatin-1 in non-diabetic or diabetic rats with surgical wounds. In male Sprague-Dawley rats, hyperglycemia was induced by intraperitoneal (ip) injection of streptozotocin (55 mg/kg). Under anesthesia, dorsum skin tissues of normoglycemic (n=16) and hyperglycemic rats were excised (2 × 2 cm, full-thickness), while control rats (n=16) had neither hyperglycemia nor wounds. Half of the rats in each group were treated ip with saline, while the others were treated with nesfatin-1 (2 μg/kg/day) for 3 days until they were decapitated. Plasma interleukin-1-beta (IL-1β), transforming growth factor-beta (TGF-β-1), IL-6 levels, and dermal tissue malondialdehyde (MDA), glutathione (GSH) levels, myeloperoxidase (MPO) and caspase-3 activity were measured. For histological examination, paraffin sections were stained with hematoxylin-eosin or Masson's trichrome and immunohistochemistry for vascular endothelial growth factor (VEGF) was applied. ANOVA and Student's t-tests were used for statistical analysis. Compared to control rats, skin MPO activity, MDA and caspase-3 levels were increased similarly in saline-treated normo- and hyperglycemic rats. Nesfatin-1 depressed MDA, caspase-3, MPO activity and IL-1β with concomitant elevations in dermal GSH and plasma TGF-β-1 levels. Histopathological examination revealed regeneration of epidermis, regular arrangement of collagen fibers in the dermis and a decrease in VEGF immunoreactivity in the epidermal keratinocytes of nesfatin-1-treated groups. Nesfatin-1 improved surgical wound healing in both normo- and hyperglycemic rats via the suppression of neutrophil recruitment, apoptosis and VEGF activation. PMID:26829459

  11. Recurrent Recruitment Manoeuvres Improve Lung Mechanics and Minimize Lung Injury during Mechanical Ventilation of Healthy Mice

    PubMed Central

    Reiss, Lucy Kathleen; Kowallik, Anke; Uhlig, Stefan

    2011-01-01

    Introduction Mechanical ventilation (MV) of mice is increasingly required in experimental studies, but the conditions that allow stable ventilation of mice over several hours have not yet been fully defined. In addition, most previous studies documented vital parameters and lung mechanics only incompletely. The aim of the present study was to establish experimental conditions that keep these parameters within their physiological range over a period of 6 h. For this purpose, we also examined the effects of frequent short recruitment manoeuvres (RM) in healthy mice. Methods Mice were ventilated at low tidal volume VT = 8 mL/kg or high tidal volume VT = 16 mL/kg and a positive end-expiratory pressure (PEEP) of 2 or 6 cmH2O. RM were performed every 5 min, 60 min or not at all. Lung mechanics were followed by the forced oscillation technique. Blood pressure (BP), electrocardiogram (ECG), heart frequency (HF), oxygen saturation and body temperature were monitored. Blood gases, neutrophil-recruitment, microvascular permeability and pro-inflammatory cytokines in bronchoalveolar lavage (BAL) and blood serum as well as histopathology of the lung were examined. Results MV with repetitive RM every 5 min resulted in stable respiratory mechanics. Ventilation without RM worsened lung mechanics due to alveolar collapse, leading to impaired gas exchange. HF and BP were affected by anaesthesia, but not by ventilation. Microvascular permeability was highest in atelectatic lungs, whereas neutrophil-recruitment and structural changes were strongest in lungs ventilated with high tidal volume. The cytokines IL-6 and KC, but neither TNF nor IP-10, were elevated in the BAL and serum of all ventilated mice and were reduced by recurrent RM. Lung mechanics, oxygenation and pulmonary inflammation were improved by increased PEEP. Conclusions Recurrent RM maintain lung mechanics in their physiological range during low tidal volume ventilation of healthy mice by preventing atelectasis and

  12. The Coagulation Factor XIIa Inhibitor rHA-Infestin-4 Improves Outcome after Cerebral Ischemia/Reperfusion Injury in Rats

    PubMed Central

    Krupka, Jennifer; May, Frauke; Weimer, Thomas; Pragst, Ingo; Kleinschnitz, Christoph; Stoll, Guido; Panousis, Con; Dickneite, Gerhard; Nolte, Marc W.

    2016-01-01

    Background and Purpose Ischemic stroke provokes severe brain damage and remains a predominant disease in industrialized countries. The coagulation factor XII (FXII)-driven contact activation system plays a central, but not yet fully defined pathogenic role in stroke development. Here, we investigated the efficacy of the FXIIa inhibitor rHA-Infestin-4 in a rat model of ischemic stroke using both a prophylactic and a therapeutic approach. Methods For prophylactic treatment, animals were treated intravenously with 100 mg/kg rHA-Infestin-4 or an equal volume of saline 15 min prior to transient middle cerebral artery occlusion (tMCAO) of 90 min. For therapeutic treatment, 100 mg/kg rHA-Infestin-4, or an equal volume of saline, was administered directly after the start of reperfusion. At 24 h after tMCAO, rats were tested for neurological deficits and blood was drawn for coagulation assays. Finally, brains were removed and analyzed for infarct area and edema formation. Results Within prophylactic rHA-Infestin-4 treatment, infarct areas and brain edema formation were reduced accompanied by better neurological scores and survival compared to controls. Following therapeutic treatment, neurological outcome and survival were still improved although overall effects were less pronounced compared to prophylaxis. Conclusions With regard to the central role of the FXII-driven contact activation system in ischemic stroke, inhibition of FXIIa may represent a new and promising treatment approach to prevent cerebral ischemia/reperfusion injury. PMID:26815580

  13. Proinflammatory cytokine-receptor interaction model improves the predictability of cerebral white matter injury in preterm infants.

    PubMed

    Bass, W Thomas; Buescher, E Stephen; Hair, Pamela S; White, Larry E; Welch, J Camille; Burke, Bonnie L

    2008-04-01

    Proinflammatory cytokines have been variably linked to development of cerebral white matter injury (WMI) in preterm infants. Because soluble receptors tightly control cytokine bioactivity, we modeled cytokine-receptor interaction as a predictor of WMI. Plasma from 100 preterm infants was assayed for cytokines (tumor necrosis factor alpha, interleukin (IL-1beta, IL-6) and their soluble receptors (sTNF-RI), sTNF-RII, sIL-1RA, and sIL-6R). Cranial ultrasound (US) results were correlated with cytokine and receptor concentrations individually and with cytokine-receptor interaction models (PROC LOGISTIC; SAS Software). Receiver operating characteristic curves were constructed to determine the predictability of WMI. Fifty-two infants with normal US exams were compared with 21 infants with evidence of WMI. There was no association between individual cytokine or receptor concentrations and the development of WMI. However, modeling cytokines with their soluble receptors significantly improved the predictability of WMI. We concluded that consideration of cytokine-receptor interaction may be more important than individual cytokine concentrations alone in determining the role of inflammation in the pathogenesis of WMI in preterm infants. PMID:18548393

  14. Pretreatment of amphiphilic comb polymer surfaces dramatically affects protein adsorption.

    PubMed

    Zhang, Zhanping; Ma, Hongwei; Hausner, Douglas B; Chilkoti, Ashutosh; Beebe, Thomas P

    2005-01-01

    New applications in regenerative biotechnology require the ability to understand and control protein-surface interactions on micrometer and submicrometer length scales. Evidence presented here shows that micropatterned amphiphilic comb polymer films exhibit a pretreatment-dependent behavior with respect to protein adsorption for the proteins fibronectin, laminin, and for serum. A micropatterned surface, consisting of protein-reactive regions, separated by comb polymer, was created and tested for protein adsorption using the surface-sensitive imaging tool TOF-SIMS. Immersion of micropatterned surfaces in solutions of fibronectin or laminin resulted in uniform protein coverage on both the comb polymer and protein-reactive regions. However, preimmersion of similarly patterned surfaces in water for 2 h prior to protein incubation was found to dramatically improve the protein-resistant properties of the comb polymer regions. These results are consistent with poly(ethylene glycol) (PEG) side chain reorientation and/or hydration and poly(methyl methacrylate) (PMMA) backbone segregation away from the interface region. PMID:16283770

  15. Local stakeholders' perspectives on improving the urban environment to reduce child pedestrian injury: implementing effective public health interventions at the local level.

    PubMed

    Frattaroli, Shannon; Defrancesco, Susan; Gielen, Andrea C; Bishai, David M; Guyer, Bernard

    2006-01-01

    Local-level public health interventions require action from multiple agencies, organizations and individuals, yet little is known about how best to work with stakeholders to facilitate change. We sought local stakeholders' perspectives on how best to address impediments to implementing interventions designed to reduce child pedestrian injury by improving the pedestrian environment. We conducted 20 in-person, key informant interviews with people who would be the likely advocates for environmental change to improve the pedestrian environment in one US city, Baltimore, Maryland. We discuss the importance of reframing child pedestrian injury risk as a livability issue, increasing awareness about the potential impact of environmental changes to improve public safety, and the need for a formal efficient process to facilitate communication between local government and other stakeholders. These findings provide public health professionals and advocates with useful insight into how local stakeholders view the issue and their perspectives on how best to achieve change. PMID:17164804

  16. Insulin Sensitivity and Mitochondrial Function Are Improved in Children With Burn Injury During a Randomized Controlled Trial of Fenofibrate

    PubMed Central

    Cree, Melanie G.; Zwetsloot, Jennifer J.; Herndon, David N.; Qian, Ting; Morio, Beatrice; Fram, Ricki; Sanford, Arthur P.; Aarsland, Asle; Wolfe, Robert R.

    2007-01-01

    Objective: To determine some of the mechanisms involved in insulin resistance immediately following burn trauma, and to determine the efficacy of PPAR-α agonism for alleviating insulin resistance in this population. Summary Background Data: Hyperglycemia following trauma, especially burns, is well documented. However, the underlying insulin resistance is not well understood, and there are limited treatment options. Methods: Twenty-one children 4 to 16 years of age with >40% total body surface area burns were enrolled in a double-blind, prospective, placebo-controlled randomized trial. Whole body and liver insulin sensitivity were assessed with a hyperinsulinemic-euglycemic clamp, and insulin signaling and mitochondrial function were measured in muscle biopsies taken before and after ∼2 weeks of either placebo (PLA) or 5 mg/kg of PPAR-α agonist fenofibrate (FEN) treatment, within 3 weeks of injury. Results: The change in average daily glucose concentrations was significant between groups after treatment (146 ± 9 vs. 161 ± 9 mg/dL PLA and 158 ± 7 vs. 145 ± 4 FEN; pretreatment vs. posttreatment; P = 0.004). Insulin-stimulated glucose uptake increased significantly in FEN (4.3 ± 0.6 vs. 4.5 ± 0.7 PLA and 5.2 ± 0.5 vs. 7.6 ± 0.6 mg/kg per minute FEN; pretreatment vs. posttreatment; P = 0.003). Insulin trended to suppress hepatic glucose release following fenofibrate treatment (P = 0.06). Maximal mitochondrial ATP production from pyruvate increased significantly after fenofibrate (P = 0.001) and was accompanied by maintained levels of cytochrome C oxidase and citrate synthase activity levels. Tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 in response to insulin increased significantly following fenofibrate treatment (P = 0.04 for both). Conclusions: Fenofibrate treatment started within 1 week postburn and continued for 2 weeks significantly decreased plasma glucose concentrations by improving insulin sensitivity, insulin

  17. Socio-Dramatic Affective-Relational Intervention for Adolescents with Asperger Syndrome & High Functioning Autism: Pilot Study

    ERIC Educational Resources Information Center

    Lerner, Matthew D.; Mikami, Amori Yee; Levine, Karen

    2011-01-01

    This study examined the effectiveness of a novel intervention called "socio-dramatic affective-relational intervention" (SDARI), intended to improve social skills among adolescents with Asperger syndrome and high functioning autism diagnoses. SDARI adapts dramatic training activities to focus on in vivo practice of areas of social skill deficit…

  18. Improved Cognitive Function After Transcranial, Light-Emitting Diode Treatments in Chronic, Traumatic Brain Injury: Two Case Reports

    PubMed Central

    Saltmarche, Anita; Krengel, Maxine H.; Hamblin, Michael R.; Knight, Jeffrey A.

    2011-01-01

    Abstract Objective: Two chronic, traumatic brain injury (TBI) cases, where cognition improved following treatment with red and near-infrared light-emitting diodes (LEDs), applied transcranially to forehead and scalp areas, are presented. Background: Significant benefits have been reported following application of transcranial, low-level laser therapy (LLLT) to humans with acute stroke and mice with acute TBI. These are the first case reports documenting improved cognitive function in chronic, TBI patients treated with transcranial LED. Methods: Treatments were applied bilaterally and to midline sagittal areas using LED cluster heads [2.1″ diameter, 61 diodes (9 × 633 nm, 52 × 870 nm); 12–15 mW per diode; total power: 500 mW; 22.2 mW/cm2; 13.3 J/cm2 at scalp (estimated 0.4 J/cm2 to cortex)]. Results: Seven years after closed-head TBI from a motor vehicle accident, Patient 1 began transcranial LED treatments. Pre-LED, her ability for sustained attention (computer work) lasted 20 min. After eight weekly LED treatments, her sustained attention time increased to 3 h. The patient performs nightly home treatments (5 years); if she stops treating for more than 2 weeks, she regresses. Patient 2 had a history of closed-head trauma (sports/military, and recent fall), and magnetic resonance imaging showed frontoparietal atrophy. Pre-LED, she was on medical disability for 5 months. After 4 months of nightly LED treatments at home, medical disability discontinued; she returned to working full-time as an executive consultant with an international technology consulting firm. Neuropsychological testing after 9 months of transcranial LED indicated significant improvement (+1, +2SD) in executive function (inhibition, inhibition accuracy) and memory, as well as reduction in post-traumatic stress disorder. If she stops treating for more than 1 week, she regresses. At the time of this report, both patients are continuing treatment. Conclusions: Transcranial

  19. Monocyte Locomotion Inhibitory Factor Produced by E. histolytica Improves Motor Recovery and Develops Neuroprotection after Traumatic Injury to the Spinal Cord

    PubMed Central

    Bermeo, Gabriela; García, Elisa; Flores-Romero, Adrian; Rico-Rosillo, Guadalupe; Marroquín, Rubén; Flores, Carmina; Blanco-Favela, Francisco; Silva-García, Raúl

    2013-01-01

    Monocyte locomotion inhibitory factor (MLIF) is a pentapeptide produced by Entamoeba histolytica that has a potent anti-inflammatory effect. Either MLIF or phosphate buffered saline (PBS) was administered directly onto the spinal cord (SC) immediately after injury. Motor recovery was evaluated. We also analyzed neuroprotection by quantifying the number of surviving ventral horn motor neurons and the persistence of rubrospinal tract neurons. To evaluate the mechanism through which MLIF improved the outcome of SC injury, we quantified the expression of inducible nitric oxide synthase (iNOS), interleukin-10 (IL-10), and transforming growth factor-β (TGF-β) genes at the site of injury. Finally, the levels of nitric oxide and of lipid peroxidation were also determined in peripheral blood. Results showed that MLIF improved the rate of motor recovery and this correlated with an increased survival of ventral horn and rubrospinal neurons. These beneficial effects were in turn associated with a reduction in iNOS gene products and a significant upregulation of IL-10 and TGF-β expression. In the same way, MLIF reduced the concentration of nitric oxide and the levels of lipid peroxidation in systemic circulation. The present results demonstrate for the first time the neuroprotective effects endowed by MLIF after SC injury. PMID:24294606

  20. Intrathecally Transplanting Mesenchymal Stem Cells (MSCs) Activates ERK1/2 in Spinal Cords of Ischemia-Reperfusion Injury Rats and Improves Nerve Function

    PubMed Central

    Wang, Yonghong; Liu, He; Ma, Hong

    2016-01-01

    Background We investigated whether an intrathecal transplantation of mesenchymal stem cells (MSCs) activates extracellular adjusting protein kinase1 and 2(ERK1/2) in the spinal cords of rats following an ischemia-reperfusion injury, resulting in improved spinal cord function and inhibition of apoptosis. Material/Methods We observed the relationship between the activation of ERK1/2 in the rat spinal cord and intrathecal transplantation of MSCs, as well as the effect of U0126, a MEK1/2 (upstream protein of ERK1/2) inhibitor, on a spinal cord ischemia-reperfusion injury model in rats using Basso Beattie Bresnahan (BBB) scoring, somatosensory evoked potentials (SSEPs), immunohistochemistry, and Western blot analysis. Results After transplantation of MSCs, the lower limb motor function score increased, and the incubation period of SSEPs and amplitude were improved. Moreover, following transplantation of MSCs, Bcl2 expression increased, whereas Bax expression decreased after reperfusion. Transplantation of MSCs significantly enhanced pERK1/2 expression in the spinal cord, as well as pERK1/2 in immunoreactive cells located in the grey matter of the L4/5 levels of the spinal cord, following ischemia reperfusion injury in rats. The effective dose of U0126 required to inhibit pERK1/2 expression was 200 μg/kg. Bcl-2 decreased and the level of Bax expression increased in the spinal cord after ischemia reperfusion injury, and the protective effects of MSCs were attenuated. Conclusions Our findings suggest that intrathecal transplantation of MSCs activates ERK1/2 in the spinal cord following ischemia reperfusion injury, partially improves spinal cord function, and inhibits apoptosis in rats. PMID:27135658

  1. IL-15 Superagonist Expands mCD8+ T, NK and NKT Cells after Burn Injury but Fails to Improve Outcome during Burn Wound Infection

    PubMed Central

    Patil, Naeem K.; Luan, Liming; Bohannon, Julia K.; Guo, Yin; Hernandez, Antonio; Fensterheim, Benjamin; Sherwood, Edward R.

    2016-01-01

    Background Severely burned patients are highly susceptible to opportunistic infections and sepsis, owing to the loss of the protective skin barrier and immunological dysfunction. Interleukin-15 (IL-15) belongs to the IL-2 family of common gamma chain cytokines and stimulates the proliferation and activation of T (specifically memory CD8), NK and NKT cells. It has been shown to preserve T cell function and improve survival during cecal ligation and puncture (CLP)-induced sepsis in mice. However, the therapeutic efficacy of IL-15 or IL-15 superagonist (SA) during infection after burn injury has not been evaluated. Moreover, very few, if any, studies have examined, in detail, the effect of burn injury and infection on the adaptive immune system. Thus, we examined the effect of burn and sepsis on adaptive immune cell populations and the effect of IL-15 SA treatment on the host response to infection. Methods Mice were subjected to a 35% total body surface area burn, followed by wound infection with Pseudomonas aeruginosa. In some experiments, IL-15 SA was administered after burn injury, but before infection. Leukocytes in spleen, liver and peritoneal cavity were characterized using flow cytometry. Bacterial clearance, organ injury and survival were also assessed. Results Burn wound infection led to a significant decline in total white blood cell and lymphocyte counts and induced organ injury and sepsis. Burn injury caused decline in CD4+ and CD8+ T cells in the spleen, which was worsened by infection. IL-15 treatment inhibited this decline and significantly increased cell numbers and activation, as determined by CD69 expression, of CD4+, CD8+, B, NK and NKT cells in the spleen and liver after burn injury. However, IL-15 SA treatment failed to prevent burn wound sepsis-induced loss of CD4+, CD8+, B, NK and NKT cells and failed to improve bacterial clearance and survival. Conclusion Cutaneous burn injury and infection cause significant adaptive immune dysfunction. IL-15

  2. Salidroside Improves Behavioral and Histological Outcomes and Reduces Apoptosis via PI3K/Akt Signaling after Experimental Traumatic Brain Injury

    PubMed Central

    Chen, Szu-Fu; Tsai, Hsin-Ju; Hung, Tai-Ho; Chen, Chien-Cheng; Lee, Chao Yu; Wu, Chun-Hu; Wang, Pei-Yi; Liao, Nien-Chieh

    2012-01-01

    Background Traumatic brain injury (TBI) induces a complex sequence of apopototic cascades that contribute to secondary tissue damage. The aim of this study was to investigate the effects of salidroside, a phenolic glycoside with potent anti-apoptotic properties, on behavioral and histological outcomes, brain edema, and apoptosis following experimental TBI and the possible involvement of the phosphoinositide 3-kinase/protein kinase B (PI3K)/Akt signaling pathway. Methodology/Principal Findings Mice subjected to controlled cortical impact injury received intraperitoneal salidroside (20, or 50 mg/kg) or vehicle injection 10 min after injury. Behavioral studies, histology analysis and brain water content assessment were performed. Levels of PI3K/Akt signaling-related molecules, apoptosis-related proteins, cytochrome C (CytoC), and Smac/DIABLO were also analyzed. LY294002, a PI3K inhibitor, was administered to examine the mechanism of protection. The protective effect of salidroside was also investigated in primary cultured neurons subjected to stretch injury. Treatment with 20 mg/kg salidroside_significantly improved functional recovery and reduced brain tissue damage up to post-injury day 28. Salidroside_also significantly reduced neuronal death, apoptosis, and brain edema at day 1. These changes were associated with significant decreases in cleaved caspase-3, CytoC, and Smac/DIABLO at days 1 and 3. Salidroside increased phosphorylation of Akt on Ser473 and the mitochondrial Bcl-2/Bax ratio at day 1, and enhanced phosphorylation of Akt on Thr308 at day 3. This beneficial effect was abolished by pre-injection of LY294002. Moreover, delayed administration of salidroside at 3 or 6 h post-injury reduced neuronal damage at day 1. Salidroside treatment also decreased neuronal vulnerability to stretch-induced injury in vitro. Conclusions/Significance Post-injury salidroside improved long-term behavioral and histological outcomes and reduced brain edema and apoptosis

  3. Lumbar Epidural Steroid Injection for Painful Spasticity in Cervical Spinal Cord Injury: A Case Report

    PubMed Central

    Bang, Hyun; Chun, Seong Min; Park, Hee Won; Bang, Moon Suk

    2015-01-01

    We report a case of a 53-year-old male with traumatic cervical spinal cord injury (SCI). He could not maintain a standing position because of painful spasticity in his lower limbs. A magnetic resonance imaging and electromyography indicated chronic lumbosacral radiculopathy, explaining his chronic low back pain before the injury. For diagnostic as well as therapeutic purposes, transforaminal epidural steroid injection (ESI) to the right L5 root was performed. After the intervention, the spasticity decreased and his ambulatory function improved. This case illustrates that lumbar radiculopathy concomitant with a cervical SCI can produce severe spasticity and it can be dramatically improved by ESI. PMID:26361605

  4. Video Taping and Abnormal Psychology: Dramatized Clinical Interviews.

    ERIC Educational Resources Information Center

    Lyons, Michael J.; And Others

    1984-01-01

    Students in an abnormal psychology course worked in teams to produce dramatizations of diagnostic interviews and then presented them in class. Positive and negative aspects of the activity are discussed. (RM)

  5. Writing a Book about Dorothy Heathcote's Dramatic Approach to Education.

    ERIC Educational Resources Information Center

    Bolton, Gavin

    1993-01-01

    Discusses the development of a book about Dorothy Heathcote's dramatic approach to education. Describes a lesson on "bullying" that illustrates an attempt to implement Heathcote's "Mantle of the Expert" method. (RS)

  6. Improving the Quality of Life of Caregivers of Persons With Spinal Cord Injury: A Randomized Controlled Trial

    PubMed Central

    Schulz, Richard; Czaja, Sara J.; Lustig, Amy; Zdaniuk, Bozena; Martire, Lynn M.; Perdomo, Dolores

    2009-01-01

    Objective To assess the efficacy of two psychosocial interventions for caregivers of older persons with spinal cord injury (SCI). Design A multisite, three-group, randomized controlled trial comparing two active intervention conditions with each other and to an information-only control group. One hundred seventy-three caregiver and care-recipient dyads were randomly assigned to one of three conditions: a caregiver-only treatment condition in which caregivers received a multicomponent intervention based on their risk profile; a dual-target condition in which the caregiver intervention was complemented by a treatment targeting the care recipient, designed to address both caregiver and care recipient risk factors; and an information-only control condition in which the caregiver received standard printed information about caregiving, SCI, and aging. Outcome Measures A multivariate outcome comprised of six indicators linked to the goals of the interventions was the primary outcome of the study. The multivariate outcome included measures of depressive symptoms, burden, social support and integration, self-care problems, and physical health symptoms. Results At 12 months, caregivers in the dual-target condition had improved quality of life as measured by our multivariate outcome when compared to the control condition. Using the dyad as the unit of analysis, the dual-target condition was superior to both the control condition and the caregiver-only condition in our multivariate outcomes analysis. Dyads enrolled in the dual-target condition had significantly fewer health symptoms than control condition and caregiver-only condition participants and were less depressed when compared to participants in the caregiver-only condition. In follow-up analyses we found that a higher proportion of caregivers in the dual-target condition had clinically significant improvements in depression, burden, and health symptoms when compared with the caregiver-only condition. Conclusion

  7. Do orthopaedic shoes improve local dynamic stability of gait? An observational study in patients with chronic foot and ankle injuries

    PubMed Central

    2013-01-01

    Background Complex foot and ankle fractures, such as calcaneum fractures or Lisfranc dislocations, are often associated with a poor outcome, especially in terms of gait capacity. Indeed, degenerative changes often lead to chronic pain and chronic functional limitations. Prescription footwear represents an important therapeutic tool during the rehabilitation process. Local Dynamic Stability (LDS) is the ability of locomotor system to maintain continuous walking by accommodating small perturbations that occur naturally during walking. Because it reflects the degree of control over the gait, LDS has been advocated as a relevant indicator for evaluating different conditions and pathologies. The aim of this study was to analyze changes in LDS induced by orthopaedic shoes in patients with persistent foot and ankle injuries. We hypothesised that footwear adaptation might help patients to improve gait control, which could lead to higher LDS: Methods Twenty-five middle-aged inpatients (5 females, 20 males) participated in the study. They were treated for chronic post-traumatic disabilities following ankle and/or foot fractures in a Swiss rehabilitation clinic. During their stay, included inpatients received orthopaedic shoes with custom-made orthoses (insoles). They performed two 30s walking trials with standard shoes and two 30s trials with orthopaedic shoes. A triaxial motion sensor recorded 3D accelerations at the lower back level. LDS was assessed by computing divergence exponents in the acceleration signals (maximal Lyapunov exponents). Pain was evaluated with Visual Analogue Scale (VAS). LDS and pain differences between the trials with standard shoes and the trials with orthopaedic shoes were assessed. Results Orthopaedic shoes significantly improved LDS in the three axes (medio-lateral: 10% relative change, paired t-test p < 0.001; vertical: 9%, p = 0.03; antero-posterior: 7%, p = 0.04). A significant decrease in pain level (VAS score -29%) was observed

  8. How to Know when Dramatic Change Is on Track: Leading Indicators of School Turnarounds

    ERIC Educational Resources Information Center

    Kowal, Julie; Ableidinger, Joe

    2011-01-01

    In recent years, national policymakers have placed new emphasis on "school turnarounds" as a strategy for rapid, dramatic improvement in chronically failing schools, calling on education leaders to turn around performance in the 5,000 lowest-achieving schools nationwide. This goal may seem daunting, given the dismal success rates of school…

  9. Subthreshold nitric oxide synthase inhibition improves synergistic effects of subthreshold MMP-2/MLCK-mediated cardiomyocyte protection from hypoxic injury.

    PubMed

    Bil-Lula, Iwona; Lin, Han-Bin; Biały, Dariusz; Wawrzyńska, Magdalena; Diebel, Lucas; Sawicka, Jolanta; Woźniak, Mieczyslaw; Sawicki, Grzegorz

    2016-06-01

    Injury of myocardium during ischaemia/reperfusion (I/R) is a complex and multifactorial process involving uncontrolled protein phosphorylation, nitration/nitrosylation by increased production of nitric oxide and accelerated contractile protein degradation by matrix metalloproteinase-2 (MMP-2). It has been shown that simultaneous inhibition of MMP-2 with doxycycline (Doxy) and myosin light chain kinase (MLCK) with ML-7 at subthreshold concentrations protects the heart from contractile dysfunction triggered by I/R in a synergistic manner. In this study, we showed that additional co-administration of nitric oxide synthase (NOS) inhibitor (1400W or L-NAME) in subthreshold concentrations improves this synergistic protection in the model of hypoxia-reoxygenation (H-R)-induced contractile dysfunction of cardiomyocytes. Isolated cardiomyocytes were subjected to 3 min. of hypoxia and 20 min. of reoxygenation in the presence or absence of the inhibitor cocktails. Contractility of cardiomyocytes was expressed as myocyte peak shortening. Inhibition of MMP-2 by Doxy (25-100 μM), MLCK by ML-7 (0.5-5 μM) and NOS by L-NAME (25-100 μM) or 1400W (25-100 μM) protected myocyte contractility after H-R in a concentration-dependent manner. Inhibition of these activities resulted in full recovery of cardiomyocyte contractility after H-R at the level of highest single-drug concentration. The combination of subthreshold concentrations of NOS, MMP-2 and MLCK inhibitors fully protected cardiomyocyte contractility and MLC1 from degradation by MMP-2. The observed protection with addition of L-NAME or 1400W was better than previously reported combination of ML-7 and Doxy. The results of this study suggest that addition of NOS inhibitor to the mixture of inhibitors is better strategy for protecting cardiomyocyte contractility. PMID:26992120

  10. Grafted Human Embryonic Progenitors Expressing Neurogenin-2 Stimulate Axonal Sprouting and Improve Motor Recovery after Severe Spinal Cord Injury

    PubMed Central

    Perrin, Florence E.; Lonjon, Nicolas; Serre, Angeline; Prieto, Monica; Mallet, Jacques; Privat, Alain

    2010-01-01

    Background Spinal cord injury (SCI) is a widely spread pathology with currently no effective treatment for any symptom. Regenerative medicine through cell transplantation is a very attractive strategy and may be used in different non-exclusive ways to promote functional recovery. We investigated functional and structural outcomes after grafting human embryonic neural progenitors (hENPs) in spinal cord-lesioned rats. Methods and Principal Findings With the objective of translation to clinics we have chosen a paradigm of delayed grafting, i.e., one week after lesion, in a severe model of spinal cord compression in adult rats. hENPs were either naïve or engineered to express Neurogenin 2 (Ngn2). Moreover, we have compared integrating and non-integrating lentiviral vectors, since the latter present reduced risks of insertional mutagenesis. We show that transplantation of hENPs transduced to express Ngn2 fully restore weight support and improve functional motor recovery after severe spinal cord compression at thoracic level. This was correlated with partial restoration of serotonin innervations at lumbar level, and translocation of 5HT1A receptors to the plasma membrane of motoneurons. Since hENPs were not detectable 4 weeks after grafting, transitory expression of Ngn2 appears sufficient to achieve motor recovery and to permit axonal regeneration. Importantly, we also demonstrate that transplantation of naïve hENPs is detrimental to functional recovery. Conclusions and Significance Transplantation and short-term survival of Ngn2-expressing hENPs restore weight support after SCI and partially restore serotonin fibers density and 5HT1A receptor pattern caudal to the lesion. Moreover, grafting of naïve-hENPs was found to worsen the outcome versus injured only animals, thus pointing to the possible detrimental effect of stem cell-based therapy per se in SCI. This is of major importance given the increasing number of clinical trials involving cell grafting developed for

  11. Expansion Duroplasty Improves Intraspinal Pressure, Spinal Cord Perfusion Pressure, and Vascular Pressure Reactivity Index in Patients with Traumatic Spinal Cord Injury: Injured Spinal Cord Pressure Evaluation Study

    PubMed Central

    Phang, Isaac; Werndle, Melissa C.; Saadoun, Samira; Varsos, Georgios; Czosnyka, Marek; Zoumprouli, Argyro

    2015-01-01

    Abstract We recently showed that, after traumatic spinal cord injury (TSCI), laminectomy does not improve intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), or the vascular pressure reactivity index (sPRx) at the injury site sufficiently because of dural compression. This is an open label, prospective trial comparing combined bony and dural decompression versus laminectomy. Twenty-one patients with acute severe TSCI had re-alignment of the fracture and surgical fixation; 11 had laminectomy alone (laminectomy group) and 10 had laminectomy and duroplasty (laminectomy+duroplasty group). Primary outcomes were magnetic resonance imaging evidence of spinal cord decompression (increase in intradural space, cerebrospinal fluid around the injured cord) and spinal cord physiology (ISP, SCPP, sPRx). The laminectomy and laminectomy+duroplasty groups were well matched. Compared with the laminectomy group, the laminectomy+duroplasty group had greater increase in intradural space at the injury site and more effective decompression of the injured cord. In the laminectomy+duroplasty group, ISP was lower, SCPP higher, and sPRx lower, (i.e., improved vascular pressure reactivity), compared with the laminectomy group. Laminectomy+duroplasty caused cerebrospinal fluid leak that settled with lumbar drain in one patient and pseudomeningocele that resolved completely in five patients. We conclude that, after TSCI, laminectomy+duroplasty improves spinal cord radiological and physiological parameters more effectively than laminectomy alone. PMID:25705999

  12. Improved Biomechanical and Biological Outcomes in the MRL/MpJ Murine Strain Following a Full-Length Patellar Tendon Injury

    PubMed Central

    Lalley, Andrea L.; Dyment, Nathaniel A.; Kazemi, Namdar; Kenter, Keith; Gooch, Cynthia; Rowe, David W.; Butler, David L.; Shearn, Jason T.

