Science.gov

Sample records for 90-day functional recovery

  1. Predictors of 30-Day Mortality and 90-Day Functional Recovery after Primary Intracerebral Hemorrhage : Hospital Based Multivariate Analysis in 585 Patients

    PubMed Central

    2009-01-01

    Objective The purpose of this study was to identify independent predictors of mortality and functional recovery in patients with primary intracerebral hemorrhage (PICH) and to improve functional outcome in these patients. Methods Data were collected retrospectively on 585 patients with supratentorial PICH admitted to the Stroke Unit at our hospital between 1st January 2004 and the 31st July 2008. Using multivariate logistic regression analysis, the associations between all selected variables and 30-day mortality and 90-day functional recoveries after PICH was evaluated. Results Ninety-day functional recovery was achieved in 29.1% of the 585 patients and 30-day mortality in 15.9%. Age (OR=7.384, p=0.000), limb weakness (OR=6.927, p=0.000), and hematoma volume (OR=5.293, p=0.000) were found to be powerful predictors of 90-day functional recovery. Furthermore, initial consciousness (OR=3.013, p=0.014) hematoma location (lobar, OR=2.653, p=0.003), ventricular extension of blood (OR=2.077, p=0.013), leukocytosis (OR=2.048, p=0.008), alcohol intake (drinker, OR=1.927, p=0.023), and increased serum aminotransferase (OR=1.892, p=0.035) were found to be independent predictors of 90-day functional recovery after PICH. On the other hand, a pupillary abnormality (OR=4.532, p=0.000) and initial unconsciousness (OR=3.362, p=0.000) were found to be independent predictors of 30-day mortality after PICH. Conclusion The predictors of mortality and functional recovery after PICH identified during this analysis may assist during clinical decision-making, when advising patients or family members about the prognosis of PICH and when planning intervention trials. PMID:19609417

  2. Two-hour methyl isocyanate inhalation and 90-day recovery study in B6C3F1 mice

    SciTech Connect

    Boorman, G.A.; Uraih, L.C.; Gupta, B.N.; Bucher, J.R.

    1987-06-01

    B6C3F1 mice were exposed by inhalation to 0, 3, 10, and 30 ppm methyl isocyanate for 2 hr followed by a 90-day recovery period. Sixteen of eight (20%) male mice in the 30 ppm group died following exposure. There were no other unscheduled deaths in the mice. Five mice/sex/group were examined at 2 hr or at 1, 3, 7, 14, 28, 49, or 91 days following exposure. Chemical-related changes were restricted to the respiratory system. At 30 ppm there were extensive necrosis and erosion of the respiratory and olfactory epithelium in the nasal cavity. Severe necrosis and epithelial erosion were also found in the trachea and main bronchi. Regeneration of the mucosal epithelium occurred rapidly in the nasal cavity and airways. In the turbinates, mild incomplete olfactory epithelial regeneration persisted to day 91 in the male mice. Intraluminal fibrotic projections covered by respiratory epithelium and bronchial fibrosis were found in the major airways of the 30 ppm male and female mice by day 7. The intraluminal fibrosis persisted to day 91. In males with severe bronchial fibrosis, chronic alveolitis and atelectasis were found. In mice exposed to 3 or 10 ppm, persistent pulmonary changes were not found. These studies indicate that methyl isocyanate inhalation at or near lethal concentrations can cause persistent fibrosis of the major bronchi in mice.

  3. 90-Day Cycle Handbook

    ERIC Educational Resources Information Center

    Park, Sandra; Takahashi, Sola

    2013-01-01

    90-Day Cycles are a disciplined and structured form of inquiry designed to produce and test knowledge syntheses, prototyped processes, or products in support of improvement work. With any type of activity, organizations inevitably encounter roadblocks to improving performance and outcomes. These barriers might include intractable problems at…

  4. STS-90 Day 06 Highlights

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this sixth day of the STS-90 mission, the flight crew, Cmdr. Richard A. Searfoss, Pilot Scott D. Altman, and Mission Specialists Richard M. Linnehan, Dafydd Rhys Williams and Kathryn P. Hire, and Payload Specialists Jay C. Buckey and James A. Pawelczyk are back on the job full-time as they begin the day six of on-orbit research on the human nervous system. Additional work with the Pulmonary Function Test (PFT) equipment which is collecting data on the crew's breathing patterns and blood concentrations of oxygen and carbon dioxide also takes place.

  5. STS-90 Day 14 Highlights

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this fourteenth day of the STS-90 mission, the flight crew, Cmdr. Richard A. Searfoss, Pilot Scott D. Altman, and Mission Specialists Richard M. Linnehan, Dafydd Rhys Williams and Kathryn P. Hire, and Payload Specialists Jay C. Buckey and James A. Pawelczyk focus on the efforts of Neurolab's Neuronal Plasticity Team to better understand how the adult nervous system adapts to the new environment of space. Columbia's science crew -- Mission Specialists Rick Linnehan and Dave Williams and Payload Specialists Jay Buckey and Jim Pawelczyk -- perform the second and final in-flight dissections of the adult male rats on board. The crew euthanizes and dissects nine rats and remove the vestibular or balance organs of the inner ear; the cerebellum, the part of the brain critical for maintaining balance and for processing information from the limbs so they can be moved smoothly; and the cerebrum, one part of which controls automatic functions such as body temperature regulation and the body's internal clock, and the cortical region that controls cognitive functions such as thinking. The first dissection, which was performed on the second day of the flight, went extremely well, according to Neurolab scientists.

  6. Toxicological assessment of a prototype e-cigaret device and three flavor formulations: a 90-day inhalation study in rats

    PubMed Central

    Werley, Michael S.; Kirkpatrick, Dan J.; Oldham, Michael J.; Jerome, Ann M.; Langston, Timothy B.; Lilly, Patrick D.; Smith, Donna C.; Mckinney, Willie J.

    2016-01-01

    Abstract A prototype electronic cigaret device and three formulations were evaluated in a 90-day rat inhalation study followed by a 42-day recovery period. Animals were randomly assigned to groups for exposure to low-, mid- and high-dose levels of aerosols composed of vehicle (glycerin and propylene glycol mixture); vehicle and 2.0% nicotine; or vehicle, 2.0% nicotine and flavor mixture. Daily targeted aerosol total particulate matter (TPM) doses of 3.2, 9.6 and 32.0 mg/kg/day were achieved by exposure to 1 mg/L aerosol for 16, 48 and 160 min, respectively. Pre-study evaluations included indirect ophthalmoscopy, virology and bacteriological screening. Body weights, clinical observations and food consumption were monitored weekly. Plasma nicotine and cotinine and carboxyhemoglobin levels were measured at days 28 and 90. After days 28, 56 and 90, lung function measurements were obtained. Biological endpoints after 90-day exposure and 42-day recovery period included clinical pathology, urinalysis, bronchoalveolar fluid (BALF) analysis, necropsy and histopathology. Treatment-related effects following 90 days of exposure included changes in body weight, food consumption and respiratory rate. Dose-related decreases in thymus and spleen weights, and increased BALF lactate dehydrogenase, total protein, alveolar macrophages, neutrophils and lung weights were observed. Histopathology evaluations revealed sporadic increases in nasal section 1–4 epithelial hyperplasia and vacuolization. Following the recovery period, effects in the nose and BALF were persistent while other effects were resolved. The no observed effect level based upon body weight decreases is considered to be the mid-dose level for each formulation, equivalent to a daily TPM exposure dose of approximately 9.6 mg/kg/day. PMID:26787428

  7. Toxicological assessment of a prototype e-cigaret device and three flavor formulations: a 90-day inhalation study in rats.

    PubMed

    Werley, Michael S; Kirkpatrick, Dan J; Oldham, Michael J; Jerome, Ann M; Langston, Timothy B; Lilly, Patrick D; Smith, Donna C; Mckinney, Willie J

    2016-01-01

    A prototype electronic cigaret device and three formulations were evaluated in a 90-day rat inhalation study followed by a 42-day recovery period. Animals were randomly assigned to groups for exposure to low-, mid- and high-dose levels of aerosols composed of vehicle (glycerin and propylene glycol mixture); vehicle and 2.0% nicotine; or vehicle, 2.0% nicotine and flavor mixture. Daily targeted aerosol total particulate matter (TPM) doses of 3.2, 9.6 and 32.0 mg/kg/day were achieved by exposure to 1 mg/L aerosol for 16, 48 and 160 min, respectively. Pre-study evaluations included indirect ophthalmoscopy, virology and bacteriological screening. Body weights, clinical observations and food consumption were monitored weekly. Plasma nicotine and cotinine and carboxyhemoglobin levels were measured at days 28 and 90. After days 28, 56 and 90, lung function measurements were obtained. Biological endpoints after 90-day exposure and 42-day recovery period included clinical pathology, urinalysis, bronchoalveolar fluid (BALF) analysis, necropsy and histopathology. Treatment-related effects following 90 days of exposure included changes in body weight, food consumption and respiratory rate. Dose-related decreases in thymus and spleen weights, and increased BALF lactate dehydrogenase, total protein, alveolar macrophages, neutrophils and lung weights were observed. Histopathology evaluations revealed sporadic increases in nasal section 1-4 epithelial hyperplasia and vacuolization. Following the recovery period, effects in the nose and BALF were persistent while other effects were resolved. The no observed effect level based upon body weight decreases is considered to be the mid-dose level for each formulation, equivalent to a daily TPM exposure dose of approximately 9.6 mg/kg/day. PMID:26787428

  8. 40 CFR 799.9346 - TSCA 90-day inhalation toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 33 2013-07-01 2013-07-01 false TSCA 90-day inhalation toxicity. 799.9346 Section 799.9346 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS Health Effects Test Guidelines...

  9. Recovery in skeletal muscle contractile function after prolonged hindlimb immobilization

    NASA Technical Reports Server (NTRS)

    Fitts, R. H.; Brimmer, C. J.

    1985-01-01

    The effect of three-month hindlimb immobilization (IM) in rats on contractile properties of slow-twitch soleus (SOL), fast-twitch extensor digitorum longus, and fast-twitch superficial region of the vastus lateralis were measured after 0, 14, 28, 60, and 90 days of recovery on excized, horizontally suspended muscles stimulated electrically to maximal twitch tension. IM caused decreases in muscle-to-body weight ratios for all muscles, with no complete recovery even after 90 days. The contractile properties of the fast-twitch muscles were less affected by IM than those of the slow-twitch SOL. The SOL isometric twitch duration was shortened, due to reduced contraction and half-relaxation time, both of which returned to control levels after 14 days of recovery. The peak tetanic tension, P(O), g/sq cm,, decreased with IM by 46 percent in the SOL, but recovered by the 28th day. The maximum shortening velocity was not altered by IM in any of the muscles. Thus, normal contractile function could recover after prolonged limb IM.

  10. Baroreflex Sensitivity Decreases During 90-Day Bed Rest

    NASA Technical Reports Server (NTRS)

    Stenger, M. B.; Arzeno, N. M.; Platts, S. H.

    2008-01-01

    Baroreflex sensitivity (BRS) decreases during spaceflight and simulated spaceflight (head down bed rest [BR]). However, previous studies have only examined BRS in response to a limited blood pressure (BP) range or to a single sudden change in BP. PURPOSE: The purpose of this study was to examine BRS during 90 days of 6deg head-down tilt BR over a broad range of BP perturbations. METHODS: Nineteen normal volunteers (12M, 7F) were tested one day before BR, and then near BR days 30, 60 and 90. BP was pharmacologically altered by continuous infusions of phenylephrine (PE) and sodium nitroprusside (SNP). Electrocardiogram and continuous BP were collected during 10 min of normal saline (NS), followed by increasing concentrations of PE (10 min each of 0.4, 0.8 and 1.6 micro-g/kg/min). After a 20 min break, NS was infused again for 10 min, followed by increasing concentrations of SNP (10 min each of 0.4, 0.8, 1.2 micro-g/kg/min). Baroreceptor sensitivity was measured as the slope of a sequence of 3 or more beats in which the systolic BP and following R-R interval (RR) both increased or decreased. Spectral heart rate variability (HRV) and mean RR were analyzed using data from only the NS infusions. Two-way repeated-measures analysis of variance was performed to examine the effects of BR and gender. RESULTS: RR decreased (p<0.001) from pre- BR across BR days. High frequency in normalized units, a measure of parasympathetic activity, decreased with BR (p=0.027) and was lower (p=0.046) in men (0.39+/-0.02, mean+/-SEM) than women (0.48+/-0.02). The spontaneous baroreflex slope, our measure of BRS, increased with PE and decreased with SNP across BR (p<0.001). The percentage decrease in BRS from pre- to post-BR appeared to be larger in women (43.6+/-7.0%) than in men (31.3+/-3.9%, p=0.06). CONCLUSION: Parasympathetic activity and baroreflex sensitivity decrease during 90 days of BR, and BRS tends to diminish more in women than in men.

  11. 90-Day toxicity study of dichloroacetate in dogs.

    PubMed

    Cicmanec, J L; Condie, L W; Olson, G R; Wang, S R

    1991-08-01

    Male and female juvenile beagle dogs were dosed daily for 90 days with dichloroacetate (DCA). The compound was administered orally via gelatin capsules at doses of 0, 12.5, 39.5, and 72 mg/kg/day. Each dose group consisted of five males and five females. The dogs were observed clinically and blood samples were taken at 15-day intervals for hematologic and serum chemistry values. Decreased total erythrocyte count and hemoglobin levels were observed in mid- and high-dose dogs beginning at Day 30. Serum concentrations of LDH were elevated at Days 30 and 45 in females and at Day 75 in males treated with DCA at 72 mg/kg/day. One female of the high-dose group died at Day 50 and two high-dose males died at Days 51 and 74. Hindlimb partial paralysis was observed in many high-dose dogs. Vacuolization of myelinated white tracts of cerebrum, cerebellum, and/or spinal cord was observed in many high-dose dogs as well as some mid- and low-dose subjects. Degeneration of testicular germinal epithelium and syncytial giant cell formation was noted in males of all dose groups. Hepatic vacuolar change and chronic hepatitis appeared only in DCA-treated dogs. In addition, suppurative bronchopneumonia and chronic pancreatitis were noted in many high-dose and some middose subjects. A "no-adverse-effect level" was not determined in this study. PMID:1765225

  12. The 90-day oral toxicity of d-psicose in male Wistar rats

    PubMed Central

    Matsuo, Tatsuhiro; Ishii, Reika; Shirai, Yoko

    2012-01-01

    d-Psicose is a rare sugar present in small quantities in natural products. In a previous study, we showed that d-psicose suppresses increase in plasma glucose and reduces body fat accumulation in rats. Based on acute toxicity testing in rats, d-psicose is classified as an ordinary substance (LD50 = 16 g/kg). Elucidating the effects of sub-chronic feeding of d-psicose in rats is essential before it can be utilized as a physiologically functional food. In this study, male Wistar rats (3 weeks old) were fed diets containing 3% d-psicose or sucrose for 90 days. The body weight gain and intra-abdominal adipose tissue weight did not differ between the sucrose and the d-psicose groups. The weights of the liver and kidneys were significantly higher in the d-psicose group than in the sucrose group. However, no gross pathological findings were evident at dietary doses of 3% d-psicose or were correlated with hypertrophy of the liver and kidney. In a clinical chemistry analysis, the erythrocyte and leukocyte courts were significantly higher in the d-psicose group, but that was not considered to be toxicologically significant. Therefore, the present study found no adverse effects of d-psicose in rats fed a diet containing 3% d-psicosefor 90 days. PMID:22448098

  13. 49 CFR 24.503 - Replacement housing payment for 90-day mobile home occupants.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 1 2011-10-01 2011-10-01 false Replacement housing payment for 90-day mobile home... ASSISTANCE AND REAL PROPERTY ACQUISITION FOR FEDERAL AND FEDERALLY-ASSISTED PROGRAMS Mobile Homes § 24.503 Replacement housing payment for 90-day mobile home occupants. A displaced tenant or owner-occupant of a...

  14. 49 CFR 24.503 - Replacement housing payment for 90-day mobile home occupants.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Replacement housing payment for 90-day mobile home... ASSISTANCE AND REAL PROPERTY ACQUISITION FOR FEDERAL AND FEDERALLY-ASSISTED PROGRAMS Mobile Homes § 24.503 Replacement housing payment for 90-day mobile home occupants. A displaced tenant or owner-occupant of a...

  15. 19 CFR Annex Viii-A to Part 351 - Schedule for 90-Day Sunset Reviews

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 3 2011-04-01 2011-04-01 false Schedule for 90-Day Sunset Reviews VIII Annex VIII-A to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex VIII-A Annex VIII-A to Part 351—Schedule for 90-Day...

  16. 19 CFR Annex Viii-A to Part 351 - Schedule for 90-Day Sunset Reviews

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Schedule for 90-Day Sunset Reviews VIII Annex VIII-A to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex VIII-A Annex VIII-A to Part 351—Schedule for 90-Day...

  17. 49 CFR 24.503 - Replacement housing payment for 90-day mobile home occupants.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false Replacement housing payment for 90-day mobile home occupants. 24.503 Section 24.503 Transportation Office of the Secretary of Transportation UNIFORM RELOCATION... Replacement housing payment for 90-day mobile home occupants. A displaced tenant or owner-occupant of a...

  18. 49 CFR 24.503 - Replacement housing payment for 90-day mobile home occupants.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false Replacement housing payment for 90-day mobile home occupants. 24.503 Section 24.503 Transportation Office of the Secretary of Transportation UNIFORM RELOCATION... Replacement housing payment for 90-day mobile home occupants. A displaced tenant or owner-occupant of a...

  19. 49 CFR 24.503 - Replacement housing payment for 90-day mobile home occupants.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false Replacement housing payment for 90-day mobile home occupants. 24.503 Section 24.503 Transportation Office of the Secretary of Transportation UNIFORM RELOCATION... Replacement housing payment for 90-day mobile home occupants. A displaced tenant or owner-occupant of a...

  20. Neuroplasticity and functional recovery in multiple sclerosis

    PubMed Central

    Tomassini, Valentina; Matthews, Paul M.; Thompson, Alan J.; Fuglø, Daniel; Geurts, Jeroen J.; Johansen-Berg, Heidi; Jones, Derek K.; Rocca, Maria A.; Wise, Richard G.; Barkhof, Frederik; Palace, Jacqueline

    2013-01-01

    The development of therapeutic strategies that promote functional recovery is a major goal of multiple sclerosis (MS) research. Neuroscientific and methodological advances have improved our understanding of the brain’s recovery from damage, generating novel hypotheses for potential targets or modes of intervention and laying the foundation for the development of scientifically informed strategies promoting recovery in interventional studies. This Review aims to encourage the transition from characterization of recovery mechanisms to the development of strategies that promote recovery in MS. We discuss current evidence for functional reorganization that underlies recovery and its implications for development of new recovery-oriented strategies in MS. Promotion of functional recovery requires an improved understanding of recovery mechanisms modulated by interventions and the development of reliable measures of therapeutic effects. As imaging methods can be used to measure functional and structural alterations associated with recovery, this Review discusses their use as reliable markers to measure the effects of interventions. PMID:22986429

  1. A 90-Day Subchronic Toxicity Study of Submerged Mycelial Culture of Cordyceps cicadae (Ascomycetes) in Rats.

    PubMed

    Chen, Yen-Lien; Yeh, Shu-Hsing; Lin, Ting-Wei; Chen, Chin-Chu; Chen, Chin-Shuh; Kuo, Chia-Feng

    2015-01-01

    Cordyceps cicadae is a parasitic fungus that hibernates inside a host (Cicada flammata Dist.) and then grows its fruiting body on the surface of the insect. The complete insect/fungus combination of C. cicadae has been widely applied in Chinese traditional medicine. Recent studies have demonstrated that the medicinal benefits of cultured mycelia are as effective as those found in the wild. However, toxicological information regarding the chronic consumption of C. cicadae mycelia culture is not available. This study was conducted to evaluate the possible toxicity arising from repeated exposure to freeze-dried submerged mycelial culture of C. cicadae for 90 days. A total of eighty 8-week-old Sprague-Dawley rats were divided into 4 groups (10 males and 10 females in each group). C. cicadae was administered daily to animals by gavage at doses of 0, 500, 1000, and 2000 mg/kg body weight for 90 days. No animal deaths occurred and no treatment-related clinical signs were observed during the study period. No statistical differences in body weight gain, relative organ weight, hematology, serum chemistry, and urinalysis were observed. Gross necropsy and histopathological findings indicated that there was no treatment-related abnormality. Based on the results, the no observed adverse effect level of C. cicadae whole broth is determined to be > 2000 mg/kg for male and female Sprague-Dawley rats. The results of this study provides support for the use of C. cicadae fermentation product as a safe agent in functional food. PMID:26559863

  2. A 90-day subchronic toxicity study of neem oil, a Azadirachta indica oil, in mice.

    PubMed

    Wang, C; Cao, M; Shi, D-X; Yin, Z-Q; Jia, R-Y; Wang, K-Y; Geng, Y; Wang, Y; Yao, X-P; Yang, Z-R; Zhao, J

    2013-09-01

    To determine the no-observed-adverse-effect level (NOAEL) of exposure and target organs of neem oil for establishing safety criteria for human exposure, the subchronic toxicity study with neem oil in mice was evaluated. The mice (10 per sex for each dose) was orally administered with neem oil with the doses of 0 (to serve as a control), 177, 533 and 1600 mg/kg/day for 90 days. After the treatment period, observation of reversibility or persistence of any toxic effects, mice were continuously fed without treatment for the following 30 days. During the two test periods, the serum biochemistry, organ weight and histopathology were examined. The results showed that the serum biochemistry and organ coefficient in experimental groups had no statistical difference compared with those of the control group. At the 90th day, the histopathological examinations showed that the 1600 mg/kg/day dose of neem oil had varying degrees of damage on each organ except heart, uterus and ovarian. After 30-day recovery, the degree of lesions to the tissues was lessened or even restored. The NOAEL of neem oil was 177 mg/kg/day for mice and the target organs of neem oil were determined to be testicle, liver and kidneys. PMID:23444337

  3. 90-Day subchronic toxicity study of sodium molybdate dihydrate in rats.

    PubMed

    Murray, F Jay; Sullivan, Frank M; Tiwary, Asheesh K; Carey, Sandra

    2014-12-01

    This study investigated the subchronic toxicity of molybdenum (Mo) in Sprague-Dawley rats given sodium molybdate dihydrate in the diet for 90days at dose levels of 0, 5, 17 or 60mgMo/kgbw/day. The study complied with OECD Test Guideline (TG) 408, with additional examination of estrus cycles and sperm count, motility, and morphology from OECD TG 416. The overall no-observed-adverse-effect level was 17mgMo/kgbw/day, based on effects on body weight, body weight gain, food conversion efficiency and renal histopathology (females only) at 60mgMo/kgbw/day. No treatment-related adverse effects on reproductive organ weights or histopathology, estrus cycles or sperm parameters were observed at any dose level. No adverse effects were observed in the high dose animals after the 60-day recovery period, with the exception that male rats did not fully recover from reduced body weight. Serum blood, liver and kidney samples were analyzed for molybdenum, copper, zinc, manganese, iron, cobalt and selenium; high levels of molybdenum and copper were found in the serum, blood, liver and kidneys of rats treated with 60mgMo/kgbw/day. In conclusion, the LOAEL and NOAEL for molybdenum were determined to be 60 and 17mgMo/kgbw/day, respectively. PMID:24041747

  4. A 90-day subchronic toxicity study with sodium formononetin-3'-sulphonate (Sul-F) delivered to dogs via intravenous administration.

    PubMed

    Li, Chunmei; Li, Guisheng; Gao, Yonglin; Sun, Chengfeng; Wang, Xiaoyan

    2016-06-01

    Sodium formononetin-3'-sulphonate (Sul-F) is a water-soluble derivate of formononetin, and an increasing number of studies have shown that Sul-F not only possesses favorable water solubility but also exhibits good lipid-lowering and bioactivities. In the current study, the toxicity of Sul-F was evaluated in dogs after 90-day intravenous infusion. Dogs were treated with Sul-F at dose of 0, 33.3, 100, and 300 mg/kg, and observed for 90-day followed by 28-day recovery period. Weekly measurement of body weight, temperature and food consumption were conducted. Ophthalmoscopy, ECG examination, urinalysis, serum biochemistry and hematology examination were performed at pre-test, on days 45 and 90, and following by 28-day recovery period. Histological examination was performed on day 90 and 28-day recovery period. No mortality, ophthalmic abnormalities or treatment-related findings in body weight, clinical chemistry, hematology, and histopathological examination were detected. However, a white crystal (non-metabolic Sul-F), transient vomiting and recoverable vascular stimulation were observed in 300 mg/kg/day Sul-F treated dogs. Under the conditions, the no-observed-adverse-effect-level (NOAEL) for Sul-F was 100 mg/kg in dogs. PMID:26924788

  5. Visual-motor response of crewmen during a simulated 90-day space mission as measured by the critical task battery

    NASA Technical Reports Server (NTRS)

    Allen, R. W.; Jex, H. R.

    1973-01-01

    In order to test various components of a regenerative life support system and to obtain data on the physiological and psychological effects of long duration exposure to confinement in a space station atmosphere, four carefully screened young men were sealed in a space station simulator for 90 days and administered a tracking test battery. The battery included a clinical test (Critical Instability Task) designed to measure a subject's dynamic time delay, and a more conventional steady tracking task, during which dynamic response (describing functions) and performance measures were obtained. Good correlation was noted between the clinical critical instability scores and more detailed tracking parameters such as dynamic time delay and gain-crossover frequency. The levels of each parameter span the range observed with professional pilots and astronaut candidates tested previously. The chamber environment caused no significant decrement on the average crewman's dynamic response behavior, and the subjects continued to improve slightly in their tracking skills during the 90-day confinement period.

  6. Effects of 30-, 60-, and 90-Day Bed Rest on Postural Control in Men and Women

    NASA Technical Reports Server (NTRS)

    Esteves, Julie; Taylor, Laura C.; Vanya, Robert D.; Dean, S. Lance; Wood, Scott J.

    2011-01-01

    INTRODUCTION Head-down-tilt bed rest (HDT) has been used as a safe gr ound-based analog to mimic and develop countermeasures for the physiological effects of spaceflight, including decrements in postural stability. The purpose of this investigation was to characterize the effects of 30-, 60-, and 90-day bed rest on postural control in men and women. METHODS Twenty-nine subjects (18M,11F) underwent 13 days of ambula tory acclimatization and were placed in 6? HDT for 30 (n=12), 60 (n=8), or 90 (n=9) days, followed by 14 days of ambulatory recovery. Computerized dynamic posturography (CDP) was used to assess changes in sensory and motor components of postural control, and recovery after HDT. Sensory Organization Tests (SOTs) objectively evaluate one?s ability to effectively use or suppress visual, vestibular, and proprioceptive information for postural control. Stability during the SOTs was assessed using peak-to-peak sway and convergence toward stability limits to derive an equilibrium score. Motor Control Tests (MCTs) evaluate one?s ability to recover from unexpected support surface perturbations, with performance determined by center-of-pressure path length. Whole-body kinematic data were collected to determine body-sway strategy used to maintain stability during each condition. Baselines were determined pre-HDT. Recovery was tracked post-HDT on days 0, 1, 2, and 4. RESULTS Immediately after HDT, subjects showed decreased performance on most SOTs, primarily on sway-referenced support conditions, typically returning to baseline levels within 4 days. MCT performance was not significantly affected. There were no significant gender or duration differences in performance. Kinematic data revealed a tendency to use ankle strategy to maintain an upright stance during most SOT conditions. Interestingly, six subjects (2M,4F) experienced orthostatic intolerance and were unable to complete day 0 testing. CONCLUSION HDT mimics some un loading mechanisms of spaceflight and

  7. Zinc oxide nanoparticles: a 90-day repeated-dose dermal toxicity study in rats

    PubMed Central

    Ryu, Hwa Jung; Seo, Mu Yeb; Jung, Sung Kyu; Maeng, Eun Ho; Lee, Seung-Young; Jang, Dong-Hyouk; Lee, Taek-Jin; Jo, Ki-Yeon; Kim, Yu-Ri; Cho, Kyu-Bong; Kim, Meyoung-Kon; Lee, Beom Jun; Son, Sang Wook

    2014-01-01

    Zinc oxide (ZnO) works as a long-lasting, broad-spectrum physical sunblock, and can prevent skin cancer, sunburn, and photoaging. Nanosized ZnO particles are used often in sunscreens due to consumer preference over larger sizes, which appear opaque when dermally applied. Although the US Food and Drug Administration approved the use of nanoparticles (NPs) in sunscreens in 1999, there are ongoing safety concerns. The aim of this study was to evaluate the subchronic toxicity of ZnO NPs after dermal application according to the Organization for Economic Cooperation and Development Test Guidelines 411 using Good Laboratory Practice. Sprague Dawley rats were randomly divided into eight (one control, one vehicle control, three experimental, and three recovery) groups. Different concentrations of ZnO NPs were dermally applied to the rats in the experimental groups for 90 days. Clinical observations as well as weight and food consumption were measured and recorded daily. Hematology and biochemistry parameters were determined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. Analyses of tissue were undertaken to determine target organ tissue distribution. There was no increased mortality in the experimental group. Although there was dose-dependent irritation at the site of application, there were no abnormal findings related to ZnO NPs in other organs. Increased concentrations of ZnO in the liver, small intestine, large intestine, and feces were thought to result from oral ingestion of ZnO NPs via licking. Penetration of ZnO NPs through the skin seemed to be limited via the dermal route. This study demonstrates that there was no observed adverse effect of ZnO NPs up to 1,000 mg/kg body weight when they are applied dermally. PMID:25565832

  8. Zinc oxide nanoparticles: a 90-day repeated-dose dermal toxicity study in rats.

    PubMed

    Ryu, Hwa Jung; Seo, Mu Yeb; Jung, Sung Kyu; Maeng, Eun Ho; Lee, Seung-Young; Jang, Dong-Hyouk; Lee, Taek-Jin; Jo, Ki-Yeon; Kim, Yu-Ri; Cho, Kyu-Bong; Kim, Meyoung-Kon; Lee, Beom Jun; Son, Sang Wook

    2014-01-01

    Zinc oxide (ZnO) works as a long-lasting, broad-spectrum physical sunblock, and can prevent skin cancer, sunburn, and photoaging. Nanosized ZnO particles are used often in sunscreens due to consumer preference over larger sizes, which appear opaque when dermally applied. Although the US Food and Drug Administration approved the use of nanoparticles (NPs) in sunscreens in 1999, there are ongoing safety concerns. The aim of this study was to evaluate the subchronic toxicity of ZnO NPs after dermal application according to the Organization for Economic Cooperation and Development Test Guidelines 411 using Good Laboratory Practice. Sprague Dawley rats were randomly divided into eight (one control, one vehicle control, three experimental, and three recovery) groups. Different concentrations of ZnO NPs were dermally applied to the rats in the experimental groups for 90 days. Clinical observations as well as weight and food consumption were measured and recorded daily. Hematology and biochemistry parameters were determined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. Analyses of tissue were undertaken to determine target organ tissue distribution. There was no increased mortality in the experimental group. Although there was dose-dependent irritation at the site of application, there were no abnormal findings related to ZnO NPs in other organs. Increased concentrations of ZnO in the liver, small intestine, large intestine, and feces were thought to result from oral ingestion of ZnO NPs via licking. Penetration of ZnO NPs through the skin seemed to be limited via the dermal route. This study demonstrates that there was no observed adverse effect of ZnO NPs up to 1,000 mg/kg body weight when they are applied dermally. PMID:25565832

  9. Readmission After Robot-assisted Radical Cystectomy: Outcomes and Predictors at 90-Day Follow-up

    PubMed Central

    Al-Daghmin, Ali; Aboumohamed, Ahmed; Din, Rakeeba; Khan, Aabroo; Raza, Syed Johar; Sztorc, Jenna; Mehedint, Diana; Sharif, Mohammad; Shi, Yi; Wilding, Gregory; Guru, Khurshid A.

    2015-01-01

    OBJECTIVE To characterize the outcomes and predictors of readmission after robot-assisted radical cystectomy (RARC) during early (30-day) and late (31–90–day) postoperative periods. METHODS We retrospectively evaluated our prospectively maintained RARC quality assurance database of 272 consecutive patients operated between 2005 and 2012. We evaluated the relationship of readmission with perioperative outcomes and examined possible predictors during the postoperative period. RESULTS Overall 30- and 90-day mortality was 0.7% and 4.8%, respectively, with 25.5% patients readmitted within 90 days after RARC (61% of them were readmitted within 30 days and 39% were readmitted between 31–90 days postoperatively). Infection-related problems were the most common cause of readmission during early and late periods. Overall operative time and obesity were significantly associated with readmission (P = .034 and .033, respectively). Body mass index and female gender were independent predictors of 90-day readmission (P = .004 and .014, respectively). Having any type of complication correlated with 90-day readmission (P = .0045); meanwhile, when complications were graded on the basis of Clavien grading system, only grade 1–2 complications statistically correlated with readmission (P = .046). Four patients needed reoperation (2 patients in early “for appendicitis and adhesive small bowel obstruction” and 2 in late “for ureteroenteric stricture” readmission); meanwhile, 6 patients needed percutaneous procedures (4 patients in early “1 for anastomotic leak and 3 for pelvic collections” and 2 “for pelvic collections and ureterocutaneous fistula” in late readmission). CONCLUSION The rate of readmission within 90 days after RARC is significant. Female gender and body mass index are independent predictors of readmission. Outcomes at 90 days provide more thorough results, essential to proper patient counseling. PMID:24468509

  10. Recovery in schizophrenia: focus on neurocognitive functioning.

    PubMed

    Zaytseva, Yuliya; Gurovich, Isaac Ya; Goland, Etel; Storozhakova, Yaina A

    2012-09-01

    Recovery encompasses symptom remission and functional elements such as cognition, social functioning and quality of life. Personal recovery is also important in illness management to help the person stay on track with treatment and focus on activities unrelated to taking medication that maintain mental health. In the present study we aimed to identify neurocognitive functioning in two clinically stable groups of patients with personal recovery and non-recovered patients. The results showered generalized cognitive deficits in both groups while the non-recovery group was more impaired in verbal and visual memory, acoustic and tactile gnosis and neurodynamics and executing functioning. Interestingly the recovery group demonstrated lack of programming of actions and sufficient error monitoring and self-correction whereas the non-recovery group was significantly more impaired in all executive domains. The obtained results could be beneficial in identifying a target for psychosocial treatments and specifically cognitive remediation for patients with schizophrenia to facilitate the process of recovery. PMID:22945216

  11. A 90-day subchronic toxicity study and reproductive toxicity studies on ACE-inhibiting lactotripeptide.

    PubMed

    Dent, M P; O'Hagan, S; Braun, W H; Schaetti, P; Marburger, A; Vogel, O

    2007-08-01

    In recent years there has been an increasing body of literature describing the antihypertensive effects of peptides produced from milk protein. The tripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP), isolated from hydrolysed casein have been shown to lower blood pressure by inhibiting angiotensin I-converting enzyme (ACE). This has led to the use of these tripeptides, collectively referred to as lactotripeptide (LTP) as ingredients of functional foods intended to help control blood pressure. A programme of studies including a 90-day repeat-dose oral gavage toxicity study in the rat and an embryo-fetal (pre-natal) development study in the rabbit was conducted to ensure the safety of this ACE-inhibiting ingredient. In addition, a non-standard pre- and post-natal development study in the rat was performed. This study included direct dosing of the neonates, and was designed specifically to investigate renal development and to ensure that the bioactive peptides were not associated with the same type of fetopathy exhibited by ACE inhibiting drugs. These studies showed that there were no adverse effects of treatment at the highest doses tested. PMID:17383063

  12. A 90-day oral (dietary) toxicity study of rebaudioside A in Sprague-Dawley rats.

    PubMed

    Nikiforov, Andrey I; Eapen, Alex K

    2008-01-01

    Rebaudioside A is one of several glycosides found in the leaves of Stevia rebaudiana (Bertoni) Bertoni (Compositae) stevia that has been identified as a potential sweetener. The present study (initiated in April 2006 and completed in October 2006) evaluated the safety of this sweetener when administered as a dietary admix at target exposure levels of 500, 1000, and 2000 mg/kg/day to Sprague-Dawley rats for 90 days. There were no treatment-related effects on the general condition and behavior of the animals as determined by clinical observations, functional observational battery, and locomotor activity assessments. Evaluation of clinical pathology parameters revealed no toxicologically relevant, treatment-related effects on hematology, serum chemistry, or urinalysis. Macroscopic and microscopic findings revealed no treatment-related effects on any organ evaluated. Lower mean body weight gains were noted in males in the 2000 mg/kg/day group throughout the study, which was considered to be test article related; however, given the small magnitude of the difference as compared to controls, this effect was not considered to be adverse. Results of this study clearly demonstrate that dietary administration of high concentrations of rebaudioside A for 90 consecutive days to Sprague-Dawley rats was not associated with any signs of toxicity. PMID:18293214

  13. SUBCHRONIC 90-DAY TOXICITY OF DICHLOROACETIC AND TRICHLORACETIC ACID IN RATS

    EPA Science Inventory

    Male Sprague-Dawley rats were treated with either dichloroacetic acid (DCA) or trichloroacetic acid (TCA) in the drinking water at levels of 0, 50, 500 and 5000 ppm for a period of 90 days to determine the toxicities associated with subchronic exposure. ll animals were sacrificed...

  14. ACUTE, 14-DAY REPEATED DOSING, AND 90-DAY SUBCHRONIC TOXICITY STUDIES OF POTASSIUM PICLORAM (JOURNAL VERSION)

    EPA Science Inventory

    Potassium picloram was administered either by gavage (acute studies) or in drinking water to male and female Sprague-Dawley derived rats (14-day and 90-day studies). The acute oral LD50 was 950 mg/kg (812-1120) for males and 686 mg/kg (599-786) for females. Depression, prostratio...

  15. 49 CFR 24.402 - Replacement housing payment for 90-day occupants.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Replacement housing payment for 90-day occupants. 24.402 Section 24.402 Transportation Office of the Secretary of Transportation UNIFORM RELOCATION... classified as “low income” by the U.S. Department of Housing and Urban Development's Annual Survey of...

  16. 49 CFR 24.402 - Replacement housing payment for 90-day occupants.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false Replacement housing payment for 90-day occupants. 24.402 Section 24.402 Transportation Office of the Secretary of Transportation UNIFORM RELOCATION ASSISTANCE AND REAL PROPERTY ACQUISITION FOR FEDERAL AND FEDERALLY-ASSISTED PROGRAMS Replacement...

  17. 49 CFR 24.402 - Replacement housing payment for 90-day occupants.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... occupied the displacement dwelling for at least 90 days immediately prior to the initiation of negotiations... or she moves from the displacement dwelling; or (ii) For an owner-occupant, the later of: (A) The date he or she receives final payment for the displacement dwelling, or in the case of...

  18. 49 CFR 24.402 - Replacement housing payment for 90-day occupants.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... occupied the displacement dwelling for at least 90 days immediately prior to the initiation of negotiations... or she moves from the displacement dwelling; or (ii) For an owner-occupant, the later of: (A) The date he or she receives final payment for the displacement dwelling, or in the case of...

  19. 49 CFR 24.402 - Replacement housing payment for 90-day occupants.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... occupied the displacement dwelling for at least 90 days immediately prior to the initiation of negotiations... or she moves from the displacement dwelling; or (ii) For an owner-occupant, the later of: (A) The date he or she receives final payment for the displacement dwelling, or in the case of...

  20. A 90-Day Tenofovir Reservoir Intravaginal Ring for Mucosal HIV Prophylaxis

    PubMed Central

    Johnson, Todd J.; Clark, Meredith R.; Albright, Theodore H.; Nebeker, Joel S.; Tuitupou, Anthony L.; Clark, Justin T.; Fabian, Judit; McCabe, R. Tyler; Chandra, Neelima; Doncel, Gustavo F.; Friend, David R.

    2012-01-01

    A vaginal gel containing the antiretroviral tenofovir (TFV) recently demonstrated 39% protection against HIV infection in women. We designed and evaluated a novel reservoir TFV intravaginal ring (IVR) to potentially improve product effectiveness by providing a more controlled and sustained vaginal dose to maintain cervicovaginal concentrations. Polyurethane tubing of various hydrophilicities was filled with a high-density TFV/glycerol/water semisolid paste and then end-sealed to create IVRs. In vitro, TFV release increased with polyurethane hydrophilicity, with 35 weight percent water-swelling polyurethane IVRs achieving an approximately 10-mg/day release for 90 days with mechanical stiffness similar to that of the commercially available NuvaRing. This design was evaluated in two 90-day in vivo sheep studies for TFV pharmacokinetics and safety. Overall, TFV vaginal tissue, vaginal fluid, and plasma levels were relatively time independent over the 90-day duration at approximately 104 ng/g, 106 ng/g, and 101 ng/ml, respectively, near or exceeding the highest observed concentrations in a TFV 1% gel control group. TFV vaginal fluid concentrations were approximately 1,000-fold greater than levels shown to provide significant protection in women using the TFV 1% gel. There were no toxicological findings following placebo and TFV IVR treatment for 28 or 90 days, although slight to moderate increases in inflammatory infiltrates in the vaginal epithelia were observed in these animals compared to naïve animals. In summary, the controlled release of TFV from this reservoir IVR provided elevated sheep vaginal concentrations for 90 days to merit its further evaluation as an HIV prophylactic. PMID:23006751

  1. Dietary and Food Processing for a 90-day Bioregenerative Life Support Experiment in the Lunar Palace 1

    NASA Astrophysics Data System (ADS)

    Zhao, Zhiruo; Fu, Yuming; Dong, Chen; Liu, Guanghui

    A 4-day cycle dietary menu was developed to meet the requirements of balanced diet of the crew within the 90-day closed experiment of bioregenerative life support in the Lunar Palace 1. The menu consisted of items prepared from crops and insect grown inside the system, as well as prestored food. Dairy recipe was composed of breads, vegetables, meats and soups, which provided about 2900 kcal per crew member per day. During food processing, to maximize nutrient recovery and minimize waste production, the whole wheat grains and chufa nuts were milled. Further, the carrot leaves and yellow mealworms were used as salad materials and bread ingredients, respectively. The sensory acceptability of the dishes in the menu was evaluated by flavor, texture, and appearance. Our results show that all dishes in the 4-day cycle menu were highly acceptable, which satisfies nutritional requirement of the crew members in the closed habitation.

  2. Subchronic 90-day oral (Gavage) toxicity study of a Luo Han Guo mogroside extract in dogs.

    PubMed

    Qin, X; Xiaojian, S; Ronggan, L; Yuxian, W; Zhunian, T; Shouji, G; Heimbach, J

    2006-12-01

    A combined 28-day and 90-day oral (Gavage) study was conducted in male and female dogs to investigate the safety of PureLo, a non-caloric sweetener derived from the Chinese fruit Luo Han Guo, which achieves its sweetness from the presence of triterpene glycosides known as mogrosides. Three dogs of each sex were administered 10 mL/kg bw/day of either an aqueous solution providing 3000 mg/kg bw/day of PureLo or distilled water for either 28 days or 90 days. Measurements included clinical observations, body weight, food consumption, hematology, blood chemistry, urinalysis, gross necropsy, organ weight, and histopathology. There were no significant adverse effects on any of these measures. Based on the lack of toxicological effects in the study, the NOAEL for PureLo is 3000 mg/kg bw/day when administered to dogs by Gavage for 90 consecutive days. PMID:17011100

  3. Safety assessment of meat from transgenic cattle by 90-day feeding study in rats.

    PubMed

    Liu, Shan; Li, Chen-Xi; Feng, Xiao-Lian; Wang, Hui-Ling; Liu, Hai-Bo; Zhi, Yuan; Geng, Gui-Ying; Zhao, Jie; Xu, Hai-Bin

    2013-07-01

    The study was carried out to evaluate the subchronic toxicity of meat derived from human lactoferrin gene-modified cattle in male and female Wistar rats. Rats were fed 5% or 10% transgenic meat diet, 5% or 10% conventional meat diet, or AIN93G diet for 90 days. During the study, body weight and food consumption were weighed weekly and clinical observations were conducted daily. At the end of the study, urinary examination, hematology and blood biochemistry examination, macroscopic and microscopic examinations were performed. There were no biologically significant differences in these factors between the rat groups fed transgenic meat diet and conventional meat diet. Therefore, the present 90-day rodent feeding study suggests that meat derived from the transgenic cattle is equivalent to meat from conventional cattle in use as dietary supplements. PMID:23583492

  4. 12 CFR 220.117 - Exception to 90-day rule in special cash account.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... the language and intent of the above-quoted exception in § 220.4(c)(8), until it has been honored by... substantially the same as language found in section 4(f) of Regulation T as originally promulgated in 1934. The language of the subject exception to the 90-day rule of § 220.4(c)(8), i.e., the exception based...

  5. 90-Day feeding and genotoxicity studies on a refined arachidonic acid-rich oil.

    PubMed

    Casterton, P L; Curry, L L; Lina, B A R; Wolterbeek, A P M; Kruger, C L

    2009-10-01

    The safety of a refined arachidonic acid-rich oil (RAO) was evaluated for reverse mutation, chromosome aberration and gene mutation, and in a 90-day Wistar rat feeding study with in utero exposure. The results of the genotoxicity assays were all negative. The in utero phase of the 90-day study involved dietary exposure to 0.5%, 1.5% and 5% RAO and two controls diets, a standard feed low-fat diet and a high-fat diet supplemented with 5% corn oil. This exposure covered four-weeks prior to mating, through mating, gestation and lactation until offspring (F(1)) weaning. A subsequent 90-day feeding study in the F(1) rats evaluated the same test and control diets. Statistically significant effects were seen for selected histopathology, clinical chemistry and organ weight endpoints; however, other than increased absolute and relative monocytes seen in both sexes of high-dose rats, the observations were not attributed to treatment for one or more reasons. Based on these findings, no adverse treatment-related effects for RAO were seen at up to 5% in the diet, equivalent to an overall average RAO intake of 3170 mg/kg bwt/day. These and similar findings for other refined ARA-rich oils establish a strong body of evidence for the safety of this RAO. PMID:19576260

  6. Phase II, Randomized, Placebo-controlled, 90-day Study of Emixustat HCL in Geographic Atrophy Associated with Dry Age-Related Macular Degeneration

    PubMed Central

    Dugel, Pravin U.; Novack, Roger L.; Csaky, Karl G.; Richmond, Preston P.; Birch, David G.; Kubota, Ryo

    2015-01-01

    Purpose This study assessed the safety, tolerability, and pharmacodynamics of emixustat hydrochloride (ACU-4429), a novel visual cycle modulator, in subjects with geographic atrophy (GA) associated with dry age-related macular degeneration (AMD). Methods Subjects were randomly assigned to oral emixustat (2, 5, 7, or 10 mg once daily) or placebo (3:1 ratio) for 90 days. Recovery of rod photoreceptor sensitivity following a photobleach was measured by electroretinography. Safety evaluations included analysis of adverse events (AEs) and ophthalmic examinations. Results Seventy-two subjects (54 emixustat, 18 placebo) were evaluated. Emixustat suppressed rod photoreceptor sensitivity in a dose-dependent manner. Suppression plateaued by Day 14, and was reversible within 7-14 days after drug cessation. No systemic AEs of concern were noted. Dose-related ocular AEs (chromatopsia, 57% emixustat vs. 17% placebo; and delayed dark adaptation, 48% emixustat vs. 6% placebo) were mild to moderate, and the majority resolved on study or within 7-14 days after study drug cessation. Conclusions In this phase II study, emixustat produced a dose-dependent, reversible effect on rod function, and an ocular AE profile that is consistent with the proposed mechanism of action. These results support further testing of emixustat for the treatment of GA associated with dry AMD. PMID:25932553

  7. The impact of 90-day prescriptions on adherence at workplace pharmacies compared to traditional mail order.

    PubMed

    Patwardhan, Avinash; Davis, Jeffery; Murphy, Patricia; Khandelwal, Nikhil; Sherman, Bruce; Manfred, James

    2011-12-01

    This study evaluated adherence to medications used to treat chronic conditions for patients with 90-day prescriptions, comparing patients with access to workplace pharmacy services versus patients using mail order services. De-identified pharmacy claims data were used to compute medication possession ratio and gaps in therapy. Results were compared for patients who filled 90-day prescriptions at workplace pharmacies versus patients who filled 90-day prescriptions using mail order pharmacy services in a 1-year period. Statistical tests to assess between group differences were performed controlling for differences because of age, sex, number of select chronic conditions, number of unique medication therapeutic classes, and patient out-of-pocket cost per therapy day. Statistically significant differences were found between patients who filled their maintenance medications at the worksite compared to those who used mail-order pharmacy services. Patients filling prescriptions at a workplace pharmacy were 22% less likely to have a gap in therapy of over 30 days compared to similar patients using mail order services. Workplace pharmacy utilizers also had overall adherence rates 3.68% higher than patients who utilized mail order pharmacy services. Our analysis suggests that it may not be just the quantity of medication dispensed that impacts patients' adherence to their prescription medication, but a variety of other factors including pharmacist-patient interaction. Having a pharmacist on-site and available to patients with chronic considerations could provide added value. These results can aid employers and other stakeholders to decide which prescription benefits to offer their employees and members. PMID:22092153

  8. Training and certification program of the operating staff for a 90-day test of a regenerative life support system

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Prior to beginning a 90-day test of a regenerative life support system, a need was identified for a training and certification program to qualify an operating staff for conducting the test. The staff was responsible for operating and maintaining the test facility, monitoring and ensuring crew safety, and implementing procedures to ensure effective mission performance with good data collection and analysis. The training program was designed to ensure that each operating staff member was capable of performing his assigned function and was sufficiently cross-trained to serve at certain other positions on a contingency basis. Complicating the training program were budget and schedule limitations, and the high level of sophistication of test systems.

  9. 76 FR 12683 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Texas...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-08

    ... Fish and Wildlife Service 50 CFR Part 17 Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Texas Kangaroo Rat as Endangered or Threatened AGENCY: Fish and Wildlife....S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list the...

  10. 75 FR 19925 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition to List a Distinct...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-16

    ... Fish and Wildlife Service 50 CFR Part 17 Endangered and Threatened Wildlife and Plants; 90-Day Finding... 90-day finding (56 FR 1159) indicating that the fisher in the Pacific States is a distinct population... habitat needs, population size and trends, and demographic parameters (56 FR 1159). On December 29,...

  11. 76 FR 23256 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Arapahoe...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-26

    ... published two 90-day findings, on January 6, 2009 (74 FR 419), and February 5, 2009 (74 FR 6122). The February 5, 2009 (74 FR 6122), 90-day finding concluded that the petition did not present substantial..., as critical habitat for the Preble's meadow jumping mouse (Zapus hudsonius preblei) (68 FR 37275)....

  12. 77 FR 9618 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-17

    ... Fish and Wildlife Service 50 CFR Part 17 Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Thermophilic Ostracod as Endangered or Threatened AGENCY: Fish and Wildlife Service, Interior. ACTION: Notice of 90-day petition finding. SUMMARY: We, the U.S. Fish and...

  13. 78 FR 72622 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List 11 Tarantula...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-03

    ... Fish and Wildlife Service 50 CFR Part 17 Endangered and Threatened Wildlife and Plants; 90-Day Finding... AGENCY: Fish and Wildlife Service, Interior. ACTION: Notice of petition finding and initiation of status review. SUMMARY: We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on...

  14. A 90-day study of sub-chronic oral toxicity of 20 nm positively charged zinc oxide nanoparticles in Sprague Dawley rats

    PubMed Central

    Park, Hark-Soo; Kim, Seon-Ju; Lee, Taek-Jin; Kim, Geon-Yong; Meang, EunHo; Hong, Jeong-Sup; Kim, Su-Hyon; Koh, Sang-Bum; Hong, Seung-Guk; Sun, Yle-Shik; Kang, Jin Seok; Kim, Yu-Ri; Kim, Meyoung-Kon; Jeong, Jayoung; Lee, Jong-Kwon; Son, Woo-Chan; Park, Jae-Hak

    2014-01-01

    Purpose The study reported here was conducted to determine the systemic oral toxicity and to find the no-observed-adverse-effect level of 20 nm positively charged zinc oxide (ZnOSM20(+)) nanoparticles in Sprague Dawley rats for 90 days. Methods For the 90-day toxicity study, the high dose was set as 500 mg per kg of body weight (mg/kg) and the middle and low dose were set to 250 mg/kg and 125 mg/kg, respectively. The rats were held for a 14-day recovery period after the last administration, to observe for the persistence or reduction of any toxic effects. A distributional study was also carried out for the systemic distribution of ZnOSM20(+) NPs. Results No rats died during the test period. There were no significant clinical changes due to the test article during the experimental period in functional assessment, body weight, food and water consumption, ophthalmological testing, urine analysis, necropsy findings, or organ weights, but salivation was observed immediately after administration in both sexes. The total red blood cell count was increased, and hematocrit, albumin, mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration were decreased significantly compared with control in both 500 mg/kg groups. Total protein and albumin levels were decreased significantly in both sexes in the 250 and 500 mg/kg groups. Histopathological studies revealed acinar cell apoptosis in the pancreas, inflammation and edema in stomach mucosa, and retinal atrophy of the eye in the 500 mg/kg group. Conclusion There were significant parameter changes in terms of anemia in the hematological and blood chemical analyses in the 250 and 500 mg/kg groups. The significant toxic change was observed to be below 125 mg/kg, so the no-observed-adverse-effect level was not determined, but the lowest-observed-adverse-effect level was considered to be 125 mg/kg in both sexes and the target organs were found to be the pancreas, eye, and stomach. PMID:25565829

  15. Transcriptome analyses reveal molecular mechanisms underlying functional recovery after spinal cord injury

    PubMed Central

    Duan, Hongmei; Ge, Weihong; Zhang, Aifeng; Xi, Yue; Chen, Zhihua; Luo, Dandan; Cheng, Yin; Fan, Kevin S.; Horvath, Steve; Sofroniew, Michael V.; Cheng, Liming; Yang, Zhaoyang; Sun, Yi E.; Li, Xiaoguang

    2015-01-01

    Spinal cord injury (SCI) is considered incurable because axonal regeneration in the central nervous system (CNS) is extremely challenging, due to harsh CNS injury environment and weak intrinsic regeneration capability of CNS neurons. We discovered that neurotrophin-3 (NT3)-loaded chitosan provided an excellent microenvironment to facilitate nerve growth, new neurogenesis, and functional recovery of completely transected spinal cord in rats. To acquire mechanistic insight, we conducted a series of comprehensive transcriptome analyses of spinal cord segments at the lesion site, as well as regions immediately rostral and caudal to the lesion, over a period of 90 days after SCI. Using weighted gene coexpression network analysis (WGCNA), we established gene modules/programs corresponding to various pathological events at different times after SCI. These objective measures of gene module expression also revealed that enhanced new neurogenesis and angiogenesis, and reduced inflammatory responses were keys to conferring the effect of NT3-chitosan on regeneration. PMID:26460053

  16. Transcriptome analyses reveal molecular mechanisms underlying functional recovery after spinal cord injury.

    PubMed

    Duan, Hongmei; Ge, Weihong; Zhang, Aifeng; Xi, Yue; Chen, Zhihua; Luo, Dandan; Cheng, Yin; Fan, Kevin S; Horvath, Steve; Sofroniew, Michael V; Cheng, Liming; Yang, Zhaoyang; Sun, Yi E; Li, Xiaoguang

    2015-10-27

    Spinal cord injury (SCI) is considered incurable because axonal regeneration in the central nervous system (CNS) is extremely challenging, due to harsh CNS injury environment and weak intrinsic regeneration capability of CNS neurons. We discovered that neurotrophin-3 (NT3)-loaded chitosan provided an excellent microenvironment to facilitate nerve growth, new neurogenesis, and functional recovery of completely transected spinal cord in rats. To acquire mechanistic insight, we conducted a series of comprehensive transcriptome analyses of spinal cord segments at the lesion site, as well as regions immediately rostral and caudal to the lesion, over a period of 90 days after SCI. Using weighted gene coexpression network analysis (WGCNA), we established gene modules/programs corresponding to various pathological events at different times after SCI. These objective measures of gene module expression also revealed that enhanced new neurogenesis and angiogenesis, and reduced inflammatory responses were keys to conferring the effect of NT3-chitosan on regeneration. PMID:26460053

  17. Program operational summary: Operational 90 day manned test of a regenerative life support system

    NASA Technical Reports Server (NTRS)

    Jackson, J. K.; Wamsley, J. R.; Bonura, M. S.; Seeman, J. S.

    1972-01-01

    An operational 90-day manned test of a regenerative life support system was successfully completed. This test was performed with a crew of four carefully selected and trained men in a space station simulator (SSS) which had a two gas atmosphere maintained at a total pressure of 68.9, 10 psia, and composed of oxygen at a partial pressure of 3.05 psia with nitrogen as the diluent. The test was planned to provide data on regenerative life support subsystems and on integrated system operations in a closed ecology, similar to that of a space station. All crew equipment and expendables were stored onboard at the start of the mission to eliminate the need for pass-in operations. The significant accomplishments of the test, some of the pertinent test results, some of the problem areas, and conclusions are presented.

  18. Ultrastructural response of rat lung to 90 days' exposure to oxygen at 450 mm Hg

    NASA Technical Reports Server (NTRS)

    Harrison, G. A.

    1974-01-01

    Young Sprague-Dawley rats were exposed to 100% oxygen at 450 mm Hg in constant environment capsules for 90 days. Lung tissue examined by electron microscopy revealed a number of changes, many similar to those observed after exposure to oxygen at 760 mm Hg for shorter periods of time. Alterations in vesicle size and number and in mitochondrial matrix and cristae appear in both the endothelial and epithelial cells. Blebbing and rarefication of cytoplasm occur in both cell layers of the alveolo-capillary wall. Also seen are fluid in the basement membrane, platelets in the capillaries, and alveolar fluid and debris. All of these alterations occur at 1 atm exposure. However, after exposure to 450 mm Hg the changes are not as widespread nor as destructive as they are at the higher pressure.

  19. Training plan for the 1164 {lt}90-day non-radioactive hazardous waste storage building

    SciTech Connect

    Demarest, J.L., Westinghouse Hanford

    1996-07-01

    In accordance with Washington Administrative Code (WAC), Chapter 173- 303, `Dangerous Waste Regulations,` a written training plan is required for a {lt}90-day accumulation area. WAC 173-303-200, `Accumulating Dangerous Waste On-site,` requires compliance with WAC- 173-303-330, Personnel Training. This training plan complies with WAC 173-303-330. This training plan, including the names of personnel in Table 1, may be given to a regulatory agency inspector upon request provided that this plan is cleared for public release. Training records associated with personnel identified in this plan are not be given to an outside regulatory agency inspector unless prior approval by the specific individual is obtained. Training records requests by regulatory agency inspectors without the individual`s approval are to be processed via a Freedom of Information Act request through the U.S. Department of Energy, Richland Operations Office.

  20. Bioregenerative Life Support Experiment for 90-days in a Closed Integrative Experimental Facility LUNAR PALACE 1

    NASA Astrophysics Data System (ADS)

    Liu, Hong

    A 90-day bioregenerative life support experiment with three-member crew was carried out in the closed integrative experimental facility, LUNAR PALACE 1 regenerating basic living necessities and disposing wastes to provide life support for crew. It was composed of higher plant module, animal module, and waste treatment module. The higher plant module included wheat, chufa, pea, carrot and green leafy vegetables, with aim to satisfy requirement of 60% plant food and 100% O2 and water for crew. The yellow mealworm was selected as animal module to provide partial animal protein for crew, and reared on plant inedible biomass. The higher plant and yellow mealworm were both cultivated and harvested in the conveyor-type manner. The partial plant inedible biomass and human feces were mixed and co- fermented in the waste treatment module for preparation of soil-like substrate by bioconversion, maintaining gas balance and increasing closure degree. Meanwhile, in the waste treatment module, the water and partial nitrogen from human urine were recovered by physical-chemical means. Circulation of O2 and water as well as food supply from crops cultivated in the LUNAR PALACE 1 were investigated and calculated, and simultaneously gas exchange, mass flow among different components and system closure degree were also analyzed, respectively. Furthermore, the system robustness with respect to internal variation was tested and evaluated by sensitivity analysis of the aggregative index consisting of key performance indicators like crop yield, gaseous equilibrium concentration, microbial community composition, biogenic elements dynamics, etc., and comprehensively evaluating the operating state, to number change of crew from 2 to 4 during the 90-day closed experiment period.

  1. Toxicity of colloidal silica nanoparticles administered orally for 90 days in rats

    PubMed Central

    Kim, Yu-Ri; Lee, Seung-Young; Lee, Eun Jeong; Park, Sung Ha; Seong, Nak-won; Seo, Heung-Sik; Shin, Sung-Sup; Kim, Seon-Ju; Meang, Eun-Ho; Park, Myeong-Kyu; Kim, Min-Seok; Kim, Cheol-Su; Kim, Soo-Ki; Son, Sang Wook; Seo, Young Rok; Kang, Boo Hyon; Han, Beom Seok; An, Seong Soo A; Lee, Beom-Jun; Kim, Meyoung-Kon

    2014-01-01

    This study was undertaken to investigate the potential toxicity and establish the no observed adverse effect level (NOAEL) and target organ(s) of negatively charged colloidal silica particles of different sizes, ie, SiO2EN20(−) (20 nm) or SiO2EN100(−) 2(100 nm), administered by gavage in Sprague-Dawley rats. After verification of the physicochemical properties of the SiO2 particles to be tested, a preliminary dose range-finding study and 90-day repeated dose study were conducted according to the Organisation for Economic Cooperation and Development test guideline. Based on the results of the 14-day dose range-finding study, a high dose was determined to be 2,000 mg/kg, and middle and low doses were set at 1,000 and 500 mg/kg, respectively. In the 90-day toxicity study, there were no animal deaths in relation to administration of SiO2 particles of either size. In addition, no treatment-related clinical changes or histopathological findings were observed in any of the experimental groups. Moreover, no difference in toxic effects from chronic exposure to SiO2EN20(−)(20 nm) or SiO2EN100(−) (100 nm) was observed. The results of this study indicate that the NOAEL for SiO2EN20(−) and SiO2 EN100(−) would most likely be 2,000 mg/kg, and no target organ was identified in rats of either sex. PMID:25565827

  2. Co-morbidities and 90-day outcomes in hospitalized COPD exacerbations.

    PubMed

    Roberts, Christopher M; Stone, Robert A; Lowe, Derek; Pursey, Nancy A; Buckingham, Rhona J

    2011-10-01

    COPD exacerbations resulting in hospitalization are accompanied by high mortality and morbidity. The contribution of specific co-morbidities to acute outcomes is not known in detail: existing studies have used either administrative data or small clinical cohorts and have provided conflicting results. Identification of co-existent diseases that affect outcomes provides opportunities to address these conditions proactively and improve overall COPD care. Cases were identified prospectively on admission then underwent retrospective case note audit to collect data including co-morbidities on up to 60 unselected consecutive acute COPD admissions between March and May in each hospital participating in the 2008 UK National COPD audit. Outcomes recorded were death in hospital, length of stay, and death and readmission at 90 days after index admission. 232 hospitals collected data on 9716 patients, mean age 73, 50% male, mean FEV1 42% predicted. Prevalence of co-morbidities were associated with increased age but better FEV1 and ex-smoker status and with worse outcomes for all four measures. Hospital mortality risk was increased with cor pulmonale, left ventricular failure, neurological conditions and non-respiratory malignancies whilst 90 day death was also increased by lung cancer and arrhythmias. Ischaemic and other heart diseases were important factors in readmission. This study demonstrates that co-morbidities adversely affect a range of short-term patient outcomes related to acute admission to hospital with exacerbations of COPD. Recognition of relevant accompanying diseases at admission provides an opportunity for specific interventions that may improve short-term prognosis. PMID:21864116

  3. A 90 day chronic toxicity study of Nigerian herbal preparation DAS-77 in rats

    PubMed Central

    2012-01-01

    Background The herbal preparation DAS-77, used for the treatment of various ailments in Nigeria, contains the milled bark of Mangifera indica L. and root of Carica papaya L. Toxicological assessment of the preparation was carried out in this study. Methods In the acute toxicity study, DAS-77 was administered to mice p.o. up to 20 g/kg in divided doses and i.p. at 250–3000 mg/kg. Mortality within 24 h was recorded. In the chronic toxicity study, rats were treated p.o. for 90 days at doses of 80, 400 (therapeutic dose, TD) and 2000 mg/kg. By 90 days, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination, antioxidants and histopathological assessments. Results DAS-77 did not produce any lethality administered p.o. up to 20 g/kg in divided doses but the i.p. LD50 was 1122.0 mg/kg. At TD, DAS-77 produced significant (p < 0.05) reductions in body weight, food intake and K+, and increases in ovary weight, neutrophils and HDL, which were reversible. Histopathological presentations were generally normal. Effects at the other doses were comparable to those at TD except for reversible increases in antioxidants in the liver, kidney and testes, and sperm abnormality, and reductions in liver enzymes, sperm motility and count. Conclusions Findings in this study revealed that DAS-77 is relatively safe with the potential for enhancing in vivo antioxidant activity. However, possibly reversible side-effects include electrolyte imbalance and sterility in males. PMID:22892317

  4. 78 FR 10601 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition to List 44 Species of Corals as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-14

    ... National Oceanic and Atmospheric Administration RIN 0648-XC209 Endangered and Threatened Wildlife; 90-Day... Species Act AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and Atmospheric... temperature, availability of hard substrate, currents and sediment load, and seawater chemistry...

  5. 77 FR 43799 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Gila...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-26

    ... Regional Office. On December 16, 2009 (74 FR 66866), we published a partial 90-day finding on the petition... and, therefore, less habitat available. Increased siltation may be due to historical overgrazing...

  6. A 90-Day Oral Toxicological Evaluation of the Methylurate Purine Alkaloid Theacrine

    PubMed Central

    Hirka, Gábor; Glávits, Róbert; Palmer, Philip A.; Endres, John R.; Pasics Szakonyiné, Ilona

    2016-01-01

    A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on the methylurate purine alkaloid theacrine, which is found naturally in certain plants. Four groups of Hsd.Brl.Han Wistar rats (ten/sex/group) were administered theacrine by gavage doses of 0 (vehicle only), 180, 300, and 375 mg/kg bw/day. Two females and one male in the 300 and 375 mg/kg bw/day groups, respectively, died during the study. Histological examination revealed centrilobular hepatocellular necrosis as the probable cause of death. In 375 mg/kg bw/day males, slight reductions in body weight development, food consumption, and feed efficiency, decreased weight of the testes and epididymides and decreased intensity of spermatogenesis in the testes, lack or decreased amount of mature spermatozoa in the epididymides, and decreased amount of prostatic secretions were detected at the end of the three months. At 300 mg/kg bw/day, slight decreases in the weights of the testes and epididymides, along with decreased intensity of spermatogenesis in the testes, and lack or decreased amount of mature spermatozoa in the epididymides were detected in male animals. The NOAEL was considered to be 180 mg/kg bw/day, as at this dose there were no toxicologically relevant treatment-related findings in male or female animals.

  7. Toxicological evaluation of L-proline in a 90-day feeding study with Fischer 344 rats.

    PubMed

    Tada, Y; Yano, N; Takahashi, H; Yuzawa, K; Ando, H; Kubo, Y; Nagasawa, A; Ohashi, N; Ogata, A; Nakae, D

    2010-10-01

    L-proline (L-Pro) is a non-essential amino acid, and has become widely used as supplements and health foods, recently. A subchronic oral toxicity study of L-Pro was conducted with groups of 10 male and 10 female Fischer 344 rats fed a powder diet containing 0%, 0.625%, 1.25%, 2.5% and 5.0% of L-Pro for 90 days. No treatment-related clinical signs and mortality were noted. We observed no clear treatment-related effects with regard to body weight, food intake or urinalysis data. The average daily water intakes of the treated female groups were significantly increased compared to the controls. The hematology (red blood cell parameter) and serum biochemistry (glucose, blood urea nitrogen, creatinine or uric acid) of the treated male and/or female groups were lower than those of the control groups. However, these changes were lacked dose-dependence, and no abnormalities were found in corresponding pathological findings. In conclusion, the no-observed-adverse-effect-level (NOAEL) for L-Pro was determined to be a dietary dose of 5.0% (2772.9 mg/kg body weight/day for males and 3009.3mg/kg body weight/day for females) under the present experimental conditions. PMID:20447433

  8. Evaluation of silica nanoparticle toxicity after topical exposure for 90 days

    PubMed Central

    Ryu, Hwa Jung; Seong, Nak-won; So, Byoung Joon; Seo, Heung-sik; Kim, Jun-ho; Hong, Jeong-Sup; Park, Myeong-kyu; Kim, Min-Seok; Kim, Yu-Ri; Cho, Kyu-Bong; Seo, Mu Yeb; Kim, Meyoung-Kon; Maeng, Eun Ho; Son, Sang Wook

    2014-01-01

    Silica is a very common material that can be found in both crystalline and amorphous forms. Well-known toxicities of the lung can occur after exposure to the crystalline form of silica. However, the toxicities of the amorphous form of silica have not been thoroughly studied. The majority of in vivo studies of amorphous silica nanoparticles (NPs) were performed using an inhalation exposure method. Since silica NPs can be commonly administered through the skin, a study of dermal silica toxicity was necessary to determine any harmful effects from dermal exposures. The present study focused on the results of systemic toxicity after applying 20 nm colloidal silica NPs on rat skin for 90 days, in accordance with the Organization for Economic Cooperation and Development test guideline 411 with a good laboratory practice system. Unlike the inhalation route or gastrointestinal route, the contact of silica NPs through skin did not result in any toxicity or any change in internal organs up to a dose of 2,000 mg/kg in rats. PMID:25565831

  9. Evaluation of silica nanoparticle toxicity after topical exposure for 90 days.

    PubMed

    Ryu, Hwa Jung; Seong, Nak-won; So, Byoung Joon; Seo, Heung-sik; Kim, Jun-ho; Hong, Jeong-Sup; Park, Myeong-kyu; Kim, Min-Seok; Kim, Yu-Ri; Cho, Kyu-Bong; Seo, Mu Yeb; Kim, Meyoung-Kon; Maeng, Eun Ho; Son, Sang Wook

    2014-01-01

    Silica is a very common material that can be found in both crystalline and amorphous forms. Well-known toxicities of the lung can occur after exposure to the crystalline form of silica. However, the toxicities of the amorphous form of silica have not been thoroughly studied. The majority of in vivo studies of amorphous silica nanoparticles (NPs) were performed using an inhalation exposure method. Since silica NPs can be commonly administered through the skin, a study of dermal silica toxicity was necessary to determine any harmful effects from dermal exposures. The present study focused on the results of systemic toxicity after applying 20 nm colloidal silica NPs on rat skin for 90 days, in accordance with the Organization for Economic Cooperation and Development test guideline 411 with a good laboratory practice system. Unlike the inhalation route or gastrointestinal route, the contact of silica NPs through skin did not result in any toxicity or any change in internal organs up to a dose of 2,000 mg/kg in rats. PMID:25565831

  10. A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats

    PubMed Central

    Park, Hark-Soo; Shin, Sung-Sup; Meang, Eun Ho; Hong, Jeong-sup; Park, Jong-Il; Kim, Su-Hyon; Koh, Sang-Bum; Lee, Seung-Young; Jang, Dong-Hyouk; Lee, Jong-Yun; Sun, Yle-Shik; Kang, Jin Seok; Kim, Yu-Ri; Kim, Meyoung-Kon; Jeong, Jayoung; Lee, Jong-Kwon; Son, Woo-Chan; Park, Jae-Hak

    2014-01-01

    Purpose The widespread use of nanoparticles (NPs) in industrial and biomedical applications has prompted growing concern regarding their potential toxicity and impact on human health. This study therefore investigated the subchronic, systemic oral toxicity and no-observed-adverse-effect level (NOAEL) of 20 nm, negatively charged zinc oxide (ZnOSM20(−)) NPs in Sprague Dawley rats for 90 days. Methods The high-dose NP level was set at 500 mg/kg of bodyweight, and the mid- and low-dose levels were set at 250 and 125 mg/kg, respectively. The rats were observed during a 14-day recovery period after the last NP administration for the persistence or reduction of any adverse effects. Toxicokinetic and distribution studies were also conducted to determine the systemic distribution of the NPs. Results No rats died during the test period. However, ZnOSM20(−) NPs (500 mg/kg) induced changes in the levels of anemia-related factors, prompted acinar cell apoptosis and ductular hyperplasia, stimulated periductular lymphoid cell infiltration and excessive salivation, and increased the numbers of regenerative acinar cells in the pancreas. In addition, stomach lesions were seen at 125, 250, and 500 mg/kg, and retinal atrophy was observed at 250 and 500 mg/kg. The Zn concentration was dose-dependently increased in the liver, kidney, intestines, and plasma, but not in other organs investigated. Conclusion A ZnOSM20(−) NP NOAEL could not be established from the current results, but the lowest-observed-adverse-effect level was 125 mg/kg. Furthermore, the NPs were associated with a number of undesirable systemic actions. Thus, their use in humans must be approached with caution. PMID:25565828

  11. Petroleum prices and profits in the 90 days following the invasion of Kuwait

    SciTech Connect

    Not Available

    1990-11-01

    For the third in the past 20 years the world has experienced an interruption in the flow of oil from the Persian Gulf. The Iraqi invasion of Kuwait on August 2, 1990, and shut down of Kuwait oil production capacity followed by the United Nations boycott of Iraqi oil removed 8 percent of the world's oil supply. The result was a sharp increase in the process of crude oil and petroleum products. These events raised numerous questions about the performance of energy markets and energy firms. This report supplies a first answer for some of those questions. At the time this report was prepared the invasion has been in effect for 90 days. Not all the data is available to fully answer every question. Some issues can only be completely resolved after more time has passed in which the invasion and its effects have had an opportunity to be fully assimilated. This report was specifically requested by W. Henson Moore, Deputy Secretary of Energy as a way of supplying the American public with what could be said about the current situation. Rumors abound and mixconceptions have proliferated. This report strives to give a proper perspective on some of the more vexing issues which the invasion produced. The Energy Information Administration (EIA) has addressed many questions in this report. By the way of summary these are the 10 most most frequently asked questions and EIA's quick answers. The page references tell the reader where to look in the report for further explanation. These are not the only issues addressed and EIA hopes that readers will be able to satisfy their curiosity about their own questions within the pages of this report.

