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Zahra Hassannejad Shayan Abdollah Zadegan Alexander R. Vaccaro Vafa Rahimi-Movaghar Omid Sabzevari 《Injury》2019,50(2):278-285
Background
The complex pathophysiological events occurring after traumatic spinal cord injuries (TSCI) make this devastating trauma still incurable. Peptide amphiphile (PA) hydrogels are nanobiomaterials displaying desirable properties for application in regenerative medicine because they are absorbable, injectable, allowing biofunctionalization, controlling release of trophic factors and mimic extracellular matrix (ECM). In this study, we explored the potentiality of the IKVAV-functionalized PA hydrogel to provide a permissive environment for cell migration and growth as well as sustained release of BDNF at the lesion after severe compression injury model.Methods
The IKVAV-functionalized PA was synthesized by automated solid-phase approach and its secondary structure was evaluated by Circular dichroism (CD) spectroscopy. The potential of IKVAV-functionalized PA to self-assemble into nanofibers and hydrogel formation were assessed using transmission electron microscopy (TEM). Release profiles of BDNF from hydrogel and the bioactivity of the released BDNF from hydrogel were determined using ELISA and DRG bioassay, respectively. Severe spinal cord injury was induced using clip compression at T7-T8 vertebral segment. Twenty four hours post-injury the animals were treated by either IKVAV PA hydrogel, BDNF-loaded IKVAV PA hydrogel, BDNF solution or saline. Two and six weeks later, animals were sacrificed and the lesion site was evaluated based on GFAP, CD68 and ß III tubulin immunoreactivity. Also, locomotor recovery was assessed during 6 weeks using Basso, Beattie, Bresnahan (BBB) scoring test.Results
The IKVAV PA arranged into nanofibrous structure and provided a sustained release of BDNF over 21 days while preserved the bioactivity of BDNF. Also, BDNF loading influenced the hydrogel nanostructure resulting in aligned orientation of nanofibers. Injection of BDNF-loaded IKVAV PA hydrogel resulted in a considerable axon preservation and astrogliosis reduction at 6 weeks post-injury without showing any inflammatory reaction. However, the BBB score was not statistically different between different treatment groups.Conclusion
Although the locomotor functional recovery was not observed in this study, the axon preservation and minimal inflammation in animals treated with BDNF-incorporated hydrogel indicate the potentiality of the designed intervention for further evaluations in the path of developing efficient therapies for severe spinal cord injury. 相似文献3.
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Mohammadreza Hojat 《Medical education》2018,52(4):456-457
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Mohammadreza Alizadeh-Ghodsi Ali Zavvari Mohammad Reza Shiri-Shahsavar 《Nutritional neuroscience》2018,21(2):92-96
Multiple sclerosis (MS) is a disease which manifests demyelination of neuronal cells in the brain. Despite extensive research on the mechanisms of disease development and progression, the exact mechanism is not elucidated yet, which has hampered drug development and subsequent treatment of the disease. We have recently shown that the serum levels of arsenic and malondialdehyde, a lipid peroxidation marker, are high in MS patients. In this article, we would like to formulate the hypothesis that arsenic may cause MS by induction of inflammation, degeneration, and apoptosis in neuronal cells. The induction of ROS generation in cells upon exposure to arsenic as a heavy metal may be involved in the pathogenesis of MS. Tau protein, a member of the family of microtubule-associated proteins, is mainly expressed in neurons and contribute to the assembly of neuronal microtubules network. Arsenic may affect the hyperphosphorylation and aggregation of tau proteins and may be involved in the cascade leading to deregulation of tau function associated with neurodegeneration. For validation of this hypothesis, studies might be conducted to evaluate the association of arsenic levels and tau protein levels in MS patients. Further studies might also focus on the trafficking along microtubules in neurons of MS patient with regard to hyperphosphorylation of tau protein. This hypothesis may add a new dimension to the understanding of MS etiology and help to design novel therapeutic agents against potential targets that might be discovered. If this hypothesis proves to be true, tau phosphorylation inhibitors can be potential candidates for MS drug development. 相似文献
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Mohammadreza Hojat Jennifer DeSantis Stephen C. Shannon Luke H. Mortensen Mark R. Speicher Lynn Bragan Marianna LaNoue Leonard H. Calabrese 《Advances in health sciences education : theory and practice》2018,23(5):899-920
The Jefferson Scale of Empathy (JSE) is a broadly used instrument developed to measure empathy in the context of health professions education and patient care. Evidence in support of psychometrics of the JSE has been reported in health professions students and practitioners with the exception of osteopathic medical students. This study was designed to examine measurement properties, underlying components, and latent variable structure of the JSE in a nationwide sample of first-year matriculants at U.S. colleges of osteopathic medicine, and to develop a national norm table for the assessment of JSE scores. A web-based survey was administered at the beginning of the 2017–2018 academic year which included the JSE, a scale to detect “good impression” responses, and demographic/background information. Usable surveys were received from 6009 students enrolled in 41 college campuses (median response rate?=?92%). The JSE mean score and standard deviation for the sample were 116.54 and 10.85, respectively. Item-total score correlations were positive and statistically significant (p?<?0.01), and Cronbach α?=?0.82. Significant gender differences were observed on the JSE scores in favor of women. Also, significant differences were found on item scores between top and bottom third scorers on the JSE. Three factors of Perspective Taking, Compassionate Care, and Walking in Patient’s Shoes emerged in an exploratory factor analysis by using half of the sample. Results of confirmatory factor analysis with another half of the sample confirmed the 3-factor model. We also developed a national norm table which is the first to assess students’ JSE scores against national data. 相似文献
10.
Mojdeh Ghabaee Ali Zandieh Shahrzad Mohebbi Mohammad Fakhri Homa Sadeghian Fatemeh Divani Hamed Amirifard Mohammadreza Mousavi-Mirkala Majid Ghaffarpour 《Acta neurologica Belgica》2014,114(1):41-45
We aimed to compare the association of high-sensitivity C-reactive protein (CRP) and National Institutes of Health Stroke Scale (NIHSS) score with mortality risk and to determine the optimal threshold of CRP for prediction of mortality in ischemic-stroke patients. A series of 162 patients with first-ever ischemic-stroke admitted within 24 h after onset of symptoms was enrolled. CRP and NIHSS score were estimated on admission and their predictive abilities for mortality at 7 days were determined by logistic-regression analyses. Receiver-Operating Characteristic (ROC) curves were depicted to identify the optimal cut-off of CRP, using the maximum Youden-index and the shortest-distance methods. Deceased patients had higher levels of CRP and NIHSS on admission (8.87 ± 7.11 vs. 2.20 ± 4.71 mg/l for CRP, and 17.31 ± 6.36 vs. 8.70 ± 4.85 U for NIHSS, respectively, P < 0.01). CRP and NIHSS were correlated with each other (r 2 = 0.39, P < 0.001) and were also independently associated with increased risk of mortality [odds ratios (95 % confidence interval) of 1.16 (1.05–1.28) and 1.20 (1.07–1.35) for CRP and NIHSS, respectively, P < 0.01]. The areas under the ROC curves of CRP and NIHSS for mortality were 0.82 and 0.84, respectively. The CRP value of 2.2 mg/l was identified as the optimal cut-off value for prediction of mortality within 7 days (sensitivity: 0.81, specificity: 0.80). Thus, CRP as an independent predictor of mortality following ischemic-stroke is comparable with NIHSS and the value of 2.2 mg/l yields the optimum sensitivity and specificity for mortality prediction. 相似文献