    2016-01-01

    Musculoskeletal injuries greatly affect the U.S. population and current clinical approaches fail to restore long-term native tissue structure and function. Tissue engineering is a strategy advocated to improve tendon healing; however, the field still needs to establish biological benchmarks for assessing the effectiveness of tissue-engineered structures. Investigating superior healing models, such as the MRL/MpJ, offers the opportunity to first characterize successful healing and then apply experimental findings to tissue-engineered therapies. This study seeks to evaluate the MRL/MpJ’s healing response following a central patellar tendon injury compared to wildtype. Gene expression and histology were assessed at 3, 7, and 14 days following injury and mechanical properties were measured at 2, 5, and 8 weeks. Native patellar tendon biological and mechanical properties were not different between strains. Following injury, the MRL/MpJ displayed increased mechanical properties between 5 and 8 weeks; however, early tenogenic expression patterns were not different between the strains. Furthermore, expression of the cyclin-dependent kinase inhibitor, p21, was not different between strains, suggesting an alternative mechanism may be driving the healing response. Future studies will investigate collagen structure and alignment of the repair tissue and characterize the complete healing transcriptome to identify mechanisms driving the MRL/MpJ response. PMID:25982892

  13. Fumigaclavine C improves concanavalin A-induced liver injury in mice mainly via inhibiting TNF-alpha production and lymphocyte adhesion to extracellular matrices.

    PubMed

    Zhao, Ying; Liu, Junyan; Wang, Jun; Wang, Lei; Yin, Hao; Tan, Renxiang; Xu, Qiang

    2004-06-01

    Fumigaclavine C, an alkaloidal metabolite, was produced by Aspergillus fumigatus (strain No. CY018). This study examined the effect of this compound on concanavalin A (Con A)-induced liver injury in mice, a T cell-dependent model of liver damage. Con A administration resulted in severe liver injury, T lymphocyte activation and a strong increment in spleen cell adhesion, as well as in tumour necrosis factor-alpha (TNF-alpha) production. Against this liver injury, the intraperitoneal administration of fumigaclavine C dose-dependently inhibited the elevation in transaminase activity, TNF-alpha production in serum and the histological changes, including inflammatory infiltration, hepatocyte necrosis and degeneration and Kupffer cell hyperplasia. In addition, this compound in-vitro also inhibited the proliferation of spleen cells induced by Con A, and reduced their IL-2 and TNF-alpha production. Moreover, the intraperitoneal administration of fumigaclavine C inhibited the potential of spleen cells isolated from the liver-injured mice to adhere to fibronectin, laminin and type IV collagen. These results suggest that the improvement of this T cell-mediated liver injury by fumigaclavine C may be related to the inhibition of lymphocyte activation, proliferation and adhesion to extracellular matrices as well as the reduction in TNF-alpha production. PMID:15231043

  14. Failure of Intravenous or Intracardiac Delivery of Mesenchymal Stromal Cells to Improve Outcomes after Focal Traumatic Brain Injury in the Female Rat

    PubMed Central

    Turtzo, L. Christine; Budde, Matthew D.; Dean, Dana D.; Gold, Eric M.; Lewis, Bobbi K.; Janes, Lindsay; Lescher, Jacob; Coppola, Tiziana; Yarnell, Angela; Grunberg, Neil E.; Frank, Joseph A.

    2015-01-01

    Mesenchymal stromal cells secrete a variety of anti-inflammatory factors and may provide a regenerative medicine option for the treatment of traumatic brain injury. The present study investigates the efficacy of multiple intravenous or intracardiac administrations of rat mesenchymal stromal cells or human mesenchymal stromal cells in female rats after controlled cortical impact by in vivo MRI, neurobehavior, and histopathology evaluation. Neither intravenous nor intracardiac administration of mesenchymal stromal cells derived from either rats or humans improved MRI measures of lesion volume or neurobehavioral outcome compared to saline treatment. Few mesenchymal stromal cells (<0.0005% of injected dose) were found within 3 days of last dosage at the site of injury after either delivery route, with no mesenchymal stromal cells being detectable in brain at 30 or 56 days post-injury. These findings suggest that non-autologous mesenchymal stromal cells therapy via intravenous or intracardiac administration is not a promising treatment after focal contusion traumatic brain injury in this female rodent model. PMID:25946089

  15. Head Injuries

    MedlinePlus

    ... before. Often, the injury is minor because your skull is hard and it protects your brain. But ... injuries can be more severe, such as a skull fracture, concussion, or traumatic brain injury. Head injuries ...

  16. Head Injuries

    MedlinePlus

    ... before. Usually, the injury is minor because your skull is hard and it protects your brain. But ... injuries can be more severe, such as a skull fracture, concussion, or traumatic brain injury. Head injuries ...

  17. Back Injuries

    MedlinePlus

    ... extending from your neck to your pelvis. Back injuries can result from sports injuries, work around the house or in the garden, ... back is the most common site of back injuries and back pain. Common back injuries include Sprains ...

  18. Head Injuries

    MedlinePlus

    ... of head injuries include bicycle or motorcycle wrecks, sports injuries, falls from windows (especially among children who live ... to watch for? When can I start playing sports again after a head injury? How can brain damage from a head injury ...

  19. Injury reduction at Fermilab

    SciTech Connect

    Griffing, Bill; /Fermilab

    2005-06-01

    In a recent DOE Program Review, Fermilab's director presented results of the laboratory's effort to reduce the injury rate over the last decade. The results, shown in the figure below, reveal a consistent and dramatic downward trend in OSHA recordable injuries at Fermilab. The High Energy Physics Program Office has asked Fermilab to report in detail on how the laboratory has achieved the reduction. In fact, the reduction in the injury rate reflects a change in safety culture at Fermilab, which has evolved slowly over this period, due to a series of events, both planned and unplanned. This paper attempts to describe those significant events and analyze how each of them has shaped the safety culture that, in turn, has reduced the rate of injury at Fermilab to its current value.

  20. Intra-articular injection of synovial mesenchymal stem cells improves cartilage repair in a mouse injury model.

    PubMed

    Mak, J; Jablonski, C L; Leonard, C A; Dunn, J F; Raharjo, E; Matyas, J R; Biernaskie, J; Krawetz, R J

    2016-01-01

    Controversy remains whether articular cartilage has an endogenous stem/progenitor cell population, since its poor healing capacity after injury can lead to diseases such as osteoarthritis. In the joint environment there are mesenchymal stem/progenitor cells (MSCs) in the synovial membrane and synovial fluid that can differentiate into cartilage, but it is still under debate if these cells contribute to cartilage repair in vivo. In this study, we isolated a Sca-1 positive, chondrogenesis capable population of mouse synovial MSCs from C57BL6 and MRL/MpJ "super-healer" strains. Intra-articular injection of Sca-1 + GFP + synovial cells from C57BL6 or MRL/MpJ into C57BL6 mice following cartilage injury led to increased cartilage repair by 4 weeks after injury. GFP expression was detected in the injury site at 2 weeks, but not 4 weeks after injury. These results suggest that synovial stem/progenitor cells, regardless of strain background, have beneficial effects when injected into an injured joint. MSCs derived from MRL/MpJ mice did not promote an increased repair capacity compared to MSCs derived from non-healing C57BL6 controls; however, MRL/MpJ MSCs were observed within the defect area at the time points examined, while C57BL6 MSCs were not. PMID:26983696

  1. Intra-articular injection of synovial mesenchymal stem cells improves cartilage repair in a mouse injury model

    PubMed Central

    Mak, J.; Jablonski, C. L.; Leonard, C. A.; Dunn, J. F.; Raharjo, E.; Matyas, J. R.; Biernaskie, J.; Krawetz, R. J.

    2016-01-01

    Controversy remains whether articular cartilage has an endogenous stem/progenitor cell population, since its poor healing capacity after injury can lead to diseases such as osteoarthritis. In the joint environment there are mesenchymal stem/progenitor cells (MSCs) in the synovial membrane and synovial fluid that can differentiate into cartilage, but it is still under debate if these cells contribute to cartilage repair in vivo. In this study, we isolated a Sca-1 positive, chondrogenesis capable population of mouse synovial MSCs from C57BL6 and MRL/MpJ “super-healer” strains. Intra-articular injection of Sca-1 + GFP + synovial cells from C57BL6 or MRL/MpJ into C57BL6 mice following cartilage injury led to increased cartilage repair by 4 weeks after injury. GFP expression was detected in the injury site at 2 weeks, but not 4 weeks after injury. These results suggest that synovial stem/progenitor cells, regardless of strain background, have beneficial effects when injected into an injured joint. MSCs derived from MRL/MpJ mice did not promote an increased repair capacity compared to MSCs derived from non-healing C57BL6 controls; however, MRL/MpJ MSCs were observed within the defect area at the time points examined, while C57BL6 MSCs were not. PMID:26983696

  2. Rho kinase inhibition following traumatic brain injury in mice promotes functional improvement and acute neuron survival but has little effect on neurogenesis, glial responses or neuroinflammation.

    PubMed

    Bye, Nicole; Christie, Kimberly J; Turbic, Alisa; Basrai, Harleen S; Turnley, Ann M

    2016-05-01

    Inhibition of the Rho/Rho kinase pathway has been shown to be beneficial in a variety of neural injuries and diseases. In this manuscript we investigate the role of Rho kinase inhibition in recovery from traumatic brain injury using a controlled cortical impact model in mice. Mice subjected to a moderately severe TBI were treated for 1 or 4weeks with the Rho kinase inhibitor Y27632, and functional outcomes and neuronal and glial cell responses were analysed at 1, 7 and 35days post-injury. We hypothesised that Y27632-treated mice would show functional improvement, with augmented recruitment of neuroblasts from the SVZ and enhanced survival of newborn neurons in the pericontusional cortex, with protection against neuronal degeneration, neuroinflammation and modulation of astrocyte reactivity and blood-brain-barrier permeability. While Rho kinase inhibition enhanced recovery of motor function after trauma, there were no substantial increases in the recruitment of DCX(+) neuroblasts or the number of BrdU(+) or EdU(+) labelled newborn neurons in the pericontusional cortex of Y27632-treated mice. Inhibition of Rho kinase significantly reduced the number of degenerating cortical neurons at 1day post-injury compared to saline controls but had no longer term effect on neuronal degeneration, with only modest effects on astrocytic reactivity and macrophage/microglial responses. Overall, this study showed that Rho kinase contributes to acute neurodegenerative processes in the injured cortex but does not play a significant role in SVZ neural precursor cell-derived adult neurogenesis, glial responses or blood-brain barrier permeability following a moderately severe brain injury. PMID:26896832

  3. Panax ginseng Improves Functional Recovery after Contusive Spinal Cord Injury by Regulating the Inflammatory Response in Rats: An In Vivo Study

    PubMed Central

    Kim, Young Ock; Kim, Youngkyung; Lee, Koeun; Na, Sae Won; Hong, Seon Pyo; Valan Arasu, Mariadhas; Yoon, Young Wook; Kim, Junesun

    2015-01-01

    Spinal cord injury (SCI) results in permanent loss of motor function below the injured site. Neuroinflammatory reaction following SCI can aggravate neural injury and functional impairment. Ginseng is well known to possess anti-inflammatory effects. The present study investigated the neuroprotective effects of Panax ginseng C.A. Mayer (P. ginseng) after SCI. A spinal contusion was made at the T11-12 spinal cord in adult male Sprague-Dawley rats (n = 47) using the NYU impactor. Motor function was assessed using the Basso-Beattie-Bresnahan (BBB) score in P. ginseng (0.1, 0.5, 1, 3, and 5 mg/kg) or vehicle (saline) treated after SCI. We also assessed the protein expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) at the lesion site by western blot and then measured the cavity area using luxol fast blue/cresyl violet staining. P. ginseng treated group in SCI showed a significant improvement in locomotor function after the injury. The protein expression of COX-2 and iNOS at the lesion site and the cavity area were decreased following SCI by P. ginseng treatment. These results suggest that P. ginseng may improve the recovery of motor function after SCI which provides neuroprotection by alleviating posttraumatic inflammatory responses. PMID:26451158

  4. Improving assessments of tropospheric ozone injury to Mediterranean montane conifer forests in California (USA) and Catalonia (Spain) with GIS models related to plant water relations

    NASA Astrophysics Data System (ADS)

    Kefauver, Shawn C.; Peñuelas, Josep; Ustin, Susan L.

    2012-12-01

    The impacts of tropospheric ozone on conifer health in the Sierra Nevada of California, USA, and the Pyrenees of Catalonia, Spain, were measured using field assessments and GIS variables of landscape gradients related to plant water relations, stomatal conductance and hence to ozone uptake. Measurements related to ozone injury included visible chlorotic mottling, needle retention, needle length, and crown depth, which together compose the Ozone Injury Index (OII). The OII values observed in Catalonia were similar to those in California, but OII alone correlated poorly to ambient ozone in all sites. Combining ambient ozone with GIS variables related to landscape variability of plant hydrological status, derived from stepwise regressions, produced models with R2 = 0.35, p = 0.016 in Catalonia, R2 = 0.36, p < 0.001 in Yosemite and R2 = 0.33, p = 0.007 in Sequoia/Kings Canyon National Parks in California. Individual OII components in Catalonia were modeled with improved success compared to the original full OII, in particular visible chlorotic mottling (R2 = 0.60, p < 0.001). The results show that ozone is negatively impacting forest health in California and Catalonia and also that modeling ozone injury improves by including GIS variables related to plant water relations.

  5. Panax ginseng Improves Functional Recovery after Contusive Spinal Cord Injury by Regulating the Inflammatory Response in Rats: An In Vivo Study.

    PubMed

    Kim, Young Ock; Kim, Youngkyung; Lee, Koeun; Na, Sae Won; Hong, Seon Pyo; Valan Arasu, Mariadhas; Yoon, Young Wook; Kim, Junesun

    2015-01-01

    Spinal cord injury (SCI) results in permanent loss of motor function below the injured site. Neuroinflammatory reaction following SCI can aggravate neural injury and functional impairment. Ginseng is well known to possess anti-inflammatory effects. The present study investigated the neuroprotective effects of Panax ginseng C.A. Mayer (P. ginseng) after SCI. A spinal contusion was made at the T11-12 spinal cord in adult male Sprague-Dawley rats (n = 47) using the NYU impactor. Motor function was assessed using the Basso-Beattie-Bresnahan (BBB) score in P. ginseng (0.1, 0.5, 1, 3, and 5 mg/kg) or vehicle (saline) treated after SCI. We also assessed the protein expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) at the lesion site by western blot and then measured the cavity area using luxol fast blue/cresyl violet staining. P. ginseng treated group in SCI showed a significant improvement in locomotor function after the injury. The protein expression of COX-2 and iNOS at the lesion site and the cavity area were decreased following SCI by P. ginseng treatment. These results suggest that P. ginseng may improve the recovery of motor function after SCI which provides neuroprotection by alleviating posttraumatic inflammatory responses. PMID:26451158

  6. Passive hind-limb cycling improves cardiac function and reduces cardiovascular disease risk in experimental spinal cord injury

    PubMed Central

    West, Christopher R; Crawford, Mark A; Poormasjedi-Meibod, Malihe-Sadat; Currie, Katharine D; Fallavollita, Andre; Yuen, Violet; McNeill, John H; Krassioukov, Andrei V

    2014-01-01

    Spinal cord injury (SCI) causes altered autonomic control and severe physical deconditioning that converge to drive maladaptive cardiac remodelling. We used a clinically relevant experimental model to investigate the cardio-metabolic responses to SCI and to establish whether passive hind-limb cycling elicits a cardio-protective effect. Initially, 21 male Wistar rats were evenly assigned to three groups: uninjured control (CON), T3 complete SCI (SCI) or T3 complete SCI plus passive hind-limb cycling (SCI-EX; 2 × 30 min day−1, 5 days week−1 for 4 weeks beginning 6 days post-SCI). On day 32, cardio-metabolic function was assessed using in vivo echocardiography, ex vivo working heart assessments, cardiac histology/molecular biology and blood lipid profiles. Twelve additional rats (n = 6 SCI and n = 6 SCI-EX) underwent in vivo echocardiography and basal haemodynamic assessments pre-SCI and at days 7, 14 and 32 post-SCI to track temporal cardiovascular changes. Compared with CON, SCI exhibited a rapid and sustained reduction in left ventricular dimensions and function that ultimately manifested as reduced contractility, increased myocardial collagen deposition and an up-regulation of transforming growth factor beta-1 (TGFβ1) and mothers against decapentaplegic homolog 3 (Smad3) mRNA. For SCI-EX, the initial reduction in left ventricular dimensions and function at day 7 post-SCI was completely reversed by day 32 post-SCI, and there were no differences in myocardial contractility between SCI-EX and CON. Collagen deposition was similar between SCI-EX and CON. TGFβ1 and Smad3 were down-regulated in SCI-EX. Blood lipid profiles were improved in SCI-EX versus SCI. We provide compelling novel evidence that passive hind-limb cycling prevents cardiac dysfunction and reduces cardiovascular disease risk in experimental SCI. PMID:24535438

  7. Therapeutic options to enhance coma arousal after traumatic brain injury: state of the art of current treatments to improve coma recovery.

    PubMed

    Cossu, Giulia

    2014-04-01

    Traumatic brain injury is a leading cause of death and disability. Optimizing the recovery from coma is a priority in seeking to improve patients' functional outcomes. Standards of care have not been established: pharmacological interventions, right median nerve and sensory stimulation, dorsal column stimulation (DCS), deep brain stimulation, transcranial magnetic stimulation, hyperbaric oxygen therapy and cell transplantation have all been utilized with contrasting results. The aim of this review is to clarify the indications for the various techniques and to guide the clinical practice towards an earlier coma arousal. A systematic bibliographic search was undertaken using the principal search engines (Pubmed, Embase, Ovid and Cochrane databases) to locate the most pertinent studies. Traumatic injury is a highly individualized process, and subsequent impairments are dependent on multiple factors: this heterogeneity influences and determines therapeutic responses to the various interventions. PMID:24090192

  8. Traumatic brain injury: the lag between diagnosis and treatment.

    PubMed

    Retsinas, J

    1993-01-01

    Ogburn described the "culture lag" between technology and attitudes, as people take time to assimilate new technologies, and new facts, into their worldviews. Traumatic brain injury is now a common diagnosis, thanks to neurosurgical expertise. Where thirty years ago mortality from head injuries was high, today mortality rates have improved dramatically; yet even while neurosurgeons spare thousands of people each year, our society struggles to develop appropriate rehabilitation protocols. To date, we are in the lag phase, between diagnosis and treatment. This paper discusses that lag, including reasons for the lack of an effective rehabilitation protocol (the paucity of funds for research, the nature of brain injuries per se), the reluctance of insurers to cover brain injury rehabilitation (the lengthy time involved in rehabilitation, the blurring between rehabilitation and long term care, the nature of experience-rated contracting to businesses for health care insurance, the burgeoning of proprietary brain injury rehabilitation centers), and the prospects for closing the gap in the near future. The paper concludes that preventive measures (seat belt laws, motorcycle helmet laws, laws for helmets in contact sports) allow policy-makers to confront the growing societal problem of the mounting census of head-injured, by avoiding that census and focusing instead on the prevention, or diminution, of future head injuries. PMID:10125462

  9. Improving the Understanding of Psychological Factors Contributing to Horse-Related Accident and Injury: Context, Loss of Focus, Cognitive Errors and Rigidity

    PubMed Central

    DeAraugo, Jodi; McLaren, Suzanne; McManus, Phil; McGreevy, Paul D.

    2016-01-01

    Simple Summary There is a high risk of injury for people involved with horses in their work or recreational pursuits. High risks are particularly evident for racing employees and veterinarians. Elevated risks of injury may be associated with misjudging how to handle situations, reduced attention caused by distractions, taking a general view, and failing to consider other strategies that may reduce risks. To improve safety for humans and horses, it is important to identify safety strategies that are flexible, focused and specific. Abstract While the role of the horse in riding hazards is well recognised, little attention has been paid to the role of specific theoretical psychological processes of humans in contributing to and mitigating risk. The injury, mortality or compensation claim rates for participants in the horse-racing industry, veterinary medicine and equestrian disciplines provide compelling evidence for improving risk mitigation models. There is a paucity of theoretical principles regarding the risk of injury and mortality associated with human–horse interactions. In this paper we introduce and apply the four psychological principles of context, loss of focus, global cognitive style and the application of self as the frame of reference as a potential approach for assessing and managing human–horse risks. When these principles produce errors that are combined with a rigid self-referenced point, it becomes clear how rapidly risk emerges and how other people and animals may repeatedly become at risk over time. Here, with a focus on the thoroughbred racing industry, veterinary practice and equestrian disciplines, we review the merits of contextually applied strategies, an evolving reappraisal of risk, flexibility, and focused specifics of situations that may serve to modify human behaviour and mitigate risk. PMID:26891333

  10. Probabilistic Linkage of Police and Emergency Department Sources of Information on Motor-Vehicle Injury Cases: A Proposal for Improvement.

    PubMed Central

    Cirera, Eva; Plasència, Antoni; Ferrando, Josep; Arribas, Pere

    1999-01-01

    BACKGROUND The availability of complete data on traffic injury cases including both the crash circumstances as well as health outcomes is a key tool to tailor appropriate motor-vehicle injury prevention policies at local and regional levels. OBJECTIVE To explore the feasibility of the probabilistic linkage of police and hospital emergency department data regarding motor-vehicle injury cases in Barcelona (Spain), including the use of methodologies to optimize the linkage process. METHODS A probabilistic linkage process was performed using local police reports (n=12,481) as well as hospital emergency department data (n=16,733) from all traffic injury cases having occurred in 1997. The common variables in both files used were: age, sex, position, vehicle, hospital, date of the crash, and postal code of place of residence. RESULTS In all linked pairs at least one variable coincided, while in almost two out of every three pairs at least five of the seven variables coincided, and in 7,3% of the cases all variables coincided fully. CONCLUSION This work has allowed the empirical development of combined methods for the linkage of police and health care sources of information at the local level, as preliminary steps towards the construction of a data base including information on the circumstances and the consequences of motor-vehicle crashes.

  11. Parahydrogen and Synthesis Allow Dramatically Enhanced Nuclear Alignment

    NASA Astrophysics Data System (ADS)

    Bowers, Clifford Russell

    The PASADENA effect is a method for transient high-sensitivity proton spin-labelling by molecular addition of dihydrogen. When the parahydrogen mole fraction differs from the high-temperature limit of 1/4, this population difference constitutes a form of spin order which can be converted to magnetization observable by NMR. Large NMR signals are observed, if subsequent to the hydrogen addition, the two protons experience magnetic inequivalence and spin -spin coupling and if observation is made before spin-lattice relaxation restores the equilibrium spin order. The analogous effect for D_2 is also possible. The kinetic mechanisms of the homogeneous hydrogenation catalysts which permit the realization of the PASADENA effect have been the target of the experimental applications. Rates determined in PASADENA studies pertain to the active catalytic species, since only these molecules can contribute to the enhanced signals from which all kinetic inferences are made. The sensitivity enhancement has also led to the identification of a novel intermediate in the mechanism for the Rh(DIPHOS)^+ catalyzed hydrogenation of styrene. The rate of conversion of this species into product and starting material has been studied using two -dimensional NMR. The dramatically improved sensitivity should make it possible to observe key catalytic intermediates which do not build up in sufficient quantity to allow detection by conventional NMR arising from Curie-Law magnetization. The study of surface sites which bind pairwise with H_2 is also a potentially fruitful area for future experimental work. The ambient temperature NMR spectroscopy of surfaces is not often feasible due to sensitivity limitations. Simulations have been performed using typical shift and coupling parameters in an effort to characterize the enhanced lineshapes which can be expected. The inverse of the PASADENA effect has also been proposed, whereby the spin order of a molecule containing hydrogen is probed by measuring

  12. Use of Dramatic Enquiry to Explore Controversies in Science

    ERIC Educational Resources Information Center

    Phillipson, Neil; Poad, Gordon

    2010-01-01

    With the increasing prominence of "How science works" in science courses in England and the imperative of equipping students to engage with the controversies thrown up by the advance of science, science departments need new teaching strategies. Here we describe the application of "Dramatic Enquiry" to GCSE science. The project, developed by…

  13. Dramatic Play: Root Meaning of Drama/Theatre.

    ERIC Educational Resources Information Center

    Koste, Virginia Glasgow

    The processes involved in drama and the dramatic play of children are essentially the same in that they rely on an imitation of nature, involve a transformation of reality through imagination, connect seemingly irrelevant elements creatively, and bring a temporary, limited order to an emotional experience. When child's play is used as a basis for…

  14. Assessment to Make "Dramatic Advance;" Coherency, Comprehensiveness Key

    ERIC Educational Resources Information Center

    Armistead, Lew

    2010-01-01

    Assessment in America's high schools is about to undergo its most dramatic advance in decades, according to a policy brief released in February by the Alliance for Excellent Education (AEE), a Washington, DC, based organization devoted to promoting high school transformation. "There is widespread concern that the most prominent assessments…

  15. Piaget in Performance: The Role of "Games" in Creative Dramatics.

    ERIC Educational Resources Information Center

    Ratliff, Gerald Lee

    Jean Piaget's theories of child development and the nature of intelligence are adapted to creative dramatics in this description of two games for children aged 6 through 12. The first game discussed incorporates a "touchy-feely box," a cardboard construction with openings on two sides so that a child may reach inside, select, and describe an…

  16. Burke Bingo: Using Active Learning to Introduce Dramatism

    ERIC Educational Resources Information Center

    Krueger, Ben

    2011-01-01

    Kenneth Burke is typically regarded as the single most significant figure in 20th-century rhetorical studies. Undergraduate textbooks in rhetorical criticism, rhetorical theory, and communication theory typically include coverage of Burke's theory of dramatism. In this article, the author describes a classroom activity dubbed "Burke Bingo" that…

  17. Celebrating Diversity through Northeastern Asian Children's Literature and Dramatic Productions.

    ERIC Educational Resources Information Center

    Richardson, Maurine V.; And Others

    At the University of South Dakota, as part of a campus-wide celebration of diversity focused on northeastern Asia (China, Japan, Korea), undergraduate and graduate Children's Literature classes participated by locating relevant literature and presenting them dramatically. Students were divided into six small cooperative groups. Each group chose a…

  18. Astronaut to Zoologist: Changing the Dramatic Play Area!

    ERIC Educational Resources Information Center

    Brouette, Scott J.

    Changing the dramatic play area in a child care setting promotes creativity and gives children the chance to experience a place they may never experience in real life. Whenever possible, the children should be involved in the process of changing the area, by moving furniture and exchanging props, as well as brainstorming ideas for changes. The…

  19. Frost Bite: A Dramatic Tale of Research in Aesthetic Education

    ERIC Educational Resources Information Center

    Hirsch, Miriam

    2008-01-01

    This article follows the author's research on the integration of an aesthetic arts initiative in a private elementary school with an established traditional arts program. The narrative describes the sequence of events, interpersonal interactions, and learning experiences in the format of a full-length dramatic performance. Informed by Ben Peretz's…

  20. Soaps and Suspicious Activity: Dramatic Experiences in British Classrooms.

    ERIC Educational Resources Information Center

    Ferree, Angela M.