  12. Intra- and Inter-Patient Symptom Variability in Fibromyalgia: Results of a 90-Day Assessment.

    PubMed

    Toussaint, Loren; Vincent, Ann; McAllister, Samantha J; Whipple, Mary

    2015-06-01

    Symptoms of fibromyalgia (FM)--chronic widespread pain, fatigue, unrefreshing sleep, dyscognition etcetera--present with varying degrees of severity in different individuals; however, studies reporting daily estimates of variability of symptoms are sparse. Given the limited literature on the stability and variability of FM symptoms, the purpose of the present study was to determine the feasibility of daily visual analogue, self-report measures to assess daily variability and time trends in core FM symptoms. Ten female patients completed daily assessments of common FM symptoms (pain, fatigue, anxiety, depression, stress, cognitive dysfunction, unrefreshing sleep and lightheadedness) for approximately 90 days. The completion rate was excellent (89.6%). The results demonstrated that average symptom intensity differs markedly across the different symptoms that were measured. Unrefreshing sleep, fatigue and pain are clearly higher in intensity than other symptoms and are followed by memory problems, stress, anxiety and depression. There is also notable average intra-individual change across time (10-15 points on a 100-point scale). Average symptom intensity does not appear to be related to the amount of symptom change within individuals. The results of the present study confirm that intensive longitudinal study, using comprehensive symptom assessment in patients with FM, is both possible and informative, in the sense that a rich description of the daily experience of living with FM can be obtained. Future work, utilizing larger samples, will offer the opportunity to investigate better the causes, consequences and correlates of the daily ups and downs of key symptoms that compromise quality of life in patients with FM. PMID:25408116

  13. An estimate of equatorial wave energy flux at 9- to 90-day periods in the Central Pacific

    NASA Technical Reports Server (NTRS)

    Eriksen, Charles C.; Richman, James G.

    1988-01-01

    Deep fluctuations in current along the equator in the Central Pacific are dominated by coherent structures which correspond closely to narrow-band propagating equatorial waves. Currents were measured roughly at 1500 and 3000 m depths at five moorings between 144 and 148 deg W from January 1981 to March 1983, as part of the Pacific Equatorial Ocean Dynamics program. In each frequency band resolved, a single complex empirical orthogonal function accounts for half to three quarters of the observed variance in either zonal or meridional current. Dispersion for equatorial first meridional Rossby and Rossby gravity waves is consistent with the observed vertical-zonal coherence structure. The observations indicate that energy flux is westward and downward in long first meridional mode Rossby waves at periods 45 days and longer, and eastward and downward in short first meridional mode Rossby waves and Rossby-gravity waves at periods 30 days and shorter. A local minimum in energy flux occurs at periods corresponding to a maximum in upper-ocean meridional current energy contributed by tropical instability waves. Total vertical flux across the 9- to 90-day period range is 2.5 kW/m.

  14. Recent Trends in the Dispensing of 90-Day-Supply Prescriptions at Retail Pharmacies: Implications for Improved Convenience and Access

    PubMed Central

    Liberman, Joshua N.; Girdish, Charmaine

    2011-01-01

    Background Mail-service pharmacies offer consumers the convenience of prescriptions filled with a 90-day supply of medication. Unlike mail-service pharmacies, retail pharmacies traditionally dispensed maintenance medication prescriptions with a 30-day supply. However, the retail landscape changed in May 2008 with Walmart's announcement of an extension of its $4 Prescription Program to include 90-day-supply prescriptions. Objective To evaluate recent changes in access to and use of 90-day-supply maintenance medications dispensed via retail pharmacy. Summary As of the first quarter of 2007, the proportion of retail-dispensed maintenance medications with a 90-day supply (compared with all maintenance prescriptions dispensed) among Medicare Part D plans, self-insured employers, and private health plans was 5.1%, 5.1%, and 5.0%, respectively. As of December 2009, this ratio had risen to 8.0% for Medicare plans and 8.1% for commercial health plans; the ratio among employers had risen more modestly to 6.1%. Of particular interest and importance, the proportion increased similarly for brand and for generic medications. Conclusion There has been substantial growth in 90-day prescriptions dispensed via retail pharmacy, a trend that is likely to continue as more insurance providers adopt compatible benefit designs. It is important to continue monitoring these trends and to identify opportunities to rigorously evaluate their impact on medication adherence and healthcare costs. PMID:25126341

  15. Comparative 90-day dietary study of paraffin wax in Fischer-344 and Sprague-Dawley rats.

    PubMed

    Griffis, L C; Twerdok, L E; Francke-Carroll, S; Biles, R W; Schroeder, R E; Bolte, H; Faust, H; Hall, W C; Rojko, J

    2010-01-01

    Highly refined mineral hydrocarbons (MHCs) such as low melting point paraffin wax (LMPW) and low viscosity white oils can cause inflammatory changes in the liver and mesenteric lymph nodes (MLNs) of the Fischer-344 (F-344) rat. In contrast, only minimal MLN changes are seen in the Sprague-Dawley (S-D) rat with no changes in the liver. In this study, the response of female F-344 and S-D rats was compared after 90days dietary treatment with 0%, 0.2% or 2% LMPW. Effects in the F-344 rats were significantly greater than in the S-D rats: increased liver and splenic weights and inflammatory changes (hepatic microgranulomas) in these tissues were observed only in the F-344 rats. Microgranulomas in the MLNs were observed in both strains but the effects were substantially greater in the F-344 rats. Cellular markers of inflammation were examined in a subset of rats from each group using immunohistochemical staining. An increase in staining for CD3 (T-cells), CD8a (suppresser/cytotoxic T-cells) and CD4 (helper T-cells) correlated with an increase in lymphoid cells in the livers of treated F-344 rats. The majority of macrophages in the hepatic microgranulomas of treated F-344 rats were negative for the ED2 marker, indicating a likely origin from non-resident macrophages. Electron microscopy showed Kupffer cell hypertrophy and hyperplasia in treated F-344 rats. However, lysozyme staining (indicating activation of epithelioid macrophages) decreased with increasing granuloma size. Non-ED2 expressing cells may have been recruited but not sufficiently activated to be lysozyme positive. Inflammatory changes in the cardiac mitral valve noted in previous studies of LMPW were also seen in the F-344 rats in this study but not in the S-D rats. Chemical analysis showed that MHC accumulated in livers from treated F-344 but not S-D rats and the concentration was more than 2-fold greater in MLNs from the F-344 than from the S-D rats. The F-344 appears to be more immunologically sensitive to

  16. A 90-day dietary study on kappa carrageenan with emphasis on the gastrointestinal tract.

    PubMed

    Weiner, Myra L; Nuber, David; Blakemore, William R; Harriman, Jay F; Cohen, Samuel M

    2007-01-01

    Groups of Fischer 344 rats (20/sex/group) received control or treated diets at levels of 0, 25,000 or 50,000 ppm kappa carrageenan with a molecular weight range (Mw) of 196,000-257,000 Da for 90 days. The Low Molecular Weight Tail (LMT) ranged between 1.9% and 12.0%<50 kDa (mean 7%) based on the results of a program initiated to develop a validated analytical method to measure the LMT. This is the first GLP dietary study in which carrageenan is characterized by percentage LMT. Clinical examinations were performed daily. Individual food consumption/body weight measurements were made weekly. Ophthalmic exam was conducted prior to and at the end of treatment. Hematology/serum chemistry and urinalysis evaluations were done at necropsy, as were organ weight determinations for adrenals, brain, heart, kidneys, liver, ovaries, spleen, testes and thyroid with parathyroids. Full histopathological evaluation of organs was conducted on the control and 50,000 ppm groups, including hematoxylin-eosin-stained cross sections of paraffin-embedded rolled colon. Clinical signs were limited to soft feces in high dose rats and to a lesser extent in low dose rats. There were no treatment-related effects on body weights, urinalysis, hematology or clinical chemistry parameters, or on organ weights or ophthalmic, macroscopic or microscopic findings. The gastrointestinal tract appeared normal in detailed histopathological evaluation using the Swiss roll technique. The NOAEL is 50,000 ppm in the diet (mean calculated test material consumption of 3394+/-706 mg/kg/day in males, 3867+/-647 mg/kg/day in females). The results of the study provide evidence that it is not necessary to characterize carrageenan by a specification for LMT (less than 5% below 50 kDa) as has been done in Commission Directive 2004/45/EC of 16 April 2004 (Commission Directive, 2004/45/EC of 16 April 2004 amending Directive 96/77/EC laying down specific purity criteria on food additives other than colors and sweeteners

  17. 76 FR 10299 - Endangered and Threatened Wildlife and Plants: 90-Day Finding on a Petition To List the Wild...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-24

    ... completed a 90-day finding on August 15, 2007 (72 FR 45717). Based upon the information available at that... FR 54707), for the Arctic grayling (Thymallus arcticus) and a 12-month finding published on September 22, 2010, for the plant Agave eggersiana (75 FR 57720), we have focused on wild populations in...

  18. 77 FR 59582 - Endangered and Threatened Wildlife; 90-Day Finding on Petitions To List the Northeastern Pacific...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-28

    ...We, NMFS, announce a 90-day finding on two petitions received to list the northeastern Pacific Ocean population of great white shark (Carcharodon carcharias) as a threatened or endangered distinct population segment (DPS) under the Endangered Species Act (ESA) and to designate critical habitat concurrently with the listing. We find that the petitions and information in our files present......

  19. 78 FR 69376 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition To List 19 Species and 3...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-19

    ...We (NMFS) announce a 90-day finding on a petition to list 19 species and 3 subpopulations of sharks as threatened or endangered under the Endangered Species Act (ESA). We find that the petition presents substantial scientific or commercial information indicating that the petitioned action may be warranted for 9 species: Centrophorus harrissoni, Isogomphodon oxyrhynchus, Mustelus fasciatus,......

  20. 75 FR 18782 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List Thorne's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE INTERIOR Fish and Wildlife Service 50 CFR Part 17 Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List Thorne's Hairstreak Butterfly as Endangered Correction In Federal...

  1. 78 FR 23533 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To Delist the Wood Bison

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-19

    ... February 8, 2011 (76 FR ] 6734). Please refer to that document for the complete listing history. Here we... Wildlife, which was published in the Federal Register on June 2, 1970 (35 FR 8491). In 1974, the first list... of Wild Fauna and Flora (CITES). In a 90-day finding published on November 25, 1998 (63 FR 65164),...

  2. 77 FR 47583 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List Desert...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-09

    ...We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list desert massasauga (Sistrurus catenatus edwardsii), a rattlesnake found in the southwestern United States, as endangered or threatened under the Endangered Species Act of 1973, as amended (Act), and to designate critical habitat. Based on our review, we find that the petition presents substantial......

  3. 77 FR 55458 - Endangered and Threatened Species; 90-Day Finding on Petition To Delist the Southern Oregon...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-10

    ... these petitions was published on October 7, 2011 (76 FR 62375) and a second negative 90-day finding for the fourth petition was published on January 11, 2012 (77 FR 1668). The new petition largely..., changes in salmon landings over the past 1-2 decades, and increases in Pacific Ocean water temperature....

  4. 75 FR 42059 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Giant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-20

    ... that listing the GPE may be warranted (72 FR 57273). On January 24, 2008, the petitioners filed a... presented a threat (72 FR 57273). The 2009 petition includes a letter of support from Samuel W. James... educational purposes as a potential threat to the GPE. In our October 9, 2007, 90-day finding (72 FR 57273)...

  5. 77 FR 1900 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Humboldt...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-12

    ...We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list the Humboldt marten (Martes americana humboldtensis) as endangered or threatened and designate critical habitat under the Endangered Species Act of 1973, as amended (Act). Based on our review, we find that the petition presents substantial scientific or commercial information indicating that......

  6. 78 FR 66675 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition To List Multiple Species of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-06

    ... purposes of listing, delisting, and reclassifying a species under the ESA (``DPS Policy''; 61 FR 4722; February 7, 1996). A species, subspecies, or DPS is ``endangered'' if it is in danger of extinction... extinction risk of concern for the species at issue. To make a 90-day finding on a petition to list a...

  7. 78 FR 57611 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition To List Alabama Shad as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-19

    ... In 1997, we added Alabama shad to our Candidate Species List (62 FR 37562; July 14, 1997). At that... (49 FR 38900; October 1, 1984). In 2004, we created the Species of Concern list (69 FR 19975; April 15... published a negative 90-day finding in the Federal Register (76 FR 9320) stating that the petition did...

  8. 78 FR 29098 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition To List Iliamna Lake Seals as a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-17

    ... Vertebrate Population Segments under the ESA (DPS Policy, 61 FR 4722; February 7, 1996). This policy... species under the ESA (61 FR 4722; February 7, 1996). The policy established two criteria that must be met... Threatened Wildlife; 90-Day Finding on a Petition To List Iliamna Lake Seals as a Threatened or...

  9. 75 FR 67341 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Bay...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-02

    ... on a Petition To List the Bay Springs Salamander as Endangered AGENCY: Fish and Wildlife Service..., announce a 90-day finding on a petition to list the Bay Springs salamander (Plethodon ainsworthi) as... Springs salamander or its habitat at any time. DATES: The finding announced in this document was made...

  10. 77 FR 21920 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Eastern...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-12

    ... a notice of a 90-day finding for the petition in the Federal Register on July 22, 1994 (59 FR 37439... warranted but precluded by other higher priority actions (60 FR 15281). At that time, a listing priority..., 2005 (70 FR 24870). On October 7, 2002, as part of an agreement regarding multiple species, the...

  11. 75 FR 13068 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition to List the Berry...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-18

    ...We, the U.S. Fish and Wildlife Service, announce a 90-day finding on a petition to list the Berry Cave salamander (Gyrinophilus gulolineatus) as endangered under the Endangered Species Act of 1973, as amended. Based on our review, we find that the petition presents substantial scientific or commercial information indicating that listing this species may be warranted. Therefore, with the......

  12. 77 FR 71757 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List Phoenix...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-04

    ...We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list Phoenix dactylifera `Sphinx' (sphinx date palm) as endangered or threatened under the Endangered Species Act of 1973, as amended (Act). We find that the petition does not present substantial scientific or commercial information indicating that the petitioned action may be warranted. We find that......

  13. 75 FR 51969 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition to List the Oklahoma...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-24

    ...We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list Calopogon oklahomensis (Oklahoma grass pink orchid) as endangered or threatened under the Endangered Species Act of 1973, as amended (Act). Based on our review, we find that the petition presents substantial scientific or commercial information indicating that listing the plant species, C.......

  14. 75 FR 13720 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition to List the Striped...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-23

    ...We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list the striped newt (Notophthalmus perstriatus) as threatened under the Endangered Species Act of 1973, as amended (Act). We find that the petition presents substantial scientific or commercial information indicating that listing the striped newt may be warranted. Therefore, with the publication of......

  15. 77 FR 4973 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition to List the San...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-01

    ...We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list the San Bernardino flying squirrel (Glaucomys sabrinus californicus) as endangered or threatened and to designate critical habitat under the Endangered Species Act of 1973, as amended (Act). Based on our review, we find that the petition presents substantial scientific or commercial information......

  16. 77 FR 27403 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Eastern...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-10

    ...We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list the eastern diamondback rattlesnake (Crotalus adamanteus) as threatened under the Endangered Species Act of 1973, as amended (Act) and to designate critical habitat. Based on our review, we find that the petition presents substantial scientific or commercial information indicating that listing the......

  17. 76 FR 60431 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the American...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-29

    ..., 2005, the Service issued a 90-day finding (70 FR 38849), which found that the petition presented... threatened or ] endangered was not warranted (72 FR 4967). Species Information This section is a summary of the species information presented in the Service's 2007 12-month finding (72 FR 4967),...

  18. Renal function recovery in chronic dialysis patients.

    PubMed

    Chu, Jay K; Folkert, Vaughn W

    2010-01-01

    Renal function recovery (RFR) from acute kidney injury requiring dialysis occurs at a high frequency. RFR from chronic dialysis, on the other hand, is an uncommon but well-recognized phenomenon, occurring at a rate of 1.0-2.4% according to data from large observational studies. The underlying etiology of renal failure is the single most important predicting factor of RFR in chronic dialysis patients. The disease types with the highest RFR rates are atheroembolic renal disease, systemic autoimmune disease, renovascular diseases, and scleroderma. The disease types with the lowest RFR rates are diabetic nephropathy and cystic kidney disease. Initial dialysis modality does not appear to influence RFR. Careful observation and history taking are needed to recognize the often nonspecific clinical and laboratory signs of RFR. When RFR is suspected in a chronic dialysis patient, a 24-hour urine urea and creatinine clearance should be measured. Based on the renal clearance, along with other clinical factors, the dialysis prescription may be gradually reduced until a complete discontinuation of dialysis. After RFR from maintenance dialysis, patients require close follow-up in an office setting for chronic kidney disease management. PMID:21166875

  19. Plasticity and functional recovery in neurology.

    PubMed

    Ramachandran, V S

    2005-01-01

    Experiments on patients with phantom limbs suggest that neural connections in the adult human brain are much more malleable than previously assumed. Three weeks after amputation of an arm, sensations from the ipsilateral face are referred to the phantom; this effect is caused by the sensory input from the face skin 'invading' and activating deafferented hand zones in the cortex and thalamus. Many phantom arms are 'paralysed' in a painful position. If a mirror is propped vertically in the sagittal plane and the patient looks at the reflection of his/her normal hand, this reflection appears superimposed on the 'felt' position of the phantom. Remarkably, if the real arm is moved, the phantom is felt to move as well and this sometimes relieves the painful cramps in the phantom. Mirror visual feedback (MVF) has shown promising results with chronic regional pain syndrome and hemiparesis following stroke. These results suggest two reasons for a paradigm shift in neurorehabilitation. First, there appears to be tremendous latent plasticity even in the adult brain. Second, the brain should be thought of, not as a hierarchy of organised autonomous modules, each of which delivers its output to the next level, but as a set of complex interacting networks that are in a state of dynamic equilibrium with the brain's environment. Both principles can be potentially exploited in a clinical context to facilitate recovery of function. PMID:16138492

  20. 76 FR 9309 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Sand...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-17

    ...We, the U.S. Fish and Wildlife Service, announce a 90-day finding on a petition to list the sand verbena moth, Copablepharon fuscum, as endangered or threatened under the Endangered Species Act of 1973, as amended. Based on our review, we find the petition presents substantial information indicating that listing the sand verbena moth may be warranted. Therefore, with the publication of this......

  1. 76 FR 36049 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Utah...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-21

    ...We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list the Utah population of the Gila monster (Heloderma suspectum) as an endangered or a threatened distinct population segment (DPS) under the Endangered Species Act of 1973, as amended (Act), and to designate critical habitat. Based on our review, we find that the petition does not present......

  2. 77 FR 39666 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List Maytenus cymosa

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-05

    ...We, the U.S. Fish and Wildlife Service (Service), announce a 90-day finding on a petition to list the Maytenus cymosa (Caribbean mayten), a tree, as endangered or threatened under the Endangered Species Act of 1973, as amended (Act), and to designate critical habitat. Based on our review, we find that the petition does not present substantial information indicating that listing M. cymosa may......

  3. Influences of northward propagating 25-90-day and quasi-biweekly oscillations on eastern China summer rainfall

    NASA Astrophysics Data System (ADS)

    Chen, Jiepeng; Wen, Zhiping; Wu, Renguang; Chen, Zesheng; Zhao, Ping

    2015-07-01

    The present study reveals that rainfall anomalies associated with the 25-90-day (quasi-biweekly) tropical convective activity propagates northward (northwestward) into northern China (the Yangtze River). Enhanced rainfall over southern China results directly from enhanced convection propagating northward from the South China Sea (SCS)-western north Pacific (WNP), strengthened northward water vapor transport and intensified upper-level divergence. The anomalous anticyclone over SCS-WNP, which is induced by local lower sea surface temperature, provides a favorable condition for transporting more moisture to southern China. Stronger subtropical westerly jet and South Asia high strengthen upper-level divergence. The northward propagating 25-90-day oscillation over eastern China reaches farther north than the quasi-biweekly oscillation (QBWO). The intensity of QBWO in summer rainfall has significantly strengthened over southern China after 1993 but not for the 25-90-day oscillation. This is mainly contributed by an interdecadal increase in rainfall over southern China and the Yangtze River Basin in the wet phases of QBWO. The interdecadal enhancement of rainfall associated with the QBWO is attributed to three factors. One is lower tropospheric convergence caused by anomalous anticyclone over the WNP and anomalous cyclone over Korean Peninsula and Japan. The second is upper tropospheric divergence resulting from strengthening of subtropical westerly jet and the South Asia high. The last is enhanced ascent over South China through meridional vertical circulation.

  4. First Report of 90-Day Support of Two Calves with a Continuous-Flow Total Artificial Heart

    PubMed Central

    Karimov, Jamshid H.; Moazami, Nader; Kobayashi, Mariko; Sale, Shiva; Such, Kimberly; Byram, Nicole; Sunagawa, Gengo; Horvath, David; Gao, Shengqiang; Kuban, Barry; Golding, Leonard A.; Fukamachi, Kiyotaka

    2015-01-01

    Objective The Cleveland Clinic continuous-flow total artificial heart (CFTAH) is a compact, single-piece, valveless, pulsatile pump providing self-regulated hemodynamic output to left/right circulation. We evaluated chronic in vivo pump performance, physiologic and hemodynamic parameters, and biocompatibility of the CFTAH in a well-established calf model. Methods CFTAH pumps have been implanted in 17 calves total. Hemodynamics, pump performance, and device-related adverse events were evaluated during studies and at necropsy. Results In vivo experiments demonstrated good hemodynamic performance (pump flow, 7.3 ± 0.7 L/min; left atrial pressure [LAP], 16 ± 3 mm Hg; right atrial pressure [RAP], 17 ± 3 mm Hg; RAP-LAP difference, 1 ± 2 mm Hg; mean arterial pressure, 103 ± 7 mm Hg; arterial pulse pressure, 30 ± 11 mm Hg; pulmonary arterial pressure, 34 ± 5 mm Hg). The CFTAH has operated within design specifications and never failed. With ever-improving pump design, the implants have shown no chronic hemolysis. Three recent animals with the CFTAH recovered well, with no postoperative anticoagulation, during planned in vivo durations of 30, 90, and 90 days (last two were intended to be 90-day studies). All these longest-surviving cases showed good biocompatibility, with no thromboembolism in organs. Conclusions The current CFTAH has demonstrated reliable self-regulation of hemodynamic output and acceptable biocompatibility without anticoagulation throughout 90 days of chronic implantation in calves. Meeting these milestones is in accord with our strategy to achieve transfer of this unique technology to surgical practice, thus filling the urgent need for cardiac replacement devices as destination therapy. PMID:26173607

  5. The development and succession of microbial communities in 90-day Bioregenerative Life Support Experiment in the Lunar Palace 1

    NASA Astrophysics Data System (ADS)

    Sun, Yi; Liu, Hong; Fu, Yuming; Liu, Bojie; Su, Qiang; Xie, Beizhen; Qin, Youcai; Dong, Chen; Liu, Guanghui

    Lunar Palace 1, as an integrative experiment facility for permanent astrobase life-support artificial closed ecosystem, is an artificial ecosystem which consists of plant cultivation, animal breeding and waste treatment units. It has been used to carry out a 90-day bioregenerative life support experiment with three crew members. Apparently, it’s hard to prevent the growth of microorganisms in such closed ecosystem for their strong adaptive capacity. Original microorganisms in the cabin, microbes in the course of loads delivery and the autologous microorganism by crew members and animals themselves are all the main source of the interior microorganisms, which may grow and regenerate in air, water and plants. Therefore, if these microorganisms could not be effectively monitored and controlled, it may cause microbial contamination and even lead to the unsteadiness of the whole closed ecosystem. In this study, the development and succession of the microbial communities of air, water system, plant system, and key facilities surfaces in Lunar Palace 1 were continuously monitored and analyzed by using plate counting method and molecular biological method during the 90-day experiment. The results were quite useful for the controlling of internal microorganisms and the safe operation of the whole system, and could also reveal the succession rules of microorganisms in an artificial closed ecosystem.

  6. Safety assessment of essential oil from Minthostachys verticillata (Griseb.) Epling (peperina): 90-days oral subchronic toxicity study in rats.

    PubMed

    Escobar, Franco Matías; Sabini, María Carola; Cariddi, Laura Noelia; Sabini, Liliana Inés; Mañas, Fernando; Cristofolini, Andrea; Bagnis, Guillermo; Gallucci, Mauro Nicolas; Cavaglieri, Lilia Renée

    2015-02-01

    Minthostachys verticillata (Lamiaceae), popularly known as peperina is largely used in popular medicine for its digestive, carminative, antispasmodic and antirheumatic properties. There are no reports of repeated exposure toxicity to guarantee their safety. The present study investigated the chemical composition, analyzed by GC-FID, and the 90-day toxicity and genotoxicity effect of M. verticillata essential oil (Mv-EO), using Wistar rats as test animals. The rats were divided into four groups (5 rats/sex/group) and Mv-EO was administered on diet at doses of 0, 1, 4 and 7 g/kg feed. The main components of Mv-EO were pulegone (64.65%) and menthone (23.92%). There was no mortality, adverse effects on general conditions or changes in body weight, food consumption and feed conversion efficiency throughout the study in male and female rats. Subchronic administration of Mv-EO did not alter the weights, morphological and histopathological analyses of liver, kidney and intestine. Genotoxicity was tested by micronucleus and comet assays. Mv-EO up to a concentration of 7 g/kg feed for 90 days did not exert a cyto-genotoxic effect on the bone marrow and cells blood of Wistar rats. These results suggest that Mv-EO appears to be safe and could be devoid of any toxic risk. PMID:25445298

  7. Recovery from silver-nanoparticle-exposure-induced lung inflammation and lung function changes in Sprague Dawley rats.

    PubMed

    Song, Kyung Seuk; Sung, Jae Hyuck; Ji, Jun Ho; Lee, Ji Hyun; Lee, Jong Seong; Ryu, Hyeon Ryol; Lee, Jin Kyu; Chung, Yong Hyun; Park, Hyun Min; Shin, Beom Soo; Chang, Hee Kyung; Kelman, Bruce; Yu, Il Je

    2013-03-01

    In a previous study, the lung function, as indicated by the tidal volume, minute volume, and peak inspiration flow, decreased during 90 days of exposure to silver nanoparticles and was accompanied by inflammatory lesions in the lung morphology. Therefore, this study investigated the recovery from such lung function changes in rats following the cessation of 12 weeks of nanoparticle exposure. Male and female rats were exposed to silver nanoparticles (14-15 nm diameter) at concentrations of 0.66 × 10(6) particles/cm(3) (49 μg/m(3), low dose), 1.41 × 10(6) particles/cm(3) (117 μg/m(3), middle dose), and 3.24 × 10(6) particles/cm(3) (381 μg/m(3), high dose) for 6 h/day in an inhalation chamber for 12 weeks. The rats were then allowed to recover. The lung function was measured every week during the exposure period and after the cessation of exposure, plus animals were sacrificed after the 12-week exposure period, and 4 weeks and 12 weeks after the exposure cessation. An exposure-related lung function decrease was measured in the male rats after the 12-week exposure period and 12 weeks after the exposure cessation. In contrast, the female rats did not show a consistent lung function decrease either during the exposure period or following the exposure cessation. The histopathology showed a gradual recovery from the lung inflammation in the female rats, whereas the male rats in the high-dose group exhibited persistent inflammation throughout the 12-week recovery period. Therefore, the present results suggest a potential persistence of lung function changes and inflammation induced by silver nanoparticle exposure above the no observed adverse effect level. PMID:22264098

  8. Pulmonary toxicity of simulated lunar and Martian dusts in mice: I. Histopathology 7 and 90 days after intratracheal instillation

    NASA Technical Reports Server (NTRS)

    Lam, Chiu-Wing; James, John T.; McCluskey, Richard; Cowper, Shawn; Balis, John; Muro-Cacho, Carlos

    2002-01-01

    NASA is contemplating sending humans to Mars and to the moon for further exploration. Volcanic ashes from Arizona and Hawaii with mineral properties similar to those of lunar and Martian soils, respectively, are used to simulate lunar and Martian environments for instrument testing. Martian soil is highly oxidative; this property is not found in Earth's volcanic ashes. NASA is concerned about the health risk from potential exposure of workers in the test facilities. Fine lunar soil simulant (LSS), Martian soil simulant (MSS), titanium dioxide, or quartz in saline was intratracheally instilled into groups of 4 mice (C57BL/6J) at 0.1 mg/mouse (low dose, LD) or 1 mg/mouse (high dose, HD). Separate groups of mice were exposed to ozone (0.5 ppm for 3 h) prior to MSS instillation. Lungs were harvested for histopathological examination 7 or 90 days after the single dust treatment. The lungs of the LSS-LD groups showed no evidence of inflammation, edema, or fibrosis; clumps of particles and an increased number of macrophages were visible after 7 days but not 90 days. In the LSS-HD-7d group, the lungs showed mild to moderate alveolitis, and perivascular and peribronchiolar inflammation. The LSS-HD-90d group showed signs of mild chronic pulmonary inflammation, septal thickening, and some fibrosis. Foci of particle-laden macrophages (PLMs) were still visible. Lung lesions in the MSS-LD-7d group were similar to those observed in the LSS-HD-7d group. The MSS-LD-90d group had PLMs and scattered foci of mild fibrosis in the lungs. The MSS-HD-7d group showed large foci of PLMs, intra-alveolar debris, mild-to-moderate focal alveolitis, and perivascular and peribronchiolar inflammation. The MSS-HD-90d group showed focal chronic mild-to-moderate alveolitis and fibrosis. The findings in the O(3)-MSS-HD-90d group included widespread intra-alveolar debris, focal moderate alveolitis, and fibrosis. Lung lesions in the MSS groups were more severe with the ozone pretreatment. The effects of

  9. APPLYING EXPERIENCE SAMPLING METHODS TO PARTNER VIOLENCE RESEARCH: SAFETY AND FEASIBILITY IN A 90-DAY STUDY OF COMMUNITY WOMEN

    PubMed Central

    Sullivan, Tami P.; Khondkaryan, Enna; Dos Santos, Nancy P.; Peters, Erica N.

    2011-01-01

    An experience sampling method (ESM) rarely has been applied in studies of intimate partner violence (IPV) despite the benefits to be gained. Because ESM approaches and women who experience IPV present unique challenges for data collection an empirical question exists: is it safe and feasible to apply ESM to community women who currently are experiencing IPV? A 90-day, design-driven feasibility study examined daily telephone data collection, daily paper diaries, and monthly retrospective semi-structured interview methods among a community sample of 123 women currently experiencing IPV to study within-person relationships between IPV and substance use. Findings suggest that ESM is a promising method for collecting data among this population and can elucidate daily dynamics of victimization as well as associated behaviors and experiences. Lessons learned from the application of ESM to this population are also discussed. PMID:21307033

  10. A 90-day study of three bruchid-resistant mung bean cultivars in Sprague-Dawley rats.

    PubMed

    Yao, Yang; Cheng, Xuzhen; Ren, Guixing

    2015-02-01

    Mung bean has been traditionally and widely used as an edible and medicinal plant in the South and Southeast Asia. Bruchid resistance mung bean has more potential in commercial use, but scarcely been evaluated for safety through standard in vivo toxicological studies. In the present study, subchronic oral toxicity studies of bruchid-resistant mung bean were designed and conducted in Sprague-Dawley (SD) rats for 90 days. During the subchronic oral toxicity study, no mortality and toxicologically significant changes in clinical signs, food consumption, opthalmoscopic examination, hematology, clinical biochemistry, macroscopic findings, organ weights and histopathological examination were noted in animal administered diet containing bruchid-resistant mung bean. These results demonstrated that bruchid resistant mung bean is as safe as conventional mung bean. PMID:25533792

  11. [Ophthalmoscopic observations of ocular fundus in colony-born cynomolgus monkeys aged from 0 day to 90 days].

    PubMed

    Suzuki, M T; Narita, H; Tanaka, Y; Cho, F; Fukui, M

    1984-04-01

    Apparently healthy 242 colony-born cynomolgus monkeys (Macaca fascicularis) aged from 0 day to 90 days were examined for the findings of ocular fundus by using ophthalmoscope. One drop of mixed solution of 0.5% tropicamide and 0.5% phenylephrine hydrochloride was instilled into each eye of the monkey. Then, those monkeys were anesthetized with ketamine-HC1 at the dose level of 10mg/kg B. W. Regular and fluorescein photographs were taken with Kowa RC-II ophthalmoscope-camera by using daylight typed color film. Following findings were obtained in each age class: Retinal color was salmon pink with 0 to 3-days-old neonates, salmon pink and blue to green with 7 days to 14-days-old animals and blue to green with 60-days to 90-days-old monkeys. As regards optic disc, 0- to 14-days-old animals were observed to be light orange in color, and the infant aged more than 28-days showed orange color. Retinal arteries and veins were lightly reddish in color with every age class. Macular color was salmon pink in 0-day-old cases, slightly dark in 3-days-old neonates and very dark after 14-days of age. Lightly retinal reflex was noted in 0- and 7-days-old animals. The reflex was observable in 14-days-old animals without any case of exception. Retinal hemorrhages were recorded in 22 (67%) of 36 neonates born in natural condition and 10 (33%) of 30 neonates born by cesarean section. These findings will be useful as the criteria for ophthalmoscopic observations of the cynomolgus monkeys as laboratory use. PMID:6468512

  12. Toxicity of 100 nm zinc oxide nanoparticles: a report of 90-day repeated oral administration in Sprague Dawley rats

    PubMed Central

    Kim, Yu-Ri; Park, Jong-Il; Lee, Eun Jeong; Park, Sung Ha; Seong, Nak-won; Kim, Jun-Ho; Kim, Geon-Yong; Meang, Eun-Ho; Hong, Jeong-Sup; Kim, Su-Hyon; Koh, Sang-Bum; Kim, Min-Seok; Kim, Cheol-Su; Kim, Soo-Ki; Son, Sang Wook; Seo, Young Rok; Kang, Boo Hyon; Han, Beom Seok; An, Seong Soo A; Yun, Hyo-In; Kim, Meyoung-Kon

    2014-01-01

    Nanoparticles (NPs) are used commercially in health and fitness fields, but information about the toxicity and mechanisms underlying the toxic effects of NPs is still very limited. The aim of this study is to investigate the toxic effect(s) of 100 nm negatively (ZnOAE100[−]) or positively (ZnOAE100[+]) charged zinc oxide (ZnO) NPs administered by gavage in Sprague Dawley rats, to establish a no observed adverse effect level, and to identify target organ(s). After verification of the primary particle size, morphology, hydrodynamic size, and zeta potential of each test article, we performed a 90-day study according to Organisation for Economic Co-operation and Development test guideline 408. For the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses were set at 125 mg/kg and 31.25 mg/kg, respectively. Both ZnO NPs had significant changes in hematological and blood biochemical analysis, which could correlate with anemia-related parameters, in the 500 mg/kg groups of both sexes. Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions. We speculate that this inflammatory damage might result from continuous irritation caused by both test articles. Therefore, the target organs for both ZnOAE100(−) and ZnOAE100(+) are considered to be the stomach, pancreas, eye, and prostate gland. Also, the no observed adverse effect level for both test articles was identified as 31.25 mg/kg for both sexes, because the adverse effects were observed at all doses greater than 125 mg/kg. PMID:25565830

  13. Toxicity of 100 nm zinc oxide nanoparticles: a report of 90-day repeated oral administration in Sprague Dawley rats.

    PubMed

    Kim, Yu-Ri; Park, Jong-Il; Lee, Eun Jeong; Park, Sung Ha; Seong, Nak-won; Kim, Jun-Ho; Kim, Geon-Yong; Meang, Eun-Ho; Hong, Jeong-Sup; Kim, Su-Hyon; Koh, Sang-Bum; Kim, Min-Seok; Kim, Cheol-Su; Kim, Soo-Ki; Son, Sang Wook; Seo, Young Rok; Kang, Boo Hyon; Han, Beom Seok; An, Seong Soo A; Yun, Hyo-In; Kim, Meyoung-Kon

    2014-01-01

    Nanoparticles (NPs) are used commercially in health and fitness fields, but information about the toxicity and mechanisms underlying the toxic effects of NPs is still very limited. The aim of this study is to investigate the toxic effect(s) of 100 nm negatively (ZnO(AE100[-])) or positively (ZnO(AE100[+])) charged zinc oxide (ZnO) NPs administered by gavage in Sprague Dawley rats, to establish a no observed adverse effect level, and to identify target organ(s). After verification of the primary particle size, morphology, hydrodynamic size, and zeta potential of each test article, we performed a 90-day study according to Organisation for Economic Co-operation and Development test guideline 408. For the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses were set at 125 mg/kg and 31.25 mg/kg, respectively. Both ZnO NPs had significant changes in hematological and blood biochemical analysis, which could correlate with anemia-related parameters, in the 500 mg/kg groups of both sexes. Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions. We speculate that this inflammatory damage might result from continuous irritation caused by both test articles. Therefore, the target organs for both ZnO(AE100(-)) and ZnO(AE100(+)) are considered to be the stomach, pancreas, eye, and prostate gland. Also, the no observed adverse effect level for both test articles was identified as 31.25 mg/kg for both sexes, because the adverse effects were observed at all doses greater than 125 mg/kg. PMID:25565830

  14. A 90-Day Toxicology Study of Meat from Genetically Modified Sheep Overexpressing TLR4 in Sprague-Dawley Rats

    PubMed Central

    Hu, Rui; Kan, Tongtong; Li, Yan; Zhang, Xiaosheng; Zhang, Jinlong; Lian, Ling; Han, Hongbing; Lian, Zhengxing

    2015-01-01

    Genetic modification offers alternative strategies to traditional animal breeding. However, the food safety of genetically modified (GM) animals has attracted increasing levels of concern. In this study, we produced GM sheep overexpressing TLR4, and the transgene-positive offsprings (F1) were confirmed using the polymerase chain reaction (PCR) and Southern blot. The expression of TLR4 was 2.5-fold compared with that of the wild-type (WT) sheep samples. During the 90-day safety study, Sprague-Dawley rats were fed with three different dietary concentrations (3.75%, 7.5%, and 15% wt/wt) of GM sheep meat, WT sheep meat or a commercial diet (CD). Blood samples from the rats were collected and analyzed for hematological and biochemical parameters, and then compared with hematological and biochemical reference ranges. Despite a few significant differences among the three groups in some parameters, all other values remained within the normal reference intervals and thus were not considered to be affected by the treatment. No adverse diet-related differences in body weights or relative organ weights were observed. Furthermore, no differences were observed in the gross necropsy findings or microscopic pathology of the rats whose diets contained the GM sheep meat compared with rats whose diets contained the WT sheep meat. Therefore, the present 90-day rat feeding study suggested that the meat of GM sheep overexpressing TLR4 had no adverse effect on Sprague-Dawley rats in comparison with WT sheep meat. These results provide valuable information regarding the safety assessment of meat derived from GM animals. PMID:25874566

  15. Distribution, elimination, and biopersistence to 90 days of a systemically introduced 30 nm ceria-engineered nanomaterial in rats.

    PubMed

    Yokel, Robert A; Au, Tu C; MacPhail, Robert; Hardas, Sarita S; Butterfield, D Allan; Sultana, Rukhsana; Goodman, Michael; Tseng, Michael T; Dan, Mo; Haghnazar, Hamed; Unrine, Jason M; Graham, Uschi M; Wu, Peng; Grulke, Eric A

    2012-05-01

    Nanoceria is used as a catalyst in diesel fuel, as an abrasive in printed circuit manufacture, and is being pursued as an antioxidant therapeutic. Our objective is to extend previous findings showing that there were no reductions of cerium in organs of the mononuclear phagocyte (reticuloendothelial) system up to 30 days after a single nanoscale ceria administration. An ~5% aqueous dispersion of citrate-stabilized 30 nm ceria, synthesized and characterized in-house, or vehicle, was iv infused into rats terminated 1, 7, 30, or 90 days later. Cageside observations were obtained daily, body weight weekly. Daily urinary and fecal cerium outputs were quantified for 2 weeks. Nine organs were weighed and samples collected from 14 tissues/organs/systems, blood and cerebrospinal fluid for cerium determination. Histology and oxidative stress were assessed. Less than 1% of the nanoceria was excreted in the first 2 weeks, 98% in feces. Body weight gain was initially impaired. Spleen weight was significantly increased in some ceria-treated groups, associated with abnormalities. Ceria was primarily retained in the spleen, liver, and bone marrow. There was little decrease of ceria in any tissue over the 90 days. Granulomas were observed in the liver. Time-dependent oxidative stress changes were seen in the liver and spleen. Nanoscale ceria was persistently retained by organs of the mononuclear phagocyte system, associated with adverse changes. The results support concern about the long-term fate and adverse effects of inert nanoscale metal oxides that distribute throughout the body, are persistently retained, and produce adverse changes. PMID:22367688

  16. Effect of 90-day space flight (MDS-ISS) on immunological parameters in mice: lymphocyte distribution and function

    NASA Astrophysics Data System (ADS)

    Roberts, Arthur; Lhuillier, Andrew; Liu, Yi; Ruggiu, Alessandra; Shi, Yufang

    Elucidation of the effects of space flight on the immune system of astronauts and other animal species is important for the survival and success of manned space flight, especially long-term missions. Space flight exposes astronauts to microgravity, galactic cosmic radiation (GCR), and various psycho-social stressors. Blood samples from astronauts returning from space flight have shown changes in the numbers and types of circulating leukocytes. Similarly, normal lym-phocyte homeostasis has been shown to be severely affected in mice using ground-based models of microgravity and GCR exposure, as demonstrated by profound effects on several immuno-logical parameters examined by other investigators and ourselves. In particular, lymphocyte numbers are significantly reduced and subpopulation distribution is altered in the spleen, thy-mus, and peripheral blood following hindlimb unloading (HU) in mice. Lymphocyte depletion was found to be mediated through corticosteroid-induced apoptosis, although the molecular mechanism of apoptosis induction is still under investigation. The proliferative capacity of TCR-stimulated lymphocytes was also inhibited after HU. We have similarly shown that mice exposed to high-energy 56Fe ion radiation have decreased lymphocyte numbers and perturba-tions in proportions of various subpopulations, including CD4+ and CD8+ T cells, and B cells in the spleen, and maturation stages of immature T cells in the thymus. To compare these ground-based results to the effects of actual space-flight, fresh spleen and thymus samples were recently obtained from normal and transgenic mice immediately after 90 d. space-flight in the MDS, and identically-housed ground control mice. Total leukocyte numbers in each organ were enumerated, and subpopulation distribution was examined by flow cytometric analysis of CD3, CD4, CD8, CD19, CD25, DX-5, and CD11b. Splenic T cells were stimulated with anti-CD3 and assessed for proliferation after 2-4 d., and production of several cytokines was examined using Luminex technology and quantitative PCR. These data are currently being collected and analyzed.

  17. Recovery of Motor Function After Stroke

    PubMed Central

    Sharma, Nikhil; Cohen, Leonardo G.

    2016-01-01

    The human brain possesses a remarkable ability to adapt in response to changing anatomical (e.g., aging) or environmental modifications. This form of neuroplasticity is important at all stages of life but is critical in neurological disorders such as amblyopia and stroke. This review focuses upon our new understanding of possible mechanisms underlying functional deficits evidenced after adult-onset stroke. We review the functional interactions between different brain regions that may contribute to motor disability after stroke and, based on this information, possible interventional approaches to motor stroke disability. New information now points to the involvement of non-primary motor areas and their interaction with the primary motor cortex as areas of interest. The emergence of this new information is likely to impact new efforts to develop more effective neurorehabilitative interventions using transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) that may be relevant to other neurological disorders such as amblyopia. PMID:22415914

  18. Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study

    PubMed Central

    2012-01-01

    Introduction Positive fluid balance has been associated with an increased risk for mortality in critically ill patients with acute kidney injury with or without renal replacement therapy (RRT). Data on fluid accumulation prior to RRT initiation and mortality are limited. We aimed to study the association between fluid accumulation at RRT initiation and 90-day mortality. Methods We conducted a prospective, multicenter, observational cohort study in 17 Finnish intensive care units (ICUs) during a five-month period. We collected data on patient characteristics, RRT timing, and parameters at RRT initiation. We studied the association of parameters at RRT initiation, including fluid overload (defined as cumulative fluid accumulation > 10% of baseline weight) with 90-day mortality. Results We included 296 RRT-treated critically ill patients. Of 283 patients with complete data on fluid balance, 76 (26.9%) patients had fluid overload. The median (interquartile range) time from ICU admission to RRT initiation was 14 (3.3 to 41.5) hours. The 90-day mortality rate of the whole cohort was 116 of 296 (39.2%; 95% confidence interval 38.6 to 39.8%). The crude 90-day mortality of patients with or without fluid overload was 45 of 76 (59.2%) vs. 65 of 207 (31.4%), P < 0.001. In logistic regression, fluid overload was associated with an increased risk for 90-day mortality (odds ratio 2.6) after adjusting for disease severity, time of RRT initiation, initial RRT modality, and sepsis. Of the 168 survivors with data on RRT use at 90 days, 34 (18.9%, 95% CI 13.2 to 24.6%) were still dependent on RRT. Conclusions Patients with fluid overload at RRT initiation had twice as high crude 90-day mortality compared to those without. Fluid overload was associated with increased risk for 90-day mortality even after adjustments. PMID:23075459

  19. A 90-day subchronic feeding study of genetically modified rice expressing Cry1Ab protein in Sprague-Dawley rats.

    PubMed

    Song, Huan; He, Xiaoyun; Zou, Shiying; Zhang, Teng; Luo, Yunbo; Huang, Kunlun; Zhu, Zhen; Xu, Wentao

    2015-04-01

    Bacillus thuringiensis (Bt) transgenic rice line (mfb-MH86) expressing a synthetic cry1Ab gene can be protected against feeding damage from Lepidopteran insects, including Sesamia inferens, Chilo suppressalis, Tryporyza incertulas and Cnaphalocrocis medinalis. Rice flour from mfb-MH86 and its near-isogenic control MH86 was separately formulated into rodent diets at concentrations of 17.5, 35 and 70 % (w/w) for a 90-day feeding test with rats, and all of the diets were nutritionally balanced. In this study, the responses of rats fed diets containing mfb-MH86 were compared to those of rats fed flour from MH86. Overall health, body weight and food consumption were comparable between groups fed diets containing mfb-MH86 and MH86. Blood samples were collected prior to sacrifice and a few significant differences (p < 0.05) were observed in haematological and biochemical parameters between rats fed genetically modified (GM) and non-GM diets. However, the values of these parameters were within the normal ranges of values for rats of this age and sex, thus not considered treatment related. In addition, upon sacrifice a large number of organs were weighed, macroscopic and histopathological examinations were performed with only minor changes to report. In conclusion, these results demonstrated that no toxic effect was observed in the conditions of the experiment, based on the different parameters assessed. GM rice mfb-MH86 is as safe and nutritious as non-GM rice. PMID:25367203

  20. Toxicological evaluation of an Allium-based commercial product in a 90-day feeding study in Sprague-Dawley rats.

    PubMed

    Mellado-García, P; Puerto, M; Pichardo, S; Llana-Ruiz-Cabello, M; Moyano, R; Blanco, A; Jos, A; Cameán, A M

    2016-04-01

    Proallium AP(®) is a commercial Allium extract intended to be used in active food packaging as the antibacterial and antioxidant effects of some organosulfur compounds are well known. However, there is little information on its toxicity and the Scientific Committee on Food (UE) requires the safety assessment of substances used in food contact materials. Thus, the aim of this study was to conduct for the first time a subchronic oral toxicity study of Proallium AP(®) with groups of 10 males and 10 females Sprague-Dawley rats fed a diet containing 0, 25, 100, 400 mg/kg/d for 90 days. No treatment-related clinical signs or mortality were noted. Besides, no treatment-related effects with regard to any of the toxicological biomarkers considered were observed, including biochemical, haematological and histopathology parameters. In conclusion, the non-observed-adverse-effect-level (NOAEL) for Proallium AP(®) in rats was determined to be a dietary dose of 400 mg/kg/d under the present experimental conditions, a value 500-fold higher than the exposure derived from its potential use in active packaging. PMID:26827789

  1. A 90-day toxicology study of high-amylose transgenic rice grain in Sprague-Dawley rats.

    PubMed

    Zhou, Xing Hua; Dong, Ying; Xiao, Xiang; Wang, Yun; Xu, Yong; Xu, Bin; Shi, Wei Dong; Zhang, Yi; Zhu, Li Jia; Liu, Qiao Quan

    2011-12-01

    A transgenic rice line (TRS) with high amylose level has been developed by antisense RNA inhibition of starch branching enzymes. Compositional analysis of TRS demonstrated that the content of resistant starch (RS) was significantly higher compared to conventional non-transgenic rice. High level of RS is an important raw material in food industry and has various physiological effects for human health. In order to provide the reliable theory basis for field release of TRS rice, we evaluated the potential health effects of long-term consumption of the TRS. The 90-day toxicology feeding experiment was conducted in Sprague-Dawley rats fed with diets containing 70% of either TRS rice flour, its near-isogenic rice flour or the control diet. The clinical performance variables (body weight, body weight gain and food consumption) were measured and pathological responses (hematological parameters and serum chemistry at the midterm and the completion of the experiment, urinalysis profile and serum sex hormone response at the completion of the experiment) were performed. Besides, clinical signs, relative organ weights and microscopic observations were also compared between TRS group and its near-isogenic rice group. The combined data indicates that high-amylose TRS grain is as safe as the conventional non-transgenic rice for rat consumption. PMID:21967780

  2. Collagen content in the vastus lateralis and the soleus muscle following a 90-day bed rest period with or without resistance exercises

    PubMed Central

    Nielsen, Rasmus Oestergaard; Schjerling, Peter; Tesch, Per; Stål, Per; Langberg, Henning

    2015-01-01

    Summary Introduction spaceflight seems associated with deterioration of the function of the skeletal muscles. Since muscle collagen is critical for muscle function, an improved understanding of the content of the muscle collagen during long-term inactivity seems important. Bed-rest with in-bed resistance training serves as a proxy for the conditions in space. Therefore, ground-based studies may improve the understanding of the consequences of long-term inactivity. Purpose the purpose is to compare the change in collagen protein in the vastus lateralis (VL) and the soleus (SOL) muscle amongst persons exposed to a 90-day bed rest with or without resistance exercise. Methods an explorative analysis was completed based on data from a randomized, controlled trial. The intervention group (BRE, SOL n=4, VL n=8) performed supine-based squat exercises, whereas the controls (BE, SOL n=6, VL n=12) remained inactive during follow-up. Muscle biopsies from vastus lateralis and soleus were taken at baseline (pre) and after 90-days’ follow-up (post). Muscle collagen (μg collagen/mg protein) was quantified. Two-way repeated measurements ANOVA was used to compare the interaction between the intervention (BRE/BR) and time (pre/post) for each muscle. Results the collagen content of VL was similar between pre and post in the BRE group (−3.8 μg collagen/mg protein [95% CI: −22.0; 14.4], p=0.68) while it rose amongst individuals in the BR group (14.9 μg collagen/mg protein [95% CI: −0.01; 29.7], p=0.05). The difference of 18.66 [95% CI: −6.5; 43.9] between BRE and BR across time was, however, not significant (p=0.14). No significant reduction in SOL muscle collagen content was observed from pre to post in the BR group (−9.3 μg collagen/mg protein [95% CI: −24.9; 6.4], p=0.25) or in the BRE group (−6.5 μg collagen/mg protein [95% CI: −25.6; 12.6], p=0.50). There was no difference in the effect of BR versus BRE over time (mean difference −2.78 μg collagen

  3. Herd-level risk factors for infectious diseases in Swedish dairy calves aged 0-90 days.

    PubMed

    Lundborg, G K; Svensson, E C; Oltenacu, P A

    2005-05-10

    The effect of environmental factors and management routines on the risk of diarrhoea, respiratory disease and other infectious diseases was investigated in 3081 heifer calves 0-90 days old in 122 Swedish dairy herds. The farmers kept records on cases of diseases in their heifer calves and in addition, project veterinarians clinically examined all calves every 2-3 months. At each visit, the veterinarians also measured the ammonia concentration and relative air humidity in the housing facilities for the calves. The cleanliness of the animals and their environment was recorded as a measure of the hygienic status of the farm. The presence or absence of draught (i.e. wind velocity>0.5 m/s) was recorded twice during the study period. The effect of these factors, as well as the placing of the calf pens, the nature of the pen walls, air volume per animal, management factors (such as the status of the caretaker and feeding routines) and presence or absence of a bovine viral diarrhoea virus (BVDV) infection in the herd, was evaluated by means of a two-level variance component logistic model. The placing of calf pens along an outer wall was significantly associated with the risk of diarrhoea (odds ratio (OR): 1.92, P<0.01). The risk for respiratory disease was significantly associated with an ammonia concentration below 6 ppm (OR: 0.42, P<0.05) while the odds ratio for moderately to severely increased respiratory sounds was significantly associated with a BVDV infection in the herd (OR: 2.39, P<0.05) and draught (OR: 3.7, P<0.02). Absence of draught was significantly associated with the risk for infectious diseases other than diarrhoea and respiratory disease (OR: 0.42, P<0.01). PMID:15820112

  4. Effects of 90-Day Feeding of Transgenic Maize BT799 on the Reproductive System in Male Wistar Rats

    PubMed Central

    Guo, Qian-ying; He, Li-xia; Zhu, Han; Shang, Jun-li; Zhu, Ling-yan; Wang, Jun-bo; Li, Yong

    2015-01-01

    BT799 is a genetically modified (GM) maize plant that expresses the Cry1Ac gene from Bacillus thuringiensis (Bt). The Cry1Ac gene was introduced into maize line Zhen58 to encode the Bt crystal protein and thus produce insect-resistant maize BT799. Expression of Bt protein in planta confers resistance to Lepidopteran pests and corn rootworms. The present study was designed to investigate any potential effects of BT799 on the reproductive system of male rats and evaluate the nutritional value of diets containing BT799 maize grain in a 90-day subchronic rodent feeding study. Male Wistar rats were fed with diets containing BT799 maize flours or made from its near isogenic control (Zhen58) at a concentration of 84.7%, nutritionally equal to the standard AIN-93G diet. Another blank control group of male rats were treated with commercial AIN-93G diet. No significant differences in body weight, hematology and serum chemistry results were observed between rats fed with the diets containing transgenic BT799, Zhen58 and the control in this 13-week feeding study. Results of serum hormone levels, sperm parameters and relative organ/body weights indicated no treatment-related side effects on the reproductive system of male rats. In addition, no diet-related changes were found in necropsy and histopathology examinations. Based on results of the current study, we did not find any differences in the parameters tested in our study of the reproductive system of male rats between BT799 and Zhen58 or the control. PMID:26633453

  5. Effects of 90-Day Feeding of Transgenic Maize BT799 on the Reproductive System in Male Wistar Rats.

    PubMed

    Guo, Qian-ying; He, Li-xia; Zhu, Han; Shang, Jun-li; Zhu, Ling-yan; Wang, Jun-bo; Li, Yong

    2015-12-01

    BT799 is a genetically modified (GM) maize plant that expresses the Cry1Ac gene from Bacillus thuringiensis (Bt). The Cry1Ac gene was introduced into maize line Zhen58 to encode the Bt crystal protein and thus produce insect-resistant maize BT799. Expression of Bt protein in planta confers resistance to Lepidopteran pests and corn rootworms. The present study was designed to investigate any potential effects of BT799 on the reproductive system of male rats and evaluate the nutritional value of diets containing BT799 maize grain in a 90-day subchronic rodent feeding study. Male Wistar rats were fed with diets containing BT799 maize flours or made from its near isogenic control (Zhen58) at a concentration of 84.7%, nutritionally equal to the standard AIN-93G diet. Another blank control group of male rats were treated with commercial AIN-93G diet. No significant differences in body weight, hematology and serum chemistry results were observed between rats fed with the diets containing transgenic BT799, Zhen58 and the control in this 13-week feeding study. Results of serum hormone levels, sperm parameters and relative organ/body weights indicated no treatment-related side effects on the reproductive system of male rats. In addition, no diet-related changes were found in necropsy and histopathology examinations. Based on results of the current study, we did not find any differences in the parameters tested in our study of the reproductive system of male rats between BT799 and Zhen58 or the control. PMID:26633453

  6. Recovery of vestibular function following hair cell destruction by streptomycin

    NASA Technical Reports Server (NTRS)

    Jones, T. A.; Nelson, R. C.

    1992-01-01

    Can the vestibular periphery of warm-blooded vertebrates recover functionally from severe sensory hair cell loss? Recent findings in birds suggest a mechanism for recovery but in fact no direct functional evidence has been reported. We produced vestibular hair cell lesions using the ototoxic agent streptomycin sulfate (600 mg/kg/day, 8 days, chicks, Gallus domesticus). Compound action potentials of the vestibular nerve were used as a direct measure of peripheral vestibular function. Vestibular thresholds, neural activation latencies and amplitudes were documented. Eight days of drug treatment elevated thresholds significantly (P < 0.001) and eliminated all but remnants of vestibular activity. Virtually complete physiological recovery occurred in all animals studied over a period of 70 days following treatment. Thresholds recovered within two weeks of drug treatment whereas the return of response morphologies including activation latencies and amplitudes required an additional 6-8 weeks.

  7. 75 FR 32869 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List a Distinct...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-10

    .... irremotus) and the eastern timber wolf (C. l. lycaon) in the Great Lakes region (39 FR 1158, January 4, 1974..., 1976 (41 FR 17736), in Mexico and the southwestern United States. On June 14, 1976 (41 FR 24062), we... threatened listing in Minnesota (43 FR 9607, March 9, 1978). Recovery efforts that followed were...

  8. 77 FR 32922 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To Delist or...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-04

    ... (75 FR 28636, May 21, 2010; Service 2009b, p. 15). Lane Mountain milk-vetch was listed as endangered... (76 FR 29108, May 19, 2011). No recovery plan has been completed for Lane Mountain milk-vetch. A... designated concurrent with the listing (52 FR 28780, August 3, 1987). At the time of listing, this...

  9. 76 FR 36053 - Endangered and Threatened Wildlife and Plants; Revised 90-Day Finding on a Petition To Reclassify...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-21

    ... Utah prairie dogs (see Figure 1 below) (UDWR 2005, entire; 72 FR 7843). As of 2010, the Awapa Plateau... FR 22330), the 1991 Utah Prairie Dog Recovery Plan (Service 1991, pp. iv, 11), and the 2010 Draft...-day finding published on February 21, 2007 (72 FR 7843), constituted our compliance with...

  10. 77 FR 45571 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition To Delist the Green Turtle in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-01

    ...,'' or DPS (61 FR 4722; February 7, 1996). The DPS Policy requires the consideration of two elements when... commercial data available after conducting a review of the species' status, that the species is no longer... under the ESA is no longer required. A species may be delisted on the basis of recovery only if the...

  11. 78 FR 55046 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To Delist or...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-09

    ... The gypsum wild-buckwheat was federally listed as threatened on February 18, 1981 (46 FR 5730, January... habitat on November 5, 1987 (52 FR 37420, October 6, 1987). A recovery plan was issued September 30, 1991... was federally listed as endangered without critical habitat on October 31, 1988 (53 FR...

  12. 75 FR 46894 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Mexican...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-04

    ... endangered subspecies on April 28, 1976 (41 FR 17742). The gray wolf species (Canis lupus) in North America... threatened (43 FR 9607). This listing of the species as a whole subsumed the previous Mexican wolf subspecies... the purpose of research and conservation (43 FR 9607). We initiated recovery programs for the...

  13. Recovery of impaired muscle function in severe sciatica.

    PubMed

    Balagué, F; Nordin, M; Sheikhzadeh, A; Echegoyen, A C; Skovron, M L; Bech, H; Chassot, D; Helsen, M

    2001-06-01

    This is a prospective cohort study of patients with acute treated severe sciatica. The objectives of the study are, firstly, to describe the recovery of muscle performance by manual and isokinetic muscle testing in patients with acute severe sciatica over 1 year, and secondly, to discuss the potential clinical relevance of the isokinetic testing of the ankle for patients with acute sciatica. In clinical daily practice, muscle performance is evaluated by means of isometric manual tests. Different authors using manual muscle tests have reported the long-term outcome of the muscle function in patients with sciatica. Overall, the results are good in terms of the recovery of muscle strength. However, it is not clear whether the isometric strength is sufficiently relevant to evaluate the more complete muscle performance of the affected muscles in patients with sciatica. This study presents data on the muscle recovery measured with manual testing and isokinetic testing of patients with severe sciatica. Consecutive patients admitted to the Cantonal Hospital for conservative management of severe acute sciatica were eligible for inclusion in the study. Patients were evaluated at admission, discharge, and follow-up at 3, 6, and 12 months. All the visits included a standardized clinical examination and the completion of questionnaires. Imaging and electromyography were conducted at the first visit. Isokinetic muscle tests at 30 degrees/s and 120 degrees/s were performed at discharge and follow-up visits. Manual and isokinetic tests were performed on foot and ankle flexor and extensor muscles. Eighty-two consecutive patients (66% men), with a mean age of 43 (+/-10.3) years, entered the study. The prevalence of major muscle weakness was low, with 7% of patients unable to perform toe walking and 11% unable to walk on the heel at visit one. Moreover, motor deficit defined as a score of 4 or less (out of 5) was found in 15% of subjects at the first evaluation. Such severe deficits

  14. Recovery of hand function through mental practice: A study protocol

    PubMed Central

    Ietswaart, Magdalena; Johnston, Marie; Dijkerman, H Chris; Scott, Clare L; Joice, Sara A; Hamilton, Steven; MacWalter, Ronald S

    2006-01-01

    Background The study aims to assess the therapeutic benefits of motor imagery training in stroke patients with persistent motor weakness. There is evidence to suggest that mental rehearsal of movement can produce effects normally attributed to practising the actual movements. Imagining hand movements could stimulate the redistribution of brain activity, which accompanies recovery of hand function, thus resulting in a reduced motor deficit. Methods/Design A multi-centre randomised controlled trial recruiting individuals between one and six months post-stroke (n = 135). Patients are assessed before and after a four-week evaluation period. In this trial, 45 patients daily mentally rehearse movements with their affected arm under close supervision. Their recovery is compared to 45 patients who perform closely supervised non-motor mental rehearsal, and 45 patients who are not engaged in a training program. Motor imagery training effectiveness is evaluated using outcome measures of motor function, psychological processes, and level of disability. Discussion The idea of enhancing motor recovery through the use of motor imagery rehabilitation techniques is important with potential implications for clinical practice. The techniques evaluated as part of this randomised controlled trial are informed by the current understanding in cognitive neuroscience and the trial is both of scientific and applied interest. PMID:17067370

  15. Maximising functional recovery following hip fracture in frail seniors.

    PubMed

    Beaupre, Lauren A; Binder, Ellen F; Cameron, Ian D; Jones, C Allyson; Orwig, Denise; Sherrington, Cathie; Magaziner, Jay

    2013-12-01

    This review discusses factors affecting recovery following hip fracture in frail older people as well as interventions associated with improved functional recovery. Prefracture function, cognitive status, co-morbidities, depression, nutrition and social support impact recovery and may interact to affect post-fracture outcome. There is mounting evidence that exercise is beneficial following hip fracture with higher-intensity/duration programmes showing more promising outcomes. Pharmacologic management for osteoporosis has benefits in preventing further fractures, and interest is growing in pharmacologic treatments for post-fracture loss of muscle mass and strength. A growing body of evidence suggests that sub-populations - those with cognitive impairment, residing in nursing homes or males - also benefit from rehabilitation after hip fracture. Optimal post-fracture care may entail the use of multiple interventions; however, more work is needed to determine optimal exercise components, duration and intensity as well as exploring the impact of multimodal interventions that combine exercise, pharmacology, nutrition and other interventions. PMID:24836335

  16. 7 CFR Appendix B to Subpart C of... - FSA-2510, Notice of Availability of Loan Servicing to Borrowers Who Are 90 Days Past Due

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 7 2011-01-01 2011-01-01 false FSA-2510, Notice of Availability of Loan Servicing to Borrowers Who Are 90 Days Past Due B Appendix B to Subpart C of Part 766 Agriculture Regulations of the... LOAN SERVICING-SPECIAL Loan Servicing Programs Pt. 766, Subpt. C, App. B Appendix B to Subpart C...

  17. 7 CFR Appendix B to Subpart C of... - FSA-2510, Notice of Availability of Loan Servicing to Borrowers Who Are 90 Days Past Due

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false FSA-2510, Notice of Availability of Loan Servicing to Borrowers Who Are 90 Days Past Due B Appendix B to Subpart C of Part 766 Agriculture Regulations of the... LOAN SERVICING-SPECIAL Loan Servicing Programs Pt. 766, Subpt. C, App. B Appendix B to Subpart C...

  18. Sensorimotor integration for functional recovery and the Bobath approach.

    PubMed

    Levin, Mindy F; Panturin, Elia

    2011-04-01

    Bobath therapy is used to treat patients with neurological disorders. Bobath practitioners use hands-on approaches to elicit and reestablish typical movement patterns through therapist-controlled sensorimotor experiences within the context of task accomplishment. One aspect of Bobath practice, the recovery of sensorimotor function, is reviewed within the framework of current motor control theories. We focus on the role of sensory information in movement production, the relationship between posture and movement and concepts related to motor recovery and compensation with respect to this therapeutic approach. We suggest that a major barrier to the evaluation of the therapeutic effectiveness of the Bobath concept is the lack of a unified framework for both experimental identification and treatment of neurological motor deficits. More conclusive analysis of therapeutic effectiveness requires the development of specific outcomes that measure movement quality. PMID:21628730

  19. Embedded pupil function recovery for Fourier ptychographic microscopy

    PubMed Central

    Ou, Xiaoze; Zheng, Guoan; Yang, Changhuei

    2014-01-01

    We develop and test a pupil function determination algorithm, termed embedded pupil function recovery (EPRY), which can be incorporated into the Fourier ptychographic microscopy (FPM) algorithm and recover both the Fourier spectrum of sample and the pupil function of imaging system simultaneously. This EPRY-FPM algorithm eliminates the requirement of the previous FPM algorithm for a priori knowledge of the aberration in the imaging system to reconstruct a high quality image. We experimentally demonstrate the effectiveness of this algorithm by reconstructing high resolution, large field-of-view images of biological samples. We also illustrate that the pupil function we retrieve can be used to study the spatially varying aberration of a large field-of-view imaging system. We believe that this algorithm adds more flexibility to FPM and can be a powerful tool for the characterization of an imaging system’s aberration. PMID:24663835

  20. The Model for End-stage Liver Disease accurately predicts 90-day liver transplant wait-list mortality in Atlantic Canada

    PubMed Central

    Renfrew, Paul Douglas; Quan, Hude; Doig, Christopher James; Dixon, Elijah; Molinari, Michele

    2011-01-01

    OBJECTIVE: To determine the generalizability of the predictions for 90-day mortality generated by Model for End-stage Liver Disease (MELD) and the serum sodium augmented MELD (MELDNa) to Atlantic Canadian adults with end-stage liver disease awaiting liver transplantation (LT). METHODS: The predictive accuracy of the MELD and the MELDNa was evaluated by measurement of the discrimination and calibration of the respective models’ estimates for the occurrence of 90-day mortality in a consecutive cohort of LT candidates accrued over a five-year period. Accuracy of discrimination was measured by the area under the ROC curves. Calibration accuracy was evaluated by comparing the observed and model-estimated incidences of 90-day wait-list failure for the total cohort and within quantiles of risk. RESULTS: The area under the ROC curve for the MELD was 0.887 (95% CI 0.705 to 0.978) – consistent with very good accuracy of discrimination. The area under the ROC curve for the MELDNa was 0.848 (95% CI 0.681 to 0.965). The observed incidence of 90-day wait-list mortality in the validation cohort was 7.9%, which was not significantly different from the MELD estimate of 6.6% (95% CI 4.9% to 8.4%; P=0.177) or the MELDNa estimate of 5.8% (95% CI 3.5% to 8.0%; P=0.065). Global goodness-of-fit testing found no evidence of significant lack of fit for either model (Hosmer-Lemeshow χ2 [df=3] for MELD 2.941, P=0.401; for MELDNa 2.895, P=0.414). CONCLUSION: Both the MELD and the MELDNa accurately predicted the occurrence of 90-day wait-list mortality in the study cohort and, therefore, are generalizable to Atlantic Canadians with end-stage liver disease awaiting LT. PMID:21876856

  1. Platelet-to-Lymphocyte Ratio: A Novel Prognostic Factor for Prediction of 90-day Outcomes in Critically Ill Patients With Diabetic Ketoacidosis.

    PubMed

    Liu, Wen-Yue; Lin, Shi-Gang; Wang, Li-Ren; Fang, Chen-Chen; Lin, Yi-Qian; Braddock, Martin; Zhu, Gui-Qi; Zhang, Zhongheng; Zheng, Ming-Hua; Shen, Fei-Xia

    2016-01-01

    Diabetic ketoacidosis (DKA) is a life-threatening acute complication of diabetes mellitus and the novel systemic inflammation marker platelet-to-lymphocyte ratio (PLR) may be associated with clinical outcome in patients with DKA. This study aimed to investigate the utility of PLR in predicting 90-day clinical outcomes in patients with DKA. Patient data exacted from the Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC II) database was analyzed. A cutoff value for PLR of 267.67 was determined using Youden index (P < 0.05) and used to categorize subjects into a high PLR group and a low PLR group. The hazard ratios (HRs) and 95% confidence intervals (CIs) for DKA were calculated across PLR. Clinical outcomes in our study were defined as intensive care unit (ICU) 90-day readmission and all-cause mortality. A total of 278 ICU admissions were enrolled and stratified by cutoff value of PLR. The incidence of readmission and mortality was 17.8% in the high PLR group, significantly higher than 7.4% in the low PLR group. In the multivariable model, after adjusting for known confounding variables including clinical parameters, comorbidities, laboratory parameters, the HRs for DKA were 2.573 (95% CI 1.239-5.345; P = 0.011), 2.648 (95% CI 1.269-5.527; P = 0.009), and 2.650 (95% CI 1.114-6.306; P = 0.028), respectively. The Kaplan-Meier survival curve showed that a high PLR level was associated with a higher risk for 90-day outcomes in patients with DKA. The authors report that higher PLR presents a higher risk for 90-day incidence of readmission and mortality in patients with DKA. It appears to be a novel independent predictor of 90-day outcomes in critically ill DKA patients in ICU units. PMID:26825908

  2. The added value of the 90-day repeated dose oral toxicity test for industrial chemicals with a low (sub)acute toxicity profile in a high quality dataset.

    PubMed

    Taylor, Katy; Andrew, David J; Rego, Laura

    2014-08-01

    A survey conducted on the EU Notification of New Substances (NONS) database suggested that for industrial chemicals with a profile of low toxicity in (sub)acute toxicity tests there is little added value to the conduct of the 90-day repeated dose study. Avoiding unnecessary animal testing is a central aim of the EU REACH chemicals legislation; therefore we sought to verify the profile using additional data. The OECD's eChemPortal was searched for substances that had both a 28-day and a 90-day study and their robust study summaries were then examined from the ECHA CHEM database. Out of 182 substances with high quality 28-day and 90-day study results, only 18 reported no toxicity of any kind in the (sub)acute tests. However, for 16 of these there were also no reported signs of toxicity at or close to the limit dose (1000mg/kgbw/d) in the 90-day study. Restricting the 'low (sub)acute toxicity in a high quality dataset' profile to general industrial chemicals of no known biological activity, whilst allowing irritant substances, increases the data set and improves the prediction to 95% (20 substances out of 21 substances). The low toxicity profile appears to be of low prevalence within industrial chemicals (10-15%), nevertheless, avoidance of the conduct of a redundant 90-day study for this proportion of the remaining REACH phase-in substances would avoid the use of nearly 50,000 animals and save industry 50million Euros, with no impact on the assessment of human health. PMID:24768988

  3. Robotic Mirror Therapy System for Functional Recovery of Hemiplegic Arms.

    PubMed

    Beom, Jaewon; Koh, Sukgyu; Nam, Hyung Seok; Kim, Wonshik; Kim, Yoonjae; Seo, Han Gil; Oh, Byung-Mo; Chung, Sun Gun; Kim, Sungwan

    2016-01-01

    Mirror therapy has been performed as effective occupational therapy in a clinical setting for functional recovery of a hemiplegic arm after stroke. It is conducted by eliciting an illusion through use of a mirror as if the hemiplegic arm is moving in real-time while moving the healthy arm. It can facilitate brain neuroplasticity through activation of the sensorimotor cortex. However, conventional mirror therapy has a critical limitation in that the hemiplegic arm is not actually moving. Thus, we developed a real-time 2-axis mirror robot system as a simple add-on module for conventional mirror therapy using a closed feedback mechanism, which enables real-time movement of the hemiplegic arm. We used 3 Attitude and Heading Reference System sensors, 2 brushless DC motors for elbow and wrist joints, and exoskeletal frames. In a feasibility study on 6 healthy subjects, robotic mirror therapy was safe and feasible. We further selected tasks useful for activities of daily living training through feedback from rehabilitation doctors. A chronic stroke patient showed improvement in the Fugl-Meyer assessment scale and elbow flexor spasticity after a 2-week application of the mirror robot system. Robotic mirror therapy may enhance proprioceptive input to the sensory cortex, which is considered to be important in neuroplasticity and functional recovery of hemiplegic arms. The mirror robot system presented herein can be easily developed and utilized effectively to advance occupational therapy. PMID:27583794

  4. 76 FR 20911 - Endangered and Threatened Wildlife and Plants; 90-Day Finding on a Petition To List the Prairie...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-14

    ..., saltcedar and Russian olive encroachment has been shown to alter stream geomorphology by narrowing and... functions of a stream in terms of hydrology, biology, geomorphology, connectivity, and water quality at...

  5. Toxicity studies on agent GA (Phase 2): 90 day subchronic study of GA (Tabun) in cd rats. Appendices. Final report, July 1985-August 1991

    SciTech Connect

    Not Available

    1992-03-01

    The purpose of the report is to provide essential toxicologic information on Tabun administration over a 90 day period. This toxicologic information may be used to adjust the maximum-tolerated dose for subsequent dominant-lethal and two-generation reproduction studies. The objectives were to determine the toxic effects of nerve agent exposure (e.g., target organs); and to determine the effects of nerve agent GA on sperm morphology and motility and vaginal cytology.

  6. Vitamin D deficiency at admission is not associated with 90-day mortality in patients with severe sepsis or septic shock: Observational FINNAKI cohort study.

    PubMed

    Ala-Kokko, Tero I; Mutt, Shivaprakash J; Nisula, Sara; Koskenkari, Juha; Liisanantti, Janne; Ohtonen, Pasi; Poukkanen, Meri; Laurila, Jouko J; Pettilä, Ville; Herzig, Karl-Heinz

    2016-01-01

    Introduction Low levels of vitamin D have been associated with increased mortality in patients that are critically ill. This study explored whether vitamin D levels were associated with 90-day mortality in severe sepsis or septic shock. Methods Plasma vitamin D levels were measured on admission to the intensive care unit (ICU) in a prospective multicentre observational study. Results 610 patients with severe sepsis were included; of these, 178 (29%) had septic shock. Vitamin D deficiency (<50 nmol/L) was present in 333 (55%) patients. The 90-day mortality did not differ among patients with or without vitamin D deficiency (28.3% vs. 28.5%, p = 0.789). Diabetes was more common among patients deficient compared to those not deficient in vitamin D (30% vs. 18%, p < 0.001). Hospital-acquired infections at admission were more prevalent in patients with a vitamin D deficiency (31% vs. 16%, p < 0.001). A multivariable adjusted Cox regression model showed that low vitamin D levels could not predict 90-day mortality (<50 nmol/L: hazard ratio (HR) 0.99 (95% CI: 0.72-1.36), p > 0.9; and <25 nmol/L: HR 0.44 (95% CI: 0.22-0.87), p = 0.018). Conclusions Vitamin D deficiency detected upon ICU admission was not associated with 90-day mortality in patients with severe sepsis or septic shock. Key messages In severe sepsis and septic shock, a vitamin D deficiency upon ICU admission was not associated with increased mortality. Compared to patients with sufficient vitamin D, patients with deficient vitamin D more frequently exhibited diabetes, elevated C-reactive protein levels, and hospital-acquired infections upon ICU admission, and they more frequently developed acute kidney injury. PMID:26800186

  7. 29 CFR 37.80 - What happens if a recipient fails to issue a Notice of Final Action within 90 days of the date on...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true What happens if a recipient fails to issue a Notice of Final Action within 90 days of the date on which a complaint was filed? 37.80 Section 37.80 Labor Office of the Secretary of Labor IMPLEMENTATION OF THE NONDISCRIMINATION AND EQUAL OPPORTUNITY PROVISIONS OF THE WORKFORCE INVESTMENT ACT OF 1998...

