Advances in Neurorestoratology-Current status and future developments.

Neurorestoratology constitutes a novel discipline aimed at the restoration of damaged neural structures and impaired neurological functions. This area of knowledge integrates and compiles all concepts and strategies dealing with the neurorestoration. Although currently, this discipline has already been well recognized by physicians and scientists throughout the world, this article aimed at broadening its knowledge to the academic circle and the public society. Here we shortly introduced why and how Neurorestoratology was born since the fact that the central nervous system (CNS) can be repaired and the subsequent scientific evidence of the neurorestorative mechanisms behind, such as neurostimulation or neuromodulation, neuroprotection, neuroplasticity, neurogenesis, neuroregeneration or axonal regeneration or sprouting, neuroreplacement, loop reconstruction, remyelination, immunoregulation, angiogenesis or revascularization, and others. The scope of this discipline is the improvement of therapeutic approaches for neurological diseases and the development of neurorestorative strategies through the comprehensive efforts of experts in the different areas and all articulated by the associations of Neurorestoratology and its journals. Strikingly, this article additionally explores the "state of art" of the Neurorestoratology field. This includes the development process of the discipline, the achievements and advances of novel neurorestorative treatments, the most efficient procedures exploring and evaluating outcome after the application of pioneer therapies, all the joining of a multidisciplinary expert associations and the specialized journals being more and more impact. We believe that in a near future, this discipline will evolve fast, leading to a general application of cell-based comprehensive neurorestorative treatments to fulfill functional recovery demands for patients with neurological deficits or dysfunctions.

Positive and negative cell therapy in randomized control trials for central nervous system diseases.

Neurorestorative cell therapies have been tested to treat patients with nervous system diseases for over 20 years. Now it is still hard to answer which kinds of cells can really play a role on improving these patients' quality of life. Non-randomized clinical trials or studies could not provide strong evidences in answering this critical question. In this review, we summarized randomized clinical trials of cell therapies for central nervous diseases, such as stroke, spinal cord injury, cerebral palsy (CP), Parkinson's disease (PD), multiple sclerosis (MS), brain trauma, amyotrophic lateral sclerosis (ALS), etc. Most kinds of cell therapies demonstrated negative results for stoke, brain trauma and amyotrophic lateral sclerosis. A few kinds of cell therapies showed neurorestorative effects in this level of evidence-based medicine, such as olfactory ensheating cells for chronic ischemic stroke. Some kinds of cells showed positive or negative effects from different teams in the same or different diseases. We analyzed the possible failed reasons of negative results and the cellular bio-propriety basis of positive results. Based on therapeutic results of randomized control trials and reasonable analysis, we recommend: (1) to further conduct trials for successful cell therapies with positive results to increase neurorestorative effects; (2) to avoid in repeating failed cell therapies with negative results in same diseases because it is nonsense for them to be done with similar treatment methods, such as cell dosage, transplanting way, time of window, etc. Furthermore, we strongly suggest not to do non-randomized clinical trials for cells that had shown negative results in randomized clinical trials.

Distinct gene expression patterns of SOX2 and SOX2OT variants in different types of brain tumours.

Numerous investigations have been recently published on the dysregulated expression of long-noncoding RNAs (lncRNAs) in various cancer types, emphasizing that abnormal lncRNA expression is a major contributor to tumourigenesis. A broad spectrum of lncRNAs is expressed in the central nervous system, where these RNAs seem to play key roles in brain development and function. In addition to expressing SOX2, a master regulator of pluripotency that lies within its third intron, lncRNA SOX2OT has a proposed role in regulating neural development. Based on our previous studies, alternative splicing of SOX2OT generates two alternatively spliced variants (SOX2OT-S1 and SOX2OT-S2). The present study investigated the expression patterns of SOX2OT variants and SOX2 in three principal types of brain tumours (gliomas, meningiomas and pituitary adenomas) and in four brain tumour cell lines (U87-MG, 1321N1, A172 and DAOY). Total RNAwas extracted from 34 human brain tumour specimens, and the expression profile of target genes was measured using a real-time reverse transcription PCR approach. Our data revealed distinct expression patterns for SOX2OT variants and SOX2 in the brain tumour samples, indicating their potential involvement in brain tumourigenesis. Moreover, our results highlighted the potential usefulness of SOX2OT-S1, SOX2OT-S2, and SOX2 in molecular diagnosis and brain tumour classification.

Evaluation of Hippocampal Function in Temporal Lobe Epilepsy: Spatial Bayesian Variable Selection and Grouping the Regression Coefficient in Multilevel Functional Magnetic Resonance Imaging Data Analysis.

Background: A pre-surgical evaluation of cognitive functions in patients with mesial temporal lobe epilepsy (mTLE) is critical. The limitations of the usual brain analysis model were resolved by the spatial Bayesian variable selection (SBVS) method. An Ising and Dirichlet Process (Ising-DP) model considers SBVS and the grouping of a large number of voxels. The present study aimed to identify brain areas involved in episodic memory in patients with right mTLE and controls via the Ising-DP model. The model was extended to include between-subject factors (BSFs), and the results were compared with other classical methods. Methods: The present cross-sectional study was conducted on 15 patients with right mTLE and 20 controls in Tehran, Iran, in 2018. During functional magnetic resonance imaging, the subjects were tested with the face-encoding memory task, followed by a recognition memory test. The participants demographic factors such as age, sex, marital status, area of residence, and years of schooling were considered to comprise BSFs. The independent t test, the chi-square test, and the correlation test were conducted using the SPSS software (version 20.0). The image processing was carried out using SPM (version 12.0) and MATLAB (version R2014a). Results: The Ising-DP model appropriately (R2=0.642) detected activated hippocampal areas. The model adjusted for BSFs indicated a better fit by the significant effect of age (P((γ]>0.91), sex (P[γ]>0.87), and years of schooling (P[γ]>0.89). The heat maps exhibited decreased activation in the right hippocampal region in the patients compared with the controls (P<0.0001). Right hippocampal activity had a significant positive correlation with the recognition memory test in the mTLE group (r=0.665) and the control group (r=0.593). Conclusion: The Ising-DP model was sufficiently sensitive to detect activated areas in our patients with right mTLE during the face-encoding memory task. Since the model adjusted for BSFs improved sensitivity, we recommend the use of more detailed BSFs such as seizure history in future research.