    2001-01-01

    Offers examples of dramatic experiences (student produced soap operas) in two classrooms in British comprehensive secondary schools. Concludes that students in other countries would find such experiences as meaningful and enjoyable as their British counterparts. Notes that the two teachers managed to be flexible, appropriating effective…

  1. Windows into Children's Thinking: A Guide to Storytelling and Dramatization

    ERIC Educational Resources Information Center

    Wright, Cheryl; Bacigalupa, Chiara; Black, Tyler; Burton, Michael

    2008-01-01

    Telling and dramatizing stories is an increasingly popular addition to the preschool curriculum, largely due to the attention this activity has received through the writings of Vivian Paley (Bad guys don't have birthdays: fantasy play at four. The University of Chicago Press, Chicago, 1988; The boy who would be a helicopter: the uses of…

  2. Sports injuries in children.

    PubMed

    Buckley, S L

    1994-02-01

    More children are participating in organized sports than ever before. Although improved coaching, equipment, officiating, and rules have been implemented to reduce injuries, a significant number of young athletes continue to be injured. Fortunately, most injuries sustained by young athletes are minor requiring only symptomatic treatment. However, because of the unique features of the immature skeleton, particularly the presence of open physes, these injuries can nonetheless result in permanent alteration of bone growth with long-term morbidity and disability. Furthermore, the prognosis and natural history of sports injuries in children may be different than that for similar injuries in adults. It is important that the practitioner dealing with young athletes be aware of the unique features of children's sports injuries so that proper treatment may be initiated and prognosis and expected outcome may be intelligently discussed with the patient and parents. This review provides current information regarding sports injuries in children by summarizing the most recent pertinent articles. PMID:8205179

  3. A novel inhibitor of p75-neurotrophin receptor improves functional outcomes in two models of traumatic brain injury.

    PubMed

    Delbary-Gossart, Sandrine; Lee, Sangmi; Baroni, Marco; Lamarche, Isabelle; Arnone, Michele; Canolle, Benoit; Lin, Amity; Sacramento, Jeffrey; Salegio, Ernesto A; Castel, Marie-Noelle; Delesque-Touchard, Nathalie; Alam, Antoine; Laboudie, Patricia; Ferzaz, Badia; Savi, Pierre; Herbert, Jean-Marc; Manley, Geoffrey T; Ferguson, Adam R; Bresnahan, Jacqueline C; Bono, Françoise; Beattie, Michael S

    2016-06-01

    The p75 neurotrophin receptor is important in multiple physiological actions including neuronal survival and neurite outgrowth during development, and after central nervous system injury. We have discovered a novel piperazine-derived compound, EVT901, which interferes with p75 neurotrophin receptor oligomerization through direct interaction with the first cysteine-rich domain of the extracellular region. Using ligand binding assays with cysteine-rich domains-fused p75 neurotrophin receptor, we confirmed that EVT901 interferes with oligomerization of full-length p75 neurotrophin receptor in a dose-dependent manner. Here we report that EVT901 reduces binding of pro-nerve growth factor to p75 neurotrophin receptor, blocks pro-nerve growth factor induced apoptosis in cells expressing p75 neurotrophin receptor, and enhances neurite outgrowth in vitro Furthermore, we demonstrate that EVT901 abrogates p75 neurotrophin receptor signalling by other ligands, such as prion peptide and amyloid-β. To test the efficacy of EVT901 in vivo, we evaluated the outcome in two models of traumatic brain injury. We generated controlled cortical impacts in adult rats. Using unbiased stereological analysis, we found that EVT901 delivered intravenously daily for 1 week after injury, reduced lesion size, protected cortical neurons and oligodendrocytes, and had a positive effect on neurological function. After lateral fluid percussion injury in adult rats, oral treatment with EVT901 reduced neuronal death in the hippocampus and thalamus, reduced long-term cognitive deficits, and reduced the occurrence of post-traumatic seizure activity. Together, these studies provide a new reagent for altering p75 neurotrophin receptor actions after injury and suggest that EVT901 may be useful in treatment of central nervous system trauma and other neurological disorders where p75 neurotrophin receptor signalling is affected. PMID:27084575

  4. A novel inhibitor of p75-neurotrophin receptor improves functional outcomes in two models of traumatic brain injury

    PubMed Central

    Delbary-Gossart, Sandrine; Lee, Sangmi; Baroni, Marco; Lamarche, Isabelle; Arnone, Michele; Canolle, Benoit; Lin, Amity; Sacramento, Jeffrey; Salegio, Ernesto A.; Castel, Marie-Noelle; Delesque-Touchard, Nathalie; Alam, Antoine; Laboudie, Patricia; Ferzaz, Badia; Savi, Pierre; Herbert, Jean-Marc; Manley, Geoffrey T.; Ferguson, Adam R.; Bresnahan, Jacqueline C.

    2016-01-01

    The p75 neurotrophin receptor is important in multiple physiological actions including neuronal survival and neurite outgrowth during development, and after central nervous system injury. We have discovered a novel piperazine-derived compound, EVT901, which interferes with p75 neurotrophin receptor oligomerization through direct interaction with the first cysteine-rich domain of the extracellular region. Using ligand binding assays with cysteine-rich domains-fused p75 neurotrophin receptor, we confirmed that EVT901 interferes with oligomerization of full-length p75 neurotrophin receptor in a dose-dependent manner. Here we report that EVT901 reduces binding of pro-nerve growth factor to p75 neurotrophin receptor, blocks pro-nerve growth factor induced apoptosis in cells expressing p75 neurotrophin receptor, and enhances neurite outgrowth in vitro. Furthermore, we demonstrate that EVT901 abrogates p75 neurotrophin receptor signalling by other ligands, such as prion peptide and amyloid-β. To test the efficacy of EVT901 in vivo, we evaluated the outcome in two models of traumatic brain injury. We generated controlled cortical impacts in adult rats. Using unbiased stereological analysis, we found that EVT901 delivered intravenously daily for 1 week after injury, reduced lesion size, protected cortical neurons and oligodendrocytes, and had a positive effect on neurological function. After lateral fluid percussion injury in adult rats, oral treatment with EVT901 reduced neuronal death in the hippocampus and thalamus, reduced long-term cognitive deficits, and reduced the occurrence of post-traumatic seizure activity. Together, these studies provide a new reagent for altering p75 neurotrophin receptor actions after injury and suggest that EVT901 may be useful in treatment of central nervous system trauma and other neurological disorders where p75 neurotrophin receptor signalling is affected. PMID:27084575

  5. The Role of the Nervous System in the Pathophysiology of Psoriasis: A Review of Cases of Psoriasis Remission or Improvement Following Denervation Injury.

    PubMed

    Zhu, Tian Hao; Nakamura, Mio; Farahnik, Benjamin; Abrouk, Michael; Lee, Kristina; Singh, Rasnik; Gevorgyan, Alexander; Koo, John; Bhutani, Tina

    2016-06-01

    As most efforts in the last decade have focused on the immunologic basis of inflammatory skin disease, there has been less emphasis on the role of the nervous system in the disease process of psoriasis. Evidence in support of the neurocutaneous pathway has come from observations of patients experiencing unilateral improvement and even complete remission following nerve damage in the affected dermatomal region. The aim of this review was to investigate the role of neuropeptides in the intricate pathophysiology of psoriasis. The PubMed database was searched for individual case reports or case series that reported clearance or significant improvement in psoriatic disease in patients following documented nerve injury. A total of 11 cases were found that reported improvement of psoriatic lesions in areas afflicted by central or peripheral nerve injury. The most common causes of denervation were inadvertent surgical interruption, cerebrovascular accident, and poliomyelitis. In four cases the patients eventually regained neurologic function, which was associated with a recurrence of skin lesions. In cases of permanent nerve damage, there was remission of psoriasis. The cases reported in the literature to date provide clinical evidence that absence of neural input leads to psoriasis improvement, suggesting a crucial role of the nervous system in the pathophysiology of psoriatic disease. In fact, neuropeptides such as nerve growth factor, substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide may be important contributors of psoriatic disease and potential targets for future therapies. PMID:26935938

  6. Detection of Thermal Sublethal Injury in Escherichia coli via the Selective Medium Plating Technique: Mechanisms and Improvements

    PubMed Central

    Espina, Laura; García-Gonzalo, Diego; Pagán, Rafael

    2016-01-01

    In food preservation, the synergistic combination of different technologies aims to maximize the total lethality of the process and minimize the intensity of each hurdle. This is especially the case when at least one of the treatments can cause sublethal (reparable) injury in a great proportion of the population, so that sublethally injured cells can end up being entirely inactivated by the other hurdle(s). The selective medium plating technique (SMPT) is extensively used to enumerate bacterial sublethal injury after inimical treatments, being sodium chloride added to the recovery medium to detect damaged bacterial envelopes. However, little work has been done to explain the reasons for the inability of sublethally injured cells to outgrow in selective agar media, whereas they are able to grow in non-selective agar. In the present paper, the performance of SMPT on Escherichia coli cells after heat treatments is explored by applying different selective agents in the recovery media, using mutants lacking factors involved in osmoregulation, and also by examining the integrity of the cytoplasmic membrane. In view of the results, the possibility of a specific toxic effect of Na+ as the main mechanism under SMPT was discarded, since the same level of sublethal injury was detected using KCl instead of NaCl. The synthesis of the osmoprotectant trehalose determined the maximum osmotolerance of intact cells to the selective agents, but was not crucial in the quantification of sublethal injury. Moreover, for the first time, the extent of sublethal injury detected via SMPT was directly correlated with the physical loss of integrity of the cell membrane in 99.999% of the initial population. This was achieved through statistical analysis of flow cytometry data using propidium iodide-exclusion technique when that dye was added before thermal treatments. The present work confirms the adequacy of SMPT as a tool for detecting the occurrence and quantity of sublethally injured cells

  7. Detection of Thermal Sublethal Injury in Escherichia coli via the Selective Medium Plating Technique: Mechanisms and Improvements.

    PubMed

    Espina, Laura; García-Gonzalo, Diego; Pagán, Rafael

    2016-01-01

    In food preservation, the synergistic combination of different technologies aims to maximize the total lethality of the process and minimize the intensity of each hurdle. This is especially the case when at least one of the treatments can cause sublethal (reparable) injury in a great proportion of the population, so that sublethally injured cells can end up being entirely inactivated by the other hurdle(s). The selective medium plating technique (SMPT) is extensively used to enumerate bacterial sublethal injury after inimical treatments, being sodium chloride added to the recovery medium to detect damaged bacterial envelopes. However, little work has been done to explain the reasons for the inability of sublethally injured cells to outgrow in selective agar media, whereas they are able to grow in non-selective agar. In the present paper, the performance of SMPT on Escherichia coli cells after heat treatments is explored by applying different selective agents in the recovery media, using mutants lacking factors involved in osmoregulation, and also by examining the integrity of the cytoplasmic membrane. In view of the results, the possibility of a specific toxic effect of Na(+) as the main mechanism under SMPT was discarded, since the same level of sublethal injury was detected using KCl instead of NaCl. The synthesis of the osmoprotectant trehalose determined the maximum osmotolerance of intact cells to the selective agents, but was not crucial in the quantification of sublethal injury. Moreover, for the first time, the extent of sublethal injury detected via SMPT was directly correlated with the physical loss of integrity of the cell membrane in 99.999% of the initial population. This was achieved through statistical analysis of flow cytometry data using propidium iodide-exclusion technique when that dye was added before thermal treatments. The present work confirms the adequacy of SMPT as a tool for detecting the occurrence and quantity of sublethally injured

  8. Combining Biochemical and Imaging Markers to Improve Diagnosis and Characterization of Mild Traumatic Brain Injury in the Acute Setting: Results from a Pilot Study

    PubMed Central

    Kou, Zhifeng; Gattu, Ramtilak; Kobeissy, Firas; Welch, Robert D.; O’Neil, Brian J.; Woodard, John L.; Ayaz, Syed Imran; Kulek, Andrew; Kas-Shamoun, Robert; Mika, Valerie; Zuk, Conor; Tomasello, Francesco; Mondello, Stefania

    2013-01-01

    Background Mild traumatic brain injury (mTBI) is a significant healthcare burden and its diagnosis remains a challenge in the emergency department. Serum biomarkers and advanced magnetic resonance imaging (MRI) techniques have already demonstrated their potential to improve the detection of brain injury even in patients with negative computed tomography (CT) findings. The objective of this study was to determine the clinical value of a combinational use of both blood biomarkers and MRI in mTBI detection and their characterization in the acute setting (within 24 hours after injury). Methods Nine patients with mTBI were prospectively recruited from the emergency department. Serum samples were collected at the time of hospital admission and every 6 hours up to 24 hours post injury. Neuronal (Ubiquitin C-terminal Hydrolase-L1 [UCH-L1]) and glial (glial fibrillary acidic protein [GFAP]) biomarker levels were analyzed. Advanced MRI data were acquired at 9±6.91 hours after injury. Patients’ neurocognitive status was assessed by using the Standard Assessment of Concussion (SAC) instrument. Results The median serum levels of UCH-L1 and GFAP on admission were increased 4.9 folds and 10.6 folds, respectively, compared to reference values. Three patients were found to have intracranial hemorrhages on SWI, all of whom had very high GFAP levels. Total volume of brain white matter (WM) with abnormal fractional anisotropy (FA) measures of diffusion tensor imaging (DTI) were negatively correlated with patients’ SAC scores, including delayed recall. Both increased and decreased DTI-FA values were observed in the same subjects. Serum biomarker level was not correlated with patients’ DTI data nor SAC score. Conclusions Blood biomarkers and advanced MRI may correlate or complement each other in different aspects of mTBI detection and characterization. GFAP might have potential to serve as a clinical screening tool for intracranial bleeding. UCH-L1 complements MRI in injury

  9. Auger injuries in children.

    PubMed Central

    Letts, R. M.; Gammon, W.

    1978-01-01

    A 6-year review of auger injuries in Manitoba children revealed that 23 children sustained major injuries resulting in amputation of 17 limbs. Auger injuries are the main cause of traumatic amputation in children in Manitoba. Improved safety education for the entire farm family as well as better design of safety shields would decrease this carnage. Images FIG. 1 FIG. 3 FIG. 4 FIG. 5 FIG. 6 FIG. 9 PMID:630513

  10. Injuries from hovercraft racing.

    PubMed

    Cattermole, H R

    1997-01-01

    A 31-year-old man presented with a potentially serious neck injury following a racing hovercraft accident. Previous reports of hovercrafting injuries could not be found, and a review of the sport's own records was undertaken. This shows there to be a wide range of injuries sustained from the sport, although most of them are minor. However, there are some worrying trends, and further studies are being undertaking in order to improve the sport's safety record. PMID:9196622

  11. The University of the National Football League: How Technology, Injury Surveillance, and Health Care Have Improved the Safety of America's Game.

    PubMed

    Matava, Matthew J; Görtz, Simon

    2016-07-01

    American football has become one of the most popular sports in the United States. Despite the millions of players at all levels of competition who gain the physical, social, and psychological rewards that football provides, many interested stakeholders continue to ask, "Is football safe?" Although there are only approximately 1,700 players on National Football League (NFL) rosters, the injuries they sustain have garnered the most attention-and criticism-from the national media. Increased public awareness of the injury potential football possesses has led to an open debate and a major shift in public sentiment over the past 5 years. Although no sport is perfectly safe, the question is whether it can be made relatively safe and if the long-term consequences are worth the risk. This article reviews the methods by which one sports league-the NFL-has used advances in medical technology and injury surveillance to improve the health and safety of its players. PMID:27258045

  12. Ghrelin Therapy Improves Survival after Whole-Body Ionizing Irradiation or Combined with Burn or Wound: Amelioration of Leukocytopenia, Thrombocytopenia, Splenomegaly, and Bone Marrow Injury

    PubMed Central

    Kiang, Juliann G.; Zhai, Min; Liao, Pei-Jyun; Elliott, Thomas B.; Gorbunov, Nikolai V.

    2014-01-01

    Exposure to ionizing radiation alone (RI) or combined with traumatic tissue injury (CI) is a crucial life-threatening factor in nuclear and radiological events. In our laboratory, mice exposed to 60Co-γ-photon radiation (9.5 Gy, 0.4 Gy/min, bilateral) followed by 15% total-body-surface-area skin wounds (R-W CI) or burns (R-B CI) experienced an increment of ≥18% higher mortality over a 30-day observation period compared to RI alone. CI was accompanied by severe leukocytopenia, thrombocytopenia, erythropenia, and anemia. At the 30th day after injury, numbers of WBC and platelets still remained very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and hematocrit were recovered towards preirradiation levels. Only RI induced splenomegaly. RI and CI resulted in bone-marrow cell depletion. In R-W CI mice, ghrelin (a hunger-stimulating peptide) therapy increased survival, mitigated body-weight loss, accelerated wound healing, and increased hematocrit. In R-B CI mice, ghrelin therapy increased survival and numbers of neutrophils, lymphocytes, and platelets and ameliorated bone-marrow cell depletion. In RI mice, this treatment increased survival, hemoglobin, and hematocrit and inhibited splenomegaly. Our novel results are the first to suggest that ghrelin therapy effectively improved survival by mitigating CI-induced leukocytopenia, thrombocytopenia, and bone-marrow injury or the RI-induced decreased hemoglobin and hematocrit. PMID:25374650

  13. Are Child Passengers Bringing Up the Rear? Evidence For Differential Improvements in Injury Risk Between Drivers and their Child Passengers

    PubMed Central

    Winston, Flaura K; Xie, Dawei; Durbin, Dennis R; Elliott, Michael R

    2007-01-01

    Since nearly half of children fatally injured in automobile crashes were restrained, optimizing occupant protection systems for children is essential to reducing morbidity and mortality. Data from the Partners for Child Passenger Safety study were used to compare the differential injury risk between drivers and their child passengers in the same crash, with a focus on vehicle model year. A matched cohort design and conditional logistic regression model were used in the analyses. Overall, injury risk for drivers was higher than for children, but the risk difference was largest for the oldest model year vehicles, particularly for children aged 4–8 in seat belts. While drivers experienced significant benefits in safety with increasing model years, children restrained by safety belts alone derived less safety benefit from newer vehicles. PMID:18184488

  14. Injury Trends in Major League Baseball Over 18 Seasons: 1998-2015.

    PubMed

    Conte, Stan; Camp, Christopher L; Dines, Joshua S

    2016-01-01

    Since Major League Baseball (MLB) expanded to its current size of 30 teams in 1998, a comprehensive and longitudinal study of injury trends has not been performed. The purpose of this work is to report the epidemiology of injuries in MLB over that time utilizing disabled list (DL) data. Additionally, we sought to determine the financial impact of these injuries for MLB teams. During this analysis, we focused special attention on injuries of the medial ulnar collateral ligament (MUCL) and conducted a comprehensive review of all MUCL reconstructions ever performed on MLB players. Over the study period, there were a total of 8357 DL designations (mean of 464 annually). Players lost a total of 460,432 days (25,186 days annually) due to injury. Both the number of DL assignments and number of DL days increased from year to year (P < .001 and P = .003, respectively). Average length of DL assignments remained steady over time at 55.1 days (P = .647). Although shoulder injuries decreased (P = .023), this was met with a reciprocal increase in elbow injuries (P = .015). The average annual cost of designating players to the DL was $423,267,634 and a total of $7,618,817,407 was spent over the entire 18 seasons. Regarding MUCL injuries, a total of 400 MUCL reconstructions were performed in MLB players between 1974 and 2015, and the mean time to return to MLB competition was 17.1 months. The annual incidence of MUCL reconstructions increased dramatically from year to year (P < .001) and nearly one-third (n = 131, 32.8%) of all procedures performed over the 42-year period occurred in the last 5 years (2011 to 2015). In summary, overall injury rates and DL assignments continue to rise. Although shoulder injuries are declining, this improvement is countered by increasing elbow injuries, and these injuries continue to represent a significant source of lost revenue. PMID:26991562

  15. Dramatic changes in electronic structure revealed by fractionally charged nuclei

    SciTech Connect

    Cohen, Aron J.; Mori-Sánchez, Paula

    2014-01-28

    Discontinuous changes in the electronic structure upon infinitesimal changes to the Hamiltonian are demonstrated. These are revealed in one and two electron molecular systems by full configuration interaction (FCI) calculations when the realm of the nuclear charge is extended to be fractional. FCI electron densities in these systems show dramatic changes in real space and illustrate the transfer, hopping, and removal of electrons. This is due to the particle nature of electrons seen in stretched systems and is a manifestation of an energy derivative discontinuity at constant number of electrons. Dramatic errors of density functional theory densities are seen in real space as this physics is missing from currently used approximations. The movements of electrons in these simple systems encapsulate those in real physical processes, from chemical reactions to electron transport and pose a great challenge for the development of new electronic structure methods.

  16. Nasal vaccination with troponin reduces troponin specific T-cell responses and improves heart function in myocardial ischemia–reperfusion injury

    PubMed Central

    Frenkel, Dan; Pachori, Alok S.; Zhang, Lunan; Dembinsky-Vaknin, Adi; Farfara, Dorit; Petrovic-Stojkovic, Sanja; Dzau, Victor J.

    2009-01-01

    Myocardial ischemia with subsequent reperfusion (MI/R) can lead to significant myocardial damage. Ischemia initiates inflammation at the blood–microvascular endothelial cell interface and contributes significantly to both acute injury and repair of the damaged tissue. We have found that MI/R injury in mice is associated with a cellular immune response to troponin. Myocardial cells exclusively synthesize troponin and release the troponin into the bloodstream following injury. Mucosally administered proteins induce T cells that secrete anti-inflammatory cytokines such as IL-10 and transforming growth factor β at the anatomical site where the protein localizes. We found that nasal administration of the three subunits of troponin (C, I and T isoforms), given prior to or 1 h following MI/R, decreased infarct size by 40% measured 24 h later. At 1.5 months following MI/R, there was a 50% reduction in infarct size and improvement in cardiac function as measured by echocardiography. Protection was associated with a reduction of cellular immunity to troponin. Immunohistochemistry demonstrated increased IL-10 and reduced IFN-γ in the area surrounding the ischemic infarct following nasal troponin. Adoptive transfer of CD4+ T cells to mice from nasally troponin-treated mice 1 h after the MI/R decreased infarct size by 72%, whereas CD4+ T cells from IL-10−/− mice or nasally BSA-treated mice had no effect. Our results demonstrate that IL-10-secreting CD4+ T cells induced by nasal troponin reduce injury following MI/R. Modulation of cardiac inflammation by nasal troponin provides a novel treatment to decrease myocardial damage and enhance recovery after myocardial ischemia. PMID:19515797

  17. Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology in Critically Ill Children (AWARE): A Prospective Study to Improve Diagnostic Precision

    PubMed Central

    Basu, Rajit K; Kaddourah, Ahmad; Terrell, Tara; Mottes, Theresa; Arnold, Patricia; Jacobs, Judd; Andringa, Jennifer; Armor, Melissa; Hayden, Lauren; Goldstein, Stuart L

    2015-01-01

    Background Acute kidney injury (AKI) is associated with poor outcomes in critically ill children. Recent international consensus panels recommend standardized classification systems to improve the precision of AKI diagnosis, but there is a paucity of data to enable this refinement, particularly in pediatric critical care. Methods/Design This is a prospective observational study. We anticipate collecting data from more than 5500 critically ill children admitted to 32 pediatric intensive care units (PICUs) across the world, during the calendar year of 2014. Data will be collected continuously for three months at each center on all children older than 90 days and younger than 25 years admitted to the ICU. Demographic, resuscitative, and daily physiological and lab data will be captured at individual centers using MediData Rave™, a commercial system designed to manage and report clinical research data. Kidney specific measured variables include changes in serum creatinine and urine output, cumulative fluid overload (%), serum creatinine corrected for fluid balance, and KDIGO AKI stage. Urinary AKI biomarkers to be measured include: urinary neutrophil gelatinase lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (l-FABP), and interleukin-18 (IL-18). Biomarker combinations will be created from different pairs and triplets of urinary biomarkers. The primary analysis will compare the discrimination of these panels versus changes in creatinine for prediction of severe AKI by Day 7 of ICU admission. Secondary analysis will investigate the prediction of biomarkers for injury ‘time based phenotypes’: duration (>2 days), severity (KDIGO stage, use of renal replacement therapy), reversibility (time to return of serum creatinine to baseline), association with fluid overload > 10%, and disease association (sepsis, hypovolemia, hypoxemia, or nephrotoxic). Discussion The Assessment of Worldwide Acute Kidney Injury, Renal Angina and

  18. Early co-administration of vitamin E acetate and methylcobalamin improves thermal hyperalgesia and motor nerve conduction velocity following sciatic nerve crush injury in rats.

    PubMed

    Morani, Aashish S; Bodhankar, Subhash L

    2010-01-01

    Our previous studies have shown that early administration of vitamin E acetate (50 mg/kg, ip (VEA)) and methylcobalamin (500 microg/kg, ip (MCA)) for 30 days improved conduction velocity and neuropathic pain behavior. Here, we evaluated the effect of early co-administration of VEA and MCA (MVE) on thermal hyperlagesia (TH) and motor nerve conduction velocity (MNCV) in rats with sciatic nerve crush injury (SNCI). Fifteen days post-surgery, a reduction in paw withdrawal latency (PWL) was observed in untreated (UNTR) rats. However, latency improved in MVE-treated animals, comparable to the placebo. On day 15, a decrease in MNCV was observed in the UNTR group of animals, and this effect was not observed for the MVE and placebo groups of animals. The results of this study indicate that early exposure to MVE attenuates the progression of TH and improves MNCV in rats with SNCI. PMID:20508297

  19. Rosemary extract improves cognitive deficits in a rats model of repetitive mild traumatic brain injury associated with reduction of astrocytosis and neuronal degeneration in hippocampus.

    PubMed

    Song, Hai; Xu, Lincheng; Zhang, Rongping; Cao, Zhenzhen; Zhang, Huan; Yang, Li; Guo, Zeyun; Qu, Yongqiang; Yu, Jianyun

    2016-05-27

    In this study, we investigated whether Rosemary extract (RE) improved cognitive deficits in repetitive mild Traumatic brain injury (rmTBI) rats and its potential mechanisms. The present results showed that rmTBI caused cognitive deficits, such as increased latency to find platform and decreased time spent in target quadrant in Morris water maze (MWM). These behavioral alterations were accompanying with the increased neuronal degeneration and glial fibrillary acidic protein (GFAP)-positive cells, increased Reactive oxygen species (ROS) generation, decreased activity of Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx) and Catalase (CAT), elevated protein level of IL-1β, IL-6 and TNF-α in hippocampus. Treatment with RE prevented these changes above. Our findings confirmed the effect of rosemary extract on improvement of cognitive deficits and suggested its mechanisms might be mediated by anti-oxidative and anti-inflammatory. Therefore, rosemary extract may be a potential treatment to improve cognitive deficits in rmTBI patients. PMID:27113205

  20. Effectiveness of Interventions Within the Scope of Occupational Therapy Practice to Improve Motor Function of People With Traumatic Brain Injury: A Systematic Review.

    PubMed

    Chang, Pei-Fen J; Baxter, Mary Frances; Rissky, Jenna

    2016-01-01

    After traumatic brain injury (TBI), many people experience significant motor function impairments. To help occupational therapy practitioners make informed decisions in choosing treatment strategies to improve clients' motor function, we undertook a systematic review and synthesized applicable findings of intervention studies. Of 2,306 articles identified in the literature search, we reviewed 47 full-text articles, of which 16 met approved criteria. We found moderate evidence that various exercise programs increase motor function and limited evidence that people with TBI can benefit from rehabilitation and computer-based programs. We offer implications for practice, education, and research. PMID:27089286

  1. Dramatic Resolution of an Unresectable Giant Basal Cell Carcinoma Treated with Intensity-Modulated Radiation Therapy (IMRT) - A Case Report

    PubMed Central

    Wandrey, Narine; Chen, Tiffany

    2015-01-01

    A 59-year-old man presented with an unresectable bulky giant basal cell carcinoma on his upper back. A trial of chemotherapy did not help relieve his symptoms or reduce the tumor. He was referred for and received definitive radiation therapy via IMRT with dramatic regression. The patient had been unable to lie on his back for many years but currently can sleep comfortably on his back without pain, which has dramatically improved his quality of life. PMID:26848409

  2. Editorial. Bicycle injuries and injury prevention.

    PubMed

    Pless, I B

    2014-07-01

    In 1989, long before this journal added injuries to its title, it published two papers on childhood injuries and I was asked to write an editorial for this occasion. I chose the title "Challenges for Injury Prevention: Two Neglected Aspects" because I thought the papers neglected to mention the inadequacy of injury statistics (at the time there were no emergency department data) and also failed to emphasize the public health importance of childhood injuries. It is instructive, therefore, to compare this issue's offerings with how matters stood nearly 25 years ago and see what progress we've made. Papers in this and the previous issue of this journal discuss bicycle safety in general and helmet use in particular. Although this is a somewhat narrow focus, it serves as one indicator of how the field has evolved and what remains to be done to improve both the science and policy in this domain. PMID:24991769

  3. Eye Injuries

    MedlinePlus

    The structure of your face helps protect your eyes from injury. Still, injuries can damage your eye, sometimes severely enough that you could lose your vision. Most eye injuries are preventable. If you play sports or ...

  4. Head Injuries

    MedlinePlus

    ... injuries internal head injuries, which may involve the skull, the blood vessels within the skull, or the brain Fortunately, most childhood falls or ... knock the brain into the side of the skull or tear blood vessels. Some internal head injuries ...

  5. Back Injuries

    MedlinePlus

    ... the most common site of back injuries and back pain. Common back injuries include Sprains and strains Herniated disks Fractured vertebrae These injuries can cause pain and limit your movement. Treatments vary but might ...

  6. Eye Injuries

    MedlinePlus

    ... of your face helps protect your eyes from injury. Still, injuries can damage your eye, sometimes severely enough that you could lose your vision. Most eye injuries are preventable. If you play sports or work ...

  7. Blast Injuries

    MedlinePlus

    ... Service Members & Veterans Family & Caregivers Medical Providers Blast Injuries U.S. Army photo by Sgt. Gustavo Olgiati How ... tertiary injury Does a blast cause different brain injuries than blunt trauma? There currently is no evidence ...

  8. Ocular Injury

    MedlinePlus

    ... usually occur from blunt trauma, such as a sports injury or a fall with injury to the nose ... of protective goggles at all times. Even in sports like baseball, eye injuries can be prevented by using batting helmets that ...

  9. Sports Injuries

    MedlinePlus

    ... sometimes you can injure yourself when you play sports or exercise. Accidents, poor training practices, or improper ... can also lead to injuries. The most common sports injuries are Sprains and strains Knee injuries Swollen ...

  10. Midfoot and Forefoot Injuries.

    PubMed

    Gorbachova, Tetyana

    2015-08-01

    Sports injuries of the midfoot and forefoot encompass a spectrum of osseous and soft tissue trauma. Magnetic resonance imaging serves as a primary or important supplementary diagnostic modality in evaluation of various injuries, most important of which include Lisfranc complex injury, stress fractures, and injury to the first metatarsophalangeal joint, aka "turf toe." Current technical advances in magnetic resonance and improved knowledge of regional anatomy enable thorough evaluation of the complex anatomic structures of the foot and facilitate accurate diagnosis in the setting of trauma. PMID:26244619

  11. Serotonin and Histamine Therapy Increases Tetanic Forces of Myoblasts, Reduces Muscle Injury, and Improves Grip Strength Performance of Dmd(mdx) Mice.