  8. 29 CFR 37.79 - If, before the 90-day period has expired, a recipient issues a Notice of Final Action with which...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true If, before the 90-day period has expired, a recipient issues a Notice of Final Action with which the complainant is dissatisfied, how long does the complainant have to file a complaint with the Director? 37.79 Section 37.79 Labor Office of the Secretary of Labor IMPLEMENTATION OF THE NONDISCRIMINATION...

  9. IN VIVO EVALUATION OF THE SEALING ABILITY OF TWO ENDODONTIC SEALERS IN ROOT CANALS EXPOSED TO THE ORAL ENVIRONMENT FOR 45 AND 90 DAYS

    PubMed Central

    Kopper, Patrícia Maria Poli; Vanni, José Roberto; Della Bona, Álvaro; de Figueiredo, José Antônio Poli; Porto, Sérgio

    2006-01-01

    This in vivo study evaluated the sealing ability of a resin-based sealer (AH Plus) and a zinc oxide-eugenol sealer (Endofill) in dogs' teeth, exposed to the oral environment for 45 and 90 days. Forty eight lower incisors from 8 dogs were endodonticaly treated. A stratified randomization determined the sealer use in each root canal. All canals were filled using the lateral condensation technique. The excess filling material at the cervical portion of the root canal was sectioned, leaving a 10-mm obturation length inside the canal. Teeth were provisionally sealed with glass ionomer cement for 24 h and the canals were exposed to the oral environment for either 45 or 90 days. Therefore, the experimental groups were as follows: A45- AH Plus for 45 days; A90- AH Plus for 90 days; E45- Endofill for 45 days; and E90- Endofill for 90 days (n=12). After the experimental period, the dogs were killed and the lower jaw was removed. The incisors were extracted and the roots were covered with two coats of nail varnish. The teeth were immersed in India ink for 96 h and submitted to diaphanization. Dye leakage (in mm) was measured using stereomicroscopy (10x magnification). The results were statistically analyzed using two-way ANOVA and Tukey test for multiple comparisons (á = 0.05). Group E90 (2.03±0.94) showed significantly higher mean leakage value than all other groups (p<0.001). None of the sealers, in both study conditions, were able to prevent dye leakage. PMID:19089029

  10. Influence of CO2 change during 90-day experiment on growth characteristics and photosynthetic activity in vegetables grown in Lunar Palace 1

    NASA Astrophysics Data System (ADS)

    Shao, Lingzhi; Liu, Hong; Wang, Minjuan; Fu, Yuming; Dong, Chen; Liu, Guanghui

    To establish bioregenerative life support system (BLSS) on lunar or Mars bases in the future, it is necessary to firstly conduct manned simulation experiments on the ground. For this purpose, Lunar palace 1 as an integrative experimental facility for permanent astrobase life support artificial closed ecosystem was set up, and 90-day experiment was carried out in this system. Vegtables as one of the important plant units, provide various nutrient content for crews in the system, such as vitamin, antioxidants and so on. However, it is not clear yet that how the CO _{2} change during 90-day experiment to affect on growth characteristics and photosynthetic activity in vegtables grown in the system. In this study, red lettuce, red rape, romaine lettuce, and bibb lettuce grown in the system were chosen as the subject investigated. Growth, expressed as dry weight, length of shoot and root, leaf area, was mearsured, and photosynthesis,expressed as net photosynthetic rate, intercellular CO _{2} concentration, chlorophyll contents and fluorescence was analyzed to detemind influence of CO _{2} change during 90-day experiment on growth in vegtables grown in the system.

  11. Intermittent hypoxia induces functional recovery following cervical spinal injury

    PubMed Central

    Vinit, Stéphane; Lovett-Barr, Mary Rachael; Mitchell, Gordon S.

    2009-01-01

    Respiratory-related complications are the leading cause of death in spinal cord injury (SCI) patients. Few effective SCI treatments are available after therapeutic interventions are performed in the period shortly after injury (e.g. spine stabilization and prevention of further spinal damage). In this review we explore the capacity to harness endogenous spinal plasticity induced by intermittent hypoxia to optimize function of surviving (spared) neural pathways associated with breathing. Two primary questions are addressed: 1) does intermittent hypoxia induce plasticity in spinal synaptic pathways to respiratory motor neurons following experimental SCI? and 2) can this plasticity improve respiratory function? In normal rats, intermittent hypoxia induces serotonin-dependent plasticity in spinal pathways to respiratory motor neurons. Early experiments suggest that intermittent hypoxia also enhances respiratory motor output in experimental models of cervical SCI, (cervical hemisection) and that the capacity to induce functional recovery is greater with longer durations post-injury. Available evidence suggests that intermittent hypoxia-induced spinal plasticity has considerable therapeutic potential to treat respiratory insufficiency following chronic cervical spinal injury. PMID:19651247

  12. Renal functional reserve and renal recovery after acute kidney injury.

    PubMed

    Sharma, Aashish; Mucino, Marìa Jimena; Ronco, Claudio

    2014-01-01

    Renal functional reserve (RFR) represents the capacity of the kidney to increase glomerular filtration rate (GFR) in response to certain physiological or pathological stimuli or conditions. Once baseline GFR is determined, RFR can be assessed clinically after an oral protein load or intravenous amino acid infusion. In clinical practice, baseline GFR displays variable levels due to diet or other factors. RFR is the difference between peak 'stress' GFR induced by the test (p.o. or i.v.) and the baseline GFR. In clinical scenarios where hyperfiltration is present (high baseline GFR due to pregnancy, hypertension or diabetic nephropathy, in solitary kidney or kidney donors), RFR may be fully or partially used to achieve normal or supranormal renal function. Since commonly used renal function markers, such as GFR, may remain within normal ranges until 50% of nephrons are lost or in patients with a single remnant kidney, the RFR test may represent a sensitive and early way to assess the functional decline in the kidney. RFR assessment may become an important tool to evaluate the ability of the kidney to recover completely or partially after a kidney attack. In case of healing with a defect and progressive fibrosis, recovery may appear complete clinically, but a reduced RFR may be a sign of a maladaptive repair or subclinical loss of renal mass. Thus, a reduction in RFR may represent the equivalent of renal frailty or susceptibility to insults. The main aim of this article is to review the concept of RFR, its utility in different clinical scenarios, and future perspective for its use. PMID:25343829

  13. Functional Task Test: 2. Spaceflight-Induced Cardiovascular Change and Recovery During NASA's Functional Task Test

    NASA Technical Reports Server (NTRS)

    Phillips, Tiffany; Arzeno, Natalia M.; Stenger, Michael; Lee, Stuart M. C.; Bloomberg, Jacob J.; Platts, Steven H.

    2011-01-01

    The overall objective of the functional task test (FTT) is to correlate spaceflight-induced physiological adaptations with changes in performance of high priority exploration mission-critical tasks. This presentation will focus on the recovery from fall/stand test (RFST), which measures the cardiovascular response to the transition from the prone posture (simulated fall) to standing in normal gravity, as well as heart rate (HR) during 11 functional tasks. As such, this test describes some aspects of spaceflight-induced cardiovascular deconditioning and the course of recovery in Space Shuttle and International Space Station (ISS) astronauts. The sensorimotor and neuromuscular components of the FTT are described in two separate abstracts: Functional Task Test 1 and 3.

  14. MELD-Na as a prognostic indicator of 30- and 90-day mortality in patients with end-stage liver disease after creation of transjugular intrahepatic portosystemic shunt.

    PubMed

    Ahmed, Rezwan; Santhanam, Prasanna; Rayyan, Yaser

    2015-10-01

    Previous studies have shown that the Model for End-Stage Liver Disease (MELD) score is superior to other liver disease scoring systems to establish optimal candidates for transjugular intrahepatic portosystemic shunt (TIPS) procedure and liver transplantation. Our aim was to compare MELD-Na score with MELD score as a predictor of 30-day as well as 90-day mortality for individuals with end-stage liver disease (ESLD) after creation of TIPS. We performed a chart review on cirrhotic patients who underwent TIPS procedure and documented presence and severity of ascites and hepatic encephalopathy, patient laboratory values, and results from TIPS procedures. We compared continuous variables by Student's t-test for independent samples and categorical variables by χ-test(s). In non-normal distributions, a nonparametric test was used. We performed a logistic regression to determine the effects of several variables and analyzed variable predictors of likelihood of death within 30 and 90 days of TIPS procedure. Of the six predictor variables, only MELD-Na score was a statistically significant predictor of 30- and 90-day mortality following TIPS procedure for ESLD (P=0.028). For each one point increase in MELD-Na score, the odds of death increased by 1.15 times [95% confidence interval (1.02-1.30), P=0.28]. Since hyponatremia may be associated with poor prognostic features of overall health, its incorporation into the MELD scoring system to predict mortality in ESLD after creation of TIPS serves a useful purpose. Our single-center experience suggests that the MELD-Na score is the most effective predictor of survival after TIPS creation. PMID:26111072

  15. Dam-related effects on heart girth at birth, morbidity and growth rate from birth to 90 days of age in Swedish dairy calves.

    PubMed

    Lundborg, G K; Oltenacu, P A; Maizon, D O; Svensson, E C; Liberg, P G A

    2003-08-01

    We investigated the effects of dam-related factors (such as calving performance, milk leakage, diseases, milk production, and somatic-cell count (SCC)) on heart girth at birth and the incidence risk of diarrhoea and respiratory disease during the first 90 days in Swedish dairy calves. The effects of these dam-related factors and environmental and management-related (but not dietary) factors on the calves' growth rate during the first 90 days of life also were analysed. The study used nearly 3,000 heifer calves born in 1998 on 122 farms in the south-west of Sweden. Individual health records were kept by the farmers and visiting project veterinarians. The calf's heart girth was measured at birth and weaning. We used generalised linear mixed models for the size of the calf at birth and growth rate. Variables associated with the heart girth at birth were breed, calving performance, mastitis in the dam in the last 49 days before calving, milk production and parity. Variables associated with the growth rate were breed, calving performance, disease in the calf during its first 90 days of life, heart girth at birth, and housing of calves. The effect of the dam on the relative risk of diarrhoea and/or respiratory disease in the calf was evaluated by a generalised linear mixed model with a logit link. Morbidity in the dam during late pregnancy, retained placenta and SCC were associated with the relative risk of respiratory disease in the calf. None of the explanatory variables (other then breed) was associated with the relative risk of diarrhoea. PMID:12900157

  16. Recovery

    NASA Video Gallery

    This video discusses the recovery events that occur in high-power rocketry and the various devices used in safely recovering the rocket. The video includes a discussion of black powder and ejection...

  17. [Recovery].

    PubMed

    Estingoy, Pierrette; Gilliot, Élodie; Parisot, Clément

    2015-01-01

    The historical fatalism of the impossibility of recovering from psychosis eased from the 1970s with the shaping of the idea of a possible recovery. Recovery is today the objective for the patient and caregivers. The key to achieving this lies in the encounter with Others. A collective approach, on the level of the institution, must be established. The aim is to create opportunities for the patient to express their doubts and feelings. PMID:26363659

  18. STS-90 Day 11 Highlights

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this eleventh day of the STS-90 mission, the flight crew, Cmdr. Richard A. Searfoss, Pilot Scott D. Altman, and Mission Specialists Richard M. Linnehan, Dafydd Rhys Williams and Kathryn P. Hire, and Payload Specialists Jay C. Buckey and James A. Pawelczyk once again take part in an experiment aimed at exploring the influence of gravity on blood pressure. The lower body negative pressure test places a stress on the cardiovascular system similar to that experienced when standing in Earth's gravity. Pawelczyk also takes part in the Valsalva test, which stimulates the pressure receptors in the neck and chest and measures those responses. Both Buckey and Pawelzyk participate as subjects and as operators in tests of the autonomic nervous system. All four science crew members conduct tests of their pulmonary systems as well as additional runs in a rotating chair to measure the response of their eyes and inner ears in maintaining balance in a weightless environment.

  19. STS-90 Day 03 Highlights

    NASA Technical Reports Server (NTRS)

    1998-01-01

    On this third day of the STS-90 mission, the flight crew, Cmdr. Richard A. Searfoss, Pilot Scott D. Altman, and Mission Specialists Richard M. Linnehan, Dafydd Rhys Williams and Kathryn P. Hire, and Payload Specialists Jay C. Buckey and James A. Pawelczyk continue to conduct both human and animal research experiments in the Spacelab module. During the morning, the payload crew members Linnehan, Williams, Buckey and Pawelczyk performs transfer activities with the Animal Enclosure Module, setting up the General Purpose Work Station (GPWS) and operations with the ball catch experiment. In the afternoon, their attention will be on injections and dissections of some of the research animals and an objects recognition test.

  20. A 90-Day Dietary Toxicity Study of Genetically Modified Rice T1C-1 Expressing Cry1C Protein in Sprague Dawley Rats

    PubMed Central

    Tang, Xueming; Han, Fangting; Zhao, Kai; Xu, Yan; Wu, Xiao; Wang, Jinbin; Jiang, Lingxi; Shi, Wei

    2012-01-01

    In a 90-day study, Sprague Dawley rats were fed transgenic T1C-1 rice expressing Cry1C protein and were compared with rats fed non-transgenic parental rice Minghui 63 and rats fed a basal diet. No adverse effects on animal behavior or weight gain were observed during the study. Blood samples were collected and analyzed, and standard hematological and biochemical parameters were compared. A few of these parameters were found to be significantly different, but were within the normal reference intervals for rats of this breed and age, and were thus not considered to be treatment-related. Following sacrifice, a large number of organs were weighed, and macroscopic and histopathological examinations were performed with no changes reported. The aim of this study was to use a known animal model to determine the safety of the genetically modified (GM) rice T1C-1. The results showed no adverse or toxic effects due to T1C-1 rice when tested in this 90-day study. PMID:23300690

  1. Catecholaminergic based therapies for functional recovery after TBI.

    PubMed

    Osier, Nicole D; Dixon, C Edward

    2016-06-01

    Among the many pathophysiologic consequences of traumatic brain injury are changes in catecholamines, including dopamine, epinephrine, and norepinephrine. In the context of TBI, dopamine is the one most extensively studied, though some research exploring epinephrine and norepinephrine have also been published. The purpose of this review is to summarize the evidence surrounding use of drugs that target the catecholaminergic system on pathophysiological and functional outcomes of TBI using published evidence from pre-clinical and clinical brain injury studies. Evidence of the effects of specific drugs that target catecholamines as agonists or antagonists will be discussed. Taken together, available evidence suggests that therapies targeting the catecholaminergic system may attenuate functional deficits after TBI. Notably, it is fairly common for TBI patients to be treated with catecholamine agonists for either physiological symptoms of TBI (e.g. altered cerebral perfusion pressures) or a co-occuring condition (e.g. shock), or cognitive symptoms (e.g. attentional and arousal deficits). Previous clinical trials are limited by methodological limitations, failure to replicate findings, challenges translating therapies to clinical practice, the complexity or lack of specificity of catecholamine receptors, as well as potentially counfounding effects of personal and genetic factors. Overall, there is a need for additional research evidence, along with a need for systematic dissemination of important study details and results as outlined in the common data elements published by the National Institute of Neurological Diseases and Stroke. Ultimately, a better understanding of catecholamines in the context of TBI may lead to therapeutic advancements. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID:26711850

  2. Incidence, clinical course, and predictors of prolonged recovery time following sport-related concussion in high school and college athletes.

    PubMed

    McCrea, Michael; Guskiewicz, Kevin; Randolph, Christopher; Barr, William B; Hammeke, Thomas A; Marshall, Stephen W; Powell, Matthew R; Woo Ahn, Kwang; Wang, Yanzhi; Kelly, James P

    2013-01-01

    Sport-related concussion (SRC) is typically followed by clinical recovery within days, but reports of prolonged symptoms are common. We investigated the incidence of prolonged recovery in a large cohort (n = 18,531) of athlete seasons over a 10-year period. A total of 570 athletes with concussion (3.1%) and 166 controls who underwent pre-injury baseline assessments of symptoms, neurocognitive functioning and balance were re-assessed immediately, 3 hr, and 1, 2, 3, 5, 7, and 45 or 90 days after concussion. Concussed athletes were stratified into typical (within 7 days) or prolonged (> 7 days) recovery groups based on symptom recovery time. Ten percent of athletes (n = 57) had a prolonged symptom recovery, which was also associated with lengthier recovery on neurocognitive testing (p < .001). At 45-90 days post-injury, the prolonged recovery group reported elevated symptoms, without deficits on cognitive or balance testing. Prolonged recovery was associated with unconsciousness [odds ratio (OR), 4.15; 95% confidence interval (CI) 2.12-8.15], posttraumatic amnesia (OR, 1.81; 95% CI, 1.00-3.28), and more severe acute symptoms (p < .0001). These results suggest that a small percentage of athletes may experience symptoms and functional impairments beyond the typical window of recovery after SRC, and that prolonged recovery is associated with acute indicators of more severe injury. PMID:23058235

  3. Neuromotor recovery from stroke: computational models at central, functional, and muscle synergy level

    PubMed Central

    Casadio, Maura; Tamagnone, Irene; Summa, Susanna; Sanguineti, Vittorio

    2013-01-01

    Computational models of neuromotor recovery after a stroke might help to unveil the underlying physiological mechanisms and might suggest how to make recovery faster and more effective. At least in principle, these models could serve: (i) To provide testable hypotheses on the nature of recovery; (ii) To predict the recovery of individual patients; (iii) To design patient-specific “optimal” therapy, by setting the treatment variables for maximizing the amount of recovery or for achieving a better generalization of the learned abilities across different tasks. Here we review the state of the art of computational models for neuromotor recovery through exercise, and their implications for treatment. We show that to properly account for the computational mechanisms of neuromotor recovery, multiple levels of description need to be taken into account. The review specifically covers models of recovery at central, functional and muscle synergy level. PMID:23986688

  4. Genome-wide gene expression effects in B6C3F1 mouse intestinal epithelia following 7 and 90 days of exposure to hexavalent chromium in drinking water

    SciTech Connect

    Kopec, Anna K.; Kim, Suntae; Forgacs, Agnes L.; Zacharewski, Timothy R.; Proctor, Deborah M.; Harris, Mark A.; Haws, Laurie C.; Thompson, Chad M.

    2012-02-15

    Chronic administration of high doses of hexavalent chromium [Cr(VI)] as sodium dichromate dihydrate (SDD) elicits alimentary cancers in mice. To further elucidate key events underlying tumor formation, a 90-day drinking water study was conducted in B6C3F1 mice. Differential gene expression was examined in duodenal and jejunal epithelial samples following 7 or 90 days of exposure to 0, 0.3, 4, 14, 60, 170 or 520 mg/L SDD in drinking water. Genome-wide microarray analyses identified 6562 duodenal and 4448 jejunal unique differentially expressed genes at day 8, and 4630 and 4845 unique changes, respectively, in the duodenum and jejunum at day 91. Comparative analysis identified significant overlap in duodenal and jejunal differential gene expression. Automated dose–response modeling identified > 80% of the differentially expressed genes exhibited sigmoidal dose–response curves with EC{sub 50} values ranging from 10 to 100 mg/L SDD. Only 16 genes satisfying the dose-dependent differential expression criteria had EC{sub 50} values < 10 mg/L SDD, 3 of which were regulated by Nrf2, suggesting oxidative stress in response to SDD at low concentrations. Analyses of differentially expressed genes identified over-represented functions associated with oxidative stress, cell cycle, lipid metabolism, and immune responses consistent with the reported effects on redox status and histopathology at corresponding SDD drinking water concentrations. Collectively, these data are consistent with a mode of action involving oxidative stress and cytotoxicity as early key events. This suggests that the tumorigenic effects of chronic Cr(VI) oral exposure likely require chronic tissue damage and compensatory epithelial cell proliferation. Highlights: ► Mouse small intestine gene expression is highly responsive to hexavalent chromium [Cr(VI)]. ► Cr(VI) elicits more differential gene expression after 7 days of exposure than 90 days of exposure. ► Oral exposure to Cr(VI) leads to

  5. Recovery after prolonged sleep deprivation: residual effects of slow-release caffeine on recovery sleep, sleepiness and cognitive functions.

    PubMed

    Beaumont, Maurice; Batéjat, Denise; Coste, Olivier; Doireau, Philippe; Chauffard, Françoise; Enslen, Marc; Lagarde, Didier; Pierard, Christophe

    2005-01-01

    A long work schedule often results in sleep deprivation, sleepiness, impaired performance and fatigue. We investigated the residual effects of slow-release caffeine (SRC) on sleep, sleepiness and cognitive performance during a 42-hour recovery period following a 64-hour continuous wakefulness period in 16 healthy males, according to a double-blind, randomised, placebo-controlled, crossover study. Three hundred milligrams of SRC or placebo was given twice a day at 21:00 and 9:00 during the first 48 h of wakefulness. Recovery sleep was analysed with electroencephalography (EEG) and wrist actigraphy, daytime sleepiness with continuous EEG, sleep latency tests and actigraphy and cognitive functions with computerized tests from the NATO AGARD STRES battery. Both drug groups exhibited almost the same sleep architecture with a rebound of slow-wave sleep during both recovery nights and of REM sleep during the second night. Wakefulness level and cognitive functions were similarly impaired in both groups on the first day of recovery and partially returned to baseline on the second. To conclude, SRC appears to have no unwanted side-effects on recovery sleep, wakefulness and cognitive performance after a long period of sleep deprivation and might therefore be a useful choice over other psychostimulants for a long work schedule. PMID:15627809

  6. Induction of multiple granulomas in the liver with severe hepatocyte damage by montan wax, a natural food additive, in a 90-day toxicity study in F344 rats.

    PubMed

    Ikeda, Mico; Yamakawa, Keiko; Saoo, Kousuke; Matsuda, Yoko; Hosokawa, Kyoko; Takeuchi, Hijiri; Li, Jia-Qing; Zeng, Yu; Yokohira, Masanao; Imaida, Katsumi

    2008-02-01

    Montan wax is a mineral wax extracted from lignite type coal. It has been registered as a food additive in Japan though there have been no reports of toxicological evaluation, mainly due to the fact that it is considered a natural product. As part of a general safety assessment of montan wax, we have performed a 90-day toxicity study in Fisher 344 (F344) rats. Groups of 10 males and 10 females were given the material at dose levels of 0 (Group 1), 0.56 (Group 2), 1.67 (Group 3), or 5% (Group 4) in the diet for 90 days. During the experiment, there were no remarkable changes in general conditions and no deaths occurred in any group. On hematological examination, Hb, Ht, MCV and MCH were significantly decreased and WBC was significantly increased in all treated rats. On serum biochemical examination, AST and ALT were found to be elevated more than four fold in all treated groups as compared to the respective control group values in both sexes. Furthermore, relative organ weights for the liver, spleen, lung and kidneys were increased in all treated groups of both sexes. Histopathological examination revealed diffuse multiple granulomas in the livers with severe hepatocyte damage and lymphocytic infiltration. Granulomatous lesions were also apparent in the mesenteric lymph nodes in all treated males and females. These findings clearly demonstrate that montan wax, at doses of more than 0.56% in the diet, induces multiple granulomas with severe inflammation in the liver. Because pathological, hematological and serum biochemical changes were observed in the lowest dose group, a no-observed-adverse-effect level (NOAEL) could not be determined in the present study. PMID:17950973

  7. Vagal Recovery From Cognitive Challenge Moderates Age-Related Deficits in Executive Functioning.

    PubMed

    Crowley, Olga V; Kimhy, David; McKinley, Paula S; Burg, Matthew M; Schwartz, Joseph E; Lachman, Margie E; Tun, Patricia A; Ryff, Carol D; Seeman, Teresa E; Sloan, Richard P

    2016-05-01

    Decline in executive functioning (EF) is a hallmark of cognitive aging. We have previously reported that faster vagal recovery from cognitive challenge is associated with better EF. This study examined the association between vagal recovery from cognitive challenge and age-related differences in EF among 817 participants in the Midlife in the U.S. study (aged 35-86). Cardiac vagal control was measured as high-frequency heart rate variability. Vagal recovery moderated the association between age and EF (β = .811, p = .004). Secondary analyses revealed that older participants (aged 65-86) with faster vagal recovery had superior EF compared to their peers who had slower vagal recovery. In contrast, among younger (aged 35-54) and middle-aged (aged 55-64) participants, vagal recovery was not associated with EF. We conclude that faster vagal recovery from cognitive challenge is associated with reduced deficits in EF among older, but not younger individuals. PMID:26303063

  8. Vagal Recovery From Cognitive Challenge Moderates Age-Related Deficits in Executive Functioning

    PubMed Central

    Crowley, Olga V.; Kimhy, David; McKinley, Paula S.; Burg, Matthew M.; Schwartz, Joseph E.; Lachman, Margie E.; Tun, Patricia A.; Ryff, Carol D.; Seeman, Teresa E.; Sloan, Richard P.

    2015-01-01

    Decline in executive functioning (EF) is a hallmark of cognitive aging. We have previously reported that faster vagal recovery from cognitive challenge is associated with better EF. This study examined the association between vagal recovery from cognitive challenge and age-related differences in EF among 817 participants in the Midlife in the U.S. study (aged 35–86). Cardiac vagal control was measured as high-frequency heart rate variability. Vagal recovery moderated the association between age and EF (β = .811, p = .004). Secondary analyses revealed that older participants (aged 65–86) with faster vagal recovery had superior EF compared to their peers who had slower vagal recovery. In contrast, among younger (aged 35–54) and middle-aged (aged 55–64) participants, vagal recovery was not associated with EF. We conclude that faster vagal recovery from cognitive challenge is associated with reduced deficits in EF among older, but not younger individuals. PMID:26303063

  9. Brain plasticity as a basis for recovery of function in humans.

    PubMed

    Bach-y-Rita, P

    1990-01-01

    One of the factors leading to the virtual neglect of the long-term potential for functional recovery following brain damage was the eclipse of plasticity concepts during the 100 years following Broca's 1861 publication on location of function. However, in the last 30 years evidence has been accumulating that demonstrates the plasticity of the brain and thus recovery potential is a subject of practical as well as theoretical interest. "Unmasking" of relatively inactive pathways, the taking over of functional representation by undamaged brain tissue, and neuronal group selection are among the mechanisms that are being explored. Human models of recovery of function include hemispherectomy patients that have regained bilateral function, facial paralysis patients who recover function (with appropriate rehabilitation) after VII-XII cranial nerve anastomosis, and patients with muscle transpositions to re-establish lost motor functions. The role of early and late rehabilitation, with attention to psychosocial and environmental factors, appears to be critical for recovery. PMID:2395525

  10. Functional Outcomes of Decompressive Craniectomy in Patients with Malignant Middle Cerebral Artery Infarction and Their Association with Preoperative Thalamus Deformation: An Analysis of 12 Patients.

    PubMed

    Fukuoka, Takuya; Hayashi, Takeshi; Ohira, Masayuki; Kato, Yuji; Deguchi, Ichiro; Maruyama, Hajime; Abe, Tetsuya; Sano, Hiroyasu; Mizuno, Satoko; Nagamine, Yuito; Kurita, Hiroki; Takao, Masaki; Tanahashi, Norio

    2016-01-01

    Objective Decompressive craniectomy (DC) in patients with malignant middle cerebral artery (MCA) infarction is known to decrease the mortality rate. However, the functional outcomes (communication and oral intake) of this procedure remain unclear. Most patients with malignant MCA infarction exhibit a loss of consciousness, which may be principally governed by the thalamus. We herein investigated the functional outcomes of DC at 90 days after the onset of malignant MCA infarction and their association with preoperative thalamus deformation, which can occur due to pressure and edema. Methods Twelve of 2,692 patients with acute cerebral infarction were diagnosed with malignant MCA infarction and underwent DC. We evaluated preoperative thalamus damage using brain computed tomography and its association with communication and oral intake abilities and the modified Rankin Scale (mRS) and Barthel index scores at 90 days after stroke onset. Results The mRS score at 90 days was 0-4 in five patients. Seven patients could communicate immediately after surgery, while five could do so by 90 days. Five patients were able to resume the oral intake of food at 90 days. All patients with preoperative thalamus deformation showed a poor recovery, while those with absent or slight preoperative thalamus deformation showed a good recovery. Conclusion Patients with preoperative thalamus deformation caused by pressure and edema show a poor oral intake and communication abilities after DC, suggesting that preoperative thalamus deformation is a predictor of poor functional outcomes after DC in patients with malignant MCA infarction. PMID:27477404

  11. Effect of complications within 90 days on patient-reported outcomes 3 months and 12 months following elective surgery for lumbar degenerative disease.

    PubMed

    Chotai, Silky; Parker, Scott L; Sivaganesan, Ahilan; Sielatycki, J Alex; Asher, Anthony L; McGirt, Matthew J; Devin, Clinton J

    2015-12-01

    OBJECT There is a paradigm shift toward rewarding providers for quality rather than volume. Complications appear to occur at a fairly consistent frequency in large aggregate data sets. Understanding how complications affect long-term patient-reported outcomes (PROs) following degenerative lumbar surgery is vital. The authors hypothesized that 90-day complications would adversely affect long-term PROs. METHODS Nine hundred six consecutive patients undergoing elective surgery for degenerative lumbar disease over a period of 4 years were enrolled into a prospective longitudinal registry. The following PROs were recorded at baseline and 12-month follow-up: Oswestry Disability Index (ODI) score, numeric rating scales for back and leg pain, quality of life (EQ-5D scores), general physical and mental health (SF-12 Physical Component Summary [PCS] and Mental Component Summary [MCS] scores) and responses to the North American Spine Society (NASS) satisfaction questionnaire. Previously published minimum clinically important difference (MCID) threshold were used to define meaningful improvement. Complications were divided into major (surgicalsite infection, hardware failure, new neurological deficit, pulmonary embolism, hematoma and myocardial infarction) and minor (urinary tract infection, pneumonia, and deep venous thrombosis). RESULTS Complications developed within 90 days of surgery in 13% (118) of the patients (major in 12% [108] and minor in 8% [68]). The mean improvement in ODI scores, EQ-5D scores, SF-12 PCS scores, and satisfaction at 3 months after surgery was significantly less in the patients with complications than in those who did not have major complications (ODI: 13.5 ± 21.2 vs 21.7 ± 19, < 0.0001; EQ-5D: 0.17 ± 0.25 vs 0.23 ± 0.23, p = 0.04; SF-12 PCS: 8.6 ± 13.3 vs 13.0 ± 11.9, 0.001; and satisfaction: 76% vs 90%, p = 0.002). At 12 months after surgery, the patients with major complications had higher ODI scores than those without complications (29.1

  12. In vivo genotoxicity evaluation of lung cells from Fischer 344 rats following 28 days of inhalation exposure to MWCNTs, plus 28 days and 90 days post-exposure.

    PubMed

    Kim, Jin Sik; Sung, Jae Hyuck; Choi, Byung Gil; Ryu, Hyeon Yeol; Song, Kyung Seuk; Shin, Jae Hoon; Lee, Jong Seong; Hwang, Joo Hwan; Lee, Ji Hyun; Lee, Gun Ho; Jeon, Kisoo; Ahn, Kang Ho; Yu, Il Je

    2014-03-01

    Despite their useful physico-chemical properties, carbon nanotubes (CNTs) continue to cause concern over occupational and human health due to their structural similarity to asbestos. Thus, to evaluate the toxic and genotoxic effect of multi-wall carbon nanotubes (MWCNTs) on lung cells in vivo, eight-week-old rats were divided into four groups (each group = 25 animals), a fresh air control (0 mg/m(3)), low (0.17 mg/m(3)), middle (0.49 mg/m(3)), and high (0.96 mg/m(3)) dose group, and exposed to MWCNTs via nose-only inhalation 6 h per day, 5 days per week for 28 days. The count median length and geometric standard deviation for the MWCNTs determined by TEM were 330.18 and 1.72 nm, respectively, and the MWCNT diameters ranged from 10 to 15 nm. Lung cells were isolated from five male and five female rats in each group on day 0, day 28 (only from males) and day 90 following the 28-day exposure. The total number of animals used was 15 male and 10 female rats for each concentration group. To determine the genotoxicity of the MWCNTs, a single cell gel electrophoresis assay (Comet assay) was conducted on the rat lung cells. As a result of the exposure, the olive tail moments were found to be significantly higher (p < 0.05) in the male and female rats from all the exposed groups when compared with the fresh air control. In addition, the high-dose exposed male and middle and high-dose exposed female rats retained DNA damage, even 90 days post-exposure (p < 0.05). To investigate the mode of genotoxicity, the intracellular reactive oxygen species (ROS) levels and inflammatory cytokine levels (TNF-α, TGF- β, IL-1, IL-2, IL-4, IL-5, IL-10, IL-12 and IFN-γ) were also measured. For the male rats, the H2O2 levels were significantly higher in the middle (0 days post-exposure) and high- (0 days and 28 days post-exposure) dose groups (p < 0.05). Conversely, the female rats showed no changes in the H2O2 levels. The inflammatory cytokine levels in the

  13. Functional Cure of SIVagm Infection in Rhesus Macaques Results in Complete Recovery of CD4+ T Cells and Is Reverted by CD8+ Cell Depletion

    PubMed Central

    Pandrea, Ivona; Gaufin, Thaidra; Gautam, Rajeev; Kristoff, Jan; Mandell, Daniel; Montefiori, David; Keele, Brandon F.; Ribeiro, Ruy M.; Veazey, Ronald S.; Apetrei, Cristian

    2011-01-01

    Understanding the mechanism of infection control in elite controllers (EC) may shed light on the correlates of control of disease progression in HIV infection. However, limitations have prevented a clear understanding of the mechanisms of elite controlled infection, as these studies can only be performed at randomly selected late time points in infection, after control is achieved, and the access to tissues is limited. We report that SIVagm infection is elite-controlled in rhesus macaques (RMs) and therefore can be used as an animal model for EC HIV infection. A robust acute infection, with high levels of viral replication and dramatic mucosal CD4+ T cell depletion, similar to pathogenic HIV-1/SIV infections of humans and RMs, was followed by complete and durable control of SIVagm replication, defined as: undetectable VLs in blood and tissues beginning 72 to 90 days postinoculation (pi) and continuing at least 4 years; seroreversion; progressive recovery of mucosal CD4+ T cells, with complete recovery by 4 years pi; normal levels of T cell immune activation, proliferation, and apoptosis; and no disease progression. This “functional cure” of SIVagm infection in RMs could be reverted after 4 years of control of infection by depleting CD8 cells, which resulted in transient rebounds of VLs, thus suggesting that control may be at least in part immune mediated. Viral control was independent of MHC, partial APOBEC restriction was not involved in SIVagm control in RMs and Trim5 genotypes did not impact viral replication. This new animal model of EC lentiviral infection, in which complete control can be predicted in all cases, permits research on the early events of infection in blood and tissues, before the defining characteristics of EC are evident and when host factors are actively driving the infection towards the EC status. PMID:21829366

  14. Safety assessment of SDA soybean oil: results of a 28-day gavage study and a 90-day/one generation reproduction feeding study in rats.

    PubMed

    Hammond, Bruce G; Lemen, Joan K; Ahmed, Gulam; Miller, Kathleen D; Kirkpatrick, Jeannie; Fleeman, Tammye

    2008-12-01

    Long chain polyunsaturated fatty acids (LC-PUFAs) in the diet reduce risk of cardiac mortality. Fish oils are a dietary source of LC-PUFAs (EPA, DHA) but intake is low in Western diets. Adding beneficial amounts of LC-PUFAs to foods is limited by their instability and potential to impart off-flavors. Stearidonic acid (SDA), a precursor of EPA in man, is more stable than EPA/DHA in food matrices. SDA is present in fish oils (0.5-4%) and in nutraceuticals (echium, borage oil). Genes for Delta6, Delta15 desaturases were introduced into soybeans that convert linoleic and alpha-linolenic acid to SDA (15-30% fatty acids). Since addition of SDA soybean oil into human foods increases SDA intake, toxicology studies were undertaken to assess its safety. In a 28-day pilot study, rats were gavaged with SDA soybean oil at dosages up to 3g/kg body weight/day; no treatment-related adverse effects were observed. A 90-day/one generation rat reproduction study was subsequently conducted where SDA soybean oil was added to diets to provide daily doses of 1.5 and 4 g/kg body weight. There were no treatment-related adverse effects on parental animals or on reproductive performance and progeny development. PMID:18804141

  15. Evaluation of 90-day Repeated Dose Oral Toxicity, Glycometabolism, Learning and Memory Ability, and Related Enzyme of Chromium Malate Supplementation in Sprague-Dawley Rats.

    PubMed

    Feng, Weiwei; Wu, Huiyu; Li, Qian; Zhou, Zhaoxiang; Chen, Yao; Zhao, Ting; Feng, Yun; Mao, Guanghua; Li, Fang; Yang, Liuqing; Wu, Xiangyang

    2015-11-01

    Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the 90-day oral toxicity of chromium malate in Sprague-Dawley rats. The present study inspected the effect of chromium malate on glycometabolism, glycometabolism-related enzymes, lipid metabolism, and learning and memory ability in metabolically healthy Sprague-Dawley rats. The results showed that all rats survived and pathological, toxic, feces, and urine changes were not observed. Chromium malate did not cause measurable damage on liver, brain, and kidney. The fasting blood glucose, serum insulin, insulin resistance index, C-peptide, hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels of normal rats in chromium malate groups had no significant change when compared with control group and chromium picolinate group under physiologically relevant conditions. The serum and organ content of Cr in chromium malate groups had no significant change compared with control group. No significant changes were found in morris water maze test and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and true choline esterase (TChE) activity. The results indicated that supplementation with chromium malate did not cause measurable toxicity and has no obvious effect on glycometabolism and related enzymes, learning and memory ability, and related enzymes and lipid metabolism of female and male rats. The results of this study suggest that chromium malate is safe for human consumption. PMID:25900579

  16. Evaluation of the 90-day inhalation toxicity of petroleum and oil shale JP-5 jet fuel. Technical report, July 1977-July 1983

    SciTech Connect

    Gaworski, C.L.; MacEwen, J.D.; Vernot, E.H.; Haun, C.C.; Leahy, H.F.

    1985-04-01

    Subchronic 90-day inhalation studies were conducted to compare the toxicity of Petroleum and Oil Shale derived JP-5 jet fuel. Beagle dogs, Fischer 344 rats, and C57BL/6 mice were continuously exposed to JP-5 at concentrations of 150 mg/m cum and 750 mg/cum 3. Unexposed control groups were also maintained. All dogs and a portion of each rodent group were sacrificed and examined at exposure termination. Remaining rodents were held for observation up to 21 months postexposure. The most significant exposure related effect occurred in male rats, where JP-5 produced nephropathy characterized by hyaline droplets, necrosis, and intratubular casts. Accentuated tubular degeneration and medullary mineralization were noted in exposed rats held for long-term postexposure observation. Female rats were free of significant JP-5 related renal damage. Consistent with the pathologic changes in male rats exposed to 750 mg/cu m 3 were increased kidney weight and increased serum creatinine and BUN levels. Reduced body weight gains also occurred in male rats exposed to JP-5. No pathologic lesions were observed in dogs exposed to JP-5. Hepatocellular vacuolization and fatty change occurred in mice exposed to JP-5 from either source and in rats exposed to Shale JP-5. The results of this study suggest that there are no substantial differences between Petroleum and Shale JP-5.

  17. Cariogram outcome after 90 days of oral treatment with Streptococcus salivarius M18 in children at high risk for dental caries: results of a randomized, controlled study.

    PubMed

    Di Pierro, Francesco; Zanvit, Alberto; Nobili, Piero; Risso, Paolo; Fornaini, Carlo

    2015-01-01

    Dental caries is the most common chronic disease of childhood. Cariogram is a well-recognized algorithm-based software program based on different caries-related risk factors and intended to aid clinicians in performing more objective and consistent dental caries risk assessments. This type of approach precedes the diagnosis of caries and allows the dentist to identify at-risk patients and then take appropriate preventive measures before caries develop further. One of the etiological factors favoring the development of dental caries is the mutans streptococci. These acidogenic dental plaque inhabitants can be effectively antagonized by the activity of bacteriocins released by the probiotic Streptococcus salivarius M18 (salivarius M18). Moreover, salivarius M18 after colonizing the human oral mucosa produces the enzymes dextranase and urease that are able to counteract plaque formation and saliva acidity, respectively. Seventy-six subjects at high risk of dental caries were randomized and then either treated or not treated for 90 days with an oral formulation containing the oral probiotic salivarius M18 (Carioblis(®)). The results indicate that the use of salivarius M18 increases the chances of avoiding new dental caries development in children, and its application could be proposed as a new tool in the dentist's armory to be adopted in subjects considered at high risk on the basis of their Cariogram outcome. PMID:26491371

  18. Cariogram outcome after 90 days of oral treatment with Streptococcus salivarius M18 in children at high risk for dental caries: results of a randomized, controlled study

    PubMed Central

    Di Pierro, Francesco; Zanvit, Alberto; Nobili, Piero; Risso, Paolo; Fornaini, Carlo

    2015-01-01

    Dental caries is the most common chronic disease of childhood. Cariogram is a well-recognized algorithm-based software program based on different caries-related risk factors and intended to aid clinicians in performing more objective and consistent dental caries risk assessments. This type of approach precedes the diagnosis of caries and allows the dentist to identify at-risk patients and then take appropriate preventive measures before caries develop further. One of the etiological factors favoring the development of dental caries is the mutans streptococci. These acidogenic dental plaque inhabitants can be effectively antagonized by the activity of bacteriocins released by the probiotic Streptococcus salivarius M18 (salivarius M18). Moreover, salivarius M18 after colonizing the human oral mucosa produces the enzymes dextranase and urease that are able to counteract plaque formation and saliva acidity, respectively. Seventy-six subjects at high risk of dental caries were randomized and then either treated or not treated for 90 days with an oral formulation containing the oral probiotic salivarius M18 (Carioblis®). The results indicate that the use of salivarius M18 increases the chances of avoiding new dental caries development in children, and its application could be proposed as a new tool in the dentist’s armory to be adopted in subjects considered at high risk on the basis of their Cariogram outcome. PMID:26491371

  19. Safety assessment of freeze-dried powdered Tenebrio molitor larvae (yellow mealworm) as novel food source: Evaluation of 90-day toxicity in Sprague-Dawley rats.

    PubMed

    Han, So-Ri; Lee, Byoung-Seok; Jung, Kyung-Jin; Yu, Hee-Jin; Yun, Eun-Young; Hwang, Jae Sam; Moon, Kyoung-Sik

    2016-06-01

    Worldwide demand for novel food source has grown and edible insects are a promising food sources for humans. Tenebrio molitor, as known as yellow mealworm, has advantages of being rich in protein, and easy to raise as a novel food source. The objective of this study was to evaluate subchronic toxicity, including potential hypersensitivity, of freeze-dried powdered T. molitor larvae (fdTML) in male and female Sprague-Dawley rats. The fdTML was administered orally once daily at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 90 days. A toxicological assessment was performed, which included mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings, histopathologic examination and allergic reaction. There were no fdTML- related findings in clinical signs, urinalysis, hematology and serum chemistry, gross examination, histopathologic examination or allergic reaction. In conclusion, the No Observed Adverse Effect Level (NOAEL) for fdTML was determined to be in excess of 3000 mg/kg/day in both sexes of rats under the experimental conditions of this study. PMID:26993751

  20. Assessment of the reporting of quality and outcome measures in hepatic resections: a call for 90-day reporting in all hepatectomy series

    PubMed Central

    Egger, Michael E; Ohlendorf, Joanna M; Scoggins, Charles R; McMasters, Kelly M; Martin, Robert C G

    2015-01-01

    Background The aim of this paper is to assess the current state of quality and outcomes measures being reported for hepatic resections in the recent literature. Methods Medline and PubMed databases were searched for English language articles published between 1 January 2002 and 30 April 2013. Two examiners reviewed each article and relevant citations for appropriateness of inclusion, which excluded papers of liver donor hepatic resections, repeat hepatectomies or meta-analyses. Data were extracted and summarized by two examiners for analysis. Results Fifty-five studies were identified with suitable reporting to assess peri-operative mortality in hepatic resections. In only 35% (19/55) of the studies was the follow-up time explicitly stated, and in 47% (26/55) of studies peri-operative mortality was limited to in-hospital or 30 days. The time period in which complications were captured was not explicitly stated in 19 out of 28 studies. The remaining studies only captured complications within 30 days of the index operation (8/28). There was a paucity of quality literature addressing truly patient-centred outcomes. Conclusion Quality outcomes after a hepatic resection are inconsistently reported in the literature. Quality outcome studies for a hepatectomy should report mortality and morbidity at a minimum of 90 days after surgery. PMID:26228262

  1. PLANKTON RESPIRATION AND BIOMASS AS FUNCTIONAL INDICATORS OF RECOVERY IN RESTORED PRAIRIE WETLANDS

    EPA Science Inventory

    Reliable ecological indicators of wetland integrity are necessary for assessing recovery of restored wetlands, yet little consensus currently exists on which indicators are most appropriate. We employed indicators derived from simple, standard measures of ecosystem function selec...

  2. Intracerebral hemorrhage in mouse models: therapeutic interventions and functional recovery

    PubMed Central

    Carmichael, S. Thomas

    2014-01-01

    There has been strong pre-clinical research on mechanisms of initial cell death and tissue injury in intracerebral hemorrhage (ICH). This data has led to the evaluation of several therapeutics for neuroprotection or the mitigation of early tissue damage. Most of these studies have been done in the rat. Also, there has been little study of the mechanisms of tissue repair and recovery. This review examines the testing of candidate therapeutics in mouse models of ICH for their effect on tissue protection and repair. This review will help the readers compare it to the extensively researched rat model of ICH and thus enhance work that are pending in mouse model. PMID:24810632

  3. Vagus Nerve Stimulation during Rehabilitative Training Improves Functional Recovery after Intracerebral Hemorrhage

    PubMed Central

    Hays, Seth A.; Khodaparast, Navid; Hulsey, Daniel R.; Ruiz, Andrea; Sloan, Andrew M.; Rennaker, Robert L.; Kilgard, Michael P.

    2014-01-01

    Background and Purpose Vagus nerve stimulation (VNS) delivered during rehabilitative training enhances neuroplasticity and improves recovery in models of cortical ischemic stroke. However, VNS therapy has not been applied in a model of subcortical intracerebral hemorrhage (ICH). We hypothesized that VNS paired with rehabilitative training after ICH would enhance recovery of forelimb motor function beyond rehabilitative training alone. Methods Rats were trained to perform an automated, quantitative measure of forelimb function. Once proficient, rats received an intrastriatal injection of bacterial collagenase to induce ICH. Rats then underwent VNS paired with rehabilitative training (VNS+Rehab; N = 14) or rehabilitative training without VNS (Rehab; N = 12). Rehabilitative training began at least 9 days after ICH and continued for 6 weeks. Results VNS paired with rehabilitative training significantly improved recovery of forelimb function compared to rehabilitative training without VNS. The VNS+Rehab group displayed a 77% recovery of function, while the Rehab group only exhibited 29% recovery. Recovery was sustained after cessation of stimulation. Both groups performed similar amounts of trials during rehabilitative and lesion size was not different between groups. Conclusions VNS paired with rehabilitative training confers significantly improved forelimb recovery following ICH compared to rehabilitative training without VNS. PMID:25147331

  4. Sleep's function in the spontaneous recovery and consolidation of memories.

    PubMed

    Drosopoulos, Spyridon; Schulze, Claudia; Fischer, Stefan; Born, Jan

    2007-05-01

    Building on 2 previous studies (B. R. Ekstrand, 1967; B. R. Ekstrand, M. J. Sullivan, D. F. Parker, & J. N. West, 1971), the authors present 2 experiments that were aimed at characterizing the role of retroactive interference in sleep-associated declarative memory consolidation. Using an A-B, A-C paradigm with lists of word pairs in Experiment 1, the authors showed that sleep provides recovery from retroactive interference induced at encoding, whereas no such recovery was seen in several wake control conditions. Noninterfering word-pair lists were used in Experiment 2 (A-B, C-D). Sleeping after learning, in comparison with waking after learning, enhanced retention of both lists to a similar extent when encoding was less intense because of less list repetition and briefer word-pair presentations. With intense encoding, sleep-associated improvements were not seen for either list. In combination, the results indicate that the benefit of sleep for declarative memory consolidation is greater for weaker associations, regardless of whether weak associations result from retroactive interference or poor encoding. PMID:17500644

  5. Recovery of Olfactory Function following Pediatric Traumatic Brain Injury: A Longitudinal Follow-Up.

    PubMed

    Bakker, Kathleen; Catroppa, Cathy; Anderson, Vicki

    2016-04-15

    There is increasing evidence that disruption of olfactory function after pediatric traumatic brain injury (TBI) is common. Olfactory dysfunction (OD) has been linked to significant functional implications in areas of health, safety, and quality of life, but longitudinal research investigating olfactory recovery is limited. This study aimed to investigate recovery trajectories for olfaction following pediatric TBI and explore predictors of early and late olfactory outcomes. The olfactory function of 37 children with TBI ages 8-16 years was assessed on average at 1.5, 8.0, and 18.0 months post-injury using the University of Pennsylvania Smell Identification Test. A significant improvement in olfactory performance was seen over time in those with acute OD, however, only 16% of those with the most severe OD showed recovery to normal olfactory function, with the remainder demonstrating ongoing olfactory impairment at the 18 month follow-up. Predictors of early (0-3 month) and late (18 month) olfactory outcomes varied with site of impact, a significant predictor of later olfactory performance. In summary, while there was evidence of recovery of OD over time in pediatric TBI, the majority of children with severe OD did not show any recovery. In light of limited recovery of function for more severely affected children, the importance of appropriate education and implementation of rehabilitation management strategies is highlighted. PMID:26413938

  6. Modifications of azoxymethane-induced carcinogenesis and 90-day oral toxicities of 2-tetradecylcyclobutanone as a radiolytic product of stearic acid in F344 rats

    PubMed Central

    Sato, Makoto; Todoriki, Setsuko; Takahashi, Tetsuyuki; Hafez, Ezar; Takasu, Chie; Uehara, Hisanori; Yamakage, Kohji; Kondo, Takashi; Matsumoto, Kozo; Furuta, Masakazu; Izumi, Keisuke

    2015-01-01

    A 90-day oral toxicity test in rats was performed to evaluate the toxicity of 2-tetradecylcyclobutanone (2-tDCB), a unique radiolytic product of stearic acid. Six-week-old male and female F344 rats (n=15/group) were given 2-tDCB at concentrations of 0, 12, 60 and 300 ppm in a powder diet for 13 weeks. Slight dose-dependent increases in serum total protein and albumin in male rats were found, but these changes were not considered to be a toxic effect. The fasting, but not non-fasting, blood glucose levels of the male rats in the 300 ppm group and female rats in the 60 and 300 ppm groups were lower than those of the controls. Gas chromatography-mass spectrometry analysis showed dose-dependent accumulation of 2-tDCB in adipose tissue, notably in males. Next, we performed an azoxymethane (AOM)-induced two-stage carcinogenesis study. After injection of 6-week-old male F344 rats (n=30/group) once a week for 3 weeks, the animals received 2-tDCB at concentrations of 0, 10, 50 and 250 ppm in a powder diet for 25 weeks. The incidences of colon tumors for the 2-tDCB dosages were 34%, 45%, 40% and 37%, respectively, and were not statistically significant. These data suggest that 2-tDCB shows no toxic or tumor-modifying effects under the present conditions, and that the no-observed-adverse-effect level for 2-tDCB is 300 ppm in both sexes, equivalent to 15.5 mg/kg b.w./day in males and 16.5 mg/kg b.w./day in females. PMID:26028819

  7. Modifications of azoxymethane-induced carcinogenesis and 90-day oral toxicities of 2-tetradecylcyclobutanone as a radiolytic product of stearic acid in F344 rats.

    PubMed

    Sato, Makoto; Todoriki, Setsuko; Takahashi, Tetsuyuki; Hafez, Ezar; Takasu, Chie; Uehara, Hisanori; Yamakage, Kohji; Kondo, Takashi; Matsumoto, Kozo; Furuta, Masakazu; Izumi, Keisuke

    2015-04-01

    A 90-day oral toxicity test in rats was performed to evaluate the toxicity of 2-tetradecylcyclobutanone (2-tDCB), a unique radiolytic product of stearic acid. Six-week-old male and female F344 rats (n=15/group) were given 2-tDCB at concentrations of 0, 12, 60 and 300 ppm in a powder diet for 13 weeks. Slight dose-dependent increases in serum total protein and albumin in male rats were found, but these changes were not considered to be a toxic effect. The fasting, but not non-fasting, blood glucose levels of the male rats in the 300 ppm group and female rats in the 60 and 300 ppm groups were lower than those of the controls. Gas chromatography-mass spectrometry analysis showed dose-dependent accumulation of 2-tDCB in adipose tissue, notably in males. Next, we performed an azoxymethane (AOM)-induced two-stage carcinogenesis study. After injection of 6-week-old male F344 rats (n=30/group) once a week for 3 weeks, the animals received 2-tDCB at concentrations of 0, 10, 50 and 250 ppm in a powder diet for 25 weeks. The incidences of colon tumors for the 2-tDCB dosages were 34%, 45%, 40% and 37%, respectively, and were not statistically significant. These data suggest that 2-tDCB shows no toxic or tumor-modifying effects under the present conditions, and that the no-observed-adverse-effect level for 2-tDCB is 300 ppm in both sexes, equivalent to 15.5 mg/kg b.w./day in males and 16.5 mg/kg b.w./day in females. PMID:26028819

  8. Cold water immersion enhances recovery of submaximal muscle function after resistance exercise.

    PubMed

    Roberts, Llion A; Nosaka, Kazunori; Coombes, Jeff S; Peake, Jonathan M

    2014-10-15

    We investigated the effect of cold water immersion (CWI) on the recovery of muscle function and physiological responses after high-intensity resistance exercise. Using a randomized, cross-over design, 10 physically active men performed high-intensity resistance exercise followed by one of two recovery interventions: 1) 10 min of CWI at 10°C or 2) 10 min of active recovery (low-intensity cycling). After the recovery interventions, maximal muscle function was assessed after 2 and 4 h by measuring jump height and isometric squat strength. Submaximal muscle function was assessed after 6 h by measuring the average load lifted during 6 sets of 10 squats at 80% of 1 repetition maximum. Intramuscular temperature (1 cm) was also recorded, and venous blood samples were analyzed for markers of metabolism, vasoconstriction, and muscle damage. CWI did not enhance recovery of maximal muscle function. However, during the final three sets of the submaximal muscle function test, participants lifted a greater load (P < 0.05, Cohen's effect size: 1.3, 38%) after CWI compared with active recovery. During CWI, muscle temperature decreased ∼7°C below postexercise values and remained below preexercise values for another 35 min. Venous blood O2 saturation decreased below preexercise values for 1.5 h after CWI. Serum endothelin-1 concentration did not change after CWI, whereas it decreased after active recovery. Plasma myoglobin concentration was lower, whereas plasma IL-6 concentration was higher after CWI compared with active recovery. These results suggest that CWI after resistance exercise allows athletes to complete more work during subsequent training sessions, which could enhance long-term training adaptations. PMID:25121612

  9. Hyperforin promotes post-stroke functional recovery through interleukin (IL)-17A-mediated angiogenesis.

    PubMed

    Zhang, Jiancheng; Yao, Chengye; Chen, Jiayi; Zhang, Yujing; Yuan, Shiying; Lin, Yun

    2016-09-01

    Hyperforin, the main active ingredient of the medicinal plant Hypericum perforatum, has been shown to be neuroprotective against acute ischemic stroke. However, the long-term actions of hyperforin on the post-stroke functional recovery and underlying mechanisms have not been investigated. C57BL/6 wild-type mice or interleukin (IL)-17A knock-out mice underwent middle cerebral artery occlusion (60min) followed by reperfusion for 28 days. Here, we found that delayed treatment with hyperforin significantly promoted functional recovery and increased IL-17A expression in the ischemic hemisphere at 28 days post-ischemia (dpi). IL-17A knock-out or anti-IL-17A monoclonal antibody (mAb) treatment significantly attenuated the promoting effects of hyperforin on functional recovery. After screening for neurotrophic factors, we revealed that blocking IL-17A significantly decreased, whereas recombinant mouse IL-17A (rIL-17A) treatment significantly increased vascular endothelial growth factor (VEGF) expression. Our data also showed that rIL-17A treatment significantly increased CD34 expression and promoted functional recovery at 28dpi, and the promoting effects were attenuated by VEGF neutralizing antibody treatment. Furthermore, hyperforin treatment significantly increased the expression of VEGF and CD34 in the ischemic hemisphere at 28dpi, and the effects were attenuated by blocking IL-17A. Furthermore, VEGF neutralizing antibody significantly attenuated the promoting role of hyperforin on the cerebral CD34 expression. Thus, our results suggest that, in addition to the acute neuroprotection when delivered immediately after ischemic stroke, hyperforin could also promote functional recovery when delivered in the later phases of stroke recovery. Our results also reveal a previously uncharacterized property of IL-17A/VEGF signaling-induced angiogenesis in hyperforin-mediated functional recovery. PMID:27328426

  10. Remodelling of spared proprioceptive circuit involving a small number of neurons supports functional recovery

    PubMed Central

    Hollis, Edmund R.; Ishiko, Nao; Pessian, Maysam; Tolentino, Kristine; Lee-Kubli, Corinne A.; Calcutt, Nigel A.; Zou, Yimin

    2016-01-01

    Studies show that limited functional recovery can be achieved by plasticity and adaptation of the remaining circuitry in partial injuries in the central nervous system, although the new circuits that arise in these contexts have not been clearly identified or characterized. We show here that synaptic contacts from dorsal root ganglions to a small number of dorsal column neurons, a caudal extension of nucleus gracilis, whose connections to the thalamus are spared in a precise cervical level 1 lesion, underwent remodeling over time. These connections support proprioceptive functional recovery in a conditioning lesion paradigm, as silencing or eliminating the remodelled circuit completely abolishes the recovered proprioceptive function of the hindlimb. Furthermore, we show that blocking repulsive Wnt signalling increases axon plasticity and synaptic connections that drive greater functional recovery. PMID:25597627

  11. Morbidity in Swedish dairy calves from birth to 90 days of age and individual calf-level risk factors for infectious diseases.

    PubMed

    Svensson, Catarina; Lundborg, Karin; Emanuelson, Ulf; Olsson, Sven-Ove

    2003-05-15

    The health of 3081 heifer calves born in 122 dairy herds in the south-west of Sweden from 1 January to 31 December, 1998, was monitored from birth until 90 days of age. The calves were kept either in individual pens (n=2167), in group pens, with 3-8 calves to a pen and manual feeding of milk (n=440), in group pens with 6-30 calves per pen and an automatic milk-feeding system (n=431), or with their dams (n=43). Disease incidence was recorded by farmers and project veterinarians, who clinically examined the calves and auscultated their lungs every 2-3 months. A disease was graded as 'severe' if the general loss of condition or of appetite in the calf continued for >2 days or if the animal suffered severe weight loss due to the disease. The effects of season, breed, housing, and type of colostrum feeding, and time, place and supervision of calving on the incidences of diarrhea, severe diarrhea, respiratory disease, other infectious disease and moderately to severely increased respiratory sounds, were analyzed by logistic-regression models (with herd as a random effect). The total morbidity rate was 0.081 cases per calf-month at risk. Incidence rates of arthritis, diarrhea, omphalophlebitis, respiratory disease and ringworm were 0.002, 0.035, 0.005, 0.025 and 0.009 cases per calf-months at risk, respectively. The odds ratios for diarrhea and severe diarrhea were increased in Swedish Red and Whites (OR: 1.6, 2.3) and in calves that received colostrum from first-lactation cows (OR: 1.3-1.8), and for severe diarrhea in calves born in summer or that received colostrum through suckling (OR: 1.7, 1.8). The odds ratios for respiratory disease and increased respiratory sounds were increased in calves housed in large-group pens with an automatic milk-feeding system (OR: 2.2, 2.8). Supervision of calving was associated with a decreased odds ratio for respiratory disease (OR: 0.7) and birth in individual maternity pen or tie stalls with a decreased odds ratio for increased

  12. Daidzein Augments Cholesterol Homeostasis via ApoE to Promote Functional Recovery in Chronic Stroke

    PubMed Central

    Kim, Eunhee; Woo, Moon-Sook; Qin, Luye; Ma, Thong; Beltran, Cesar D.; Bao, Yi; Bailey, Jason A.; Corbett, Dale; Ratan, Rajiv R.; Lahiri, Debomoy K.

    2015-01-01

    Stroke is the world's leading cause of physiological disability, but there are currently no available agents that can be delivered early after stroke to enhance recovery. Daidzein, a soy isoflavone, is a clinically approved agent that has a neuroprotective effect in vitro, and it promotes axon growth in an animal model of optic nerve crush. The current study investigates the efficacy of daidzein on neuroprotection and functional recovery in a clinically relevant mouse model of stroke recovery. In light of the fact that cholesterols are essential lipid substrates in injury-induced synaptic remodeling, we found that daidzein enhanced the cholesterol homeostasis genetic program, including Lxr and downstream transporters, Apoe, Abca1, and Abcg1 genes in vitro. Daidzein also elevated the cholesterol homeostasis genes in the poststroke brain with Apoe, the highest expressing transporter, but did not affect infarct volume or hemispheric swelling. Despite the absence of neuroprotection, daidzein improved motor/gait function in chronic stroke and elevated synaptophysin expression. However, the daidzein-enhanced functional benefits and synaptophysin expression were abolished in Apoe-knock-out mice, suggesting the importance of daidzein-induced ApoE upregulation in fostering stroke recovery. Dissociation between daidzein-induced functional benefits and the absence of neuroprotection further suggest the presence of nonoverlapping mechanisms underlying recovery processes versus acute pathology. With its known safety in humans, early and chronic use of daidzein aimed at augmenting ApoE may serve as a novel, translatable strategy to promote functional recovery in stroke patients without adverse acute effect. SIGNIFICANCE STATEMENT There have been recurring translational failures in treatment strategies for stroke. One underlying issue is the disparity in outcome analysis between animal and clinical studies. The former mainly depends on acute infarct size, whereas long

  13. The influence of functional electrical stimulation on hand motor recovery in stroke patients: a review

    PubMed Central

    2014-01-01

    Neuromuscular stimulation has been used as one potential rehabilitative treatment option to restore motor function and improve recovery in patients with paresis. Especially stroke patients who often regain only limited hand function would greatly benefit from a therapy that enhances recovery and restores movement. Multiple studies investigated the effect of functional electrical stimulation on hand paresis, the results however are inconsistent. Here we review the current literature on functional electrical stimulation on hand motor recovery in stroke patients. We discuss the impact of different parameters such as stage after stoke, degree of impairment, spasticity and treatment protocols on the functional outcome. Importantly, we outline the results from recent studies investigating the cortical effects elicited by functional electrical stimulation giving insights into the underlying mechanisms responsible for long-term treatment effects. Bringing together the findings from present research it becomes clear that both, treatment outcomes as well as the neurophysiologic mechanisms causing functional recovery, vary depending on patient characteristics. In order to develop unified treatment guidelines it is essential to conduct homogenous studies assessing the impact of different parameters on rehabilitative success. PMID:25276333

  14. 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

  15. Resting State Alpha-band Functional Connectivity and Recovery after Stroke

    PubMed Central

    Westlake, Kelly P.; Hinkley, Leighton B.; Bucci, Monica; Guggisberg, Adrian G.; Findlay, Anne M.; Byl, Nancy; Henry, Roland G.; Nagarajan, Srikantan S.

    2013-01-01

    After cerebral ischemia, disruption and subsequent reorganization of functional connections occur both locally and remote to the lesion. However, the unpredictable timing and extent of sensorimotor recovery reflects a gap in understanding of these underlying neural mechanisms. We aimed to identify plasticity of alpha-band functional neural connections within the perilesional area and the predictive value of functional connectivity with respect to motor recovery of the upper extremity after stroke. Our results show improvements in upper extremity motor recovery in relation to distributed changes in MEG-based alpha band functional connectivity, both in the perilesional area and contralesional cortex. Motor recovery was found to be predicted by increased connectivity at baseline in the ipsilesional somatosensory area, supplementary motor area, and cerebellum, contrasted with reduced connectivity of contralesional motor regions, after controlling for age, stroke onset-time and lesion size. These findings support plasticity within a widely distributed neural network and define brain regions in which the extent of network participation predicts post-stroke recovery potential PMID:22750324

  16. Functional recovery of hibernating myocardium after coronary bypass surgery: Does it coincide with improvement in perfusion

    SciTech Connect

    Takeishi, Y.; Tono-oka, I.; Kubota, I.; Ikeda, K.; Masakane, I.; Chiba, J.; Abe, S.; Tsuiki, K.; Komatani, A.; Yamaguchi, I. )

    1991-09-01

    To determine the relationship between functional recovery and improvement in perfusion after coronary artery bypass graft surgery (CABG), 49 patients were studied. Radionuclide angiography was performed before, 1 month after, and 6 to 12 months after CABG to evaluate regional wall motion. Exercise thallium-201 myocardial perfusion imaging was done before and 1 month after CABG to assess regional perfusion. Preoperative asynergy was observed in 108 segments, and 74 of them showed an improvement in wall motion 1 month after CABG (segment A). Sixty-six of these segments (89%) were associated with an improvement in perfusion. Eight segments that had not improved 1 month after CABG demonstrated a delayed recovery of wall motion 6 to 12 months after CABG (segment B). However, seven of eight segments (88%) already showed an improvement in perfusion 1 month after CABG. A total of 82 segments exhibited functional recovery after CABG and were considered hibernating segments. In the preoperative study segment B more frequently had areas of akinesis or dyskinesis than segment A (75% vs 34%, p less than 0.05). The mean percent thallium-201 uptake in segment B was lower than that in segment A (74% {plus minus} 9% vs 83% {plus minus} 8%, p less than 0.05). Functional recovery of hibernating myocardium usually coincided with an improvement in perfusion. However, delayed functional recovery after reperfusion was observed in some instances. Severe asynergy and severe thallium-201 defects were more frequently observed in these segments with delayed recovery. Hibernating myocardium might remain stunned during those recovery periods.

  17. Functional testing of hepatocytes following their recovery from cryopreservation.

    PubMed

    Innes, G K; Fuller, B J; Hobbs, K E

    1988-02-01

    Various tests of function have been suggested for assessing hepatocytes recovered from cryopreservation. In this study we have investigated hepatocyte attachment during tissue culture and cellular density in order to assess function and compared them with two classical dye exposure tests. The ability of hepatocytes to exclude trypan blue dye (TB) and metabolize fluorescein diacetate (FDA) was demonstrated. In populations of freshly prepared hepatocytes 88.07% were able to exclude TB and 87.31% were able to metabolize FDA. However in populations of hepatocytes recovered after cryopreservation using 1.5 M dimethyl sulfoxide as cryoprotectant only 33.44% were able to exclude TB and 31.59% able to metabolize FDA. Both of these tests gave the same estimate of functional ability. Density gradient centrifugation of hepatocytes on Percoll 400 (Pharmacia, Uppsala, Sweden) separated two populations of hepatocytes; one (density ca.1.07 g/ml Percoll) in which most of the cells were able to exclude TB and the second (density ca. 1.02 g/ml Percoll) in which they were stained blue. The dense population was highly enriched in dye-excluding hepatocytes: freshly prepared hepatocytes, 92.4%, and cryopreserved hepatocytes, 88.66%. When samples of these cells (2 x 10(6) dye-excluding cells per dish) were tested for their ability to attach to tissue culture dishes only 17.28% of the cryopreserved hepatocytes were able to attach compared to 55.28% of the freshly prepared cells. We conclude that cryopreservation of hepatocytes produces a population of cells which are not metabolically identical to a population of freshly prepared hepatocytes even though they appear to have the same buoyant density and dye-excluding capabilities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3349809

  18. A Review of Instruments for Measuring Functional Recovery in Those Diagnosed With Psychosis

    PubMed Central

    Mausbach, Brent T.; Moore, Raeanne; Bowie, Christopher; Cardenas, Veronica; Patterson, Thomas L.

    2009-01-01

    The task of judging an individual's functional recovery is not an easy one for healthcare professionals. Indeed, increasing one's accuracy in predicting one's ability to self-maintain would be of great value for determining if functional recovery has or is occurring. The purpose of this review is to examine existing measures for assessing remission/normalization of functional status among people with psychosis. Our review evaluates 8 measures of functional ability encompassing self-report, clinical, and performance-based measures. We elected to utilize a grading system to aid readers in understanding the merit of a scale for use in assessing functional recovery. In this approach, a letter grade (A, B, or C) was assigned to each of 4 domains we deemed important to professionals in electing to use specific assessments: (1) Ease of Administration, (2) Reliability, (3) Validity/Relationship to Real-World Outcomes, and (4) Sensitivity to Change/Use in Clinical Trials. Results indicated that no “gold standard” measure has been developed to date, but performance-based measures appear to have the most evidence for predicting concurrent self-maintenance abilities (eg, residing independently or maintaining work). More research on existing measures is needed, and greater funding for developing new measures of functional recovery is strongly recommended. PMID:19023122

  19. Detrimental effects of immobilization on functional recovery after sciatic nerve crush.

    PubMed

    Sarikcioglu, Levent; Ozkan, Olcay; Gurer, Elif Inanc

    2005-07-01

    Peripheral-nerve trauma has been a challenge to surgeons, with significant advances in the surgery of repair. Immobilization of the injured limb after repair has been the traditional method of treatment. Although peripheral-nerve regeneration has been studied extensively, the correlation between functional recovery and the immobilization period has not been well-documented. In the present study, the authors studied the effects of immobilization on axonal regeneration after sciatic crush injury. They found a detrimental effect of immobilization on the functional recovery. PMID:15971165

  20. Edaravone promotes functional recovery after mechanical peripheral nerve injury

    PubMed Central

    Zhang, Teng; Li, Zhengwei; Dong, Jianli; Nan, Feng; Li, Tao; Yu, Qing

    2014-01-01

    Edaravone has been shown to reduce ischemia/reperfusion-induced peripheral nerve injury. However, the therapeutic effect of edaravone on peripheral nerve injury caused by mechanical factors is unknown. In the present study, we established a peripheral nerve injury model by crushing the sciatic nerve using hemostatic forceps, and then administered edaravone 3 mg/kg intraperitoneally. The sciatic functional index and superoxide dismutase activity of the sciatic nerve were increased, and the malondialdehyde level was decreased in animals in the edaravone group compared with those in the model group. Bcl-2 expression was increased, but Bax expression was decreased in anterior horn cells of the L4-6 spinal cord segments. These results indicated that edaravone has a neuroprotective effect following peripheral nerve injury caused by mechanical factors through alleviating free radical damage to cells and inhibiting lipid peroxidation, as well as regulating apoptosis-related protein expression. PMID:25374594

  1. Functional Recovery following Critical Illness in Children: the “Wee-cover” Pilot Study

    PubMed Central

    Choong, Karen; Al-Harbi, Samah; Siu, Katie; Wong, Katie; Cheng, Ji; Baird, Burke; Pogorzelski, David; Timmons, Brian; Gorter, Jan-Willem; Thabane, Lehana; Khetani, Mary

    2015-01-01

    Objective To determine the feasibility of conducting a longitudinal prospective study to evaluate functional recovery and predictors of impaired functional recovery in critically ill children. Design Prospective pilot study. Setting Single center Pediatric Intensive Care Unit (PICU) at McMaster Children’s Hospital, Hamilton, Canada. Patients Children aged 12 months to 17 years, with at least one organ dysfunction, limited mobility or bed-rest during the first 48 hours of PICU admission, and a minimum 48 hour PICU length of stay, were eligible. Patients transferred from a neonatal intensive care unit prior to ever being discharged home, already mobilizing well or at baseline functional status at time of screening, with an English language barrier, and prior enrollment into this study were excluded. Measurements The primary outcome was feasibility, as defined by the ability to screen, enroll eligible patients, and execute the study procedures and measurements on participants. Secondary outcomes included functional status at baseline, 3 and 6 months, PICU morbidity and mortality. Functional status was measured using the Pediatric Evaluation of Disability Inventory (PEDI), and the Participation and Environment Measure for Children and Youth (PEM-CY). Main results Thirty-three patients were enrolled between October 2012 and April 2013. Consent rate was 85%, follow-up rates 93% at 3 months, and 71% at 6 months. We were able to execute the study procedures and measurements, demonstrating feasibility of conducting a future longitudinal study. Functional status deteriorated following critical illness. Recovery appears to be influenced by baseline health or functional status, and severity of illness. Conclusion Longitudinal research is needed to understand how children recover after a critical illness. Our results suggest factors that may influence the recovery trajectory, and were used to inform the methodology, outcomes of interest, and appropriate sample size of a

  2. Prognostic value of FMRI in recovery of hand function in subcortical stroke patients.

    PubMed

    Loubinoux, Isabelle; Dechaumont-Palacin, S; Castel-Lacanal, E; De Boissezon, X; Marque, Philippe; Pariente, Jérémie; Albucher, Jean-François; Berry, Isabelle; Chollet, François

    2007-12-01

    The first objective of the study was to determine whether functional magnetic resonance imaging (fMRI) signal was correlated with motor performance at different stages of poststroke recovery. The second objective was to assess the existence of prognostic factors for recovery in early functional MR images. Eight right-handed patients with pure motor deficit secondary to a first lacunar infarct localized on the pyramidal tract were included. This study concerned moderately impaired patients and recovery of handgrip strength and finger-tapping speed. The fMRI task was a calibrated flexion-extension movement. Ten healthy subjects served as a control group. The intensity of the activation in the "classical" motor network (ipsilesional S1M1, ipsilesional ventral premotor cortex [BA 6], contralesional cerebellum) 20 days after stroke was indicative of the performance (positive correlation). The cluster in M1 was posterior and circumscribed to BA 4p. No area was associated with bad performance (negative correlation). No correlation was found 4 and 12 months after stroke. Prognosis factors were evidenced. The higher early the activation in the ipsilesional M1 (BA 4p), S1, and insula, the better the recovery 1 year after stroke. Although the lesions partly deefferented the primary motor cortex, patients who activated the posterior primary motor cortex early had a better recovery of hand function. This suggests that there is benefit in increasing ipsilesional M1 activity shortly after stroke as a rehabilitative approach in mildly impaired patients. PMID:17389628

  3. Generalized recovery algorithm for 3D super-resolution microscopy using rotating point spread functions.

    PubMed

    Shuang, Bo; Wang, Wenxiao; Shen, Hao; Tauzin, Lawrence J; Flatebo, Charlotte; Chen, Jianbo; Moringo, Nicholas A; Bishop, Logan D C; Kelly, Kevin F; Landes, Christy F

    2016-01-01

    Super-resolution microscopy with phase masks is a promising technique for 3D imaging and tracking. Due to the complexity of the resultant point spread functions, generalized recovery algorithms are still missing. We introduce a 3D super-resolution recovery algorithm that works for a variety of phase masks generating 3D point spread functions. A fast deconvolution process generates initial guesses, which are further refined by least squares fitting. Overfitting is suppressed using a machine learning determined threshold. Preliminary results on experimental data show that our algorithm can be used to super-localize 3D adsorption events within a porous polymer film and is useful for evaluating potential phase masks. Finally, we demonstrate that parallel computation on graphics processing units can reduce the processing time required for 3D recovery. Simulations reveal that, through desktop parallelization, the ultimate limit of real-time processing is possible. Our program is the first open source recovery program for generalized 3D recovery using rotating point spread functions. PMID:27488312

  4. Generalized recovery algorithm for 3D super-resolution microscopy using rotating point spread functions

    NASA Astrophysics Data System (ADS)

    Shuang, Bo; Wang, Wenxiao; Shen, Hao; Tauzin, Lawrence J.; Flatebo, Charlotte; Chen, Jianbo; Moringo, Nicholas A.; Bishop, Logan D. C.; Kelly, Kevin F.; Landes, Christy F.

    2016-08-01

    Super-resolution microscopy with phase masks is a promising technique for 3D imaging and tracking. Due to the complexity of the resultant point spread functions, generalized recovery algorithms are still missing. We introduce a 3D super-resolution recovery algorithm that works for a variety of phase masks generating 3D point spread functions. A fast deconvolution process generates initial guesses, which are further refined by least squares fitting. Overfitting is suppressed using a machine learning determined threshold. Preliminary results on experimental data show that our algorithm can be used to super-localize 3D adsorption events within a porous polymer film and is useful for evaluating potential phase masks. Finally, we demonstrate that parallel computation on graphics processing units can reduce the processing time required for 3D recovery. Simulations reveal that, through desktop parallelization, the ultimate limit of real-time processing is possible. Our program is the first open source recovery program for generalized 3D recovery using rotating point spread functions.

  5. Generalized recovery algorithm for 3D super-resolution microscopy using rotating point spread functions

    PubMed Central

    Shuang, Bo; Wang, Wenxiao; Shen, Hao; Tauzin, Lawrence J.; Flatebo, Charlotte; Chen, Jianbo; Moringo, Nicholas A.; Bishop, Logan D. C.; Kelly, Kevin F.; Landes, Christy F.

    2016-01-01

    Super-resolution microscopy with phase masks is a promising technique for 3D imaging and tracking. Due to the complexity of the resultant point spread functions, generalized recovery algorithms are still missing. We introduce a 3D super-resolution recovery algorithm that works for a variety of phase masks generating 3D point spread functions. A fast deconvolution process generates initial guesses, which are further refined by least squares fitting. Overfitting is suppressed using a machine learning determined threshold. Preliminary results on experimental data show that our algorithm can be used to super-localize 3D adsorption events within a porous polymer film and is useful for evaluating potential phase masks. Finally, we demonstrate that parallel computation on graphics processing units can reduce the processing time required for 3D recovery. Simulations reveal that, through desktop parallelization, the ultimate limit of real-time processing is possible. Our program is the first open source recovery program for generalized 3D recovery using rotating point spread functions. PMID:27488312

  6. Modifying lipid rafts promotes regeneration and functional recovery.

    PubMed

    Tassew, Nardos G; Mothe, Andrea J; Shabanzadeh, Alireza P; Banerjee, Paromita; Koeberle, Paulo D; Bremner, Rod; Tator, Charles H; Monnier, Philippe P

    2014-08-21

    Ideal strategies to ameliorate CNS damage should promote both neuronal survival and axon regeneration. The receptor Neogenin promotes neuronal apoptosis. Its ligand prevents death, but the resulting repulsive guidance molecule a (RGMa)-Neogenin interaction also inhibits axonal growth, countering any prosurvival benefits. Here, we explore strategies to inhibit Neogenin, thus simultaneously enhancing survival and regeneration. We show that bone morphogenetic protein (BMP) and RGMa-dependent recruitment of Neogenin into lipid rafts requires an interaction between RGMa and Neogenin subdomains. RGMa or Neogenin peptides that prevent this interaction, BMP inhibition by Noggin, or reduction of membrane cholesterol all block Neogenin raft localization, promote axon outgrowth, and prevent neuronal apoptosis. Blocking Neogenin raft association influences axonal pathfinding, enhances survival in the developing CNS, and promotes survival and regeneration in the injured adult optic nerve and spinal cord. Moreover, lowering cholesterol disrupts rafts and restores locomotor function after spinal cord injury. These data reveal a unified strategy to promote both survival and regeneration in the CNS. PMID:25127134

  7. The Role of Species Traits in Mediating Functional Recovery during Matrix Restoration

    PubMed Central

    Barnes, Andrew D.; Emberson, Rowan M.; Krell, Frank-Thorsten; Didham, Raphael K.

    2014-01-01

    Reversing anthropogenic impacts on habitat structure is frequently successful through restoration, but the mechanisms linking habitat change, community reassembly and recovery of ecosystem functioning remain unknown. We test for the influence of edge effects and matrix habitat restoration on the reassembly of dung beetle communities and consequent recovery of dung removal rates across tropical forest edges. Using path modelling, we disentangle the relative importance of community-weighted trait means and functional trait dispersion from total biomass effects on rates of dung removal. Community trait composition and biomass of dung beetle communities responded divergently to edge effects and matrix habitat restoration, yielding opposing effects on dung removal. However, functional dispersion—used in this study as a measure of niche complementarity—did not explain a significant amount of variation in dung removal rates across habitat edges. Instead, we demonstrate that the path to functional recovery of these altered ecosystems depends on the trait-mean composition of reassembling communities, over and above purely biomass-dependent processes that would be expected under neutral theory. These results suggest that any ability to manage functional recovery of ecosystems during habitat restoration will demand knowledge of species' roles in ecosystem processes. PMID:25502448

  8. Ryk controls remapping of motor cortex during functional recovery after spinal cord injury.

    PubMed

    Hollis, Edmund R; Ishiko, Nao; Yu, Ting; Lu, Chin-Chun; Haimovich, Ariela; Tolentino, Kristine; Richman, Alisha; Tury, Anna; Wang, Shih-Hsiu; Pessian, Maysam; Jo, Euna; Kolodkin, Alex; Zou, Yimin

    2016-05-01

    Limited functional recovery can be achieved through rehabilitation after incomplete spinal cord injury. Eliminating the function of a repulsive Wnt receptor, Ryk, in mice and rats by either conditional knockout in the motor cortex or monoclonal antibody infusion resulted in increased corticospinal axon collateral branches with presynaptic puncta in the spinal cord and enhanced recovery of forelimb reaching and grasping function following a cervical dorsal column lesion. Using optical stimulation, we observed that motor cortical output maps underwent massive changes after injury and that hindlimb cortical areas were recruited to control the forelimb over time. Furthermore, a greater cortical area was dedicated to controlling the forelimb in Ryk conditional knockout mice than in controls (wild-type or heterozygotes). In the absence of weekly task-specific training, recruitment of ectopic cortical areas was greatly reduced and there was no significant functional recovery even in Ryk conditional knockout mice. Our study provides evidence that maximal circuit reorganization and functional recovery can be achieved by combining molecular manipulation and targeted rehabilitation. PMID:27065364

  9. A meta-analysis of functional group responses to forest recovery outside of the tropics.

    PubMed

    Spake, Rebecca; Ezard, Thomas H G; Martin, Philip A; Newton, Adrian C; Doncaster, C Patrick

    2015-12-01

    Both active and passive forest restoration schemes are used in degraded landscapes across the world to enhance biodiversity and ecosystem service provision. Restoration is increasingly also being implemented in biodiversity offset schemes as compensation for loss of natural habitat to anthropogenic development. This has raised concerns about the value of replacing old-growth forest with plantations, motivating research on biodiversity recovery as forest stands age. Functional diversity is now advocated as a key metric for restoration success, yet it has received little analytical attention to date. We conducted a meta-analysis of 90 studies that measured differences in species richness for functional groups of fungi, lichens, and beetles between old-growth control and planted or secondary treatment forests in temperate, boreal, and Mediterranean regions. We identified functional-group-specific relationships in the response of species richness to stand age after forest disturbance. Ectomycorrhizal fungi averaged 90 years for recovery to old-growth values (between 45 years and unrecoverable at 95% prediction limits), and epiphytic lichens took 180 years to reach 90% of old-growth values (between 140 years and never for recovery to old-growth values at 95% prediction limits). Non-saproxylic beetle richness, in contrast, decreased as stand age of broadleaved forests increased. The slow recovery by some functional groups essential to ecosystem functioning makes old-growth forest an effectively irreplaceable biodiversity resource that should be exempt from biodiversity offsetting initiatives. PMID:26040756

  10. Recovery of Adrenal Function in Patients with Glucocorticoids Induced Secondary Adrenal Insufficiency

    PubMed Central

    Baek, Jong Ha; Kim, Soo Kyoung; Jung, Jung Hwa; Hahm, Jong Ryeal

    2016-01-01

    Background The chronic use of glucocorticoids (GC) suppresses function of the hypothalamic-pituitary-adrenal axis and often results in secondary adrenal insufficiency (AI). The present study aimed to determine the recovery rate of adrenal function in patients with secondary AI within 1 to 2 years and to assess the factors predictive of adrenal function recovery. Methods This was a retrospective observational study that enrolled patients diagnosed with GC-induced secondary AI between 2007 and 2013. AI was defined by peak serum cortisol levels <18 µg/dL during a standard-dose short synacthen test (SST). A follow-up SST was performed after 1 to 2 years, and responders were defined as those with adrenocorticotropic hormone (ACTH)-stimulated peak serum cortisol levels ≥18 µg/dL. Results Of the total 34 patients diagnosed with GC-induced secondary AI at first, 20 patients (58.8%) recovered normal adrenal function by the time of the follow-up SST (median follow-up period, 16.5 months). Although the baseline serum ACTH and cortisol levels at the first SST did not differ between responders and non-responders, the incremental cortisol response during the first SST was higher in responders than that of non-responders (7.88 vs. 3.56, P<0.01). Additionally, higher cortisol increments during the first SST were an independent predictive factor of the adrenal function recovery (odds ratio, 1.58; 95% confidence interval, 1.02 to 2.46; P<0.05). Conclusion In the present study, adrenal function recovery was achieved frequently in patients with GC-induced secondary AI within 1 to 2 years. Additionally, an incremental cortisol response at the first SST may be an important predictive factor of adrenal function recovery. PMID:26676337

  11. Integrated Treatment to Achieve Functional Recovery for First-Episode Psychosis

    PubMed Central

    Valencia, Marcelo; Juarez, Francisco; Ortega, Hector

    2012-01-01

    This study describes an integrated treatment approach that was implemented to enhance functional recovery in first-episode psychotic patients. Patients were randomized to two treatment conditions: either to an integrated treatment approach: pharmacotherapy, psychosocial treatment, and psychoeducation (experimental group: N = 39) or to medication alone (control group: N = 34). Patients were evaluated at baseline and after one year of treatment. Functional recovery was assessed according to symptomatic and functional remission. At the end of treatment, experimental patients showed a 94.9% of symptomatic remission compared to 58.8% of the control group. Functional remission was 56.4% for the experimental group and 3.6% for the control group, while 56.4% of the experimental group met both symptomatic and functional remission criteria and were considered recovered compared to 2.9% of the control group. PMID:22970366

  12. Intrinsic Functional Connectivity Patterns Predict Consciousness Level and Recovery Outcome in Acquired Brain Injury

    PubMed Central

    Wu, Xuehai; Zou, Qihong; Hu, Jin; Tang, Weijun; Mao, Ying; Gao, Liang; Zhu, Jianhong; Jin, Yi; Wu, Xin; Lu, Lu; Zhang, Yaojun; Zhang, Yao; Dai, Zhengjia; Gao, Jia-Hong; Weng, Xuchu; Northoff, Georg; Giacino, Joseph T.; He, Yong

    2015-01-01

    For accurate diagnosis and prognostic prediction of acquired brain injury (ABI), it is crucial to understand the neurobiological mechanisms underlying loss of consciousness. However, there is no consensus on which regions and networks act as biomarkers for consciousness level and recovery outcome in ABI. Using resting-state fMRI, we assessed intrinsic functional connectivity strength (FCS) of whole-brain networks in a large sample of 99 ABI patients with varying degrees of consciousness loss (including fully preserved consciousness state, minimally conscious state, unresponsive wakefulness syndrome/vegetative state, and coma) and 34 healthy control subjects. Consciousness level was evaluated using the Glasgow Coma Scale and Coma Recovery Scale-Revised on the day of fMRI scanning; recovery outcome was assessed using the Glasgow Outcome Scale 3 months after the fMRI scanning. One-way ANOVA of FCS, Spearman correlation analyses between FCS and the consciousness level and recovery outcome, and FCS-based multivariate pattern analysis were performed. We found decreased FCS with loss of consciousness primarily distributed in the posterior cingulate cortex/precuneus (PCC/PCU), medial prefrontal cortex, and lateral parietal cortex. The FCS values of these regions were significantly correlated with consciousness level and recovery outcome. Multivariate support vector machine discrimination analysis revealed that the FCS patterns predicted whether patients with unresponsive wakefulness syndrome/vegetative state and coma would regain consciousness with an accuracy of 81.25%, and the most discriminative region was the PCC/PCU. These findings suggest that intrinsic functional connectivity patterns of the human posteromedial cortex could serve as a potential indicator for consciousness level and recovery outcome in individuals with ABI. SIGNIFICANCE STATEMENT Varying degrees of consciousness loss and recovery are commonly observed in acquired brain injury patients, yet the

  13. [Effects of a vitamin B complex on functional recovery after nerve injury (author's transl)].

    PubMed

    Hasegawa, K; Mikuni, N; Sakai, Y

    1978-09-01

    Functional recovery after nerve crushing was investigated in the following manner: Under pentobarbital anesthesia the sciatic nerve of the rat was crushed at the level of the hip (proximal crush) or the thigh (distal crush). The recovery processes after the nerve crushing were followed by measuring distances between the first and fifth digits(DBD.1 approximately 5) and between the second and fourth digits (DBD.2 approximately 4) of the hind paw, and by observing changes in "behavior" scored on a scale of 10 according to the degree of behavioral disorder of the hind paw and leg. Results obtained by these methods showed good reproducibility. The DBD values and the scores for behavior recovered significantly faster after weak nerve crushing than after strong crushing, and after distal rather than after proximal crushing. When a segment of the sciatic nerve was resected, there was no recovery. These results suggest that DBD.1 approximately 5, DBD.2 approximately 4, and the behavior observed in these experiments serve as good indices for evaluating the degree of functional recovery after nerve injury in unanesthetized and unrestrained animals. Effects of a preparation of vitamins B1, B6, and B12 (B complex) on these three parameters and on weights of 9 muscles of the hind leg were also studied. These studies showed that the B complex facilitated functional recovery from nerve injury faster than its components, and that on muscle atrophy the B complex had its most effects on the soleus. It was also shown that B1 and B12 by themselves had significant facilitating effects on the functional recovery. PMID:711031

  14. ADATSA Follow-Up Study of Extended Outpatient Care: A Comparison of 90 Days versus 180 Days of Outpatient Treatment for Clients of Washington State's Alcoholism and Drug Addiction Treatment and Support Act.

    ERIC Educational Resources Information Center

    Van Der Hyde, Vincent A.; And Others

    This study was designed to compare outcomes for two groups of alcohol and substance abuse clients (N=230): a control group assigned to regular 90 days of outpatient treatment, and an experimental group assigned to 180 days of extended outpatient care. Outcomes were compared in the following nine categories: (1) relapse, measured as reported…

  15. Functional recovery after cervical spinal cord injury: Role of neurotrophin and glutamatergic signaling in phrenic motoneurons.

    PubMed

    Gill, Luther C; Gransee, Heather M; Sieck, Gary C; Mantilla, Carlos B

    2016-06-01

    Cervical spinal cord injury (SCI) interrupts descending neural drive to phrenic motoneurons causing diaphragm muscle (DIAm) paralysis. Recent studies using a well-established model of SCI, unilateral spinal hemisection of the C2 segment of the cervical spinal cord (SH), provide novel information regarding the molecular and cellular mechanisms of functional recovery after SCI. Over time post-SH, gradual recovery of rhythmic ipsilateral DIAm activity occurs. Recovery of ipsilateral DIAm electromyogram (EMG) activity following SH is enhanced by increasing brain-derived neurotrophic factor (BDNF) in the region of the phrenic motoneuron pool. Delivery of exogenous BDNF either via intrathecal infusion or via mesenchymal stem cells engineered to release BDNF similarly enhance recovery. Conversely, recovery after SH is blunted by quenching endogenous BDNF with the fusion-protein TrkB-Fc in the region of the phrenic motoneuron pool or by selective inhibition of TrkB kinase activity using a chemical-genetic approach in TrkB(F616A) mice. Furthermore, the importance of BDNF signaling via TrkB receptors at phrenic motoneurons is highlighted by the blunting of recovery by siRNA-mediated downregulation of TrkB receptor expression in phrenic motoneurons and by the enhancement of recovery evident following virally-induced increases in TrkB expression specifically in phrenic motoneurons. BDNF/TrkB signaling regulates synaptic plasticity in various neuronal systems, including glutamatergic pathways. Glutamatergic neurotransmission constitutes the main inspiratory-related, excitatory drive to motoneurons, and following SH, spontaneous neuroplasticity is associated with increased expression of ionotropic N-methyl-d-aspartate (NMDA) receptors in phrenic motoneurons. Evidence for the role of BDNF/TrkB and glutamatergic signaling in recovery of DIAm activity following cervical SCI is reviewed. PMID:26506253

  16. The Crossed Phrenic Phenomenon and Recovery of Function Following Spinal Cord Injury

    PubMed Central

    Goshgarian, Harry G.

    2009-01-01

    This review will focus on neural plasticity and recovery of respiratory function after spinal cord injury and feature the “crossed phrenic phenomenon” (CPP) as a model for demonstrating such plasticity and recovery. A very brief summary of the earlier literature on the CPP will be followed by a more detailed review of the more recent studies. Two aspects of plasticity associated with the CPP that have been introduced in the literature recently have been spontaneous recovery of ipsilateral hemidiaphragmatic function following chronic spinal cord injury and drug-induced persistent recovery of the ipsilateral hemidiaphragm lasting long after animals have been weaned from drug treatment. The underlying mechanisms for this plasticity and resultant recovery will be discussed in this review. Moreover, two new models involving the CPP have been introduced: a mouse model which now provides for an opportunity to study CPP plasticity at a molecular level using a genetic approach and light-stimulated induction of the CPP accomplished by transfecting mammalian cells with channelrhodopsin. Both models provide an opportunity to sort out the intracellular signaling cascades that may be involved in motor recovery in the respiratory system after spinal cord injury. Finally, the review will examine developmental plasticity of the CPP and discuss how the expression of the CPP changes in neonatal rats as they mature to adults. Understanding the underlying mechanisms behind the spontaneous expression of the crossed phrenic pathway either in the developing animal or after chronic spinal cord injury in the adult animal may provide clues to initiating respiratory recovery sooner to alleviate human suffering and eventually eliminate the leading cause of death in human cases of spinal cord injury. PMID:19539790

  17. Reorganization of Functional Connectivity as a Correlate of Cognitive Recovery in Acquired Brain Injury

    ERIC Educational Resources Information Center

    Castellanos, Nazareth P.; Paul, Nuria; Ordonez, Victoria E.; Demuynck, Olivier; Bajo, Ricardo; Campo, Pablo; Bilbao, Alvaro; Ortiz, Tomas; del-Pozo, Francisco; Maestu, Fernando

    2010-01-01

    Cognitive processes require a functional interaction between specialized multiple, local and remote brain regions. Although these interactions can be strongly altered by an acquired brain injury, brain plasticity allows network reorganization to be principally responsible for recovery. The present work evaluates the impact of brain injury on…

  18. A meta‐analysis of functional group responses to forest recovery outside of the tropics

    PubMed Central

    Ezard, Thomas H. G.; Martin, Philip A.; Newton, Adrian C.; Doncaster, C. Patrick

    2015-01-01

    Abstract Both active and passive forest restoration schemes are used in degraded landscapes across the world to enhance biodiversity and ecosystem service provision. Restoration is increasingly also being implemented in biodiversity offset schemes as compensation for loss of natural habitat to anthropogenic development. This has raised concerns about the value of replacing old‐growth forest with plantations, motivating research on biodiversity recovery as forest stands age. Functional diversity is now advocated as a key metric for restoration success, yet it has received little analytical attention to date. We conducted a meta‐analysis of 90 studies that measured differences in species richness for functional groups of fungi, lichens, and beetles between old‐growth control and planted or secondary treatment forests in temperate, boreal, and Mediterranean regions. We identified functional‐group–specific relationships in the response of species richness to stand age after forest disturbance. Ectomycorrhizal fungi averaged 90 years for recovery to old‐growth values (between 45 years and unrecoverable at 95% prediction limits), and epiphytic lichens took 180 years to reach 90% of old‐growth values (between 140 years and never for recovery to old‐growth values at 95% prediction limits). Non‐saproxylic beetle richness, in contrast, decreased as stand age of broadleaved forests increased. The slow recovery by some functional groups essential to ecosystem functioning makes old‐growth forest an effectively irreplaceable biodiversity resource that should be exempt from biodiversity offsetting initiatives. PMID:26040756

  19. Functional Recovery of Older Hip-Fracture Patients after Interdisciplinary Intervention Follows Three Distinct Trajectories

    ERIC Educational Resources Information Center

    Tseng, Ming-Yueh; Shyu, Yea-Ing L.; Liang, Jersey

    2012-01-01

    Purpose To assess the effects of an interdisciplinary intervention on the trajectories of functional recovery among older patients with hip fracture during 2 years after hospitalization. Design and Methods In a randomized controlled trial with 24-month follow-up, 162 patients [greater than or equal to]60 years were enrolled after hip-fracture…

  20. 3 CFR - Assignment of Reporting Function Under the American Recovery and Reinvestment Act of 2009

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 3 The President 1 2010-01-01 2010-01-01 false Assignment of Reporting Function Under the American Recovery and Reinvestment Act of 2009 Presidential Documents Other Presidential Documents Memorandum of May... by the Constitution and the laws of the United States, including section 301 of title 3,...

  1. Recruitment of Polysynaptic Connections Underlies Functional Recovery of a Neural Circuit after Lesion

    PubMed Central

    Tamvacakis, Arianna N.

    2016-01-01

    Abstract The recruitment of additional neurons to neural circuits often occurs in accordance with changing functional demands. Here we found that synaptic recruitment plays a key role in functional recovery after neural injury. Disconnection of a brain commissure in the nudibranch mollusc, Tritonia diomedea, impairs swimming behavior by eliminating particular synapses in the central pattern generator (CPG) underlying the rhythmic swim motor pattern. However, the CPG functionally recovers within a day after the lesion. The strength of a spared inhibitory synapse within the CPG from Cerebral Neuron 2 (C2) to Ventral Swim Interneuron B (VSI) determines the level of impairment caused by the lesion, which varies among individuals. In addition to this direct synaptic connection, there are polysynaptic connections from C2 and Dorsal Swim Interneurons to VSI that provide indirect excitatory drive but play only minor roles under normal conditions. After disconnecting the pedal commissure (Pedal Nerve 6), the recruitment of polysynaptic excitation became a major source of the excitatory drive to VSI. Moreover, the amount of polysynaptic recruitment, which changed over time, differed among individuals and correlated with the degree of recovery of the swim motor pattern. Thus, functional recovery was mediated by an increase in the magnitude of polysynaptic excitatory drive, compensating for the loss of direct excitation. Since the degree of susceptibility to injury corresponds to existing individual variation in the C2 to VSI synapse, the recovery relied upon the extent to which the network reorganized to incorporate additional synapses. PMID:27570828

  2. Recruitment of Polysynaptic Connections Underlies Functional Recovery of a Neural Circuit after Lesion.

    PubMed

    Sakurai, Akira; Tamvacakis, Arianna N; Katz, Paul S

    2016-01-01

    The recruitment of additional neurons to neural circuits often occurs in accordance with changing functional demands. Here we found that synaptic recruitment plays a key role in functional recovery after neural injury. Disconnection of a brain commissure in the nudibranch mollusc, Tritonia diomedea, impairs swimming behavior by eliminating particular synapses in the central pattern generator (CPG) underlying the rhythmic swim motor pattern. However, the CPG functionally recovers within a day after the lesion. The strength of a spared inhibitory synapse within the CPG from Cerebral Neuron 2 (C2) to Ventral Swim Interneuron B (VSI) determines the level of impairment caused by the lesion, which varies among individuals. In addition to this direct synaptic connection, there are polysynaptic connections from C2 and Dorsal Swim Interneurons to VSI that provide indirect excitatory drive but play only minor roles under normal conditions. After disconnecting the pedal commissure (Pedal Nerve 6), the recruitment of polysynaptic excitation became a major source of the excitatory drive to VSI. Moreover, the amount of polysynaptic recruitment, which changed over time, differed among individuals and correlated with the degree of recovery of the swim motor pattern. Thus, functional recovery was mediated by an increase in the magnitude of polysynaptic excitatory drive, compensating for the loss of direct excitation. Since the degree of susceptibility to injury corresponds to existing individual variation in the C2 to VSI synapse, the recovery relied upon the extent to which the network reorganized to incorporate additional synapses. PMID:27570828

  3. Organism-Sediment Interactions Govern Post-Hypoxia Recovery of Ecosystem Functioning

    PubMed Central

    Van Colen, Carl; Rossi, Francesca; Montserrat, Francesc; Andersson, Maria G. I.; Gribsholt, Britta; Herman, Peter M. J.; Degraer, Steven; Vincx, Magda; Ysebaert, Tom; Middelburg, Jack J.

    2012-01-01

    Hypoxia represents one of the major causes of biodiversity and ecosystem functioning loss for coastal waters. Since eutrophication-induced hypoxic events are becoming increasingly frequent and intense, understanding the response of ecosystems to hypoxia is of primary importance to understand and predict the stability of ecosystem functioning. Such ecological stability may greatly depend on the recovery patterns of communities and the return time of the system properties associated to these patterns. Here, we have examined how the reassembly of a benthic community contributed to the recovery of ecosystem functioning following experimentally-induced hypoxia in a tidal flat. We demonstrate that organism-sediment interactions that depend on organism size and relate to mobility traits and sediment reworking capacities are generally more important than recovering species richness to set the return time of the measured sediment processes and properties. Specifically, increasing macrofauna bioturbation potential during community reassembly significantly contributed to the recovery of sediment processes and properties such as denitrification, bedload sediment transport, primary production and deep pore water ammonium concentration. Such bioturbation potential was due to the replacement of the small-sized organisms that recolonised at early stages by large-sized bioturbating organisms, which had a disproportionately stronger influence on sediment. This study suggests that the complete recovery of organism-sediment interactions is a necessary condition for ecosystem functioning recovery, and that such process requires long periods after disturbance due to the slow growth of juveniles into adult stages involved in these interactions. Consequently, repeated episodes of disturbance at intervals smaller than the time needed for the system to fully recover organism-sediment interactions may greatly impair the resilience of ecosystem functioning. PMID:23185440

  4. Functional recovery in spinal cord injured rats using polypyrrole/iodine implants and treadmill training.

    PubMed

    Alvarez-Mejia, Laura; Morales, Juan; Cruz, Guillermo J; Olayo, María-Guadalupe; Olayo, Roberto; Díaz-Ruíz, Araceli; Ríos, Camilo; Mondragón-Lozano, Rodrigo; Sánchez-Torres, Stephanie; Morales-Guadarrama, Axayacatl; Fabela-Sánchez, Omar; Salgado-Ceballos, Hermelinda

    2015-07-01

    Currently, there is no universally accepted treatment for traumatic spinal cord injury (TSCI), a pathology that can cause paraplegia or quadriplegia. Due to the complexity of TSCI, more than one therapeutic strategy may be necessary to regain lost functions. Therefore, the present study proposes the use of implants of mesoparticles (MPs) of polypyrrole/iodine (PPy/I) synthesized by plasma for neuroprotection promotion and functional recovery in combination with treadmill training (TT) for neuroplasticity promotion and maintenance of muscle tone. PPy/I films were synthesized by plasma and pulverized to obtain MPs. Rats with a TSCI produced by the NYU impactor were divided into four groups: Vehicle (saline solution); MPs (PPy/I implant); Vehicle-TT (saline solution + TT); and MPs-TT (PPy/I implant + TT). The vehicle or MPs (30 μL) were injected into the lesion site 48 h after a TSCI. Four days later, TT was carried out 5 days a week for 2 months. Functional recovery was evaluated weekly using the BBB motor scale for 9 weeks and tissue protection using histological and morphometric analysis thereafter. Although the MPs of PPy/I increased nerve tissue preservation (P = 0.03) and promoted functional recovery (P = 0.015), combination with TT did not produce better neuroprotection, but significantly improved functional results (P = 0.000) when comparing with the vehicle group. So, use these therapeutic strategies by separately could stimulate specific mechanisms of neuroprotection and neuroregeneration, but when using together they could mainly potentiate different mechanisms of neuronal plasticity in the preserved spinal cord tissue after a TSCI and produce a significant functional recovery. The implant of mesoparticles of polypyrrole/iodine into the injured spinal cord displayed good integration into the nervous tissue without a response of rejection, as well as an increased in the amount of preserved tissue and a better functional recovery than the group without

  5. Recovery time course in contractile function of fast and slow skeletal muscle after hindlimb immobilization

    NASA Technical Reports Server (NTRS)

    Witzmann, F. A.; Kim, D. H.; Fitts, R. H.

    1982-01-01

    The present study was undertaken to characterize the time course and extent of recovery in the isometric and isotonic contractile properties of fast and slow skeletal muscle following 6 wk of hindlimb immobilization. Female Sprague-Dawley rats were randomly assigned to an immobilized group or a control group. The results of the study show that fast and slow skeletal muscles possess the ability to completely recover normal contractile function following 6 wk of hindlimb immobilization. The rate of recovery is dependent on the fiber type composition of the affected muscle.

  6. The optimal recovery of a function from an inaccurate information on its k-plane transform

    NASA Astrophysics Data System (ADS)

    Bagramyan, Tigran

    2016-06-01

    We consider the optimal recovery of the β th degree of the Laplacian value on a function from the information on its k-plane transform, measured with an error. We present the error of the optimal recovery and the set of optimal methods on classes with the bounded α th degree of the Laplacian, where 0≤slant β \\lt α . As a consequence, we give one inequality for the norms of the degree of the Laplace operator and the k-plane transform. Particular cases include new inversion methods and inequalities for the classical Radon and x-ray transforms.

  7. Resolution of hypophosphatemia is associated with recovery of hepatic function in children with fulminant hepatic failure.

    PubMed

    Quirós-Tejeira, Rubén E; Molina, Ricardo A; Katzir, Lirona; Lie, Angela; Vargas, Jorge H; Ament, Marvin E; McDiarmid, Sue V; Martín, Martín G

    2005-09-01

    Fulminant hepatic failure (FHF) is a rare but often fatal disease in children. Clinical and laboratory predictors of liver regeneration and recovery, however, have not been well established. We hypothesized that hypophosphatemia may indicate recovery of liver synthetic function in children with FHF. We retrospectively reviewed the medical records of children with FHF who were admitted to UCLA and recovered hepatic function either spontaneously or by liver transplantation (LTx). Serum phosphate (Ph) and prothrombin time or international normalized ratio (INR) were compared over the patient's clinical course. Records of 39 children who spontaneously recovered experienced profound hypophosphatemia that resolved as liver synthetic function improved. Similar patterns were seen in the 84 children who recovered after LTx. We found that hypophosphatemia precedes the recovery of liver synthetic function in children with FHF who recovered with or without transplantation, and that Ph levels return to normal as liver synthetic function improves. These data suggest that hypophosphatemia may be a useful laboratory indicator of recovering liver function in children with FHF. PMID:16101727

  8. Defining recovery from an eating disorder: Conceptualization, validation, and examination of psychosocial functioning and psychiatric comorbidity.

    PubMed

    Bardone-Cone, Anna M; Harney, Megan B; Maldonado, Christine R; Lawson, Melissa A; Robinson, D Paul; Smith, Roma; Tosh, Aneesh

    2010-03-01

    Conceptually, eating disorder recovery should include physical, behavioral, and psychological components, but such a comprehensive approach has not been consistently employed. Guided by theory and recent recovery research, we identified a "fully recovered" group (n = 20) based on physical (body mass index), behavioral (absence of eating disorder behaviors), and psychological (Eating Disorder Examination-Questionnaire) indices, and compared them with groups of partially recovered (n = 15), active eating disorder (n = 53), and healthy controls (n = 67). The fully recovered group was indistinguishable from controls on all eating disorder-related measures used, while the partially recovered group was less disordered than the active eating disorder group on some measures, but not on body image. Regarding psychosocial functioning, both the fully and partially recovered groups had psychosocial functioning similar to the controls, but there was a pattern of more of the partially recovered group reporting eating disorder aspects interfering with functioning. Regarding other psychopathology, the fully recovered group was no more likely than the controls to experience current Axis I pathology, but they did have elevated rates of current anxiety disorder. Results suggest that a stringent definition of recovery from an eating disorder is meaningful. Clinical implications and future directions regarding defining eating disorder recovery are discussed. PMID:19945094

  9. Defining Recovery from an Eating Disorder: Conceptualization, Validation, and Examination of Psychosocial Functioning and Psychiatric Comorbidity

    PubMed Central

    Bardone-Cone, Anna M.; Harney, Megan B.; Maldonado, Christine R.; Lawson, Melissa A.; Robinson, D. Paul; Smith, Roma; Tosh, Aneesh

    2009-01-01

    Conceptually, eating disorder recovery should include physical, behavioral, and psychological components, but such a comprehensive approach has not been consistently employed. Guided by theory and recent recovery research, we identified a “fully recovered” group (n=20) based on physical (body mass index), behavioral (absence of eating disorder behaviors), and psychological (Eating Disorder Examination-Questionnaire) indices, and compared them with groups of partially recovered (n=15), active eating disorder (n=53), and healthy controls (n=67). The fully recovered group was indistinguishable from controls on all eating disorder-related measures used, while the partially recovered group was less disordered than the active eating disorder group on some measures, but not on body image. Regarding psychosocial functioning, both the fully and partially recovered groups had psychosocial functioning similar to the controls, but there was a pattern of more of the partially recovered group reporting eating disorder aspects interfering with functioning. Regarding other psychopathology, the fully recovered group was no more likely than the controls to experience current Axis I pathology, but they did have elevated rates of current anxiety disorder. Results suggest that a stringent definition of recovery from an eating disorder is meaningful. Clinical implications and future directions regarding defining eating disorder recovery are discussed. PMID:19945094

  10. GDF10 Is a Signal for Axonal Sprouting and Functional Recovery after Stroke

    PubMed Central

    Li, S; Nie, EH; Yin, Y; Benowitz, LI; Tung, S; Vinters, HV; Bahjat, FR; Stenzel-Poore, MP; Kawaguchi, R; Coppola, G; Carmichael, ST

    2016-01-01

    Stroke produces a limited process of neural repair. Axonal sprouting in cortex adjacent to the infarct is part of this recovery process, but the signal that initiates axonal sprouting is not known. Growth and Differentiation Factor 10 (GDF10) is induced in peri-infarct neurons in mouse, non-human primate and human. GDF10 promotes axonal outgrowth in vitro in mouse, rat and human neurons through TGFβRI/II signaling. Using pharmacogenetic gain and loss of function studies, GDF10 produces axonal sprouting and enhanced functional recovery after stroke; knocking down GDF10 blocks axonal sprouting and reduces recovery. RNA-seq from peri-infarct cortical neurons indicates that GDF10 downregulates PTEN and upregulates PI3 kinase signaling and induces specific axonal guidance molecules. Unsupervised genome-wide association analysis of the GDF10 transcriptome shows that it is not related to neurodevelopment but may partially overlap with other CNS injury patterns. GDF10 is a stroke-induced signal for axonal sprouting and functional recovery. PMID:26502261

  11. Hand motor recovery after stroke: tuning the orchestra to improve hand motor function.

    PubMed

    Fregni, Felipe; Pascual-Leone, Alvaro

    2006-03-01

    The motor deficits after stroke are not only the manifestation of the injured brain region, but rather the expression of the ability of the rest of the brain to maintain function. After a lesion in the primary motor cortex, parallel motor circuits might be activated to generate some alternative input to the spinal motoneurons. These parallel circuits may originate from areas such as the contralateral, undamaged primary motor area, bilateral premotor areas, bilateral supplementary motor areas, bilateral somatosensory areas, cerebellum, and basal ganglia. Most importantly, the efferent, cortico-spinal output pathways must be preserved for a desired behavioral result. Most of the recovery of function after a stroke may represent actual relearning of the skills with the injured brain. The main neural mechanisms underlying this relearning process after stroke involve shifts of distributed contributions across a specific neural network (fundamentally the network engaged in skill learning in the healthy). If these notions are indeed correct, then neuromodulatory approaches, such as transcranial magnetic stimulation, targeting these parallel circuits might be useful to limit injury and promote recovery after a stroke. This paper reviews the stroke characteristics that can predict a good recovery and compensations across brain areas that can be implemented after a stroke to accelerate motor function recovery. PMID:16633016

  12. Interaction between Vestibular Compensation Mechanisms and Vestibular Rehabilitation Therapy: 10 Recommendations for Optimal Functional Recovery

    PubMed Central

    Lacour, Michel; Bernard-Demanze, Laurence

    2015-01-01

    This review questions the relationships between the plastic events responsible for the recovery of vestibular function after a unilateral vestibular loss (vestibular compensation), which has been well described in animal models in the last decades, and the vestibular rehabilitation (VR) therapy elaborated on a more empirical basis for vestibular loss patients. The main objective is not to propose a catalog of results but to provide clinicians with an understandable view on when and how to perform VR therapy, and why VR may benefit from basic knowledge and may influence the recovery process. With this perspective, 10 major recommendations are proposed as ways to identify an optimal functional recovery. Among them are the crucial role of active and early VR therapy, coincidental with a post-lesion sensitive period for neuronal network remodeling, the instructive role that VR therapy may play in this functional reorganization, the need for progression in the VR therapy protocol, which is based mainly on adaptation processes, the necessity to take into account the sensorimotor, cognitive, and emotional profile of the patient to propose individual or “à la carte” VR therapies, and the importance of motivational and ecologic contexts. More than 10 general principles are very likely, but these principles seem crucial for the fast recovery of vestibular loss patients to ensure good quality of life. PMID:25610424

  13. Viewing Nature Scenes Positively Affects Recovery of Autonomic Function Following Acute-Mental Stress

    PubMed Central

    2013-01-01

    A randomized crossover study explored whether viewing different scenes prior to a stressor altered autonomic function during the recovery from the stressor. The two scenes were (a) nature (composed of trees, grass, fields) or (b) built (composed of man-made, urban scenes lacking natural characteristics) environments. Autonomic function was assessed using noninvasive techniques of heart rate variability; in particular, time domain analyses evaluated parasympathetic activity, using root-mean-square of successive differences (RMSSD). During stress, secondary cardiovascular markers (heart rate, systolic and diastolic blood pressure) showed significant increases from baseline which did not differ between the two viewing conditions. Parasympathetic activity, however, was significantly higher in recovery following the stressor in the viewing scenes of nature condition compared to viewing scenes depicting built environments (RMSSD; 50.0 ± 31.3 vs 34.8 ± 14.8 ms). Thus, viewing nature scenes prior to a stressor alters autonomic activity in the recovery period. The secondary aim was to examine autonomic function during viewing of the two scenes. Standard deviation of R-R intervals (SDRR), as change from baseline, during the first 5 min of viewing nature scenes was greater than during built scenes. Overall, this suggests that nature can elicit improvements in the recovery process following a stressor. PMID:23590163

  14. Inosine promotes recovery of skilled motor function in a model of focal brain injury.

    PubMed

    Smith, Justin M; Lunga, Precious; Story, David; Harris, Neil; Le Belle, Janel; James, Michael F; Pickard, John D; Fawcett, James W

    2007-04-01

    Recovery of function following traumatic brain injury (TBI) is partly through neuronal plasticity. However plasticity is limited in the adult CNS compared with young animals. In order to test whether treatments that enhance CNS plasticity might improve functional recovery after TBI, a new rat head injury model was developed, in which a computer-controlled impactor produced full thickness lesions of the forelimb region of the sensorimotor cortex. Behavioural deficits were seen in several sensorimotor tasks, most of which recovered spontaneously by 21 days. However, skilled paw reaching behaviour, a task that requires corticospinal function, was only approximately 40% recovered by 28 days. In order to promote plasticity inosine was infused into the lateral ventricles for 28 days. This treatment produced an almost complete recovery of skilled paw reaching ability, associated with sprouting of the uninjured corticospinal axons across the midline into the territory of the lesioned pathway. In the cervical spinal cord the number of corticospinal axons originating from the uninjured cortex that innervated the contralateral cervical cord was five times that of controls, and in the red nucleus the number of contralaterally projecting axons was four times control values. Inosine treatment did not affect recovery in unskilled behavioural tasks, most of which recovered to normal levels by 28 days without treatment. Animals were placed in an enriched environment as an alternative method to promote plasticity. This resulted in more rapid recovery in several tasks including skilled paw function, but by 28 days normally housed animals had caught up to the same level of improvement. PMID:17293357

  15. Role of the Contralesional Hemisphere in Post-Stroke Recovery of Upper Extremity Motor Function

    PubMed Central

    Buetefisch, Cathrin M.

    2015-01-01

    Identification of optimal treatment strategies to improve recovery is limited by the incomplete understanding of the neurobiological principles of recovery. Motor cortex (M1) reorganization of the lesioned hemisphere (ipsilesional M1) plays a major role in post-stroke motor recovery and is a primary target for rehabilitation therapy. Reorganization of M1 in the hemisphere contralateral to the stroke (contralesional M1) may, however, serve as an additional source of cortical reorganization and related recovery. The extent and outcome of such reorganization depends on many factors, including lesion size and time since stroke. In the chronic phase post-stroke, contralesional M1 seems to interfere with motor function of the paretic limb in a subset of patients, possibly through abnormally increased inhibition of lesioned M1 by the contralesional M1. In such patients, decreasing contralesional M1 excitability by cortical stimulation results in improved performance of the paretic limb. However, emerging evidence suggests a potentially supportive role of contralesional M1. After infarction of M1 or its corticospinal projections, there is abnormally increased excitatory neural activity and activation in contralesional M1 that correlates with favorable motor recovery. Decreasing contralesional M1 excitability in these patients may result in deterioration of paretic limb performance. In animal stroke models, reorganizational changes in contralesional M1 depend on the lesion size and rehabilitation treatment and include long-term changes in neurotransmitter systems, dendritic growth, and synapse formation. While there is, therefore, some evidence that activity in contralesional M1 will impact the extent of motor function of the paretic limb in the subacute and chronic phase post-stroke and may serve as a new target for rehabilitation treatment strategies, the precise factors that specifically influence its role in the recovery process remain to be defined. PMID:26528236

  16. E2F4 Promotes Neuronal Regeneration and Functional Recovery after Spinal Cord Injury in Zebrafish

    PubMed Central

    Sasagawa, Shota; Nishimura, Yuhei; Hayakawa, Yuka; Murakami, Soichiro; Ashikawa, Yoshifumi; Yuge, Mizuki; Okabe, Shiko; Kawaguchi, Koki; Kawase, Reiko; Tanaka, Toshio

    2016-01-01

    Mammals exhibit poor recovery after spinal cord injury (SCI), whereas non-mammalian vertebrates exhibit significant spontaneous recovery after SCI. The mechanisms underlying this difference have not been fully elucidated; therefore, the purpose of this study was to investigate these mechanisms. Using comparative transcriptome analysis, we demonstrated that genes related to cell cycle were significantly enriched in the genes specifically dysregulated in zebrafish SCI. Most of the cell cycle-related genes dysregulated in zebrafish SCI were down-regulated, possibly through activation of e2f4. Using a larval zebrafish model of SCI, we demonstrated that the recovery of locomotive function and neuronal regeneration after SCI were significantly inhibited in zebrafish treated with an E2F4 inhibitor. These results suggest that activation of e2f4 after SCI may be responsible, at least in part, for the significant recovery in zebrafish. This provides novel insight into the lack of recovery after SCI in mammals and informs potential therapeutic strategies. PMID:27242526

  17. Fluoxetine treatment promotes functional recovery in a rat model of cervical spinal cord injury

    PubMed Central

    Scali, Manuela; Begenisic, Tatjana; Mainardi, Marco; Milanese, Marco; Bonifacino, Tiziana; Bonanno, Giambattista; Sale, Alessandro; Maffei, Lamberto

    2013-01-01

    Spinal cord injury (SCI) is a severe condition leading to enduring motor deficits. When lesions are incomplete, promoting spinal cord plasticity might be a useful strategy to elicit functional recovery. Here we investigated whether long-term fluoxetine administration in the drinking water, a treatment recently demonstrated to optimize brain plasticity in several pathological conditions, promotes motor recovery in rats that received a C4 dorsal funiculus crush. We show that fluoxetine administration markedly improved motor functions compared to controls in several behavioral paradigms. The improved functional effects correlated positively with significant sprouting of intact corticospinal fibers and a modulation of the excitation/inhibition balance. Our results suggest a potential application of fluoxetine treatment as a non invasive therapeutic strategy for SCI-associated neuropathologies. PMID:23860568

  18. A novel functional full-fat hard cheese containing liposomal nanoencapsulated green tea catechins: manufacture and recovery following simulated digestion.

    PubMed

    Rashidinejad, Ali; Birch, E John; Everett, David W

    2016-07-13

    (+)-Catechin or green tea extract were encapsulated in soy lecithin nanoliposomes and incorporated into a full-fat cheese, then ripened at 8 °C for 90 days. Cheese samples were subjected to simulated gastrointestinal digestion to measure total phenolic content (TPC) and antioxidant activity of the cheese digesta, and to determine the catechin recovery after digestion by high performance liquid chromatography (HPLC). Addition of catechin or green tea extract significantly (P ≤ 0.05) increased TPC and antioxidant activity (measured by ferric reducing antioxidant power and oxygen radical absorbance capacity) of the full-fat cheese without affecting pH or proximate composition. HPLC analysis confirmed retention of encapsulated catechins in the cheese curd; however, individual catechins were recovered in differing amounts (15-52%) from cheese digesta after 6 h of digestion. Transmission electron microscopy and Fourier transform infrared spectroscopy provided evidence for association of nanoliposomes with the surface of milk fat globules inside the cheese matrix. The study shows the potential for using cheese as a delivery vehicle for green tea antioxidants. PMID:27374326

  19. Functional consequences of cocaine re-exposure after discontinuation of cocaine availability.

    PubMed

    Beveridge, Thomas J R; Smith, Hilary R; Nader, Susan H; Nader, Michael A; Porrino, Linda J

    2014-10-01

    Cocaine users exhibit a wide range of behavioral impairments accompanied by brain structural, neurochemical and functional abnormalities. Metabolic mapping studies in cocaine users and animal models have shown extensive functional alterations throughout the striatum, limbic system, and cortex. Few studies, however, have evaluated the persistence of these effects following cessation of cocaine availability. The purpose of this study, therefore, was to assess the functional effects of re-exposure to cocaine in nonhuman primates after the discontinuation of cocaine self-administration for 30 or 90 days, using the quantitative autoradiographic 2-[14C]deoxyglucose (2DG) method. Rhesus monkeys self-administered cocaine (fixed interval 3-min schedule, 30 infusions per session, 0.3 mg/kg/infusion) for 100 sessions followed by 30 (n=4) or 90 days (n=3) during which experimental sessions were not conducted. Food-reinforced control animals (n=5) underwent identical schedules of reinforcement. Animals were then re-exposed to cocaine or food for one final session and the 2DG method applied immediately after session completion. Compared to controls, re-exposure to cocaine after 30 or 90 day drug-free periods resulted in lower rates of glucose utilization in ventral and dorsal striatum, prefrontal and temporal cortex, limbic system, thalamus, and midbrain. These data demonstrate that vulnerability to the effects of cocaine persists for as long as 90 days after cessation of drug use. While there was some evidence for recovery (fewer brain areas were affected by cocaine re-exposure at 90 days as compared to 30 days), this was not uniform across regions, thus suggesting that recovery occurs at different rates in different brain systems. PMID:24953829

  20. Functional Consequences of Cocaine Re-exposure after Discontinuation of Cocaine Availability

    PubMed Central

    Beveridge, Thomas J.R.; Smith, Hilary R.; Nader, Susan H.; Nader, Michael A.; Porrino, Linda J.

    2014-01-01

    Cocaine users exhibit a wide range of behavioral impairments accompanied by brain structural, neurochemical and functional abnormalities. Metabolic mapping studies in cocaine users and animal models have shown extensive functional alterations throughout the striatum, limbic system, and cortex. Few studies, however, have evaluated the persistence of these effects following cessation of cocaine availability. The purpose of this study, therefore, was to assess the functional effects of re-exposure to cocaine in nonhuman primates after the discontinuation of cocaine self-administration for 30 or 90 days, using the quantitative autoradiographic 2-[14C]deoxyglucose (2DG) method. Rhesus monkeys self-administered cocaine (fixed interval 3-min schedule, 30 infusions per session, 0.3 mg/kg/infusion) for 100 sessions followed by 30 (n=4) or 90 days (n=3) during which experimental sessions were not conducted. Food-reinforced control animals (n=5) underwent identical schedules of reinforcement. Animals were then re-exposed to cocaine or food for one final session and the 2DG method applied immediately after session completion. Compared to controls, re-exposure to cocaine after 30 or 90 day drug-free periods resulted in lower rates of glucose utilization in ventral and dorsal striatum, prefrontal and temporal cortex, limbic system, thalamus, and midbrain. These data demonstrate that vulnerability to the effects of cocaine persists for as long as 90 days after cessation of drug use. While there was some evidence for recovery (fewer brain areas were affected by cocaine re-exposure at 90 days as compared to 30 days), this was not uniform across regions, thus suggesting that recovery occurs at different rates in different brain systems. PMID:24953829

  1. Advanced magnetic resonance neuroimaging of language function recovery after aphasic stroke: a technical review.

    PubMed

    Smits, Marion; Visch-Brink, Evy G; van de Sandt-Koenderman, Mieke E; van der Lugt, Aad

    2012-01-01

    Two advanced magnetic resonance neuroimaging techniques, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), have recently made their way into clinically oriented research and hold great promise to study the brain's adaptive changes of function and structure after aphasic stroke, respectively. Such functional and structural neuroplasticity is thought to underlie the recovery of language function, occurring spontaneously and/or in the context of therapeutic intervention. With fMRI, brain activity can be visualized. Spontaneous brain activity, present in multiple brain networks, is measured with resting-state fMRI and language-related brain activity by having the subject perform a language task during scanning (task-based fMRI). With DTI the major white matter tracts, such as the dorsal and ventral language pathways and the commissural fibers, can be visualized and quantified. Both techniques are entirely noninvasive and thus offer the unique opportunity to perform multiple assessments within the same subject. To gain more insight in functional and structural neuroplasticity after aphasic stroke, advanced magnetic resonance neuroimaging studies in specific patient populations, at several stages after stroke and in the course of language recovery, are needed. Such studies will help to clarify the influence of the many factors that play a role in the recovery of language function and are thus vital to further the development of aphasia therapy. Application of these techniques in aphasic stroke patients, however, is not without challenge. The purpose of this article is to discuss the methodologic challenges of fMRI and DTI in the assessment of language recovery after aphasic stroke. PMID:22202190

  2. Mechanisms of recovery of visual function in adult amblyopia through a tailored action video game.

    PubMed

    Vedamurthy, Indu; Nahum, Mor; Bavelier, Daphne; Levi, Dennis M

    2015-01-01

    Amblyopia is a deficit in vision that arises from abnormal visual experience early in life. It was long thought to develop into a permanent deficit, unless properly treated before the end of the sensitive period for visual recovery. However, a number of studies now suggest that adults with long-standing amblyopia may at least partially recover visual acuity and stereopsis following perceptual training. Eliminating or reducing interocular suppression has been hypothesized to be at the root of these changes. Here we show that playing a novel dichoptic video game indeed results in reduced suppression, improved visual acuity and, in some cases, improved stereopsis. Our relatively large cohort of adults with amblyopia, allowed us, for the first time, to assess the link between visual function recovery and reduction in suppression. Surprisingly, no significant correlation was found between decreased suppression and improved visual function. This finding challenges the prevailing view and suggests that while dichoptic training improves visual acuity and stereopsis in adult amblyopia, reduced suppression is unlikely to be at the root of visual recovery. These results are discussed in the context of their implication on recovery of amblyopia in adults. PMID:25719537

  3. Mechanisms of recovery of visual function in adult amblyopia through a tailored action video game

    PubMed Central

    Vedamurthy, Indu; Nahum, Mor; Bavelier, Daphne; Levi, Dennis M.

    2015-01-01

    Amblyopia is a deficit in vision that arises from abnormal visual experience early in life. It was long thought to develop into a permanent deficit, unless properly treated before the end of the sensitive period for visual recovery. However, a number of studies now suggest that adults with long-standing amblyopia may at least partially recover visual acuity and stereopsis following perceptual training. Eliminating or reducing interocular suppression has been hypothesized to be at the root of these changes. Here we show that playing a novel dichoptic video game indeed results in reduced suppression, improved visual acuity and, in some cases, improved stereopsis. Our relatively large cohort of adults with amblyopia, allowed us, for the first time, to assess the link between visual function recovery and reduction in suppression. Surprisingly, no significant correlation was found between decreased suppression and improved visual function. This finding challenges the prevailing view and suggests that while dichoptic training improves visual acuity and stereopsis in adult amblyopia, reduced suppression is unlikely to be at the root of visual recovery. These results are discussed in the context of their implication on recovery of amblyopia in adults. PMID:25719537

  4. Binge Ethanol Prior to Traumatic Brain Injury Worsens Sensorimotor Functional Recovery in Rats

    PubMed Central

    Vaagenes, Ian C.; Tsai, Shih-Yen; Ton, Son T.; Husak, Vicki A.; McGuire, Susan O.; O’Brien, Timothy E.; Kartje, Gwendolyn L.

    2015-01-01

    A significant number of patients suffering from traumatic brain injury (TBI) have a high blood alcohol level at the time of injury. Furthermore, drinking alcohol in a binge-like pattern is now recognized as a national problem, leading to a greater likelihood of being injured. Our objective was to determine the consequences of a binge paradigm of alcohol intoxication at the time of TBI on long-term functional outcome using a sensitive test of sensorimotor function. We trained adult, male, Sprague Dawley rats on the skilled forelimb reaching task and then administered a single binge dose of ethanol (2g/kg, i.p.) or saline for three consecutive days (for a total of 3 doses). One hour after the final ethanol dose, rats underwent a TBI to the sensorimotor cortex corresponding to the preferred reaching forelimb. Animals were then tested for seven weeks on the skilled forelimb reaching task to assess the profile of recovery. We found that the group given ethanol prior to TBI displayed a slower recovery curve with a lower recovery plateau as compared to the control group. Therefore, even a relatively short (3 day) episode of binge alcohol exposure can negatively impact long-term recovery from a TBI, underscoring this significant public health problem. PMID:25768795

  5. Compression socks and functional recovery following marathon running: a randomized controlled trial.

    PubMed

    Armstrong, Stuart A; Till, Eloise S; Maloney, Stephen R; Harris, Gregory A

    2015-02-01

    Compression socks have become a popular recovery aid for distance running athletes. Although some physiological markers have been shown to be influenced by wearing these garments, scant evidence exists on their effects on functional recovery. This research aims to shed light onto whether the wearing of compression socks for 48 hours after marathon running can improve functional recovery, as measured by a timed treadmill test to exhaustion 14 days following marathon running. Athletes (n = 33, age, 38.5 ± 7.2 years) participating in the 2012 Melbourne, 2013 Canberra, or 2013 Gold Coast marathons were recruited and randomized into the compression sock or placebo group. A graded treadmill test to exhaustion was performed 2 weeks before and 2 weeks after each marathon. Time to exhaustion, average and maximum heart rates were recorded. Participants were asked to wear their socks for 48 hours immediately after completion of the marathon. The change in treadmill times (seconds) was recorded for each participant. Thirty-three participants completed the treadmill protocols. In the compression group, average treadmill run to exhaustion time 2 weeks after the marathon increased by 2.6% (52 ± 103 seconds). In the placebo group, run to exhaustion time decreased by 3.4% (-62 ± 130 seconds), P = 0.009. This shows a significant beneficial effect of compression socks on recovery compared with placebo. The wearing of below-knee compression socks for 48 hours after marathon running has been shown to improve functional recovery as measured by a graduated treadmill test to exhaustion 2 weeks after the event. PMID:25627452

  6. COMPRESSION SOCKS AND FUNCTIONAL RECOVERY FOLLOWING MARATHON RUNNING: A RANDOMISED CONTROLLED TRIAL.

    PubMed

    Armstrong, Stuart A; Till, Eloise S; Maloney, Stephen; Harris, Gregory

    2014-09-01

    Compression socks have become a popular recovery aid for distance running athletes. Although some physiological markers have been shown to be influenced by wearing these garments, scant evidence exists on their effects on functional recovery. This research aims to shed light onto whether the wearing of compression socks for 48 hours after marathon running can improve functional recovery, as measured by a timed treadmill test to exhaustion 14 days following marathon running.Athletes (n=33, age = 38.5 ±7.2yrs) participating in the 2012 Melbourne, 2013 Canberra or 2013 Gold Coast marathons were recruited and randomised into the compression sock or placebo group. A graded treadmill test to exhaustion was performed 2 weeks prior and 2 weeks following each marathon. Time to exhaustion, average and maximum heart rates were recorded. Participants were asked to wear their socks for 48 hours immediately after completion of the marathon. The change in treadmill times (seconds) was recorded for each participant.33 participants completed the treadmill protocols. In the compression group average treadmill run to exhaustion time 2 weeks following the marathon increased by 2.6% (52s ±103s). In the placebo group run to exhaustion time decreased by 3.4% (-62s ±130s). P=0.009. This shows a significant beneficial effect of compression socks on recovery compared to placebo.The wearing of below knee compression socks for 48 hours after marathon running has been shown to improve functional recovery as measured by a graduated treadmill test to exhaustion 2 weeks following the event. PMID:25187242

  7. Stimulus electrodiagnosis and motor and functional evaluations during ulnar nerve recovery

    PubMed Central

    Fernandes, Luciane F. R. M.; Oliveira, Nuno M. L.; Pelet, Danyelle C. S.; Cunha, Agnes F. S.; Grecco, Marco A. S.; Souza, Luciane A. P. S.

    2016-01-01

    BACKGROUND: Distal ulnar nerve injury leads to impairment of hand function due to motor and sensorial changes. Stimulus electrodiagnosis (SE) is a method of assessing and monitoring the development of this type of injury. OBJECTIVE: To identify the most sensitive electrodiagnostic parameters to evaluate ulnar nerve recovery and to correlate these parameters (Rheobase, Chronaxie, and Accommodation) with motor function evaluations. METHOD: A prospective cohort study of ten patients submitted to ulnar neurorrhaphy and evaluated using electrodiagnosis and motor assessment at two moments of neural recovery. A functional evaluation using the DASH questionnaire (Disability of the Arm, Shoulder, and Hand) was conducted at the end to establish the functional status of the upper limb. RESULTS: There was significant reduction only in the Chronaxie values in relation to time of injury and side (with and without lesion), as well as significant correlation of Chronaxie with the motor domain score. CONCLUSION: Chronaxie was the most sensitive SE parameter for detecting differences in neuromuscular responses during the ulnar nerve recovery process and it was the only parameter correlated with the motor assessment. PMID:26786072

  8. Increasing functional connectivity of the anterior cingulate cortex during the course of recovery from Bell's palsy.

    PubMed

    Hu, Sheng; Wu, Yuanyuan; Li, Chuanfu; Park, Kyungmo; Lu, Guangming; Mohamed, Abdalla Z; Wu, Hongli; Xu, Chunsheng; Zhang, Wei; Wang, Linying; Yang, Jun; Qiu, Bensheng

    2015-01-01

    Bell's palsy (BP), a unilateral and idiopathic palsy of the facial nerve, is a common disorder generally followed by a good natural recovery. The aim of this study was to investigate the relationship between the functional connectivity of the anterior cingulate cortex (ACC) and the recovery process of BP. Thirty-seven healthy volunteers and 67 patients were studied by functional MRI (fMRI). The seed regions of bilateral ACC were first extracted from the task-state fMRI data of healthy participants performing the task of mouth opening and closing. The connectivity of bilateral ACC was calculated from resting-state fMRI data of patients in whom only resting-state fMRI data were collected. The correlation between the strength of ACC's connectivity with the duration (time course of disease) was computed by analysis of covariance. It was found that the functional connectivity of the ACC ipsilateral to the lesioned side was enforced as the duration increased. The enforced brain areas included the sensorimotor areas and the ACC contralateral to the palsy. It was suggested that enforced functional connectivity of ACC might be related to cortical reorganization, which is important in the process of BP recovery. PMID:25426823

  9. Supplementary motor area deactivation impacts the recovery of hand function from severe peripheral nerve injury

    PubMed Central

    Lu, Ye-chen; Liu, Han-qiu; Hua, Xu-yun; Shen, Yun-dong; Xu, Wen-dong; Xu, Jian-guang; Gu, Yu-dong

    2016-01-01

    Although some patients have successful peripheral nerve regeneration, a poor recovery of hand function often occurs after peripheral nerve injury. It is believed that the capability of brain plasticity is crucial for the recovery of hand function. The supplementary motor area may play a key role in brain remodeling after peripheral nerve injury. In this study, we explored the activation mode of the supplementary motor area during a motor imagery task. We investigated the plasticity of the central nervous system after brachial plexus injury, using the motor imagery task. Results from functional magnetic resonance imaging showed that after brachial plexus injury, the motor imagery task for the affected limbs of the patients triggered no obvious activation of bilateral supplementary motor areas. This result indicates that it is difficult to excite the supplementary motor areas of brachial plexus injury patients during a motor imagery task, thereby impacting brain remodeling. Deactivation of the supplementary motor area is likely to be a serious problem for brachial plexus injury patients in terms of preparing, initiating and executing certain movements, which may be partly responsible for the unsatisfactory clinical recovery of hand function. PMID:27212933

  10. Dexamethasone enhanced functional recovery after sciatic nerve crush injury in rats.

    PubMed

    Feng, Xinhong; Yuan, Wei

    2015-01-01

    Dexamethasone is currently used for the treatment of peripheral nerve injury, but its mechanisms of action are not completely understood. Inflammation/immune response at the site of nerve lesion is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration. In this study, we observed the effects of various doses of dexamethasone on the functional recovery after sciatic nerve crush injury in a rat model. Motor functional recovery was monitored by walking track analysis and gastrocnemius muscle mass ratio. The myelinated axon number was counted by morphometric analysis. Rats administered dexamethasone by local intramuscular injection had a higher nerve function index value, increased gastrocnemius muscle mass ratio, reduced Wallerian degeneration severity, and enhanced regenerated myelinated nerve fibers. Immunohistochemical analysis was performed for CD3 expression, which is a marker for T-cell activation, and infiltration in the sciatic nerve. Dexamethasone-injected rats had fewer CD3-positive cells compared to controls. Furthermore, we found increased expression of GAP-43, which is a factor associated with development and plasticity of the nervous system, in rat nerves receiving dexamethasone. These results provide strong evidence that dexamethasone enhances sciatic nerve regeneration and function recovery in a rat model of sciatic nerve injury through immunosuppressive and potential neurotrophic effects. PMID:25839037

  11. Dexamethasone Enhanced Functional Recovery after Sciatic Nerve Crush Injury in Rats

    PubMed Central

    Feng, Xinhong; Yuan, Wei

    2015-01-01

    Dexamethasone is currently used for the treatment of peripheral nerve injury, but its mechanisms of action are not completely understood. Inflammation/immune response at the site of nerve lesion is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration. In this study, we observed the effects of various doses of dexamethasone on the functional recovery after sciatic nerve crush injury in a rat model. Motor functional recovery was monitored by walking track analysis and gastrocnemius muscle mass ratio. The myelinated axon number was counted by morphometric analysis. Rats administered dexamethasone by local intramuscular injection had a higher nerve function index value, increased gastrocnemius muscle mass ratio, reduced Wallerian degeneration severity, and enhanced regenerated myelinated nerve fibers. Immunohistochemical analysis was performed for CD3 expression, which is a marker for T-cell activation, and infiltration in the sciatic nerve. Dexamethasone-injected rats had fewer CD3-positive cells compared to controls. Furthermore, we found increased expression of GAP-43, which is a factor associated with development and plasticity of the nervous system, in rat nerves receiving dexamethasone. These results provide strong evidence that dexamethasone enhances sciatic nerve regeneration and function recovery in a rat model of sciatic nerve injury through immunosuppressive and potential neurotrophic effects. PMID:25839037

  12. Brain-Controlled Neuromuscular Stimulation to Drive Neural Plasticity and Functional Recovery

    PubMed Central

    Ethier, C.; Gallego, J.A.; Miller, L.E.

    2015-01-01

    There is mounting evidence that appropriately timed neuromuscular stimulation can induce neural plasticity and generate functional recovery from motor disorders. This review addresses the idea that coordinating stimulation with a patient’s voluntary effort might further enhance neurorehabilitation. Studies in cell cultures and behaving animals have delineated the rules underlying neural plasticity when single neurons are used as triggers. However, the rules governing more complex stimuli and larger networks are less well understood. We argue that functional recovery might be optimized if stimulation were modulated by a brain machine interface, to matched the details of the patient’s voluntary intent. The potential of this novel approach highlights the need for a better understanding of the complex rules underlying this form of plasticity. PMID:25827275

  13. Brain-controlled neuromuscular stimulation to drive neural plasticity and functional recovery.

    PubMed

    Ethier, C; Gallego, J A; Miller, L E

    2015-08-01

    There is mounting evidence that appropriately timed neuromuscular stimulation can induce neural plasticity and generate functional recovery from motor disorders. This review addresses the idea that coordinating stimulation with a patient's voluntary effort might further enhance neurorehabilitation. Studies in cell cultures and behaving animals have delineated the rules underlying neural plasticity when single neurons are used as triggers. However, the rules governing more complex stimuli and larger networks are less well understood. We argue that functional recovery might be optimized if stimulation were modulated by a brain machine interface, to match the details of the patient's voluntary intent. The potential of this novel approach highlights the need for a better understanding of the complex rules underlying this form of plasticity. PMID:25827275

  14. Recovery of partial differential operators on classes of periodic functions with mixed smoothness

    NASA Astrophysics Data System (ADS)

    Balgimbayeva, Sholpan

    2016-08-01

    We consider the problem of optimal linear recovery for mixed partial differential operator A on the unit ball SBpθ r(Tn) of the Nikol'skii-Besov space of periodic functions with mixed smoothness. We find error bounds sharp in order for optimal linear recovery of operator A on class SBpθ r(Tn) . As information IMδ(f ) about the functions f from class SBpθ r(Tn) we shall use Fourier coefficients with numbers from step "hyperbolic" cross. As the linear method using the information about Fourier coefficients, we shall consider action of the mixed partial differential operator A on the special "private" sum of decomposition on system (type as wavelets) trigonometric polynomials.

  15. Stimulation of autophagy promotes functional recovery in diabetic rats with spinal cord injury

    PubMed Central

    Zhou, Kai-liang; Zhou, Yi-fei; Wu, Kai; Tian, Nai-feng; Wu, Yao-sen; Wang, Yong-li; Chen, De-heng; Zhou, Bin; Wang, Xiang-yang; Xu, Hua-zi; Zhang, Xiao-lei

    2015-01-01

    In this study we examined the relationship between autophagy and apoptosis in diabetic rats after spinal cord injury (SCI), also we determined the role of autophagy in diabetes-aggravated neurological injury in vivo and in vitro. Our results showed that diabetes decreased the survival of neurons, promoted astrocytes proliferation, increased inflammatory cells infiltration and inhibited functional recovery after SCI. Diabetes was shown to confer increased activation of apoptotic pathways, along with an increase in autophagy; similar effects were also observed in vitro in neuronal PC12 cells. Treatment with rapamycin, an autophagy activator, partially abolished the adverse effect of diabetes, suggesting that diabetes may enhance neurological damage and suppress locomotor recovery after SCI, in addition to its effects on apoptosis and autophagy. In contrast, further stimulation of autophagy improved neurological function via inhibition of apoptosis. These results explained how diabetes exacerbates SCI in cellular level and suggested autophagy stimulation to be a new therapeutic strategy for diabetic SCI. PMID:26597839

  16. Less incidence of coronary artery disease in general anesthesia compared to spinal-epidural anesthesia after total knee replacement: 90-day follow-up period by a population-based dataset.

    PubMed

    Hsieh, Jui-Yang; Lin, Hui-Wen

    2015-07-01

    Total knee replacement (TKR) is an effective and safe procedure. However, large-scale study to compare the incidence of coronary artery disease (CAD) after spinal or epidural anesthesia (SA-EA) or general anesthesia (GA) for TKR has not ever been conducted. To do so, we studied a population-based dataset from the Taiwan National Health Research Institute and hypothesized that the incidence of CAD might be different with regional than with general anesthesia. The risk of CAD-related events during a 90-day follow-up period among patients who received TKR under SA-EA or GA was evaluated in the present study. A total of 1500 patients from the Taiwan National Health Insurance claims database who underwent TKR from January 1, 2004, to December 31, 2006, were allocated into two groups. Group 1 included 1012 patients who received SA-EA during TKR procedure. Group 2 included 488 patients who received GA during this procedure. The number of patients who developed CAD during the 90-day follow-up period was 31 (3.1 %) in group 1 and 6 (1.2 %) in group 2. The Kaplan-Meier survival analysis of IHD-free cumulative survival rate during the 90-day follow-up period for patients who underwent TKR was significantly lower in group 1 than in group 2. The hazard ratio for the occurrence of CAD was 2.80 (95 % CI 1.16-6.78), and the hazard was higher for patients who received SA-EA than for patients who received GA after adjusted potential confounding factors. After the performance of TKR, patients had a potentially increased risk for CAD in SA-EA compared to GA during the 90-day follow-up period. PMID:25761988

  17. 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

  18. Plasminogen deficiency causes reduced corticospinal axonal plasticity and functional recovery after stroke in mice.

    PubMed

    Liu, Zhongwu; Li, Yi; Qian, Jianyong; Cui, Yisheng; Chopp, Michael

    2014-01-01

    Tissue plasminogen activator (tPA) has been implicated in neurite outgrowth and neurological recovery post stroke. tPA converts the zymogen plasminogen (Plg) into plasmin. In this study, using plasminogen knockout (Plg-/-) mice and their Plg-native littermates (Plg+/+), we investigated the role of Plg in axonal remodeling and neurological recovery after stroke. Plg+/+ and Plg-/- mice (n = 10/group) were subjected to permanent intraluminal monofilament middle cerebral artery occlusion (MCAo). A foot-fault test and a single pellet reaching test were performed prior to and on day 3 after stroke, and weekly thereafter to monitor functional deficit and recovery. Biotinylated dextran amine (BDA) was injected into the left motor cortex to anterogradely label the corticospinal tract (CST). Animals were euthanized 4 weeks after stroke. Neurite outgrowth was also measured in primary cultured cortical neurons harvested from Plg+/+ and Plg-/- embryos. In Plg+/+ mice, the motor functional deficiency after stroke progressively recovered with time. In contrast, recovery in Plg-/- mice was significantly impaired compared to Plg+/+ mice (p<0.01). BDA-positive axonal density of the CST originating from the contralesional cortex in the denervated side of the cervical gray matter was significantly reduced in Plg-/- mice compared with Plg+/+ mice (p<0.05). The behavioral outcome was highly correlated with the midline-crossing CST axonal density (R2>0.82, p<0.01). Plg-/- neurons exhibited significantly reduced neurite outgrowth. Our data suggest that plasminogen-dependent proteolysis has a beneficial effect during neurological recovery after stroke, at least in part, by promoting axonal remodeling in the denervated spinal cord. PMID:24732409

  19. Factors affecting recovery of postoperative bowel function after pediatric laparoscopic surgery

    PubMed Central

    Michelet, Daphnée; Andreu-Gallien, Juliette; Skhiri, Alia; Bonnard, Arnaud; Nivoche, Yves; Dahmani, Souhayl

    2016-01-01

    Background and Aims: Laparoscopic pediatric surgery allows a rapid postoperative rehabilitation and hospital discharge. However, the optimal postoperative pain management preserving advantages of this surgical technique remains to be determined. This study aimed to identify factors affecting the postoperative recovery of bowel function after laparoscopic surgery in children. Material and Methods: A retrospective analysis of factors affecting recovery of bowel function in children and infants undergoing laparoscopic surgery between January 1, 2009 and September 30, 2009, was performed. Factors included were: Age, weight, extent of surgery (extensive, regional or local), chronic pain (sickle cell disease or chronic intestinal inflammatory disease), American Society of Anaesthesiologists status, postoperative analgesia (ketamine, morphine, nalbuphine, paracetamol, nonsteroidal anti-inflammatory drugs [NSAIDs], nefopam, regional analgesia) both in the Postanesthesia Care Unit and in the surgical ward; and surgical complications. Data analysis used classification and regression tree analysis (CART) with a 10-fold cross validation. Results: One hundred and sixty six patients were included in the analysis. Recovery of bowel function depended upon: The extent of surgery, the occurrence of postoperative surgical complications, the administration of postoperative morphine in the surgical ward, the coadministration of paracetamol and NSAIDs and/or nefopam in the surgical ward and the emergency character of the surgery. The CART method generated a decision tree with eight terminal nodes. The percentage of explained variability of the model and the cross validation were 58% and 49%, respectively. Conclusion: Multimodal analgesia using nonopioid analgesia that allows decreasing postoperative morphine consumption should be considered for the speed of bowel function recovery after laparoscopic pediatric surgery.

  20. Promoting plasticity in the spinal cord with chondroitinase improves functional recovery after peripheral nerve repair.