    PubMed

    Gurel, Volkan; 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 Dmd(mdx) 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. Dmd(mdx) 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 Dmd(mdx) 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

  12. Pain relief and functional improvement in patients with neuropathic pain associated with spinal cord injury: an exploratory analysis of pregabalin clinical trials

    PubMed Central

    Sadosky, Alesia; Parsons, Bruce; Emir, Birol; Nieshoff, Edward C

    2016-01-01

    Background Characterizing relationships between pain relief and function can inform patient management decisions. This analysis explored graphically the relationship between pain relief and functional improvement in patients with neuropathic pain associated with spinal cord injury in two clinical trials of pregabalin. Methods This was a post hoc analysis of two randomized, double-blind, clinical trials in patients who were treated with pregabalin (n=181) or placebo (n=172) for neuropathic pain associated with spinal cord injury. The bivariate relationship between percent pain relief and absolute change in the functional outcomes with placebo and pregabalin was evaluated graphically using scatter plots, and loess curves illustrated the extent of the relationship between pain and function. Linear trend analysis evaluated the statistical significance of these relationships using Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT)-based thresholds of pain reduction (<15%, 15% <30%, 30% to <50%, and ≥50%). Outcome measures included modified Brief Pain Inventory pain interference with function in one of the studies and the Medical Outcomes Study Sleep Scale (an 11-point Numeric Rating Scale) and the Hospital Anxiety and Depression Scale (HADS) for the pooled studies. Results Data ellipses showed a shift with pregabalin relative to placebo toward greater improvement with increasing pain relief for all outcome measures except HADS. Loess curves suggested a relationship between increased pain relief and improved function except for HADS, with the clearest relationship observed for sleep. Linear trend analysis showed significant relationships between pain and Medical Outcomes Study Sleep Scale (P<0.0001) and between pain and function on the modified Brief Pain Inventory Interference Index and most individual items (P<0.05). Conclusion Greater functional improvements were generally achieved at higher levels of clinically significant pain

  13. Digital Gaming for Improving the Functioning of People With Traumatic Brain Injury: Protocol of a Feasibility Study

    PubMed Central

    Korkeila, Jyrki; Kauppi, Kaisa; Kaakinen, Johanna K; Holm, Suvi; Vahlo, Jukka; Tenovuo, Olli; Hämäläinen, Heikki; Sarajuuri, Jaana; Rantanen, Pekka; Orenius, Tage; Koponen, Aki

    2016-01-01

    Background Traumatic brain injury (TBI) is a critical public health problem. The recovery process for people with TBI is typically slow and dependent on complex and intensive assisted rehabilitation programs. Objective To evaluate the effects and feasibility of digital games for cognitive functioning and general well-being among people with traumatic brain injury. Methods This is a single-site feasibility study conducted in Finland, which uses a pragmatic, randomized controlled trial with three arms, and will recruit patients from the Turku University Hospital, Division of Clinical Neurosciences in Finland. Participants must meet the following inclusion criteria: (1) a Finnish speaking adult, aged 18-65 years; (2) diagnosed with a traumatic brain injury (diagnostic criteria ICD-10, S06.X, T90.5) in the University Hospital; (3) access to a TV, a computer, and the Internet at home; (4) not an active digital gamer (5 hours or less a week); (5) willing to participate in the study. Participants must have been discharged from the neurologic treatment period for traumatic brain injury for over 12 months before the commencement of the trial, and they may not have actively participated in cognitive rehabilitation during the 3 months prior to the trial. Written informed consent will be mandatory for acceptance into the trial. Exclusion criteria are as follows: (1) sensory, cognitive, or physical impairment (eg, severe cognitive impairment); (2) a deficiency restricting the use of computers or computer game control system unaided (eg, impairment in vision, severe astigmatism, hemiplegia, disorder in visuospatial perception, dysfunction of the central vestibular system); (3) apathy identified in previous neuropsychological evaluations; (4) diagnosed severe mental disorders (eg, schizophrenia or severe depressive disorders to be identified in medical records as the secondary diagnosis). Results The preparatory phase for the study is fulfilled. Recruitment started in June 2015

  14. A new injury prevention programme for children's football--FIFA 11+ Kids--can improve motor performance: a cluster-randomised controlled trial.

    PubMed

    Rössler, R; Donath, L; Bizzini, M; Faude, O

    2016-01-01

    The present study evaluated the effects of a newly developed injury prevention programme for children's football ("FIFA 11+ Kids") on motor performance in 7-12-year-old children. We stratified 12 football teams (under-9/-11/-13 age categories) into intervention (INT, N = 56 players) and control groups (CON, N = 67). INT conducted the 15-min warm-up programme "FIFA 11+ Kids" twice a week for 10 weeks. CON followed a standard warm-up (sham treatment). Pre- and post-tests were conducted using: single leg stance; Y-balance test; drop and countermovement jump; standing long jump; 20-m sprint; agility run; slalom dribble; and wall volley test. We used magnitude-based inferences and linear mixed-effects models to analyse performance test results. We observed likely beneficial effects favouring INT in Y-balance (right leg; +3.2%; standardised mean difference (SMD) = 0.34; P = 0.58) and agility run (+3.6%; SMD = 0.45; P = 0.008). Possibly beneficial effects were found in Y-balance, drop jump reactive strength index, drop jump height, countermovement jump, standing long jump, slalom dribble and wall volley test. At least possibly beneficial improvements in favour of "FIFA 11+ Kids" were observed in nearly all parameters. Most effects were small, but slight improvements in motor performance may potentially contribute to a reduction of injury risk. PMID:26508531

  15. Lavandula angustifolia Extract Improves the Result of Human Umbilical Mesenchymal Wharton's Jelly Stem Cell Transplantation after Contusive Spinal Cord Injury in Wistar Rats

    PubMed Central

    Yaghoobi, Kayvan; Kaka, Gholamreza; Mansouri, Korosh; Davoodi, Shaghayegh; Sadraie, Seyed Homayoon; Hosseini, Seyed Ruhollah

    2016-01-01

    Introduction. The primary trauma of spinal cord injury (SCI) results in severe damage to nervous functions. At the cellular level, SCI causes astrogliosis. Human umbilical mesenchymal stem cells (HUMSCs), isolated from Wharton's jelly of the umbilical cord, can be easily obtained. Previously, we showed that the neuroprotective effects of Lavandula angustifolia can lead to improvement in a contusive SCI model in rats. Objective. The aim of this study was to investigate the effect of L. angustifolia (Lav) on HUMSC transplantation after acute SCI. Materials and Methods. Sixty adult female rats were randomly divided into eight groups. Every week after SCI onset, all animals were evaluated for behavior outcomes. H&E staining was performed to examine the lesions after injury. GFAP expression was assessed for astrogliosis. Somatosensory evoked potential (SEP) testing was performed to detect the recovery of neural conduction. Results. Behavioral tests showed that the HUMSC group improved in comparison with the SCI group, but HUMSC + Lav 400 was very effective, resulting in a significant increase in locomotion activity. Sensory tests and histomorphological and immunohistochemistry analyses verified the potentiation effects of Lav extract on HUMSC treatment. Conclusion. Transplantation of HUMSCs is beneficial for SCI in rats, and Lav extract can potentiate the functional and cellular recovery with HUMSC treatment in rats after SCI. PMID:27057171

  16. Lavandula angustifolia Extract Improves the Result of Human Umbilical Mesenchymal Wharton's Jelly Stem Cell Transplantation after Contusive Spinal Cord Injury in Wistar Rats.

    PubMed

    Yaghoobi, Kayvan; Kaka, Gholamreza; Mansouri, Korosh; Davoodi, Shaghayegh; Sadraie, Seyed Homayoon; Hosseini, Seyed Ruhollah

    2016-01-01

    Introduction. The primary trauma of spinal cord injury (SCI) results in severe damage to nervous functions. At the cellular level, SCI causes astrogliosis. Human umbilical mesenchymal stem cells (HUMSCs), isolated from Wharton's jelly of the umbilical cord, can be easily obtained. Previously, we showed that the neuroprotective effects of Lavandula angustifolia can lead to improvement in a contusive SCI model in rats. Objective. The aim of this study was to investigate the effect of L. angustifolia (Lav) on HUMSC transplantation after acute SCI. Materials and Methods. Sixty adult female rats were randomly divided into eight groups. Every week after SCI onset, all animals were evaluated for behavior outcomes. H&E staining was performed to examine the lesions after injury. GFAP expression was assessed for astrogliosis. Somatosensory evoked potential (SEP) testing was performed to detect the recovery of neural conduction. Results. Behavioral tests showed that the HUMSC group improved in comparison with the SCI group, but HUMSC + Lav 400 was very effective, resulting in a significant increase in locomotion activity. Sensory tests and histomorphological and immunohistochemistry analyses verified the potentiation effects of Lav extract on HUMSC treatment. Conclusion. Transplantation of HUMSCs is beneficial for SCI in rats, and Lav extract can potentiate the functional and cellular recovery with HUMSC treatment in rats after SCI. PMID:27057171

  17. Firecracker injuries to the hand.

    PubMed

    MacKenzie, D N; Green, J A; Viglione, W

    2001-03-01

    Between September 1999 and April 2000, the Hand Unit at St George Hospital, Sydney, treated three young men with severe injuries caused by holding a lighted firecracker. These cases illustrate the typical injuries seen with this mechanism of injury. They highlight the dangers of these explosive devices and the potential to improve the laws relating to fireworks. PMID:11280694

  18. THERAPEUTIC NEUTRALIZATION OF THE NLRP1 INFLAMMASOME REDUCES THE INNATE IMMUNE RESPONSE AND IMPROVES HISTOPATHOLOGY AFTER TRAUMATIC BRAIN INJURY

    PubMed Central

    de Rivero Vaccari, Juan Pablo; Lotocki, George; Alonso, Ofelia F.; Bramlett, Helen M.; Dietrich, W. Dalton; Keane, Robert W.

    2010-01-01

    Traumatic brain injury (TBI) elicits acute inflammation that in turn exacerbates primary brain damage. A crucial part of innate immunity in the immune privileged central nervous system involves production of proinflammatory cytokines mediated by inflammasome signaling. Here we show that the nucleotide-binding, leucine-rich repeat pyrin domain containing protein 1 (NLRP1) inflammasome consisting of NLRP1, caspases-1 and -11, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), the X-linked inhibitor of apoptosis protein (XIAP) and pannexin 1 is expressed in neurons of the cerebral cortex. Moderate parasagittal fluid percussion injury (FPI) induced processing of interleukin-1β (IL-1β), activation of caspase-1, cleavage of XIAP and promoted assembly of the NLRP1 inflammasome complex. Anti-ASC neutralizing antibodies administered immediately after FPI to injured rats reduced caspase-1 activation, XIAP cleavage and processing of IL-1β resulting in a significant decrease in contusion volume. These studies show that the NLRP1 inflammasome constitutes an important component of the innate CNS inflammatory response after TBI and may be a novel therapeutic target for reducing the damaging effects of post-traumatic brain inflammation. PMID:19401709

  19. Effectiveness of Occupation- and Activity-Based Interventions to Improve Everyday Activities and Social Participation for People With Traumatic Brain Injury: A Systematic Review.

    PubMed

    Powell, Janet M; Rich, Timothy J; Wise, Elizabeth K

    2016-01-01

    This systematic review presents research on the effectiveness of occupation- and activity-based interventions to improve everyday activities and areas of occupation and social participation for people with traumatic brain injury (TBI). Nineteen studies identified through a comprehensive database search were reviewed and synthesized into five themes: (1) multidisciplinary and interdisciplinary treatment approaches, (2) community-based rehabilitation programs, (3) treatment approaches using client-centered goals and relevant contexts, (4) social skills training and peer mentoring interventions, and (5) community mobility interventions. Evidence supports the use of multidisciplinary and interdisciplinary approaches across a variety of settings, with no single treatment approach or setting clearly superior to another. The specific contributions of occupational therapy practitioners and the nature of occupational therapy interventions have not been well studied, making it difficult to determine the extent to which occupation- and activity-based interventions provided by occupational therapy practitioners improve occupational performance and social participation after TBI. PMID:27089288

  20. Normabaric Hyperoxia Treatment Improved Locomotor Activity of C57BL/6J Mice through Enhancing Dopamine Genes Following Fluid-Percussion Injury in Striatum

    PubMed Central

    Muthuraju, Sangu; Taha, Syed; Pati, Soumya; Rafique, Mohamed; Jaafar, Hasnan; Abdullah, Jafri Malin

    2013-01-01

    Closed traumatic brain injury (CTBI) leads to increase mortality rates in developing countries. However, a sustainable therapeutic approach has not been established yet. Therefore, the present study was designed to evaluate the impact of normabaric hyperoxia treatment (NBOT) on striatum associated Locomotor Activity (LA) in IntelliCage after Fluid-Percussion Injury (FPI). Animals were divided in four groups: Group I control (n=24), Group II sham (n=24), Group III FPI (n=24) and Group IV FPI with NBOT (n=24). Animals were habituated in IntelliCage for 4 days following transponder implanted in mice neck region on day 5. Then the LA of all groups was assessed 6hr daily for 5 days before inducing FPI. On day 6, cannula was implanted on the striatum, on day 7 FPI was performed in Group III (kept in normal environment) and IV (immediately exposed to NBOT for 3 hr). LA (in terms of number of visits in all four corners) was assessed 6 hr at days 1, 7, 14, 21 and 28 following FPI. After the animals were sacrificed to study the neuronal damage, dopamine receptors and transporters expression in striatum. The results suggested that the LA of FPI impaired mice as compared to the control and sham showed less number of visits in all four corners in IntelliCage. Morphological results revealed that FPI induced neuronal damage as compared to sham and control. Dopamine receptors and transporters were down regulated in the FPI group as compared to the control. Immediate exposure to NBOT improved LA in terms of increased number of visits in all four corners, reduced number of cell death and improved receptor expression as compared to FPI. In conclusion, NBOT exposure could improve the LA of mice following FPI through prevention of neuronal damage, improved dopamine receptors and transporters. PMID:24711754

  1. Surfactant before the first inflation at birth improves spatial distribution of ventilation and reduces lung injury in preterm lambs.

    PubMed

    Tingay, David G; Wallace, Megan J; Bhatia, Risha; Schmölzer, Georg M; Zahra, Valerie A; Dolan, Melinda J; Hooper, Stuart B; Davis, Peter G

    2014-02-01

    The interrelationship between the role of surfactant and a sustained inflation (SI) to aid ex utero transition of the preterm lung is unknown. We compared the effect of surfactant administered before and after an initial SI on gas exchange, lung mechanics, spatial distribution of ventilation, and lung injury in preterm lambs. Gestational-age lambs (127 days; 9 per group) received 100 mg/kg of a surfactant (Curosurf) either prior (Surf+SI) or 10 min after birth (SI+Surf). At birth, a 20-s, 35 cmH2O SI was applied, followed by 70 min of positive pressure ventilation. Oxygenation, carbon dioxide removal, respiratory system compliance, end-expiratory thoracic volume (via respiratory inductive plethysmography), and distribution of end-expiratory volume and ventilation (via electrical impedance tomography) were measured throughout. Early markers of lung injury were analyzed using quantitative RT-PCR. During the first 15 min, oxygenation, carbon dioxide removal, and compliance were better in the Surf+SI group (all P < 0.05). End-expiratory volume on completion of the sustained inflation was higher in the Surf+SI group than the SI+Surf group; 11 ± 1 ml/kg vs. 7 ± 1 ml/kg (mean ± SE) (P = 0.043; t-test), but was not different at later time points. Although neither achieved homogenous aeration, spatial ventilation was more uniform in the Surf+SI group throughout; 50.1 ± 10.9% of total ventilation in the left hemithorax at 70 min vs. 42.6 ± 11.1% in the SI+Surf group. Surf+SI resulted in lower mRNA levels of CYR61 and EGR1 compared with SI+Surf (P < 0.001, one-way ANOVA). Surfactant status of the fetal preterm lung at birth influences the mechanical and injury response to a sustained inflation and ventilation by changing surface tension of the air/fluid interface. PMID:24356523

  2. Omega-conotoxin MVIIC attenuates neuronal apoptosis in vitro and improves significant recovery after spinal cord injury in vivo in rats

    PubMed Central

    Oliveira, Karen M; Lavor, Mário Sérgio L; Silva, Carla Maria O; Fukushima, Fabíola B; Rosado, Isabel R; Silva, Juneo F; Martins, Bernardo C; Guimarães, Laís B; Gomez, Marcus Vinícius; Melo, Marília M; Melo, Eliane G

    2014-01-01

    Excessive accumulation of intracellular calcium is the most critical step after spinal cord injury (SCI). Reducing the calcium influx should result in a better recovery from SCI. Calcium channel blockers have been shown a great potential in reducing brain and spinal cord injury. In this study, we first tested the neuroprotective effect of MVIIC on slices of spinal cord subjected to ischemia evaluating cell death and caspase-3 activation. Thereafter, we evaluated the efficacy of MVIIC in ameliorating damage following SCI in rats, for the first time in vivo. The spinal cord slices subjected a pretreatment with MVIIC showed a cell protection with a reduction of dead cells in 24.34% and of caspase-3-specific protease activation. In the in vivo experiment, Wistar rats were subjected to extradural compression of the spinal cord at the T12 vertebral level using a weigh of 70 g/cm, following intralesional treatment with either placebo or MVIIC in different doses (15, 30 and 60 pmol) five minutes after injury. Behavioral testing of hindlimb function was done using the Basso Beattie Bresnahan locomotor rating scale, and revealed significant recovery with 15 pmol (G15) compared to other trauma groups. Also, histological bladder structural revealed significant outcome in G15, with no morphological alterations, and anti-NeuN and TUNEL staining showed that G15 provided neuron preservation and indicated that this group had fewer neuron cell death, similar to sham. These results showed the neuroprotective effects of MVIIC in in vitro and in vivo model of SCI with neuronal integrity, bladder and behavioral improvements. PMID:25120731

  3. The adenosine 2A receptor agonist GW328267C improves lung function after acute lung injury in rats.

    PubMed

    Folkesson, Hans G; Kuzenko, Stephanie R; Lipson, David A; Matthay, Michael A; Simmons, Mark A

    2012-08-01

    There is a significant unmet need for treatments of patients with acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). The primary mechanism that leads to resolution of alveolar and pulmonary edema is active vectorial Na(+) and Cl(-) transport across the alveolar epithelium. Several studies have suggested a role for adenosine receptors in regulating this fluid transport in the lung. Furthermore, these studies point to the A(2A) subtype of adenosine receptor (A(2A)R) as playing a role to enhance fluid transport, suggesting that activation of the A(2A)R may enhance alveolar fluid clearance (AFC). The current studies test the potential therapeutic value of the A(2A)R agonist GW328267C to accelerate resolution of alveolar edema and ALI/ARDS in rats. GW328267C, at concentrations of 10(-5) M to 10(-3) M, instilled into the airspaces, increased AFC in control animals. GW328267C did not increase AFC beyond that produced by maximal β-adrenergic stimulation. The effect of GW328267C was inhibited by amiloride but was not affected by cystic fibrosis transmembrane conductance regulator inhibition. The drug was tested in three models of ALI, HCl instillation 1 h, LPS instillation 16 h, and live Escherichia coli instillation 2 h before GW328267C instillation. After either type of injury, GW328267C (10(-4) M) decreased pulmonary edema formation and restored AFC, measured 1 h after GW328267C instillation. These findings show that GW328267C has beneficial effects in experimental models of ALI and may be a useful agent for treating patients with ALI or prophylactically to prevent ALI. PMID:22659881

  4. Combined therapy with danazol, pegilated interferon, and ribavirin improves thrombocytopenia and liver injury in rats with fibrosis.

    PubMed

    Alvarez, Guillermo Cabrera; Madrid-Marina, Vicente; Jimenez-Mendez, Ricardo; Buitimea, Angel Leon; Román, Margarita Bahena; Cortez-Gomez, Rudyard; Esparza, Jorge Reyes; Rodríguez-Fragoso, Lourdes

    2007-01-01

    The aim of this study was to investigate the effects of combinations of pegilated-interferon (PEG-IFN), ribavirin, and danazol on thrombocytopenia and liver injury in rats with fibrosis. Male adult Wistar rats were treated with either mineral oil, danazol (0.83 mg/kg per day), PEG-interferon alpha-2a (PEG-IFN, 0.3 microg/ week) + ribavirin (12 mg/kg per day), PEG-IFN + ribavirin + danazol, CCl(4) (4 g/kg for eight weeks), CCl(4) + PEG-IFN + ribavirin, or CCl(4) + PEG-IFN + ribavirin+ danazol. The following assays were conducted: hematology, clinical chemistry, liver function, liver fibrosis, lymphocyte cytokine mRNA expression, and bone-marrow DNA content. Platelet counts were low in sham-treated animals and animals treated with PEG- IFN + ribavirin (30% and 25% respectively; P < 0.05). PEG-IFN + ribavirin + danazol reduced platelet counts of fibrotic animals by only 9% (P < 0.05). PEG- IFN + ribavirin reduced hepatic collagen content by 50%, whereas danazol + PEG-IFN + ribavirin reduced hepatic collagen content by 60% (P < 0.05). PEG-IFN + ribavirin reduced the total bilirubin concentration by 27%, alanine amino transferase (ALT) activity by 75% and gamma-glutamyl transpeptidase (gamma-GTP) activity by 74% (P < 0.05). In contrast, danazol + PEG-IFN + ribavirin reduced total bilirubin levels by 61%, alkaline phosphatase activity by 45%, ALT activity by 76%, and gamma-GTP activity by 74% (P < 0.05). The only treatment that increased interleukin 10 (IL-10) mRNA in fibrotic rats was PEG-IFN + ribavirin. However, danazol + PEG-IFN + ribavirin reduced the expression of IL-6, IL-10, tumor necrosis factor alpha and transforming growth factor ss. Bone-marrow DNA content was not altered by any treatment. In conclusion, PEG-IFN + ribavirin + danazol could be a new therapeutic option for patients with liver injury, fibrosis, and thrombocytopenia. PMID:18007553

  5. Prostacyclin post-treatment improves LPS-induced acute lung injury and endothelial barrier recovery via Rap1

    PubMed Central

    Birukova, Anna A.; Meng, Fanyong; Tian, Yufeng; Meliton, Angelo; Sarich, Nicolene; Quilliam, Lawrence A.; Birukov, Konstantin G.

    2015-01-01

    Protective effects of prostacyclin (PC) or its stable analog beraprost against agonist-induced lung vascular inflammation have been associated with elevation of intracellular cAMP and Rac GTPase signaling which inhibited the RhoA GTPase-dependent pathway of endothelial barrier dysfunction. This study investigated a distinct mechanism of PC-stimulated lung vascular endothelial (EC) barrier recovery and resolution of LPS-induced inflammation mediated by small GTPase Rap1. Efficient barrier recovery was observed in LPS-challenged pulmonary EC after prostacyslin administration even after 15 hrs of initial inflammatory insult and was accompanied by the significant attenuation of p38 MAP kinase and NFkB signaling and decreased production of IL-8 and soluble ICAM1. These effects were reproduced in cells post-treated with 8CPT, a small molecule activator of Rap1-specific nucleotide exchange factor Epac. By contrast, pharmacologic Epac inhibitor, Rap1 knockdown, or knockdown of cell junction-associated Rap1 effector afadin attenuated EC recovery caused by PC or 8CPT post-treatment. The key role of Rap1 in lung barrier restoration was further confirmed in the murine model of LPS-induced acute lung injury. Lung injury was monitored by measurements of bronchoalveolar lavage protein content, cell count, and Evans blue extravasation and live imaging of vascular leak over 6 days using a fluorescent tracer. The data showed significant acceleration of lung recovery by PC and 8CPT post-treatment, which was abrogated in Rap1a−/− mice. These results suggest that post-treatment with PC triggers the Epac/Rap1/afadin-dependent mechanism of endothelial barrier restoration and downregulation of p38MAPK and NFkB inflammatory cascades, altogether leading to accelerated lung recovery. PMID:25545047

  6. Docosahexaenoic acid reduces ER stress and abnormal protein accumulation and improves neuronal function following traumatic brain injury.

    PubMed

    Begum, Gulnaz; Yan, Hong Q; Li, Liaoliao; Singh, Amneet; Dixon, C Edward; Sun, Dandan

    2014-03-01

    In this study, we investigated the development of endoplasmic reticulum (ER) stress after traumatic brain injury (TBI) and the efficacy of post-TBI administration of docosahexaenoic acid (DHA) in reducing ER stress. TBI was induced by cortical contusion injury in Sprague-Dawley rats. Either DHA (16 mg/kg in DMSO) or vehicle DMSO (1 ml/kg) was administered intraperitoneally at 5 min after TBI, followed by a daily dose for 3-21 d. TBI triggered sustained expression of the ER stress marker proteins including phosphorylated eukaryotic initiation factor-2α, activating transcription factor 4, inositol requiring kinase 1, and C/EBP homologous protein in the ipsilateral cortex at 3-21 d after TBI. The prolonged ER stress was accompanied with an accumulation of abnormal ubiquitin aggregates and increased expression of amyloid precursor protein (APP) and phosphorylated tau (p-Tau) in the frontal cortex after TBI. The ER stress marker proteins were colocalized with APP accumulation in the soma. Interestingly, administration of DHA attenuated all ER stress marker proteins and reduced the accumulation of both ubiquitinated proteins and APP/p-Tau proteins. In addition, the DHA-treated animals exhibited early recovery of their sensorimotor function after TBI. In summary, our study demonstrated that TBI induces a prolonged ER stress, which is positively correlated with abnormal APP accumulation. The sustained ER stress may play a role in chronic neuronal damage after TBI. Our findings illustrate that post-TBI administration of DHA has therapeutic potentials in reducing ER stress, abnormal protein accumulation, and neurological deficits. PMID:24599472

  7. Improvement of hind-limb paralysis following traumatic spinal cord injury in rats by grafting normal human keratinocytes: new cell-therapy strategy for nerve regeneration.

    PubMed

    Inoue, Hajime; Takenaga, Mitsuko; Ohta, Yuki; Tomioka, Miyuki; Watabe, Yu-Ichi; Aihara, Masaki; Kumagai, Norio

    2011-12-01

    Somatic (adult) stem cells are thought to have pluripotency, just as do embryotic stem (ES) cells. We investigated the possibility that grafted epithelial keratinocytes could induce spinal cord regeneration in an animal model of spinal cord injury (SCI). Normal human keratinocytes were cultured by the routine technique, and normal human dermal fibroblasts were cultured by a similar method as a control group. SCI model was prepared by dropping a 10-g weight onto the exposed spinal cord of rats from a height of 25 mm, and 8 days later, the cultured cells were grafted into the injury site. Motor function was significantly improved in the cultured-keratinocyte-grafted group compared with that in the fibroblast-grafted group. After functional observation, human nestin- and nuclei-positive cells were found at the grafted spinal cord. Grafted cultured keratinocytes induced in vitro morphological changes in the neural induction medium. These results indicated one possibility that some of the grafted cultured keratinocytes survived and could have contributed to neural regeneration. On the other hand, it should be noted that the grafted cultured keratinocytes secreted a large amount of enzymes and/or growth factors. Therefore, another possibility is that the grafted-keratinocyte-derived factors could induce survived cell growth and endogenous neural differentiation of spinal-nerve-derived stem cells surrounding the injured spinal cord, leading to functional recovery. Epithelial stem cell therapy may be applied clinically in the near future to treat SCI. PMID:21842261

  8. Improving the care of people with traumatic brain injury through the Neurotrauma Evidence Translation (NET) program: protocol for a program of research.

    PubMed

    Green, Sally E; Bosch, Marije; McKenzie, Joanne E; O'Connor, Denise A; Tavender, Emma J; Bragge, Peter; Chau, Marisa; Pitt, Veronica; Rosenfeld, Jeffrey V; Gruen, Russell L

    2012-01-01

    The Neurotrauma Evidence Translation (NET) program was funded in 2009 to increase the uptake of research evidence in the clinical care of patients who have sustained traumatic brain injury. This paper reports the rationale and plan for this five-year knowledge translation research program. The overarching aims of the program are threefold: to improve outcomes for people with traumatic brain injury; to create a network of neurotrauma clinicians and researchers with expertise in knowledge translation and evidence-based practice; and to contribute knowledge to the field of knowledge translation research. The program comprises a series of interlinked projects spanning varying clinical environments and disciplines relevant to neurotrauma, anchored within four themes representing core knowledge translation activities: reviewing research evidence; understanding practice; developing and testing interventions for practice change; and building capacity for knowledge translation in neurotrauma. The program uses a range of different methods and study designs, including: an evidence fellowship program; conduct of and training in systematic reviews; mixed method study designs to describe and understand factors that influence current practices (e.g., semi-structured interviews and surveys); theory-based methods to develop targeted interventions aiming to change practice; a cluster randomised trial to test the effectiveness of a targeted theory-informed intervention; stakeholder involvement activities; and knowledge translation events such as consensus conferences. PMID:22866892

  9. Improving the Understanding of Psychological Factors Contributing to Horse-Related Accident and Injury: Context, Loss of Focus, Cognitive Errors and Rigidity.

    PubMed

    DeAraugo, Jodi; McLaren, Suzanne; McManus, Phil; McGreevy, Paul D

    2016-01-01

    While the role of the horse in riding hazards is well recognised, little attention has been paid to the role of specific theoretical psychological processes of humans in contributing to and mitigating risk. The injury, mortality or compensation claim rates for participants in the horse-racing industry, veterinary medicine and equestrian disciplines provide compelling evidence for improving risk mitigation models. There is a paucity of theoretical principles regarding the risk of injury and mortality associated with human-horse interactions. In this paper we introduce and apply the four psychological principles of context, loss of focus, global cognitive style and the application of self as the frame of reference as a potential approach for assessing and managing human-horse risks. When these principles produce errors that are combined with a rigid self-referenced point, it becomes clear how rapidly risk emerges and how other people and animals may repeatedly become at risk over time. Here, with a focus on the thoroughbred racing industry, veterinary practice and equestrian disciplines, we review the merits of contextually applied strategies, an evolving reappraisal of risk, flexibility, and focused specifics of situations that may serve to modify human behaviour and mitigate risk. PMID:26891333

  10. Significant Improvements in Cognitive Performance Post-Transcranial, Red/Near-Infrared Light-Emitting Diode Treatments in Chronic, Mild Traumatic Brain Injury: Open-Protocol Study

    PubMed Central

    Zafonte, Ross; Krengel, Maxine H.; Martin, Paula I.; Frazier, Judith; Hamblin, Michael R.; Knight, Jeffrey A.; Meehan, William P.; Baker, Errol H.

    2014-01-01

    Abstract This pilot, open-protocol study examined whether scalp application of red and near-infrared (NIR) light-emitting diodes (LED) could improve cognition in patients with chronic, mild traumatic brain injury (mTBI). Application of red/NIR light improves mitochondrial function (especially in hypoxic/compromised cells) promoting increased adenosine triphosphate (ATP) important for cellular metabolism. Nitric oxide is released locally, increasing regional cerebral blood flow. LED therapy is noninvasive, painless, and non-thermal (cleared by the United States Food and Drug Administration [FDA], an insignificant risk device). Eleven chronic, mTBI participants (26–62 years of age, 6 males) with nonpenetrating brain injury and persistent cognitive dysfunction were treated for 18 outpatient sessions (Monday, Wednesday, Friday, for 6 weeks), starting at 10 months to 8 years post- mTBI (motor vehicle accident [MVA] or sports-related; and one participant, improvised explosive device [IED] blast injury). Four had a history of multiple concussions. Each LED cluster head (5.35 cm diameter, 500 mW, 22.2 mW/cm2) was applied for 10 min to each of 11 scalp placements (13 J/cm2). LEDs were placed on the midline from front-to-back hairline; and bilaterally on frontal, parietal, and temporal areas. Neuropsychological testing was performed pre-LED, and at 1 week, and 1 and 2 months after the 18th treatment. A significant linear trend was observed for the effect of LED treatment over time for the Stroop test for Executive Function, Trial 3 inhibition (p=0.004); Stroop, Trial 4 inhibition switching (p=0.003); California Verbal Learning Test (CVLT)-II, Total Trials 1–5 (p=0.003); and CVLT-II, Long Delay Free Recall (p=0.006). Participants reported improved sleep, and fewer post-traumatic stress disorder (PTSD) symptoms, if present. Participants and family reported better ability to perform social, interpersonal, and occupational functions. These open-protocol data suggest

  11. Significant improvements in cognitive performance post-transcranial, red/near-infrared light-emitting diode treatments in chronic, mild traumatic brain injury: open-protocol study.