    PubMed

    Galtrey, Clare M; Asher, Richard A; Nothias, Fatiha; Fawcett, James W

    2007-04-01

    Functional recovery after peripheral nerve repair in humans is often disappointing. A major reason for this is the inaccuracy of re-innervation of muscles and sensory structures. We hypothesized that promoting plasticity in the spinal cord, through digestion of chondroitin sulphate proteoglycans (CSPGs) with chondroitinase ABC (ChABC), might allow the CNS to compensate for inaccurate peripheral re-innervation and improve functional recovery. The median and ulnar nerves were injured and repaired to produce three grades of inaccuracy of peripheral re-innervation by (i) crush of both nerves; (ii) correct repair of median to median and ulnar to ulnar; and (iii) crossover of the median and ulnar nerves. Mapping of the motor neuron pool of the flexor carpi radialis muscle showed precise re-innervation after nerve crush, inaccurate regeneration after correct repair, more inaccurate after crossover repair. Recovery of forelimb function, assessed by skilled paw reaching, grip strength and sensory testing varied with accuracy of re-innervation. This was not due to differences in the number of regenerated axons. Single injections of ChABC into the spinal cord led to long-term changes in the extracellular matrix, with hyaluronan and neurocan being removed and not fully replaced after 8 weeks. ChABC treatment produce increased sprouting visualized by MAP1BP staining and improved functional recovery in skilled paw reaching after correct repair and in grip strength after crossover repair. There was no hyperalgesia. Enhanced plasticity in the spinal cord, therefore, allows the CNS to compensate for inaccurate motor and sensory re-innervation of the periphery, and may be a useful adjunct therapy to peripheral nerve repair. PMID:17255150

  1. Hydrogen-rich saline promotes motor functional recovery following peripheral nerve autografting in rats

    PubMed Central

    ZHANG, YONG-GUANG; SHENG, QING-SONG; WANG, ZHI-JUN; LV, LI; ZHAO, WEI; CHEN, JIAN-MEI; XU, HAO

    2015-01-01

    Despite the application of nerve grafts and considerable microsurgical innovations, the functional recovery across a long peripheral nerve gap is generally partial and unsatisfactory. Thus, additional strategies are required to improve nerve regeneration across long nerve gaps. Hydrogen possesses antioxidant and anti-apoptotic properties, which could be neuroprotective in the treatment of peripheral nerve injury; however, such a possibility has not been experimentally tested in vivo. The aim of the present study was to investigate the effectiveness of hydrogen-rich saline in promoting nerve regeneration after 10-mm sciatic nerve autografting in rats. The rats were randomly divided into two groups and intraperitoneally administered a daily regimen of 5 ml/kg hydrogen-rich or normal saline. Axonal regeneration and functional recovery were assessed through a combination of behavioral analyses, electrophysiological evaluations, Fluoro-Gold™ retrograde tracings and histomorphological observations. The data showed that rats receiving hydrogen-rich saline achieved better axonal regeneration and functional recovery than those receiving normal saline. These findings indicated that hydrogen-rich saline promotes nerve regeneration across long gaps, suggesting that hydrogen-rich saline could be used as a neuroprotective agent for peripheral nerve injury therapy. PMID:26622383

  2. Atorvastatin activates autophagy and promotes neurological function recovery after spinal cord injury

    PubMed Central

    Gao, Shuang; Zhang, Zhong-ming; Shen, Zhao-liang; Gao, Kai; Chang, Liang; Guo, Yue; Li, Zhuo; Wang, Wei; Wang, Ai-mei

    2016-01-01

    Atorvastatin, a lipid-lowering medication, provides neuroprotective effects, although the precise mechanisms of action remain unclear. Our previous studies confirmed activated autophagy following spinal cord injury, which was conducive to recovery of neurological functions. We hypothesized that atorvastatin could also activate autophagy after spinal cord injury, and subsequently improve recovery of neurological functions. A rat model of spinal cord injury was established based on the Allen method. Atorvastatin (5 mg/kg) was intraperitoneally injected at 1 and 2 days after spinal cord injury. At 7 days post-injury, western blot assay, reverse transcription-polymerase chain reaction, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining results showed increased Beclin-1 and light chain 3B gene and protein expressions in the spinal cord injury + atorvastatin group. Additionally, caspase-9 and caspase-3 expression was decreased, and the number of TUNEL-positive cells was reduced. Compared with the spinal cord injury + saline group, Basso, Beattie, and Bresnahan locomotor rating scale scores significantly increased in the spinal cord injury + atorvastatin group at 14–42 days post-injury. These findings suggest that atorvastatin activated autophagy after spinal cord injury, inhibited apoptosis, and promoted recovery of neurological function. PMID:27482228

  3. Exercise promotes motor functional recovery in rats with corticospinal tract injury: anti-apoptosis mechanism

    PubMed Central

    Hou, Ting-ting; Yang, Xiao-yu; Xia, Peng; Pan, Su; Liu, Jian; Qi, Zhi-ping

    2015-01-01

    Studies have shown that exercise interventions can improve functional recovery after spinal cord injury, but the mechanism of action remains unclear. To investigate the mechanism, we established a unilateral corticospinal tract injury model in rats by pyramidotomy, and used a single pellet reaching task and horizontal ladder walking task as exercise interventions postoperatively. Functional recovery of forelimbs and forepaws in the rat models was noticeably enhanced after the exercises. Furthermore, TUNEL staining revealed significantly fewer apoptotic cells in the spinal cord of exercised rats, and western blot analysis showed that spinal cord expression of the apoptosis-related protein caspase-3 was significantly lower, and the expression of Bcl-2 was significantly higher, while the expression of Bax was not signifiantly changed after exercise, compared with the non-exercised group. Expression of these proteins decreased with time after injury, towards the levels observed in sham-operated rats, however at 4 weeks postoperatively, caspase-3 expression remained significantly greater than in sham-operated rats. The present findings indicate that a reduction in apoptosis is one of the mechanisms underlying the improvement of functional recovery by exercise interventions after corticospinal tract injury. PMID:26170828

  4. Atorvastatin activates autophagy and promotes neurological function recovery after spinal cord injury.

    PubMed

    Gao, Shuang; Zhang, Zhong-Ming; Shen, Zhao-Liang; Gao, Kai; Chang, Liang; Guo, Yue; Li, Zhuo; Wang, Wei; Wang, Ai-Mei

    2016-06-01

    Atorvastatin, a lipid-lowering medication, provides neuroprotective effects, although the precise mechanisms of action remain unclear. Our previous studies confirmed activated autophagy following spinal cord injury, which was conducive to recovery of neurological functions. We hypothesized that atorvastatin could also activate autophagy after spinal cord injury, and subsequently improve recovery of neurological functions. A rat model of spinal cord injury was established based on the Allen method. Atorvastatin (5 mg/kg) was intraperitoneally injected at 1 and 2 days after spinal cord injury. At 7 days post-injury, western blot assay, reverse transcription-polymerase chain reaction, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining results showed increased Beclin-1 and light chain 3B gene and protein expressions in the spinal cord injury + atorvastatin group. Additionally, caspase-9 and caspase-3 expression was decreased, and the number of TUNEL-positive cells was reduced. Compared with the spinal cord injury + saline group, Basso, Beattie, and Bresnahan locomotor rating scale scores significantly increased in the spinal cord injury + atorvastatin group at 14-42 days post-injury. These findings suggest that atorvastatin activated autophagy after spinal cord injury, inhibited apoptosis, and promoted recovery of neurological function. PMID:27482228

  5. Consumer return chronology alters recovery trajectory of stream ecosystem structure and function following drought.

    PubMed

    Murdock, Justin N; Gido, Keith B; Dodds, Walter K; Bertrand, Katie N; Whiles, Matt R

    2010-04-01

    Consumers are increasingly being recognized as important drivers of ecological succession, yet it is still hard to predict the nature and direction of consumer effects in nonequilibrium environments. We used stream consumer exclosures and large outdoor mesocosms to study the impact of macroconsumers (i.e., fish and crayfish) on recovery of intermittent prairie streams after drying. In the stream, macroconsumers altered system recovery trajectory by decreasing algal and macroinvertebrate biomass, primary productivity, and benthic nutrient uptake rates. However, macroconsumer influence was transient, and differences between exclosures and controls disappeared after 35 days. Introducing and removing macroconsumers after 28 days resulted mainly in changes to macroinvertebrates. In mesocosms, a dominant consumer (the grazing minnow Phoxinus erythrogaster) reduced macroinvertebrate biomass but had little effect on algal assemblage structure and ecosystem rates during recovery. The weak effect of P. erythrogaster in mesocosms, in contrast to the strong consumer effect in the natural stream, suggests that both timing and diversity of returning consumers are important to their overall influence on stream recovery patterns. Although we found that consumers significantly altered ecosystem structure and function in a system experiencing rapid changes in abiotic and biotic factors following disturbance, consumer effects diminished over time and trajectories converged to similar states with respect to primary producers, in spite of differences in consumer colonization history. Thus, consumer impacts can be substantial in recovering ecosystems and are likely to be dependent on the disturbance regime and diversity of the consumer community. PMID:20462119

  6. [Stigmatization on the way to recovery in mental illness - the factors associated with social functioning].

    PubMed

    Podogrodzka-Niell, Magdalena; Tyszkowska, Magdalena

    2014-01-01

    Persons with mental disorders often experience stigmatization. There is a number of social factors that may affect the process of recovery and at the same time, in certain circumstances, could be a source of stigma. Mentally ill may find strength in themselves to fight against the disease or the opposite - can internalize the negative attitudes of the society and become self-stigmatized. The patient's family, on the one hand, is often the only source of social support, on the other hand, can experience a destructive influence of courtesy-stigma. Mentally ill have to face social reluctance which is reinforced by stereotypical media coverage of mental disorders. The social network of patients is poor and often limited to a family system. Negative views about persons diagnosed with mental illness are most visible in the labour market. Patients experience many types of discrimination at work,have lower employment rates and lower mean wages than healthy ones. Structural discrimination is a form of stigma which is revealed in underfunded and inefficient system of mental health care. All the social factors mentioned above are necessary for recovery (positive stimulation of functioning), but can also increase stigma and become a significant barrier in the recovery of psychiatric patients. This paper highlights the complex and ambiguous nature of the relationship between social factors and the recovery of the mentally ill basing on the data from the literature. PMID:25717489

  7. Treating to target in major depressive disorder: response to remission to functional recovery.

    PubMed

    McIntyre, Roger S; Lee, Yena; Mansur, Rodrigo B

    2015-12-01

    Treating to target in chronic diseases [e.g. Major Depressive Disorder (MDD)] fosters precision, consistency, and appropriateness of treatment selection and sequencing. Therapeutic target definitions/endpoints in MDD should satisfy patient-, provider-, and societal expectations. Functional recovery in depression and return to both physical and mental health are the overarching therapeutic objectives. Treating to target in MDD implies multidimensional symptomatic remission, with a particular emphasis on cognitive function and aspects of positive mental health. Several atypical antipsychotic agents (i.e. brexpiprazole, aripiprazole, quetiapine) are FDA-approved as augmentation agents in MDD. Vortioxetine, duloxetine, and psychostimulants have evidence of independent, direct, and robust effects on cognitive function in MDD. Vortioxetine is the only agent that demonstrates efficacy across multiple cognitive domains in MDD associated with functional recovery. Measurement-based care, health information technology/systems, and integrated care models (e.g. medical homes) provide requisite tools and health environments for optimal health outcomes in MDD. Achieving remission in MDD does not equate to health. Return to positive mental health as well as full functioning provide the impetus to pivot away from traditional provider-defined outcomes toward an inclusive perspective involving patient- and society-defined outcomes (i.e. optimization of human capital). As in other chronic diseases, treating to target (e.g. cognitive function) further increases the probability of achieving optimal health outcomes. PMID:26683526

  8. Cortical effect and functional recovery by the electromyography-triggered neuromuscular stimulation in chronic stroke patients.

    PubMed

    Shin, Hwa Kyung; Cho, Sang Hyun; Jeon, Hye-seon; Lee, Young-Hee; Song, Jun Chan; Jang, Sung Ho; Lee, Chu-Hee; Kwon, Yong Hyun

    2008-09-19

    We investigated the effect of electromyography (EMG)-triggered neuromuscular electrical stimulation (NMES; EMG-stim) on functional recovery of the hemiparetic hand and the related cortical activation pattern in chronic stroke patients. We enrolled 14 stroke patients, who were randomly assigned to the EMG-stim (n=7) or the control groups (n=7). The EMG-stim was applied to the wrist extensor of the EMG-stim group for two sessions (30 min/session) a day, five times per week for 10 weeks. Four functional tests (box and block, strength, the accuracy index, and the on/offset time of muscle contraction) and functional MRI (fMRI) were performed before and after treatment. fMRI was measured at 1.5 T in parallel with timed finger flexion-extension movements at a fixed rate. Following treatment, the EMG-stim group showed a significant improvement in all functional tests. The main cortical activation change with such functional improvement was shifted from the ipsilateral sensorimotor cortex (SMC) to the contralateral SMC. We demonstrated that 10-week EMG-stim can induce functional recovery and change of cortical activation pattern in the hemiparetic hand of chronic stroke patients. PMID:18644424

  9. N-acetylcysteine amide preserves mitochondrial bioenergetics and improves functional recovery following spinal trauma.

    PubMed

    Patel, Samir P; Sullivan, Patrick G; Pandya, Jignesh D; Goldstein, Glenn A; VanRooyen, Jenna L; Yonutas, Heather M; Eldahan, Khalid C; Morehouse, Johnny; Magnuson, David S K; Rabchevsky, Alexander G

    2014-07-01

    Mitochondrial dysfunction is becoming a pivotal target for neuroprotective strategies following contusion spinal cord injury (SCI) and the pharmacological compounds that maintain mitochondrial function confer neuroprotection and improve long-term hindlimb function after injury. In the current study we evaluated the efficacy of cell-permeating thiol, N-acetylcysteine amide (NACA), a precursor of endogenous antioxidant glutathione (GSH), on mitochondrial function acutely, and long-term tissue sparing and hindlimb locomotor recovery following upper lumbar contusion SCI. Some designated injured adult female Sprague-Dawley rats (n=120) received either vehicle or NACA (75, 150, 300 or 600mg/kg) at 15min and 6h post-injury. After 24h the total, synaptic, and non-synaptic mitochondrial populations were isolated from a single 1.5cm spinal cord segment (centered at injury site) and assessed for mitochondrial bioenergetics. Results showed compromised total mitochondrial bioenergetics following acute SCI that was significantly improved with NACA treatment in a dose-dependent manner, with maximum effects at 300mg/kg (n=4/group). For synaptic and non-synaptic mitochondria, only 300mg/kg NACA dosage showed efficacy. Similar dosage (300mg/kg) also maintained mitochondrial GSH near normal levels. Other designated injured rats (n=21) received continuous NACA (150 or 300mg/kg/day) treatment starting at 15min post-injury for one week to assess long-term functional recovery over 6weeks post-injury. Locomotor testing and novel gait analyses showed significantly improved hindlimb function with NACA that were associated with increased tissue sparing at the injury site. Overall, NACA treatment significantly maintained acute mitochondrial bioenergetics and normalized GSH levels following SCI, and prolonged delivery resulted in significant tissue sparing and improved recovery of hindlimb function. PMID:24805071

  10. N-acetylcysteineamide Preserves Mitochondrial Bioenergetics and Improves Functional Recovery Following Spinal Trauma

    PubMed Central

    Patel, Samir P.; Sullivan, Patrick G.; Pandya, Jignesh D.; Goldstein, Glenn A.; VanRooyen, Jenna L.; Yonutas, Heather M.; Eldahan, Khalid C.; Morehouse, Johnny; Magnuson, David S. K.; Rabchevsky, Alexander G.

    2014-01-01

    Mitochondrial dysfunction is becoming a pivotal target for neuroprotective strategies following contusion spinal cord injury (SCI) and the pharmacological compounds that maintain mitochondrial function confer neuroprotection and improve long-term hindlimb function after injury. In the current study we evaluated the efficacy of cell-permeating thiol, N-acetylcysteineamide (NACA), a precursor of endogenous antioxidant glutathione (GSH), on mitochondrial function acutely, and long-term tissue sparing and hindlimb locomotor recovery following upper lumbar contusion SCI. Some designated injured adult female Sprague-Dawley rats (n=120) received either Vehicle or NACA (75, 150, 300 or 600 mg/kg) at 15min and 6hrs post-injury. After 24hr the total, synaptic, and non-synaptic mitochondrial populations were isolated from a single 1.5cm spinal cord segment (centered at injury site) and assessed for mitochondrial bioenergetics. Results showed compromised total mitochondrial bioenergetics following acute SCI that was significantly improved with NACA treatment in a dose-dependent manner, with maximum effects at 300 mg/kg (n=4/group). For synaptic and non-synaptic mitochondria, only 300 mg/kg NACA dosage showed efficacy. Similar dosage (300mg/kg) also maintained mitochondrial GSH near normal levels. Other designated injured rats (n=21) received continuous NACA (150 or 300mg/kg/day) treatment starting at 15min post-injury for one week to assess long-term functional recovery over 6 weeks post-injury. Locomotor testing and novel gait analyses showed significantly improved hindlimb function with NACA that were associated with increased tissue sparing at the injury site. Overall, NACA treatment significantly maintained acute mitochondrial bioenergetics and normalized GSH levels following SCI, and prolonged delivery resulted in significant tissue sparing and improved recovery of hindlimb function. PMID:24805071

  11. Brain stimulation used as biofeedback training for recovery of motor functions deteriorated by stroke.

    PubMed

    Calomeni, Mauricio Rocha; Rocha, José Antonio Martins da Silva; Silva, Alair Pedro Ribeiro da; Ribeiro, Luiz Henrique Brandão; Marques, Luciene; Siza, Maria Auxiliadora Freire; Silva, Vernon Furtado da

    2013-03-01

    According to World Health Organization, approximately 15 million people are affected by cerebrovascular accident in the world. We study the effect of brain stimulation plus an imaging procedure used as biofeedback training for recovery of motor functions impaired by CVA. Four individuals aged between 33 and 72 years were included in the study, of both genders, with hemiparesis on the left arm due to the CVA. They had their brain activity monitored by EEG. Functional tasks were evaluated according to an observational model proposed by the international classification of functioning and by runtime. The training was composed of 12 sessions of 30 minutes of stimulation by light and sound, as well as imaging procedures. Results revealed that improvements in the performance of the task, with regard to both the runtime and the functional quality of movements, are more related to the increase of effectiveness of neuronal function. PMID:23563715

  12. Androgen induced acceleration of functional recovery after rat sciatic nerve injury.

    PubMed

    Brown, Todd J.; Khan, Talat; Jones, Kathryn J.

    1999-01-01

    PURPOSE: Testosterone (T) treatment accelerates recovery from facial paralysis after facial nerve crush in hamsters. In this study, we extended those studies to another injury model and asked the following question: Will T treatment accelerate recovery from lower limb paralysis following sciatic nerve crush in the rat? METHODS: Castrated adult male rats received a right side sciatic nerve crush at the level of the sciatic notch, with the left side serving as control. Half the animals received a subcutaneous implant of a propionated form of T (TP), the others were sham-implanted. Weekly testing using the Sciatic Functional Index (SFI), a quantitative measure of locomotion, was done for 7 weeks postoperative (wpo). RESULTS: Between 3 and 5 weeks post-op, the average SFI score of the TP-treated group was higher than controls. This difference was significant at 4 wpo, indicating an accelerated degree of functional recovery. At these timepoints, the differences were attributable to the footprint or paw length and associated with calf muscle reinnervation rather than the toespreading component associated with intrinsic foot muscle rein-nervation. Beyond 5 wpo, there were no differences in the SFI scores. CONCLUSION: The results indicate that, as with facial nerve regeneration in the hamster, testosterone accelerates functional recovery from hind limb paralysis following sciatic nerve injury in the rat. While the responses of spinal motoneurons to injury can differ from those of cranial motoneurons, in this case it appears that they share a similar response to the trophic actions of androgen. This is important in the context of designing therapeutic strategies for dealing with direct trauma to motoneurons resulting from both peripheral and central nervous system trauma, such as spinal cord injury. PMID:12671219

  13. The role of recovery of mitochondrial structure and function in desiccation tolerance of pea seeds.

    PubMed

    Wang, Wei-Qing; Cheng, Hong-Yan; Møller, Ian M; Song, Song-Quan

    2012-01-01

    Mitochondrial repair is of fundamental importance for seed germination. When mature orthodox seeds are imbibed and germinated, they lose their desiccation tolerance in parallel. To gain a better understanding of this process, we studied the recovery of mitochondrial structure and function in pea (Pisum sativum cv. Jizhuang) seeds with different tolerance to desiccation. Mitochondria were isolated and purified from the embryo axes of control and imbibed-dehydrated pea seeds after (re-)imbibition for various times. Recovery of mitochondrial structure and function occurred both in control and imbibed-dehydrated seed embryo axes, but at different rates and to different maximum levels. The integrity of the outer mitochondrial membrane reached 96% in all treatments. However, only the seeds imbibed for 12 h and then dehydrated recovered the integrity of the inner mitochondrial membrane (IMM) and State 3 (respiratory state in which substrate and ADP are present) respiration (with NADH and succinate as substrate) to the control level after re-imbibition. With increasing imbibition time, the degree to which each parameter recovered decreased in parallel with the decrease in desiccation tolerance. The tolerance of imbibed seeds to desiccation increased and decreased when imbibed in CaCl(2) and methylviologen solution, respectively, and the recovery of the IMM integrity similarly improved and weakened in these two treatments, respectively. Survival of seeds after imbibition-dehydration linearly increased with the increase in ability to recover the integrity of IMM and State 3 respiration, which indicates that recovery of mitochondrial structure and function during germination has an important role in seed desiccation tolerance. PMID:21910735

  14. 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

  15. Recovery of gastrointestinal function with thoracic epidural vs. systemic analgesia following gastrointestinal surgery.

    PubMed

    Shi, W-Z; Miao, Y-L; Yakoob, M Y; Cao, J-B; Zhang, H; Jiang, Y-G; Xu, L-H; Mi, W-D

    2014-09-01

    The objective of this review was to systematically assess the effect of thoracic epidural analgesia (TEA) vs. systemic analgesia (SA) on the recovery of gastrointestinal (GI) function in patients following GI surgery. We performed a comprehensive literature search to identify randomized controlled trials of adult patients undergoing GI surgery, comparing the effect of two postoperative analgesia regimens. Patients postoperatively receiving local anesthesia-based TEA with or without opioids were compared to patients receiving opioid-based SA. The outcomes considered were times to GI function recovery, GI complications, and specific side effects. Twelve studies with 331 patients in the TEA group and 319 in the SA group were included. Compared to SA, TEA improved the GI recovery after GI procedures by shortening the time to first passage of flatus by 31.3 h, 95% confidence intervals (CIs): -33.2 to -29.4, P < 0.01; and shortening the time to first passage of stool by 24.1 h, 95% CIs: -27.2 to -20.9, P < 0.001. There was no difference between the groups in the incidence of anastomotic leakage and ileus. The occurrence of postoperative hypotension was relatively higher in the TEA group, risk ratio: 7.9, 95% CIs: 2.4 to 26.5, P = 0.001; other side effects (such as pruritus and vomiting) were similar in the two groups. There is evidence that TEA (compared to SA) improves the recovery of GI function after GI procedures without any increased risk of GI complications. To further confirm these effects, larger, better quality randomized controlled trials with standard outcome measurements are needed. PMID:25060245

  16. Structural and functional alterations to rat medial prefrontal cortex following chronic restraint stress and recovery

    PubMed Central

    Goldwater, Deena S.; Pavlides, Constantine; Hunter, Richard G.; Bloss, Erik B.; Hof, Patrick R.; McEwen, Bruce S.; Morrison, John H.

    2009-01-01

    Chronic stress has been shown in animal models to result in altered dendritic morphology of pyramidal neurons of the medial prefrontal cortex (mPFC). It has been hypothesized that the stress-induced dendritic retractions and spine loss lead to disrupted connectivity that results in stress-induced functional impairment of mPFC. While these alterations were initially viewed as a neurodegenerative event, it has recently been established that stress induced dendritic alterations are reversible if animals are given time to recover from chronic stress. However, whether spine growth accompanies dendritic extension remains to be demonstrated. It is also not known if recovery-phase dendritic extension allows for re-establishment of functional capacity. The goal of this study, therefore, was to characterize the structural and functional effects of chronic stress and recovery on the infralimbic (IL) region of the rat mPFC. We compared neuronal morphology of layer V IL pyramidal neurons from animals subjected to 21 days of chronic restraint stress (CRS) to those that experienced CRS followed by a 21 day recovery period. Layer V pyramidal cell functional capacity was assessed by intra-IL long-term potentiation (LTP) both in the absence and presence of SKF38393, a dopamine receptor partial agonist and a known PFC LTP modulator. We found that stress-induced IL apical dendritic retraction and spine loss co-occur with receptor-mediated impairments to catecholaminergic facilitation of synaptic plasticity. We also found that while post-stress recovery did not reverse distal dendritic retraction, it did result in over-extension of proximal dendritic neuroarchitecture and spine growth as well as a full reversal of CRS-induced impairments to catecholaminergic-mediated synaptic plasticity. Our results support the hypothesis that disease-related PFC dysfunction is a consequence of network disruption secondary to altered structural and functional plasticity and that circuitry

  17. Voluntary forced use of the impaired limb following stroke facilitates functional recovery in the rat.

    PubMed

    Livingston-Thomas, Jessica M; McGuire, Emily P; Doucette, Tracy A; Tasker, R Andrew

    2014-03-15

    Constraint induced movement therapy (CIMT), which forces use of the impaired arm following stroke, improves functional recovery. The mechanisms underlying recovery are not well understood, necessitating further investigation into how rehabilitation may affect neuroplasticity using animal models. Animal motivation and stress make modelling CIMT in animals challenging. We have shown that following focal ischemia, voluntary forced use therapy using pet activity balls could engage the impaired forelimb and result in a modest acceleration in recovery. In this study, we investigated the effects of a more intensive appetitively motivated regimen that included task specific reaching exercises. Adult male Sprague Dawley rats were subjected to focal unilateral stroke using intracerebral injections of endothelin-1 or sham surgery. Three days later, stroke animals were assigned to daily rehabilitation or control therapy. Rehabilitation consisted of 30 min of generalized movement sessions in activity balls, followed by 30 min of voluntary task-specific movement using reaching boxes. Rats were tested weekly to measure forelimb deficit and recovery. After 30 days, animals were euthanized and tissue was examined for infarct volume, brain derived neurotrophic factor expression, and the presence of new neurons using doublecortin immunohistochemistry. Rehabilitation resulted in a significant acceleration of forelimb recovery in several tests, and a significant increase in the number of doublecortin-expressing cells. Furthermore, while the proportion of cells expressing BDNF in the peri-infarct region did not change, there was a shift in the cellular origin of expressed BDNF, resulting in significantly more non-neuronal, non-astrocytic BDNF, presumed to be of microglial origin. PMID:24388978

  18. Simple functionalization strategies for enhancing nanoparticle separation and recovery with asymmetric flow field flow fractionation.

    PubMed

    Mudalige, Thilak K; Qu, Haiou; Sánchez-Pomales, Germarie; Sisco, Patrick N; Linder, Sean W

    2015-02-01

    Due to the increasing use of engineered nanomaterials in consumer products, regulatory agencies and other research organizations have determined that the development of robust, reliable, and accurate methodologies to characterize nanoparticles in complex matrices is a top priority. Of particular interest are methods that can separate and determine the size of nanomaterials in samples that contain polydisperse and/or multimodal nanoparticle populations. Asymmetric-flow field flow fractionation (AF4) has shown promise for the separation of nanoparticles with wide size range distributions; however, low analyte recoveries and decreased membrane lifetimes, due to membrane fouling, have limited its application. Herein, we report straightforward strategies to minimize membrane fouling and improve nanoparticle recovery by functionalizing the surface of the nanoparticles, as well as that of the AF4 membranes. Gold nanoparticles (AuNP) were stabilized through functionalization with a phosphine molecule, whereas the surface of the membranes was coated with a negatively charged polystyrenesulfonate polymer. Improved nanoparticle separation, recoveries of 99.1 (±0.5) %, and a detection limit of 6 μg/kg were demonstrated by analyzing AuNP reference materials of different sizes (e.g., 10, 30, and 60 nm), obtained from the National Institute of Standards and Technology (NIST). Furthermore, the stability of the polymer coating and its specificity toward minimizing membrane fouling were demonstrated. PMID:25556296

  19. Local delivery of FTY720 in PCL membrane improves SCI functional recovery by reducing reactive astrogliosis.

    PubMed

    Wang, Junjuan; Wang, Jiaqiu; Lu, Ping; Cai, Youzhi; Wang, Yafei; Hong, Lan; Ren, Hao; Heng, Boon Chin; Liu, Hua; Zhou, Jing; Ouyang, Hongwei

    2015-09-01

    FTY720 has recently been approved as an oral drug for treating relapsing forms of multiple sclerosis, and exerts its therapeutic effect by acting as an immunological inhibitor targeting the sphingosine-1-phosphate (S1P) receptor subtype (S1P1) of T cells. Recently studies demonstrated positive efficacy of this drug on spinal cord injury (SCI) in animal models after systemic administration, albeit with significant adverse side effects. We hereby hypothesize that localized delivery of FTY720 can promote SCI recovery by reducing pathological astrogliosis. The mechanistic functions of FTY720 were investigated in vitro and in vivo utilizing immunofluorescence, histology, MRI and behavioral analysis. The in vitro study showed that FTY720 can reduce astrocyte migration and proliferation activated by S1P. FTY720 can prolong internalization of S1P1 and exert antagonistic effects on S1P1. In vivo study of SCI animal models demonstrated that local delivery of FTY720 with polycaprolactone (PCL) membrane significantly decreased S1P1 expression and glial scarring compared with the control group. Furthermore, FTY720-treated groups exhibited less cavitation volume and neuron loss, which significantly improved recovery of motor function. These findings demonstrated that localized delivery of FTY720 can promote SCI recovery by targeting the S1P1 receptor of astrocytes, provide a new therapeutic strategy for SCI treatment. PMID:26036174

  20. Accidental bilateral Q-switched neodymium laser exposure: treatment and recovery of visual function

    NASA Astrophysics Data System (ADS)

    Zwick, Harry; Stuck, Bruce E.; Dunlap, Weldon; Scales, David K.; Lund, David J.; Ness, James W.

    1998-05-01

    A 21 year old female was accidentally exposed in both eyes when she looked into the 10 cm exit aperture of a military laser designator emitting 1064 nm q-switched (30 ns) pulses at a 10 pulse per second rate. Steroid therapy (methylprednisolone sodium succinate) was initiated within 6 hours post exposure. Initial ophthalmoscopic observation revealed small contained macular hemorrhages in each eye. Fluorescein angiography (FA) showed minimal leakage. Visual acuity was 20/100 and 20/60 in OD and OS respectively. Contrast sensitivity in both eyes was depressed across all spatial frequencies by more than 1.5 log units. At four weeks post exposure, no significant macular scarring was apparent and visual acuity returned to 20/25 in both eyes. Contrast sensitivity had improved to normal levels with a peak at 3 cycles/degree. At one year post exposure, visual acuity was 20/13 in both eyes and measures of contrast sensitivity were within normal limits. During the course of recovery, the patient's fixation shifted from a slightly superior temporal site back to the central foveal region. The foveal lesion sites were still evident by ophthalmoscopy and Amsler grid measurements but were deemed functional when the patient placed small targets generated by the scanning laser ophthalmoscope in the lesion site for discrimination. This outcome indicates remarkable recovery of visual function and suggests that early administration of steroids may assist in preserving the natural neural recovery process of the photoreceptor matrix by minimizing intraretinal scar formation.

  1. Human Hepatocyte Growth Factor Promotes Functional Recovery in Primates after Spinal Cord Injury

    PubMed Central

    Kitamura, Kazuya; Fujiyoshi, Kanehiro; Yamane, Jun-ichi; Toyota, Fumika; Hikishima, Keigo; Nomura, Tatsuji; Funakoshi, Hiroshi; Nakamura, Toshikazu; Aoki, Masashi; Toyama, Yoshiaki; Okano, Hideyuki; Nakamura, Masaya

    2011-01-01

    Many therapeutic interventions for spinal cord injury (SCI) using neurotrophic factors have focused on reducing the area damaged by secondary, post-injury degeneration, to promote functional recovery. Hepatocyte growth factor (HGF), which is a potent mitogen for mature hepatocytes and a mediator of the inflammatory responses to tissue injury, was recently highlighted as a potent neurotrophic factor in the central nervous system. We previously reported that introducing exogenous HGF into the injured rodent spinal cord using a herpes simplex virus-1 vector significantly reduces the area of damaged tissue and promotes functional recovery. However, that study did not examine the therapeutic effects of administering HGF after injury, which is the most critical issue for clinical application. To translate this strategy to human treatment, we induced a contusive cervical SCI in the common marmoset, a primate, and then administered recombinant human HGF (rhHGF) intrathecally. Motor function was assessed using an original open field scoring system focusing on manual function, including reach-and-grasp performance and hand placement in walking. The intrathecal rhHGF preserved the corticospinal fibers and myelinated areas, thereby promoting functional recovery. In vivo magnetic resonance imaging showed significant preservation of the intact spinal cord parenchyma. rhHGF-treatment did not give rise to an abnormal outgrowth of calcitonin gene related peptide positive fibers compared to the control group, indicating that this treatment did not induce or exacerbate allodynia. This is the first study to report the efficacy of rhHGF for treating SCI in non-human primates. In addition, this is the first presentation of a novel scale for assessing neurological motor performance in non-human primates after contusive cervical SCI. PMID:22140459

  2. Association of home care needs and functional recovery among community-dwelling elderly hip fracture patients.

    PubMed

    Wu, Li-Chu; Chou, Ming-Yueh; Liang, Chih-Kuang; Lin, Yu-Te; Ku, Yan-Chiou; Wang, Ruey-Hsia

    2013-01-01

    The aim of this study was to assess the home care needs and task difficulty of community-dwelling aged hip fracture and the association of functional recovery with care received. A cohort of hip fracture patients admitted to orthopedic wards for surgery was collected from August 2009 to December 2010. Patients transferred to long-term care facilities after surgery were excluded. Functional status (feeding, clothing, grooming, bathing, getting in/out of bed, walking, toileting, standing up/sitting down, and walking up/down stairs) and task difficulty for caregivers were recorded at discharge, one week and one month after discharge. In total, 116 patients (mean age: 79.4 ± 8.5 years, 51.7% males) were enrolled. The mean age of primary caregivers was 53.4 ± 14.2 years, and most were daughters or sons (54.3%), spouses (34.5%) or foreign workers (11.0%). The most common care needs were wound care (95.7%), medical visits (94.8%), cleaning and maintaining living quarters (92.2%) and vigilance to ensure patient safety (92.2%). The care needs and task difficulty significantly correlated with physical function before, one week and one month after discharge (r=-0.530, p<0.001; r=-0.326, p=0.001; r=-0.432, p<0.001; r=-0.684, p<0.001; and r=-0.475, p<0.001, respectively). The complex and taxing home care needs of community-dwelling elderly hip fracture patients were significantly associated with functional recovery. Comprehensive geriatric assessment and related special medical services may greatly help caregivers and promote the practice of aging in place. Further study is needed to develop appropriate caregiver education to promote the functional recovery of elderly hip fracture patients at home. PMID:23746577

  3. Disparities between black and white patients in functional improvement after hospitalization for an acute illness.

    PubMed

    Sands, Laura P; Landefeld, C Seth; Ayers, Sandra Moody; Yaffe, Kristine; Palmer, Robert; Fortinsky, Richard; Counsell, Steven R; Covinsky, Kenneth E

    2005-10-01

    The aim of this study was to determine whether older black and white patients experience different rates of improvement in functioning after being acutely hospitalized. Of the 2,364 community-living patients in this prospective cohort study, 25% self-reported their race/ethnicity to be black. The outcomes were improvement in basic activities of daily living (ADLs) and instrumental activities of daily living (IADLs) from admission to discharge and 90 days postdischarge. Multivariable models that included statistical adjustment for age, illness severity, in-hospital social service referral, dementia, admission level of functioning, and change in functioning from 2 weeks before admission were computed to determine whether black and white patients experienced significantly different rates of recovery at discharge and 90 days after discharge in ADL and IADL functioning. Black patients were as likely as white patients to improve in ADL functioning by discharge (odds ratio (OR)=0.97, 95% confidence interval (CI)=0.76-1.24) or by 90 days after discharge (OR=0.95, 95% CI=0.73-1.24) but significantly less likely to improve IADL functioning by discharge (OR=0.72, 95% CI=0.56-0.93) or by 90 days after discharge (OR=0.68, 95% CI=0.51-0.90). The findings suggest that differential rates of recovery in functioning after an acute hospitalization may contribute to racial/ethnic disparities in IADL functioning, which has implications for the setting of future interventions oriented toward reducing these disparities. PMID:16181184

  4. Carbohydrate vs protein supplementation for recovery of neuromuscular function following prolonged load carriage

    PubMed Central

    2010-01-01

    Background This study examined the effect of carbohydrate and whey protein supplements on recovery of neuromuscular function after prolonged load carriage. Methods Ten male participants (body mass: 81.5 ± 10.5 kg, age: 28 ± 9 years, O2max: 55.0 ± 5.5 ml·kg-1·min-1) completed three treadmill walking tests (2 hr, 6.5 km·h-1), carrying a 25 kg backpack consuming 500 ml of either: (1) Placebo (flavoured water) [PLA], (2) 6.4% Carbohydrate Solution [CHO] or (3) 7.0% Whey Protein Solution [PRO]. For three days after load carriage, participants consumed two 500 ml supplement boluses. Muscle performance was measured before and at 0, 24, 48 and 72 h after load carriage, during voluntary and electrically stimulated contractions. Results Isometric knee extension force decreased immediately after load carriage with no difference between conditions. During recovery, isometric force returned to pre-exercise values at 48 h for CHO and PRO but at 72 h for PLA. Voluntary activation decreased immediately after load carriage and returned to pre-exercise values at 24 h in all conditions (P = 0.086). During recovery, there were no differences between conditions for the change in isokinetic peak torque. Following reductions immediately after load carriage, knee extensor and flexor peak torque (60°·s-1) recovered to pre-exercise values at 72 h. Trunk extensor and flexor peak torque (15°·s-1) recovered to pre-exercise values at 24 h (P = 0.091) and 48 h (P = 0.177), respectively. Conclusion Recovery of neuromuscular function after prolonged load carriage is improved with either carbohydrate or whey protein supplementation for isometric contractions but not for isokinetic contractions. PMID:20157419

  5. Space Station Freedom regenerative water recovery system configuration selection

    NASA Technical Reports Server (NTRS)

    Reysa, R.; Edwards, J.

    1991-01-01

    The Space Station Freedom (SSF) must recover water from various waste water sources to reduce 90 day water resupply demands for a four/eight person crew. The water recovery system options considered are summarized together with system configuration merits and demerits, resource advantages and disadvantages, and water quality considerations used to select the SSF water recovery system.

  6. The functional connectivity of semantic task changes in the recovery from stroke aphasia

    NASA Astrophysics Data System (ADS)

    Lu, Jie; Wu, Xia; Yao, Li; Li, Kun-Cheng; Shu, Hua; Dong, Qi

    2007-03-01

    Little is known about the difference of functional connectivity of semantic task between the recovery aphasic patients and normal subject. In this paper, an fMRI experiment was performed in a patient with aphasia following a left-sided ischemic lesion and normal subject. Picture naming was used as semantic activation task in this study. We compared the preliminary functional connectivity results of the recovery aphasic patient with the normal subject. The fMRI data were separated by independent component analysis (ICA) into 90 components. According to our experience and other papers, we chose a region of interest (ROI) of semantic (x=-57, y=15, z=8, r=11mm). From the 90 components, we chose one component as the functional connectivity of the semantic ROI according to one criterion. The criterion is the mean value of the voxels in the ROI. So the component of the highest mean value of the ROI is the functional connectivity of the ROI. The voxel with its value higher than 2.4 was thought as activated (p<0.05). And the functional connectivity networks of the normal subjects were t-tested as group network. From the result, we can know the semantic functional connectivity of stroke aphasic patient and normal subjects are different. The activated areas of the left inferior frontal gyrus and inferior/middle temporal gyrus are larger than the ones of normal. The activated area of the right inferior frontal gyrus is smaller than the ones of normal. The functional connectivity of stroke aphasic patient under semantic condition is different with the normal one. The focus of the stroke aphasic patient can affect the functional connectivity.

  7. Citalopram Enhances Neurovascular Regeneration and Sensorimotor Functional Recovery after Ischemic Stroke in Mice

    PubMed Central

    Espinera, Alyssa R.; Ogle, Molly E.; Gu, Xiaohuan; Wei, Ling

    2013-01-01

    Recent clinical trials have demonstrated that treatment with selective serotonin reuptake inhibitors (SSRIs) after stroke enhances motor functional recovery; however, the underlying mechanisms remain to be further elucidated. We hypothesized that daily administration of the clinical drug citalopram would produce these functional benefits via enhancing neurovascular repair in the ischemic peri-infarct region. To test this hypothesis, focal ischemic stroke was induced in male C57/B6 mice by permanent ligation of distal branches of the middle cerebral artery to the barrel cortex and 7-min occlusion of the bilateral common carotid arteries. Citalopram (10 mg/kg, i.p.) was injected 24 hrs after stroke and daily thereafter. To label proliferating cells, bromo-deoxyuridine was injected daily beginning 3 days after stroke. Immunohistochemical and functional assays were performed to elucidate citalopram-mediated cellular and sensorimotor changes after stroke. Citalopram treatment had no significant effect on infarct formation or edema 3 days after stroke; however, citalopram-treated mice had better functional recovery than saline-treated controls 3 and 14 days after stroke in the adhesive removal test. Increased expression of brain derived neurotrophic factor was detected in the peri-infarct region 7 days after stroke in citalopram-treated animals. The number of proliferating neural progenitor cells and the distance of neuroblast migration from the sub-ventricular zone towards the ischemic cortex were significantly greater in citalopram-treated mice at 7 days after stroke. Immunohistochemical staining and co-localization analysis showed that citalopram-treated animals generated more new neurons and microvessels in the peri-infarct region 21 and 28 days after stroke. Taken together, these results suggest that citalopram promotes post-stroke sensorimotor recovery likely via enhancing neurogenesis, neural cell migration and the microvessel support in the peri-infarct region of

  8. Impact of obesity on recovery and pulmonary functions of obese women undergoing major abdominal gynecological surgeries.

    PubMed

    Moustafa, Ahmed A M; Abdelazim, Ibrahim A

    2016-06-01

    To determine impact of obesity on recovery parameters and pulmonary functions of women undergoing major abdominal gynecological surgeries. Eighty women undergoing major gynecological surgeries were included in this study. Anesthesia was induced by remifentanil bolus, followed by propofol and cisatracurium to facilitate oro-tracheal intubation and was maintained by balanced anesthesia of remifentanil intravenous infusion and sevoflurane in oxygen and air. Time from discontinuation of maintenance anesthesia to fully awake were recorded at 1-min intervals and time from discontinuation of anesthesia until patient was transferred to post-anesthesia care unit (PACU) and discharged from PACU was also recorded. Pulmonary function tests were performed before surgery and repeated 4 h, days 1, 2 and 3 post-operative for evaluation of forced vital capacity, forced expiratory volume in 1 s and peak expiratory flow rate. Occurrence of post-operative complications, re-admission to ICU, hospital stay and morbidities were also recorded. Induction of anesthesia using remifentanil bolus injection resulted in significant decrease of heart rate and arterial pressures compared to pre-operative and pre-induction values. Recovery times were significantly shorter in obese compared to morbidly obese women. Post-operative pulmonary function tests showed significant deterioration compared to pre-operative measures but showed progressive improvement through first 3 post-operative days. Hospital stay was significantly shorter for obese compared to morbid obese women. Obesity delays recovery from general anesthesia, adversely affects pulmonary functions and increases post-operative complications. Remifentanil infusion and sevoflurane could be appropriate combination for obese and morbidly obese women undergoing major surgeries. PMID:26072156

  9. The Impact of Acute Phase Domain-Specific Cognitive Function on Post-stroke Functional Recovery

    PubMed Central

    Park, Jihong; Lee, Gangpyo; Lee, Shi-Uk

    2016-01-01

    Objective To assess whether the cognitive function in the acute stage evaluated by domain-specific neuropsychological assessments would be an independent predictor of functional outcome after stroke. Methods Forty patients underwent 4 domain-specific neuropsychological examinations about 3 weeks after the onset of stroke. The tests included the Boston Naming Test (BNT), the construction recall test (CRT), the construction praxis test (CPT), and the verbal fluency test (VFT). The Korean version of Modified Barthel Index (K-MBI) at 3 months and the modified Rankin Scale (mRS) at 6 months were investigated as functional outcome after stroke. Functional improvement was assessed using the change in K-MBI during the first 3 months and subjects were dichotomized into 'good status' and 'poor status' according to mRS at 6 months. The domain-specific cognitive function along with other possible predictors for functional outcome was examined using regression analysis. Results The z-score of CPT (p=0.044) and CRT (p<0.001) were independent predictors for functional improvement measured by the change in K-MBI during the first 3 months after stroke. The z-score of CPT (p=0.049) and CRT (p=0.048) were also independent predictors of functional status at post-stroke 6 months assessed by mRS. Conclusion Impairment in visuospatial construction and memory within one month after stroke can be an independent prognostic factor of functional outcome. Domain-specific neuropsychological assessments could be considered in patients with stroke in the acute phase to predict long-term functional outcome. PMID:27152270

  10. Snake and Spider Toxins Induce a Rapid Recovery of Function of Botulinum Neurotoxin Paralysed Neuromuscular Junction

    PubMed Central

    Duregotti, Elisa; Zanetti, Giulia; Scorzeto, Michele; Megighian, Aram; Montecucco, Cesare; Pirazzini, Marco; Rigoni, Michela

    2015-01-01

    Botulinum neurotoxins (BoNTs) and some animal neurotoxins (β-Bungarotoxin, β-Btx, from elapid snakes and α-Latrotoxin, α-Ltx, from black widow spiders) are pre-synaptic neurotoxins that paralyse motor axon terminals with similar clinical outcomes in patients. However, their mechanism of action is different, leading to a largely-different duration of neuromuscular junction (NMJ) blockade. BoNTs induce a long-lasting paralysis without nerve terminal degeneration acting via proteolytic cleavage of SNARE proteins, whereas animal neurotoxins cause an acute and complete degeneration of motor axon terminals, followed by a rapid recovery. In this study, the injection of animal neurotoxins in mice muscles previously paralyzed by BoNT/A or /B accelerates the recovery of neurotransmission, as assessed by electrophysiology and morphological analysis. This result provides a proof of principle that, by causing the complete degeneration, reabsorption, and regeneration of a paralysed nerve terminal, one could favour the recovery of function of a biochemically- or genetically-altered motor axon terminal. These observations might be relevant to dying-back neuropathies, where pathological changes first occur at the neuromuscular junction and then progress proximally toward the cell body. PMID:26670253

  11. Structural and functional shifts in zoobenthos induced by organic enrichment — Implications for community recovery potential

    NASA Astrophysics Data System (ADS)

    Villnäs, A.; Perus, J.; Bonsdorff, E.

    2011-01-01

    Habitat change induced by organic enrichment is a growing concern for the sustainability of benthic communities in coastal aquatic environments. This case study describes the spatial and temporal response patterns and the recovery potential of low-diversity benthic communities to organic enrichment at two fish farm locations, during the rearing periods (15 and 20 years, respectively) and the following recovery periods (2 years). The spatial extent of disturbance differed depending on the hydromorphological characteristics of the rearing sites, but degraded macrobenthic communities close to both fish farms were recorded soon after the activity started. Continued organic enrichment resulted in high species turnover-rates and in an altered benthic community composition at both locations. After fish farm abatement, a partial recovery was detected in species richness, but abundance and biomass values were reduced and changes in structural composition remained. Alterations in benthic biological traits were observed at both fish farm locations, implying that organic enrichment might cause changes in benthic community function within low-diversity benthic communities.

  12. 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

  13. Effect of melatonin on the functional recovery from experimental traumatic compression of the spinal cord

    PubMed Central

    Schiaveto-de-Souza, A.; da-Silva, C.A.; Defino, H.L.A.; Bel, E.A.Del

    2013-01-01

    Spinal cord injury is an extremely severe condition with no available effective therapies. We examined the effect of melatonin on traumatic compression of the spinal cord. Sixty male adult Wistar rats were divided into three groups: sham-operated animals and animals with 35 and 50% spinal cord compression with a polycarbonate rod spacer. Each group was divided into two subgroups, each receiving an injection of vehicle or melatonin (2.5 mg/kg, intraperitoneal) 5 min prior to and 1, 2, 3, and 4 h after injury. Functional recovery was monitored weekly by the open-field test, the Basso, Beattie and Bresnahan locomotor scale and the inclined plane test. Histological changes of the spinal cord were examined 35 days after injury. Motor scores were progressively lower as spacer size increased according to the motor scale and inclined plane test evaluation at all times of assessment. The results of the two tests were correlated. The open-field test presented similar results with a less pronounced difference between the 35 and 50% compression groups. The injured groups presented functional recovery that was more evident in the first and second weeks. Animals receiving melatonin treatment presented more pronounced functional recovery than vehicle-treated animals as measured by the motor scale or inclined plane. NADPH-d histochemistry revealed integrity of the spinal cord thoracic segment in sham-operated animals and confirmed the severity of the lesion after spinal cord narrowing. The results obtained after experimental compression of the spinal cord support the hypothesis that melatonin may be considered for use in clinical practice because of its protective effect on the secondary wave of neuronal death following the primary wave after spinal cord injury. PMID:23579633

  14. Electrical stimulation accelerates nerve regeneration and functional recovery in delayed peripheral nerve injury in rats.

    PubMed

    Huang, Jinghui; Zhang, Yongguang; Lu, Lei; Hu, Xueyu; Luo, Zhuojing

    2013-12-01

    The present study aims to investigate the potential of brief electrical stimulation (ES; 3 V, 20 Hz, 20 min) in improving functional recovery in delayed nerve injury repair (DNIR). The sciatic nerve of Sprague Dawley rats was transected, and the repair of nerve injury was delayed for different time durations (2, 4, 12 and 24 weeks). Brief depolarizing ES was applied to the proximal nerve stump when the transected nerve stumps were bridged with a hollow nerve conduit (5 mm in length) after delayed periods. We found that the diameter and number of regenerated axons, the thickness of myelin sheath, as well as the number of Fluoro-Gold retrograde-labeled motoneurons and sensory neurons were significantly increased by ES, suggesting that brief ES to proximal nerve stumps is capable of promoting nerve regeneration in DNIR with different delayed durations, with the longest duration of 24 weeks. In addition, the amplitude of compound muscle action potential (gastrocnemius muscle) and nerve conduction velocity were also enhanced, and gastrocnemius muscle atrophy was partially reversed by brief ES, indicating that brief ES to proximal nerve stump was able to improve functional recovery in DNIR. Furthermore, brief ES was capable of increasing brain-derived neurotrophic factor (BDNF) expression in the spinal cord in DNIR, suggesting that BDNF-mediated neurotrophin signaling might be one of the contributing factors to the beneficial effect of brief ES on DNIR. In conclusion, the present findings indicate the potential of using brief ES as a useful method to improve functional recovery for delayed repair of peripheral nerve lesions. PMID:24118464

  15. 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

  16. The effect of claustrum lesions on human consciousness and recovery of function.

    PubMed

    Chau, Aileen; Salazar, Andres M; Krueger, Frank; Cristofori, Irene; Grafman, Jordan

    2015-11-01

    Crick and Koch proposed that the claustrum plays a crucial role in consciousness. Their proposal was based on the structure and connectivity of the claustrum that suggested it had a role in coordinating a set of diverse brain functions. Given the few human studies investigating this claim, we decided to study the effects of claustrum lesions on consciousness in 171 combat veterans with penetrating traumatic brain injuries. Additionally, we studied the effects of claustrum lesions and loss of consciousness on long-term cognitive abilities. Claustrum damage was associated with the duration, but not frequency, of loss of consciousness, indicating that the claustrum may have an important role in regaining, but not maintaining, consciousness. Total brain volume loss, but not claustrum lesions, was associated with long-term recovery of neurobehavioral functions. Our findings constrain the current understanding of the neurobehavioral functions of the claustrum and its role in maintaining and regaining consciousness. PMID:26186439

  17. Cardiac autonomic function during sleep: effects of alcohol dependence and evidence of partial recovery with abstinence

    PubMed Central

    de Zambotti, Massimiliano; Willoughby, Adrian R.; Baker, Fiona C.; Sugarbaker, David S.; Colrain, Ian M.

    2015-01-01

    Chronic alcoholism is associated with the development of cardiac and peripheral autonomic nervous system (ANS) pathology. The aim of the present study was to evaluate the extent to which recovery in ANS function could be demonstrated over the first 4 months of abstinence. Fifteen alcoholics (7 women) were studied on three occasions: within a month of detoxification, at approximately 2 months post-detox, and at 4 months post-detox. Thirteen control subjects (6 women) were also studied on three occasions with inter-study intervals matching those of the alcoholics. Six alcoholics relapsed, 48.7 ± 27.9 days following the initial PSG session. ANS function was assessed in the first part of stable non-rapid eye movement sleep. Frequency-domain power spectral analysis of heart rate variability (HRV) produced variables including: heart rate (HR), total power (TP; an index representing total HR variability), High Frequency power (HFa; an index reflecting cardiac vagal modulation), HF proportion of total power (HFprop sympathovagal balance), and HF peak frequency (HFpf; an index reflecting respiration rate). Overall, high total and high frequency variability and low sympathovagal balance and myocardial contractility are considered as desired conditions to promote cardiovascular health. At initial assessment, alcoholics had a higher HR (p < 0.001) and respiratory rate (p < 0.01), and lower vagal activity (HFa; p < 0.01) than controls. Alcoholics showed evidence of recovery in HR (p = 0.039) and HFa (p = 0.031) with 4 months of abstinence. Alcoholics with higher TP at the initial visit showed a greater improvement in TP from the initial to the 4-month follow-up session (r = 0.75, p < 0.05). Alcoholics showed substantial recovery in HR and vagal modulation of HRV with 4 months of abstinence, with evidence that the extent of recovery in HRV may be partially determined by the extent of alcohol dependence-related insult to the cardiac ANS system. These data support other studies

  18. Factors Associated With Neurological Recovery of Brainstem Function Following Postoperative Conformal Radiation Therapy for Infratentorial Ependymoma

    SciTech Connect

    Merchant, Thomas E.; Chitti, Ramana M.; Li Chenghong; Xiong Xiaoping; Sanford, Robert A.; Khan, Raja B.

    2010-02-01

    Purpose: To identify risk factors associated with incomplete neurological recovery in pediatric patients with infratentorial ependymoma treated with postoperative conformal radiation therapy (CRT). Methods: The study included 68 patients (median age +- standard deviation of 2.6 +- 3.8 years) who were followed for 5 years after receiving CRT (54-59.4 Gy) and were assessed for function of cranial nerves V to VII and IX to XII, motor weakness, and dysmetria. The mean (+- standard deviation) brainstem dose was 5,487 (+-464) cGy. Patients were divided into four groups representing those with normal baseline and follow-up, those with abnormal baseline and full recovery, those with abnormal baseline and partial or no recovery, and those with progressive deficits at 12 (n = 62 patients), 24 (n = 57 patients), and 60 (n = 50 patients) months. Grouping was correlated with clinical and treatment factors. Results: Risk factors (overall risk [OR], p value) associated with incomplete recovery included gender (male vs. female, OR = 3.97, p = 0.036) and gross tumor volume (GTV) (OR/ml = 1.23, p = 0.005) at 12 months, the number of resections (>1 vs. 1; OR = 23.7, p = 0.003) and patient age (OR/year = 0.77, p = 0.029) at 24 months, and cerebrospinal fluid (CSF) shunting (Yes vs. No; OR = 21.9, p = 0.001) and GTV volume (OR/ml = 1.18, p = 0.008) at 60 months. An increase in GTV correlated with an increase in the number of resections (p = 0.001) and CSF shunting (p = 0.035); the number of resections correlated with CSF shunting (p < 0.0001), and male patients were more likely to undergo multiple tumor resections (p = 0.003). Age correlated with brainstem volume (p < 0.0001). There were no differences in outcome based on the absolute or relative volume of the brainstem that received more than 54 Gy. Conclusions: Incomplete recovery of brainstem function after CRT for infratentorial ependymoma is related to surgical morbidity and the volume and the extent of tumor.

  19. Cardiac autonomic function during sleep: effects of alcohol dependence and evidence of partial recovery with abstinence.

    PubMed

    de Zambotti, Massimiliano; Willoughby, Adrian R; Baker, Fiona C; Sugarbaker, David S; Colrain, Ian M

    2015-06-01

    Chronic alcoholism is associated with the development of cardiac and peripheral autonomic nervous system (ANS) pathology. The aim of the present study was to evaluate the extent to which recovery in ANS function could be demonstrated over the first 4 months of abstinence. Fifteen alcoholics (7 women) were studied on three occasions: within a month of detoxification, at approximately 2 months post-detox, and at 4 months post-detox. Thirteen control subjects (6 women) were also studied on three occasions with inter-study intervals matching those of the alcoholics. Six alcoholics relapsed, 48.7 ± 27.9 days following the initial PSG session. ANS function was assessed in the first part of stable non-rapid eye movement sleep. Frequency-domain power spectral analysis of heart rate variability (HRV) produced variables including: heart rate (HR), total power (TP; an index representing total HR variability), High Frequency power (HFa; an index reflecting cardiac vagal modulation), HF proportion of total power (HFprop sympathovagal balance), and HF peak frequency (HFpf; an index reflecting respiration rate). Overall, high total and high frequency variability and low sympathovagal balance and myocardial contractility are considered as desired conditions to promote cardiovascular health. At initial assessment, alcoholics had a higher HR (p < 0.001) and respiratory rate (p < 0.01), and lower vagal activity (HFa; p < 0.01) than controls. Alcoholics showed evidence of recovery in HR (p = 0.039) and HFa (p = 0.031) with 4 months of abstinence. Alcoholics with higher TP at the initial visit showed a greater improvement in TP from the initial to the 4 month follow-up session (r = 0.75, p < 0.05). Alcoholics showed substantial recovery in HR and vagal modulation of HRV with 4 months of abstinence, with evidence that the extent of recovery in HRV may be partially determined by the extent of alcohol dependence-related insult to the cardiac ANS system. These data support other studies

  20. Role of Neurotrophins in Recovery of Phrenic Motor Function Following Spinal Cord Injury

    PubMed Central

    Sieck, Gary C.; Mantilla, Carlos B.

    2009-01-01

    Many individuals who sustain a cervical spinal cord injury are unable to maintain adequate ventilation due to diaphragm muscle paralysis. These patients become dependent on mechanical ventilators and this situation is associated with ongoing problems with pulmonary clearance, infections, and lung injury leading to significant morbidity and reduced life expectancy. Therefore, functional recovery of rhythmic phrenic activity and the ability to generate expulsive forces would dramatically affect the quality of life of patients with cervical spinal cord injury. Neurotrophins are very promising in that they have been shown to play an important role in modulating functional neuroplasticity. Specifically, brain-derived neurotrophic factor (BDNF) acting via the tropomyosin-related kinase receptor type B (TrkB) has been implicated in neuroplasticity following spinal cord injury. Our central hypothesis is that functional recovery of rhythmic phrenic activity after cervical spinal cord injury is enhanced by an increase in BDNF/TrkB signaling in phrenic motoneurons, providing a novel therapeutic target for patients. PMID:19703592

  1. Carboxy alkyl esters of Uncaria tomentosa augment recovery of sensorineural functions following noise injury.

    PubMed

    Guthrie, O'neil W; Gearhart, Caroline A; Fulton, Sherry; Fechter, Laurence D

    2011-08-17

    This study tested the hypothesis that hydrophilic chemotypes of the medicinal vine Uncaria tomentosa (UT) would facilitate recovery of sensorineural functions following exposure to a damaging level of noise. The particular chemotypes investigated were carboxy alkyl esters (CAE) which are known to exhibit multifunctional cytoprotective properties that include: enhanced cellular DNA repair, antioxidation and anti-inflammation. Long-Evans rats were divided into four treatment groups: vehicle-control, noise-only, CAE-only and CAE+noise. The noise exposure was an 8kHz octave band of noise at 105dB SPL for 4h. Outer hair cell (OHC) function was measured with the cubic 2f(1)-f(2) distortion product otoacoustic emissions (DPOAE) at the start of the study (baseline) and at time-points that corresponded to 1day, 1week and 4weeks post-noise exposure to determine within-group effects. Compound action potentials to puretone stimuli were recorded from the VIIIth craniofacial nerve at 4weeks post-noise exposure to determine between-group effects. Additionally, cytocochleograms were constructed for each row of OHCs from each group. Noise exposure produced significant sensorineural impairments. However, CAE treatment facilitated almost complete recovery of OHC function and limited the magnitude of cell loss. The loss of neural sensitivity to puretone stimuli was inhibited with CAE treatment. Therefore, it appears that the multifunctional cytoprotective capacity of CAE from UT may generalize to otoprotection from acoustic over-exposure. PMID:21762882

  2. Polysialic Acid Glycomimetic Promotes Functional Recovery and Plasticity After Spinal Cord Injury in Mice

    PubMed Central

    Mehanna, Ali; Jakovcevski, Igor; Acar, Ayşe; Xiao, Meifang; Loers, Gabriele; Rougon, Geneviève; Irintchev, Andrey; Schachner, Melitta

    2009-01-01

    Regeneration after injury of the central nervous system is poor due to the abundance of molecules inhibiting axonal growth. Here we pursued to promote regeneration after thoracic spinal cord injury in young adult C57BL/6J mice using peptides which functionally mimic polysialic acid (PSA) and human natural killer cell-1 (HNK-1) glycan, carbohydrate epitopes known to promote neurite outgrowth in vitro. Subdural infusions were performed with an osmotic pump, over 2 weeks. When applied immediately after injury, the PSA mimetic and the combination of PSA and HNK-1 mimetics, but not the HNK-1 mimetic alone, improved functional recovery as assessed by locomotor rating and video-based motion analysis over a 6-week observation period. Better outcome in PSA mimetic-treated mice was associated with higher, as compared with control mice, numbers of cholinergic and glutamatergic terminals and monaminergic axons in the lumbar spinal cord, and better axonal myelination proximal to the injury site. In contrast to immediate post-traumatic application, the PSA mimetic treatment was ineffective when initiated 3 weeks after spinal cord injury. Our data suggest that PSA mimetic peptides can be efficient therapeutic tools improving, by augmenting plasticity, functional recovery when applied during the acute phase of spinal cord injury. PMID:19826404

  3. Recovery of laryngeal function after intraoperative injury to the recurrent laryngeal nerve

    PubMed Central

    Hydman, Jonas; Svensson, Mikael

    2015-01-01

    Loss of function in the recurrent laryngeal nerve (RLN) during thyroid/parathyroid surgery, despite a macroscopically intact nerve, is a challenge which highlights the sensitivity and complexity of laryngeal innervation. Furthermore, the uncertain prognosis stresses a lack of capability to diagnose the reason behind the impaired function. There is a great deal of literature considering risk factors, surgical technique and mechanisms outside the nerve affecting the incidence of RLN paresis during surgery. To be able to prognosticate recovery in cases of laryngeal dysfunction and voice changes after thyroid surgery, the surgeon would first need to define the presence, location, and type of laryngeal nerve injury. There is little data describing the events within the nerve and the neurobiological reasons for the impaired function related to potential recovery and prognosis. In addition, very little data has been presented in order to clarify any differences between the transient and permanent injury of the RLN. This review aims, from an anatomical and neurobiological perspective, to provide an update on the current understandings of surgically-induced injury to the laryngeal nerves. PMID:25713777

  4. Gait and Glasgow Coma Scale scores can predict functional recovery in patients with traumatic brain injury.

    PubMed

    Bilgin, Sevil; Guclu-Gunduz, Arzu; Oruckaptan, Hakan; Kose, Nezire; Celik, Bülent

    2012-09-01

    Fifty-one patients with mild (n = 14), moderate (n = 10) and severe traumatic brain injury (n = 27) received early rehabilitation. Level of consciousness was evaluated using the Glasgow Coma Score. Functional level was determined using the Glasgow Outcome Score, whilst mobility was evaluated using the Mobility Scale for Acute Stroke. Activities of daily living were assessed using the Barthel Index. Following Bobath neurodevelopmental therapy, the level of consciousness was significantly improved in patients with moderate and severe traumatic brain injury, but was not greatly influenced in patients with mild traumatic brain injury. Mobility and functional level were significantly improved in patients with mild, moderate and severe traumatic brain injury. Gait recovery was more obvious in patients with mild traumatic brain injury than in patients with moderate and severe traumatic brain injury. Activities of daily living showed an improvement but this was insignificant except for patients with severe traumatic brain injury. Nevertheless, complete recovery was not acquired at discharge. Multiple regression analysis showed that gait and Glasgow Coma Scale scores can be considered predictors of functional outcomes following traumatic brain injury. PMID:25624828

  5. Recovery of motor and cognitive function after cerebellar lesions in a songbird – role of estrogens

    PubMed Central

    Spence, Rory D.; Zhen, Yin; White, Stephanie; Schlinger, Barney A.; Day, Lainy B.

    2010-01-01

    In addition to its key role in complex motor function, the cerebellum is increasingly recognized to have a role in cognition. Songbirds are particularly good models for the investigation of motor and cognitive processes but little is known about the role of the songbird cerebellum in these processes. To explore cerebellar function in a songbird, we lesioned the cerebellum of adult female zebra finches and examined the effects on a spatial working memory task and on motor function during this task. There is evidence for steroid synthesis in the songbird brain and neurosteroids may have an impact on some forms of neural plasticity in adult songbirds. We therefore hypothesized that neurosteroids would affect motor and cognitive function after a cerebellar injury. We found that cerebellar lesions produced deficits in motor and cognitive aspects of a spatial task. In line with our prediction, birds in which estrogen synthesis was blocked had impaired performance in our spatial task compared with those that had estrogen synthesis blocked but estrogen replaced. There was no clear effect of estrogen replacement on motor function. We also found that lesions induced expression of the estrogen synthetic enzyme aromatase in reactive astrocytes and Bergmann glia around a cerebellar lesion. These data suggest that the cerebellum of songbirds mediates both motor and cognitive function and that estrogens may improve the recovery of cognitive aspects of cerebellar function after injury. PMID:19302157

  6. Counseling the post-radical prostatectomy patients about functional recovery: high predictiveness of current status

    PubMed Central

    Vickers, Andrew J.; Kent, Matthew; Mulhall, John; Sandhu, Jaspreet

    2014-01-01

    Objectives To develop prediction models to help counsel post-radical prostatectomy patients about functional recovery. Methods The study included 2162 patients undergoing radical prostatectomy at a major cancer center who reported urinary and erectile function at one year or at two years and at least 1 prior follow-up at 3, 6, 9, or 12 months. We created logistic regression models predicting function at one or two years on the basis of function at 3, 6, 9, and 12 months (2 years only), with the additional predictors of age, stage, grade, PSA, nerve-sparing status and baseline functional score. Results No variable other than current functional score had a consistent, statistically significant relationship with outcome. The area-under-the-curves for predicting function at 2 years based on current function alone at 3, 6, 9, and 12 months were, respectively, 0.796, 0.831, 0.882, and 0.885 for erectile function and 0.789, 0.862, 0.869 and 0.876 for urinary function. Patients using one pad at 6 months had only a 50% probability of being pad free at 2 years; this dropped to 36% for patients using 2 pads. This suggests that there is an opportunity for early identification and possible referral of patients likely to have long-term urinary dysfunction. Conclusions Assessment of urinary and erectile function in the first post-operative year is strongly predictive of long-term outcome and can guide patient counseling and decisions about rehabilitative treatments. PMID:24824411

  7. Functional and Transcriptomic Recovery of Infarcted Mouse Myocardium Treated with Bone Marrow Mononuclear Cells

    PubMed Central

    Lachtermacher, Stephan; Esporcatte, Bruno L. B.; da Silva de Azevedo Fortes, Fábio; Rocha, Nazareth Novaes; Montalvão, Fabrício; Costa, Patricia C.; Belem, Luciano; Rabischoffisky, Arnaldo; Neto, Hugo C. C. Faria; Vasconcellos, Rita; Iacobas, Dumitru A.; Iacobas, Sanda; Spray, David C.; Thomas, Neil M.; Goldenberg, Regina C. S.; de Carvalho, Antonio C. Campos

    2011-01-01

    Although bone marrow-derived mononuclear cells (BMNC) have been extensively used in cell therapy for cardiac diseases, little mechanistic information is available to support reports of their efficacy. To address this shortcoming, we compared structural and functional recovery and associated global gene expression profiles in post-ischaemic myocardium treated with BMNC transplantation. BMNC suspensions were injected into cardiac scar tissue 10 days after experimental myocardial infarction. Six weeks later, mice undergoing BMNC therapy were found to have normalized antibody repertoire and improved cardiac performance measured by ECG, treadmill exercise time and echocardiography. After functional testing, gene expression profiles in cardiac tissue were evaluated using high-density oligonucleotide arrays. Expression of more than 18% of the 11981 quantified unigenes was significantly altered in the infarcted hearts. BMNC therapy restored expression of 2099 (96.2%) of the genes that were altered by infarction but led to altered expression of 286 other genes, considered to be a side effect of the treatment. Transcriptional therapeutic efficacy, a metric calculated using a formula that incorporates both recovery and side effect of treatment, was 73%. In conclusion, our results confirm a beneficial role for bone marrow-derived cell therapy and provide new information on molecular mechanisms operating after BMNC transplantation on post ischemic heart failure in mice. PMID:21671060

  8. Early renal function recovery and long-term graft survival in kidney transplantation.

    PubMed

    Wan, Susan S; Cantarovich, Marcelo; Mucsi, Istvan; Baran, Dana; Paraskevas, Steven; Tchervenkov, Jean

    2016-05-01

    Following kidney transplantation (KTx), renal function improves gradually until a baseline eGFR is achieved. Whether or not a recipient achieves the best-predicted eGFR after KTx may have important implications for immediate patient management, as well as for long-term graft survival. The aim of this cohort study was to calculate the renal function recovery (RFR) based on recipient and donor eGFR and to evaluate the association between RFR and long-term death-censored graft failure (DCGF). We studied 790 KTx recipients between January 1990 and August 2014. The last donor SCr prior to organ procurement was used to estimate donor GFR. Recipient eGFR was calculated using the average of the best three SCr values observed during the first 3 months post-KTx. RFR was defined as the ratio of recipient eGFR to half the donor eGFR. 53% of recipients had an RFR ≥1. There were 127 death-censored graft failures (16%). Recipients with an RFR ≥1 had less DCGF compared with those with an RFR <1 (HR 0.56; 95% CI 0.37-0.85; P = 0.006). Transplant era, acute rejection, ECD and DGF were also significant determinants of graft failure. Early recovery of predicted eGFR based on donor eGFR is associated with less DCGF after KTx. PMID:26988072

  9. Mesenchymal stem cell therapy promotes the improvement and recovery of renal function in a preclinical model.

    PubMed

    Urt, Antônio Filho; Oliveira, Rodrigo Juliano; Hermeto, Larissa Correa; Pesarini, João Renato; David, Natan de; Cantero, Wilson de Barros; Falcão, Gustavo; Marks, Guido; Antoniolli-Silva, Andréia Conceição Milan Brochado

    2016-06-01

    Acute renal failure (ARF) is an extremely important public health issue in need of novel therapies. The present study aimed to evaluate the capacity of mesenchymal stem cell (MSC) therapy to promote the improvement and recovery of renal function in a preclinical model. Wistar rats were used as the experimental model, and our results show that cisplatin (5mg/kg) can efficiently induce ARF, as measured by changes in biochemical (urea and creatinine) and histological parameters. MSC therapy performed 24h after the administration of chemotherapy resulted in normalized plasma urea and creatinine levels 30 and 45d after the onset of kidney disease. Furthermore, MSC therapy significantly reduced histological changes (intratubular cast formation in protein overload nephropathy and tubular hydropic degeneration) in this ARF model. Thus, considering that current therapies for ARF are merely palliative and that MSC therapy can promote the improvement and recovery of renal function in this model system, we suggest that innovative/alternative therapies involving MSCs should be considered for clinical studies in humans to treat ARF. PMID:27275667

  10. Physiological, Sensory, and Functional Measures in a Model of Wrist Muscle Injury and Recovery

    PubMed Central

    Brown, Lindsay; Brant, Aron; Enns, Deborah; Bryden, Pamela J.