    PubMed

    Naeser, Margaret A; Zafonte, Ross; Krengel, Maxine H; Martin, Paula I; Frazier, Judith; Hamblin, Michael R; Knight, Jeffrey A; Meehan, William P; Baker, Errol H

    2014-06-01

    This pilot, open-protocol study examined whether scalp application of red and near-infrared (NIR) light-emitting diodes (LED) could improve cognition in patients with chronic, mild traumatic brain injury (mTBI). Application of red/NIR light improves mitochondrial function (especially in hypoxic/compromised cells) promoting increased adenosine triphosphate (ATP) important for cellular metabolism. Nitric oxide is released locally, increasing regional cerebral blood flow. LED therapy is noninvasive, painless, and non-thermal (cleared by the United States Food and Drug Administration [FDA], an insignificant risk device). Eleven chronic, mTBI participants (26-62 years of age, 6 males) with nonpenetrating brain injury and persistent cognitive dysfunction were treated for 18 outpatient sessions (Monday, Wednesday, Friday, for 6 weeks), starting at 10 months to 8 years post- mTBI (motor vehicle accident [MVA] or sports-related; and one participant, improvised explosive device [IED] blast injury). Four had a history of multiple concussions. Each LED cluster head (5.35 cm diameter, 500 mW, 22.2 mW/cm(2)) was applied for 10 min to each of 11 scalp placements (13 J/cm(2)). LEDs were placed on the midline from front-to-back hairline; and bilaterally on frontal, parietal, and temporal areas. Neuropsychological testing was performed pre-LED, and at 1 week, and 1 and 2 months after the 18th treatment. A significant linear trend was observed for the effect of LED treatment over time for the Stroop test for Executive Function, Trial 3 inhibition (p=0.004); Stroop, Trial 4 inhibition switching (p=0.003); California Verbal Learning Test (CVLT)-II, Total Trials 1-5 (p=0.003); and CVLT-II, Long Delay Free Recall (p=0.006). Participants reported improved sleep, and fewer post-traumatic stress disorder (PTSD) symptoms, if present. Participants and family reported better ability to perform social, interpersonal, and occupational functions. These open-protocol data suggest that placebo

  12. Dramatic rigidification of a peptide-decorated lamellar phase

    NASA Astrophysics Data System (ADS)

    Tsapis, N.; Urbach, W.; Ober, R.

    2001-04-01

    We have performed small-angle x-ray scattering on a lamellar (Lα) phase made of a nonionic surfactant (C12E4), decane, and water, after the insertion of a triblock peptide. The hydrophilic part of the peptide is rigid and organized in an α helix in the presence of membranes. Surface tension measurements and spectrofluorometry show that the peptide lies on the membrane surface. The Caillé parameter η and the smectic compressibility modulus B¯ decrease with peptide concentration, whereas the membrane bending rigidity κ increases threefold for mole ratio of peptide to surfactant as low as 5.2×10-4. The published models for rigid inclusions in membranes cannot account for this dramatic rigidification. However, experimental results are well fitted by a Heuristic renormalization of the membrane thickness.

  13. Reduced mitochondrial Ca2+ loading and improved functional recovery after ischemia-reperfusion injury in old vs. young guinea pig hearts

    PubMed Central

    Camara, Amadou K. S.; Heisner, James S.; Riess, Matthias L.; Aldakkak, Mohammed; Stowe, David F.

    2012-01-01

    Oxidative damage and impaired cytosolic Ca2+ concentration ([Ca2+]cyto) handling are associated with mitochondrial [Ca2+] ([Ca2+]mito) overload and depressed functional recovery after cardiac ischemia-reperfusion (I/R) injury. We hypothesized that hearts from old guinea pigs would demonstrate impaired [Ca2+]mito handling, poor functional recovery, and a more oxidized state after I/R injury compared with hearts from young guinea pigs. Hearts from young (∼4 wk) and old (>52 wk) guinea pigs were isolated and perfused with Krebs-Ringer solution (2.1 mM Ca2+ concentration at 37°C). Left ventricular pressure (LVP, mmHg) was measured with a balloon, and NADH, [Ca2+]mito (nM), and [Ca2+]cyto (nM) were measured by fluorescence with a fiber optic probe placed against the left ventricular free wall. After baseline (BL) measurements, hearts were subjected to 30 min global ischemia and 120 min reperfusion (REP). In old vs. young hearts we found: 1) percent infarct size was lower (27 ± 9 vs. 57 ± 2); 2) developed LVP (systolic-diastolic) was higher at 10 min (57 ± 11 vs. 29 ± 2) and 60 min (55 ± 10 vs. 32 ± 2) REP; 3) diastolic LVP was lower at 10 and 60 min REP (6 ± 3 vs. 29 ± 4 and 3 ± 3 vs. 21 ± 4 mmHg); 4) mean [Ca2+]cyto was higher during ischemia (837 ± 39 vs. 541 ± 39), but [Ca2+]mito was lower (545 ± 62 vs. 975 ± 38); 5) [Ca2+]mito was lower at 10 and 60 min REP (129 ± 2 vs. 293 ± 23 and 122 ± 2 vs. 234 ± 15); 6) reduced inotropic responses to dopamine and digoxin; and 7) NADH was elevated during ischemia in both groups and lower than BL during REP. Contrary to our stated hypotheses, old hearts showed reduced [Ca2+]mito, decreased infarction, and improved basal mechanical function after I/R injury compared with young hearts; no differences were noted in redox state due to age. In this model, aging-associated protection may be linked to limited [Ca2+]mito loading after I/R injury despite higher [Ca2+]cyto load during ischemia in old vs. young hearts

  14. Neurological injuries and extracorporeal membrane oxygenation: the challenge of the new ECMO era.

    PubMed

    Martucci, Gennaro; Lo Re, Vincenzina; Arcadipane, Antonio

    2016-07-01

    Extracorporeal membrane oxygenation (ECMO) is a life-saving mechanical respiratory and/or circulatory support for potentially reversible severe heart or respiratory injury untreatable with conventional therapies. Thanks to the technical and management improvements the use of ECMO has increased dramatically in the last few years. Data in the literature show a progressive increase in the overall outcome. Considering the improving survival rate of patients on ECMO, and the catastrophic effect of neurological injuries in such patients, the topic of neurological damage during the ICU stay in ECMO is gaining importance. We present a case series of six neurological injuries that occurred in 1 year during the ECMO run or after the ECMO weaning. In each case the neurological complication had a dramatic effect: ranging from brain death to prolonged ICU stay and long term disability. This case series has an informative impact for the multidisciplinary teams treating ECMO patients because of its heterogeneity in pathogenesis and clinical manifestation: cerebral hemorrhage, ischemic stroke due to cerebral fat embolism, acute disseminated encephalomyelitis due to H1N1 Influenza. In our ECMO hub we started strict neurological monitoring involving intensivists, a neurologist and our radiology service, but neurological complications are still an insidious diagnosis and treatment. Considering several possible neurological injuries may help reduce delay in diagnosis and speed rehabilitation. PMID:26895322

  15. Improved vision in forensic documentation: forensic 3D/CAD-supported photogrammetry of bodily injury external surfaces combined with volumetric radiologic scanning of bodily injury internal structures provides more investigative leads and stronger forensic evidence

    NASA Astrophysics Data System (ADS)

    Thali, Michael J.; Braun, Marcel; Kneubuehl, Beat P.; Brueschweiler, Walter; Vock, Peter; Dirnhofer, Richard

    2000-05-01

    In the field of the documentation of forensics-relevant injuries, from the reconstructive point of view, the Forensic, 3D/CAD-supported Photometry plays an important role; particularly so when a detailed 3D reconstruction is vital. This was demonstrated with an experimentally-produced 'injury' to a head model, the 'skin-skull-brain model'. The injury-causing instrument, drawn from a real forensic case, was a specifically formed weapon.

  16. [Tracheal rupture--a rare and dramatic emergency].

    PubMed

    Sobiegalla, M; von Hintzenstern, U; Weidenbecher, M; Rupprecht, H

    2003-01-01

    A tracheal tear requires fast and proper treatment. A 55-year-old man working in a sewage pipe slipped and hit his neck on the edge of a concrete ring. The patient showed the following symptoms: cervical bruising, neck emphysema and increasing dyspnea. After several unsuccessful attempts to intubate the patient, a necklace incision was made immediately at the scene, under the suspected diagnosis of a torn trachea. A finger was used to look for the lower tracheal stump lying in the mediastinum. The lower stump was then intubated. In the hospital, an end-to-end anastomosis of the trachea as well as tracheotomy were performed on the patient. Because of the fracture of the larynx, an endolaryngeal stent was used to stabilize the lumen. Due to an injury to both laryngeal nerves, the patient suffered from dysphagea, whispered speech and dyspnea on minimal exertion as long-term side-effects. A lateralization of the vocal cord was made eight months later. Because of the quick assessment of the situation and proper treatment of the patient at the site of the accident, the patient was able to survive the injury. PMID:12872541

  17. Sitting Tai Chi Improves the Balance Control and Muscle Strength of Community-Dwelling Persons with Spinal Cord Injuries: A Pilot Study

    PubMed Central

    Tsang, William W. N.; Gao, Kelly L.; Chan, K. M.; Purves, Sheila; Macfarlane, Duncan J.; Fong, Shirley S. M.

    2015-01-01

    Objective. To investigate the effects of sitting Tai Chi on muscle strength, balance control, and quality of life (QOL) among survivors with spinal cord injuries (SCI). Methods. Eleven SCI survivors participated in the sitting Tai Chi training (90 minutes/session, 2 times/week for 12 weeks) and eight SCI survivors acted as controls. Dynamic sitting balance was evaluated using limits of stability test and a sequential weight shifting test in sitting. Handgrip strength was also tested using a hand-held dynamometer. QOL was measured using the World Health Organization's Quality of Life Scale. Results. Tai Chi practitioners achieved significant improvements in their reaction time (P = 0.042); maximum excursion (P = 0.016); and directional control (P = 0.025) in the limits of stability test after training. In the sequential weight shifting test, they significantly improved their total time to sequentially hit the 12 targets (P = 0.035). Significant improvement in handgrip strength was also found among the Tai Chi practitioners (P = 0.049). However, no significant within and between-group differences were found in the QOL outcomes (P > 0.05). Conclusions. Twelve weeks of sitting Tai Chi training could improve the dynamic sitting balance and handgrip strength, but not QOL, of the SCI survivors. PMID:25688276

  18. Sitting tai chi improves the balance control and muscle strength of community-dwelling persons with spinal cord injuries: a pilot study.

    PubMed

    Tsang, William W N; Gao, Kelly L; Chan, K M; Purves, Sheila; Macfarlane, Duncan J; Fong, Shirley S M

    2015-01-01

    Objective. To investigate the effects of sitting Tai Chi on muscle strength, balance control, and quality of life (QOL) among survivors with spinal cord injuries (SCI). Methods. Eleven SCI survivors participated in the sitting Tai Chi training (90 minutes/session, 2 times/week for 12 weeks) and eight SCI survivors acted as controls. Dynamic sitting balance was evaluated using limits of stability test and a sequential weight shifting test in sitting. Handgrip strength was also tested using a hand-held dynamometer. QOL was measured using the World Health Organization's Quality of Life Scale. Results. Tai Chi practitioners achieved significant improvements in their reaction time (P = 0.042); maximum excursion (P = 0.016); and directional control (P = 0.025) in the limits of stability test after training. In the sequential weight shifting test, they significantly improved their total time to sequentially hit the 12 targets (P = 0.035). Significant improvement in handgrip strength was also found among the Tai Chi practitioners (P = 0.049). However, no significant within and between-group differences were found in the QOL outcomes (P > 0.05). Conclusions. Twelve weeks of sitting Tai Chi training could improve the dynamic sitting balance and handgrip strength, but not QOL, of the SCI survivors. PMID:25688276

  19. HMGB1 promotes EC angiogenic behavior in vitro and improves muscle perfusion in vivo in response to ischemic injury

    PubMed Central

    Sachdev, Ulka; Cui, Xiangdong; Hong, Guiying; Namkoong, Seung; Karlsson, Jenny M.; Baty, Catherine J.; Tzeng, Edith

    2013-01-01

    Objectives The angiogenic drive in skeletal muscle ischemia remains poorly understood. Innate inflammatory pathways are activated during tissue injury and repair, suggesting that this highly conserved pathway may be involved in ischemia-induced angiogenesis. We hypothesize that one of the endogenous ligands for innate immune signaling, high mobility group box 1 (HMGB1), in combination with autophagic responses to hypoxia or nutrient deprivation plays an important role in angiogenesis. Methods Human dermal microvascular endothelial cells (EC) were cultured in normoxia or hypoxia (1% oxygen). Immunocytochemical analysis of HMGB1 subcellular localization, evaluation of tube formation, and Western blot analysis of myotubule light-chain 3 (LC3I) conversion to LC3II, as a marker of autophagy, were conducted. 3-methyladenine (3MA), chloroquine (CQ), or rapamycin were administered to inhibit or promote autophagy, respectively. In vivo, a murine hind-limb ischemia model was performed. Muscle samples were collected at 4 hours to evaluate for nuclear HMGB1 and at 14 days to examine endothelial density. Perfusion recovery in the hind-limbs was calculated by laser Doppler perfusion imaging (LDPI). Results Hypoxic EC exhibited reduced nuclear HMGB1 staining compared with normoxic cells (mean fluorescence intensity 186.9 ± 17.1 vs. 236.0 ± 1.6, respectively, P = 0.01) with a concomitant increase in cytosolic staining. HMGB1 treatment of ECs enhanced tube formation, an angiogenic phenotype of ECs. Neutralization of endogenous HMGB1 markedly impaired tube formation and inhibited LC3II formation. Inhibition of autophagy with 3MA or CQ abrogated tube formation while its induction with rapamycin enhanced tubing and promoted HMGB1 translocation. In vivo, ischemic skeletal muscle showed reduced the numbers of HMGB1 positive myocyte nuclei compared with nonischemic muscle (34.9% ± 1.9 vs. 51.7% ± 2.0, respectively, P<0.001). Injection of HMGB1 into ischemic hind-limbs increased

  20. Lisfranc injuries.

    PubMed

    Welck, M J; Zinchenko, R; Rudge, B

    2015-04-01

    Lisfranc injuries are commonly asked about in FRCS Orthopaedic trauma vivas. The term "Lisfranc injury" strictly refers to an injury where one or more of the metatarsals are displaced from the tarsus. The term is more commonly used to describe an injury to the midfoot centred on the 2nd tarsometatarsal joint. The injury is named after Jacques Lisfranc de St. Martin (1790-1847), a French surgeon and gynaecologist who first described the injury in 1815. 'Lisfranc injury' encompasses a broad spectrum of injuries, which can be purely ligamentous or involve the osseous and articular structures. They are often difficult to diagnose and treat, but if not detected and appropriately managed they can cause long-term disability. This review outlines the anatomy, epidemiology, classification, investigation and current evidence on management of this injury. PMID:25543185

  1. Pancreatic injury.

    PubMed

    Ahmed, Nasim; Vernick, Jerome J

    2009-12-01

    Injury to the pancreas, because of its retroperitoneal location, is a rare occurrence, most commonly seen with penetrating injuries (gun shot or stab wounds). Blunt trauma to the pancreas accounts for only 25% of the cases. Pancreatic injuries are associated with high morbidity and mortality due to accompanying vascular and duodenal injuries. Pancreatic injuries are not always easy to diagnose resulting in life threatening complications. Physical examination as well as serum amylase is not diagnostic following blunt trauma. Computed tomography (CT) scan can delineate the injury or transaction of the pancreas. Endoscopic retrograde pancreaticography (ERCP) is the main diagnostic modality for evaluation of the main pancreatic duct. Unrecognized ductal injury leads to pancreatic pseudocyst, fistula, abscess, and other complications. Management depends upon the severity of the pancreatic injury as well as associated injuries. Damage control surgery in hemodynamic unstable patients reduces morbidity and mortality. PMID:20016434

  2. DBS in the basolateral amygdala improves symptoms of autism and related self-injurious behavior: a case report and hypothesis on the pathogenesis of the disorder

    PubMed Central

    Sturm, Volker; Fricke, Oliver; Bührle, Christian P.; Lenartz, Doris; Maarouf, Mohammad; Treuer, Harald; Mai, Jürgen K.; Lehmkuhl, Gerd

    2013-01-01

    We treated a 13-year-old boy for life-threatening self-injurious behavior (SIB) and severe Kanner's autism with deep brain stimulation (DBS) in the amygdaloid complex as well as in the supra-amygdaloid projection system. Two DBS-electrodes were placed in both structures of each hemisphere. The stimulation contacts targeted the paralaminar, the basolateral (BL), the central amygdala as well as the supra-amygdaloid projection system. DBS was applied to each of these structures, but only stimulation of the BL part proved effective in improving SIB and core symptoms of the autism spectrum in the emotional, social, and even cognitive domains over a follow up of now 24 months. These results, which have been gained for the first time in a patient, support hypotheses, according to which the amygdala may be pivotal in the pathogeneses of autism and point to the special relevance of the BL part. PMID:23346052

  3. Rutin improves endotoxin-induced acute lung injury via inhibition of iNOS and VCAM-1 expression.

    PubMed

    Huang, Yi-Chun; Horng, Chi-Ting; Chen, Shyan-Tarng; Lee, Shiuan-Shinn; Yang, Ming-Ling; Lee, Chien-Ying; Kuo, Wu-Hsien; Yeh, Chung-Hsin; Kuan, Yu-Hsiang

    2016-02-01

    Endotoxins exist anywhere including in water pools, dust, humidifier systems, and machining fluids. The major causal factor is endotoxins in many serious diseases, such as fever, sepsis, multi-organ failure, meningococcemia, and severe morbidities like neurologic disability, or hearing loss. Endotoxins are also called lipopolysaccharide (LPS) and are important pathogens of acute lung injury (ALI). Rutin has potential beneficial effects including anti-inflammation, antioxidation, anti-hyperlipidemia, and anti-platelet aggregation. Pre-treatment with rutin inhibited LPS-induced neutrophil infiltration in the lungs. LPS-induced expression of vascular cell adhesion molecule (VCAM)-1 and inducible nitric oxide synthase (iNOS) was suppressed by rutin, but there was no influence on expression of intercellular adhesion molecule-1 and cyclooxygenase-2. In addition, activation of the nuclear factor (NF)κB was reduced by rutin. Furthermore, we found that the inhibitory concentration of rutin on expression of VCAM-1 and iNOS was similar to NFκB activation. In conclusion, rutin is a potential protective agent for ALI via inhibition of neutrophil infiltration, expression of VCAM-1 and iNOS, and NFκB activation. PMID:25080890

  4. Chrysin, a PPAR-γ agonist improves myocardial injury in diabetic rats through inhibiting AGE-RAGE mediated oxidative stress and inflammation.

    PubMed

    Rani, Neha; Bharti, Saurabh; Bhatia, Jagriti; Nag, T C; Ray, Ruma; Arya, Dharamvir Singh

    2016-04-25

    AGE-RAGE interaction mediated oxidative stress and inflammation is the key mechanism involved in the pathogenesis of cardiovascular disease in diabetes. Inhibition of AGE-RAGE axis by several PPAR-γ agonists has shown positive results in ameliorating cardio-metabolic disease conditions. Chrysin, a natural flavonoid has shown to possess PPAR-γ agonist activity along with antioxidant and anti-inflammatory effect. Therefore, the present study was designed to evaluate the effect of chrysin in isoproterenol-induced myocardial injury in diabetic rats. In male albino Wistar rats, diabetes was induced by single injection of streptozotocin (70 mg/kg, i.p.). After confirmation of the diabetes, rats were treated with vehicle (1.5 mL/kg, p.o.), chrysin (60 mg/kg, p.o.) or PPAR-γ antagonist GW9662 (1 mg/kg, i.p.) for 28 days. Simultaneously, on 27th and 28th day myocardial injury was induced by isoproterenol (85 mg/kg, s.c.). Chrysin significantly ameliorated cardiac dysfunction as reflected by improved MAP, ±LVdP/dtmax and LVEDP in diabetic rats. This improvement was associated with increased PPAR-γ expression and reduced RAGE expression in diabetic rats. Chrysin significantly decreased inflammation through inhibiting NF-κBp65/IKK-β expression and TNF-α level. Additionally, chrysin significantly reduced apoptosis as indicated by augmented Bcl-2 expression and decreased Bax and caspase-3 expressions. Furthermore, chrysin inhibited nitro-oxidative stress by normalizing the alteration in 8-OHdG, GSH, TBARS, NO and CAT levels and Nox4, MnSOD, eNOS and NT expressions. Co-administration of GW9662 significantly blunted the chrysin mediated cardioprotective effect as there was increase in oxidative stress, inflammation and apoptosis markers. Chrysin significantly ameliorated isoproterenol-induced myocardial injury in diabetic rats via PPAR-γ activation and inhibition of AGE-RAGE mediated oxidative stress and inflammation. PMID:26972669

  5. Basketball injuries.

    PubMed

    Newman, Joel S; Newberg, Arthur H

    2010-11-01

    Basketball injuries are most prevalent in the lower extremity, especially at the ankle and knee. Most basketball injuries are orthopedic in nature and commonly include ligament sprains, musculotendinous strains, and overuse injuries including stress fractures. By virtue of its excellent contrast resolution and depiction of the soft tissues and trabecular bone, magnetic resonance imaging has become the principal modality for evaluating many basketball injuries. In this article, commonly encountered basketball injuries and their imaging appearances are described. The epidemiology of basketball injuries across various age groups and levels of competition and between genders are reviewed. PMID:21094400

  6. A season of football injuries.

    PubMed

    Stokes, M A; McKeever, J A; McQuillan, R F; O'Higgins, N J

    1994-06-01

    All rugby and soccer players presenting to the Accident & Emergency department during the football season 1992-1993 (a total of 871) were prospectively studied to compare the injuries sustained in the two sports. The nature and site of injury, treatment required, age, fitness, experience and position of the player, situation giving rise to injury, and medical attention at the grounds were all analysed. The results show that rugby and soccer players had the same number of injuries, and while there were some differences in the nature of the injuries, there was no difference in overall severity. Rugby flankers and soccer goalkeepers are particularly at risk. Competitive matches produce more injuries than training sessions. Experience or fitness did not appear to be a factor and 45% of rugby injuries and 15% of soccer injuries were from school matches. Law changes (e.g. the rugby scrum and the use of gum-shields) have reduced some injuries, but other areas (e.g. jumping for the ball in soccer, rucks and mauls in rugby) also warrant consideration. There was one death, but no spinal cord injuries. Medical attention at the grounds was limited. Rugby injuries, therefore, do not appear to be more numerous or severe than soccer injuries. Law changes have been of benefit but they need to be enforced and perhaps more should be considered. Medical attention at sports grounds could be improved and Registers of injuries kept by the sporting bodies would be of benefit. PMID:8050871

  7. Mountain biking injuries: an update.

    PubMed

    Kronisch, Robert L; Pfeiffer, Ronald P

    2002-01-01

    This article reviews the available literature regarding injuries in off-road bicyclists. Recent progress in injury research has allowed the description of several patterns of injury in this sport. Mountain biking remains popular, particularly among young males, although sales and participation figures have decreased in the last several years. Competition in downhill racing has increased, while cross-country racing has decreased somewhat in popularity. Recreational riders comprise the largest segment of participants, but little is known about the demographics and injury epidemiology of noncompetitive mountain cyclists. Most mountain bikers participating in surveys reported a history of previous injuries, but prospective studies conducted at mountain bike races have found injury rates of <1%. The most common mechanism of injury involves a forward fall over the handlebars, usually while riding downhill, which can result in direct trauma to the head, torso and upper extremities. A variety of factors can be associated with this type of fall, including trail surface irregularities, mechanical failures and loss of control. In mountain bike racing the risk of injury may be higher for women than men. Minor injuries such as abrasions and contusions occur frequently, but are usually of little consequence. Fractures usually involve the torso or upper extremities, and shoulder injuries are common. Head and face injuries are not always prevented by current helmet designs. Fatal injuries are rare but have been reported. Improvements in safety equipment, rider training and racecourse design are suggested injury prevention measures. The authors encourage continued research in this sport. PMID:12076178

  8. A dramatic effect of oxygen on protection of human cells against γ-radiation by lycopene.

    PubMed

    Boehm, Fritz; Edge, Ruth; Truscott, Terence George; Witt, Christian

    2016-04-01

    Reducing radiation damage is important and dietary antioxidants that can protect cells from such damage are of value. Dietary lycopene, a carotenoid found in tomatoes, protects human lymphoid cell membranes from damage by γ-radiation. We report that such protective effects are remarkably reduced as the oxygen concentration increases - near zero at 100% oxygen from fivefold protection at 20% oxygen and, dramatically, from 50-fold protection at 0% oxygen. Such huge differences imply that under higher oxygen concentrations lycopene could lead to improved cancer therapy using γ-radiation. The cells are not efficiently protected from the superoxide radical by lycopene. Noncellular studies suggest molecular mechanisms for the oxygen effect. PMID:26991327

  9. Shoshin Beriberi With Low Cardiac Output and Hemodynamic Deterioration Treated Dramatically by Thiamine Administration.

    PubMed

    Imamura, Teruhiko; Kinugawa, Koichiro

    2015-01-01

    "Shoshin beriberi", which is a fulminant form of cardiovascular beriberi accompanied by hemodynamic deterioration with high cardiac output and decreased systemic blood pressure, caused by thiamine deficiency due to alcoholic abuse or malnutrition, is often difficult to address because of its rarity and non-specific symptoms. We here present a patient with a history of alcoholic abuse who had suffered hemodynamic deterioration with extremely low cardiac output refractory to extracorporeal membrane oxygenation and intravenous catecholamine support, which was improved dramatically by bolus intravenous thiamine administration. Such a type with low cardiac output would be the most severe form of Shoshin beriberi, and cannot be rescued without diagnostic administration of thiamine. PMID:26346515

  10. The Relationship between Dramatic Play and Self-Concept in Middle Class Kindergarten Children.

    ERIC Educational Resources Information Center

    Gootman, Marilyn Eisenstadt

    This study attempted to determine the relationships between the dramatic play of children aged three to seven and their self-concept; between dramatic play and two components of self-concept--self-esteem and identification with friends; between dramatic play ability and self-concept; and between dramatic play and the teacher's attitude toward…

  11. Implementation of a Shoulder Soft Tissue Injury Triage Service in a UK NHS Teaching Hospital Improves Time to Surgery for Acute Rotator Cuff Tears.

    PubMed Central

    Bateman, Marcus; Davies-Jones, Gareth; Tambe, Amol; Clark, David I

    2016-01-01

    others. 7 missed fractures were identified. 12 patients subsequently underwent rotator cuff repair surgery, 10 GHJ stabilisation, and 1 ACJ stabilisation. Mean referral time to first clinical assessment improved from 37 days to 8 days. For rotator cuff repair: mean referral to surgery time was 86 days compared with 115 days on the old pathway. 58% of patients underwent surgery within 90 days of injury compared with 20% previously. Our new service resulted in surgical repair of traumatic rotator cuff tears 29 days faster than the traditional system with an extra 38% of patients having surgery within 90 days of injury - a benchmark thought to improve outcome. Future work will aim to improve this percentage further and include long term patient follow up of outcome measures after surgery.

  12. Implementation of a Shoulder Soft Tissue Injury Triage Service in a UK NHS Teaching Hospital Improves Time to Surgery for Acute Rotator Cuff Tears.

    PubMed

    Bateman, Marcus; Davies-Jones, Gareth; Tambe, Amol; Clark, David I

    2016-01-01

    others. 7 missed fractures were identified. 12 patients subsequently underwent rotator cuff repair surgery, 10 GHJ stabilisation, and 1 ACJ stabilisation. Mean referral time to first clinical assessment improved from 37 days to 8 days. For rotator cuff repair: mean referral to surgery time was 86 days compared with 115 days on the old pathway. 58% of patients underwent surgery within 90 days of injury compared with 20% previously. Our new service resulted in surgical repair of traumatic rotator cuff tears 29 days faster than the traditional system with an extra 38% of patients having surgery within 90 days of injury - a benchmark thought to improve outcome. Future work will aim to improve this percentage further and include long term patient follow up of outcome measures after surgery. PMID:27335643

  13. Increased Trauma Center Volume Is Associated With Improved Survival After Severe Injury: Results of a Resuscitation Outcomes Consortium Study

    PubMed Central

    Minei, Joseph P.; Fabian, Timothy C.; Guffey, Danielle M.; Newgard, Craig D.; Bulger, Eileen M.; Brasel, Karen J.; Sperry, Jason L.; MacDonald, Russell D.

    2014-01-01

    Structured Abstract OBJECTIVE The Resuscitation Outcomes Consortium (ROC) is a network of 11 centers and 60 hospitals conducting emergency care research. For many procedures, high volume centers demonstrate superior outcomes versus low volume centers. This remains controversial for trauma center outcomes. This study investigated the relationship of trauma center volume on outcome. METHODS This study was a secondary analysis of prospectively collected data from the ROC multicenter out-of-hospital Hypertonic Saline Trial in patients with GCS ≤ 8 (traumatic brain injury [TBI]) or SBP ≤ 90 and pulse ≥ 110 (shock). Regression analyses evaluated associations between trauma volume and the following outcomes: 24 hour mortality, 28 day mortality, ventilator free days (VFD), Multiple Organ Dysfunction Scale (MODS) incidence, worst MODS score, and poor 6 month Glasgow outcome scale extended. RESULTS 2070 patients were analyzed: 1251 in the TBI cohort and 819 in the shock cohort. Overall, 24-hour and 28-day mortality were 16% and 25%, respectively. For every increase of 500 trauma center admissions, there was a 7% decreased odds of both 24-hour and 28-day mortalities for all patients. As trauma center volume increased, non-organ dysfunction complications increased, VFD increased and worst MODS score decreased. The associations with higher trauma center volume were similar for the TBI cohort, including better neurologic outcomes at 6 months, but not for the shock cohort. CONCLUSIONS Increased trauma center volume was associated with increased survival, more ventilator free days and less severe organ failure. Trauma system planning and implementation should avoid unnecessary duplication of services. PMID:25115421

  14. Anions dramatically enhance proton transfer through aqueous interfaces

    PubMed Central

    Mishra, Himanshu; Enami, Shinichi; Nielsen, Robert J.; Hoffmann, Michael R.; Goddard, William A.; Colussi, Agustín J.

    2012-01-01

    Proton transfer (PT) through and across aqueous interfaces is a fundamental process in chemistry and biology. Notwithstanding its importance, it is not generally realized that interfacial PT is quite different from conventional PT in bulk water. Here we show that, in contrast with the behavior of strong nitric acid in aqueous solution, gas-phase HNO3 does not dissociate upon collision with the surface of water unless a few ions (> 1 per 106 H2O) are present. By applying online electrospray ionization mass spectrometry to monitor in situ the surface of aqueous jets exposed to HNO3(g) beams we found that production increases dramatically on > 30-μM inert electrolyte solutions. We also performed quantum mechanical calculations confirming that the sizable barrier hindering HNO3 dissociation on the surface of small water clusters is drastically lowered in the presence of anions. Anions electrostatically assist in drawing the proton away from lingering outside the cluster, whose incorporation is hampered by the energetic cost of opening a cavity therein. Present results provide both direct experimental evidence and mechanistic insights on the counterintuitive slowness of PT at water-hydrophobe boundaries and its remarkable sensitivity to electrostatic effects. PMID:22689964

  15. [A mixed germ cell tumor that underwent dramatic size changes].

    PubMed

    Kuwayama, Kazuyuki; Takai, Hiroki; Nishiyama, Akira; Hirai, Satoshi; Yokosuka, Kimihiko; Toi, Hiroyuki; Hirano, Kazuhiro; Matsubara, Shunji; Uno, Masaaki; Nishimura, Hirotake

    2014-09-01

    This report describes a mixed germ cell tumor that underwent dramatic size changes. A 12-year-old boy presented to our hospital with a headache that had persisted for two months. Initial magnetic resonance imaging (MRI) revealed a pineal tumor and hydrocephalus. The patient required external ventricular drainage and underwent two endoscopic biopsies. His evaluation involved a total of nine computed tomography (CT) scans prior to the second biopsy;the tumor size had decreased before the second endoscopic biopsy. The tumor consisted of both a germinoma and a teratoma component. The patient was treated with three courses of carboplatin-etoposide (CBDCA-VP) chemotherapy and whole-ventricle radiotherapy (32.1 Gy). However, during the adjuvant therapy, the tumor size increased, necessitating total tumor resection. We speculate that the tumor's initial size reduction was caused by leakage of the cyst component and exposure to the brain CT irradiation. The tumor's subsequent increase in size was due to the recollection of the cystic components and intracranial growing teratoma syndrome (iGTS). Therefore, frequent brain CTs and angiography should be avoided before definitive pathological diagnosis is achieved. Further, the tumor size should be considered, with surgical resection being performed at the optimal time. PMID:25179200

  16. Unusual Dramatic Surface Restructuring of Silicon Substrate during Epitaxy

    NASA Astrophysics Data System (ADS)

    Gupta, Tanya; Steingart, Daniel; Hannon, James; Princeton University Collaboration; IBM Collaboration

    2015-03-01

    Interfacial strain is unavoidable in heteroepitaxial growth and can have a profound impact on the morphology and properties of thin films. In fact, ``engineering'' thin-film strain is a critical component in many advanced technologies. For example, straining the silicon in advanced CMOS devices can increase the device speed by as much as 90 percent.order to control interfacial strain, its effects on growth must be understood. The common picture is that the growth substrate is essentially passive: its role is to provide the lattice mismatch that the growing film must respond to. As the film grows thicker, the stress in the film evolves, which can lead to morphological changes in the film, e.g. dislocations, or a change in growth mode from 2D, planar growth to 3D, quantum dot growth., in both of these examples, the action is in the growing film. In this work we describe a growth system that behaves in a completely unexpected manner that does not fit into this conventional picture. Interfacial strain that accompanies the growth of SiC nanoparticles is relieved by a dramatic restructuring of the *substrate* rather than the nanoparticles. The growth of nanoparticles induces a massive change in the substrate. In situ measurements of the Si mound formation was done with the use of LEEM. Using a simple, illustrative model with parameters taken from the literature, we show that the shapes and heights of the mounds are consistent with a strain-driven formation mechanism.

  17. Polyanhydride Nanoparticle Delivery Platform Dramatically Enhances Killing of Filarial Worms

    PubMed Central

    Binnebose, Andrea M.; Haughney, Shannon L.; Martin, Richard; Imerman, Paula M.; Narasimhan, Balaji; Bellaire, Bryan H.

    2015-01-01

    Filarial diseases represent a significant social and economic burden to over 120 million people worldwide and are caused by endoparasites that require the presence of symbiotic bacteria of the genus Wolbachia for fertility and viability of the host parasite. Targeting Wolbachia for elimination is a therapeutic approach that shows promise in the treatment of onchocerciasis and lymphatic filariasis. Here we demonstrate the use of a biodegradable polyanhydride nanoparticle-based platform for the co-delivery of the antibiotic doxycycline with the antiparasitic drug, ivermectin, to reduce microfilarial burden and rapidly kill adult worms. When doxycycline and ivermectin were co-delivered within polyanhydride nanoparticles, effective killing of adult female Brugia malayi filarial worms was achieved with approximately 4,000-fold reduction in the amount of drug used. Additionally the time to death of the macrofilaria was also significantly reduced (five-fold) when the anti-filarial drug cocktail was delivered within polyanhydride nanoparticles. We hypothesize that the mechanism behind this dramatically enhanced killing of the macrofilaria is the ability of the polyanhydride nanoparticles to behave as a Trojan horse and penetrate the cuticle, bypassing excretory pumps of B. malayi, and effectively deliver drug directly to both the worm and Wolbachia at high enough microenvironmental concentrations to cause death. These provocative findings may have significant consequences for the reduction in the amount of drug and the length of treatment required for filarial infections in terms of patient compliance and reduced cost of treatment. PMID:26496201

  18. Polyanhydride Nanoparticle Delivery Platform Dramatically Enhances Killing of Filarial Worms.

    PubMed

    Binnebose, Andrea M; Haughney, Shannon L; Martin, Richard; Imerman, Paula M; Narasimhan, Balaji; Bellaire, Bryan H

    2015-01-01

    Filarial diseases represent a significant social and economic burden to over 120 million people worldwide and are caused by endoparasites that require the presence of symbiotic bacteria of the genus Wolbachia for fertility and viability of the host parasite. Targeting Wolbachia for elimination is a therapeutic approach that shows promise in the treatment of onchocerciasis and lymphatic filariasis. Here we demonstrate the use of a biodegradable polyanhydride nanoparticle-based platform for the co-delivery of the antibiotic doxycycline with the antiparasitic drug, ivermectin, to reduce microfilarial burden and rapidly kill adult worms. When doxycycline and ivermectin were co-delivered within polyanhydride nanoparticles, effective killing of adult female Brugia malayi filarial worms was achieved with approximately 4,000-fold reduction in the amount of drug used. Additionally the time to death of the macrofilaria was also significantly reduced (five-fold) when the anti-filarial drug cocktail was delivered within polyanhydride nanoparticles. We hypothesize that the mechanism behind this dramatically enhanced killing of the macrofilaria is the ability of the polyanhydride nanoparticles to behave as a Trojan horse and penetrate the cuticle, bypassing excretory pumps of B. malayi, and effectively deliver drug directly to both the worm and Wolbachia at high enough microenvironmental concentrations to cause death. These provocative findings may have significant consequences for the reduction in the amount of drug and the length of treatment required for filarial infections in terms of patient compliance and reduced cost of treatment. PMID:26496201

  19. Dramatic long-term X-ray variability in AGNs

    NASA Astrophysics Data System (ADS)

    Moran, Edward C.

    2016-04-01

    Dramatic X-ray and optical variability on ˜ 10 year timescales has been discovered recently in a handful of quasars, which may provide important new insight into the issue of how luminous AGNs are fueled. We have assembled a new sample of extremely variable X-ray sources from archival Einstein and ROSAT data that could increase substantially the number of such objects known. The sources in our sample varied in X-ray flux by at least a factor of 7-8 over a 10-year span, and most exhibited significantly larger variability amplitudes (10 to over 100). We present the details of how our sample was assembled and preliminary results regarding the identifications, properties, and X-ray histories of the objects. Although a heterogeneous population is expected, some sources in the sample are associated with broad-line AGNs, including a radio-quiet quasar at z = 1.3 that decreased in X-ray luminosity by a factor of 40.

  20. New therapies for hereditary angioedema: disease outlook changes dramatically.

    PubMed

    Frank, Michael M; Jiang, Haixiang

    2008-01-01

    Hereditary angioedema (HAE) is an autosomal dominant disease associated with episodic attacks of nonpitting edema that may affect any external or mucosal body surface. Attacks most often affect the extremities, causing local swelling, the GI tract, leading to severe abdominal pain, and the mouth and throat, at times causing asphyxiation. Most patients with HAE have low levels of the plasma serine protease inhibitor C1 inhibitor. The edema in these patients is caused by unregulated generation of bradykinin. Effective chronic therapy of patients with impeded androgens or plasmin inhibitors has been available for decades, but in the United States, we do not have therapy for acute attacks. Five companies have completed or are in the process of conducting phase 3 clinical trials, double-blind, placebo-controlled studies of products designed to terminate acute attacks or to be used in prophylaxis. Two companies, Lev Pharmaceuticals and CSL Behring, have preparations of C1 inhibitor purified from plasma that have been used in Europe for decades (trade names Cinryze and Berinert P, respectively). One company, Pharming, has developed a recombinant C1 inhibitor preparation. One company, Dyax, is testing a kallikrein inhibitor (ecallantide), and one company, Jerini, is completing testing of a bradykinin type 2 receptor antagonist (Icatibant). Although little has been published thus far, all of these products may prove effective. It is likely that HAE treatment will change dramatically within the next few years. PMID:18206518

  1. A Dramatic Change in the Polarization of V Hya

    NASA Astrophysics Data System (ADS)

    Johnson, J. J.

    1993-12-01

    The unusual carbon star, V Hydrae, is a semiregular variable with a period of 530 days superimposed on a longer, large amplitude period of 6500 days. It has been observed to have bipolar CO outflow (Kahane et al., 1988), and is believed to be an early precursor of a bipolar planetary nebula (Tsuji et al., 1988). In an earlier program (Johnson and Jones, 1991), we observed V Hya with a broad-band polarimeter. We found that it was intrinsically polarized with P on the order of 0.7% at V. We re-observed V Hya at the University of Wisconsin's Pine Bluff Observatory using a spectropolarimeter, and found that the polarization has increased dramatically to 10% at V, with a near 90 degree rotation in position angle from the earlier observation. Near the epoch when we observed V Hya for the second time, it was reported by T. L. Evans that V Hya was experiencing a decline in visible light. The infrared colors have also become redder, suggesting a possible dust ejection episode. V Hya is expected to reach a deep minimum sometime in 1994. We combine our polarimetric observations with our infrared and optical photometry and optical spectroscopy to propose a possible explanation for the polarimetric variations.

  2. Taming Self-Organization Dynamics to Dramatically Control Porous Architectures.

    PubMed

    Daly, Ronan; Sader, John E; Boland, John J

    2016-03-22

    We demonstrate templating of functional materials with unexpected and intricate micro- and nanostructures by controlling the condensation, packing, and evaporation of water droplets on a polymer solution. Spontaneous evaporation of a polymer solution induces cooling of the liquid surface and water microdroplet condensation from the ambient vapor. These droplets pack together and act as a template to imprint an entangled polymer film. This breath figure (BF) phenomenon is an example of self-organization that involves the long-range ordering of droplets. Equilibrium-based analysis provides many insights into contact angles and drop stability of individual drops, but the BF phenomenon remains poorly understood thus far, preventing translation to real applications. Here we investigate the dynamics of this phenomenon to separate out the competing influences and then introduce a modulation scheme to ultimately manipulate the water vapor-liquid equilibrium independently from the solvent evaporation. This approach to BF control provides insights into the mechanism, a rationale for microstructure design, and evidence for the benefits of dynamical control of self-organization systems. We finally present dramatically different porous architectures from this approach reminiscent of microscale Petri dishes, conical flasks, and test tubes. PMID:26828573

  3. Anions dramatically enhance proton transfer through aqueous interfaces.

    PubMed

    Mishra, Himanshu; Enami, Shinichi; Nielsen, Robert J; Hoffmann, Michael R; Goddard, William A; Colussi, Agustín J

    2012-06-26

    Proton transfer (PT) through and across aqueous interfaces is a fundamental process in chemistry and biology. Notwithstanding its importance, it is not generally realized that interfacial PT is quite different from conventional PT in bulk water. Here we show that, in contrast with the behavior of strong nitric acid in aqueous solution, gas-phase HNO(3) does not dissociate upon collision with the surface of water unless a few ions (> 1 per 10(6) H(2)O) are present. By applying online electrospray ionization mass spectrometry to monitor in situ the surface of aqueous jets exposed to HNO(3(g)) beams we found that NO(3)(-) production increases dramatically on > 30-μM inert electrolyte solutions. We also performed quantum mechanical calculations confirming that the sizable barrier hindering HNO(3) dissociation on the surface of small water clusters is drastically lowered in the presence of anions. Anions electrostatically assist in drawing the proton away from NO(3)(-) lingering outside the cluster, whose incorporation is hampered by the energetic cost of opening a cavity therein. Present results provide both direct experimental evidence and mechanistic insights on the counterintuitive slowness of PT at water-hydrophobe boundaries and its remarkable sensitivity to electrostatic effects. PMID:22689964

  4. Spinal injury

    MedlinePlus

    ... head. Alternative Names Spinal cord injury; SCI Images Skeletal spine Vertebra, cervical (neck) Vertebra, lumbar (low back) Vertebra, thoracic (mid back) Vertebral column Central nervous system Spinal cord injury Spinal anatomy Two person roll - ...

  5. Corneal injury

    MedlinePlus

    ... as sand or dust Ultraviolet injuries: Caused by sunlight, sun lamps, snow or water reflections, or arc- ... a corneal injury if you: Are exposed to sunlight or artificial ultraviolet light for long periods of ...

  6. Inhalation Injuries

    MedlinePlus

    ... you can inhale that can cause acute internal injuries. Particles in the air from fires and toxic ... and lung diseases worse. Symptoms of acute inhalation injuries may include Coughing and phlegm A scratchy throat ...

  7. Cycling injuries.

    PubMed Central

    Cohen, G. C.

    1993-01-01

    Bicycle-related injuries have increased as cycling has become more popular. Most injuries to recreational riders are associated with overuse or improper fit of the bicycle. Injuries to racers often result from high speeds, which predispose riders to muscle strains, collisions, and falls. Cyclists contact bicycles at the pedals, seat, and handlebars. Each is associated with particular cycling injuries. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:8471908

  8. Improvement of Mercuric Chloride-Induced Testis Injuries and Sperm Quality Deteriorations by Spirulina platensis in Rats

    PubMed Central

    El-Desoky, Gaber E.; Bashandy, Samir A.; Alhazza, Ibrahim M.; Al-Othman, Zeid A.; Aboul-Soud, Mourad A. M.; Yusuf, Kareem

    2013-01-01

    -induced testicular injuries and suggest some therapeutic potential in mammals. Further investigation of therapeutic strategies employing Spirulina against heavy metals toxicity in humans is therefore warranted. PMID:23555627

  9. Orienteering injuries

    PubMed Central

    Folan, Jean M.

    1982-01-01

    At the Irish National Orienteering Championships in 1981 a survey of the injuries occurring over the two days of competition was carried out. Of 285 individual competitors there was a percentage injury rate of 5.26%. The article discusses the injuries and aspects of safety in orienteering. Imagesp236-ap237-ap237-bp238-ap239-ap240-a PMID:7159815

  10. Blockage of the Upregulation of Voltage-Gated Sodium Channel Nav1.3 Improves Outcomes after Experimental Traumatic Brain Injury

    PubMed Central

    Huang, Xian-jian; Li, Wei-ping; Lin, Yong; Feng, Jun-feng; Jia, Feng

    2014-01-01

    Abstract Excessive active voltage-gated sodium channels are responsible for the cellular abnormalities associated with secondary brain injury following traumatic brain injury (TBI). We previously presented evidence that significant upregulation of Nav1.3 expression occurs in the rat cortex at 2 h and 12 h post-TBI and is correlated with TBI severity. In our current study, we tested the hypothesis that blocking upregulation of Nav1.3 expression in vivo in the acute stage post-TBI attenuates the secondary brain injury associated with TBI. We administered either antisense oligodeoxynucleotides (ODN) targeting Nav1.3 or artificial cerebrospinal fluid (aCSF) at 2 h, 4 h, 6 h, and 8 h following TBI. Control sham animals received aCSF administration at the same time points. At 12 h post-TBI, Nav1.3 messenger ribonucleic acid (mRNA) levels in bilateral hippocampi of the aCSF group were significantly elevated, compared with the sham and ODN groups (p<0.01). However, the Nav1.3 mRNA levels in the uninjured contralateral hippocampus of the ODN group were significantly lowered, compared with the sham group (p<0.01). Treatment with antisense ODN significantly decreased the number of degenerating neurons in the ipsilateral hippocampal CA3 and hilar region (p<0.01). A set of left-to-right ratio value analyzed by magnetic resonance imaging T2 image on one day, three days, and seven days post-TBI showed marked edema in the ipsilateral hemisphere of the aCSF group, compared with that of the ODN group (p<0.05). The Morris water maze memory retention test showed that both the aCSF and ODN groups took longer to find a hidden platform, compared with the sham group (p<0.01). However, latency in the aCSF group was significantly higher than in the ODN group (p<0.05). Our in vivo Nav1.3 inhibition studies suggest that therapeutic strategies to block upregulation of Nav1.3 expression in the brain may improve outcomes following TBI. PMID:24313291

  11. Impacts on Coralligenous Outcrop Biodiversity of a Dramatic Coastal Storm

    PubMed Central

    Teixidó, Núria; Casas, Edgar; Cebrián, Emma; Linares, Cristina; Garrabou, Joaquim

    2013-01-01

    Extreme events are rare, stochastic perturbations that can cause abrupt and dramatic ecological change within a short period of time relative to the lifespan of organisms. Studies over time provide exceptional opportunities to detect the effects of extreme climatic events and to measure their impacts by quantifying rates of change at population and community levels. In this study, we show how an extreme storm event affected the dynamics of benthic coralligenous outcrops in the NW Mediterranean Sea using data acquired before (2006–2008) and after the impact (2009–2010) at four different sites. Storms of comparable severity have been documented to occur occasionally within periods of 50 years in the Mediterranean Sea. We assessed the effects derived from the storm comparing changes in benthic community composition at sites exposed to and sheltered from this extreme event. The sites analyzed showed different damage from severe to negligible. The most exposed and impacted site experienced a major shift immediately after the storm, represented by changes in the species richness and beta diversity of benthic species. This site also showed higher compositional variability immediately after the storm and over the following year. The loss of cover of benthic species resulted between 22% and 58%. The damage across these species (e.g. calcareous algae, sponges, anthozoans, bryozoans, tunicates) was uneven, and those with fragile forms were the most impacted, showing cover losses up to 50 to 100%. Interestingly, small patches survived after the storm and began to grow slightly during the following year. In contrast, sheltered sites showed no significant changes in all the studied parameters, indicating no variations due to the storm. This study provides new insights into the responses to large and rare extreme events of Mediterranean communities with low dynamics and long-lived species, which are among the most threatened by the effects of global change. PMID:23326496

  12. Dramatic inhibition of amiodarone metabolism induced by grapefruit juice

    PubMed Central

    Libersa, Christian C; Brique, Serge A; Motte, Kokou B; Caron, Jacques F; Guédon-Moreau, Laurence M; Humbert, Luc; Vincent, A; Devos, Patrick; Lhermitte, Michel A

    2000-01-01

    Aims Grapefruit juice increases blood concentrations of many drugs metabolized by CYP3A. Amiodarone is metabolized by CYP3A to N-desethylamiodarone (N-DEA). The aim of this study was to determine amiodarone kinetics when administrated with and without grapefruit juice. Methods Eleven healthy adult volunteers took part in a single sequence, repeated-measures design study. Each subject, who had been evaluated 6 months previously for amiodarone pharmacokinetics, was given a single oral dose of amiodarone (17 mg kg−1) with three glasses of 300 ml of grapefruit juice on the same day. Results Grapefruit juice completely inhibited the production of N-DEA, the major metabolite of amiodarone, in all subjects and increased the area-under-the-curve (AUC) and maximum concentration of amiodarone (Cmax) by 50% and 84%, respectively, as compared with the control period during which water had been administrated instead of grapefruit juice (AUC: 35.9 ± 14.3 vs 23.9 ± 11.2 µg ml−1 h, P < 0.005 and Cmax: 3.45 ± 1.7 vs 1.87 ± 0.6 µg ml−1, P < 0. 02, respectively) (means ± s.d.). This inhibition of N-DEA production led to a decrease in the alterations caused by amiodarone on PR and QTc intervals. Conclusions Grapefruit juice dramatically alters the metabolism of amiodarone with complete inhibition of N-DEA production. These results are in agreement with in vitro data pointing to the involvement of CYP3 A in the metabolism of amiodarone and suggests that this interaction should be taken into account when prescribing this antiarrhythmic drug. PMID:10759694

  13. Dorsal Raphe Neuroinflammation Promotes Dramatic Behavioral Stress Dysregulation

    PubMed Central

    Howerton, Alexis R.; Roland, Alison V.

    2014-01-01

    Impulsivity, risk-taking behavior, and elevated stress responsivity are prominent symptoms of mania, a behavioral state common to schizophrenia and bipolar disorder. Though inflammatory processes activated within the brain are involved in the pathophysiology of both disorders, the specific mechanisms by which neuroinflammation drives manic behavior are not well understood. Serotonin cell bodies originating within the dorsal raphe (DR) play a major role in the regulation of behavioral features characteristic of mania. Therefore, we hypothesized that the link between neuroinflammation and manic behavior may be mediated by actions on serotonergic neurocircuitry. To examine this, we induced local neuroinflammation in the DR by viral delivery of Cre recombinase into interleukin (IL)-1βXAT transgenic male and female mice, resulting in overexpressing of the proinflammatory cytokine, IL-1β. For assertion of brain-region specificity of these outcomes, the prefrontal cortex (PFC), as a downstream target of DR serotonergic projections, was also infused. Inflammation within the DR, but not the PFC, resulted in a profound display of manic-like behavior, characterized by increased stress-induced locomotion and responsivity, and reduced risk-aversion/fearfulness. Microarray analysis of the DR revealed a dramatic increase in immune-related genes, and dysregulation of genes important in GABAergic, glutamatergic, and serotonergic neurotransmission. Behavioral and physiological changes were driven by a loss of serotonergic neurons and reduced output as measured by high-performance liquid chromatography, demonstrating inflammation-induced serotonergic hypofunction. Behavioral changes were rescued by acute selective serotonin reuptake inhibitor treatment, supporting the hypothesis that serotonin dysregulation stemming from neuroinflammation in the DR underlies manic-like behaviors. PMID:24849347

  14. α-Lipoic acid attenuates LPS-induced liver injury by improving mitochondrial function in association with GR mitochondrial DNA occupancy.

    PubMed

    Liu, Zhiqing; Guo, Jun; Sun, Hailin; Huang, Yanping; Zhao, Ruqian; Yang, Xiaojing

    2015-09-01

    α-Lipoic acid (LA) has been demonstrated to be a key regulator of energy metabolism. However, whether LA can protect the liver from inflammation, as well as the underlying mechanism involved, are still largely unclear. In the present study, mice treated with lipopolysaccharide (LPS) and injected with LA were used as a model. Liver injury, energy metabolism and mitochondrial regulation were investigated to assess the protective effect of LA on the liver and explore the possible mechanisms involved. Our results showed that LA attenuated liver injury, as evidenced by the decreased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels after LA treatment compared with the LPS-treated group. The hepatic ATP and NADH levels, expression levels of most mitochondrial DNA (mtDNA)-encoded genes as well as mitochondrial complex I, IV and V activities were all significantly increased in the LA-treated group compared with the LPS-treated group. Levels of Sirt3 protein, which is essential for the regulation of mitochondrial metabolism, were also increased in the LA-treated group. Regarding the regulation of mtDNA-encoded genes expression, we observed no obvious change in the methylation status of the mtDNA D-loop region. However, compared to the LPS-treated group, LA treatment increased glucocorticoid receptor (GR) protein expression in the liver, as well as the level of GR occupancy on the mtDNA D-loop region. Our study demonstrates that LA exerts a liver-protective effect in an inflammation state by improving mitochondrial function. Furthermore, to the best of our knowledge, we demonstrate for the first time that GR may be involved in this effect via an enhanced binding to the mtDNA transcriptional control region, thereby regulating the expression of mtDNA-encoded genes. PMID:26133658

  15. Long term study of deoxyribozyme administration to XT-1 mRNA promotes corticospinal tract regeneration and improves behavioral outcome after spinal cord injury.

    PubMed

    Koenig, Brigitte; Pape, Daniel; Chao, Owen; Bauer, Jordana; Grimpe, Barbara

    2016-02-01

    Spinal cord injury (SCI) affects approximately 3 million people around the world, who are desperately awaiting treatment. The pressing need for the development of therapeutics has spurred medical research for decades. To respond to this pressing need, our group developed a potential therapeutic to reduce the presence of proteoglycans at the injury site after acutely traumatizing the spinal cord of rats. With the aid of a DNA enzyme against the mRNA of xylosyltransferase-1 (DNAXT-1as) we adjourn the glycosylation and prevent the assembly of the proteoglycan core protein into the extracellular matrix. Hence, endogenous repair is strengthened due to the allocation of a more growth permissive environment around the lesion site. Here, we present data on a long term study of animals with a dorsal hemisection treated with DNAXT-1as, DNAXT-1mb (control DNA enzyme) or PBS via osmotic minipumps. After successful digestion of the XT-1 mRNA shown by qPCR we observed an overall behavioral improvement of DNAXT-1as treated rats at 8, 10 and 14 weeks after insult to the spine compared to the control animals. This is accompanied by the growth of the cortical spinal tract (CST) in DNAXT-1as treated animals after a 19 week survival period. Furthermore, after evaluating the lesion size tissue-protective effects in the DNAXT-1as treated animals compared to DNAXT-1mb and PBS treated rats are revealed. The results yield new insights into the regeneration processes and provide confirmation to involve DNA enzyme administration in future therapeutic strategies to medicate SCI. PMID:26428904

  16. Use of quadrupedal step training to re-engage spinal interneuronal networks and improve locomotor function after spinal cord injury

    PubMed Central

    Garcia-Alias, Guillermo; Choe, Jaehoon; Gad, Parag; Gerasimenko, Yury; Tillakaratne, Niranjala; Zhong, Hui; Roy, Roland R.

    2013-01-01

    Can lower limb motor function be improved after a spinal cord lesion by re-engaging functional activity of the upper limbs? We addressed this issue by training the forelimbs in conjunction with the hindlimbs after a thoracic spinal cord hemisection in adult rats. The spinal circuitries were more excitable, and behavioural and electrophysiological analyses showed improved hindlimb function when the forelimbs were engaged simultaneously with the hindlimbs during treadmill step-training as opposed to training only the hindlimbs. Neuronal retrograde labelling demonstrated a greater number of propriospinal labelled neurons above and below the thoracic lesion site in quadrupedally versus bipedally trained rats. The results provide strong evidence that actively engaging the forelimbs improves hindlimb function and that one likely mechanism underlying these effects is the reorganization and re-engagement of rostrocaudal spinal interneuronal networks. For the first time, we provide evidence that the spinal interneuronal networks linking the forelimbs and hindlimbs are amenable to a rehabilitation training paradigm. Identification of this phenomenon provides a strong rationale for proceeding toward preclinical studies for determining whether training paradigms involving upper arm training in concert with lower extremity training can enhance locomotor recovery after neurological damage. PMID:24103912

  17. Liven up Your Student Dramatics with Commedia dell' Arte.

    ERIC Educational Resources Information Center

    Potter, Jonathan

    1980-01-01

    Suggests using the ancient Commedia dell' Arte technique of establishing characters and a plot and then allowing the actors to create their own play. Indicates that this improves student performances even in more traditional plays. (TJ)

  18. Head injury.

    PubMed

    Hureibi, K A; McLatchie, G R

    2010-05-01

    Head injury is one of the commonest injuries in sport. Most are mild but some can have serious outcomes. Sports medicine doctors should be able to recognise the clinical features and evaluate athletes with head injury. It is necessary during field assessment to recognise signs and symptoms that help in assessing the severity of injury and making a decision to return-to-play. Prevention of primary head injury should be the aim. This includes protective equipment like helmets and possible rule changes. PMID:20533694

  19. Synthesis and characterization of novel indole derivatives reveal improved therapeutic agents for treatment of ischemia/reperfusion (I/R) injury.

    PubMed

    Bi, Wei; Bi, Yue; Xue, Ping; Zhang, Yanrong; Gao, Xiang; Wang, Zhibo; Li, Meng; Baudy-Floc'h, Michèle; Ngerebara, Nathaniel; Gibson, K Michael; Bi, Lanrong

    2010-09-23

    To develop more potent therapeutic agents with therapeutic efficacy for ischemia/reperfusion (I/R) injury, we linked an antiinflammatory moiety (1,3-dioxane derivative) to the key pharmacophoric moiety of melatonin. We hypothesized that the resulting new indole derivatives might induce a synergistic protection against oxidative damage associated with I/R injury. Our results indicate that one of these indole derivatives (7) manifests potent antiinflammatory antioxidant effects and exerts a protective effect against skeletal muscle injury and associated lung injury following limb I/R in rats. PMID:20731361

  20. Nanosecond pulsed platelet-rich plasma (nsPRP) improves mechanical and electrical cardiac function following myocardial reperfusion injury.

    PubMed

    Hargrave, Barbara; Varghese, Frency; Barabutis, Nektarios; Catravas, John; Zemlin, Christian

    2016-02-01

    Ischemia and reperfusion (I/R) of the heart is associated with biochemical and ionic changes that result in cardiac contractile and electrical dysfunction. In rabbits, platelet-rich plasma activated using nanosecond pulsed electric fields (nsPRP) has been shown to improve left ventricular pumping. Here, we demonstrate that nsPRP causes a similar improvement in mouse left ventricular function. We also show that nsPRP injection recovers electrical activity even before reperfusion begins. To uncover the mechanism of nsPRP action, we studied whether the enhanced left ventricular function in nsPRP rabbit and mouse hearts was associated with increased expression of heat-shock proteins and altered mitochondrial function under conditions of oxidative stress. Mouse hearts underwent 30 min of global ischemia and 1 h of reperfusion in situ. Rabbit hearts underwent 30 min of ischemia in vivo and were reperfused for 14 days. Hearts treated with nsPRP expressed significantly higher levels of Hsp27 and Hsp70 compared to hearts treated with vehicle. Also, pretreatment of cultured H9c2 cells with nsPRP significantly enhanced the "spare respiratory capacity (SRC)" also referred to as "respiratory reserve capacity" and ATP production in response to the uncoupler FCCP. These results suggest a cardioprotective effect of nsPRP on the ischemic heart during reperfusion. PMID:26908713

  1. Dramatic decrease of carnitine esters after interruption of exogenous carnitine supply in hemodialysis patients.

    PubMed

    Bene, Judit; Csiky, Botond; Wittmann, Istvan; Sulyok, Endre; Melegh, Bela

    2012-01-01

    L-carnitine supplementation is extensively used in patients on maintenance hemodialysis (HD) to improve dialysis-related clinical symptoms. In a series of studies, we investigated the dynamics of carnitine pool in carnitine-supplemented HD patients; here we report dramatic decrease with special changes of the ester profile due to interruption of the exogenous intake after the last HD session. Serum samples were collected from 18 L-carnitine-repleted end-stage renal disease (ESRD) patients before the L-carnitine supplementation, after completion of a carnitine supplementation period treatment (12 weeks, 1 g/IV/HD), right before the HD session, and 44 h after the dialysis. Levels of free carnitine (FC) and the individual esters were determined using electrospray MS/MS technique. Normally, L-carnitine supplementation causes significant elevation of all carnitine compounds to supraphysiological levels, which reaches a standard steady-state-like profile. In this study we found a dramatic decrease in the level of FC, and in short- and medium-chain acylcarnitines (ACs) 44 h after the last dialysis. At the end of this interdialytic period, FC levels increased to only 65% of the predialysis level, whereas the amounts of C2 and C3 esters recovered to only 50%. The level of C6 was 65% of the predialysis level, whereas the amount of C8 chain length ACs returned to 72% of the predialysis level. No significant change was seen in AC concentrations above C10 chain length. Omission of one single dosage of supplemental carnitine in long-term administration schemes results in dramatic decrease and reprofiling of carnitine esters even after the usual 44 h of interdialytic period. PMID:22417076

  2. Improvement of attention span and reaction time with hyperbaric oxygen treatment in patients with toxic injury due to mold exposure

    PubMed Central

    Ezra, N.; Dang, K.