    2008-01-01

    ABSTRACT Purpose: To evaluate the effectiveness of muscle rehabilitation modalities, it is first necessary to develop a model to test measures that would assess physiological, sensory, and functional muscle recovery. This study attempted to develop such a model for wrist injury. Subjects: Healthy male and female adults (n = 25). Methods: Subjects performed wrist muscle damage assessment, soreness, discomfort, difficulty, and functional motor task tests before and 1, 2, and 7 days after eccentric wrist muscle contractions. Wrist-related motor task tests, including the perception of discomfort and difficulty during performance, were also conducted. Results: At 24 hours post–eccentric exercises, wrist extension and flexion force declined (p < 0.05) and soreness (p < 0.05) and circumference (p < 0.05) increased; all returned to normal by 7 days post-exercise. At 24 and 48 hours post-exercise, perception of discomfort and difficulty was elevated during performance of motor tasks (p < 0.05). The completion speed of motor tasks was unaffected at any time post–eccentric exercise (p > 0.05). Conclusions: Loss of wrist muscle force, increased soreness, task discomfort, and difficulty were noted following eccentric exercise. However, subjects appeared able to compensate, such that the speed of completion of motor tasks was not slowed. Longer or more specific motor tasks may be necessary to mimic real work performance decrement and recovery. PMID:20145740

  11. Mesenchymal stem cell therapy promotes the improvement and recovery of renal function in a preclinical model

    PubMed Central

    Urt-Filho, Antônio; Oliveira, Rodrigo Juliano; Hermeto, Larissa Correa; Pesarini, João Renato; de David, Natan; Cantero, Wilson de Barros; Falcão, Gustavo; Marks, Guido; Antoniolli-Silva, Andréia Conceição Milan Brochado

    2016-01-01

    Abstract Acute renal failure (ARF) is an extremely important public health issue in need of novel therapies. The present study aimed to evaluate the capacity of mesenchymal stem cell (MSC) therapy to promote the improvement and recovery of renal function in a preclinical model. Wistar rats were used as the experimental model, and our results show that cisplatin (5mg/kg) can efficiently induce ARF, as measured by changes in biochemical (urea and creatinine) and histological parameters. MSC therapy performed 24h after the administration of chemotherapy resulted in normalized plasma urea and creatinine levels 30 and 45d after the onset of kidney disease. Furthermore, MSC therapy significantly reduced histological changes (intratubular cast formation in protein overload nephropathy and tubular hydropic degeneration) in this ARF model. Thus, considering that current therapies for ARF are merely palliative and that MSC therapy can promote the improvement and recovery of renal function in this model system, we suggest that innovative/alternative therapies involving MSCs should be considered for clinical studies in humans to treat ARF. PMID:27275667

  12. Clinical characteristics of functional recovery after coronary artery bypass graft surgery in Japanese octogenarians

    PubMed Central

    Tobita, Ryo; Iwata, Kentaro; Kamisaka, Kenta; Yuguchi, Satoshi; Tahara, Masayuki; Oura, Keisuke; Morisawa, Tomoyuki; Ohhashi, Satoko; Kumamaru, Megumi; Hanafusa, Yusuke; Kato, Michitaka; Saitoh, Masakazu; Sakurada, Koji; Takahashi, Tetsuya

    2016-01-01

    [Purpose] This study aimed to elucidate characteristics of postoperative physical functional recovery in octogenarians undergoing coronary artery bypass graft surgery. [Subjects and Methods] This was a multi-center, retrospective study. Nine hundred and twenty-seven elective isolated coronary artery bypass graft surgeries were evaluated (746 males and 181 females, mean age: 68.6 years, range: 31–86 years). Participants were stratified according to age < 80 years (n = 840; mean age, 67.1; range, 31–79) or > 80 years (n = 87; mean age, 82.2; range, 80–86). Patient characteristics and postoperative physical functional recovery outcomes were compared between groups. [Results] There was no significant difference between groups when considering the postoperative day at which patients could sit on the edge of the bed, stand at bedside, or walk around the bed. The postoperative day at which patients could walk 100 m independently was later in octogenarians, when compared with non-octogenarians (6.1 ± 3.2 days vs. 4.9 ± 3.9 days). In octogenarians, the percentage of patients who could walk 100 m independently within 8 days after surgery was 79.5%. [Conclusion] A postoperative target time in octogenarians for independent walking, following coronary artery bypass grafting, can be set at approximately 6 days. PMID:27065553

  13. In vivo imaging of functional disruption, recovery and alteration in rat olfactory circuitry after lesion.

    PubMed

    Cross, Donna J; Flexman, Jennifer A; Anzai, Yoshimi; Morrow, Thomas J; Maravilla, Kenneth R; Minoshima, Satoshi

    2006-09-01

    Compensatory changes following disruption of neuronal circuitry have been indicated by previous imaging studies of stroke and other brain injury, but evidence of the pathways involved in such dynamic changes has not been shown in vivo. We imaged rats before and after lesion-induced disruption of the lateral olfactory tract to investigate the subsequent recovery and/or reorganization of functional neuronal circuitry. Serial magnetic resonance imaging was performed following intranasal administration of a paramagnetic track tracer Mn(2+). Images were analyzed using statistical mapping techniques in the stereotactic coordinate system. At 1 week post-lesion, Mn(2+) transport caudal to lesion was reduced as expected, and more importantly, increased transport through the anterior commissure was seen. At 4 weeks post-lesion, there was recovery of transport caudal to lesion, and increased transport through the anterior commissure extended to the contralateral olfactory cortex. Correlation analysis of regional Mn(2+) transport indicated that contralateral enhancement was not simply due to septal window spillover. This study demonstrates for the first time in vivo evidence of compensatory changes in functional neuronal activity to a contralateral pathway through the commissure following brain injury. PMID:16859928

  14. Advanced Echocardiography in Adult Zebrafish Reveals Delayed Recovery of Heart Function after Myocardial Cryoinjury

    PubMed Central

    Kossack, Mandy; Juergensen, Lonny; Fuchs, Dieter; Katus, Hugo A.; Hassel, David

    2015-01-01

    Translucent zebrafish larvae represent an established model to analyze genetics of cardiac development and human cardiac disease. More recently adult zebrafish are utilized to evaluate mechanisms of cardiac regeneration and by benefiting from recent genome editing technologies, including TALEN and CRISPR, adult zebrafish are emerging as a valuable in vivo model to evaluate novel disease genes and specifically validate disease causing mutations and their underlying pathomechanisms. However, methods to sensitively and non-invasively assess cardiac morphology and performance in adult zebrafish are still limited. We here present a standardized examination protocol to broadly assess cardiac performance in adult zebrafish by advancing conventional echocardiography with modern speckle-tracking analyses. This allows accurate detection of changes in cardiac performance and further enables highly sensitive assessment of regional myocardial motion and deformation in high spatio-temporal resolution. Combining conventional echocardiography measurements with radial and longitudinal velocity, displacement, strain, strain rate and myocardial wall delay rates after myocardial cryoinjury permitted to non-invasively determine injury dimensions and to longitudinally follow functional recovery during cardiac regeneration. We show that functional recovery of cryoinjured hearts occurs in three distinct phases. Importantly, the regeneration process after cryoinjury extends far beyond the proposed 45 days described for ventricular resection with reconstitution of myocardial performance up to 180 days post-injury (dpi). The imaging modalities evaluated here allow sensitive cardiac phenotyping and contribute to further establish adult zebrafish as valuable cardiac disease model beyond the larval developmental stage. PMID:25853735

  15. Comparison of growth, serum biochemistries and n-6 fatty acid metabolism in rats fed diets supplemented with high-gamma-linolenic acid safflower oil or borage oil for 90 days.

    PubMed

    Tso, Patrick; Caldwell, Jody; Lee, Dana; Boivin, Gregory P; DeMichele, Stephen J

    2012-06-01

    Recently, steps have been taken to further developments toward increasing gamma-linolenic acid (GLA) concentration and lowering costs in plant seed oils using transgenic technology. Through identification and expression of a fungal delta-6 desaturase gene in the high linoleic acid safflower plant, the seeds from this genetic transformation produce oil with >40% GLA (high GLA safflower oil (HGSO)). The aim of the study was to compare the effects of feeding HGSO to a generally recognized as safe source of GLA, borage oil, in a 90 day safety study in rats. Weanling male and female Sprague-Dawley rats were fed a semi-synthetic, fat free, pelleted diet (AIN93G) supplemented with a 10% (wt/wt) oil blend containing HGSO or borage oil, with equivalent GLA levels. Results demonstrated that feeding diets containing HGSO or borage oil for 90 days had similar biologic effects with regard to growth characteristics, body composition, behavior, organ weight and histology, and parameters of hematology and serum biochemistries in both sexes. Metabolism of the primary n-6 fatty acids in plasma and organ phospholipids was similar, despite minor changes in females. We conclude that HGSO is biologically equivalent to borage oil and provides a safe alternative source of GLA in the diet. PMID:22265940

  16. NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury.

    PubMed

    Yang, Zhaoyang; Zhang, Aifeng; Duan, Hongmei; Zhang, Sa; Hao, Peng; Ye, Keqiang; Sun, Yi E; Li, Xiaoguang

    2015-10-27

    Neural stem cells (NSCs) in the adult mammalian central nervous system (CNS) hold the key to neural regeneration through proper activation, differentiation, and maturation, to establish nascent neural networks, which can be integrated into damaged neural circuits to repair function. However, the CNS injury microenvironment is often inhibitory and inflammatory, limiting the ability of activated NSCs to differentiate into neurons and form nascent circuits. Here we report that neurotrophin-3 (NT3)-coupled chitosan biomaterial, when inserted into a 5-mm gap of completely transected and excised rat thoracic spinal cord, elicited robust activation of endogenous NSCs in the injured spinal cord. Through slow release of NT3, the biomaterial attracted NSCs to migrate into the lesion area, differentiate into neurons, and form functional neural networks, which interconnected severed ascending and descending axons, resulting in sensory and motor behavioral recovery. Our study suggests that enhancing endogenous neurogenesis could be a novel strategy for treatment of spinal cord injury. PMID:26460015

  17. Prognostic Factors Predicting Early Recovery of Pre-fracture Functional Mobility in Elderly Patients With Hip Fracture

    PubMed Central

    Lee, Daegu; Jo, Jae Yong; Jung, Ji Sun

    2014-01-01

    Objective To investigate the prognostic factors predicting the recovery of pre-fracture functional mobility, we evaluated this by the use of ambulatory assistive devices in short-term follow-up. Methods Five hundred and fifty-three elderly patients who had undergone hip fracture operations from January 2006 to June 2013 were enrolled in this retrospective study. Clinical characteristics and predicted factors affecting functional recovery, such as the delay of rehabilitation after the operation, were reviewed. The functional status of the gait was classified as either a bedridden state, wheelchair-bound state, walker gait, single cane gait, and self-gait without any ambulatory assistance device. When this functional grade in patients who recovered after the surgery was compared to before the surgery, this state was considered 'functional recovery'. Results One hundred and ninety-two patients (34.7%) showed recovery of preoperative mobility in the first month after their operation. Multiple logistic regression analysis identified that the following four factors were significantly associated with a deterioration of functional recovery: old age (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.92-0.97), delays in rehabilitation after operation (OR, 0.94; 95% CI, 0.89-0.98), the presence of cognitive dysfunction (OR, 0.36; 95% CI, 0.18-0.71), and trochanteric fracturing (OR, 0.58; 95% CI, 0.36-0.94). Conclusion We found that old age, cognitive dysfunction, trochanteric fracture type, and delay of rehabilitation were associated with the deterioration of functional recovery after a hip fracture operation in the short-term. Therefore, early rehabilitation was required to acquire functional recovery after a hip fracture operation in the short-term. PMID:25566483

  18. The Asparaginyl Endopeptidase Legumain Is Essential for Functional Recovery after Spinal Cord Injury in Adult Zebrafish

    PubMed Central

    Ma, Liping; Shen, Yan-Qin; Khatri, Harsh P.; Schachner, Melitta

    2014-01-01

    Unlike mammals, adult zebrafish are capable of regenerating severed axons and regaining locomotor function after spinal cord injury. A key factor for this regenerative capacity is the innate ability of neurons to re-express growth-associated genes and regrow their axons after injury in a permissive environment. By microarray analysis, we have previously shown that the expression of legumain (also known as asparaginyl endopeptidase) is upregulated after complete transection of the spinal cord. In situ hybridization showed upregulation of legumain expression in neurons of regenerative nuclei during the phase of axon regrowth/sprouting after spinal cord injury. Upregulation of Legumain protein expression was confirmed by immunohistochemistry. Interestingly, upregulation of legumain expression was also observed in macrophages/microglia and neurons in the spinal cord caudal to the lesion site after injury. The role of legumain in locomotor function after spinal cord injury was tested by reducing Legumain expression by application of anti-sense morpholino oligonucleotides. Using two independent anti-sense morpholinos, locomotor recovery and axonal regrowth were impaired when compared with a standard control morpholino. We conclude that upregulation of legumain expression after spinal cord injury in the adult zebrafish is an essential component of the capacity of injured neurons to regrow their axons. Another feature contributing to functional recovery implicates upregulation of legumain expression in the spinal cord caudal to the injury site. In conclusion, we established for the first time a function for an unusual protease, the asparaginyl endopeptidase, in the nervous system. This study is also the first to demonstrate the importance of legumain for repair of an injured adult central nervous system of a spontaneously regenerating vertebrate and is expected to yield insights into its potential in nervous system regeneration in mammals. PMID:24747977

  19. FUNCTIONAL RECOVERY FOLLOWING MOTOR CORTEX LESIONS IN NON-HUMAN PRIMATES: EXPERIMENTAL IMPLICATIONS FOR HUMAN STROKE PATIENTS

    PubMed Central

    Darling, Warren G.; Pizzimenti, Marc A.; Morecraft, Robert J.

    2013-01-01

    This review discusses selected classical works and contemporary research on recovery of contralesional fine hand motor function following lesions to motor areas of the cerebral cortex in non-human primates. Findings from both the classical literature and contemporary studies show that lesions of cortical motor areas induce paresis initially, but are followed by remarkable recovery of fine hand/digit motor function that depends on lesion size and post-lesion training. Indeed, in recent work where considerable quantification of fine digit function associated with grasping and manipulating small objects has been observed, very favorable recovery is possible with minimal forced use of the contralesional limb. Studies of the mechanisms underlying recovery have shown that following small lesions of the digit areas of primary motor cortex (M1), there is expansion of the digit motor representations into areas of M1 that did not produce digit movements prior to the lesion. However, after larger lesions involving the elbow, wrist and digit areas of M1, no such expansion of the motor representation was observed, suggesting that recovery was due to other cortical or subcortical areas taking over control of hand/digit movements. Recently, we showed that one possible mechanism of recovery after lesion to the arm areas of M1 and lateral premotor cortex is enhancement of corticospinal projections from the medially located supplementary motor area (M2) to spinal cord laminae containing neurons which have lost substantial input from the lateral motor areas and play a critical role in reaching and digit movements. Because human stroke and brain injury patients show variable, and usually poorer, recovery of hand motor function than that of nonhuman primates after motor cortex damage, we conclude with a discussion of implications of this work for further experimentation to improve recovery of hand function in human stroke patients. PMID:21960307

  20. Vagus nerve stimulation during rehabilitative training enhances recovery of forelimb function after ischemic stroke in aged rats.

    PubMed

    Hays, Seth A; Ruiz, Andrea; Bethea, Thelma; Khodaparast, Navid; Carmel, Jason B; Rennaker, Robert L; Kilgard, Michael P

    2016-07-01

    Advanced age is associated with a higher incidence of stroke and worse functional outcomes. Vagus nerve stimulation (VNS) paired with rehabilitative training has emerged as a potential method to improve recovery after brain injury but to date has only been evaluated in young rats. Here, we evaluated whether VNS paired with rehabilitative training would improve recovery of forelimb function after ischemic lesion of the motor cortex in rats 18 months of age. Rats were trained to perform the isometric pull task, an automated, quantitative measure of volitional forelimb strength. Once proficient, rats received an ischemic lesion of the motor cortex and underwent rehabilitative training paired with VNS for 6 weeks. VNS paired with rehabilitative training significantly enhances recovery of forelimb function after lesion. Rehabilitative training without VNS results in a 34% ± 19% recovery, whereas VNS paired with rehabilitative training yields a 98% ± 8% recovery of prelesion of forelimb function. VNS does not significantly reduce lesion size. These findings demonstrate that VNS paired with rehabilitative training enhances motor recovery in aged subjects in a model of stroke and may suggest that VNS therapy may effectively translate to elderly stroke patients. PMID:27255820

  1. Functional recovery from sciatic nerve crush lesion in the rat correlates with individual differences in responses to chronic intermittent stress.

    PubMed

    van Meeteren, N L; Brakkee, J H; Helders, P J; Wiegant, V M; Gispen, W H

    1997-06-15

    The aim of the present study was to monitor the influence of chronic stress on functional recovery from a sciatic nerve crush lesion in the rat. Male Wistar rats underwent standard unilateral sciatic nerve crush. Subsequently, chronic stress was induced during the recovery phase using a daily 30 min shock box session where rats received three electric footshocks each session (0.5 sec, 1 mA). Reduced body weight gain, adrenal gland hypertrophy, and thymus involution indicated that the stress rats were chronically stressed. Evaluation of sensorimotor function revealed significant differences in recovery between control and stress groups. Correlational analysis of individual stress rats indicated that recovery of the walking pattern was negatively correlated with adrenal gland and medulla enlargement, thymus involution, and plasma levels of adrenocorticotrophic hormone (ACTH) and corticosterone 45 min following the final stress session. In control rats, the index of sciatic nerve function (SF index, expressed as the difference between the injured paw and the intact contralateral paw as a percentage) was significantly correlated with adrenal medulla weight only. The present study reveals that chronic intermittent footshock stress impedes sensorimotor recovery following a sciatic nerve crush lesion and that the consequences of chronic intermittent stress are individually determined. We suggest that the quality of functional locomotor recovery after nerve crush lesion is related to the adaptive capacity or coping style of the individual rat. PMID:9210522

  2. Recovery of language function in Korean-Japanese crossed bilingual aphasia following right basal ganglia hemorrhage.

    PubMed

    Lee, Boram; Moon, Hyun Im; Lim, Sung Hee; Cho, Hyesuk; Choi, Hyunjoo; Pyun, Sung-Bom

    2016-06-01

    Few studies have investigated language recovery patterns and the mechanisms of crossed bilingual aphasia following a subcortical stroke. In particular, Korean-Japanese crossed bilingual aphasia has not been reported. A 47-year-old, right-handed man was diagnosed with an extensive right basal ganglia hemorrhage. He was bilingual, fluent in both Korean and Japanese. After his stroke, the patient presented with crossed aphasia. We investigated changes in the Korean (L1) and Japanese (L2) language recovery patterns. Both Korean and Japanese versions of the Western Aphasia Battery (WAB) were completed one month after the stroke, and functional magnetic resonance imaging (fMRI) was performed using picture-naming tasks. The WAB showed a paradoxical pattern of bilingual aphasia, with an aphasia quotient (AQ) of 32 for Korean and 50.6 for Japanese, with Broca's aphasia. The patient scored better in the Japanese version of all domains of the tests. The fMRI study showed left lateralized activation in both language tasks, especially in the inferior frontal gyrus. After six months of language therapy targeting L1, the Korean-WAB score improved significantly, while the Japanese-WAB score showed slight improvement. In this case, the subcortical lesion contributed to crossed bilingual aphasia more highly affecting L1 due to loss of the cortico-subcortical control mechanism in the dominant hemisphere. The paradoxical pattern of bilingual aphasia disappeared after lengthy language therapy targeting L1, and the therapy effect did not transfer to L2. Language recovery in L1 might have been accomplished by reintegrating language networks, including the contralesional language homologue area in the left hemisphere. PMID:26853846

  3. Intrathecal Morphine Attenuates Recovery of Function after a Spinal Cord Injury

    PubMed Central

    Moreno, Georgina; Woller, Sarah; Puga, Denise; Hoy, Kevin; Balden, Robyn; Grau, James W.

    2009-01-01

    Abstract Prior work has shown that a high dose (20 mg/kg) of systemic morphine, required to produce significant analgesia in the acute phase of a contusion injury, undermines the long-term health of treated subjects and increases lesion size. Moreover, a single dose of systemic morphine in the early stage of injury (24 h post-injury) led to symptoms of neuropathic pain 3 weeks later, in the chronic phase. The present study examines the locus of the effects using intrathecal morphine administration. Subjects were treated with one of three doses (0, 30, or 90 μg) of intrathecal morphine 24 h after a moderate contusion injury. The 90-μg dose produced significant analgesia when subjects were exposed to noxious stimuli (thermal and incremented shock) below the level of injury. Yet, despite analgesic efficacy, intrathecal morphine significantly attenuated the recovery of locomotor function and increased lesion size rostral to the injury site. A single dose of 30 or 90 μg of intrathecal morphine also decreased weight gain, and more than doubled the incidence of mortality and autophagia when compared to vehicle-treated controls. Morphine is one of the most effective pharmacological agents for the treatment of neuropathic pain and, therefore, is indispensable for the spinally injured. Treatment can, however, adversely affect the recovery process. A morphine-induced attenuation of recovery may result from increases in immune cell activation and, subsequently, pro-inflammatory cytokine concentrations in the contused spinal cord. PMID:19388818

  4. CatWalk gait analysis in assessment of functional recovery after sciatic nerve injury.

    PubMed

    Bozkurt, A; Deumens, R; Scheffel, J; O'Dey, D M; Weis, J; Joosten, E A; Führmann, T; Brook, G A; Pallua, N

    2008-08-15

    Following peripheral nerve injury repair, improved behavioural outcome may be the most important evidence of functionality of axon regeneration after any repair strategy. A range of behavioural testing paradigms have been developed for peripheral nerve injury research. Complete injury of the adult rat sciatic nerve is frequently used in combination with walking track analysis. Despite its wide-spread use, these walking track analyses are unsuitable for the simultaneous assessment of both dynamic and static gait parameters. Conversely, a novel automated gait analysis system, i.e. CatWalk can simultaneously measure dynamic as well as static gait parameters and, importantly, it's easy to control for the speed of locomotion which can strongly affect gait parameters. In a previous study, CatWalk was already successfully used to examine deficits in both dynamic and static gait parameters using the sciatic nerve lesion model with a 1cm gap characterized by absence of recovery [Deumens R, Jaken RJ, Marcus MA, Joosten EA. The CatWalk gait analysis in assessment of both dynamic and static gait changes after adult rat sciatic nerve resection. J Neurosci Methods 2007;164:120-30]. Using the sciatic nerve crush injury model (validated with the static sciatic index) and a follow-up period of 12 weeks, we now show that CatWalk can also measure behavioural recovery. In particular dynamic gait parameters, coordination measures, and the intensity of paw prints are of interest in detecting recovery as far as these parameters completely return to pre-operative values after crush injury. We conclude that CatWalk can be used as a complementary approach to other behavioural testing paradigms to assess clinically relevant behavioural benefits, with a main advantage that CatWalk demonstrates both static and dynamic gait parameters at the same time. PMID:18577402

  5. Functionalization of micromodels with kaolinite for investigation of low salinity oil-recovery processes.

    PubMed

    Song, Wen; Kovscek, Anthony R

    2015-08-21

    Sandstone formations are ubiquitous in both aquifers and petroleum reservoirs, of which clay is a major constituent. The release of clay particles from pore surfaces as a result of reduced injection fluid salinity can greatly modify the recovery of hydrocarbons from subsurface formations by shifting the wettability properties of the rock. In this paper we demonstrate a microfluidic approach whereby kaolinite is deposited into a two-dimensional microfluidic network (micromodel) to enable direct pore-scale, real-time visualization of fluid-solid interactions with representative pore-geometry and realistic surface interactions between the reservoir fluids and the formation rock. Structural characterization of deposited kaolinite particles agrees well with natural modes of occurrence in Berea sandstones; hence, the clay deposition method developed in this work is validated. Specifically, more than 90% of the deposited clay particles formed pore-lining structures and the remainder formed pore bridging structures. Further, regions of highly concentrated clay deposition likely leading to so-called Dalmatian wetting properties were found throughout the micromodel. Two post-deposition treatments are described whereby clay is adhered to the silicon surface reversibly and irreversibly resulting in microfluidic systems that are amenable to studies on (i) the fundamental mechanisms governing the increased oil recovery during low salinity waterfloods and (ii) the effect of a mixed-wet surface on oil recovery, respectively. The reversibly functionalized platform is used to determine the conditions at which stably adhered clay particles detach. Specifically, injection brine salinity below 6000 ppm of NaCl induced kaolinite particle release from the silicon surface. Furthermore, when applied to an aged system with crude oil, the low salinity waterflood recovered an additional 14% of the original oil in place compared to waterflooding with the formation brine. PMID:26151880

  6. Longitudinal Assessment of Motor Recovery of Contralateral Hand after Basal Ganglia Infarction Using Functional Magnetic Resonance Imaging

    PubMed Central

    Fu, Yue; Zhang, Quan; Yu, Chunshui; Zhang, Jing; Wang, Ning; Zuo, Shanhuai; Zhang, Ningnannan

    2016-01-01

    We used functional fMRI to study the brain activation during active finger movements at different time points during the recovery phase following basal ganglia infarction. Four hemiplegic patients with basal ganglia infarction were serially evaluated at different time points spanning the acute and chronic phase using fMRI. To evaluate motor recovery, the patients were asked to perform functional tasks arranged in a block design manner with their hand. On follow-up (chronic phase), three patients achieved significant recovery of motor function of affected limbs. Activation of bilateral sensorimotor cortex (SMC) was observed in two of these patients, while activation of cerebellum was observed in all patients. No remarkable recovery of motor function was noted in one patient with left basal ganglia infarction. In this patient, the activation domain was located in SMC of both sides in acute phase and in ipsilateral SMC in chronic phase. Contralateral SMC appears to be involved in the functional rehabilitation following basal ganglia infarction. The cerebellum may act as an intermediary during functional recovery following basal ganglia infarction. The activation domain associated with active finger movement may be bilateral in acute phase; one patient was ipsilateral in the chronic stage. PMID:27069924

  7. Longitudinal Assessment of Motor Recovery of Contralateral Hand after Basal Ganglia Infarction Using Functional Magnetic Resonance Imaging.

    PubMed

    Fu, Yue; Zhang, Quan; Yu, Chunshui; Zhang, Jing; Wang, Ning; Zuo, Shanhuai; Zhang, Ningnannan

    2016-01-01

    We used functional fMRI to study the brain activation during active finger movements at different time points during the recovery phase following basal ganglia infarction. Four hemiplegic patients with basal ganglia infarction were serially evaluated at different time points spanning the acute and chronic phase using fMRI. To evaluate motor recovery, the patients were asked to perform functional tasks arranged in a block design manner with their hand. On follow-up (chronic phase), three patients achieved significant recovery of motor function of affected limbs. Activation of bilateral sensorimotor cortex (SMC) was observed in two of these patients, while activation of cerebellum was observed in all patients. No remarkable recovery of motor function was noted in one patient with left basal ganglia infarction. In this patient, the activation domain was located in SMC of both sides in acute phase and in ipsilateral SMC in chronic phase. Contralateral SMC appears to be involved in the functional rehabilitation following basal ganglia infarction. The cerebellum may act as an intermediary during functional recovery following basal ganglia infarction. The activation domain associated with active finger movement may be bilateral in acute phase; one patient was ipsilateral in the chronic stage. PMID:27069924

  8. Watering, fertilization, and slurry inoculation promote recovery of biological crust function in degraded soils.

    PubMed

    Maestre, Fernando T; Martín, Noelia; Díez, Beatriz; López-Poma, Rosario; Santos, Fernando; Luque, Ignacio; Cortina, Jordi

    2006-10-01

    Biological soil crusts are very sensitive to human-induced disturbances and are in a degraded state in many areas throughout their range. Given their importance in the functioning of arid and semiarid ecosystems, restoring these crusts may contribute to the recovery of ecosystem functionality in degraded areas. We conducted a factorial microcosm experiment to evaluate the effects of inoculation type (discrete fragments vs slurry), fertilization (control vs addition of composted sewage sludge), and watering frequency (two vs five times per week) on the cyanobacterial composition, nitrogen fixation, chlorophyll content, and net CO2 exchange rate of biological soil crusts inoculated on a semiarid degraded soil from SE Spain. Six months after the inoculation, the highest rates of nitrogen fixation and chlorophyll a content were found when the biological crusts were inoculated as slurry, composted sewage sludge was added, and the microcosms were watered five times per week. Net CO2 exchange rate increased when biological crusts were inoculated as slurry and the microcosms were watered five times per week. Denaturing gradient gel electrophoresis fingerprints and phylogenetic analyses indicated that most of the cyanobacterial species already present in the inoculated crust had the capability to spread and colonize the surface of the surrounding soil. These analyses showed that cyanobacterial communities were less diverse when the microcosms were watered five times per week, and that watering frequency (followed in importance by the addition of composted sewage sludge and inoculation type) was the treatment that most strongly influenced their composition. Our results suggest that the inoculation of biological soil crusts in the form of slurry combined with the addition of composted sewage sludge could be a suitable technique to accelerate the recovery of the composition and functioning of biological soil crusts in drylands. PMID:16710791

  9. The administration of intermittent parathyroid hormone affects functional recovery from trochanteric fractured neck of femur

    PubMed Central

    Chesser, T. J. S.; Fox, R.; Harding, K.; Halliday, R.; Barnfield, S.; Willett, K.; Lamb, S.; Yau, C.; Javaid, M. K.; Gray, A. C.; Young, J.; Taylor, H.; Shah, K.; Greenwood, R.

    2016-01-01

    Aims We wished to assess the feasibility of a future randomised controlled trial of parathyroid hormone (PTH) supplements to aid healing of trochanteric fractures of the hip, by an open label prospective feasibility and pilot study with a nested qualitative sub study. This aimed to inform the design of a future powered study comparing the functional recovery after trochanteric hip fracture in patients undergoing standard care, versus those who undergo administration of subcutaneous injection of PTH for six weeks. Patients and Methods We undertook a pilot study comparing the functional recovery after trochanteric hip fracture in patients 60 years or older, admitted with a trochanteric hip fracture, and potentially eligible to be randomised to either standard care or the administration of subcutaneous PTH for six weeks. Our desired outcomes were functional testing and measures to assess the feasibility and acceptability of the study. Results A total of 724 patients were screened, of whom 143 (20%) were eligible for recruitment. Of these, 123 were approached and 29 (4%) elected to take part. However, seven patients did not complete the study. Compliance with the injections was 11 out of 15 (73%) showing the intervention to be acceptable and feasible in this patient population. Take home message: Only 4% of patients who met the inclusion criteria were both eligible and willing to consent to a study involving injections of PTH, so delivering this study on a large scale would carry challenges in recruitment and retention. Methodological and sample size planning would have to take this into account. PTH administration to patients to enhance fracture healing should still be considered experimental. Cite this article: Bone Joint J 2016;98-B:840–5. PMID:27235530

  10. Surface functionalized nanostructured ceramic sorbents for the effective collection and recovery of uranium from seawater.

    PubMed

    Chouyyok, Wilaiwan; Pittman, Jonathan W; Warner, Marvin G; Nell, Kara M; Clubb, Donald C; Gill, Gary A; Addleman, R Shane

    2016-07-28

    The ability to collect uranium from seawater offers the potential for a nearly limitless fuel supply for nuclear energy. We evaluated the use of functionalized nanostructured sorbents for the collection and recovery of uranium from seawater. Extraction of trace minerals from seawater and brines is challenging due to the high ionic strength of seawater, low mineral concentrations, and fouling of surfaces over time. We demonstrate that rationally assembled sorbent materials that integrate high affinity surface chemistry and high surface area nanostructures into an application relevant micro/macro structure enables collection performance that far exceeds typical sorbent materials. High surface area nanostructured silica with surface chemistries composed of phosphonic acid, phosphonates, 3,4 hydroxypyridinone, and EDTA showed superior performance for uranium collection. A few phosphorous-based commercial resins, specifically Diphonix and Ln Resin, also performed well. We demonstrate an effective and environmentally benign method of stripping the uranium from the high affinity sorbents using inexpensive nontoxic carbonate solutions. The cyclic use of preferred sorbents and acidic reconditioning of materials was shown to improve performance. Composite thin films composed of the nanostructured sorbents and a porous polymer binder are shown to have excellent kinetics and good capacity while providing an effective processing configuration for trace mineral recovery from solutions. Initial work using the composite thin films shows significant improvements in processing capacity over the previously reported sorbent materials. PMID:27184739

  11. Functional motor recovery is improved due to local placement of GDNF microspheres after delayed nerve repair.

    PubMed

    Wood, Matthew D; Gordon, Tessa; Kemp, Stephen W P; Liu, Edward H; Kim, Howard; Shoichet, Molly S; Borschel, Gregory H

    2013-05-01

    The majority of bioengineering strategies to promote peripheral nerve regeneration after injury have focused on therapies to bridge large nerve defects while fewer therapies are being developed to treat other nerve injuries, such as nerve transection. We constructed delivery systems using fibrin gels containing either free GDNF or polylactide-glycolic acid (PLGA) microspheres with GDNF to treat delayed nerve repair, where ELISA verified GDNF release. We determined the formulation of microspheres containing GDNF that optimized nerve regeneration and functional recovery in a rat model of delayed nerve repair. Experimental groups underwent delayed nerve repair and treatment with GDNF microspheres in fibrin glue at the repair site or control treatments (empty microspheres or free GDNF without microspheres). Contractile muscle force, muscle mass, and MUNE were measured 12 weeks following treatment, where GDNF microspheres (2 weeks formulation) were superior compared to either no GDNF or short-term release of free GDNF to nerve. Nerve histology distal to the repair site demonstrated increased axon counts and fiber diameters due to GDNF microspheres (2 weeks formulation). GDNF microspheres partially reversed the deleterious effects of chronic nerve injury, and recovery was slightly favored with the 2 weeks formulation compared to the 4 weeks formulation. PMID:23239194

  12. Local Administration of AAV-BDNF to Subventricular Zone Induces Functional Recovery in Stroke Rats

    PubMed Central

    Yu, Seong-Jin; Tseng, Kuan-Yin; Shen, Hui; Harvey, Brandon K.; Airavaara, Mikko; Wang, Yun

    2013-01-01

    Migration of new neuroprogenitor cells (NPCs) from the subventricular zone (SVZ) plays an important role in neurorepair after injury. Previous studies have shown that brain derived neurotrophic factor (BDNF) enhances the migration of NPCs from SVZ explants in neonatal mice in vitro. The purpose of this study was to identify the role of BDNF in SVZ cells using AAV-BDNF in an animal model of stroke. BDNF protein production after AAV‐BDNF infection was verified in primary neuronal culture. AAV-BDNF or AAV-RFP was injected into the left SVZ region of adult rats at 14 days prior to right middle cerebral artery occlusion (MCAo). SVZ tissues were collected from the brain and placed in Metrigel cultures 1 day after MCAo. Treatment with AAV-BDNF significantly increased the migration of SVZ cells in the stroke brain in vitro. In another set of animals, AAV-GFP was co-injected with AAV-BDNF or AAV-RFP to label cells in left SVZ prior to right MCAo. Local administration of AAV-BDNF significantly enhanced recovery of locomotor function and migration of GFP-positive cells from the SVZ toward the lesioned hemisphere in stroke rats. Our data suggest that focal administration of AAV-BDNF to the SVZ increases behavioral recovery post stroke, possibly through the enhancement of migration of cells from SVZ in stroke animals. Regional manipulation of BDNF expression through AAV may be a novel approach for neurorepair in stroke brains. PMID:24312581

  13. 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

  14. Anterior thalamic nuclei lesions and recovery of function: Relevance to cognitive thalamus.

    PubMed

    Dalrymple-Alford, John C; Harland, Bruce; Loukavenko, Elena A; Perry, Brook; Mercer, Stephanie; Collings, David A; Ulrich, Katharina; Abraham, Wickliffe C; McNaughton, Neil; Wolff, Mathieu

    2015-07-01

    Injury to the anterior thalamic nuclei (ATN) and their neural connections is the most consistent neuropathology associated with diencephalic amnesia. ATN lesions in rats produce memory impairments that support a key role for this region within an extended hippocampal system of complex overlapping neural connections. Environmental enrichment is a therapeutic tool that produces substantial, although incomplete, recovery of memory function after ATN lesions, even after the lesion-induced deficit has become established. Similarly, the neurotrophic agent cerebrolysin, also counters the negative effects of ATN lesions. ATN lesions substantially reduce c-Fos expression and spine density in the retrosplenial cortex, and reduce spine density on CA1 neurons; only the latter is reversed by enrichment. We discuss the implications of this evidence for the cognitive thalamus, with a proposal that there are genuine interactions among different but allied thalamo-cortical systems that go beyond a simple summation of their separate effects. PMID:25637779

  15. A functional analysis of verbal delay in preschool children: Implications for prevention and total recovery

    PubMed Central

    Drash, Philip W.; Tudor, Roger M.

    1993-01-01

    Delays in acquiring age-appropriate verbal repertoires in preschool children with no known organic etiology may be explained by defective or absent behavior-environmental contingencies. This paper presents six possible behavioral paradigms that describe verbal episodes between parents and their preschool children and how these interactions may inhibit or prevent the acquisition of verbal behavior. These paradigms are contrasted with parent-child interactions that typically result in age-appropriate verbal repertoires. Identifying the reinforcement contingencies that produce delays in acquisition of verbal behavior could lead to the development of more effective behavioral programs for remediating nonorganic language delay. Recommendations for prevention, treatment and total recovery from functional verbal delay and associated mental retardation are presented. The relation between contingency-shaped and rule-governed behavior in the shaping of verbal behavior is discussed. PMID:22477077

  16. Two is More Than One: How to Combine Brain Stimulation Rehabilitative Training for Functional Recovery?

    PubMed Central

    Koganemaru, Satoko; Fukuyama, Hidenao; Mima, Tatsuya

    2015-01-01

    A number of studies have shown that non-invasive brain stimulation has an additional effect in combination with rehabilitative therapy to enhance functional recovery than either therapy alone. The combination enhances use-dependent plasticity induced by repetitive training. The neurophysiological mechanism of the effects of this combination is based on associative plasticity. However, these effects were not reported in all cases. We propose a list of possible strategies to achieve an effective association between rehabilitative training with brain stimulation for plasticity: (1) control of temporal aspect between stimulation and task execution; (2) the use of a shaped task for the combination; (3) the appropriate stimulation of neuronal circuits where use-dependent plastic changes occur; and (4) phase synchronization between rhythmically patterned brain stimulation and task-related patterned activities of neurons. To better utilize brain stimulation in neuro-rehabilitation, it is important to develop more effective techniques to combine them. PMID:26617497

  17. Enhanced regeneration and functional recovery after spinal root avulsion by manipulation of the proteoglycan receptor PTPσ

    PubMed Central

    Li, Heng; Wong, Connie; Li, Wen; Ruven, Carolin; He, Liumin; Wu, Xiaoli; Lang, Bradley T.; Silver, Jerry; Wu, Wutian

    2015-01-01

    Following root avulsion, spinal nerves are physically disconnected from the spinal cord. Severe motoneuron death and inefficient axon regeneration often result in devastating motor dysfunction. Newly formed axons need to extend through inhibitory scar tissue at the CNS-PNS transitional zone before entering into a pro-regenerative peripheral nerve trajectory. CSPGs are dominant suppressors in scar tissue and exert inhibition via neuronal receptors including PTPσ. Previously, a small peptide memetic of the PTPσ wedge region named ISP (Intracellular Sigma Peptide) was generated, and its capabilities to target PTPσ and relieve CSPG inhibition were validated. Here, we demonstrate that after ventral root avulsion and immediate re-implantation, modulation of PTPσ by systemic delivery of ISP remarkably enhanced regeneration. ISP treatment reduced motoneuron death, increased the number of axons regenerating across scar tissue, rebuilt healthy neuromuscular junctions and enhanced motor functional recovery. Our study shows that modulation of PTPσ is a potential therapeutic strategy for root avulsion. PMID:26464223

  18. Uncoupling PSD-95 interactions leads to rapid recovery of cortical function after focal stroke

    PubMed Central

    Srejic, Luka R; Hutchison, William D; Aarts, Michelle M

    2013-01-01

    Since the most significant ischemic sequelae occur within hours of stroke, it is necessary to understand how neuronal function changes during this time. While histologic and behavioral models show the extent of stroke-related damage, only in vivo recordings can illustrate changes in brain activity during stroke and validate effectiveness of neuroprotective compounds. Spontaneous and evoked field potentials (fEPs) were recorded in the deep layers of the cortex with a linear microelectrode array for 3 hours after focal stroke in anesthetized rats. Tat-NR2B9c peptide, which confers neuroprotection by uncoupling the PSD-95 protein from N-methyl-D-aspartate receptor (NMDAR), was administered 5 minutes before ischemia. Evoked field potentials were completely suppressed within 3 minutes of infarct in all ischemic groups. Evoked field potential recovery after stroke in rats treated with Tat-NR2B9c (83% of baseline) was greater compared with stroke-only (61% of baseline) or control peptide (Tat-NR2B-AA; 67% of baseline) groups (P<0.001). Electroencephalography (EEG) power was higher in Tat-NR2B9c-treated animals at both 20 minutes and 1 hour (50% and 73% of baseline, respectively) compared with stroke-only and Tat-NR2B-AA-treated rats (P<0.05). Tat-NR2B9c significantly reduces stroke-related cortical dysfunction as evidenced by greater recovery of fEPs and EEG power; illustrating the immediate effects of the compound on poststroke brain function. PMID:24022623

  19. Short-term galvanic vestibular stimulation promotes functional recovery and neurogenesis in unilaterally labyrinthectomized rats.

    PubMed

    Shaabani, Moslem; Lotfi, Yones; Karimian, Seyed Morteza; Rahgozar, Mehdi; Hooshmandi, Mehdi

    2016-10-01

    Current experimental research on the therapeutic effects of galvanic vestibular stimulation (GVS) has mainly focused on neurodegenerative disorders. However, it primarily stimulates the vestibular nuclei and could be potentially effective in modulating imbalance between them in the case of unilateral labyrinthectomy (UL). Fifty male Wistar rats (180-220g) were used in 5 groups of 10: intact, sham, right-UL (RUL; without intervention), and two other right-UL groups with GVS intervention [one group treated with low rate GVS (GVS.LF; 6-7Hz), and the other treated with high rate GVS (GVS.HF; 17-18Hz)]. The UL models were prepared by intratympanic injection of sodium arsanilate. GVS protocols were implemented 30min/day and continued for 14 days via ring-shaped copper electrodes inserted subcutaneously over each mastoid. Functional recovery was assessed by several postural tests including support surface area, landing and air-righting reflexes, and rotarod procedure. Immunohistochemical investigations were performed on ipsi- and contra-lesional medial vestibular nuclei (MVN) using bromodeoxyuridine (BrdU) and Ki67, as markers of cell proliferation. Behavioral evaluations showed significant functional recovery of GVS-treated groups compared to RUL group. The percent of marked cells with BrdU and Ki67 were significantly higher in the ipsilesional MVN of both GVS-treated groups compared with other groups. Our findings confirmed the effectiveness of GVS-intervention in accelerating static and dynamic vestibular compensation. This could be explained by the cell proliferation in ipsilesional MVN cells and rapid rebalancing of the VNs and the modulation of their motor outputs. Therefore, GVS could be promising for rehabilitating patients with unilateral vestibular weakness. PMID:27444558

  20. Acetyl salicylic acid locally enhances functional recovery after sciatic nerve transection in rat.

    PubMed

    Mohammadi, Rahim; Amini, Keyvan; Abdollahi-Pirbazari, Mehdi; Yousefi, Alireza

    2013-01-01

    Local effect of acetyl salicylic acid (ASA) on peripheral nerve regeneration was studied using a rat sciatic nerve transection model. Forty-five male healthy White Wistar rats were divided into three experimental groups (n = 15), randomly: Sham-operation (SHAM), control (SIL), and ASA-treated (SIL/ASA) groups. In SHAM group after anesthesia left sciatic nerve was exposed through a gluteal muscle incision and after homeostasis the muscle was sutured. In SIL group the left sciatic nerve was exposed the same way and transected proximal to tibio-peroneal bifurcation leaving a 10-mm gap. Proximal and distal stumps were each inserted into a silicone tube and filled with 10 μl phosphate buffered solution. In SIL/ASA group defect was bridged using a silicone tube filled with 10 μl acetyl salisylic acid (0.1 mg/ml). Each group was subdivided into three subgroups of five animals each and were studied 4, 8, and 12 weeks after surgery. Data were analyzed statistically by factorial analysis of variance (ANOVA) and the Bonferroni test for pair-wise comparisons. Functional study confirmed faster and better recovery of regenerated axons in SIL/ASA than in SIL group (p < 0.05). Gastrocnemius muscle mass in SIL/ASA was significantly more than in SIL group. Morphometric indices of regenerated fibers showed that the number and diameter of the myelinated fibers in SIL/ASA were significantly higher than in control group. In immuohistochemistry, location of reactions to S-100 in SIL/ASA was clearly more positive than in SIL group. Response to local treatment of ASA demonstrates that it influences and improves functional recovery of peripheral nerve regeneration. PMID:24140781

  1. Heavy particle irradiation, neurochemistry and behavior: thresholds, dose-response curves and recovery of function

    NASA Astrophysics Data System (ADS)

    Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.

    2004-01-01

    Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation-induced disruption of dopaminergic function affects a variety of behaviors that are dependent upon the integrity of this system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current report reviews the data relevant to the degree to which these characteristics are common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity.

  2. Heavy particle irradiation, neurochemistry and behavior: thresholds, dose-response curves and recovery of function

    NASA Technical Reports Server (NTRS)

    Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.

    2004-01-01

    Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation-induced disruption of dopaminergic function affects a variety of behaviors that are dependent upon the integrity of this system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current report reviews the data relevant to the degree to which these characteristics are common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

  3. CITED4 induces physiologic hypertrophy and promotes functional recovery after ischemic injury

    PubMed Central

    Bezzerides, Vassilios J.; Platt, Colin; Lerchenmüller, Carolin; Paruchuri, Kaavya; Oh, Nul Loren; Xiao, Chunyang; Cao, Yunshan; Mann, Nina; Spiegelman, Bruce M.; Rosenzweig, Anthony

    2016-01-01

    The mechanisms by which exercise mediates its multiple cardiac benefits are only partly understood. Prior comprehensive analyses of the cardiac transcriptional components and microRNAs dynamically regulated by exercise suggest that the CBP/p300-interacting protein CITED4 is a downstream effector in both networks. While CITED4 has documented functional consequences in neonatal cardiomyocytes in vitro, nothing is known about its effects in the adult heart. To investigate the impact of cardiac CITED4 expression in adult animals, we generated transgenic mice with regulated, cardiomyocyte-specific CITED4 expression. Cardiac CITED4 expression in adult mice was sufficient to induce an increase in heart weight and cardiomyocyte size with normal systolic function, similar to the effects of endurance exercise training. After ischemia-reperfusion, CITED4 expression did not change initial infarct size but mediated substantial functional recovery while reducing ventricular dilation and fibrosis. Forced cardiac expression of CITED4 also induced robust activation of the mTORC1 pathway after ischemic injury. Moreover, pharmacological inhibition of mTORC1 abrogated CITED4’s effects in vitro and in vivo. Together, these data establish CITED4 as a regulator of mTOR signaling that is sufficient to induce physiologic hypertrophy at baseline and mitigate adverse ventricular remodeling after ischemic injury. PMID:27430023

  4. Intraoperative Neural Response Telemetry and Neural Recovery Function: a Comparative Study between Adults and Children

    PubMed Central

    Carvalho, Bettina; Hamerschmidt, Rogerio; Wiemes, Gislaine

    2014-01-01

    Introduction Neural response telemetry (NRT) is a method of capturing the action potential of the distal portion of the auditory nerve in cochlear implant (CI) users, using the CI itself to elicit and record the answers. In addition, it can also measure the recovery function of the auditory nerve (REC), that is, the refractory properties of the nerve. It is not clear in the literature whether the responses from adults are the same as those from children. Objective To compare the results of NRT and REC between adults and children undergoing CI surgery. Methods Cross-sectional, descriptive, and retrospective study of the results of NRT and REC for patients undergoing IC at our service. The NRT is assessed by the level of amplitude (microvolts) and REC as a function of three parameters: A (saturation level, in microvolts), t0 (absolute refractory period, in seconds), and tau (curve of the model function), measured in three electrodes (apical, medial, and basal). Results Fifty-two patients were evaluated with intraoperative NRT (26 adults and 26 children), and 24 with REC (12 adults and 12 children). No statistically significant difference was found between intraoperative responses of adults and children for NRT or for REC's three parameters, except for parameter A of the basal electrode. Conclusion The results of intraoperative NRT and REC were not different between adults and children, except for parameter A of the basal electrode. PMID:25992145

  5. Intraspinal Delivery of Polyethylene Glycol-coated Gold Nanoparticles Promotes Functional Recovery After Spinal Cord Injury

    PubMed Central

    Papastefanaki, Florentia; Jakovcevski, Igor; Poulia, Nafsika; Djogo, Nevena; Schulz, Florian; Martinovic, Tamara; Ciric, Darko; Loers, Gabrielle; Vossmeyer, Tobias; Weller, Horst; Schachner, Melitta; Matsas, Rebecca

    2015-01-01

    Failure of the mammalian central nervous system (CNS) to regenerate effectively after injury leads to mostly irreversible functional impairment. Gold nanoparticles (AuNPs) are promising candidates for drug delivery in combination with tissue-compatible reagents, such as polyethylene glycol (PEG). PEG administration in CNS injury models has received interest for potential therapy, but toxicity and low bioavailability prevents clinical application. Here we show that intraspinal delivery of PEG-functionalized 40-nm-AuNPs at early stages after mouse spinal cord injury is beneficial for recovery. Positive outcome of hind limb motor function was accompanied by attenuated inflammatory response, enhanced motor neuron survival, and increased myelination of spared or regrown/sprouted axons. No adverse effects, such as body weight loss, ill health, or increased mortality were observed. We propose that PEG-AuNPs represent a favorable drug-delivery platform with therapeutic potential that could be further enhanced if PEG-AuNPs are used as carriers of regeneration-promoting molecules. PMID:25807288

  6. Methods to evaluate functional nerve recovery in adult rats: walking track analysis, video analysis and the withdrawal reflex.

    PubMed

    Dijkstra, J R; Meek, M F; Robinson, P H; Gramsbergen, A

    2000-03-15

    The aim of this study was to compare different methods for the evaluation of functional nerve recovery. Three groups of adult male Wistar rats were studied. In group A, a 12-mm gap between nerve ends was bridged by an autologous nerve graft; in rats of group B we performed a crush lesion of the sciatic nerve and group C consisted of non-operated control rats. The withdrawal reflex, elicited by an electric stimulus, was used to evaluate the recovery of sensory nerve function. To investigate motor nerve recovery we analyzed the walking pattern. Three different methods were used to obtain data for footprint analysis: photographic paper with thickened film developer on the paws, normal white paper with finger paint, and video recordings. The footprints were used to calculate the sciatic function index (SFI). From the video recordings, we also analyzed stepcycles. The withdrawal reflex is a convenient and reproducible test for the evaluation of global sensory nerve recovery. Recording walking movements on video and the analysis of footplacing is a perfect although time-consuming method for the evaluation of functional aspects of motor nerve recovery. PMID:10720672

  7. Arm function after stroke. An evaluation of grip strength as a measure of recovery and a prognostic indicator.

    PubMed Central

    Sunderland, A; Tinson, D; Bradley, L; Hewer, R L

    1989-01-01

    The value of strength of voluntary grip as an indicator of recovery of arm function was assessed by testing 38 recent stroke patients using a sensitive electronic dynamometer, and comparing the results with those from five other arm movement and function tests (Motricity Index, Motor Club Assessment, Nine Hole Peg Test, and Frenchay Arm Test). This procedure allowed measurement of grip in a large proportion of patients, and strength correlated highly with performance on the other tests. Measuring grip over a six month follow up period was a sensitive method of charting intrinsic neurological recovery. The presence of voluntary grip at one month indicates that there will be some functional recovery at six months. PMID:2592969

  8. Causal Link between the Cortico-Rubral Pathway and Functional Recovery through Forced Impaired Limb Use in Rats with Stroke

    PubMed Central

    Ishida, Akimasa; Isa, Kaoru; Umeda, Tatsuya; Kobayashi, Kazuto; Kobayashi, Kenta; Hida, Hideki

    2016-01-01

    Intensive rehabilitation is believed to induce use-dependent plasticity in the injured nervous system; however, its causal relationship to functional recovery is unclear. Here, we performed systematic analysis of the effects of forced use of an impaired forelimb on the recovery of rats after lesioning the internal capsule with intracerebral hemorrhage (ICH). Forced limb use (FLU) group rats exhibited better recovery of skilled forelimb functions and their cortical motor area with forelimb representation was restored and enlarged on the ipsilesional side. In addition, abundant axonal sprouting from the reemerged forelimb area was found in the ipsilateral red nucleus after FLU. To test the causal relationship between the plasticity in the cortico-rubral pathway and recovery, loss-of-function experiments were conducted using a double-viral vector technique, which induces selective blockade of the target pathway. Blockade of the cortico-rubral tract resulted in deficits of the recovered forelimb function in FLU group rats. These findings suggest that the cortico-rubral pathway is a substrate for recovery induced by intensive rehabilitation after ICH. SIGNIFICANCE STATEMENT The research aimed at determining the causal linkage between reorganization of the motor pathway induced by intensive rehabilitative training and recovery after stroke. We clarified the expansion of the forelimb representation area of the ipsilesional motor cortex by forced impaired forelimb use (FLU) after lesioning the internal capsule with intracerebral hemorrhaging (ICH) in rats. Anterograde tracing showed robust axonal sprouting from the forelimb area to the red nucleus in response to FLU. Selective blockade of the cortico-rubral pathway by the novel double-viral vector technique clearly revealed that the increased cortico-rubral axonal projections had causal linkage to the recovery of reaching movements induced by FLU. Our data demonstrate that the cortico-rubral pathway is responsible for the

  9. Primed Physical Therapy Enhances Recovery of Upper Limb Function in Chronic Stroke Patients.

    PubMed

    Ackerley, Suzanne J; Byblow, Winston D; Barber, P Alan; MacDonald, Hayley; McIntyre-Robinson, Andrew; Stinear, Cathy M

    2016-05-01

    Background Recovery of upper limb function is important for regaining independence after stroke.Objective To test the effects of priming upper limb physical therapy with intermittent theta burst stimulation (iTBS), a form of noninvasive brain stimulation.Methods Eighteen adults with first-ever chronic monohemispheric subcortical stroke participated in this randomized, controlled, triple-blinded trial. Intervention consisted of priming with real or sham iTBS to the ipsilesional primary motor cortex immediately before 45 minutes of upper limb physical therapy, daily for 10 days. Changes in upper limb function (Action Research Arm Test [ARAT]), upper limb impairment (Fugl-Meyer Scale), and corticomotor excitability, were assessed before, during, and immediately, 1 month and 3 months after the intervention. Functional magnetic resonance images were acquired before and at one month after the intervention.Results Improvements in ARAT were observed after the intervention period when therapy was primed with real iTBS, but not sham, and were maintained at 1 month. These improvements were not apparent halfway through the intervention, indicating a dose effect. Improvements in ARAT at 1 month were related to balancing of corticomotor excitability and an increase in ipsilesional premotor cortex activation during paretic hand grip.Conclusions Two weeks of iTBS-primed therapy improves upper limb function at the chronic stage of stroke, for at least 1 month postintervention, whereas therapy alone may not be sufficient to alter function. This indicates a potential role for iTBS as an adjuvant to therapy delivered at the chronic stage. PMID:26180053

  10. Anatomical and functional recovery following spinal cord transection in the chick embryo.

    PubMed

    Shimizu, I; Oppenheim, R W; O'Brien, M; Shneiderman, A

    1990-09-01

    Following complete transection of the thoracic spinal cord at various times during embryonic development, chick embryos and posthatched animals exhibited various degrees of anatomical and functional recovery depending upon the age of injury. Transection on embryonic day 2 (E2), when neurogenesis is still occurring and before descending or ascending fiber tracts have formed, produced no noticeable behavioral or anatomical deficits. Embryos hatched on their own and were behaviorally indistinguishable from control hatchlings. Similar results were found following transection on E5, an age when neurogenesis is complete and when ascending and descending fiber tracts have begun to project through the thoracic region. Within 48 h following injury on E5, large numbers of nerve fibers were observed growing across the site of transection. By E8, injections of horse-radish peroxidase (HRP) administered caudal to the lesion, retrogradely labelled rostral spinal and brainstem neurons. Embryos transected on E5 were able to hatch and could stand and locomote posthatching in a manner that was indistinguishable from controls. Following spinal cord transections on E10, anatomical recovery of the spinal cord at the site of injury was not quite as complete as after E5 transection. Nonetheless, anatomical continuity was restored at the site of injury, axons projected across this region, and rostral spinal and brainstem neurons could be retrogradely labelled following HRP injections administered caudal to the lesion. At least part of this anatomical recovery may be mediated by the regeneration or regrowth of lesioned axons. Although none of the embryos transected on E10 that survived to hatching were able to hatch on their own, because several sham-operated embryos were also unable to hatch, we do not attribute this deficit to the spinal transection. When E10-transected embryos were aided in escaping from the shell, they were able to support their own weight, could stand, and locomote

  11. Chronic behavioral testing after focal ischemia in the mouse: functional recovery and the effects of gender.

    PubMed

    Li, Xiaoling; Blizzard, Kathleen K; Zeng, Zhiyuan; DeVries, A Courtney; Hurn, Patricia D; McCullough, Louise D

    2004-05-01

    Several useful behavioral tests exist for measuring behavioral recovery after ischemia in higher-order animals and rats. With the increasing use of mice in focal stroke research, simple, reliable, and reproducible behavioral testing has become a priority. As neuroprotective agents are tested, long-term outcome must be assessed, especially in studies focused on neuronal plasticity and regeneration after ischemia. Our laboratory and others have previously shown that estrogen (E2) is neuroprotective in rodent stroke paradigms. We examined a battery of behavioral tests in male and female mice subjected to 90 min of middle cerebral artery occlusion (MCAO) to determine the most sensitive tests for detecting sensorimotor dysfunction after stroke, and to determine the functional significance of E2-mediated neuroprotection. Only two tests, the corner test and the cylinder test, were able to differentiate between groups (sham and stroke) after several days of repeated testing. The cylinder test was sensitive to the neuroprotective/neurorestorative effects of E2, but 2 weeks after stroke, the cylinder test was unable to distinguish between sham and stroke animals treated with E2. In contrast, the corner test was able to differentiate stroke and sham animals even 6 weeks after stroke, but did not distinguish animals treated with E2 vs. vehicle. These tests provide a simple, rapid, reliable assessment of sensorimotor dysfunction in the mouse after focal ischemia. Hormonal status influences speed of recovery on cylinder testing in animals of both genders. This suggests that a short battery of tests including the neurological score, cylinder, and corner test may be adequate to rapidly and repeatedly assess sensorimotor dysfunction in mice of both genders. PMID:15081592

  12. Rewiring the Brain: Potential Role of the Premotor Cortex in Motor Control, Learning, and Recovery of Function Following Brain Injury

    PubMed Central

    Kantak, Shailesh S.; Stinear, James W.; Buch, Ethan R.; Cohen, Leonardo G.

    2016-01-01

    The brain is a plastic organ with a capability to reorganize in response to behavior and/or injury. Following injury to the motor cortex or emergent corticospinal pathways, recovery of function depends on the capacity of surviving anatomical resources to recover and repair in response to task-specific training. One such area implicated in poststroke reorganization to promote recovery of upper extremity recovery is the premotor cortex (PMC). This study reviews the role of distinct subdivisions of PMC: dorsal (PMd) and ventral (PMv) premotor cortices as critical anatomical and physiological nodes within the neural networks for the control and learning of goal-oriented reach and grasp actions in healthy individuals and individuals with stroke. Based on evidence emerging from studies of intrinsic and extrinsic connectivity, transcranial magnetic stimulation, functional neuroimaging, and experimental studies in animals and humans, the authors propose 2 distinct patterns of reorganization that differentially engage ipsilesional and contralesional PMC. Research directions that may offer further insights into the role of PMC in motor control, learning, and poststroke recovery are also proposed. This research may facilitate neuroplasticity for maximal recovery of function following brain injury. PMID:21926382

  13. Angiopoietin-1 preconditioning enhances survival and functional recovery of mesenchymal stem cell transplantation*

    PubMed Central

    Liu, Xian-bao; Chen, Han; Chen, Hui-qiang; Zhu, Mei-fei; Hu, Xin-yang; Wang, Ya-ping; Jiang, Zhi; Xu, Yin-chuan; Xiang, Mei-xiang; Wang, Jian-an

    2012-01-01

    Objective: Mesenchymal stem cell (MSC) transplantation is a promising therapy for ischemic heart diseases. However, poor cell survival after transplantation greatly limits the therapeutic efficacy of MSCs. The purpose of this study was to investigate the protective effect of angiopoietin-1 (Ang1) preconditioning on MSC survival and subsequent heart function improvement after transplantation. Methods: MSCs were cultured with or without 50 ng/ml Ang1 in complete medium for 24 h prior to experiments on cell survival and transplantation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Hoechst staining were applied to evaluate MSC survival after serum deprivation in vitro, while cell survival in vivo was detected by terminal deoxynucleotidyl transferase biotin-dUPT nick end labeling (TUNEL) assay 24 and 72 h after transplantation. Heart function and infarct size were measured four weeks later by small animal echocardiography and Masson’s trichrome staining, respectively. Results: Ang1 preconditioning induced Akt phosphorylation and increased expression of Bcl-2 and the ratio of Bcl-2/Bax. In comparison with non-preconditioned MSCs, Ang1-preconditioned cell survival was significantly increased while the apoptotic rate decreased in vitro. However, the PI3K/Akt pathway inhibitor, LY294002, abrogated the protective effect of Ang1 preconditioning. After transplantation, the Ang1-preconditioned-MSC group showed a lower death rate, smaller infarct size, and better heart functional recovery compared to the non-preconditioned-MSC group. Conclusions: Ang1 preconditioning enhances MSC survival, contributing to further improvement of heart function. PMID:22843181

  14. Testing a Family-centered Intervention to Promote Functional and Cognitive Recovery in Hospitalized Older Adults

    PubMed Central

    Boltz, Marie; Resnick, Barbara; Chippendale, Tracy; Galvin, James

    2016-01-01

    A comparative trial using repeated measures design evaluated the feasibility and outcomes of the Family-centered Function-focused Care (Fam-FFC) intervention intended to promote functional recovery in the hospitalized older adult. A three component intervention (1) environmental assessment/ modification, 2) staff education, 3) family/patient education and partnership in care planning with post-acute follow-up) was implemented by a family-centered resource nurse and a facility champion. Control units were exposed to function-focused care education only. Ninety-seven dyads of medical patients age 65 and older and family caregivers (FCGs) were recruited from three medical units of a community teaching hospital. The majority of patients were female (53%); white (89%), married (51%) or widowed (40%), with a mean age of 80.8 (± 7.5). The majority of FCGs were married (78%) daughters (34%), followed by female spouses/partners (31%), in the age range of 46–65 (38%). Outcomes for patients included: functional outcomes (ADL and walking performance, gait, balance), and delirium severity and duration. FCG outcomes included preparedness for caregiving, anxiety, depression, role strain, and mutuality. The intervention group demonstrated less severity and duration of delirium, and better ADL and walking performance, but not gait/balance as compared to the control group. FCG who participated in Fam-FFC showed a significant increase in preparedness for caregiving, less anxiety and less depression from admission to two months post-discharge, but no significant differences in strain and mutuality, as compared to FCG in the control group. Fam-FFC is feasible and has the potential to improve outcomes for hospitalized older adults and family caregivers. PMID:25481973

  15. Intramyocardial stem cell injection in patients with ischemic cardiomyopathy: Functional recovery and reverse remodeling

    PubMed Central

    Williams, Adam R.; Trachtenberg, Barry; Velazquez, Darcy L.; McNiece, Ian; Altman, Peter; Rouy, Didier; Mendizabal, Adam M.; Pattany, Pradip M.; Lopera, Gustavo A.; Fishman, Joel; Zambrano, Juan P.; Heldman, Alan W.; Hare, Joshua M.

    2012-01-01

    Rationale Transcatheter, intramyocardial injections of bone marrow derived cell therapy produces reverse remodeling in large animal models of ischemic cardiomyopathy. Objective We used cardiac magnetic resonance imaging (CMR) in patients with LV dysfunction related to remote myocardial infarction (MI) to test the hypothesis that bone marrow progenitor cell injection cause functional recovery of scarred myocardium and reverse remodeling. Methods and Results Eight patients (age 57.2±13.3) received transendocardial, intramyocardial injection of autologous bone marrow progenitor cells (mononuclear or mesenchymal stem cells) in LV scar and border zone. All patients tolerated the procedure with no serious adverse events. CMR at 1-year demonstrated a decrease in end-diastolic volume (208.7±20.4 vs. 167.4±7.32mL; p=0.03), a trend towards decreased end-systolic volume (142.4±16.5 vs. 107.6±7.4mL; p=0.06), decreased infarct size (p<0.05), and improved regional LV function by peak Ecc in the treated infarct zone (-8.1±1.0 vs. -11.4±1.3; p=0.04). Improvements in regional function were evident at 3 months, while the changes in chamber dimensions were not significant until 6 months. Improved regional function in the infarct zone strongly correlated with reduction of EDV (r2=0.69, p=0.04) and ESV (r2=0.83, p=0.01). Conclusions These data suggest that transcatheter, intramyocardial injections of autologous bone marrow progenitor cells improve regional contractility of a chronic myocardial scar and these changes predict subsequent reverse remodeling. The findings support the potential clinical benefits of this new treatment strategy and ongoing randomized clinical trials. PMID:21415390

  16. Recovery of Vibratory Function After Vocal Fold Microflap in a Rabbit Model

    PubMed Central

    Kojima, Tsuyoshi; Mitchell, Joshua R.; Garrett, C. Gaelyn; Rousseau, Bernard

    2015-01-01

    Objectives/Hypothesis The purpose of this study was to evaluate the return of vibratory function and restoration of vibration amplitude and symmetry after vocal fold microflap surgery. Study Design Prospective in vivo animal model. Methods Microflap surgery was performed on 30 New Zealand white breeder rabbits. The left vocal fold received a 3-mm epithelial incision and mucosal elevation, while the contralateral vocal fold was left intact to serve as an internal control. Quantitative analysis of amplitude ratio and lateral phase difference were measured using high-speed laryngeal imaging at a frame rate of 10,000 frames per second from animals undergoing evoked phonation on postoperative days 0, 1, 3, 5, and 7. Results Quantitative measures revealed a significantly reduced amplitude ratio and lateral phase difference on day 0 after microflap. These impairments of vibratory function on day 0 were associated with separation of the vocal fold’s bodycover layer. Amplitude ratio increased significantly by day 3 after microflap, with further increases in vibration amplitude on days 5 and 7. While the amplitude ratio improved significantly on day 3, lateral phase difference decreased significantly on day 3, and returned to normal on days 5 and 7. Conclusions High-speed laryngeal imaging was used to investigate the natural time course of postmicroflap recovery of vibratory function. Results revealed the restoration of vibration amplitude and lateral phase difference by days 3 to 7 after microflap. The time period of improved vibratory function observed in this study coincides with the end of the well-documented inflammatory phase of vocal fold wound repair. PMID:23901003

  17. Functional recovery of anterior semicircular canal afferents following hair cell regeneration in birds

    NASA Technical Reports Server (NTRS)

    Boyle, Richard; Highstein, Stephen M.; Carey, John P.; Xu, Jinping

    2002-01-01

    Streptomycin sulfate (1.2 g/kg i.m.) was administered for 5 consecutive days to 5-7-day-old white Leghorn chicks; this causes damage to semicircular canal hair cells that ultimately regenerate to reform the sensory epithelium. During the recovery period, electrophysiological recordings were taken sequentially from anterior semicircular canal primary afferents using an indentation stimulus of the canal that has been shown to mimic rotational stimulation. Chicks were assigned to an early (14-18 days; n = 8), intermediate (28-34 days; n = 5), and late (38-58 days; n = 4) period based on days after treatment. Seven untreated chicks, 15-67 days old, provided control data. An absence of background and indent-induced discharge was the prominent feature of afferents in the early period: only "silent" afferents were encountered in 5/8 experiments. In several of these chicks, fascicles of afferent fibers were seen extending up to the epithelium that was void of hair cells, and intra- and extracellular biocytin labeling revealed afferent processes penetrating into the supporting cell layer of the crista. In 3/8 chicks 74 afferents could be characterized, and they significantly differed from controls (n = 130) by having a lower discharge rate and a negligible response to canal stimulation. In the intermediate period there was considerable variability in discharge properties of 121 afferents, but as a whole the number of "silent" fibers in the canal nerve diminished, the background rate increased, and a response to canal stimulation detected. Individually biocytin-labeled afferents had normal-appearing terminal specializations in the sensory epithelium by 28 days poststreptomycin. In the late period, afferents (n = 58) remained significantly different from controls in background discharge properties and response gain. The evidence suggests that a considerable amount of variability exists between chicks in the return of vestibular afferent function following ototoxic injury and

  18. Motor cortex electrical stimulation augments sprouting of the corticospinal tract and promotes recovery of motor function

    PubMed Central

    Carmel, Jason B.; Martin, John H.

    2014-01-01

    The corticospinal system—with its direct spinal pathway, the corticospinal tract (CST) – is the primary system for controlling voluntary movement. Our approach to CST repair after injury in mature animals was informed by our finding that activity drives establishment of connections with spinal cord circuits during postnatal development. After incomplete injury in maturity, spared CST circuits sprout, and partially restore lost function. Our approach harnesses activity to augment this injury-dependent CST sprouting and to promote function. Lesion of the medullary pyramid unilaterally eliminates all CST axons from one hemisphere and allows examination of CST sprouting from the unaffected hemisphere. We discovered that 10 days of electrical stimulation of either the spared CST or motor cortex induces CST axon sprouting that partially reconstructs the lost CST. Stimulation also leads to sprouting of the cortical projection to the magnocellular red nucleus, where the rubrospinal tract originates. Coordinated outgrowth of the CST and cortical projections to the red nucleus could support partial re-establishment of motor systems connections to the denervated spinal motor circuits. Stimulation restores skilled motor function in our animal model. Lesioned animals have a persistent forelimb deficit contralateral to pyramidotomy in the horizontal ladder task. Rats that received motor cortex stimulation either after acute or chronic injury showed a significant functional improvement that brought error rate to pre-lesion control levels. Reversible inactivation of the stimulated motor cortex reinstated the impairment demonstrating the importance of the stimulated system to recovery. Motor cortex electrical stimulation is an effective approach to promote spouting of spared CST axons. By optimizing activity-dependent sprouting in animals, we could have an approach that can be translated to the human for evaluation with minimal delay. PMID:24994971

  19. Enhanced Functional Recovery in MRL/MpJ Mice after Spinal Cord Dorsal Hemisection

    PubMed Central

    Thuret, Sandrine; Thallmair, Michaela; Horky, Laura L.; Gage, Fred H.

    2012-01-01

    Adult MRL/MpJ mice have been shown to possess unique regeneration capabilities. They are able to heal an ear-punched hole or an injured heart with normal tissue architecture and without scar formation. Here we present functional and histological evidence for enhanced recovery following spinal cord injury (SCI) in MRL/MpJ mice. A control group (C57BL/6 mice) and MRL/MpJ mice underwent a dorsal hemisection at T9 (thoracic vertebra 9). Our data show that MRL/MpJ mice recovered motor function significantly faster and more completely. We observed enhanced regeneration of the corticospinal tract (CST). Furthermore, we observed a reduced astrocytic response and fewer micro-cavities at the injury site, which appear to create a more growth-permissive environment for the injured axons. Our data suggest that the reduced astrocytic response is in part due to a lower lesion-induced increase of cell proliferation post-SCI, and a reduced astrocytic differentiation of the proliferating cells. Interestingly, we also found an increased number of proliferating microglia, which could be involved in the MRL/MpJ spinal cord repair mechanisms. Finally, to evaluate the molecular basis of faster spinal cord repair, we examined the difference in gene expression changes in MRL/MpJ and C57BL/6 mice after SCI. Our microarray data support our histological findings and reveal a transcriptional profile associated with a more efficient spinal cord repair in MRL/MpJ mice. PMID:22348029

  20. Inhibition of LINGO-1 promotes functional recovery after experimental spinal cord demyelination.

    PubMed

    Zhang, Yongjie; Zhang, Yi Ping; Pepinsky, Blake; Huang, Guanrong; Shields, Lisa B E; Shields, Christopher B; Mi, Sha

    2015-04-01

    Blocking LINGO-1 has been shown to enhance remyelination in the rat lysolecithin-induced focal spinal cord demyelination model. We used transcranial magnetic motor-evoked potentials (tcMMEPs) to assess the effect of blocking LINGO-1 on recovery of axonal function in a mouse lysolecithin model at 1, 2 and 4weeks after injury. The role of LINGO-1 was assessed using LINGO-1 knockout (KO) mice and in wild-type mice after intraperitoneal administration of anti-LINGO-1 antagonist monoclonal antibody (mAb3B5). Response rates (at 2 and 4weeks) and amplitudes (at 4weeks) were significantly increased in LINGO-1 KO and mAb3B5-treated mice compared with matched controls. The latency of potentials at 4weeks was significantly shorter in mAb3B5-treated mice compared with controls. Lesion areas in LINGO-1 KO and mAb3B5-treated mice were reduced significantly compared with matched controls. The number of remyelinated axons within the lesions was increased and the G-ratios of the axons were decreased in both LINGO-1 KO and mAb3B5-treated mice compared with matched controls. These data provide morphometric and functional evidence of enhancement of remyelination associated with antagonism of LINGO-1. PMID:25681574

  1. Recovery of Olfactory Function in Postviral Olfactory Dysfunction Patients after Acupuncture Treatment

    PubMed Central

    Dai, Qi; Pang, Zhihui; Yu, Hongmeng

    2016-01-01

    Introduction. The aims of this study were to assess the impact of traditional Chinese acupuncture (TCA) in postviral olfactory dysfunction (PVOD) patients who were refractory to standardized treatment and to compare the results with the impact observed in an observation group. Methods. Fifty patients who presented to the outpatient clinic with PVOD and were refractory to standardized treatment were included: 25 were treated with TCA and 25 patients were simply observed. A subjective olfactory test was performed using the University of Pennsylvania Smell Identification Test (UPSIT). The effects of TCA were compared with the results obtained in the observation group. Results. Improved olfactory function was observed in eleven patients treated with TCA compared with four patients in the observation group. This study revealed significantly improved olfactory function outcomes in patients who underwent acupuncture compared with the observation group. No significant differences in olfaction recovery were found according to age, gender, or duration of disease between the two groups; however, hyposmic patients recovered at a higher rate than anosmic patients. Conclusion. TCA may aid the treatment of PVOD patients who are refractory to drugs or other therapies. PMID:27034689

  2. Environmental Experience Modulates Ischemia-Induced Amyloidogenesis and Enhances Functional Recovery

    PubMed Central

    Rogozinska, Magdalena; Woods, Julie

    2009-01-01

    Abstract In this study, we examined whether ischemia-induced amyloidogenesis could be modulated by environmental “experience,” and whether this modulation is associated with improved cognitive functioning. Rats were subjected to either global ischemia or sham surgery and then were randomly assigned to either enriched environment housing (EE) or socially paired housing (controls). After 14 days of differential environmental housing, the rats were tested in the water maze. Our results show decreased C-terminal fragments of the β-amyloid precursor protein (βAPP) and decreased amyloid beta (Aβ) load in the ischemic EE rats compared to the ischemic control animals. In addition, Aβ oligomerization was significantly decreased in the ischemic EE animals compared to the ischemic control rats. Further, significantly increased levels of neprilysin, but not insulin-degrading enzyme, amyloid-degrading enzymes, were seen in the ischemic EE rats compared to the ischemic control animals. Behavioral analyses showed that ischemic EE rats performed significantly better on the memory task compared to the ischemic control group. These results suggest that use of multi-sensory environmental enrichment following cerebral ischemia may reduce the accumulation of Aβ peptide in the more pathologic oligomeric form, and consequently may enhance functional recovery. PMID:19271963

  3. Plasminogen activator induction facilitates recovery of respiratory function following spinal cord injury.

    PubMed

    Minor, Kenneth H; Seeds, Nicholas W

    2008-01-01

    The possibility that plasminogen activator (PA) plays a role in synaptic plasticity was explored in the spinal cord during the crossed phrenic phenomenon (CPP), where respiratory functional plasticity develops following spinal cord injury. Synaptic remodeling on phrenic motorneurons occurs during the characteristic delay period following spinal cord injury before CPP recovery of respiratory function. The molecular mechanisms underlying this plasticity are not well-defined. During the critical 1-2 h delay period required for this synaptic plasticity following a C2 hemisection in mice, uPA and tPA mRNAs are rapidly induced in C4-5 ventral spinal cord neurons in the ipsilateral phrenic motor nucleus (PMN), as are uPA and tPA protein levels. A role for uPA in CPP spinal cord plasticity is confirmed by the impaired ability of uPA knockout mice to acquire a good CPP response by 6 h post-hemisection and their lack of structural remodeling of PMN synapses that underlies development of the CPP response. PMID:18042398

  4. Oct4-induced oligodendrocyte progenitor cells enhance functional recovery in spinal cord injury model.

    PubMed

    Kim, Jeong Beom; Lee, Hyunah; Araúzo-Bravo, Marcos J; Hwang, Kyujin; Nam, Donggyu; Park, Myung Rae; Zaehres, Holm; Park, Kook In; Lee, Seok-Jin

    2015-12-01

    The generation of patient-specific oligodendrocyte progenitor cells (OPCs) holds great potential as an expandable cell source for cell replacement therapy as well as drug screening in spinal cord injury or demyelinating diseases. Here, we demonstrate that induced OPCs (iOPCs) can be directly derived from adult mouse fibroblasts by Oct4-mediated direct reprogramming, using anchorage-independent growth to ensure high purity. Homogeneous iOPCs exhibit typical small-bipolar morphology, maintain their self-renewal capacity and OPC marker expression for more than 31 passages, share high similarity in the global gene expression profile to wild-type OPCs, and give rise to mature oligodendrocytes and astrocytes in vitro and in vivo. Notably, transplanted iOPCs contribute to functional recovery in a spinal cord injury (SCI) model without tumor formation. This study provides a simple strategy to generate functional self-renewing iOPCs and yields insights for the in-depth study of demyelination and regenerative medicine. PMID:26497893

  5. 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

  6. 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

  7. Synergistic effects of low-level laser and mesenchymal stem cells on functional recovery in rats with crushed sciatic nerves.

    PubMed

    Yang, Chen-Chia; Wang, John; Chen, Shyh-Chang; Hsieh, Yueh-Ling

    2016-02-01

    Transplantation of mesenchymal stem cells (MSCs) has been proposed to exert beneficial effects on peripheral nerve regeneration after a peripheral nerve injury, but the functional recovery in the denervated limb is still limited. In this study, we used low-level laser therapy (LLLT) as an adjunct therapy for MSC transplantation on the functional recovery of crushed sciatic nerve in rats. Peripheral nerve injury was induced in 48 Sprague-Dawley rats by crushing the unilateral sciatic nerve, using a vessel clamp. The animals with crushed injury were randomly divided into four groups: control group, with no treatment; MSC group, treated with MSC alone; LLLT group, treated with LLLT alone; and MSCLLLT group, treated with a combination of MSC and LLLT. The sciatic function index (SFI), vertical activity of locomotion (VA) and ankle angle (AA) of rats were examined for functional assessments after treatment. Electrophysiological, morphological and S100 immunohistochemical studies were also conducted. The MSCLLLT group showed a greater recovery in SFI, VA and AA, with significant difference from MSC, LLLT and control groups (p < 0.05). Moreover, markedly enhanced electrophysiological function and expression of S100 immunoreactivity, as well as fewer inflammatory cells and less vacuole formation were also demonstrated after nerve crush injury in the MSCLLLT group when compared with the groups receiving a single treatment (p < 0.05). MSC transplantation combined with LLLT could achieve better results in functional recovery than a conventional treatment of MSC or LLLT alone. LLLT has a synergistic effect in providing greater functional recovery with MSC transplantation after nerve crush injury. PMID:23468370

  8. Variability in Motor and Language Recovery during the Acute Stroke Period

    PubMed Central

    Dunn, Lauren E.; Schweber, Adam B.; Manson, Daniel K.; Lendaris, Andrea; Herber, Charlotte; Marshall, Randolph S.; Lazar, Ronald M.

    2016-01-01

    addition, patients only achieved about 1/3 of their remaining possible recovery based on the anticipated 70% proportion found at 90 days. These findings suggest that the complex interaction between poststroke structural repair, regeneration, and functional reorganization during the first week after stroke has yet to be elucidated. PMID:27099611

  9. Comparison of the Recovery Patterns of Language and Cognitive Functions in Patients with Post-Traumatic Language Processing Deficits and in Patients with Aphasia Following a Stroke

    ERIC Educational Resources Information Center

    Vukovic, Mile; Vuksanovic, Jasmina; Vukovic, Irena

    2008-01-01

    In this study we investigated the recovery patterns of language and cognitive functions in patients with post-traumatic language processing deficits and in patients with aphasia following a stroke. The correlation of specific language functions and cognitive functions was analyzed in the acute phase and 6 months later. Significant recovery of the…

  10. Salmon fibrin treatment of spinal cord injury promotes functional recovery and density of serotonergic innervation.

    PubMed

    Sharp, Kelli G; Dickson, Amanda R; Marchenko, Steve A; Yee, Kelly M; Emery, Pauline N; Laidmåe, Ivo; Uibo, Raivo; Sawyer, Evelyn S; Steward, Oswald; Flanagan, Lisa A

    2012-05-01

    The neural degeneration caused by spinal cord injury leaves a cavity at the injury site that greatly inhibits repair. One approach to promoting repair is to fill the cavity with a scaffold to limit further damage and encourage regrowth. Injectable materials are advantageous scaffolds because they can be placed as a liquid in the lesion site then form a solid in vivo that precisely matches the contours of the lesion. Fibrin is one type of injectable scaffold, but risk of infection from blood borne pathogens has limited its use. We investigated the potential utility of salmon fibrin as an injectable scaffold to treat spinal cord injury since it lacks mammalian infectious agents and encourages greater neuronal extension in vitro than mammalian fibrin or Matrigel®, another injectable material. Female rats received a T9 dorsal hemisection injury and were treated with either salmon or human fibrin at the time of injury while a third group served as untreated controls. Locomotor function was assessed using the BBB scale, bladder function was analyzed by measuring residual urine, and sensory responses were tested by mechanical stimulation (von Frey hairs). Histological analyses quantified the glial scar, lesion volume, and serotonergic fiber density. Rats that received salmon fibrin exhibited significantly improved recovery of both locomotor and bladder function and a greater density of serotonergic innervation caudal to the lesion site without exacerbation of pain. Rats treated with salmon fibrin also exhibited less autophagia than those treated with human fibrin, potentially pointing to amelioration of sensory dysfunction. Glial scar formation and lesion size did not differ significantly among groups. The pattern and timing of salmon fibrin's effects suggest that it acts on neuronal populations but not by stimulating long tract regeneration. Salmon fibrin clearly has properties distinct from those of mammalian fibrin and is a beneficial injectable scaffold for treatment

  11. Impaired Cerebrovascular Function in Coronary Artery Disease Patients and Recovery Following Cardiac Rehabilitation

    PubMed Central

    Anazodo, Udunna C.; Shoemaker, J. K.; Suskin, Neville; Ssali, Tracy; Wang, Danny J. J.; St. Lawrence, Keith S.

    2016-01-01

    Coronary artery disease (CAD) poses a risk to the cerebrovascular function of older adults and has been linked to impaired cognitive abilities. Using magnetic resonance perfusion imaging, we investigated changes in resting cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to hypercapnia in 34 CAD patients and 21 age-matched controls. Gray matter volume (GMV) images were acquired and used as a confounding variable to separate changes in structure from function. Compared to healthy controls, CAD patients demonstrated reduced CBF in the superior frontal, anterior cingulate (AC), insular, pre- and post-central gyri, middle temporal, and superior temporal regions. Subsequent analysis of these regions demonstrated decreased CVR in the AC, insula, post-central and superior frontal regions. Except in the superior frontal and precentral regions, regional reductions in CBF and CVR were identified in brain areas where no detectable reductions in GMV were observed, demonstrating that these vascular changes were independent of brain atrophy. Because aerobic fitness training can improve brain function, potential changes in regional CBF were investigated in the CAD patients after completion of a 6-months exercise-based cardiac rehabilitation program. Increased CBF was observed in the bilateral AC, as well as recovery of CBF in the dorsal aspect of the right AC, where the magnitude of increased CBF was roughly equal to the reduction in CBF at baseline compared to controls. These exercise-related improvements in CBF in the AC is intriguing given the role of this area in cognitive processing and regulation of cardiovascular autonomic control. PMID:26779011

  12. Differentiated adipose-derived stem cells promote the recovery of nociceptor function in rats.

    PubMed

    Nishibayashi, Akimitsu; Tomita, Koichi; Kiya, Koichiro; Yano, Kenji; Hosokawa, Ko

    2016-10-19

    The loss of nociceptive function in the skin because of trauma or surgery can impair the quality of life. The recovery of nociceptor function is mediated by two different axonal responses: nerve growth factor (NGF)-dependent collateral sprouting of undamaged nerves and NGF-independent regeneration of damaged nerves. We reported previously that adipose-derived stem cells (ASCs) can transdifferentiate into Schwann cell (SC)-like cells (dASCs) and that transplantation of dASCs increases axonal density in skin flaps. In the present study, we used an animal model that allowed for the individual assessment of collateral sprouting and regeneration. In-vitro differentiation of ASCs to dASCs significantly increased the production of NGF and brain-derived neurotrophic factor (BDNF) to levels comparable with SCs. In-vivo experiments showed that dASC and SC transplantation significantly increased the area of the mechano-nociceptive field in both collateral sprouting and regeneration models, whereas ASC transplantation exerted no significant effect. Antibody blocking experiment showed that these effects of dASC transplantation in the regeneration model were partly mediated by BDNF. Interestingly, the final areas of nociceptive fields between the two experimental models did not differ significantly for any treatment condition. These results indicate that dASC transplantation differentially facilitates collateral sprouting and axonal regeneration by delivering NGF and other neurotrophic factors (e.g. BDNF), respectively. Although there is a limit to nociceptive field enlargement irrespective of axonal response, dASC transplantation could present a new approach for improving nociceptive function in denervated skin. PMID:27513202

  13. Recovery of ovary function impaired by chemotherapy using Chinese herbal medicine in a rat model.

    PubMed

    Xia, Tian; Fu, Yu; Gao, Hui; Zhao, Zhimei; Zhao, Liying; Han, Bing

    2014-10-01

    The ovary is not only involved in female germ cell development and maturation, but also adjusts female endocrinology. Its function is severely impaired during chemotherapy, and premature ovarian failure may be induced. Chinese herbal medicine (CHM) has displayed significant potential in the treatment of female endocrine disorders; however, it is unknown whether it can recover ovarian function impaired by chemotherapy. In the present study, CHM was used to treat rat models of ovarian dysfunction impaired by chemotherapeutic drugs. Three groups were included in this study: a prevention group, a treatment group, and a prevention-treatment group. Routine gonadotropin-releasing hormone agonists (GnRHa) treatment was used as a control. The results showed that body weight, fertility, estrus days, hormone levels, and ovary weight were restored when CHM was administered in these rat models. Moreover, in the prevention-treatment group, the number of follicles at each developmental stage significantly increased compared with the prevention or treatment group. Furthermore, the number of apoptotic cells significantly decreased, and the relative mRNA expression of caspase-3 significantly decreased, in the prevention-treatment group. The results of gene expression analysis indicated that the expression of anti-Müllerianhormone (AMH) which indicates ovarian preservation was significantly up-regulated in the prevention-treatment group and was similar to normal rats. The expression of growth differentiation factor 9 (GDF9) was significantly enhanced in both the prevention-treatment group and the GnRHa group, which suggested that the oocytes were of better quality. Finally, we found that there were no differences in body weight and fertility in the offspring conceived by the drug-treated rats, which partly indicated the safety of the medicine. In conclusion, Chinese herbal medicine showed a beneficial role in the recovery of ovary function in these rat models and has significant

  14. Resource Conservation and Recovery Act permit modifications and the functional equivalency demonstration: a case study

    SciTech Connect

    Elsberry, K.; Garcia, P.; Carnes, R.; Kinker, J.; Loehr, C; Lyon, W.

    1996-02-01

    Hazardous waste operating permits issued under the Resource Conservation and Recovery Act (RCRA) often impose requirements that specific components and equipment be used. Consequently, changing these items, may first require that the owner/operator request a potentially time-consuming and costly permit modification. However, the owner/operator may demonstrate that a modification is not required because the planned changes are ``functionally equivalent.`` The Controlled-Air Incinerator at Los Alamos National Laboratory is scheduled for maintenance and improvements. The incinerator`s carbon adsorption unit/high efficiency particulate air filtration system, was redesigned to improve reliability and minimize maintenance. A study was performed to determine whether the redesigned unit would qualify as functionally equivalent to the original component. In performing this study, the following steps were taken: (a) the key performance factors were identified; (b) performance data describing the existing unit were obtained; (c) performance of both the existing and redesigned units was simulated; and (d) the performance data were compared to ascertain whether the components could qualify as functionally equivalent. In this case, the key performance data included gas residence time and distribution of flow over the activated carbon. Because both units were custom designed and fabricated, a simple comparison of manufacturers` specifications was impossible. Therefore, numerical simulation of each unit design was performed using the TEMPEST thermal-hydraulic computer code to model isothermal hydrodynamic performance under steady-state conditions. The results of residence time calculations from the model were coupled with flow proportion and sampled using a Monte Carlo-style simulation to derive distributions that describe the predicted residence times.

  15. Lentiviral-mediated transfer of CDNF promotes nerve regeneration and functional recovery after sciatic nerve injury in adult rats

    SciTech Connect

    Cheng, Lei; Liu, Yi; Zhao, Hua; Zhang, Wen; Guo, Ying-Jun; Nie, Lin

    2013-10-18

    Highlights: •CDNF was successfully transfected by a lentiviral vector into the distal sciatic nerve. •CDNF improved S-100, NF200 expression and nerve regeneration after sciatic injury. •CDNF improved the remyelination and thickness of the regenerated sciatic nerve. •CDNF improved gastrocnemius muscle weight and sciatic functional recovery. -- Abstract: Peripheral nerve injury is often followed by incomplete and unsatisfactory functional recovery and may be associated with sensory and motor impairment of the affected limb. Therefore, a novel method is needed to improve the speed of recovery and the final functional outcome after peripheral nerve injuries. This report investigates the effect of lentiviral-mediated transfer of conserved dopamine neurotrophic factor (CDNF) on regeneration of the rat peripheral nerve in a transection model in vivo. We observed notable overexpression of CDNF protein in the distal sciatic nerve after recombinant CDNF lentiviral vector application. We evaluated sciatic nerve regeneration after surgery using light and electron microscopy and the functional recovery using the sciatic functional index and target muscle weight. HE staining revealed better ordered structured in the CDNF-treated group at 8 weeks post-surgery. Quantitative analysis of immunohistochemistry of NF200 and S-100 in the CDNF group revealed significant improvement of axonal and Schwann cell regeneration compared with the control groups at 4 weeks and 8 weeks after injury. The thickness of the myelination around the axons in the CDNF group was significantly higher than in the control groups at 8 weeks post-surgery. The CDNF group displayed higher muscle weights and significantly increased sciatic nerve index values. Our findings suggest that CDNF gene therapy could provide durable and stable CDNF protein concentration and has the potential to enhance peripheral nerve regeneration, morphological and functional recovery following nerve injury, which suggests a

  16. Localized and Sustained Delivery of Erythropoietin from PLGA Microspheres Promotes Functional Recovery and Nerve Regeneration in Peripheral Nerve Injury

    PubMed Central

    Zhang, Wei; Gao, Yuan; Zhou, Yan; Liu, Jianheng; Zhang, Licheng; Long, Anhua; Zhang, Lihai; Tang, Peifu

    2015-01-01

    Erythropoietin (EPO) has been demonstrated to exert neuroprotective effects on peripheral nerve injury recovery. Though daily intraperitoneal injection of EPO during a long period of time was effective, it was a tedious procedure. In addition, only limited amount of EPO could reach the injury sites by general administration, and free EPO is easily degraded in vivo. In this study, we encapsulated EPO in poly(lactide-co-glycolide) (PLGA) microspheres. Both in vitro and in vivo release assays showed that the EPO-PLGA microspheres allowed sustained release of EPO within a period of two weeks. After administration of such EPO-PLGA microspheres, the peripheral nerve injured rats had significantly better recovery compared with those which received daily intraperitoneal injection of EPO, empty PLGA microspheres, or saline treatments. This was supported by the functional, electrophysiological, and histological evaluations of the recovery done at week 8 postoperatively. We conclude that sustained delivery of EPO could be achieved by using EPO-PLGA microspheres, and such delivery method could further enhance the recovery function of EPO in nerve injury recovery. PMID:25821803

  17. Using ecological function to develop recovery criteria for depleted species: sea otters and kelp forests in the Aleutian archipelago

    USGS Publications Warehouse

    Estes, James A.; Tinker, M. Tim; Bodkin, James L.

    2010-01-01

    Recovery criteria for depleted species or populations normally are based on demographic measures, the goal being to maintain enough individuals over a sufficiently large area to assure a socially tolerable risk of future extinction. Such demographically based recovery criteria may be insufficient to restore the functional roles of strongly interacting species. We explored the idea of developing a recovery criterion for sea otters (Enhydra lutris) in the Aleutian archipelago on the basis of their keystone role in kelp forest ecosystems. We surveyed sea otters and rocky reef habitats at 34 island-time combinations. The system nearly always existed in either a kelp-dominated or deforested phase state, which was predictable from sea otter density. We used a resampling analysis of these data to show that the phase state at any particular island can be determined at 95% probability of correct classification with information from as few as six sites. When sea otter population status (and thus the phase state of the kelp forest) was allowed to vary randomly among islands, just 15 islands had to be sampled to estimate the true proportion that were kelp dominated (within 10%) with 90% confidence. We conclude that kelp forest phase state is a more appropriate, sensitive, and cost-effective measure of sea otter recovery than the more traditional demographically based metrics, and we suggest that similar approaches have broad potential utility in establishing recovery criteria for depleted populations of other functionally important species.

  18. Knockdown of Nogo gene by short hairpin RNA interference promotes functional recovery of spinal cord injury in a rat model.

    PubMed

    Liu, Guo-Min; Luo, Yun-Gang; Li, Juan; Xu, Kun

    2016-05-01

    The specific myelin component Nogo protein is one of the major inhibitory molecules of spinal cord axonal outgrowth following spinal cord injury. The present study aimed to investigate the effects of silencing Nogo protein with shRNA interference on the promotion of functional recovery in a rat model with spinal cord hemisection. Nogo-A short hairpin RNAs (Nogo shRNAs) were constructed and transfected into rats with spinal cord hemisection by adenovirus-mediated transfection. Reverse transcription‑polymerase chain reaction and western blotting were performed to analyze the expression of Nogo-A and Growth Associated Protein 43 (GAP-43). In addition, Basso Beattie Bresnahan (BBB) scores were used to assess the functional recovery of rats following spinal cord injury. The results demonstrated that expression of the Nogo‑A gene was observed to be downregulated following transfection and GAP‑43 expression was observed to increase. The BBB scores were increased following treatment with Nogo shRNAs, indicating functional recovery of the injured nerves. Thus, Nogo-A shRNA interference can knockdown Nogo gene expression and upregulate GAP-43 to promote the functional recovery of spinal cord injury in rats. This finding may advance progress toward assisting the regeneration of injured neurons through the use of Nogo-A shRNA. PMID:27035338

  19. Initial Sensorimotor and Cardiovascular Data Acquired from Soyuz Landings: Establishing a Functional Performance Recovery Time Constant

    NASA Technical Reports Server (NTRS)

    Reschke, M. F.; Kozlovskaya, I. B.; Kofman, I. S.; Tomilovskaya, E. S.; Cerisano, J. M.; Bloomberg, J. J.; Stenger, M. B.; Platts, S. H.; Rukavishnikov, I. V.; Fomina, E. V.; Lee, S. M. C.; Wood, S. J.; Mulavara, A. P.; Feiveson, A. H.; Fisher, E. A.

    2015-01-01

    INTRODUCTION Testing of crew responses following long-duration flights has not been previously possible until a minimum of more than 24 hours after landing. As a result, it has not been possible to determine the trend of the early recovery process, nor has it been possible to accurately assess the full impact of the decrements associated with long-duration flight. To overcome these limitations, both the Russian and U.S. programs have implemented joint testing at the Soyuz landing site. This International Space Station research effort has been identified as the functional Field Test, and represents data collect on NASA, Russian, European Space Agency, and Japanese Aerospace Exploration Agency crews. RESEARCH The primary goal of this research is to determine functional abilities associated with long-duration space flight crews beginning as soon after landing as possible on the day of landing (typically within 1 to 1.5 hours). This goal has both sensorimotor and cardiovascular elements. To date, a total of 15 subjects have participated in a 'pilot' version of the full 'field test'. The full version of the 'field test' will assess functional sensorimotor measurements included hand/eye coordination, standing from a seated position (sit-to-stand), walking normally without falling, measurement of dynamic visual acuity, discriminating different forces generated with the hands (both strength and ability to judge just noticeable differences of force), standing from a prone position, coordinated walking involving tandem heel-to-toe placement (tested with eyes both closed and open), walking normally while avoiding obstacles of differing heights, and determining postural ataxia while standing (measurement of quiet stance). Sensorimotor performance has been obtained using video records, and data from body worn inertial sensors. The cardiovascular portion of the investigation has measured blood pressure and heart rate during a timed stand test in conjunction with postural ataxia

  20. Mutual connectivity analysis (MCA) using generalized radial basis function neural networks for nonlinear functional connectivity network recovery in resting-state functional MRI

    NASA Astrophysics Data System (ADS)

    D'Souza, Adora M.; Abidin, Anas Zainul; Nagarajan, Mahesh B.; Wismüller, Axel

    2016-03-01

    We investigate the applicability of a computational framework, called mutual connectivity analysis (MCA), for directed functional connectivity analysis in both synthetic and resting-state functional MRI data. This framework comprises of first evaluating non-linear cross-predictability between every pair of time series prior to recovering the underlying network structure using community detection algorithms. We obtain the non-linear cross-prediction score between time series using Generalized Radial Basis Functions (GRBF) neural networks. These cross-prediction scores characterize the underlying functionally connected networks within the resting brain, which can be extracted using non-metric clustering approaches, such as the Louvain method. We first test our approach on synthetic models with known directional influence and network structure. Our method is able to capture the directional relationships between time series (with an area under the ROC curve = 0.92 +/- 0.037) as well as the underlying network structure (Rand index = 0.87 +/- 0.063) with high accuracy. Furthermore, we test this method for network recovery on resting-state fMRI data, where results are compared to the motor cortex network recovered from a motor stimulation sequence, resulting in a strong agreement between the two (Dice coefficient = 0.45). We conclude that our MCA approach is effective in analyzing non-linear directed functional connectivity and in revealing underlying functional network structure in complex systems.

  1. Required distribution of noise sources for Green's function recovery in diffusive fields

    NASA Astrophysics Data System (ADS)

    Shamsalsadati, S.; Weiss, C. J.

    2011-12-01

    In the most general sense, noise is the part of the signal of little or no interest, due to a multitude of reasons such as operator error, imperfect instrumentation, experiment design, or inescapable background interference. Considering the latter, it has been shown that Green's function can be extracted from cross-correlation of the ambient, diffusive wavefields arising from background random noise sources. Pore pressure and low-frequency electromagnetic induction are two such examples of diffusive fields. In theory, applying Green's function method in geophysical exploration requires infinity of volumetrically distributed sources; however, in the real world the number of noise sources in an area is limited, and furthermore, unevenly distributed in time, space and spectral content. Hence, quantification of the requisite noise sources that enable us to calculate Green's function acceptably well remains an open research question. The purpose of this study is to find the area of noise sources that contribute most to the Green's function estimation in diffusive systems. We call such a region the Volume of Relevance (VoR). Our analysis builds upon recent work in 1D homogeneous system where it was shown that sources located between two receivers positions are the most important ones for the purpose of Green's function recovery. Our results confirm the previous finding but we also examine the effect of heterogeneity, dimensionality and receiver location in both 1D and 2D at a fixed frequency. We demonstrate that for receivers located symmetrically across an interface between regions of contrasting diffusivity, the VoR rapidly shifts from one side of the interface to the other, and back again, as receiver separation increases. We also demonstrate that where the receiver pair is located on the interface itself, the shifting is less rapid, and for moderate to high diffusivity contrasts, the VoR remains entirely on the more diffusive side. In addition, because classical

  2. Overexpression of Sox11 Promotes Corticospinal Tract Regeneration after Spinal Injury While Interfering with Functional Recovery

    PubMed Central

    Wang, Zimei; Reynolds, Ashley; Kirry, Adam; Nienhaus, Christopher

    2015-01-01

    Embryonic neurons, peripheral neurons, and CNS neurons in zebrafish respond to axon injury by initiating pro-regenerative transcriptional programs that enable axons to extend, locate appropriate targets, and ultimately contribute to behavioral recovery. In contrast, many long-distance projection neurons in the adult mammalian CNS, notably corticospinal tract (CST) neurons, display a much lower regenerative capacity. To promote CNS repair, a long-standing goal has been to activate pro-regenerative mechanisms that are normally missing from injured CNS neurons. Sox11 is a transcription factor whose expression is common to a many types of regenerating neurons, but it is unknown whether suboptimal Sox11 expression contributes to low regenerative capacity in the adult mammalian CNS. Here we show in adult mice that dorsal root ganglion neurons (DRGs) and CST neurons fail to upregulate Sox11 after spinal axon injury. Furthermore, forced viral expression of Sox11 reduces axonal dieback of DRG axons, and promotes CST sprouting and regenerative axon growth in both acute and chronic injury paradigms. In tests of forelimb dexterity, however, Sox11 overexpression in the cortex caused a modest but consistent behavioral impairment. These data identify Sox11 as a key transcription factor that can confer an elevated innate regenerative capacity to CNS neurons. The results also demonstrate an unexpected dissociation between axon growth and behavioral outcome, highlighting the need for additional strategies to optimize the functional output of stimulated neurons. PMID:25698749

  3. The effect of ubiquinone on functional recovery and morphometric indices of sciatic nerve regeneration

    PubMed Central

    Moradi, Z; Azizi, S; Hobbenaghi, R

    2014-01-01

    A common cause of peripheral nerve injury is trauma. The positive effect of antioxidants on the improvement of nerve regeneration has currently become a focus of attention. In this experiment, the effect of intraperitoneal administration of ubiquinone (CoQ10) on an acute experimentally sciatic nerve crush was studied in a rat model. Forty-five male Wistar rats, weighing between 160-180 g were used. The rats were randomly divided into two experimental groups (n=20). Each group was further subdivided into four subgroups of five animals each. Functional studies confirmed the faster recovery of regenerated axons in the treatment group compared to the un-treated group (P<0.05). Morphometric indices of the regenerated fibers showed the number and diameter of the myelinated fibers to be significantly higher in the treatment group than the un-treated group (P<0.05). Intraperitoneal administration of CoQ10 (10 mg/kg/day) in the early inflammatory stage of sciatic nerve crush was found to improve nerve regeneration. PMID:27175137

  4. Atrophied cardiomyocytes and their potential for rescue and recovery of ventricular function.

    PubMed

    Heckle, Mark R; Flatt, David M; Sun, Yao; Mancarella, Salvatore; Marion, Tony N; Gerling, Ivan C; Weber, Karl T

    2016-03-01

    Cardiomyocytes must be responsive to demands placed on the heart's contractile work as a muscular pump. In turn, myocyte size is largely dependent on the workload they perform. Both hypertrophied and atrophic myocytes are found in the normal and diseased ventricle. Individual myocytes become atrophic when encumbered by fibrillar collagen, such as occurs at sites of fibrosis. The mechanisms include: (a) being immobilized and subject to disuse with ensuing protein degradation mediated by redox-sensitive, proteolytic ligases of the ubiquitin-proteasome system and (b) dedifferentiated re-expressing fetal genes induced by low intracellular triiodothyronine (T3) via thyroid hormone receptor β1. This myocyte-selective, low T3 state is a consequence of heterocellular signaling emanating from juxtaposed scar tissue myofibroblasts and their secretome with its de novo generation of angiotensin II. In a paracrine manner, angiotensin II promotes myocyte Ca(2+) entry and subsequent Ca(2+) overload with ensuing oxidative stress that overwhelms antioxidant defenses to activate deiodinase-3 and its enzymatic degradation of T3. In the failing heart, atrophic myocytes represent an endogenous population of viable myocytes which could be rescued to augment contractile mass, reduce systolic wall stress (afterload) and recover ventricular function. Experimental studies have shown the potential for the rescue and recovery of atrophic myocytes in rebuilding the myocardium-a method complementary to today's quest in regenerating myocardium using progenitor cells. PMID:26872676

  5. Effects of Rolipram on Adult Rat Oligodendrocytes and Functional Recovery after Contusive Cervical Spinal Cord Injury

    PubMed Central

    Beaumont, Eric; Whitaker, Christopher M.; Burke, Darlene A.; Hetman, Michal; Onifer, Stephen M.

    2009-01-01

    Traumatic human spinal cord injury causes devastating and long-term hardships. These are due to the irreparable primary mechanical injury and secondary injury cascade. In particular, oligodendrocyte cell death, white matter axon damage, spared axon demyelination, and the ensuing dysfunction in action potential conduction lead to the initial deficits and impair functional recovery. For these reasons, and that oligodendrocyte and axon survival may be related, various neuroprotective strategies after SCI are being investigated. We previously demonstrated that oligodendrocytes in the adult rat epicenter ventrolateral funiculus express 3′-5′-cyclic adenosine monophosphate-dependent phosphodiesterase 4 subtypes and that their death was attenuated up to 3 days after contusive cervical spinal cord injury when rolipram, a specific inhibitor of phosphodiesterase 4, was administered. Here, we report that 1) there are more oligodendrocyte somata in the adult rat epicenter ventrolateral funiculus, 2) descending and ascending axonal conductivity in the ventrolateral funiculus improves, and that 3) there are fewer hindlimb footfall errors during grid-walking at 5 weeks after contusive cervical spinal cord injury when rolipram is delivered for 2 weeks. This is the first demonstration of improved descending and ascending long-tract axonal conductivity across a spinal cord injury with this pharmacological approach. Since descending long-tract axonal conductivity did not return to normal, further evaluations of the pharmacokinetics and therapeutic window of rolipram as well as optimal combinations are necessary before consideration for neuroprotection in humans with spinal cord injury. PMID:19635528

  6. Targeting the Cholinergic System for Neuroprotection and/or Enhancement of Functional Recovery Following Neurotrauma.

    PubMed

    Huber, Kathleen B G; Uteshev, Victor V; Pauly, James R

    2016-01-01

    Development of novel pharmacotherapies for the treatment of traumatic injury to the nervous system has been ongoing for over 40 years. Despite many promising compounds discovered using animal models, no treatments have successfully translated into the clinic. The central dogma in this field is that brain trauma initiates a complex chain of biochemical events leading to secondary brain damage and sustained neurological deficits. The delayed secondary brain injury is likely to result from multiple insults including oxidative stress, mitochondrial dysfunction, breakdown of the blood brain barrier, dysregulated release of glutamate, pro-inflammatory cytokines, and other mediators. However, therapies targeting these systems have generally met with failure in clinical trials. The purpose of this review is to summarize the models used for preclinical neurotrauma research, provide a brief overview of previous failed clinical trials in head and spinal cord injury, and finally, to review involvement of the cholinergic system and discuss implications for future research. Possibilities and pitfalls of targeting the cholinergic system for neuroprotection and/or enhancement of functional recovery are also discussed. PMID:26818862

  7. FGF2 and FGFR1 signaling regulate functional recovery following cuprizone demyelination.

    PubMed

    Mierzwa, Amanda J; Zhou, Yong-Xing; Hibbits, Norah; Vana, Adam C; Armstrong, Regina C

    2013-08-26

    In demyelinating diseases, such as multiple sclerosis, remyelination offers the potential to recover function of viable denuded axons by restoring saltatory conduction and/or protecting from further damage. Mice with genetic reduction of fibroblast growth factor 2 (Fgf2) or Fgf receptor 1 (Fgfr1) exhibit dramatically improved remyelination following experimental demyelination with cuprizone. The current studies are the first to test neurobehavioral outcomes with these gene deletions that improved remyelination. The cuprizone protocols used did not produce overt abnormalities but did reduce bilateral sensorimotor coordination (complex wheel task) and increase sociability (two chamber apparatus with novel mouse). A significant effect of genotype was observed on the complex wheel task but not in the sociability apparatus. Specifically, complex wheel velocities for Fgf2 nulls improved significantly after removal of cuprizone from the diet. This improvement in Fgf2 null mice occurred following either acute (6 weeks) or chronic (12 weeks) demyelination. Plp/CreERT:Fgfr1(fl/fl) mice administered tamoxifen at 10 weeks of cuprizone treatment to induce Fgfr1 knockdown also showed improved recovery of running velocities on the complex wheels. Therefore, constitutive deletion of Fgf2 or Fgfr1 knockdown in oligodendrocyte lineage cells is sufficient to overcome impairment of sensorimotor coordination after cuprizone demyelination. PMID:23684572

  8. The potential synergism by combining external counterpulsation with intermittent theta burst stimulation in post-stroke motor function recovery.

    PubMed

    He, Weijia; Au-Yeung, Suk-Yin Stephanie; Mak, Margaret; Leung, Thomas Wai Hong; Leung, Howan; Wong, Lawrence Ka Sing

    2016-08-01

    Upper limb weakness and incoordination is a common disability following ischemic stroke. Previous studies have showed that the single application of external counterpulsation (ECP) and intermittent theta burst stimulation (iTBS) can effectively enhance the cortical motor excitability and facilitate recovery. However, it remains uncertain if sequential application of these therapies would further augment the recovery. We hypothesize a synergistic effect of ECP followed by iTBS to upper limb function may happen through improvements in both cerebral perfusion and neuron excitability. PMID:27372874

  9. Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers.

    PubMed

    Kjell, Jacob; Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew; Olson, Lars

    2015-11-01

    With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines--monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)--to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. PMID:25914996

  10. Hyperbaric oxygenation enhances transplanted cell graft and functional recovery in the infarct heart

    PubMed Central

    Khan, Mahmood; Meduru, Sarath; Mohan, Iyyapu K.; Kuppusamy, M. Lakshmi; Wisel, Sheik; Kulkarni, Aditi; Rivera, Brian K.; Hamlin, Robert L.; Kuppusamy, Periannan

    2009-01-01

    A major limitation to the application of stem-cell therapy to repair ischemic heart damage is the low survival of transplanted cells in the heart, possibly due to poor oxygenation. We hypothesized that hyperbaric oxygenation (HBO) can be used as an adjuvant treatment to augment stem-cell therapy. Therefore, the goal of this study was to evaluate the effect of HBO on the engraftment of rat bone-marrow-derived mesenchymal stem cells (MSCs) transplanted in infarct rat hearts. Myocardial infarction (MI) was induced in Fisher-344 rats by permanently ligating the left-anterior-descending coronary artery. MSCs, labeled with fluorescent superparamagnetic iron oxide (SPIO) particles, were transplanted in the infarct and peri-infarct regions of the MI hearts. HBO (100% oxygen at 2 ATA for 90 min) was administered daily for 2 weeks. Four MI groups were used: untreated (MI); HBO; MSC; MSC+HBO. Echocardiography, electro-vectorcardiography, and magnetic resonance imaging were used for functional evaluations. The engraftment of transplanted MSCs in the heart was confirmed by SPIO fluorescence and Prussian-blue staining. Immunohistochemical staining was used to identify key cellular and molecular markers including CD29, troponin-T, connexin-43, VEGF, α-smooth-muscle actin, and von-Willebrand factor in the tissue. Compared to MI and MSC groups, the MSC+HBO group showed a significantly increased recovery of cardiac function including left-ventricular (LV) ejection fraction, fraction-shortening, LV wall-thickness, and QRS vector. Further, HBO treatment significantly increased the engraftment of CD29-positive cells, expression of connexin-43, troponin-T and VEGF, and angiogenesis in the infarct tissue. Thus, HBO appears to be a potential and clinically-viable adjuvant treatment for myocardial stem-cell therapy. PMID:19376124

  11. Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers

    PubMed Central

    Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I.; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew

    2015-01-01

    Abstract With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines—monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)—to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. PMID:25914996

  12. Functional recovery of supersensitive dopamine receptors after intrastriatal grafts of fetal substantia nigra

    SciTech Connect

    Dawson, T.M.; Dawson, V.L.; Gage, F.H.; Fisher, L.J.; Hunt, M.A.; Wamsley, J.K. )

    1991-03-01

    Interruption of the ascending dopamine neurons of the nigrostriatal pathway, by 6-hydroxydopamine (6-OHDA) lesion in rats, produced a significant loss of the dopamine transport complexes labeled with the phencyclidine derivative (3H)BTCP. This loss of dopamine innervation in the striatum was present at least 12 to 14 months after lesioning and was functionally manifested by ipsilateral rotation of the animals in response to amphetamine. In these same animals, in comparison to controls, there was a significant increase in the number (Bmax) of (3H)SCH 23390-labeled D-1 receptors in the striatum (36.7%) and the substantia nigra (35.1%) and a 54.4% increase in the number (Bmax) of (3H)sulpiride-labeled striatal D-2 receptors without an apparent change in affinity (Kd). Ten to twelve months after the transplantation of homologous fetal substantia nigra into the denervated striatum, there was a significant decrease in amphetamine-induced turning behavior. In these animals, there was an ingrowth of dopamine nerve terminals in the striatum as demonstrated by a return of (3H)BTCP binding. Accompanying this reinnervation was the normalization of D-1 and D-2 receptors to control values in the striatum as well as the return of D-1 receptors to prelesion densities in the substantia nigra. In a subgroup of transplanted rats, amphetamine continued to induce ipsilateral turning. In these animals both D-1 and D-2 receptors remained supersensitive. These results support the hypothesis that the functional recovery of transplanted animals is due, in part, to reinnervation of the striatum. In addition, long-term alterations in receptor density may be related to the behavioral deficits that are associated with the 6-OHDA-lesioned rat.

  13. Muscle Ciliary Neurotrophic Factor Receptor α Promotes Axonal Regeneration and Functional Recovery Following Peripheral Nerve Lesion

    PubMed Central

    Lee, Nancy; Spearry, Rachel P.; Leahy, Kendra M.; Robitz, Rachel; Trinh, Dennis S.; Mason, Carter O.; Zurbrugg, Rebekah J.; Batt, Myra K.; Paul, Richard J.; Maclennan, A. John

    2014-01-01

    Ciliary neurotrophic factor (CNTF) administration maintains, protects, and promotes the regeneration of both motor neurons (MNs) and skeletal muscle in a wide variety of models. Expression of CNTF receptor α (CNTFRα), an essential CNTF receptor component, is greatly increased in skeletal muscle following neuromuscular insult. Together the data suggest that muscle CNTFRα may contribute to neuromuscular maintenance, protection, and/or regeneration in vivo. To directly address the role of muscle CNTFRα, we selectively-depleted it in vivo by using a “floxed” CNTFRα mouse line and a gene construct (mlc1f-Cre) that drives the expression of Cre specifically in skeletal muscle. The resulting mice were challenged with sciatic nerve crush. Counting of nerve axons and retrograde tracing of MNs indicated that muscle CNTFRα contributes to MN axonal regeneration across the lesion site. Walking track analysis indicated that muscle CNTFRα is also required for normal recovery of motor function. However, the same muscle CNTFRα depletion unexpectedly had no detected effect on the maintenance or regeneration of the muscle itself, even though exogenous CNTF has been shown to affect these functions. Similarly, MN survival and lesion-induced terminal sprouting were unaffected. Therefore, muscle CNTFRα is an interesting new example of a muscle growth factor receptor that, in vivo under physiological conditions, contributes much more to neuronal regeneration than to the maintenance or regeneration of the muscle itself. This novel form of muscle–neuron interaction also has implications in the therapeutic targeting of the neuromuscular system in MN disorders and following nerve injury. PMID:23504871

  14. Whole-body vibration improves functional recovery in spinal cord injured rats.

    PubMed

    Wirth, Felicitas; Schempf, Greta; Stein, Gregor; Wellmann, Katharina; Manthou, Marilena; Scholl, Carolin; Sidorenko, Malina; Semler, Oliver; Eisel, Leonie; Harrach, Rachida; Angelova, Srebrina; Jaminet, Patrick; Ankerne, Janina; Ashrafi, Mahak; Ozsoy, Ozlem; Ozsoy, Umut; Schubert, Harald; Abdulla, Diana; Dunlop, Sarah A; Angelov, Doychin N; Irintchev, Andrey; Schönau, Eckhard

    2013-03-15

    Whole-body vibration (WBV) is a relatively novel form of exercise used to improve neuromuscular performance in healthy individuals. Its usefulness as a therapy for patients with neurological disorders, in particular spinal cord injury (SCI), has received little attention in clinical settings and, surprisingly, even less in animal SCI models. We performed severe compression SCI at a low-thoracic level in Wistar rats followed by daily WBV starting 7 (10 rats) or 14 (10 rats) days after injury (WBV7 and WBV14, respectively) and continued over a 12-week post-injury period. Rats with SCI but no WBV training (sham, 10 rats) and intact animals (10 rats) served as controls. Compared to sham-treated rats, WBV did not improve BBB score, plantar stepping, or ladder stepping during the 12-week period. Accordingly, WBV did not significantly alter plantar H-reflex, lesion volume, serotonergic input to the lumbar spinal cord, nor cholinergic or glutamatergic inputs to lumbar motoneurons at 12 weeks after SCI. However, compared to sham, WBV14, but not WBV7, significantly improved body weight support (rump-height index) during overground locomotion and overall recovery between 6-12 weeks and also restored the density of synaptic terminals in the lumbar spinal cord at 12 weeks. Most remarkably, WBV14 led to a significant improvement of bladder function at 6-12 weeks after injury. These findings provide the first evidence for functional benefits of WBV in an animal SCI model and warrant further preclinical investigations to determine mechanisms underpinning this noninvasive, inexpensive, and easily delivered potential rehabilitation therapy for SCI. PMID:23157611

  15. Thermographic evaluation of hind paw skin temperature and functional recovery of locomotion after sciatic nerve crush in rats

    PubMed Central

    Z. Sacharuk, Viviane; A. Lovatel, Gisele; Ilha, Jocemar; Marcuzzo, Simone; Severo do Pinho, Alexandre; L. Xavier, Léder; A. Zaro, Milton; Achaval, Matilde

    2011-01-01

    INTRODUCTION: Peripheral nerves are often damaged by direct mechanical injury, diseases, and tumors. The peripheral nerve injuries that result from these conditions can lead to a partial or complete loss of motor, sensory, and autonomic functions, which in turn are related to changes in skin temperature, in the involved segments of the body. The aim of this study was to evaluate the changes in hind paw skin temperature after sciatic nerve crush in rats in an attempt to determine whether changes in skin temperature correlate with the functional recovery of locomotion. METHODS: Wistar rats were divided into three groups: control (n = 7), sham (n = 25), and crush (n = 25). All groups were subjected to thermographic, functional, and histological assessments. RESULTS: ΔT in the crush group was different from the control and sham groups at the 1st, 3rd and 7rd postoperative days (p<0.05). The functional recovery from the crush group returned to normal values between the 3rd and 4th week post-injury, and morphological analysis of the nerve revealed incomplete regeneration at the 4th week after injury. DISCUSSION: This study is the first demonstration that sciatic nerve crush in rats induces an increase in hind paw skin temperature and that skin temperature changes do not correlate closely with functional recovery PMID:21876984

  16. Enhanced oil recovery with hydrophobically associating polymers containing n-vinyl-pyrrolidone functionality

    SciTech Connect

    Bridgewater, J.B.; Pace, S.J.; Gardner, G.; Schulz, D.N.

    1987-12-01

    This invention relates to a method for enhanced recovery of petroleum from a subterranean oil-bearing formation. More particularly, this invention relates to secondary or tertiary recovery of oil employing a polymer-thickened aqueous drive fluid. The polymeric viscosifier for the drive fluid is selected from a class of hydrophobically associating, water soluble polymers containing one or more water soluble monomers and a water insoluble monomer group. The water soluble groups are acrylamide and a salt of acrylic acid and the water insoluble group is a higher alkylacrylamide. These polymers, when dissolved in an aqueous brine solution, have the ability to substantially increase the viscosity of the aqueous solution. The control of displacement fluid mobility results in more uniform sweep efficiency and improved oil recovery. In addition, aqueous solutions of these hydrophobically associating polymers exhibit enhanced viscosification, reduced salt sensitivity and other desirable rheological properties found useful in chemically enhanced oil recovery processes.

  17. Apolipoprotein E Mimetic Promotes Functional and Histological Recovery in Lysolecithin-Induced Spinal Cord Demyelination in Mice

    PubMed Central

    Gu, Zhen; Li, Fengqiao; Zhang, Yi Ping; Shields, Lisa B.E.; Hu, Xiaoling; Zheng, Yiyan; Yu, Panpan; Zhang, Yongjie; Cai, Jun; Vitek, Michael P.; Shields, Christopher B.

    2014-01-01

    Objective Considering demyelination is the pathological hallmark of multiple sclerosis (MS), reducing demyelination and/or promoting remyelination is a practical therapeutic strategy to improve functional recovery for MS. An apolipoprotein E (apoE)-mimetic peptide COG112 has previously demonstrated therapeutic efficacy on functional and histological recovery in a mouse experimental autoimmune encephalomyelitis (EAE) model of human MS. In the current study, we further investigated whether COG112 promotes remyelination and improves functional recovery in lysolecithin induced focal demyelination in the white matter of spinal cord in mice. Methods A focal demyelination model was created by stereotaxically injecting lysolecithin into the bilateral ventrolateral funiculus (VLF) of T8 and T9 mouse spinal cords. Immediately after lysolecithin injection mice were treated with COG112, prefix peptide control or vehicle control for 21 days. The locomotor function of the mice was measured by the beam walking test and Basso Mouse Scale (BMS) assessment. The nerve transmission of the VLF of mice was assessed in vivo by transcranial magnetic motor evoked potentials (tcMMEPs). The histological changes were also examined by by eriochrome cyanine staining, immunohistochemistry staining and electron microscopy (EM) method. Results The area of demyelination in the spinal cord was significantly reduced in the COG112 group. EM examination showed that treatment with COG112 increased the thickness of myelin sheaths and the numbers of surviving axons in the lesion epicenter. Locomotor function was improved in COG112 treated animals when measured by the beam walking test and BMS assessment compared to controls. TcMMEPs also demonstrated the COG112-mediated enhancement of amplitude of evoked responses. Conclusion The apoE-mimetic COG112 demonstrates a favorable combination of activities in suppressing inflammatory response, mitigating demyelination and in promoting remyelination and

  18. Function-Triggering Antibodies to the Adhesion Molecule L1 Enhance Recovery after Injury of the Adult Mouse Femoral Nerve

    PubMed Central

    Guseva, Daria; Loers, Gabriele; Schachner, Melitta

    2014-01-01

    L1 is among the few adhesion molecules that favors repair after trauma in the adult central nervous system of vertebrates by promoting neuritogenesis and neuronal survival, among other beneficial features. In the peripheral nervous system, L1 is up-regulated in Schwann cells and regrowing axons after nerve damage, but the functional consequences of this expression remain unclear. Our previous study of L1-deficient mice in a femoral nerve injury model showed an unexpected improved functional recovery, attenuated motoneuronal cell death, and enhanced Schwann cell proliferation, being attributed to the persistent synthesis of neurotrophic factors. On the other hand, transgenic mice over-expressing L1 in neurons led to improved remyelination, but not improved functional recovery. The present study was undertaken to investigate whether the monoclonal L1 antibody 557 that triggers beneficial L1 functions in vitro would trigger these also in femoral nerve repair. We analyzed femoral nerve regeneration in C57BL/6J mice that received this antibody in a hydrogel filled conduit connecting the cut and sutured nerve before its bifurcation, leading to short-term release of antibody by diffusion. Video-based quantitative analysis of motor functions showed improved recovery when compared to mice treated with conduits containing PBS in the hydrogel scaffold, as a vehicle control. This improved recovery was associated with attenuated motoneuron loss, remyelination and improved precision of preferential motor reinnervation. We suggest that function-triggering L1 antibodies applied to the lesion site at the time of injury over a limited time period will not only be beneficial in peripheral, but also central nervous system regeneration. PMID:25393007

  19. Influence of Sexuality in Functional Recovery after Spinal Cord Injury in Rats

    PubMed Central

    Emamhadi, Mohammadreza; Soltani, Bahram; Babaei, Parvin; Mashhadinezhad, Hossein; Ghadarjani, Shervin

    2016-01-01

    Background: Spinal cord injury (SCI) is a major clinical condition and research is commonly done to find suitable treatment options. However, there are some degrees of spontaneous recovery after SCI and gender is said to be a contributing factor in recovery, but this is controversial. This study was done to compare the effects of sexual dimorphism on spontaneous recovery after spinal cord injury in Wistar Rats. Methods: Spinal cord lesions were made by compressing the cord at T9 level and making a spinal cord contusion. Routine care of each rat was done daily. The LSS scoring system was used to measure the locomotion of these rats and to compare the recovery rate between male and female rats. Results: The results suggested that there was no significant difference between the two sex in recovery. Conclusions: To be female does not seem to be a prognostic factor for recovery after SCI. However, this preliminary study should be repeated in other animals and in larger cohorts. PMID:26894220

  20. 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

  1. Effect of Delayed Peripheral Nerve Repair on Nerve Regeneration, Schwann Cell Function and Target Muscle Recovery

    PubMed Central

    Jonsson, Samuel; Wiberg, Rebecca; McGrath, Aleksandra M.; Novikov, Lev N.; Wiberg, Mikael; Novikova, Liudmila N.; Kingham, Paul J.

    2013-01-01

    Despite advances in surgical techniques for peripheral nerve repair, functional restitution remains incomplete. The timing of surgery is one factor influencing the extent of recovery but it is not yet clearly defined how long a delay may be tolerated before repair becomes futile. In this study, rats underwent sciatic nerve transection before immediate (0) or 1, 3, or 6 months delayed repair with a nerve graft. Regeneration of spinal motoneurons, 13 weeks after nerve repair, was assessed using retrograde labeling. Nerve tissue was also collected from the proximal and distal stumps and from the nerve graft, together with the medial gastrocnemius (MG) muscles. A dramatic decline in the number of regenerating motoneurons and myelinated axons in the distal nerve stump was observed in the 3- and 6-months delayed groups. After 3 months delay, the axonal number in the proximal stump increased 2–3 folds, accompanied by a smaller axonal area. RT-PCR of distal nerve segments revealed a decline in Schwann cells (SC) markers, most notably in the 3 and 6 month delayed repair samples. There was also a progressive increase in fibrosis and proteoglycan scar markers in the distal nerve with increased delayed repair time. The yield of SC isolated from the distal nerve segments progressively fell with increased delay in repair time but cultured SC from all groups proliferated at similar rates. MG muscle at 3- and 6-months delay repair showed a significant decline in weight (61% and 27% compared with contra-lateral side). Muscle fiber atrophy and changes to neuromuscular junctions were observed with increased delayed repair time suggestive of progressively impaired reinnervation. This study demonstrates that one of the main limiting factors for nerve regeneration after delayed repair is the distal stump. The critical time point after which the outcome of regeneration becomes too poor appears to be 3-months. PMID:23409189

  2. Employment Status as an Indicator of Recovery and Function One Year after Hematopoietic Stem Cell Transplantation.

    PubMed

    Morrison, Eleshia J; Ehlers, Shawna L; Bronars, Carrie A; Patten, Christi A; Brockman, Tabetha A; Cerhan, James R; Hogan, William J; Hashmi, Shahrukh K; Gastineau, Dennis A

    2016-09-01

    Employment after hematopoietic stem cell transplantation (HSCT) is an indicator of post-transplantation recovery and function, with economic and social implications. As survival rates for HSCT continue to improve, greater emphasis can be placed on factors affecting the quality of post-transplantation survival, including the ability to resume employment. A sample of recipients of autologous or allogeneic HSCT was accrued (n = 1000) to complete a longitudinal lifestyle survey before transplantation and at 1 year after transplantation. The present study examines associations between employment and patient characteristics, disease variables, illness status, and quality of life among 1-year survivors (n = 702). Participants had a mean age of 55 years (range, 18 to 78) and were predominately male (59.7%), married/partnered (77.1%), and non-Hispanic Caucasian (89.5%); most (79.4%) had received autologous transplantation. Of the 690 participants reporting some form of employment before illness diagnosis, 62.4% had returned to work by 1 year after HSCT. Full-time employment at 1 year after HSCT was significantly associated with remission of illness, improved illness, fewer post-transplantation hospitalizations, less fatigue and pain, higher quality of life, and higher rating of perceived health. Those unemployed because of their health reported the highest rates of fatigue and pain and lowest quality of life, and they were most likely to report poor perceived health. These findings highlight work reintegration as an important outcome and marker of survivors' overall adjustment after transplantation. Identifying factors affecting post-transplantation employment offers opportunities for behavioral interventions to target modifiable risk factors to optimize post-transplantation survivorship, inclusive of increased rates of return to work and decreased rates of associated disability. PMID:27220264

  3. Function of transected or avulsed rectus muscles following recovery using an anterior orbitotomy approach

    PubMed Central

    Pineles, Stacy L.; Laursen, Jessica; Goldberg, Robert A.; Demer, Joseph L.; Velez, Federico G.

    2013-01-01

    PURPOSE To assess the function of muscles retrieved from a retrobulbar location using an anterior orbitotomy approach and to identify the prognostic factors favoring a good outcome. METHODS The records of all patients undergoing anterior orbitotomy for the retrieval of a transected or avulsed muscle in a retrobulbar location were reviewed. Ocular motility, before and after retrieval (with ductions scaled from −4 to +4), was evaluated. RESULTS Record review identified 11 patients who had suffered trauma to 12 muscles (5 inferior, 6 medial, and 1 lateral rectus muscle). Ductions improved from −4 ± 0.4 preoperatively to −2.7 ± 0.9 postoperatively (P = 0.002); mean primary position deviation improved from 34Δ ± 14Δ-15Δ ± 9Δ (P < 0.001), and mean deviation in the field of action improved from 47Δ ± 20Δ-20Δ ± 22Δ (P = 0.02). Ductions improved by at least two units in three patients, all of whom had medial rectus trauma. Single binocular vision in primary gaze was achieved in 6 patients. Patients with medial rectus muscle injury and patients injured by sinus surgery had the lowest likelihood of recovering single binocular vision. CONCLUSIONS Our results are similar to historical series in which muscles were not retrieved and transpositions performed; however, muscle retrieval avoids risks associated with transposition surgeries such as anterior segment ischemia. Muscle recovery via the anterior orbitotomy approach may be reasonable to consider in those cases with a reasonable possibility of having active force generation postoperatively. PMID:22835914

  4. The Development of Functional Overreaching Is Associated with a Faster Heart Rate Recovery in Endurance Athletes

    PubMed Central

    Aubry, Anaël; Hausswirth, Christophe; Louis, Julien; Coutts, Aaron J.

    2015-01-01

    Purpose The aim of the study was to investigate whether heart rate recovery (HRR) may represent an effective marker of functional overreaching (f-OR) in endurance athletes. Methods and Results Thirty-one experienced male triathletes were tested (10 control and 21 overload subjects) before (Pre), and immediately after an overload training period (Mid) and after a 2-week taper (Post). Physiological responses were assessed during an incremental cycling protocol to exhaustion, including heart rate, catecholamine release and blood lactate concentration. Ten participants from the overload group developed signs of f-OR at Mid (i.e. -2.1 ± 0.8% change in performance associated with concomitant high perceived fatigue). Additionally, only the f-OR group demonstrated a 99% chance of increase in HRR during the overload period (+8 ± 5 bpm, large effect size). Concomitantly, this group also revealed a >80% chance of decreasing blood lactate (-11 ± 14%, large), plasma norepinephrine (-12 ± 37%, small) and plasma epinephrine peak concentrations (-51 ± 22%, moderate). These blood measures returned to baseline levels at Post. HRR change was negatively correlated to changes in performance, peak HR and peak blood metabolites concentrations. Conclusion These findings suggest that i) a faster HRR is not systematically associated with improved physical performance, ii) changes in HRR should be interpreted in the context of the specific training phase, the athletes perceived level of fatigue and the performance response; and, iii) the faster HRR associated with f-OR may be induced by a decreased central command and by a lower chemoreflex activity. PMID:26488766

  5. Treadmill Exercise Induced Functional Recovery after Peripheral Nerve Repair Is Associated with Increased Levels of Neurotrophic Factors

    PubMed Central

    Park, Jae-Sung; Höke, Ahmet

    2014-01-01

    Benefits of exercise on nerve regeneration and functional recovery have been reported in both central and peripheral nervous system disease models. However, underlying molecular mechanisms of enhanced regeneration and improved functional outcomes are less understood. We used a peripheral nerve regeneration model that has a good correlation between functional outcomes and number of motor axons that regenerate to evaluate the impact of treadmill exercise. In this model, the median nerve was transected and repaired while the ulnar nerve was transected and prevented from regeneration. Daily treadmill exercise resulted in faster recovery of the forelimb grip function as evaluated by grip power and inverted holding test. Daily exercise also resulted in better regeneration as evaluated by recovery of compound motor action potentials, higher number of axons in the median nerve and larger myofiber size in target muscles. Furthermore, these observations correlated with higher levels of neurotrophic factors, glial derived neurotrophic factor (GDNF), brain derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1), in serum, nerve and muscle suggesting that increase in muscle derived neurotrophic factors may be responsible for improved regeneration. PMID:24618564

  6. Sex Differences in Neuroanatomy of the Human Mirror Neuron System: Impact on Functional Recovery of Ischemic Hemiparetic Patients

    PubMed Central

    Motaqhey, Monireh; Ghanjal, Ali; Mastri Farahani, Reza; Ghabaee, Mojdeh; Kaka, Gholamreza; Noroziyan, Mohsen; Fadaee Fathabadi, Fatemeh

    2015-01-01

    Background: Considering the higher activity of mirror neuron system in females, they frequently have better performance in empathy, interpersonal sensitivity, and emotional recognition compared to males. Objectives: The purpose of this study was to assess whether gender difference in neuroanatomy of the human mirror neuron system has any impact on functional recovery of ischemic hemiparetic patients. Patients and Methods: This single-blind clinical trial was conducted on 24 patients with cerebrovascular accident (CVA) in the age range of 45 - 60 years, referring at a rehabilitation center in Tehran, Iran, during 2013 - 2014. Sampling method was stratified random sampling. The subjects were assigned to 2 groups of 12 males and 12 females. Then, each group was randomly divided into 2 groups (totally 4 groups, n = 6 for each group): women watching functional movies, control women, men watching functional movies, and control men. Movies were shown to patients and then, they were evaluated by Timed Up and Go (TUG), Six-minute walk test (SMW), Barthel index (BI), and Berg balance scale (BBS). Results: Comparison of all variables related to functional activities of all groups before and after watching movies revealed significant differences. The highest percentage of change and improvement was observed in groups 1 and 3 watching the functional movies (P = 0.0001). Percentage of improvement in women of groups 1 and 2 was higher than men in groups 3 and 4 (P = 0.0003). The changes in group of females watching the functional movies (group 1) were significantly greater than in other groups (P < 0.0001). Conclusions: The Sex differences in the neuroanatomy of the human mirror neuron system affect functional recovery of patients with hemiparesis. The improvement in studied women was found to be significantly greater than studied men. The results indicate a higher chance of recovery among hemiparetic women, especially those watching functional movies. PMID:26430528

  7. Synergist muscle ablation and recovery from nerve-repair grafting: contractile and metabolic function

    PubMed Central

    Larkin, Lisa M.; Kuzon, William M.; Halter, Jeffrey B.

    2009-01-01

    After nerve-repair grafting of medial gastrocnemius muscle, there is incomplete recovery of specific force and sustainable power, perhaps due to overcompensation by synergistic muscles. We hypothesized that increased workload due to synergist ablation would enhance graft recovery. Contractile and metabolic properties of control and nerve-repair grafted muscles, with and without synergist ablation, were determined after 120 days recovery. Specific force (N/cm2) and normalized power (W/kg) were less in the experimental groups compared with controls. Sustained power (W/kg) in the synergist-ablated nerve-repair grafted muscle was higher than nerve-repair grafted muscle, returning to control values. GLUT-4 protein was higher and glycogen content was diminished in both synergist-ablated groups. In summary, synergist ablation did not enhance the recovery of specific force or normalized power, but sustained power did recover, suggesting that metabolic and not mechanical parameters were responsible for this recovery. The enhanced endurance after synergist ablation was accompanied by increased GLUT-4 protein, suggesting a role for increased uptake of circulating glucose during contraction. PMID:11007584

  8. Functional lateralization in cingulate cortex predicts motor recovery after basal ganglia stroke.

    PubMed

    Li, Yao; Chen, Zengai; Su, Xin; Zhang, Xiaoliu; Wang, Ping; Zhu, Yajing; Xu, Qun; Xu, Jianrong; Tong, Shanbao

    2016-02-01

    The basal ganglia (BG) is involved in higher order motor control such as movement planning and execution of complex motor synergies. Neuroimaging study on stroke patients specifically with BG lesions would help to clarify the consequence of BG damage on motor control. In this paper, we performed a longitudinal study in the stroke patients with lesions in BG regions across three motor recovery stages, i.e., less than 2week (Session 1), 1-3m (Session 2) and more than 3m (Session 3). The patients showed an activation shift from bilateral hemispheres during early sessions (<3m) to the ipsilesional cortex in late session (>3m), suggesting a compensation effect from the contralesional hemisphere during motor recovery. We found that the lateralization of cerebellum(CB) for affected hand task correlated with patients' concurrent Fugl-Meyer index (FMI) in Session 2. Moreover, the cingulate cortex lateralization index in Session 2 was shown to significantly correlate with subsequent FMI change between Session 3 and Session 2, which serves as a prognostic marker for motor recovery. Our findings consolidated the close interactions between BG and CB during the motor recovery after stroke. The dominance of activation in contralateral cingulate cortex was associated with a better motor recovery, suggesting the important role of ipsilesional attention modulation in the early stage after BG stroke. PMID:26742641

  9. Glial growth factor 2 promotes functional recovery with treatment initiated up to 7 days after permanent focal ischemic stroke.

    PubMed

    Iaci, Jennifer F; Ganguly, Anindita; Finklestein, Seth P; Parry, Tom J; Ren, Jingmei; Saha, Subhash; Sietsma, Dana K; Srinivas, Maya; Vecchione, Andrea M; Caggiano, Anthony O

    2010-12-01

    Neuregulins are a family of growth factors essential for normal cardiac and nervous system development. The EGF-like domain of neuregulins contains the active site which binds and activates signaling cascades through ErbB receptors. A neuregulin-1 gene EGF-like fragment demonstrated neuroprotection in the transient middle cerebral artery occlusion (MCAO) stroke model and drastically reduced infarct volume (Xu et al., 2004). Here we use a permanent MCAO rat model to initially compare two products of the neuregulin-1 gene and also assess levels of recovery with acute versus delayed time to treatment. In the initial study full-length glial growth factor 2 (GGF2) and an EGF-like domain fragment were compared with acute intravenous delivery. In a second study GGF2 only was delivered starting at 24h, 3 days or 7 days after permanent ischemia was induced. In both studies daily intravenous administration continued for 10 days. Recovery of neurological function was assessed using limb placing and body swing tests. GGF2 had similar functional improvements compared to the EGF-like domain fragment at equimolar doses, and a higher dose of GGF2 demonstrated more robust functional improvements compared to a lower dose. GGF2 improved sensorimotor recovery with all treatment paradigms, even enhancing recovery of function with a delay of 7 days to treatment. Histological assessments did not show any associated reduction in infarct volume at either 48 h or 21 days post-ischemic event. Neurorestorative effects of this kind are of great potential clinical importance, given the difficulty of delivering neuroprotective therapies within a short time after an ischemic event in human patients. If confirmed by additional work including additional data on mechanism(s) of improved outcome with verification in other stroke models, one can make a compelling case to bring GGF2 to clinical trials as a neurorestorative approach to improving outcome following stroke injury. PMID:20691195

  10. A new method of measuring functional recovery after crushing the peripheral nerves in unanesthetized and unrestrained rats.

    PubMed

    Hasegawa, K

    1978-02-15

    The distances between the first and fifth digits and between the second and fourth digits of the rat's hind paw were measured after crushing the sciatic nerve. The distances between the digits recovered significantly faster in weak nerve crushing than in strong crushing, and faster in distal nerve crushing than in proximal crushing. These results suggest that this method is available for evaluating the functional recovery after nerve crushing. PMID:624375

  11. Omentum-Wrapped Scaffold with Longitudinally Oriented Micro-Channels Promotes Axonal Regeneration and Motor Functional Recovery in Rats

    PubMed Central

    Sheng, Qing-Song; Zhao, Wei; Luo, Zhuo-Jing

    2011-01-01

    Background Tissue-engineered nerve scaffolds hold great potential in bridging large peripheral nerve defects. However, insufficient vascularization of nerve scaffolds limited neural tissues survival and regeneration, which hampered the successful implantation and clinical application of nerve scaffolds. The omentum possesses a high vascularization capacity and enhances regeneration and maturation of tissues and constructs to which it is applied. However, combined application of nerve scaffolds and omentum on axonal regeneration and functional recovery in the treatment of large peripheral nerve defects has rarely been investigated thus far. Methods In the present study, an omentum-wrapped collagen-chitosan scaffold was used to bridge a 15-mm-long sciatic nerve defect in rats. Rats that received nerve autografts or scaffolds alone were served as positive control or negative control, respectively. The axonal regeneration and functional recovery were examined by a combination of walking track analysis, electrophysiological assessment, Fluoro-Gold (FG) retrograde tracing, as well as morphometric analyses to both regenerated nerves and target muscles. Findings The results demonstrated that axonal regeneration and functional recovery were in the similar range between the omentum-wrapping group and the autograft group, which were significantly better than those in the scaffold alone group. Further investigation showed that the protein levels of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were significantly higher in the omentum-wrapping group than those in the scaffold alone group in the early weeks after surgery. Conclusion These findings indicate that the omentum-wrapped scaffold is capable of enhancing axonal regeneration and functional recovery, which might be served as a potent alternative to nerve autografts. The beneficial effect of omentum-wrapping on nerve regeneration might be related with the

  12. Comparison of the effects of erythropoietin and anakinra on functional recovery and gene expression in a traumatic brain injury model

    PubMed Central

    Anderson, Gail D.; Peterson, Todd C.; Vonder Haar, Cole; Kantor, Eric D.; Farin, Fred M.; Bammler, Theo K.; MacDonald, James W.; Hoane, Michael R.

    2013-01-01

    The goal of this study was to compare the effects of two inflammatory modulators, erythropoietin (EPO) and anakinra, on functional recovery and brain gene expression following a cortical contusion impact (CCI) injury. Dosage regimens were designed to provide serum concentrations in the range obtained with clinically approved doses. Functional recovery was assessed using both motor and spatial learning tasks and neuropathological measurements conducted in the cortex and hippocampus. Microarray-based transcriptional profiling was used to determine the effect on gene expression at 24 h, 72 h, and 7 days post-CCI. Ingenuity Pathway Analysis was used to evaluate the effect on relevant functional categories. EPO and anakinra treatment resulted in significant changes in brain gene expression in the CCI model demonstrating acceptable brain penetration. At all three time points, EPO treatment resulted in significantly more differentially expressed genes than anakinra. For anakinra at 24 h and EPO at 24 h, 72 h, and 7 days, the genes in the top 3 functional categories were involved in cellular movement, inflammatory response and cell-to-cell signaling. For EPO, the majority of the genes in the top 10 canonical pathways identified were associated with inflammatory and immune signaling processes. This was true for anakinra only at 24 h post-traumatic brain injury (TBI). The immunomodulation effects of EPO and anakinra did not translate into positive effects on functional behavioral and lesion studies. Treatment with either EPO or anakinra failed to induce significant beneficial effects on recovery of function or produce any significant effects on the prevention of injury induced tissue loss at 30 days post-injury. In conclusion, treatment with EPO or anakinra resulted in significant effects on gene expression in the brain without affecting functional outcome. This suggests that targeting these inflammatory processes alone may not be sufficient for preventing secondary injuries

  13. Lithium accelerates functional motor recovery by improving remyelination of regenerating axons following ventral root avulsion and reimplantation.

    PubMed

    Fang, Xin-Yu; Zhang, Wen-Ming; Zhang, Chao-Fan; Wong, Wai-Man; Li, Wen; Wu, Wutian; Lin, Jian-Hua

    2016-08-01

    Brachial plexus injury (BPI) often involves the complete or partial avulsion of one or more of the cervical nerve roots, which leads to permanent paralysis of the innervated muscles. Reimplantation surgery has been attempted as a clinical treatment for brachial plexus root avulsion but has failed to achieve complete functional recovery. Lithium is a mood stabilizer drug that is used to treat bipolar disorder; however, its effects on spinal cord or peripheral nerve injuries have also been reported. The purpose of this study was to investigate whether lithium can improve functional motor recovery after ventral root avulsion and reimplantation in a rat model of BPI. The results showed that systemic treatment with a clinical dose of lithium promoted motor neuron outgrowth and increased the efficiency of motor unit regeneration through enhanced remyelination. An analysis of myelin-associated genes showed that the effects of lithium started during the early phase of remyelination and persisted through the late stage of the process. Efficient remyelination of the regenerated axons in the lithium-treated rats led to an earlier functional recovery. Therefore, we demonstrated that lithium might be a potential clinical treatment for BPI in combination with reimplantation surgery. PMID:27185485

  14. Comparison of in vivo postexercise phosphocreatine recovery and resting ATP synthesis flux for the assessment of skeletal muscle mitochondrial function.

    PubMed

    van den Broek, N M A; Ciapaite, J; Nicolay, K; Prompers, J J

    2010-11-01

    (31)P magnetic resonance spectroscopy (MRS) has been used to assess skeletal muscle mitochondrial function in vivo by measuring 1) phosphocreatine (PCr) recovery after exercise or 2) resting ATP synthesis flux with saturation transfer (ST). In this study, we compared both parameters in a rat model of mitochondrial dysfunction with the aim of establishing the most appropriate method for the assessment of in vivo muscle mitochondrial function. Mitochondrial dysfunction was induced in adult Wistar rats by daily subcutaneous injections with the complex I inhibitor diphenyleneiodonium (DPI) for 2 wk. In vivo (31)P MRS measurements were supplemented by in vitro measurements of oxygen consumption in isolated mitochondria. Two weeks of DPI treatment induced mitochondrial dysfunction, as evidenced by a 20% lower maximal ADP-stimulated oxygen consumption rate in isolated mitochondria from DPI-treated rats oxidizing pyruvate plus malate. This was paralleled by a 46% decrease in in vivo oxidative capacity, determined from postexercise PCr recovery. Interestingly, no significant difference in resting, ST-based ATP synthesis flux was observed between DPI-treated rats and controls. These results show that PCr recovery after exercise has a more direct relationship with skeletal muscle mitochondrial function than the ATP synthesis flux measured with (31)P ST MRS in the resting state. PMID:20668212

  15. Comparative effect of immature neuronal or glial cell transplantation on motor functional recovery following experimental traumatic brain injury in rats

    PubMed Central

    Quan, Fu-Shi; Chen, Jian; Zhong, Yuan; Ren, Wen-Zhi

    2016-01-01

    The present study evaluated the comparative effect of stereotaxically transplanted immature neuronal or glial cells in brain on motor functional recovery and cytokine expression after cold-induced traumatic brain injury (TBI) in adult rats. A total of 60 rats were divided into four groups (n=15/group): Sham group; TBI only group; TBI plus neuronal cells-transplanted group (NC-G); and TBI plus glial cells-transplanted group (GC-G). Cortical lesions were induced by a touching metal stamp, frozen with liquid nitrogen, to the dura mater over the motor cortex of adult rats. Neuronal and glial cells were isolated from rat embryonic and newborn cortices, respectively, and cultured in culture flasks. Rats received neurons or glia grafts (~1×106 cells) 5 days after TBI was induced. Motor functional evaluation was performed with the rotarod test prior to and following glial and neural cell grafts. Five rats from each group were sacrificed at 2, 4 and 6 weeks post-cell transplantation. Immunofluorescence staining was performed on brain section to identify the transplanted neuronal or glial cells using neural and astrocytic markers. The expression levels of cytokines, including transforming growth factor-β, glial cell-derived neurotrophic factor and vascular endothelial growth factor, which have key roles in the proliferation, differentiation and survival of neural cells, were analyzed by immunohistochemistry and western blotting. A localized cortical lesion was evoked in all injured rats, resulting in significant motor deficits. Transplanted cells successfully migrated and survived in the injured brain lesion, and the expression of neuronal and astrocyte markers were detected in the NC-G and GC-G groups, respectively. Rats in the NC-G and GC-G cell-transplanted groups exhibited significant motor functional recovery and reduced histopathologic lesions, as compared with the TBI-G rats that did not receive neural cells (P<0.05, respectively). Furthermore, GC-G treatment

  16. Characterization of tests of functional recovery after median and ulnar nerve injury and repair in the rat forelimb.

    PubMed

    Galtrey, Clare M; Fawcett, James W

    2007-03-01

    The majority of human peripheral nerve injuries occur in the upper limb but the majority of studies in the rat are performed in the hindlimb. The upper and lower limbs differ in dexterity and control by supraspinal systems, so an upper limb model is a better representation of the common form of human injury. The purpose of this study was to further develop a rat model involving lesions of the median and ulnar nerves. To produce different degrees of misdirection of axons following nerve repair, we studied nerve crush, cut and repair of the two nerves, and cut and repair with crossover. Assessment of functional recovery was performed using a battery of motor and sensory tests: the staircase test, which assesses skilled forepaw reaching; grip strength meter, which assesses grip strength; pawprint analysis, which assesses toe spread and print length; horizontal ladder, which assesses forepaw placement during skilled locomotion; modified Randall-Selitto device and electronic von Frey probes, which assess fine touch; and cold probes, which assess temperature sensation. All tests revealed deficits in forepaw function after nerve injury except the print length and modified Randall-Selitto device. The time course of functional recovery was observed over 15 weeks. The final degree of functional recovery achieved was related to the misdirection of axon regeneration. The tests that most clearly revealed the effects of axon misdirection on function were the skilled paw reaching and grip strength tests. The lesion model and functional tests that we have developed will be useful in testing therapeutic strategies for treating the consequences of inaccurate axon regeneration following peripheral nerve injury in humans. PMID:17374098

  17. Alcoholics' Recovery from Cerebral Impairment as a Function of Duration of Abstinence.

    ERIC Educational Resources Information Center

    Kish, G. B.; And Others

    1980-01-01

    Examined the time-course of recovery from cerebral impairment due to heavy drinking. Results suggest that treatment programs that use a preliminary "drying-out" period should consider lengthening this period to three weeks to ensure that patients are maximally responsive to psychotherapy. (Author)

  18. Recovery of function in humans: Cortical stimulation and pharmacological treatments after stroke

    PubMed Central

    Floel, Agnes; Cohen, Leonardo G.

    2016-01-01

    In this contribution, we first provide an overview of general principles of reorganisation in the human brain, and point out possible biomarkers of recovery. Subsequently, we expand on possibilities of adjuvant therapy in human rehabilitation using cortical stimulation and pharmacological treatments. Finally, we suggest future directions for research in this field. PMID:19520165

  19. Strength Recovery Following Rhythmic or Sustained Exercise as a Function of Time.

    ERIC Educational Resources Information Center

    Kearney, Jay T.

    The relative rates of strength recovery subsequent to bouts of rhythmic or sustained isometric exercise were investigated. The 72 undergraduates who served as subjects were tested seven times within the framework of a repeated measures design. Each testing session involved two bouts of either rhythmic or sustained isometric exercise separated by a…

  20. Plasticity of subcortical pathways promote recovery of skilled hand function in rats after corticospinal and rubrospinal tract injuries.