    2010-01-01

    It is, by now, well established that mold toxins (mycotoxins) can cause significant adverse health effects. In this study, 15 subjects who developed an attention deficit disorder (ADD) and slowing of reaction time at the time of exposure to mold toxins were identified. Deficits in attention span and reaction time were documented not only by taking a careful history, but also by performing a Test of Variables of Attention (TOVA). The TOVA test provides an objective measure of these two variables. It was found that mold-exposed subjects show statistically significant decreases in attention span and significant increases in reaction time to stimuli compared to controls. After ten sessions of hyperbaric oxygen treatment (HBOT), a statistically significant improvement was seen in both measures. This preliminary study suggests promising outcomes in treating mold-exposed patients with hyperbaric oxygen. PMID:20978814

  3. Pomegranate (Punica granatum) juice reduces oxidative injury and improves sperm concentration in a rat model of testicular torsion-detorsion

    PubMed Central

    ATILGAN, DOGAN; PARLAKTAS, BEKIR; ULUOCAK, NIHAT; GENCTEN, YUSUF; ERDEMIR, FIKRET; OZYURT, HUSEYIN; ERKORKMAZ, UNAL; ASLAN, HUSEYIN

    2014-01-01

    The present study aimed to evaluate the effect of pomegranate juice (PJ) on oxidative stress (OS) and sperm concentration in a rat model of testicular torsion-detorsion. A total of 21 Wistar albino rats were randomly divided into three groups, each consisting of seven rats, as follows: i) control group, which underwent sham surgery; ii) ischemia/reperfusion (I/R) group, designed to determine the effects of the testicular torsion-detorsion process on rats; and iii) PJ+I/R group, designed to evaluate the effect of PJ on the OS and sperm cell concentrations induced by the torsion-detorsion process. In the PJ+I/R group, the rats were given 0.4 ml/day PJ orally over a period of eight weeks prior to surgery. Ipsilateral orchiectomy was carried out and 5-cm3 blood samples were obtained from the inferior vena cava of all rats. Biochemical analyses were performed to calculate the superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in the testicular tissue and serum. The concentrations of spermatids, spermatocytes and spermatogonia in the seminiferous tubules were assessed using histopathological methods. Serum and tissue SOD and MDA levels were significantly higher in rats from the I/R group compared with the control group (P<0.001). PJ treatment significantly decreased the SOD and MDA levels in both the serum and testicular tissue of the rats (P<0.001). The spermatid, spermatocyte and spermatogonia concentrations were significantly reduced in the I/R group compared with the control group (P<0.001). PJ treatment significantly improved the concentrations of spermatids, spermatocytes and spermatogonia compared with those in the I/R group (P=0.008). The experimentally established testicular torsion-detorsion model led to OS in the rat testes. Daily consumption of PJ prior to surgery reduced OS parameters and improved sperm cell concentrations. PMID:25009604

  4. Intravenous implanted neural stem cells migrate to injury site, reduce infarct volume, and improve behavior after cerebral ischemia.

    PubMed

    Shen, Chiung-Chyi; Lin, Chen-Huan; Yang, Yi-Chin; Chiao, Ming-Tsang; Cheng, Wen-Yu; Ko, Jiunn-Liang

    2010-08-01

    Stroke represents one of the leading causes of death and disability in humans, but despite intense research, only a few options exist for the treatment of stroke-related infarction of brain tissue. Thus far, in experimental strokes, cell therapy appears to partly reverse some behavioral deficits. However, the mechanisms of action remain uncertain as most studies reveal only little, if any, evidence for neuronal replacement and observed behavioral improvements. This present study was performed to test rodent fetus forebrain derived neural stem cells (NSCs) implantation into rats subjected to suture-induced middle cerebral artery occlusion (MCAO). Efficacy of cell therapy was studied regarding behavior recovery, infarct volume, and protection possibility of related molecular mechanisms. Here, we show that grafted cells can home in on damaged regions by MCAO and significantly improve behavior of ischemic rats. Infarct volumes and brain atrophy were diminished after grafted NSCs treatment. Furthermore, we detected inflammation related molecules such as COX-2 and IL-1beta and found that grafted NSCs treatment after ischemic stroke could repress expression of inflammation molecular protein levels. We also detected protein levels of heat shock protein 27 (HSP27) as a protective protein against apoptosis. The results showed that grafted NSCs treatment induced the protein level of HSP27 and down-regulated activity of caspase-3 compared with the vehicle control. Our results demonstrate that transplanted NSCs provide benefits in behavioral function recovery after MCAO and increase neuroprotection whilst repressing inflammatory destruction. These data reveal another essential explanation of cellular transplantation therapy in damage recovery from ischemic stroke and offer new therapeutic possibilities. PMID:20560882

  5. Improvement of Neuroenergetics by Hypertonic Lactate Therapy in Patients with Traumatic Brain Injury Is Dependent on Baseline Cerebral Lactate/Pyruvate Ratio

    PubMed Central

    Quintard, Hervé; Patet, Camille; Zerlauth, Jean-Baptiste; Suys, Tamarah; Bouzat, Pierre; Pellerin, Luc; Meuli, Reto; Magistretti, Pierre J.

    2016-01-01

    Abstract Energy dysfunction is associated with worse prognosis after traumatic brain injury (TBI). Recent data suggest that hypertonic sodium lactate infusion (HL) improves energy metabolism after TBI. Here, we specifically examined whether the efficacy of HL (3h infusion, 30–40 μmol/kg/min) in improving brain energetics (using cerebral microdialysis [CMD] glucose as a main therapeutic end-point) was dependent on baseline cerebral metabolic state (assessed by CMD lactate/pyruvate ratio [LPR]) and cerebral blood flow (CBF, measured with perfusion computed tomography [PCT]). Using a prospective cohort of 24 severe TBI patients, we found CMD glucose increase during HL was significant only in the subgroup of patients with elevated CMD LPR >25 (n = 13; +0.13 [95% confidence interval (CI) 0.08–0.19] mmol/L, p < 0.001; vs. +0.04 [–0.05–0.13] in those with normal LPR, p = 0.33, mixed-effects model). In contrast, CMD glucose increase was independent from baseline CBF (coefficient +0.13 [0.04–0.21] mmol/L when global CBF was <32.5 mL/100 g/min vs. +0.09 [0.04–0.14] mmol/L at normal CBF, both p < 0.005) and systemic glucose. Our data suggest that improvement of brain energetics upon HL seems predominantly dependent on baseline cerebral metabolic state and support the concept that CMD LPR – rather than CBF – could be used as a diagnostic indication for systemic lactate supplementation following TBI. PMID:26421521

  6. Traumatic brain injury-induced sleep disorders.

    PubMed

    Viola-Saltzman, Mari; Musleh, Camelia

    2016-01-01

    Sleep disturbances are frequently identified following traumatic brain injury, affecting 30%-70% of persons, and often occur after mild head injury. Insomnia, fatigue, and sleepiness are the most frequent sleep complaints after traumatic brain injury. Sleep apnea, narcolepsy, periodic limb movement disorder, and parasomnias may also occur after a head injury. In addition, depression, anxiety, and pain are common brain injury comorbidities with significant influence on sleep quality. Two types of traumatic brain injury that may negatively impact sleep are acceleration/deceleration injuries causing generalized brain damage and contact injuries causing focal brain damage. Polysomnography, multiple sleep latency testing, and/or actigraphy may be utilized to diagnose sleep disorders after a head injury. Depending on the disorder, treatment may include the use of medications, positive airway pressure, and/or behavioral modifications. Unfortunately, the treatment of sleep disorders associated with traumatic brain injury may not improve neuropsychological function or sleepiness. PMID:26929626

  7. Traumatic brain injury-induced sleep disorders

    PubMed Central

    Viola-Saltzman, Mari; Musleh, Camelia

    2016-01-01

    Sleep disturbances are frequently identified following traumatic brain injury, affecting 30%–70% of persons, and often occur after mild head injury. Insomnia, fatigue, and sleepiness are the most frequent sleep complaints after traumatic brain injury. Sleep apnea, narcolepsy, periodic limb movement disorder, and parasomnias may also occur after a head injury. In addition, depression, anxiety, and pain are common brain injury comorbidities with significant influence on sleep quality. Two types of traumatic brain injury that may negatively impact sleep are acceleration/deceleration injuries causing generalized brain damage and contact injuries causing focal brain damage. Polysomnography, multiple sleep latency testing, and/or actigraphy may be utilized to diagnose sleep disorders after a head injury. Depending on the disorder, treatment may include the use of medications, positive airway pressure, and/or behavioral modifications. Unfortunately, the treatment of sleep disorders associated with traumatic brain injury may not improve neuropsychological function or sleepiness. PMID:26929626

  8. Accuracy of Numerical Simulations of Tip Clearance Flow in Transonic Compressor Rotors Improved Dramatically

    NASA Technical Reports Server (NTRS)

    VanZante, Dale E.; Strazisar, Anthony J.; Wood, Jerry R.; Hathaway, Michael D.; Okiishi, Theodore H.

    2000-01-01

    The tip clearance flows of transonic compressor rotors have a significant impact on rotor and stage performance. Although numerical simulations of these flows are quite sophisticated, they are seldom verified through rigorous comparisons of numerical and measured data because, in high-speed machines, measurements acquired in sufficient detail to be useful are rare. Researchers at the NASA Glenn Research Center at Lewis Field compared measured tip clearance flow details (e.g., trajectory and radial extent) of the NASA Rotor 35 with results obtained from a numerical simulation. Previous investigations had focused on capturing the detailed development of the jetlike flow leaking through the clearance gap between the rotating blade tip and the stationary compressor shroud. However, we discovered that the simulation accuracy depends primarily on capturing the detailed development of a wall-bounded shear layer formed by the relative motion between the leakage jet and the shroud.

  9. President Obama and Education: The Possibility for Dramatic Improvements in Teaching and Learning

    ERIC Educational Resources Information Center

    Darling-Hammond, Linda

    2009-01-01

    From the unique perspective gained heading Obama's education policy transition team, Darling-Hammond describes President Obama's commitment to making the education of every child a collective responsibility and reviews the major tenets of the new administration's plans for education. She reflects on the importance of suggested policy changes,…

  10. Integrated System Dramatically Improves Hydrogen Molar Yield from Biomass via Fermentation (Fact Sheet)

    SciTech Connect

    Not Available

    2010-11-01

    This fact sheet describes NREL's accomplishments in fermentative and electrohydrogenic production of hydrogen from corn stover. Work was performed by NREL's Biosciences Center and Pennsylvania State University.

  11. Upper extremity injuries in golf.

    PubMed

    Bayes, Matthew C; Wadsworth, L Tyler

    2009-04-01

    Golf is an asymmetric sport with unique patterns of injury depending upon the skill level. Higher handicap players typically experience injuries that result from swing mechanics, whereas lower handicap and professional players have overuse as the major cause of their injuries. The majority of shoulder injuries affecting golfers occur in the nondominant shoulder. Common shoulder injuries include subacromial impingement, rotator cuff pathology, glenohumeral instability, and arthritis involving the acromioclavicular and/or glenohumeral joints. Lead arm elbow pain resulting from lateral epicondylosis (tennis elbow) is the leading upper extremity injury in amateur golfers. Tendon injury is the most common problem seen in the wrist and forearm of the golfer. Rehabilitation emphasizing improvement in core muscle streng is important in the treatment of golf injury. Emerging treatments for tendinopathy include topical nitrates, ultrasound-guided injection of therapeutic substances, and eccentric rehabilitation. There is evidence supporting physiotherapy, and swing modification directed by a teaching professional, for treatment of upper extremity golf injuries. This article focuses on upper extremity injuries in golf, including a discussion of the epidemiology, causes, diagnosis, treatment, and prevention of injuries occurring in the shoulder, elbow, wrist, and hand. PMID:20048492

  12. Puerarin Improves Diabetic Aorta Injury by Inhibiting NADPH Oxidase-Derived Oxidative Stress in STZ-Induced Diabetic Rats

    PubMed Central

    Li, Wenping; Zhao, Wenwen; Wu, Qin; Lu, Yuanfu; Shi, Jingshan; Chen, Xiuping

    2016-01-01

    Objective. Puerarin is a natural flavonoid isolated from the TCM lobed kudzuvine root. This study investigated the effect and mechanisms of puerarin on diabetic aorta in rats. Methods. Streptozotocin- (STZ-) induced diabetic rats were administered with puerarin for 3 weeks. Levels of serum insulin (INS), PGE2, endothelin (ET), glycated hemoglobin (GHb), H2O2, and nitric oxide (NO) in rats were measured by ELISA and colorimetric assay kits. The aortas were stained with H&E. Moreover, the mRNA expression of ICAM-1, LOX-1, NADPH oxidase 2 (NOX2), and NOX4 and the protein expression of ICAM-1, LOX-1, NF-κB p65, E-selectin, NOX2, and NOX4 in aorta tissues were measured by real-time PCR and Western blot, respectively. The localization of ICAM-1, NF-κB p65, NOX2, and NOX4 in the aorta tissues was also determined through immunohistochemistry. Results. Puerarin treatment exerted no effect on fasting blood glucose levels but significantly reduced the serum levels of INS, GHb, PGE2, ET, H2O2, and NO. In addition, puerarin improved the pathological alterations and inhibited the expression of ICAM-1, LOX-1, NOX2, and NOX4 at both mRNA and protein levels. Puerarin also significantly reduced the number of cells showing positive staining for ICAM-1, NOX2, NOX4, and NF-κB p65. Conclusion. Puerarin demonstrated protective effect on the STZ-induced diabetic rat aorta. The protective mechanisms may include regulation of NF-κB and inhibition of NOX2 and NOX4 followed by inhibition of cell adhesion molecule expression. PMID:26881260

  13. Combined Administration of Human Ghrelin and Human Growth Hormone Attenuates Organ Injury and Improves Survival in Aged Septic Rats

    PubMed Central

    Yang, Weng-Lang; Ma, Gaifeng; Zhou, Mian; Aziz, Monowar; Yen, Hao-Ting; Marvropoulos, Spyros A; Ojamaa, Kaie; Wang, Ping

    2016-01-01

    Sepsis is a major healthcare concern, especially in the elderly population. The use of an animal model closely resembling clinical conditions in this population may provide a better prediction in translating bench studies to the bedside. Ghrelin inhibits sympathetic nerve activity and inflammation in young septic animals; however, aged animals become hyporesponsive to ghrelin. In this study, we evaluated the efficacy of combined human ghrelin and growth hormone (GH) for sepsis treatment in the elderly utilizing a clinically relevant animal model of sepsis. Male Fischer 344 rats 22 to 24 months old were subjected to cecal ligation and puncture (CLP). Human ghrelin plus GH or vehicle (normal saline) was administered subcutaneously at 5 h after CLP. At 20 h after CLP, blood and tissue samples were collected for various analyses. Combined treatment attenuated serum levels of lactate, lactate dehydrogenase, creatinine, blood urea nitrogen, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in aged septic rats. The integrity of the microscopic structure in the lungs, liver and kidneys was well preserved after treatment. Expression of IL-6, TNF-α, macrophage inflammatory protein-2 and keratinocyte-derived chemokine as well as myeloperoxidase activity and caspase-3 activation were significantly reduced in the lungs and liver of treated rats. Moreover, treated rats showed an improvement in cardiovascular function and increased expression of ghrelin receptor and c-fos in the brainstem. Finally, the 10-d survival of aged septic rats was increased from 29% to 64% after combined treatment and was associated with less body weight loss. Our findings warrant the development of combined human ghrelin and GH for sepsis treatment in the geriatric population. PMID:26835699

  14. Development of a methodology for the standardisation and improvement of 'Smartphone' photography of patterned bruises and other cutaneous injuries.

    PubMed

    Biggs, Paul R; Evans, Samuel T; Jones, Michael D; Theobald, Peter S

    2013-09-01

    Human bite-mark analyses can play a prominent role in forensic case investigations, including those involving sexual assault. High-quality photographs routinely secure a link between a bite-mark and an individual's dentition. Access to around the clock forensic photography, however, is often limited, resulting in delay and/or missed opportunities to record valuable evidence. The emergence of Smartphone high-quality photographic technology now provides a previously unimagined opportunity to gather timely forensic photographic evidence. Problems can arise, however, due to the relatively poor quality of the photographs, as a result of many of those taking photographs having received little or no forensic photography training. This study compares unassisted photography with assisted photography, by a specifically developed camera application (App), to provide a standardised method for taking forensic photographs. An App, written in Java, was hosted on the Google Android Operating System, on a Samsung Galaxy SII Smartphone. Twenty-four volunteers participated in a study to photograph a pseudo bite-mark using three methods, (1) unassisted (as a control), (2) assisted by an ABFO No.2 right-angled photographic reference scale and (3) assisted by the App. The App, method (3), was shown to consistently outperform methods (1) and (2), demonstrating greater standardisation and precision (p<0.001). Analysis of the data showed the extent to which acquiring an accurate photograph depends on the image being orthogonal to the camera. It appears likely that the relatively inaccurate photographs acquired by methods (1) and (2), were as a result of deviation from the plane, orthogonal to the bite-mark. Therefore, the App was successful in ensuring that the camera was both orthogonal and at an appropriate distance, relative to the bite-mark. Thus, the App enhanced the abilities of non-experts to acquire more accurate photographs and created the potential to significantly improve the

  15. Ginsenoside Rg1 improves lipopolysaccharide-induced acute lung injury by inhibiting inflammatory responses and modulating infiltration of M2 macrophages.

    PubMed

    Bao, Suhong; Zou, Yun; Wang, Bing; Li, Yinjiao; Zhu, Jiali; Luo, Yan; Li, Jinbao

    2015-09-01

    Ginsenoside Rg1 (Rg1), the major effective component of ginseng, has been reported to have potent anti-inflammatory properties. However, the effect of ginsenoside Rg1 on lipopolysaccharide (LPS) -induced acute lung injury (ALI) in mice was unknown. The present study was designed to investigate the protective role of Rg1 on LPS-induced ALI and explore the potential mechanisms. The mice were divided randomly into four groups: the sham group, the LPS group and the LPS+Rg1 (40 mg/kg or 200mg/kg) pretreatment groups. All mice received Rg1 or an equivalent volume of phosphate buffer saline (PBS) intraperitoneally 1h before LPS administration. Edema quantification, histology, and apoptosis were detected 6h after LPS administration. The number of inflammatory cells, the percentage of alternative activated (M2) macrophages and the exudate quantification in bronchoalveolar lavage fluid (BALF) were evaluated. The caspase 3 expression, and the levels of phosphorylated IκB-α and p65 were tested. The results showed that the Rg1 pretreatment group markedly improved lung damage, modulated the infiltration of neutrophils and M2 macrophages, prevented the production of protein and proinflammatory cytokines in BALF, and inhibited apoptosis in lung. We also found that Rg1 suppressed NF-κB and caspase 3 activation. These data suggest that Rg1 plays a protective role against LPS-induced ALI by ameliorating inflammatory responses, regulating the infiltration of M2 macrophages, and inhibiting pulmonary cell apoptosis. PMID:26122136

  16. Neutralization of interleukin-1beta modifies the inflammatory response and improves histological and cognitive outcome following traumatic brain injury in mice.

    PubMed

    Clausen, Fredrik; Hånell, Anders; Björk, Maria; Hillered, Lars; Mir, Anis K; Gram, Hermann; Marklund, Niklas

    2009-08-01

    Interleukin-1beta (IL-1beta) may play a central role in the inflammatory response following traumatic brain injury (TBI). We subjected 91 mice to controlled cortical impact (CCI) brain injury or sham injury. Beginning 5 min post-injury, the IL-1beta neutralizing antibody IgG2a/k (1.5 microg/mL) or control antibody was infused at a rate of 0.25 microL/h into the contralateral ventricle for up to 14 days using osmotic minipumps. Neutrophil and T-cell infiltration and microglial activation was evaluated at days 1-7 post-injury. Cognition was assessed using Morris water maze, and motor function using rotarod and cylinder tests. Lesion volume and hemispheric tissue loss were evaluated at 18 days post-injury. Using this treatment strategy, cortical and hippocampal tissue levels of IgG2a/k reached 50 ng/mL, sufficient to effectively inhibit IL-1betain vitro. IL-1beta neutralization attenuated the CCI-induced cortical and hippocampal microglial activation (P < 0.05 at post-injury days 3 and 7), and cortical infiltration of neutrophils (P < 0.05 at post-injury day 7). There was only a minimal cortical infiltration of activated T-cells, attenuated by IL-1beta neutralization (P < 0.05 at post-injury day 7). CCI induced a significant deficit in neurological motor and cognitive function, and caused a loss of hemispheric tissue (P < 0.05). In brain-injured animals, IL-1beta neutralizing treatment resulted in reduced lesion volume, hemispheric tissue loss and attenuated cognitive deficits (P < 0.05) without influencing neurological motor function. Our results indicate that IL-1beta is a central component in the post-injury inflammatory response that, in view of the observed positive neuroprotective and cognitive effects, may be a suitable pharmacological target for the treatment of TBI. PMID:19614750

  17. Skiing Injuries

    PubMed Central

    Bartlett, L. H.

    1975-01-01

    In the broad spectrum of orthopedic skiing injuries, ‘second aid’ on the mountain and at the base by the physician is very important. All skiing physicians should carry minimal medical supplies, including narcotic medication. Diagnosis and treatment of injuries at the hospital are outlined. Most ski fractures of the tibia can be treated by conservative methods. A more aggressive approach to diagnosis and treatment of ligamentous injuries of the knee is recommended. PMID:20469236

  18. Gunshot injuries.

    PubMed

    Hinkle, J; Betz, S

    1995-05-01

    If current trends for this nation continue, by the year 2003 the number of people killed by firearms will exceed the number of people killed in motor vehicle accidents. Critical care practitioners must understand the mechanism of injury associated with firearm injuries to provide optimal care. This article reviews internal, exterior, and terminal ballistics, bullet design, wound classification, and initial assessment and treatment of firearm injuries. PMID:7743422

  19. Small molecule-mediated up-regulation of microRNA targeting a key cell death modulator BNIP3 improves cardiac function following ischemic injury

    PubMed Central

    Lee, Se-Yeon; Lee, Seahyoung; Choi, Eunhyun; Ham, Onju; Lee, Chang Youn; Lee, Jiyun; Seo, Hyang-Hee; Cha, Min-Ji; Mun, Bohyun; Lee, Yunmi; Yoon, Cheesoon; Hwang, Ki-Chul

    2016-01-01

    Genetic ablation of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), an essential regulator of cardiac cell death, is an effective way to prevent cardiac cell death triggered by pathologic conditions. However, currently there exists no known means, such as inhibitors, to down-regulate BNIP3 in mature heart. Here, we report that a small molecule inducer of microRNA-182 (miR-182) suppressed ischemia/reperfusion (I/R)-induced cardiac cell death by down-regulating BNIP3. We first selected miR-182 as a potent BNIP3-targeting miRNA based on miRNA-target prediction databases and empirical data. The subsequent screening of small molecules for inducing miR-182 expression identified Kenpaullone as a hit compound. Both exogenous miR-182 and Kenpaullone significantly suppressed hypoxia-induced cardiomyocyte death in vitro. To investigate the effect of changing substituents of Kenpaullone on miR-182 expression, we synthesized 9 derivatives of Kenpaullone. Among these derivatives, compound 5 showed significantly improved ability to induce miR-182 expression. The results of the in vivo study showed that compound 5 significantly improved heart function following I/R-injury in rats. Our study provides strong evidence that the small molecule-mediated up-regulation of miRNAs is a viable strategy to down-regulate target proteins with no known chemical inhibitor and that compound 5 may have potential to prevent I/R-inflicted cardiac cell death. PMID:27008992

  20. Small molecule-mediated up-regulation of microRNA targeting a key cell death modulator BNIP3 improves cardiac function following ischemic injury.

    PubMed

    Lee, Se-Yeon; Lee, Seahyoung; Choi, Eunhyun; Ham, Onju; Lee, Chang Youn; Lee, Jiyun; Seo, Hyang-Hee; Cha, Min-Ji; Mun, Bohyun; Lee, Yunmi; Yoon, Cheesoon; Hwang, Ki-Chul

    2016-01-01

    Genetic ablation of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), an essential regulator of cardiac cell death, is an effective way to prevent cardiac cell death triggered by pathologic conditions. However, currently there exists no known means, such as inhibitors, to down-regulate BNIP3 in mature heart. Here, we report that a small molecule inducer of microRNA-182 (miR-182) suppressed ischemia/reperfusion (I/R)-induced cardiac cell death by down-regulating BNIP3. We first selected miR-182 as a potent BNIP3-targeting miRNA based on miRNA-target prediction databases and empirical data. The subsequent screening of small molecules for inducing miR-182 expression identified Kenpaullone as a hit compound. Both exogenous miR-182 and Kenpaullone significantly suppressed hypoxia-induced cardiomyocyte death in vitro. To investigate the effect of changing substituents of Kenpaullone on miR-182 expression, we synthesized 9 derivatives of Kenpaullone. Among these derivatives, compound 5 showed significantly improved ability to induce miR-182 expression. The results of the in vivo study showed that compound 5 significantly improved heart function following I/R-injury in rats. Our study provides strong evidence that the small molecule-mediated up-regulation of miRNAs is a viable strategy to down-regulate target proteins with no known chemical inhibitor and that compound 5 may have potential to prevent I/R-inflicted cardiac cell death. PMID:27008992

  1. Sulforaphane improves dysregulated metabolic profile and inhibits leptin-induced VSMC proliferation: Implications toward suppression of neointima formation after arterial injury in western diet-fed obese mice.

    PubMed

    Shawky, Noha M; Pichavaram, Prahalathan; Shehatou, George S G; Suddek, Ghada M; Gameil, Nariman M; Jun, John Y; Segar, Lakshman

    2016-06-01

    Sulforaphane (SFN), a dietary phase-2 enzyme inducer that mitigates cellular oxidative stress through nuclear factor erythroid 2-related factor 2 (Nrf2) activation, is known to exhibit beneficial effects in the vessel wall. For instance, it inhibits vascular smooth muscle cell (VSMC) proliferation, a major event in atherosclerosis and restenosis after angioplasty. In particular, SFN attenuates the mitogenic and pro-inflammatory actions of platelet-derived growth factor (PDGF) and tumor necrosis factor-α (TNFα), respectively, in VSMCs. Nevertheless, the vasoprotective role of SFN has not been examined in the setting of obesity characterized by hyperleptinemia and insulin resistance. Using the mouse model of western diet-induced obesity, the present study demonstrates for the first time that subcutaneous delivery of SFN (0.5mg/Kg/day) for~3weeks significantly attenuates neointima formation in the injured femoral artery [↓ (decrease) neointima/media ratio by~60%; n=5-8]. This was associated with significant improvements in metabolic parameters, including ↓ weight gain by~52%, ↓ plasma leptin by~42%, ↓ plasma insulin by~63%, insulin resistance [↓ homeostasis model assessment of insulin resistance (HOMA-IR) index by~73%], glucose tolerance (↓ AUCGTT by~24%), and plasma lipid profile (e.g., ↓ triglycerides). Under in vitro conditions, SFN significantly decreased leptin-induced VSMC proliferation by~23% (n=5) with associated diminutions in leptin-induced cyclin D1 expression and the phosphorylation of p70S6kinase and ribosomal S6 protein (n=3-4). The present findings reveal that, in addition to improving systemic metabolic parameters, SFN inhibits leptin-induced VSMC proliferative signaling that may contribute in part to the suppression of injury-induced neointima formation in diet-induced obesity. PMID:27142739

  2. Novel strategy to decrease reperfusion injuries and improve function of cold-preserved livers using normothermic ex vivo liver perfusion machine.

    PubMed

    Banan, Babak; Xiao, Zhenyu; Watson, Rao; Xu, Min; Jia, Jianluo; Upadhya, Gundumi A; Mohanakumar, Thalachallour; Lin, Yiing; Chapman, William

    2016-03-01

    Normothermic extracorporeal liver perfusion (NELP) can decrease ischemia/reperfusion injury to the greatest degree when cold ischemia time is minimized. Warm perfusion of cold-stored livers results in hepatocellular damage, sinusoidal endothelial cell (SEC) dysfunction, and Kupffer cell activation. However, the logistics of organ procurement mandates a period of cold preservation before NELP. The aim of this study was to determine the beneficial effects of gradual rewarming of cold-stored livers by placement on NELP. Three female porcine livers were used for each group. In the immediate NELP group, procured livers were immediately placed on NELP for 8 hours. In the cold NELP group, livers were cold-stored for 4 hours followed by NELP for 4 hours. In rewarming groups, livers were cold-stored for 4 hours, then gradually rewarmed in different durations to 38°C and kept on NELP for an additional 4 hours. For comparison purposes, the last 4 hours of NELP runs were considered to be the evaluation phase. Immediate NELP livers had significantly lower concentrations of liver transaminases, hyaluronic acid, and β-galactosidase and had higher bile production compared to the other groups. Rewarming livers had significantly lower concentrations of hyaluronic acid and β-galactosidase compared to the cold NELP livers. In addition, there was a significant decline in international normalized ratio values, improved bile production, reduced biliary epithelial cell damage, and improved cholangiocyte function. Thus, if a NELP machine is not available at the procurement site and livers will need to undergo a period of cold preservation, a gradual rewarming protocol before NELP may greatly reduce damages that are associated with reperfusion. In conclusion, gradual rewarming of cold-preserved livers upon NELP can minimize the hepatocellular damage, Kupffer cell activation, and SEC dysfunction. PMID:26439190

  3. World-Wide Effort Produces Dramatic "Movie" of Cosmic Jet

    NASA Astrophysics Data System (ADS)

    2001-05-01

    Astronomers using a world-wide collection of radio telescopes, including the National Science Foundation's Very Long Baseline Array (VLBA) of the National Radio Astronomy Observatory (NRAO), have made a dramatic "movie" of a voracious, superdense neutron star repeatedly spitting out subatomic particles at nearly the speed of light into two narrow jets as it pulls material from a companion star. The movie shows these jets ejecting clouds of hot plasma that are then "zapped" by pulses of energy in the jets as they move away from the neutron star. Frame from Radio-Telescope 'Movie' of Scorpius X-1 "We have directly measured the speed of energy flow in a cosmic jet for the first time," said Ed Fomalont, an astronomer at the NRAO in Charlottesville, Virginia. Fomalont worked with Barry Geldzahler and Charles Bradshaw of George Mason University in Fairfax, Virginia. The astronomers used the VLBA, the NSF's Very Large Array (VLA) and the Green Bank 140-foot telescope, along with radio telescopes from the European VLBI Network, Australia, Japan and South Africa to record the double-star system's eruptions continuously for 56 hours. "This study is going to be extremely valuable in helping us understand a phenomenon that we see throughout the universe," Fomalont said. Cosmic jets of superfast particles are ejected from the cores of numerous galaxies. On a smaller scale, similar jets are ejected from binary-star systems closer to home, in our own Milky Way Galaxy. While the jets from galaxy cores are thought to be powered by supermassive black holes millions of times more massive than the Sun, the closer "microquasars" are powered by much smaller black holes or by neutron stars only a few times more massive than the sun. "Studying one of the closer, smaller examples will help us understand how they all work, including the bigger ones," Geldzahler said. "The jets coming from distant galaxies are harder to study because of their much greater distance and the slowness of their

  4. Unique Tuft Test Facility Dramatically Reduces Brush Seal Development Costs

    NASA Technical Reports Server (NTRS)

    Fellenstein, James A.