    PubMed

    García-Alías, Guillermo; Truong, Kevin; Shah, Prithvi K; Roy, Roland R; Edgerton, V Reggie

    2015-04-01

    The corticospinal and rubrospinal tracts are the predominant tracts for controlling skilled hand function. Injuries to these tracts impair grasping but not gross motor functions such as overground locomotion. The aim of the present study was to determine whether or not, after damage to both the corticospinal and rubrospinal tracts, other spared subcortical motor pathway can mediate the recovery of skilled hand function. Adult rats received a bilateral injury to the corticospinal tract at the level of the medullar pyramids and a bilateral ablation of the rubrospinal axons at C4. One group of rats received, acutely after injury, two injections of chondroitinase-ABC at C7, and starting at 7days post-injury were enrolled in daily reaching and grasping rehabilitation (CHASE group, n=5). A second group of rats received analogous injections of ubiquitous penicillinase, and did not undergo rehabilitation (PEN group, n=5). Compared to rats in the PEN group, CHASE rats gradually recovered the ability to reach and grasp over 42days after injury. Overground locomotion was mildly affected after injury and both groups followed similar recovery. Since the reticulospinal tract plays a predominant role in motor control, we further investigated whether or not plasticity of this pathway could contribute to the animal's recovery. Reticulospinal axons were anterogradely traced in both groups of rats. The density of reticulospinal processes in both the normal and ectopic areas of the grey ventral matter of the caudal segments of the cervical spinal cord was greater in the CHASE than PEN group. The results indicate that after damage to spinal tracts that normally mediate the control of reaching and grasping in rats other complementary spinal tracts can acquire the role of those damaged tracts and promote task-specific recovery. PMID:25666586

  1. Human Adipose Stem Cells Improve Mechanical Allodynia and Enhance Functional Recovery in a Rat Model of Neuropathic Pain.

    PubMed

    Lee, Hye Yeong; Lee, Hye-Lan; Yun, Yeomin; Kim, Jin-Su; Ha, Yoon; Yoon, Do Heum; Lee, Soo-Hong; Shin, Dong Ah

    2015-07-01

    Stem cells are a promising source of tissue engineering due to their differentiation potential. Today, direct transplantation of stem cells for cell therapy is commonly performed. However, in cases of nerve injury, direct transplantation of cells could lead to secondary nerve damage. Male Sprague-Dawley rats were randomized into four groups: the phosphate-buffered saline epineural transplantation (PBS-ENT) group, the PBS intraneural transplantation (PBS-INT) group, the human adipose-derived stem cells epineural transplantation (hASCs-ENT) group, and human adipose-derived stem cells intraneural transplantation (hASCs-INT) group. Transplantation was conducted 1 week later after inflicting a crush injury with subsequent observation for 5 weeks. To evaluate pain, each group was examined with regard to paw withdrawal latency and evoked potentials. The sciatic functional index (SFI) was calculated to estimate functional recovery. The sciatic nerve was also examined histologically. The hASCs-ENT group showed a more rapid paw withdrawal threshold and SFI recovery than the other groups (p<0.05). The hASCs-ENT group also showed shorter initial latencies in both somatosensory evoked potential (SSEP) and motor evoked potential (MEP) than the PBS-INT group (p<0.05). In addition, the N1 latency of the MEP and the N1 and P1 latencies of the SSEP were significantly shorter than those of the PBS-INT group (p<0.05). Histological examination revealed that the transplanted groups showed better neural recovery and remyelination than the groups injected with PBS. These results show that the transplantation of hASCs into the injured sciatic nerve improved mechanical allodynia and functional recovery as determined by the paw withdrawal test, SFI analysis, and electrophysiological studies. ENT is superior to INT in terms of invasiveness and better outcomes. PMID:25857679

  2. Mast cells promote scar remodeling and functional recovery after spinal cord injury via mouse mast cell protease 6.

    PubMed

    Vangansewinkel, Tim; Geurts, Nathalie; Quanten, Kirsten; Nelissen, Sofie; Lemmens, Stefanie; Geboes, Lies; Dooley, Dearbhaile; Vidal, Pia M; Pejler, Gunnar; Hendrix, Sven

    2016-05-01

    An important barrier for axon regeneration and recovery after traumatic spinal cord injury (SCI) is attributed to the scar that is formed at the lesion site. Here, we investigated the effect of mouse mast cell protease (mMCP) 6, a mast cell (MC)-specific tryptase, on scarring and functional recovery after a spinal cord hemisection injury. Functional recovery was significantly impaired in both MC-deficient and mMCP6-knockout (mMCP6(-/-)) mice after SCI compared with wild-type control mice. This decrease in locomotor performance was associated with an increased lesion size and excessive scarring at the injury site. Axon growth-inhibitory chondroitin sulfate proteoglycans and the extracellular matrix components fibronectin, laminin, and collagen IV were significantly up-regulated in MC-deficient and mMCP6(-/-) mice, with an increase in scar volume between 23 and 32%. A degradation assay revealed that mMCP6 directly cleaves fibronectin and collagen IV in vitro In addition, gene expression levels of the scar components fibronectin, aggrecan, and collagen IV were increased up to 6.8-fold in mMCP6(-/-) mice in the subacute phase after injury. These data indicate that endogenous mMCP6 has scar-suppressing properties after SCI via indirect cleavage of axon growth-inhibitory scar components and alteration of the gene expression profile of these factors.-Vangansewinkel, T., Geurts, N., Quanten, K., Nelissen, S., Lemmens, S., Geboes, L., Dooley, D., Vidal, P. M., Pejler, G., Hendrix, S. Mast cells promote scar remodeling and functional recovery after spinal cord injury via mouse mast cell protease 6. PMID:26917739

  3. COMPOSITION-FUNCTION RELATIONSHIPS DURING IL-1-INDUCED CARTILAGE DEGRADATION AND RECOVERY

    PubMed Central

    Palmer, Ashley W.; Wilson, Christopher G.; Baum, Elyse J.; Levenston, Marc E.

    2009-01-01

    Objective: To examine the relationships between biochemical composition and mechanical properties of articular cartilage explants during interleukin-1 (IL-1)-induced degradation and post-exposure recovery. Design: Bovine articular cartilage explants were cultured for up to 32 days with or without 20 ng/mL interleukin-1. The dynamic shear modulus |G*dyn| and equilibrium and dynamic unconfined compression moduli (Eequil and |E*dyn|) were measured at intervals throughout the culture period. In a subsequent recovery study, explants were cultured for 4 days with or without 20ng/mL IL-1 and for an additional 16 days in control media. The dynamic moduli |E*dyn| and |G*dyn| were measured at intervals during degeneration and recovery. Conditioned media and explant digests were assayed for sulfated glycosaminoglycans (sGAG) and collagen content. Results: Continuous IL-1 stimulation triggered progressive decreases in Eequil, |E*dyn|, and |G*dyn| concomitant with the sequential release of sGAG and collagen from the explants. Brief IL-1 exposure resulted in a short release of sGAG but not collagen, followed by a gradual and incomplete repopulation of sGAG. The temporary sGAG depletion was associated with decreases in both |E*dyn| and |G*dyn| which also recovered after removal of IL-1. During IL-1-induced degradation and post-exposure recovery, explant mechanical properties correlated well with tissue sGAG concentration. Conclusions: As previously shown for developing cartilages and engineered cartilage constructs, cytokine-induced changes in sGAG concentration (i.e., fixed charge density) are coincident with changes in compressive and shear properties of articular cartilage. Further, recovery of cartilage mechanical properties can be achieved by relief from proinflammatory stimuli and subsequent restoration of tissue sGAG concentration. PMID:19281879

  4. Modulating Astrocyte Transition after Stroke to Promote Brain Rescue and Functional Recovery: Emerging Targets Include Rho Kinase

    PubMed Central

    Abeysinghe, Hima Charika S.; Phillips, Ellie L.; Chin-Cheng, Heung; Beart, Philip M.; Roulston, Carli L.

    2016-01-01

    Stroke is a common and serious condition, with few therapies. Whilst previous focus has been directed towards biochemical events within neurons, none have successfully prevented the progression of injury that occurs in the acute phase. New targeted treatments that promote recovery after stroke might be a better strategy and are desperately needed for the majority of stroke survivors. Cells comprising the neurovascular unit, including blood vessels and astrocytes, present an alternative target for supporting brain rescue and recovery in the late phase of stroke, since alteration in the unit also occurs in regions outside of the lesion. One of the major changes in the unit involves extensive morphological transition of astrocytes resulting in altered energy metabolism, decreased glutamate reuptake and recycling, and retraction of astrocyte end feed from both blood vessels and neurons. Whilst globally inhibiting transitional change in astrocytes after stroke is reported to result in further damage and functional loss, we discuss the available evidence to suggest that the transitional activation of astrocytes after stroke can be modulated for improved outcomes. In particular, we review the role of Rho-kinase (ROCK) in reactive gliosis and show that inhibiting ROCK after stroke results in reduced scar formation and improved functional recovery. PMID:26927079

  5. Ligustilide treatment promotes functional recovery in a rat model of spinal cord injury via preventing ROS production.

    PubMed

    Xiao, Weidong; Yu, Aixi; Liu, Danli; Shen, Jun; Xu, Zhigao

    2015-01-01

    Ligustilide from traditional Chinese medicine extract, angelica sinensis is one of the main active components, and has many pharmacological activities related to the effectiveness. This study sought to determine whether neuro-protection of ligustilide promotes functional recovery in a rat model of spinal cord injury (SCI) via preventing ROS production. Male Sprague-Dawley (SD) rats were induced using operation for model SCI. Furthermore, Basso, Beattie, Bresnahan (BBB) scale and footprint analysis of gait was used to assess the neuro-protection of ligustilide on SCI. The intracellular reactive oxygen species (iROS), prostaglandin E(2) (PGE(2)), interleukin-1β (IL-1β) and tumor necrosis factor (TNF)-α production levels were measured by monoclonal enzyme immunoassay kit. Inducible nitric oxide synthase (iNOS) gene expression, activator protein-1 (AP-1) and c-Jun N-terminal kinase (JNK) protein expressions were detected using Quantitative real-time reverse transcription polymerase chain reaction (Q-PCR) and western blot analyses, respectively. Interestingly, treatment with ligustilide significantly increased BBB scale and reduced recovery of coordination in SCI rats. After SCI, the iROS, PGE(2), IL-1β, TNF-α production levels and iNOS gene expression were significantly suppressed in SCI rats. These results suggest that the neuro-protection of ligustilide promotes functional recovery in a rat model of spinal cord injury via preventing ROS production. PMID:26722386

  6. Modulating Astrocyte Transition after Stroke to Promote Brain Rescue and Functional Recovery: Emerging Targets Include Rho Kinase.

    PubMed

    Abeysinghe, Hima Charika S; Phillips, Ellie L; Chin-Cheng, Heung; Beart, Philip M; Roulston, Carli L

    2016-01-01

    Stroke is a common and serious condition, with few therapies. Whilst previous focus has been directed towards biochemical events within neurons, none have successfully prevented the progression of injury that occurs in the acute phase. New targeted treatments that promote recovery after stroke might be a better strategy and are desperately needed for the majority of stroke survivors. Cells comprising the neurovascular unit, including blood vessels and astrocytes, present an alternative target for supporting brain rescue and recovery in the late phase of stroke, since alteration in the unit also occurs in regions outside of the lesion. One of the major changes in the unit involves extensive morphological transition of astrocytes resulting in altered energy metabolism, decreased glutamate reuptake and recycling, and retraction of astrocyte end feed from both blood vessels and neurons. Whilst globally inhibiting transitional change in astrocytes after stroke is reported to result in further damage and functional loss, we discuss the available evidence to suggest that the transitional activation of astrocytes after stroke can be modulated for improved outcomes. In particular, we review the role of Rho-kinase (ROCK) in reactive gliosis and show that inhibiting ROCK after stroke results in reduced scar formation and improved functional recovery. PMID:26927079

  7. Functional relations trump implied motion in recovery from extinction: evidence from the effects of animacy on extinction.

    PubMed

    Riddoch, M Jane; Riveros, Rodrigo; Humphreys, Glyn W

    2011-02-01

    Patients with extinction show a characteristic impairment in the identification of objects when two items are presented simultaneously, typically reporting the ipsilesional item only. The effect is thought to be due to a spatial bias advantaging the ipsilesional item under conditions of competing concurrent stimulation. Action relations between objects can result in recovery from extinction as the object pair may be perceived as a single group rather than competing perceptual units. However, objects interacting together can also have implied motion. Here we test whether implied motion is necessary to generate recovery from extinction. We varied orthogonally whether animate and inanimate objects were paired together in positions related or unrelated to action. Implied motion was greater when an animate object was present than when both stimuli were inanimate. Despite this, recovery from extinction was greater when actions were shown between inanimate objects. We suggest that actions between inanimate objects are perceived more easily due to the surfaces of these stimuli being designed for functional goals (e.g., the flat surface of a hammer head is designed to hit the flattened head of a nail). Attention is sensitive to the fit between potential action and the functional properties of objects, and not just to implied motion between stimuli. PMID:20672224

  8. Rates of post-fire vegetation recovery and fuel accumulation as a function of burn severity and time-since-burn in four western U.S. ecosystems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vegetation recovery and fuel accumulation rates following wildfire are useful measures of ecosystem resilience, yet few studies have quantified these variables over 10 years post-fire. Conventional wisdom is that recovery time to pre-fire condition will be slower as a function of burn severity, as i...

  9. Schwann Cells Overexpressing FGF-2 Alone or Combined with Manual Stimulation Do Not Promote Functional Recovery after Facial Nerve Injury

    PubMed Central

    Haastert, Kirsten; Grosheva, Maria; Angelova, Srebrina K.; Guntinas-Lichius, Orlando; Skouras, Emmanouil; Michael, Joern; Grothe, Claudia; Dunlop, Sarah A.; Angelov, Doychin N.

    2009-01-01

    Purpose. To determine whether transplantation of Schwann cells (SCs) overexpressing different isoforms of fibroblast growth factor 2 (FGF-2) combined with manual stimulation (MS) of vibrissal muscles improves recovery after facial nerve transection in adult rat. Procedures. Transected facial nerves were entubulated with collagen alone or collagen plus naïve SCs or transfected SCs. Half of the rats received daily MS. Collateral branching was quantified from motoneuron counts after retrograde labeling from 3 facial nerve branches. Quality assessment of endplate reinnervation was combined with video-based vibrissal function analysis. Results. There was no difference in the extent of collateral axonal branching. The proportion of polyinnervated motor endplates for either naïve SCs or FGF-2 over-expressing SCs was identical. Postoperative MS also failed to improve recovery. Conclusions. Neither FGF-2 isoform changed the extent of collateral branching or polyinnervation of motor endplates; furthermore, this motoneuron response could not be overridden by MS. PMID:19830246

  10. Maitake beta-glucan promotes recovery of leukocytes and myeloid cell function in peripheral blood from paclitaxel hematotoxicity

    PubMed Central

    Lin, Hong; de Stanchina, Elisa; Zhou, Xi Kathy; Hong, Feng; Seidman, Andrew; Fornier, Monica; Xiao, Wei-Lie; Kennelly, Edward J.; Wesa, Kathleen; Cassileth, Barrie R.

    2011-01-01

    Bone marrow myelotoxicity is a major limitation of chemotherapy. While granulocyte colony stimulating factor (G-CSF) treatment is effective, alternative approaches to support hematopoietic recovery are sought. We previously found that a beta-glucan extract from maitake mushroom Grifola frondosa (MBG) enhanced colony forming unit-granulocyte monocyte (CFU-GM) activity of mouse bone marrow and human hematopoietic progenitor cells (HPC), stimulated G-CSF production and spared HPC from doxorubicin toxicity in vitro. This investigation assessed the effects of MBG on leukocyte recovery and granulocyte/monocyte function in vivo after dose intensive paclitaxel (Ptx) in a normal mouse. After a cumulative dose of Ptx (90–120 mg/kg) given to B6D2F1 mice, daily oral MBG (4 or 6 mg/kg), intravenous G-CSF (80 μg/kg) or Ptx alone were compared for effects on the dynamics of leukocyte recovery in blood, CFU-GM activity in bone marrow and spleen, and granulocyte/monocyte production of reactive oxygen species (ROS). Leukocyte counts declined less in Ptx + MBG mice compared to Ptx-alone (p = 0.024) or Ptx + G-CSF treatment (p = 0.031). Lymphocyte levels were higher after Ptx + MBG but not Ptx + G-CSF treatment compared to Ptx alone (p < 0.01). MBG increased CFU-GM activity in bone marrow and spleen (p < 0.001, p = 0.002) 2 days after Ptx. After two additional days (Ptx post-day 4), MBG restored granulocyte/monocyte ROS response to normal levels compared to Ptx-alone and increased ROS response compared to Ptx-alone or Ptx + G-CSF (p < 0.01, both). The studies indicate that oral MBG promoted maturation of HPC to become functionally active myeloid cells and enhanced peripheral blood leukocyte recovery after chemotoxic bone marrow injury. PMID:20140432

  11. Recovery of elbow function in voluntary positioning of the hand following hemiplegia due to stroke.

    PubMed Central

    Wing, A M; Lough, S; Turton, A; Fraser, C; Jenner, J R

    1990-01-01

    Elbow movement during voluntary positioning of the hand (with the arm supported against gravity) is described in a longitudinal study of five patients recovering from hemiplegia due to stroke. Over a twelve month period, four of the patients improved their speed of movement, three exhibiting slightly better recovery of elbow extension, one of flexion. In some instances co-contraction of the elbow agonist and antagonist (measured just before the onset of movement) decreased with time after stroke. The effects of contrasting movements at the shoulder on elbow movement were also studied. Estimates of recovery were generally similar whether patients kept the shoulder still or made movements that were synergic or counter-synergic to those of the elbow. PMID:2313299

  12. Recovery of functional DNA inserts by electroendosmotic elution during gel electrophoresis.

    PubMed Central

    Tan, H V; Kitzis, A; Berthollet, T; Hamard, G; Beldjord, C; Benarous, R

    1988-01-01

    In contrast to all previous preparative electrophoresis apparatus which used a pump, electroendosmotic elution uses bound electrical charges at the end of the separating gel to generate a buffer flow. The electroendosmotic flow increased with increasing currents and decreasing buffer concentrations: its exact characteristics for the built apparatus were determined. The electroendosmotic device was able to separate two DNA fragments differing in size by only 5% with a recovery over 95%. As demonstrated in practical examples of recovery and uses of DNA inserts, up to 10 micrograms of DNA per band can be loaded at a time. The recovered DNA can be used directly for nick-translation, ligation... without further treatment. The performances of the method are expected to improve still further if the charge density and pores of the electroendosmotic medium can be "made-to-order" to provide a better flow profile of the eluting buffer. Images PMID:2833722

  13. Right ventricular functional recovery after acute myocardial infarction: relation with left ventricular function and interventricular septum motion. GISSI-3 echo substudy

    PubMed Central

    Popescu, B A; Antonini-Canterin, F; Temporelli, P L; Giannuzzi, P; Bosimini, E; Gentile, F; Maggioni, A P; Tavazzi, L; Piazza, R; Ascione, L; Stoian, I; Cervesato, E; Popescu, A C; Nicolosi, G L

    2005-01-01

    Objective: To evaluate the pattern of right ventricular (RV) functional recovery and its relation with left ventricular (LV) function and interventricular septal (IVS) motion in low risk patients after acute myocardial infarction (AMI). Design and setting: Multicentre clinical trial carried out in 47 Italian coronary care units. Patients: 500 patients from the GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico) -3 echo substudy, who underwent serial echocardiograms 24–48 hours after symptom onset and at discharge, six weeks, and six months after AMI. Results: Tricuspid annular plane systolic excursion (TAPSE) increased significantly during follow up (mean (SD) 1.79 (0.46) cm at 24–48 hours to 1.92 (0.46) cm at six months, p < 0.001) and the increase was already significant at discharge (1.88 (0.47) cm, p < 0.001). LV ejection fraction (LVEF) was the best correlate of TAPSE at 24–48 hours (r  =  0.15, p  =  0.001). TAPSE increased significantly in patients both with reduced (< 45%) and with preserved (⩾ 45%) LVEF, but the magnitude of increase was higher in patients with lower initial LVEF (p  =  0.001). Improvement in IVS wall motion score index (IVS-WMSI) was the only independent predictor of TAPSE changes during follow up (r  =  −0.12, p  =  0.007). Conclusions: In low risk patients after AMI, RV function recovered throughout six months of follow up and was already significant at discharge. TAPSE was significantly related to LVEF at 24–48 hours. The magnitude of RV functional recovery was higher in patients with lower initial LVEF. RV functional recovery is best related to IVS-WMSI improvement, suggesting that IVS motion has an important role in RV functional improvement in this setting. PMID:15772207

  14. Functional Mechanisms of Recovery after Chronic Stroke: Modeling with the Virtual Brain123

    PubMed Central

    Riley, Jeffrey D.; Jirsa, Viktor; McIntosh, Anthony R.; Elinor Chen, E.

    2016-01-01

    Abstract We have seen important strides in our understanding of mechanisms underlying stroke recovery, yet effective translational links between basic and applied sciences, as well as from big data to individualized therapies, are needed to truly develop a cure for stroke. We present such an approach using The Virtual Brain (TVB), a neuroinformatics platform that uses empirical neuroimaging data to create dynamic models of an individual’s human brain; specifically, we simulate fMRI signals by modeling parameters associated with brain dynamics after stroke. In 20 individuals with stroke and 11 controls, we obtained rest fMRI, T1w, and diffusion tensor imaging (DTI) data. Motor performance was assessed pre-therapy, post-therapy, and 6–12 months post-therapy. Based on individual structural connectomes derived from DTI, the following steps were performed in the TVB platform: (1) optimization of local and global parameters (conduction velocity, global coupling); (2) simulation of BOLD signal using optimized parameter values; (3) validation of simulated time series by comparing frequency, amplitude, and phase of the simulated signal with empirical time series; and (4) multivariate linear regression of model parameters with clinical phenotype. Compared with controls, individuals with stroke demonstrated a consistent reduction in conduction velocity, increased local dynamics, and reduced local inhibitory coupling. A negative relationship between local excitation and motor recovery, and a positive correlation between local dynamics and motor recovery were seen. TVB reveals a disrupted post-stroke system favoring excitation-over-inhibition and local-over-global dynamics, consistent with existing mammal literature on stroke mechanisms. Our results point to the potential of TVB to determine individualized biomarkers of stroke recovery. PMID:27088127

  15. Leuprolide acetate induces structural and functional recovery of injured spinal cord in rats.

    PubMed

    Díaz Galindo, Carmen; Gómez-González, Beatriz; Salinas, Eva; Calderón-Vallejo, Denisse; Hernández-Jasso, Irma; Bautista, Eduardo; Quintanar, J Luis

    2015-11-01

    Gonadotropin-releasing hormone (GnRH) and its synthetic analog leuprolide acetate, a GnRH agonist, have neurotrophic properties. This study was designed to determine whether administration of leuprolide acetate can improve locomotor behavior, gait, micturition reflex, spinal cord morphology and the amount of microglia in the lesion epicenter after spinal cord injury in rats. Rats with spinal cord compression injury were administered leuprolide acetate or saline solution for 5 weeks. At the 5(th) week, leuprolide acetate-treated rats showed locomotor activity recovery by 38%, had improvement in kinematic gait and exhibited voiding reflex recovery by 60%, as compared with the 1(st) week. By contrast, saline solution-treated rats showed locomotor activity recovery only by 7%, but voiding reflex did not recover. More importantly, leuprolide acetate treatment reduced microglial immunological reaction and induced a trend towards greater area of white and gray matter in the spinal cord. Therefore, leuprolide acetate has great potential to repair spinal cord injury. PMID:26807118

  16. Leuprolide acetate induces structural and functional recovery of injured spinal cord in rats

    PubMed Central

    Díaz Galindo, Carmen; Gómez-González, Beatriz; Salinas, Eva; Calderón-Vallejo, Denisse; Hernández-Jasso, Irma; Bautista, Eduardo; Quintanar, J Luis

    2015-01-01

    Gonadotropin-releasing hormone (GnRH) and its synthetic analog leuprolide acetate, a GnRH agonist, have neurotrophic properties. This study was designed to determine whether administration of leuprolide acetate can improve locomotor behavior, gait, micturition reflex, spinal cord morphology and the amount of microglia in the lesion epicenter after spinal cord injury in rats. Rats with spinal cord compression injury were administered leuprolide acetate or saline solution for 5 weeks. At the 5th week, leuprolide acetate-treated rats showed locomotor activity recovery by 38%, had improvement in kinematic gait and exhibited voiding reflex recovery by 60%, as compared with the 1st week. By contrast, saline solution-treated rats showed locomotor activity recovery only by 7%, but voiding reflex did not recover. More importantly, leuprolide acetate treatment reduced microglial immunological reaction and induced a trend towards greater area of white and gray matter in the spinal cord. Therefore, leuprolide acetate has great potential to repair spinal cord injury. PMID:26807118

  17. Phosphodiesterase 5A inhibitors improve functional recovery after stroke in rats: optimized dosing regimen with implications for mechanism.

    PubMed

    Menniti, Frank S; Ren, JingMei; Coskran, Timothy M; Liu, Jing; Morton, Daniel; Sietsma, Dana K; Som, Angel; Stephenson, Diane T; Tate, Barbara A; Finklestein, Seth P

    2009-12-01

    Phosphodiesterase 5A (PDE5A) inhibitors improve functional recovery after middle cerebral artery occlusion (MCA-o) in rats. We used the PDE5A inhibitor 3-(4-(2-hydroxyethyl)piperazin-1-yl)-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one hydrochloride (PF-5) to determine the timing, duration, and degree of inhibition that yields maximum efficacy. We also investigated the localization of PDE5A to determine the tissues and cells that would be targets for PDE5 inhibition and that may mediate efficacy. Nearly complete inhibition of PDE5A, starting 24 h after MCA-o and continued for 7 days, resulted in nearly complete recovery of sensorimotor function that was sustained for 3 months. Delaying administration until 72 h after MCA-o resulted in equivalent efficacy, whereas delaying treatment for 14 days was ineffective. Treatment for 7 days was equivalently efficacious to 28 or 84 days of treatment, whereas treatment for 1 day was less effective. In the normal forebrain, PDE5A immunoreactivity was prominent in smooth muscle of meningeal arteries and a few smaller blood vessels, with weak staining in a few widely scattered cortical neurons and glia. At 24 and 48 h after MCA-o, the number and intensity of blood vessel staining increased in the infarcted cortex and striatum. PDE5A immunoreactivity also was increased at 48 h in putative microglia in penumbra, whereas there was no change in staining of the scattered cortical neurons. Given the window for efficacy and the PDE5A distribution, we hypothesize that efficacy results from an effect on vasculature, and perhaps modulation of microglial function, both of which may facilitate recovery of neuronal function. PMID:19729580

  18. Adipose-Derived Stem Cells Expressing the Neurogenin-2 Promote Functional Recovery After Spinal Cord Injury in Rat.

    PubMed

    Tang, Linjun; Lu, Xiaocheng; Zhu, Ronglan; Qian, Tengda; Tao, Yi; Li, Kai; Zheng, Jinyu; Zhao, Penglai; Li, Shuai; Wang, Xi; Li, Lixin

    2016-07-01

    Neurogenin2 (Ngn2) is a proneural gene that directs neuronal differentiation of progenitor cells during development. This study aimed to investigate whether the use of adipose-derived stem cells (ADSCs) over-expressing the Ngn2 transgene (Ngn2-ADSCs) could display the characteristics of neurogenic cells and improve functional recovery in an experimental rat model of SCI. ADSCs from rats were cultured and purified in vitro, followed by genetically modified with the Ngn2 gene. Forty-eight adult female Sprague-Dawley rats were randomly assigned to three groups: the control, ADSCs, and Ngn2-ADSCs groups. The hind-limb motor function of all rats was recorded using the Basso, Beattie, and Bresnahan locomotor rating scale for 8 weeks. Moreover, hematoxylineosin staining and immunohistochemistry were also performed. After neural induction, positive expression rate of NeuN in Ngn2-ADSCs group was upon 90 %. Following transplantation, a great number of ADSCs was found around the center of the injury spinal cord at 1 and 4 weeks, which improved retention of tissue at the lesion site. Ngn2-ADSCs differentiated into neurons, indicated by the expression of neuronal markers, NeuN and Tuj1. Additionally, transplantation of Ngn2-ADSCs upregulated the trophic factors (brain-derived neurotrophic factor and vascular endothelial growth factor), and inhibited the glial scar formation, which was indicated by immunohistochemistry with glial fibrillary acidic protein. Finally, Ngn2-ADSCs-treated animals showed the highest functional recovery among the three groups. These findings suggest that transplantation of Ngn2-overexpressed ADSCs promote the functional recovery from SCI, and improve the local microenvironment of injured cord in a more efficient way than that with ADSCs alone. PMID:26283493

  19. O-GlcNAc glycosylation of p27(kip1) promotes astrocyte migration and functional recovery after spinal cord contusion.

    PubMed

    Mao, Xingxing; Zhang, Dongmei; Tao, Tao; Liu, Xiaojuan; Sun, Xiaolei; Wang, Youhua; Shen, Aiguo

    2015-12-10

    Glial scar formation derived from astrocyte proliferation and migration influences the functional recovery after spinal cord injury. Cyclin-dependent kinase inhibitor p27(kip1), whose activity is closely related to its phosphorylation state, reportedly regulates astrocyte proliferation and migration. In this study, we reported that p27(Kip1) undergoes O-GlcNAc modification at Ser 2, Ser 110 and Thr 197. Inhibiting O-GlcNAcylation on Ser 2 by gene mutation (S2A) attenuated the phosphorylation of Ser 10, and vice versa. Interestingly, compared with wild type p27(Kip1), S2A p27(Kip1) displayed a decreased interaction with CRM1 and reduced nuclear export following serum starvation and release. In addition, the interaction between stathmin and S2A p27(Kip1) was also decreased. Cytoskeletal proteins microtubules appeared high density in astrocytes transfected with S2A p27(Kip1) especially at the leading edge of the scratch wound. Accordingly, scratch-wound assay revealed that the motility of astrocytes transfected with S2A p27(Kip1) was faster than that of control. Finally, we injected lentiviral vectors immediately after spinal cord contusion, and found the lesion volume of the rat injected with S2A p27(Kip1) was smaller than that of rat injected with wild type p27(Kip1). Besides, the BBB and CBS behavioral tests showed greater functional recovery in S2A p27(Kip1) treated rats. Taken together, our findings revealed a novel function of O-GlcNAc modification of p27(Kip1) in mediating astrocytes migration and functional recovery after spinal cord contusion. PMID:26562163

  20. Does the regulation of local excitation-inhibition balance aid in recovery of functional connectivity? A computational account.

    PubMed

    Vattikonda, Anirudh; Surampudi, Bapi Raju; Banerjee, Arpan; Deco, Gustavo; Roy, Dipanjan

    2016-08-01

    Computational modeling of the spontaneous dynamics over the whole brain provides critical insight into the spatiotemporal organization of brain dynamics at multiple resolutions and their alteration to changes in brain structure (e.g. in diseased states, aging, across individuals). Recent experimental evidence further suggests that the adverse effect of lesions is visible on spontaneous dynamics characterized by changes in resting state functional connectivity and its graph theoretical properties (e.g. modularity). These changes originate from altered neural dynamics in individual brain areas that are otherwise poised towards a homeostatic equilibrium to maintain a stable excitatory and inhibitory activity. In this work, we employ a homeostatic inhibitory mechanism, balancing excitation and inhibition in the local brain areas of the entire cortex under neurological impairments like lesions to understand global functional recovery (across brain networks and individuals). Previous computational and empirical studies have demonstrated that the resting state functional connectivity varies primarily due to the location and specific topological characteristics of the lesion. We show that local homeostatic balance provides a functional recovery by re-establishing excitation-inhibition balance in all areas that are affected by lesion. We systematically compare the extent of recovery in the primary hub areas (e.g. default mode network (DMN), medial temporal lobe, medial prefrontal cortex) as well as other sensory areas like primary motor area, supplementary motor area, fronto-parietal and temporo-parietal networks. Our findings suggest that stability and richness similar to the normal brain dynamics at rest are achievable by re-establishment of balance. PMID:27177761

  1. Effects of preoperative neuromuscular electrical stimulation on quadriceps strength and functional recovery in total knee arthroplasty. A pilot study

    PubMed Central

    2010-01-01

    Background Supervised preoperative muscle strengthening programmes (prehabilitation) can improve recovery after total joint arthroplasty but are considered resource intensive. Neuromuscular electrical stimulation (NMES) has been shown to improve quadriceps femoris muscle (QFM) strength and clinical function in subjects with knee osteoarthritis (OA) however it has not been previously investigated as a prehabilitation modality. Methods This pilot study assessed the compliance of a home-based, NMES prehabilitation programme in patients undergoing total knee arthroplasty (TKA). We evaluated its effect on preoperative and postoperative isometric quadriceps femoris muscle (QFM) strength, QFM cross-sectional area (CSA) and clinical function (subjective and objective). Seventeen subjects were recruited with 14 completing the study (NMES group n = 9; Control group n = 5). Results Overall compliance with the programme was excellent (99%). Preoperative QFM strength increased by 28% (p > 0.05) with associated gains in walk, stair-climb and chair-rise times (p < 0.05). Early postoperative strength loss (approximately 50%) was similar in both groups. Only the NMES group demonstrated significant strength (53.3%, p = 0.011) and functional recovery (p < 0.05) from 6 to 12 weeks post-TKA. QFM CSA decreased by 4% in the NMES group compared to a reduction of 12% in the control group (P > 0.05) at 12 weeks postoperatively compared to baseline. There were only limited associations found between objective and subjective functional outcome instruments. Conclusions This pilot study has shown that preoperative NMES may improve recovery of quadriceps muscle strength and expedite a return to normal activities in patients undergoing TKA for OA. Recommendations for appropriate outcome instruments in future studies of prehabilitation in TKA have been provided. PMID:20540807

  2. Effects of Ankle–Foot Orthoses on Functional Recovery after Stroke: A Propensity Score Analysis Based on Japan Rehabilitation Database

    PubMed Central

    2015-01-01

    Objectives The purpose of the present study was to investigate potential effects of ankle–foot orthoses (AFOs) on the functional recovery of post-acute stroke patients following rehabilitation. Subjects and Methods This study is a retrospective cohort study. Participants were in-hospital stroke patients registered in the Japan Rehabilitation Database between 2005 and 2012. A total of 1862 patients were eligible after applying exclusion criteria. Propensity score analysis was applied to adjust for potential bias and to create two comparable groups. An additional subset analysis focused on Functional Independence Measure (FIM) scores on admission. Results In this sample, 30.7% of 1863 eligible patients were prescribed AFOs. Propensity score matched analysis showed that patients with AFOs had significantly higher scores than those without them for discharge FIM (mean: 91.3 vs 85.8; p=0.02), FIM gain (mean: 28.9 vs 23.5; p<0.001), and FIM efficiency (mean: 0.27 vs 0.22; p<0.001). Inverse probability weighting analysis showed similar results. In the subset analysis, patients with AFOs had significantly higher discharge FIM compared with those without them in the low admission FIM subgroup only. In addition, patients with AFOs performed independent exercise more than those without them (p<0.001). Conclusions These data suggest that stroke survivors may have better functional recovery if they are prescribed an AFO than if they are not prescribed an AFO. The use of AFOs is considered to be a feasible option to improve functional recovery of stroke rehabilitation patients. PMID:25837720

  3. Effects of estrogen on functional and neurological recovery after spinal cord injury: An experimental study with rats

    PubMed Central

    Letaif, Olavo Biraghi; Cristante, Alexandre Fogaça; de Barros Filho, Tarcísio Eloy Pessoa; Ferreira, Ricardo; dos Santos, Gustavo Bispo; da Rocha, Ivan Dias; Marcon, Raphael Martus

    2015-01-01

    OBJECTIVES: To evaluate the functional and histological effects of estrogen as a neuroprotective agent after a standard experimentally induced spinal cord lesion. METHODS: In this experimental study, 20 male Wistar rats were divided into two groups: one group with rats undergoing spinal cord injury (SCI) at T10 and receiving estrogen therapy with 17-beta estradiol (4mg/kg) immediately following the injury and after the placement of skin sutures and a control group with rats only subjected to SCI. A moderate standard experimentally induced SCI was produced using a computerized device that dropped a weight on the rat's spine from a height of 12.5 mm. Functional recovery was verified with the Basso, Beattie and Bresnahan scale on the 2nd, 7th, 14th, 21st, 28th, 35th and 42nd days after injury and by quantifying the motor-evoked potential on the 42nd day after injury. Histopathological evaluation of the SCI area was performed after euthanasia on the 42nd day. RESULTS: The experimental group showed a significantly greater functional improvement from the 28th to the 42nd day of observation compared to the control group. The experimental group showed statistically significant improvements in the motor-evoked potential compared with the control group. The results of pathological histomorphometry evaluations showed a better neurological recovery in the experimental group, with respect to the proportion and diameter of the quantified nerve fibers. CONCLUSIONS: Estrogen administration provided benefits in neurological and functional motor recovery in rats with SCI beginning at the 28th day after injury. PMID:26598084

  4. Relationship between T-wave normalization on exercise ECG and myocardial functional recovery in patients with acute myocardial infarction

    PubMed Central

    Kim, Kyung Jin; Shim, Wan Joo; Jung, Seong Won; Pak, Hui Nam; Lee, Soo Jin; Song, Woo Hyuk; Kim, Young Hoon; Seo, Hong Seog; Oh, Dong Joo; Ro, Young Moo

    2002-01-01

    Background Several studies suggested that T-wave normalization (TWN) in exercise ECG indicates the presence of viable myocardium. But the clinical implication of this phenomenon in patients with acute myocardial infarction who received proper revascularization therapy was not determined. Precisely the aim of this study was to investigate the relationship between TWN in exercise ECG and myocardial functional recovery after acute myocardial infarction. Methods We studied 30 acute myocardial infarction patients with negative T waves in infarct related electrocardiographic leads and who had received successful revascularization therapy. Exercise ECG was performed 10–14days after infarct onset using Naughton protocol. Patients were divided into 2 groups according to presence (group I; n=14) or not (group II; n=16) of TWN in exercise ECG. Exercise parameters and coronary angiographic findings were compared between groups. Baseline and follow-up (mean 11 months) regional and global left ventricular function was analyzed by echocardiography. Results Exercise parameters were similar between groups. There was no difference in baseline ejection fraction and wall motion score between group I and II (EF; 56±12% vs 52±11%, p=ns. WMS; 21±3 vs 23±4, p=ns) and it was improved at the tenth month by similar magnitude (group I/group II, EF % change=12±12% vs 7±6%, p=ns, WMS % change=6±6% vs 7±5%, p=ns). The finding of no relation between TWN and functional recovery was observed also when the patients were analysed according to infarct location and presence or absence of Q-waves. Conclusion As the exercise-induced TWN in patients with acute myocardial infarction was not related with better functional recovery of dysfunctional regional wall motion and ejection fraction, TWN does not appear to be an indicator of myocardial viability. PMID:12164089

  5. A Review on Locomotor Training after Spinal Cord Injury: Reorganization of Spinal Neuronal Circuits and Recovery of Motor Function

    PubMed Central

    2016-01-01

    Locomotor training is a classic rehabilitation approach utilized with the aim of improving sensorimotor function and walking ability in people with spinal cord injury (SCI). Recent studies have provided strong evidence that locomotor training of persons with clinically complete, motor complete, or motor incomplete SCI induces functional reorganization of spinal neuronal networks at multisegmental levels at rest and during assisted stepping. This neuronal reorganization coincides with improvements in motor function and decreased muscle cocontractions. In this review, we will discuss the manner in which spinal neuronal circuits are impaired and the evidence surrounding plasticity of neuronal activity after locomotor training in people with SCI. We conclude that we need to better understand the physiological changes underlying locomotor training, use physiological signals to probe recovery over the course of training, and utilize established and contemporary interventions simultaneously in larger scale research studies. Furthermore, the focus of our research questions needs to change from feasibility and efficacy to the following: what are the physiological mechanisms that make it work and for whom? The aforementioned will enable the scientific and clinical community to develop more effective rehabilitation protocols maximizing sensorimotor function recovery in people with SCI. PMID:27293901

  6. A Review on Locomotor Training after Spinal Cord Injury: Reorganization of Spinal Neuronal Circuits and Recovery of Motor Function.

    PubMed

    Smith, Andrew C; Knikou, Maria

    2016-01-01

    Locomotor training is a classic rehabilitation approach utilized with the aim of improving sensorimotor function and walking ability in people with spinal cord injury (SCI). Recent studies have provided strong evidence that locomotor training of persons with clinically complete, motor complete, or motor incomplete SCI induces functional reorganization of spinal neuronal networks at multisegmental levels at rest and during assisted stepping. This neuronal reorganization coincides with improvements in motor function and decreased muscle cocontractions. In this review, we will discuss the manner in which spinal neuronal circuits are impaired and the evidence surrounding plasticity of neuronal activity after locomotor training in people with SCI. We conclude that we need to better understand the physiological changes underlying locomotor training, use physiological signals to probe recovery over the course of training, and utilize established and contemporary interventions simultaneously in larger scale research studies. Furthermore, the focus of our research questions needs to change from feasibility and efficacy to the following: what are the physiological mechanisms that make it work and for whom? The aforementioned will enable the scientific and clinical community to develop more effective rehabilitation protocols maximizing sensorimotor function recovery in people with SCI. PMID:27293901

  7. Avoidance of Profound Hypothermia During Initial Reperfusion Improves the Functional Recovery of Hearts Donated After Circulatory Death.

    PubMed

    White, C W; Ambrose, E; Müller, A; Li, Y; Le, H; Thliveris, J; Arora, R C; Lee, T W; Dixon, I M C; Tian, G; Nagendran, J; Hryshko, L V; Freed, D H

    2016-03-01

    The resuscitation of hearts donated after circulatory death (DCD) is gaining widespread interest; however, the method of initial reperfusion (IR) that optimizes functional recovery has not been elucidated. We sought to determine the impact of IR temperature on the recovery of myocardial function during ex vivo heart perfusion (EVHP). Eighteen pigs were anesthetized, mechanical ventilation was discontinued, and cardiac arrest ensued. A 15-min standoff period was observed and then hearts were reperfused for 3 min at three different temperatures (5°C; N = 6, 25°C; N = 5, and 35°C; N = 7) with a normokalemic adenosine-lidocaine crystalloid cardioplegia. Hearts then underwent normothermic EVHP for 6 h during which time myocardial function was assessed in a working mode. We found that IR coronary blood flow differed among treatment groups (5°C = 483 ± 53, 25°C = 722 ± 60, 35°C = 906 ± 36 mL/min, p < 0.01). During subsequent EVHP, less myocardial injury (troponin I: 5°C = 91 ± 6, 25°C = 64 ± 16, 35°C = 57 ± 7 pg/mL/g, p = 0.04) and greater preservation of endothelial cell integrity (electron microscopy injury score: 5°C = 3.2 ± 0.5, 25°C = 1.8 ± 0.2, 35°C = 1.7 ± 0.3, p = 0.01) were evident in hearts initially reperfused at warmer temperatures. IR under profoundly hypothermic conditions impaired the recovery of myocardial function (cardiac index: 5°C = 3.9 ± 0.8, 25°C = 6.2 ± 0.4, 35°C = 6.5 ± 0.6 mL/minute/g, p = 0.03) during EVHP. We conclude that the avoidance of profound hypothermia during IR minimizes injury and improves the functional recovery of DCD hearts. PMID:26780159

  8. Motor recovery at 6 months after admission is related to structural and functional reorganization of the spine and brain in patients with spinal cord injury.

    PubMed

    Hou, Jingming; Xiang, Zimin; Yan, Rubing; Zhao, Ming; Wu, Yongtao; Zhong, Jianfeng; Guo, Lei; Li, Haitao; Wang, Jian; Wu, Jixiang; Sun, Tiansheng; Liu, Hongliang

    2016-06-01

    This study aimed to explore structural and functional reorganization of the brain in the early stages of spinal cord injury (SCI) and identify brain areas that contribute to motor recovery. We studied 25 patients with SCI, including 10 with good motor recovery and 15 with poor motor recovery, along with 25 matched healthy controls. The mean period post-SCI was 9.2 ± 3.5 weeks in good recoverers and 8.8 ± 2.6 weeks in poor recoverers. All participants underwent structural and functional MRI on a 3-T magnetic resonance system. We evaluated differences in cross-sectional spinal cord area at the C2/C3 level, brain cortical thickness, white matter microstructure, and functional connectivity during the resting state among the three groups. We also evaluated associations between structural and functional reorganization and the rate of motor recovery. After SCI, compared with good recoverers, poor recoverers had a significantly decreased cross-sectional spinal cord area, cortical thickness in the right supplementary motor area and premotor cortex, and fractional anisotropy (FA) in the right primary motor cortex and posterior limb of the internal capsule. Meanwhile, poor recoverers showed decreased functional connectivity between the primary motor cortex and higher order motor areas (supplementary motor area and premotor cortex), while good recoverers showed increased functional connectivity among these regions. The structural and functional reorganization of the spine and brain was associated with motor recovery rate in all SCI patients. In conclusion, structural and functional reorganization of the spine and brain directly affected the motor recovery of SCI. Less structural atrophy and enhanced functional connectivity are associated with good motor recovery in patients with SCI. Multimodal imaging has the potential to predict motor recovery in the early stage of SCI. Hum Brain Mapp 37:2195-2209, 2016. © 2016 Wiley Periodicals, Inc. PMID:26936834

  9. Age decreases macrophage IL-10 expression: Implications for functional recovery and tissue repair in spinal cord injury.

    PubMed

    Zhang, Bei; Bailey, William M; Braun, Kaitlyn J; Gensel, John C

    2015-11-01

    Macrophages with different activation states are present after spinal cord injury (SCI). M1 macrophages purportedly promote secondary injury processes while M2 cells support axon growth. The average age at the time of SCI has increased in recent decades, however, little is known about how different physiological factors contribute to macrophage activation states after SCI. Here we investigate the effect of age on IL-10, a key indicator of M2 macrophage activation. Following mild-moderate SCI in 4 and 14 month old (MO) mice we detected significantly reduced IL-10 expression with age in the injured spinal cord. Specifically, CD86/IL-10 positive macrophages, also known as M2b or regulatory macrophages, were reduced in 14 vs. 4 MO SCI animals. This age-dependent shift in macrophage phenotype was associated with impaired functional recovery and enhanced tissue damage in 14-month-old SCI mice. In vitro, M2b macrophages release anti-inflammatory cytokines without causing neurotoxicity, suggesting that imbalances in the M2b response in 14-month-old mice may be contributing to secondary injury processes. Our data indicate that age is an important factor that regulates SCI inflammation and recovery even to mild-moderate injury. Further, alterations in macrophage activation states may contribute to recovery and we have identified the M2b phenotype as a potential target for therapeutic intervention. PMID:26263843

  10. Transplantation of ciliary neurotrophic factor-expressing adult oligodendrocyte precursor cells promotes remyelination and functional recovery after spinal cord injury.

    PubMed

    Cao, Qilin; He, Qian; Wang, Yaping; Cheng, Xiaoxin; Howard, Russell M; Zhang, Yiping; DeVries, William H; Shields, Christopher B; Magnuson, David S K; Xu, Xiao-Ming; Kim, Dong H; Whittemore, Scott R

    2010-02-24

    Demyelination contributes to the dysfunction after traumatic spinal cord injury (SCI). We explored whether the combination of neurotrophic factors and transplantation of adult rat spinal cord oligodendrocyte precursor cells (OPCs) could enhance remyelination and functional recovery after SCI. Ciliary neurotrophic factor (CNTF) was the most effective neurotrophic factor to promote oligodendrocyte (OL) differentiation and survival of OPCs in vitro. OPCs were infected with retroviruses expressing enhanced green fluorescent protein (EGFP) or CNTF and transplanted into the contused adult thoracic spinal cord 9 d after injury. Seven weeks after transplantation, the grafted OPCs survived and integrated into the injured spinal cord. The survival of grafted CNTF-OPCs increased fourfold compared with EGFP-OPCs. The grafted OPCs differentiated into adenomatus polyposis coli (APC(+)) OLs, and CNTF significantly increased the percentage of APC(+) OLs from grafted OPCs. Immunofluorescent and immunoelectron microscopic analyses showed that the grafted OPCs formed central myelin sheaths around the axons in the injured spinal cord. The number of OL-remyelinated axons in ventrolateral funiculus (VLF) or lateral funiculus (LF) at the injured epicenter was significantly increased in animals that received CNTF-OPC grafts compared with all other groups. Importantly, 75% of rats receiving CNTF-OPC grafts recovered transcranial magnetic motor-evoked potential and magnetic interenlargement reflex responses, indicating that conduction through the demyelinated axons in VLF or LF, respectively, was partially restored. More importantly, recovery of hindlimb locomotor function was significantly enhanced in animals receiving grafts of CNTF-OPCs. Thus, combined treatment with OPC grafts expressing CNTF can enhance remyelination and facilitate functional recovery after traumatic SCI. PMID:20181596

  11. Transplantation of CNTF-expressing adult oligodendrocyte precursor cells promotes remyelination and functional recovery after spinal cord injury

    PubMed Central

    Cao, Qilin; He, Qian; Wang, Yaping; Cheng, Xiaoxin; Howard, Russell M.; Zhang, Yiping; DeVries, William H.; Shields, Christopher B.; Magnuson, David S.K.; Xu, Xiaoming; Kim, Dong H.; Whittemore, Scott R.

    2010-01-01

    Demyelination contributes to the dysfunction after traumatic spinal cord injury (SCI). We explored whether the combination of neurotrophic factors and transplantation of adult rat spinal cord oligodendrocyte precursor cells (OPCs) could enhance remyelination and functional recovery after SCI. Ciliary neurotrophic factor (CNTF) was the most effective neurotrophic factor to promote oligodendrocyte (OL) differentiation and survival of OPCs in vitro. OPCs were infected with retroviruses expressing EGFP or CNTF and transplanted into the contused adult thoracic spinal cord 9 days post-injury. Seven weeks after transplantation, the grafted OPCs survived and integrated into the injured spinal cord. The survival of grafted CNTF-OPCs increased 4-fold compared to EGFP-OPCs. The grafted OPCs differentiated into adenomatus polyposis coli (APC+) OLs and CNTF significantly increased the percentage of APC+ OLs from grafted OPCs. Immunofluoresent and immuno-electron microscopic analyses showed that the grafted OPCs formed central myelin sheaths around the axons in the injured spinal cord. The number of OL-remyelinated axons in ventrolateral funiculus (VLF) or lateral funiculus (LF) at the injured epiecenter was significantly increased in animals that received CNTF-OPC grafts compared to all other groups. Importantly, 75% of rats receiving CNTF-OPC grafts recovered transcranial magnetic motor-evoked potential (tcMMEP) and magnetic inter-englargement reflex (MIER) responses, indicating that conduction through the demyelinated axons in VLF or LF, respectively, was partially restored. More importantly, recovery of hindlimb locomotor function was significantly enhanced in animals receiving grafts of CNTF-OPCs. Thus, combined treatment with OPC grafts expressing CNTF can enhance remyelination and facilitate functional recovery after traumatic SCI. PMID:20181596

  12. The effects of electromyographic-triggered neuromuscular electrical muscle stimulation on the functional hand recovery among stroke survivors.

    PubMed

    Bello, A I; Rockson, B E A; Olaogun, M O B

    2009-06-01

    Restoration of functional hand following stroke still presents formidable challenges to physiotherapists. The study evaluated the effectiveness of EMG-triggered NMES on the functional hand recovery of stroke survivors. Nineteen stroke survivors referred for physiotherapy at Korle-Bu Teaching Hospital, Accra Ghana, were consecutively assigned into an Intervention (IV) and the usual care (UC) groups. The outcome measures included box and block timed manipulation test, action research arm test (ARAT) and an adapted hand dynamometry. Measurements were recorded at baseline, at 4 and 8 weeks of the treatment by an independent assessor. The intervention group received EMG-triggered NMES in addition to the usual care during the evaluation period. Statistical analysis involved Freidman Two way ANOVA by ranks to evaluate the statistical significant changes within each group whilst Mann-Whitney U test compared the differences in the post treatment variables between the two groups. Alpha level was set at P < 0.05. The mean periods of onset of stroke were 3.63 +/- 2.13 and 5.50 +/- 2.16 months for UC and IV groups respectively. There was no significant difference (P > 0.05) in the periods of onset of stroke and ages between the two groups. Within group comparison showed significant performance (P < 0.05) on the outcome measures post baseline. No significant difference occurred between both groups except in ARAT where intervention group performed significantly better (P < 0.05) at the 8th week of the evaluation. It was concluded that inclusion of EMG-triggered NMES could contribute to a better functional hand recovery among stroke survivors during recovery stage. PMID:20175423

  13. Defining and Identifying Functional Habitat to Inform Species Recovery on a Large Regulated River

    NASA Astrophysics Data System (ADS)

    Erwin, S.; Jacobson, R. B.; Elliott, C. M.; Gemeinhardt, T.; Welker, T.; DeLonay, A. J.; Chojnacki, K.

    2014-12-01

    Goals and objectives for the restoration of aquatic ecosystems often focus on species recovery, but often the primary tools available to managers involve the manipulation of flow regime and physical habitat. Management decisions thus rely on hypotheses about the links between management actions, the response of physical habitat, and the assumed response of a target organism. Ongoing efforts to inform management of the Missouri River as part of Missouri River Restoration Project are focused on the recovery of three endangered species, including the pallid sturgeon (Scaphirhynchus albus), which is endemic to the Mississippi River basin. Recovery of the pallid sturgeon is hampered by uncertainties surrounding the definition and dynamics of ecologically significant habitats for the fish across a range of life stages. Of special interest are constructed side-channel chutes. Construction of these features has emerged as one of the primary restoration techniques used on the Lower Missouri River, yet much remains to be learned about the effectiveness of these chutes in the effort to recover pallid sturgeon. It remains unclear whether these constructed features provide habitat that may be beneficial to the species and for which life stages. Biologists hypothesize that these areas may be critical for larval retention, refugia, food production, foraging, or spawning. We present the integration of a suite of data - high-resolution hydroacoustic data, hydrodynamic modeling, biotic inventories, and laboratory experiments - designed to refine our understanding of habitat dynamics critical during the early life stages of the pallid sturgeon. We present our findings in the context of ongoing restoration activities in the basin and describe how fundamental science exploring habitat dynamics may be incorporated within the existing adaptive management framework.

  14. APE1/Ref-1 facilitates recovery of gray and white matter and neurological function after mild stroke injury.

    PubMed

    Stetler, R Anne; Gao, Yanqin; Leak, Rehana K; Weng, Zhongfang; Shi, Yejie; Zhang, Lili; Pu, Hongjian; Zhang, Feng; Hu, Xiaoming; Hassan, Sulaiman; Ferguson, Carolyn; Homanics, Gregg E; Cao, Guodong; Bennett, Michael V L; Chen, Jun

    2016-06-21

    A major hallmark of oxidative DNA damage after stroke is the induction of apurinic/apyrimidinic (AP) sites and strand breaks. To mitigate cell loss after oxidative DNA damage, ischemic cells rapidly engage the base excision-repair proteins, such as the AP site-repairing enzyme AP endonuclease-1 (APE1), also named redox effector factor-1 (Ref-1). Although forced overexpression of APE1 is known to protect against oxidative stress-induced neurodegeneration, there is no concrete evidence demonstrating a role for endogenous APE1 in the long-term recovery of gray and white matter following ischemic injury. To address this gap, we generated, to our knowledge, the first APE1 conditional knockout (cKO) mouse line under control of tamoxifen-dependent Cre recombinase. Using a well-established model of transient focal cerebral ischemia (tFCI), we show that induced deletion of APE1 dramatically enlarged infarct volume and impaired the recovery of sensorimotor and cognitive deficits. APE1 cKO markedly increased postischemic neuronal and oligodendrocyte degeneration, demonstrating that endogenous APE1 preserves both gray and white matter after tFCI. Because white matter repair is instrumental in behavioral recovery after stroke, we also examined the impact of APE1 cKO on demyelination and axonal conduction and discovered that APE1 cKO aggravated myelin loss and impaired neuronal communication following tFCI. Furthermore, APE1 cKO increased AP sites and activated the prodeath signaling proteins, PUMA and PARP1, after tFCI in topographically distinct manners. Our findings provide evidence that endogenous APE1 protects against ischemic infarction in both gray and white matter and facilitates the functional recovery of the central nervous system after mild stroke injury. PMID:27274063

  15. APE1/Ref-1 facilitates recovery of gray and white matter and neurological function after mild stroke injury

    PubMed Central

    Stetler, R. Anne; Gao, Yanqin; Leak, Rehana K.; Weng, Zhongfang; Zhang, Lili; Pu, Hongjian; Zhang, Feng; Hu, Xiaoming; Hassan, Sulaiman; Ferguson, Carolyn; Homanics, Gregg E.; Cao, Guodong; Bennett, Michael V. L.; Chen, Jun

    2016-01-01

    A major hallmark of oxidative DNA damage after stroke is the induction of apurinic/apyrimidinic (AP) sites and strand breaks. To mitigate cell loss after oxidative DNA damage, ischemic cells rapidly engage the base excision-repair proteins, such as the AP site-repairing enzyme AP endonuclease-1 (APE1), also named redox effector factor-1 (Ref-1). Although forced overexpression of APE1 is known to protect against oxidative stress-induced neurodegeneration, there is no concrete evidence demonstrating a role for endogenous APE1 in the long-term recovery of gray and white matter following ischemic injury. To address this gap, we generated, to our knowledge, the first APE1 conditional knockout (cKO) mouse line under control of tamoxifen-dependent Cre recombinase. Using a well-established model of transient focal cerebral ischemia (tFCI), we show that induced deletion of APE1 dramatically enlarged infarct volume and impaired the recovery of sensorimotor and cognitive deficits. APE1 cKO markedly increased postischemic neuronal and oligodendrocyte degeneration, demonstrating that endogenous APE1 preserves both gray and white matter after tFCI. Because white matter repair is instrumental in behavioral recovery after stroke, we also examined the impact of APE1 cKO on demyelination and axonal conduction and discovered that APE1 cKO aggravated myelin loss and impaired neuronal communication following tFCI. Furthermore, APE1 cKO increased AP sites and activated the prodeath signaling proteins, PUMA and PARP1, after tFCI in topographically distinct manners. Our findings provide evidence that endogenous APE1 protects against ischemic infarction in both gray and white matter and facilitates the functional recovery of the central nervous system after mild stroke injury. PMID:27274063

  16. High-speed recovery of germanium in a convection-aided mode using functional porous hollow-fiber membranes.

    PubMed

    Ozawa, I; Saito, K; Sugita, K; Sato, K; Akiba, M; Sugo, T

    2000-08-01

    A porous hollow-fiber membrane capable of recovery of germanium from a liquid stream was prepared by radiation-induced graft polymerization of an epoxy-group-containing vinyl monomer, glycidyl methacrylate, and subsequent functionalization with 2,2'-iminodiethanol, di-2-propanolamine, N-methylglucamine, and 3-amino-1,2-propanediol. The functional group density was as high as 1.4 mol per kg of the resultant hollow fiber. The polymer chains containing functional groups surrounding the pores enabled a high-speed recovery of germanium during permeation of a germanium oxide (GeO2) solution through the pores of the hollow fiber. Because of a negligible diffusional mass-transfer resistance, germanium concentration changes with the effluent volume, i.e., breakthrough curves, overlapped irrespective of the residence time of the solution, which ranged from 0.37 to 3.7 s across the hollow fiber. After repeated use of adsorption and elution, the adsorption capacity did not deteriorate. PMID:10949471

  17. Recovery of ovarian function and pregnancy in a patient with AML after myeloablative busulphan-based conditioning regimen.

    PubMed

    Balashov, Dmitry N; Papusha, Ludmila I; Nazarenko, Tatiana A; Trakhtman, Pavel E; Revishvili, Nino A; Maschan, Alexei A; Persiantseva, Marina I; Andriutsa, Anna V; Skorobogatova, Elena V; Skvortsova, Yulia V; Rumiantsev, Alexander G

    2011-05-01

    We report a rare case of ovarian function recovery and pregnancy after hormone-replacement therapy (HRT) in the acute myeloblastic leukemia (AML) patient in third complete remission received hematopoietic stem cell transplantation (HSCT) with busulphan-based conditioning regimen. Successful engraftment of the donor cells and full donor's chimerism was achieved without the signs of leukemia. One year after HSCT the patient received a course of HRT as a treatment of hypergonadotropic hypogonadism. After 12 months of HRT the recovery of ovarian function was confirmed. Eight years after the HSCT spontaneous pregnancy occurred; heartbeat of the fetus was registered on week 7. Three weeks later a nonsevere vaginal bleeding occurred and the ultrasound examination showed a nondeveloping pregnancy. Genetic examination of the abortion material showed a full triploid genotype (69 XXX). To our knowledge this is a first case of ovarian function restoration and spontaneous pregnancy in a AML patient after multiple courses of high-dose chemotherapy and busulphan-based myeloablative conditioning for HSCT. PMID:21423042

  18. Development of Functional Recovery Training Device for Hemiplegic Fingers with Finger-expansion Facilitation Exercise by Stretch Reflex

    NASA Astrophysics Data System (ADS)

    Yu, Yong; Iwashita, Hisashi; Kawahira, Kazumi; Hayashi, Ryota

    This paper develops a functional recovery training device to perform repetition facilitating exercise for hemiplegic finger rehabilitation. On the facilitation exercise, automatic finger expansion can be realized and facilitated by stretch reflex, where a stimulation forces is applied instantaneously on flexion finger for making strech reflex and resistance forces are applied for maintaining the strech reflex. In this paper, novel parallel mechanisms, force sensing system with high sensitivity and resistance accompanying cooperation control method are proposed for sensing, controlling and realizing the stimulation force, resistance forces, strech reflex and repetition facilitating exercise. The effectivities and performances of the device are shown by some experiments.

  19. Intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury

    PubMed Central

    DePaul, Marc A.; Palmer, Marc; Lang, Bradley T.; Cutrone, Rochelle; Tran, Amanda P.; Madalena, Kathryn M.; Bogaerts, Annelies; Hamilton, Jason A.; Deans, Robert J.; Mays, Robert W.; Busch, Sarah A.; Silver, Jerry

    2015-01-01

    Following spinal cord injury (SCI), immune-mediated secondary processes exacerbate the extent of permanent neurological deficits. We investigated the capacity of adult bone marrow-derived stem cells, which exhibit immunomodulatory properties, to alter inflammation and promote recovery following SCI. In vitro, we show that human multipotent adult progenitor cells (MAPCs) have the ability to modulate macrophage activation, and prior exposure to MAPC secreted factors can reduce macrophage-mediated axonal dieback of dystrophic axons. Using a contusion model of SCI, we found that intravenous delivery of MAPCs one day, but not immediately, after SCI significantly improves urinary and locomotor recovery, which was associated with marked spinal cord tissue sparing. Intravenous MAPCs altered the immune response in the spinal cord and periphery, however biodistribution studies revealed that no MAPCs were found in the cord and instead preferentially homed to the spleen. Our results demonstrate that MAPCs exert their primary effects in the periphery and provide strong support for the use of these cells in acute human contusive SCI. PMID:26582249

  20. Changes in collagen metabolism account for ventricular functional recovery following beta-blocker therapy in patients with chronic heart failure.

    PubMed

    Fukui, Miho; Goda, Akiko; Komamura, Kazuo; Nakabo, Ayumi; Masaki, Mitsuru; Yoshida, Chikako; Hirotani, Shinichi; Lee-Kawabata, Masaaki; Tsujino, Takeshi; Mano, Toshiaki; Masuyama, Tohru

    2016-02-01

    While beta blockade improves left ventricular (LV) function in patients with chronic heart failure (CHF), the mechanisms are not well known. This study aimed to examine whether changes in myocardial collagen metabolism account for LV functional recovery following beta-blocker therapy in 62 CHF patients with reduced ejection fraction (EF). LV function was echocardiographically measured at baseline and 1, 6, and 12 months after bisoprolol therapy along with serum markers of collagen metabolism including C-terminal telopeptide of collagen type I (CITP) and matrix metalloproteinase (MMP)-2. Deceleration time of mitral early velocity (DcT) increased even in the early phase, but LVEF gradually improved throughout the study period. Heart rate (HR) was reduced from the early stage, and CITP gradually decreased. LVEF and DcT increased more so in patients with the larger decreases in CITP (r = -0.33, p < 0.05; r = -0.28, p < 0.05, respectively), and HR (r = -0.31, p < 0.05; r = -0.38, p < 0.05, respectively). In addition, there were greater decreases in CITP, MMP-2 and HR from baseline to 1, 6, or 12 months in patients with above-average improvement in LVEF than in those with below-average improvement in LVEF. Similar results were obtained in terms of DcT. There was no significant correlation between the changes in HR and CITP. In conclusion, improvement in LV systolic/diastolic function was greatest in patients with the larger inhibition of collagen degradation. Changes in myocardial collagen metabolism are closely related to LV functional recovery somewhat independently from HR reduction. PMID:25351137

  1. Preventive effects of low-dose dexmedetomidine on postoperative cognitive function and recovery quality in elderly oral cancer patients

    PubMed Central

    Guo, Yong; Sun, Lulu; Zhang, Junfeng; Li, Qifang; Jiang, Hong; Jiang, Wei

    2015-01-01

    This study analyzed the preventive effects of low-dose dexmedetomidine on postoperative cognitive function and recovery quality in elderly oral cancer patients by observing the perioperative kinetics of inflammatory cytokines, cortisol and melatonin.A total of 149 elderly oral cancer patients who had undergone tumor resection surgery were selected and randomly divided into 2 groups, Group D and Group S. After surgery, Group D was assigned to take intravenous dexmedetomidine at a dose of 0.2 μg/kg/h for 12 h, while Group S was administered physiological saline in the same manner. On the day of surgery and for the first three postoperative days, the patients were assessed with the Mini-Mental State Examination (MMSE) and a 40-item quality of recovery score questionnaire (QoR40) at 7:00 am every morning. Venous blood was harvested at the same time. Then, IL-6, CRP, cortisol and melatonin levels were measured. There were no significant between-group differences in the baseline characteristics. After surgery, the MMSE and QoR40 scores in Group D were better than those in Group S. No between-group differences were observed in the incidences of severe hypotension and bradycardia. Moreover, respiratory depression was not observed in the 2 groups. The peaks of IL-6, CRP and cortisol concentrations in Group D were lower than those in Group S. However, the melatonin levels did not differ between the 2 groups. In elderly patients, intravenous dexmedetomidine administered postoperatively for 12 h at a dose of 0.2 ug/kg/h could improve postoperative cognitive function and recovery quality by decreasing excessive inflammation and stress levels. PMID:26629132

  2. Effect of mirror therapy with tDCS on functional recovery of the upper extremity of stroke patients

    PubMed Central

    Cho, Hyuk-Shin; Cha, Hyun-gyu

    2015-01-01

    [Purpose] This study aimed to determine the effect of mirror therapy (MT) with transcranial direct current stimulation (tDCS) on the recovery of the upper extremity function of chronic stroke patients. [Subjects] Twenty-seven patients at least 6 months after stroke onset were divided randomly into an experimental group (14 patients) and a control group (13 patients). [Methods] All subjects received tDCS for 20 min followed by a 5 min rest. Then the experimental group received MT while the control group conducted the same exercises as the experimental group using a mirror that did not show the non-paretic upper extremity. The groups performed the same exercises for 20 min. All subjects received this intervention for 45-min three times a week for 6 weeks. [Results] After the intervention, the experimental group showed significant improvements in the box and block test (BBT), grip strength, and the Fugl-Meyer assessment (FMA), and a significant decrease in the Jebsen-Taylor test. The control group showed a significant increase in grip strength after the intervention, and a significant decrease in the Jebsen-Taylor test. Comparison of the result after the intervention revealed that the experimental group showed more significant increases in the BBT and grip strength than the control group. [Conclusion] These results show that MT with tDCS has a positive effect on the functional recovery of the upper extremity of stroke patients, through activating motor regions in the brain, and thus plays an important role in recovery of neuroplasticity. PMID:25995552

  3. Effect of mirror therapy with tDCS on functional recovery of the upper extremity of stroke patients.

    PubMed

    Cho, Hyuk-Shin; Cha, Hyun-Gyu

    2015-04-01

    [Purpose] This study aimed to determine the effect of mirror therapy (MT) with transcranial direct current stimulation (tDCS) on the recovery of the upper extremity function of chronic stroke patients. [Subjects] Twenty-seven patients at least 6 months after stroke onset were divided randomly into an experimental group (14 patients) and a control group (13 patients). [Methods] All subjects received tDCS for 20 min followed by a 5 min rest. Then the experimental group received MT while the control group conducted the same exercises as the experimental group using a mirror that did not show the non-paretic upper extremity. The groups performed the same exercises for 20 min. All subjects received this intervention for 45-min three times a week for 6 weeks. [Results] After the intervention, the experimental group showed significant improvements in the box and block test (BBT), grip strength, and the Fugl-Meyer assessment (FMA), and a significant decrease in the Jebsen-Taylor test. The control group showed a significant increase in grip strength after the intervention, and a significant decrease in the Jebsen-Taylor test. Comparison of the result after the intervention revealed that the experimental group showed more significant increases in the BBT and grip strength than the control group. [Conclusion] These results show that MT with tDCS has a positive effect on the functional recovery of the upper extremity of stroke patients, through activating motor regions in the brain, and thus plays an important role in recovery of neuroplasticity. PMID:25995552

  4. First results about recovery of walking function in patients with intensive care unit-acquired muscle weakness from the General Weakness Syndrome Therapy (GymNAST) cohort study

    PubMed Central

    Mehrholz, Jan; Mückel, Simone; Oehmichen, Frank; Pohl, Marcus

    2015-01-01

    Objectives To describe the time course of recovery of walking function and other activities of daily living in patients with intensive care unit (ICU)-acquired muscle weakness. Design This is a cohort study. Participants We included critically ill patients with ICU-acquired muscle weakness. Setting Post-acute ICU and rehabilitation units in Germany. Measures We measured walking function, muscle strength, activities in daily living, motor and cognitive function. Results We recruited 150 patients (30% female) who fulfilled our inclusion and exclusion criteria. The primary outcome recovery of walking function was achieved after a median of 28.5 days (IQR=45) after rehabilitation onset and after a median of 81.5 days (IQR=64) after onset of illness. Our final multivariate model for recovery of walking function included two clinical variables from baseline: the Functional Status Score ICU (adjusted HR=1.07 (95% CI 1.03 to 1.12) and the ability to reach forward in cm (adjusted HR=1.02 (95% CI 1.00 to 1.04). All secondary outcomes but not pain improved significantly in the first 8 weeks after study onset. Conclusions We found good recovery of walking function for most patients and described the recovery of walking function of people with ICU-acquired muscle weakness. Trials registrations number Sächsische Landesärztekammer EK-BR-32/13-1; DRKS00007181, German Register of Clinical Trials. PMID:26700274

  5. Riluzole promotes motor and respiratory recovery associated with enhanced neuronal survival and function following high cervical spinal hemisection.

    PubMed

    Satkunendrarajah, K; Nassiri, F; Karadimas, S K; Lip, A; Yao, G; Fehlings, M G

    2016-02-01

    Cervical spinal cord injury (SCI) can result in devastating functional deficits that involve the respiratory and hand function. The mammalian spinal cord has limited ability to regenerate and restore meaningful functional recovery following SCI. Riluzole, 2-amino-6-trifluoromethoxybenzothiazole, an anti-glutamatergic drug has been shown to reduce excitotoxicity and confer neuroprotection at the site of injury following experimental SCI. Based on promising preclinical studies, riluzole is currently under Phase III clinical trial for the treatment of SCI (ClinicalTrials.gov: NCT01597518). Riluzole's anti-glutamatergic role has the potential to regulate neuronal function and provide neuroprotection and influence glutamatergic connections distal to the initial injury leading to enhanced functional recovery following SCI. In order to investigate this novel role of riluzole we used a high cervical hemisection model of SCI, which interrupts all descending input to motoneurons innervating the ipsilateral forelimb and diaphragm muscles. Following C2 spinal cord hemisection, animals were placed into one of two groups: one group received riluzole (8 mg/kg) 1 h after injury and every 12 h thereafter for 7 days at 6 mg/kg, while the second group of injured rats received vehicle solution for the same duration of time. A third group of sham injured rats underwent a C2 laminectomy without hemisection and served as uninjured control rats. Interestingly, this study reports a significant loss of motoneurons within the cervical spinal cord caudal to C2 hemisection injury. Disruption of descending input led to a decrease in glutamatergic synapses and motoneurons caudal to the injury while riluzole treatment significantly limited this decline. Functionally, Hoffmann reflex recordings revealed an increase in the excitability of the remaining ipsilateral cervical motoneurons and significant improvements in skilled and unskilled forelimb function and respiratory motor function in the

  6. The possibility of renal function recovery in chronic hemodialysis patients should not be overlooked: Single center experience.

    PubMed

    Letachowicz, Krzysztof; Madziarska, Katarzyna; Letachowicz, Waldemar; Krajewska, Magdalena; Penar, Józef; Kusztal, Mariusz; Gołębiowski, Tomasz; Weyde, Wacław; Klinger, Marian

    2016-04-01

    Chronic hemodialysis is implemented when irreversible loss of kidney function occurs. Sometimes renal recovery is overlooked. From January 2005 to December 2014, we identified 28 patients hemodialyzed for more than 3 months who had renal replacement therapy discontinued. The group consisted of 17 (57.7%) males and 11 (42.3%) females. Patients were 18-87 years old. Time of hemodialysis ranged from 3 to 97 months. Of note, 14 (50%) patients were referred from local dialysis units for solution of vascular access problems. In 13 (46.2%) patients dialysis was abandoned within the first 6 months, in 5 (17.8%) patients between 6 and 12 months, and in 10 (35.7%) patients beyond 12 months. Estimated dialysis-free survival was 94.4% (SE 0.054) and 82% (SE 0.095) at 12 and 24 months, respectively. All physicians must be aware of possible kidney function improvement. In patients with preserved diuresis fall in periodical urea or creatinine measurements might be a sign of renal recovery. PMID:26592176

  7. 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

  8. Basic Concepts in Understanding Recovery of Function in Vestibular Reflex Networks during Vestibular Compensation

    PubMed Central

    Peusner, Kenna D.; Shao, Mei; Reddaway, Rebecca; Hirsch, June C.

    2012-01-01

    Unilateral peripheral vestibular lesions produce a syndrome of oculomotor and postural deficits with the symptoms at rest, the static symptoms, partially or completely normalizing shortly after the lesion due to a process known as vestibular compensation. The symptoms are thought to result from changes in the activity of vestibular sensorimotor reflexes. Since the vestibular nuclei must be intact for recovery to occur, many investigations have focused on studying these neurons after lesions. At present, the neuronal plasticity underlying early recovery from the static symptoms is not fully understood. Here we propose that knowledge of the reflex identity and input–output connections of the recorded neurons is essential to link the responses to animal behavior. We further propose that the cellular mechanisms underlying vestibular compensation can be sorted out by characterizing the synaptic responses and time course for change in morphologically defi