    1997-01-01

    Brush seals have been incorporated in the latest turbine engines to reduce leakage and improve efficiency. However, the life of these seals is limited by wear. Studies have shown that optimal sealing characteristics for a brush seal occur before the interference fit between the brush and shaft is excessively worn. Research to develop improved tribopairs (brush and coating) with reduced wear and lower friction has been hindered by the lack of an accurate, low-cost, efficient test methodology. Estimated costs for evaluating a new material combination in an engine company seal test program are on the order of $100,000. To address this need, the NASA Lewis Research Center designed, built, and validated a unique, innovative brush seal tuft tester that slides a single tuft of brush seal wire against a rotating shaft under controlled loads, speeds, and temperatures comparable to those in turbine engines. As an initial screening tool, the brush seal tuft tester can tribologicaly evaluate candidate seal materials for 1/10th the cost of full-scale seal tests. Previous to the development of the brush seal tuft tester facility, most relevant tribological data had been obtained from full-scale seal tests conducted primarily to determine seal leakage characteristics. However, from a tribological point of view, these tests included the confounding effects of varying contact pressures, bristle flaring, high-temperature oxidation, and varying bristle contact angles. These confounding effects are overcome in tuft testing. The interface contact pressures can be either constant or varying depending on the tuft mounting device, and bristle wear can be measured optically with inscribed witness marks. In a recent cooperative program with a U.S. turbine engine manufacturer, five metallic wire candidates were tested against a plasma-sprayed Nichrome-bonded chrome carbide. The wire materials used during this collaboration were either nickel-chrome- or cobaltchrome-based superalloys. These

  5. Restricted Field IMRT Dramatically Enhances IMRT Planning for Mesothelioma

    SciTech Connect

    Allen, Aaron M. Schofield, Deborah; Hacker, Fred; Court, Laurence E.; Czerminska, Maria M.S.

    2007-12-01

    Purpose: To improve the target coverage and normal tissue sparing of intensity-modulated radiotherapy (IMRT) for mesothelioma after extrapleural pneumonectomy. Methods and Materials: Thirteen plans from patients previously treated with IMRT for mesothelioma were replanned using a restricted field technique. This technique was novel in two ways. It limited the entrance beams to 200{sup o} around the target and three to four beams per case had their field apertures restricted down to the level of the heart or liver to further limit the contralateral lung dose. New constraints were added that included a mean lung dose of <9.5 Gy and volume receiving {>=}5 Gy of <55%. Results: In all cases, the planning target volume coverage was excellent, with an average of 97% coverage of the planning target volume by the target dose. No change was seen in the target coverage with the new technique. The heart, kidneys, and esophagus were all kept under tolerance in all cases. The average mean lung dose, volume receiving {>=}20 Gy, and volume receiving {>=}5 Gy with the new technique was 6.6 Gy, 3.0%, and 50.8%, respectively, compared with 13.8 Gy, 15%, and 90% with the previous technique (p < 0.0001 for all three comparisons). The maximal value for any case in the cohort was 8.0 Gy, 7.3%, and 57.5% for the mean lung dose, volume receiving {>=}20 Gy, and volume receiving {>=}5 Gy, respectively. Conclusion: Restricted field IMRT provides an improved method to deliver IMRT to a complex target after extrapleural pneumonectomy. An upcoming Phase I trial will provide validation of these results.

  6. Rowing injuries.

    PubMed

    Rumball, Jane S; Lebrun, Constance M; Di Ciacca, Stephen R; Orlando, Karen

    2005-01-01

    Participation in the sport of rowing has been steadily increasing in recent decades, yet few studies address the specific injuries incurred. This article reviews the most common injuries described in the literature, including musculoskeletal problems in the lower back, ribs, shoulder, wrist and knee. A review of basic rowing physiology and equipment is included, along with a description of the mechanics of the rowing stroke. This information is necessary in order to make an accurate diagnosis and treatment protocol for these injuries, which are mainly chronic in nature. The most frequently injured region is the low back, mainly due to excessive hyperflexion and twisting, and can include specific injuries such as spondylolysis, sacroiliac joint dysfunction and disc herniation. Rib stress fractures account for the most time lost from on-water training and competition. Although theories abound for the mechanism of injury, the exact aetiology of rib stress fractures remains unknown. Other injuries discussed within, which are specific to ribs, include costochondritis, costovertebral joint subluxation and intercostal muscle strains. Shoulder pain is quite common in rowers and can be the result of overuse, poor technique, or tension in the upper body. Injuries concerning the forearm and wrist are also common, and can include exertional compartment syndrome, lateral epicondylitis, deQuervain's and intersection syndrome, and tenosynovitis of the wrist extensors. In the lower body, the major injuries reported include generalised patellofemoral pain due to abnormal patellar tracking, and iliotibial band friction syndrome. Lastly, dermatological issues, such as blisters and abrasions, and miscellaneous issues, such as environmental concerns and the female athlete triad, are also included in this article.Pathophysiology, mechanism of injury, assessment and management strategies are outlined in the text for each injury, with special attention given to ways to correct

  7. Dramatic remission of anemia after thymectomy in a patient of idiopathic myelofibrosis with thymoma.

    PubMed

    Shih, Ying-Yih; Hsiao, Liang-Tsai; Yang, Ching-Fen; Wu, Yu-Chung; Chiou, Tzeon-Jye

    2008-01-01

    Anemia is one of the characteristics of idiopathic myelofibrosis (IMF), and malignant thymoma is usually associated with various hematologic disorders, including anemia, pancytopenia, and hypogammaglobulinemia. However, the relationship between IMF and malignant thymoma has not been published before. Here, we report a 48-year-old woman who was initially diagnosed of IMF with severe anemia and transfusion dependent. Five years later, malignant thymoma was found when she was examined for chronic cough. After performing extended thymectomy, her anemia dramatically recovered to normal and sustained for 2 years till last follow-up. Her splenomegaly and myelofibrosis were also improved. We hypothesized that her malignant thymoma induced the progression of IMF, especially in anemia. PMID:18224414

  8. Dramatic niche shifts and morphological change in two insular bird species

    PubMed Central

    Alström, Per; Jønsson, Knud A.; Fjeldså, Jon; Ödeen, Anders; Ericson, Per G. P.; Irestedt, Martin

    2015-01-01

    Colonizations of islands are often associated with rapid morphological divergence. We present two previously unrecognized cases of dramatic morphological change and niche shifts in connection with colonization of tropical forest-covered islands. These evolutionary changes have concealed the fact that the passerine birds madanga, Madanga ruficollis, from Buru, Indonesia, and São Tomé shorttail, Amaurocichla bocagii, from São Tomé, Gulf of Guinea, are forest-adapted members of the family Motacillidae (pipits and wagtails). We show that Madanga has diverged mainly in plumage, which may be the result of selection for improved camouflage in its new arboreal niche, while selection pressures for other morphological changes have probably been weak owing to preadaptations for the novel niche. By contrast, we suggest that Amaurocichla's niche change has led to divergence in both structure and plumage. PMID:26064613

  9. Sports Injuries

    MedlinePlus

    ... sometimes you can injure yourself when you play sports or exercise. Accidents, poor training practices, or improper gear can cause them. Some people get hurt because they are not in shape. Not warming up or stretching enough can also ... injuries are Sprains and strains Knee injuries Swollen ...

  10. Accommodating Workers with Spinal Cord Injury.

    ERIC Educational Resources Information Center

    Dowler, Denetta; Batiste, Linda; Whidden, Eddie

    1998-01-01

    Examination of over 1,000 calls to the Job Accommodation Network involving workers with spinal cord injury identified the nature of the industry, job, career progression, and accessibility solutions. The number of calls increased dramatically after passage of the Americans with Disabilities Act. (SK)

  11. Nuclear factor erythroid-2 related factor 2 overexpressed mesenchymal stem cells transplantation, improves renal function, decreases injuries markers and increases repair markers in glycerol-induced Acute kidney injury rats

    PubMed Central

    Zhaleh, Fateme; Amiri, Fatemeh; Mohammadzadeh-Vardin, Mohammad; Bahadori, Marzie; Harati, Mitra Dehghan; Roudkenar, Mehryar Habibi; Saki, Sasan

    2016-01-01

    Objective(s): Recently cell therapy is a promising therapeutic modality for many types of disease including acute kidney injury (AKI). Due to the unique biological properties, mesenchymal stem cells (MSCs) are attractive cells in this regard. This study aims to transplant MSCs equipped with nuclear factor E2-related factor 2 (Nrf2) in rat experimental models of acute kidney and evaluate regeneration potential of injured kidney especially expression of injury and repaired biomarkers. Materials and methods: Nrf2 was overexpressed in bone marrow-derived MSCs by pcDNA.3.1 plasmid. AKI was induced using glycerol in rat models. The regenerative potential of Nrf2-overexpressed MSCs was evaluated in AKI-Induced animal models using biochemical and histological methods after transplantation. Expression of repaired genes, AQP1 and CK-18, as well as injury markers, Kim-1 and Cystatin C, was also assayed in engrafted kidney sections. Results: Our results revealed that transplantation of Nrf2-overexpressed MSCs into AKI-induced rats decreased blood urea nitrogen and creatinine and ameliorated kidney regeneration throughout 14 days. Upregulation of repaired markers and downregulation of injury markers were considerable 14 days after transplantation. Conclusions: Overexpression of Nrf2 in MSCs suggests a new strategy to increase efficiency of MSC-based cell therapy in AKI. PMID:27114803

  12. PACS implementation dramatically impacts people and radiology work processes

    NASA Astrophysics Data System (ADS)

    Ouvry, Ann

    1997-05-01

    The technology is not the bottleneck anymore in PACS implementation, it has become clear that the key to the success of PACS is understanding the current process, the end-user requirements, and how these processes will change with the introduction of PACS. We will discuss how implementation of PACS changed the working procedures in the Radiology department of Visby Hospital. Visby Hospital in Gotland, Sweden has approximately 160 beds. The Radiology department performs approximately 33,000 examinations per year and is capable of offering a broad range of diagnostic imaging services including CT and MRI. When a new facility was built in 1994, the decision was made to go for filmless operation and a modern information infrastructure. The new facility went operational by the end of 1994, in August 1995 almost filmless operation was reached. Continuing effort and attention is being paid to further simplify the workflow and working procedures in the Radiology department, and to improve the services offered to referring physicians. Although the project aimed at filmless operation, the main goal was to organize for efficient operation and excellent service, thereby maintaining high quality standards and employee satisfaction.

  13. Dramatic increase in fatigue life in hierarchical graphene composites.

    PubMed

    Yavari, F; Rafiee, M A; Rafiee, J; Yu, Z-Z; Koratkar, N

    2010-10-01

    We report the synthesis and fatigue characterization of fiberglass/epoxy composites with various weight fractions of graphene platelets infiltrated into the epoxy resin as well as directly spray-coated on to the glass microfibers. Remarkably only ∼0.2% (with respect to the epoxy resin weight and ∼0.02% with respect to the entire laminate weight) of graphene additives enhanced the fatigue life of the composite in the flexural bending mode by up to 1200-fold. By contrast, under uniaxial tensile fatigue conditions, the graphene fillers resulted in ∼3-5-fold increase in fatigue life. The fatigue life increase (in the flexural bending mode) with graphene additives was ∼1-2 orders of magnitude superior to those obtained using carbon nanotubes. In situ ultrasound analysis of the nanocomposite during the cyclic fatigue test suggests that the graphene network toughens the fiberglass/epoxy-matrix interface and prevents the delamination/buckling of the glass microfibers under compressive stress. Such fatigue-resistant hierarchical materials show potential to improve the safety, reliability, and cost effectiveness of fiber-reinforced composites that are increasingly the material of choice in the aerospace, automotive, marine, sports, biomedical, and wind energy industries. PMID:20863061

  14. Dramatic performance gains of a novel circular vanadium flow battery

    NASA Astrophysics Data System (ADS)

    Zheng, Qiong; Xing, Feng; Li, Xianfeng; Liu, Tao; Lai, Qinzhi; Ning, Guiling; Zhang, Huamin

    2015-03-01

    Vanadium flow battery (VFB) holds great promise for use in large scale energy storage applications. However, one major issue that limits the battery performance is the energy storage capacity loss due to insufficient use of electrolyte. The battery structure design is flexible and acceptable to solve the issue. Based on the mass transport limitation of the conventional rectangular vanadium flow battery (RFB), a novel circular vanadium flow battery (CFB) was firstly proposed in the research. Without increasing pump consumption, the new structure of CFB is effective to achieve mass transport enhancement and concentration polarization reduction. The charge-discharge test confirmed the performance advantage of CFB, presenting a significant increment of 10.52% at 40 mA cm-2 and 30.46% at 160 mA cm-2 in the utilization of electrolyte and improved energy storage capacity by 12.56% at 40 mA cm-2 and a 2.55 times of that for RFB at 160 mA cm-2. The performance advantage of CFB becomes exceptionally evident at high current densities.

  15. Rowing Injuries

    PubMed Central

    Hosea, Timothy M.; Hannafin, Jo A.

    2012-01-01

    Context: Rowing is one of the original modern Olympic sports and was one of the most popular spectator sports in the United States. Its popularity has been increasing since the enactment of Title IX. The injury patterns in this sport are unique because of the stress applied during the rowing stroke. Evidence Acquisition: This review summarizes the existing literature describing the biomechanics of the rowing stroke and rowing-related injury patterns. Data were obtained from previously published peer-reviewed literature through a search of the entire PubMed database (up to December, 2011) as well as from textbook chapters and rowing coaching manuals. Results: Rowing injuries are primarily overuse related. The knee, lumbar spine, and ribs are most commonly affected. The injury incidence is directly related to the volume of training and technique. Conclusion: Familiarity of the injury patterns and the biomechanical forces affecting the rowing athlete will aid in prompt diagnosis and appropriate management. PMID:23016093

  16. Volleyball injuries.

    PubMed

    Eerkes, Kevin

    2012-01-01

    There has been a significant increase in the numbers of people playing indoor and beach volleyball since the early 1980s and, consequently, an increase in injuries. Most injuries are related to repetitive jumping and hitting the ball overhead. The ankle is the most commonly injured joint, but the knee, shoulder, low back, and fingers also are vulnerable. The shoulder in particular is subject to extreme torque when hitting and jump serving the ball. Some injuries have a predilection for those playing on sand versus those playing in an indoor court. The clinician caring for volleyball players should be aware of the types of injuries these players sustain and how to help them return to play promptly and appropriately. This article reviews the specific injuries that are most common as a result of participating in the sport of volleyball. PMID:22965348

  17. Toward an effective long-term strategy for preventing motor vehicle crashes and injuries.

    PubMed

    Mawson, Anthony R; Walley, E Kenneth

    2014-08-01

    Casualties due to motor vehicle crashes (MVCs) include some 40,000 deaths each year in the United States and one million deaths worldwide. One strategy that has been recommended for improving automobile safety is to lower speed limits and enforce them with speed cameras. However, motor vehicles can be hazardous even at low speeds whereas properly protected human beings can survive high-speed crashes without injury. Emphasis on changing driver behavior as the focus for road safety improvements has been largely unsuccessful; moreover, drivers today are increasingly distracted by secondary tasks such as cell phone use and texting. Indeed, the true limiting factor in vehicular safety is the capacity of human beings to sense and process information and to make rapid decisions. Given that dramatic reductions in injuries and deaths from MVCs have occurred over the past century due to improvements in safety technology, despite increases in the number of vehicles on the road and miles driven per vehicle, we propose that an effective long-term strategy for reducing MVC-related injury would be continued technological innovation in vehicle design, aimed at progressively removing the driver from routine operational decision-making. Once this is achieved, high rates of speed could be achieved on open highways, with minimal risk of crashes and injury to occupants and pedestrians. PMID:25116634

  18. Toward an Effective Long-Term Strategy for Preventing Motor Vehicle Crashes and Injuries

    PubMed Central

    Mawson, Anthony R.; Walley, E. Kenneth

    2014-01-01

    Casualties due to motor vehicle crashes (MVCs) include some 40,000 deaths each year in the United States and one million deaths worldwide. One strategy that has been recommended for improving automobile safety is to lower speed limits and enforce them with speed cameras. However, motor vehicles can be hazardous even at low speeds whereas properly protected human beings can survive high-speed crashes without injury. Emphasis on changing driver behavior as the focus for road safety improvements has been largely unsuccessful; moreover, drivers today are increasingly distracted by secondary tasks such as cell phone use and texting. Indeed, the true limiting factor in vehicular safety is the capacity of human beings to sense and process information and to make rapid decisions. Given that dramatic reductions in injuries and deaths from MVCs have occurred over the past century due to improvements in safety technology, despite increases in the number of vehicles on the road and miles driven per vehicle, we propose that an effective long-term strategy for reducing MVC-related injury would be continued technological innovation in vehicle design, aimed at progressively removing the driver from routine operational decision-making. Once this is achieved, high rates of speed could be achieved on open highways, with minimal risk of crashes and injury to occupants and pedestrians. PMID:25116634

  19. Patterns of injury associated with automobile airbag use.

    PubMed Central

    Mohamed, A. A.; Banerjee, A.

    1998-01-01

    The wide use of automobile airbags has undoubtedly reduced the mortality and the incidence of serious injuries from motor vehicle accidents. However, automobile airbags appear to be associated with a variety of injuries including fatal injuries, ocular injuries, upper limb and chest injuries. Further improvements in airbag design together with education of the general public in their use should help reduce airbag-related injuries. PMID:9926118

  20. Head injury - first aid

    MedlinePlus

    ... is shaken, is the most common type of traumatic brain injury. Scalp wounds. Skull fractures. Head injuries may cause ... of people who suffer head injuries are children. Traumatic brain injury (TBI) accounts for over 1 in 6 injury- ...

  1. Dietary Omega-3 Polyunsaturated Fatty Acids Improve the Neurolipidome and Restore the DHA Status while Promoting Functional Recovery after Experimental Spinal Cord Injury

    PubMed Central

    Figueroa, Johnny D.; Cordero, Kathia; llán, Miguel S.

    2013-01-01

    Abstract Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) confer multiple health benefits and decrease the risk of neurological disorders. Studies are needed, however, to identify promising cellular targets and to assess their prophylactic value against neurodegeneration. The present study (1) examined the efficacy of a preventive diet enriched with ω-3 PUFAs to reduce dysfunction in a well-established spinal cord injury (SCI) animal model and (2) used a novel metabolomics data analysis to identify potential neurolipidomic targets. Rats were fed with either control chow or chow enriched with ω-3 PUFAs (750 mg/kg/day) for 8 weeks before being subjected to a sham or a contusion SCI operation. We report new evidence showing that rats subjected to SCI after being pre-treated with a diet enriched with ω-3 PUFAs exhibit significantly better functional outcomes. Pre-treated animals exhibited lower sensory deficits, autonomic bladder recovery, and early improvements in locomotion that persisted for at least 8 weeks after trauma. We found that SCI triggers a robust alteration in the cord PUFA neurolipidome, which was characterized by a marked docosahexaenoic acid (DHA) deficiency. This DHA deficiency was associated with dysfunction and corrected with the ω-3 PUFA-enriched diet. Multivariate data analyses revealed that the spinal cord of animals consuming the ω-3 PUFA-enriched diet had a fundamentally distinct neurolipidome, particularly increasing the levels of essential and long chain ω-3 fatty acids and lysolipids at the expense of ω-6 fatty acids and its metabolites. Altogether, dietary ω-3 PUFAs prophylaxis confers resiliency to SCI mediated, at least in part, by generating a neuroprotective and restorative neurolipidome. PMID:23294084

  2. CXCL12/CXCR4 Axis Improves Migration of Neuroblasts Along Corpus Callosum by Stimulating MMP-2 Secretion After Traumatic Brain Injury in Rats.

    PubMed

    Mao, Weifeng; Yi, Xin; Qin, Jianbing; Tian, Meiling; Jin, Guohua

    2016-06-01

    To investigate the effect of CXCL12 on migration of neural precursor cells after traumatic brain injury (TBI). We randomly divided 48 rats into four groups: (1) the sham group, rats were performed craniotomy only, (2) the control group, saline were injected into the ipsilateral cortex after TBI, (3) the CXCL12 group, CXCL12 were injected into the ipsilateral cortex after TBI, and (4) the CXCL12 + AMD3100 group, CXCL12 and AMD3100 were mixed together and injected into the ipsilateral cortex after TBI. At 7 days after TBI, the brain tissues were subjected to immunofluorescent double-labeled staining with the antibodies of CXCR4/DCX, MMP-2/DCX, MMP-2/GFAP, MMP-2/NeuN. Western blot assay was used to measure the protein levels of MMP-2. Compared with the control group, the number of CXCR4/DCX and MMP-2 positive cells around the injured corpus callosum area were significantly increased in the CXCL12 treatment group. The area occupied by these cells expanded and the shape changed from chain distribution to radial. CXCL12 + AMD3100 treatment significantly decreased the number and distribution area of CXCR4/DCX and MMP-2 positive cells compared with the CXCL12 treatment and control group. The DCX positive cells could not form chain or radial distribution. The protein expressions of MMP-2 had the similar change trends as the results of immunofluorescent staining. MMP-2 could be secreted by DCX, GFAP and NeuN positive cells. CXCL12/CXCR4 axis can improve the migration of the neuroblasts along the corpus callosum by stimulating the MMP-2 secretion of different types of cells. PMID:26801174

  3. Dietary omega-3 polyunsaturated fatty acids improve the neurolipidome and restore the DHA status while promoting functional recovery after experimental spinal cord injury.

    PubMed

    Figueroa, Johnny D; Cordero, Kathia; Llán, Miguel S; De Leon, Marino

    2013-05-15

    Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) confer multiple health benefits and decrease the risk of neurological disorders. Studies are needed, however, to identify promising cellular targets and to assess their prophylactic value against neurodegeneration. The present study (1) examined the efficacy of a preventive diet enriched with ω-3 PUFAs to reduce dysfunction in a well-established spinal cord injury (SCI) animal model and (2) used a novel metabolomics data analysis to identify potential neurolipidomic targets. Rats were fed with either control chow or chow enriched with ω-3 PUFAs (750 mg/kg/day) for 8 weeks before being subjected to a sham or a contusion SCI operation. We report new evidence showing that rats subjected to SCI after being pre-treated with a diet enriched with ω-3 PUFAs exhibit significantly better functional outcomes. Pre-treated animals exhibited lower sensory deficits, autonomic bladder recovery, and early improvements in locomotion that persisted for at least 8 weeks after trauma. We found that SCI triggers a robust alteration in the cord PUFA neurolipidome, which was characterized by a marked docosahexaenoic acid (DHA) deficiency. This DHA deficiency was associated with dysfunction and corrected with the ω-3 PUFA-enriched diet. Multivariate data analyses revealed that the spinal cord of animals consuming the ω-3 PUFA-enriched diet had a fundamentally distinct neurolipidome, particularly increasing the levels of essential and long chain ω-3 fatty acids and lysolipids at the expense of ω-6 fatty acids and its metabolites. Altogether, dietary ω-3 PUFAs prophylaxis confers resiliency to SCI mediated, at least in part, by generating a neuroprotective and restorative neurolipidome. PMID:23294084

  4. Management of maxillofacial injuries in bear mauling cases: a review of 20 cases

    PubMed Central

    2016-01-01

    Objectives As the craniofacial and neck regions are prime areas of injury in bear attacks, the careful management of soft and hard tissue injuries and selection of reconstructive options is of the utmost importance. This study will review the incidence and patterns of bear mauling in eastern India reported to our department and the various modalities used for their treatment over a period of 7 years. It also documents the risks of infection in bear mauling cases and the complications that have occurred. Materials and Methods Twenty cases were treated over the study period. Cases were evaluated for soft and hard tissue injuries including tissue loss and corresponding management in the craniofacial region. Cases were also evaluated for other associated injuries, organ damage and related complications. Results Various modalities of treatment were used for the management of victims, ranging from simple primary repairs to free tissue transfers. Simple primary repairs were done in 75% of cases, while the management of the injured victims required reconstruction by local, regional or distant flaps in 25%. Free tissue transfers were performed in 15% of cases, and no cases of wound infection were detected in the course of treatment. Conclusion Knowledge of various reconstructive techniques is essential for managing maxillofacial injuries in bear mauling cases. Modern reconstructive procedures like free tissue transfer are reliable options for reconstruction with minimal co-morbidity and dramatic improvement in treatment outcomes. PMID:26904490

  5. Vinexin-β deficiency protects against cerebral ischaemia/reperfusion injury by inhibiting neuronal apoptosis.

    PubMed

    Li, Mingchang; Guo, Sen; Zhang, Peng; Gong, Jun; Zheng, Ankang; Zhang, Yan; Li, Hongliang

    2015-07-01

    Vinexin-β is an adaptor protein that regulates cell adhesion, cytoskeletal organization and signal transduction. Our previous work showed that Vinexin-β protects against cardiac hypertrophy. However, its function in stroke is largely unknown. In the present study, we observed a significant increase in Vinexin-β expression in both human intracerebral haemorrhage and mouse cerebral ischaemia/reperfusion (I/R) injury model, indicating that Vinexin-β is involved in stroke. Next, using Vinexin-β knockout mice, we further demonstrated that Vinexin-β deficiency significantly protected against cerebral I/R injury, as demonstrated by a dramatic decrease in the infarct volume and an improvement in neurological function. Additionally, immunofluorescence and western blotting showed that the deletion of Vinexin-β attenuated neuronal apoptosis. Mechanically, we found that Akt signalling was up-regulated in the brains of the Vinexin-β knockout mice compared with those of the WT control mice after ischaemic injury. Taken together, our results demonstrate that the deletion of Vinexin-β potently protects against ischaemic injury by inhibiting neuronal apoptosis, and this effect may occur via the up-regulation of Akt signalling. Our findings revealed that Vinexin-β acts as a novel modulator of ischaemic injury, suggesting that Vinexin-β may represent an attractive therapeutic target for the prevention of stroke. PMID:25824575

  6. Acute kidney injury.

    PubMed

    Lang, Joanna; Zuber, Kim; Davis, Jane

    2016-04-01

    Acute kidney injury (AKI) complicates up to 20% of all hospital admissions. Responding to the increase in admissions, complications, mortality, morbidity, and cost of AKI, Kidney Disease: Improving Global Outcomes convened an expert panel to study the issue, review the literature, and publish guidelines to evaluate and treat patients with AKI in the acute setting. This article reviews those guidelines. PMID:27023656

  7. Glial restricted precursor cell transplant with cyclic adenosine monophosphate improved some autonomic functions but resulted in a reduced graft size after spinal cord contusion injury in rats.

    PubMed

    Nout, Yvette S; Culp, Esther; Schmidt, Markus H; Tovar, C Amy; Pröschel, Christoph; Mayer-Pröschel, Margot; Noble, Mark D; Beattie, Michael S; Bresnahan, Jacqueline C

    2011-01-01

    Transplantation of glial restricted precursor (GRP) cells has been shown to reduce glial scarring after spinal cord injury (SCI) and, in combination with neuronal restricted precursor (NRP) cells or enhanced expression of neurotrophins, to improve recovery of function after SCI. We hypothesized that combining GRP transplants with rolipram and cAMP would improve functional recovery, similar to that seen after combining Schwann cell transplants with increasing cAMP. A short term study, (1) uninjured control, (2) SCI+vehicle, and (3) SCI+cAMP, showed that spinal cord [cAMP] was increased 14days after SCI. We used 51 male rats subjected to a thoracic SCI for a 12-week survival study: (1) SCI+vehicle, (2) SCI+GRP, (3) SCI+cAMP, (4) SCI+GRP+cAMP, and (5) uninjured endpoint age-matched control (AM). Rolipram was administered for 2weeks after SCI. At 9days after SCI, GRP transplantation and injection of dibutyryl-cAMP into the spinal cord were performed. GRP cells survived, differentiated, and formed extensive transplants that were well integrated with host tissue. Presence of GRP cells increased the amount of tissue in the lesion; however, cAMP reduced the graft size. White matter sparing at the lesion epicenter was not affected. Serotonergic input to the lumbosacral spinal cord was not affected by treatment, but the amount of serotonin immediately caudal to the lesion was reduced in the cAMP groups. Using telemetric monitoring of corpus spongiosum penis pressure we show that the cAMP groups regained the same number of micturitions per 24hours when compared to the AM group, however, the frequency of peak pressures was increased in these groups compared to the AM group. In contrast, the GRP groups had similar frequency of peak pressures compared to baseline and the AM group. Animals that received GRP cells regained the same number of erectile events per 24hours compared to baseline and the AM group. Since cAMP reduced the GRP transplant graft, and some modest positive

  8. Methodological challenges in using the Finnish Hospital Discharge Register for studying fire-related injuries leading to inpatient care

    PubMed Central

    2013-01-01

    Background The objective was to examine feasibility of using hospital discharge register data for studying fire-related injuries. Methods The Finnish National Hospital Discharge Register (FHDR) was the database used to select relevant hospital discharge data to study usability and data quality issues. Patterns of E-coding were assessed, as well as prominent challenges in defining the incidence of injuries. Additionally, the issue of defining the relevant amount of hospital days accounted for in injury care was considered. Results Directly after the introduction of the ICD-10 classification system, in 1996, the completeness of E-coding was found to be poor, but to have improved dramatically around 2000 and thereafter. The scale of the challenges to defining the incidence of injuries was found to be manageable. In counting the relevant hospital days, psychiatric and long-term care were found to be the obvious and possible sources of overestimation. Conclusions The FHDR was found to be a feasible data source for studying fire-related injuries so long as potential challenges are acknowledged and taken into account. Hospital discharge data can be a unique and powerful means for injury research as issues of representativeness and coverage of traditional probability samples can frequently be completely avoided. PMID:23496937

  9. Injury Surveillance Among NASA Astronauts Using the Barell Injury Diagnosis Matrix

    NASA Technical Reports Server (NTRS)

    Murray, J. D.; Laughlin, M. S.; Eudy, D. L.; Wear, M. L.; VanBaalen, M. G.

    2014-01-01

    Astronauts perform physically demanding tasks and risk incurring musculoskeletal injuries during both groundbased training and missions. Increased injury rates throughout the history of the U.S. space program have been attributed to numerous factors, including an aging astronaut corps, increased Weightless Environment Training Facility (WETF) and Neutral Buoyancy Laboratory (NBL) training to construct the International Space Station, and improved clinical operations that promote injury prevention and reporting. With NASA program changes through the years (including retirement of the Shuttle program) and an improved training environment (including a new astronaut gym), there is no surveillance program to systematically track injury rates. A limited number of research projects have been conducted over the past 20 years to evaluate musculoskeletal injuries: (1) to evaluate orthopedic injuries from 1987 to 1995, (2) to describe upper extremity injuries, (3) to evaluate EVA spacesuit training related injuries, and (4) to evaluate in-flight musculoskeletal injuries. Nevertheless, there has been no consistently performed comprehensive assessment of musculoskeletal injuries among astronauts. The Barell Injury Diagnosis Matrix was introduced at the 2001 meeting of the International Collaborative Effort (ICE) on Injury Statistics. The Matrix proposes a standardized method of classifying body region by nature of injury. Diagnoses are coded using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) coding system. The purpose of this study is to assess the usefulness and complexity of the Barell Injury Diagnosis Matrix to classify and track musculoskeletal injuries among NASA astronauts.

  10. High Median Nerve Injuries.