Neck pain associated with smartphone overuse: cross-sectional report of a cohort study among office workers.

PURPOSE: The aim of the current study was to investigate the extent of smartphone use, possible correlation with neck pain and/or psychological impairment in office workers. METHOD: A convenience sample of 1,602 office workers who were using smartphone for prolonged periods (≥ 4 years) participated in a cross-sectional report of a cohort study, assessing demographic, abnormal symptoms of pain in the neck, physical activity, and psychological behavior characteristics. Participants were assessed using a short version of the Smartphone Addiction Scale (SAS-SV), Depression, Anxiety and Stress Scales (DASS-42) questionnaire, as well as International Physical Activity Questionnaire-Short Form (IPAQ-SF). Multiple logistic regression model was conducted to evaluate the adjusted effect of smartphone overuse on nuchal symptoms. RESULTS: The prevalence of neck pain among the office workers was 30.1%. Significantly more female (33.3% vs. 24.5%) and younger (42.2 vs. 43.2 years) employees reported to have neck pain. Overall in 326 (20.3%, 95% CI: 18.4%-22.4%) of studied subjects had, SAS score ≥ 31 and ≥ 33 for male and females, respectively, and so smartphone overuse (SO) was diagnosed. The results of multiple logistic regression model revealed that those with SO were approximately 6 times more likely to have neck pain (95% CI: 4.44-8.09, P < 0.001). CONCLUSIONS: Smartphone overuse in office workers significantly increases the chance of neck pain by 6 times. Hence SO has been associated with, not only somatic complaints, but also psychological distress such as anxiety, stress, and depression. This may necessitate adherence to neck-school, when smartphone use is associated with neck pain.

Clinical Neurorestorative Therapeutic Guidelines for Spinal Cord Injury (IANR/CANR version 2019).

Functional restoration after spinal cord injury (SCI) is one of the most challenging tasks in neurological clinical practice. With a view to exploring effective neurorestorative methods in the acute, subacute, and chronic phases of SCI, "Clinical Therapeutic Guidelines of Neurorestoration for Spinal Cord Injury (China Version 2016)" was first â€‹proposed in 2016 by the Chinese Association of Neurorestoratology (CANR). Given the rapid advances in this field in recent years, the International Association of Neurorestoratology (IANR) and CANR formed and approved the "Clinical Neurorestorative Therapeutic Guidelines for Spinal Cord Injury (IANR/CANR version 2019)". These guidelines mainly introduce restoring damaged neurological structure and functions by varying neurorestorative strategies in acute, subacute, and chronic phases of SCI. These guidelines can provide a neurorestorative therapeutic standard or reference for clinicians and researchers in clinical practice to maximally restore functions of patients with SCI and improve their quality of life. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This guideline provided comprehensive management strategies for SCI, which contains the evaluation and diagnosis, pre-hospital first aid, treatments, rehabilitation training, and complications management. Nowadays, amounts of neurorestorative strategies have been demonstrated to be benefit in promoting the functional recovery and improving the quality of life for SCI patients by clinical trials. Also, the positive results of preclinical research provided lots of new neurorestorative strategies for SCI treatment. These promising neurorestorative strategies are worthy of translation in the future and can promote the advancement of SCI treatments.

Transplantation of miR-219 overexpressed human endometrial stem cells encapsulated in fibrin hydrogel in spinal cord injury.

Oligodendrocyte (OL) loss and demyelination occur after spinal cord injury (SCI). Stimulation of remyelination through transplantation of myelinating cells may be effective in improving function. For the repair strategy to be successful, the selection of a suitable cell and maintaining cell growth when cells are injected directly to the site of injury is important. In addition to selecting the type of cell, fibrin hydrogel was used as a suitable tissue engineering scaffold for this purpose. To test the relationship between myelination and functional improvement, the human endometrial stem cells (hEnSCs) were differentiated toward oligodendrocyte progenitor cells (OPCs) using overexpression of miR-219. Adult female Wistar rats were used to induce SCI by using a compression model and were randomly assigned to the following four experimental groups: SCI, Vehicle, hEnSC, and OPC. Ten days after injury, miR-219 overexpressed hEnSC-derived OPCs encapsulated in fibrin hydrogel, as an injectable scaffold, were injected to the injury site. In this study, with a focus on promoting functional recovery after SCI, the Basso-Beattie-Bresnahan test was performed to evaluate the recovery of motor function every week for 10 weeks and the histological assay was then performed. Results showed that the rate of motor function recovery was significantly higher in OPC group compared to SCI and vehicle groups but no marked differences were found between OPC and hEnSC groups, although, the rate of myelination in the OPC group was significantly higher than the other groups. These results demonstrated that remyelination was not the cause of recovery of motor function.

Application of an artificial neural network model for early outcome prediction of gamma knife radiosurgery in patients with trigeminal neuralgia and determining the relative importance of risk factors.

OBJECTIVES: Stereotactic radiosurgery (SRS) is a minimally invasive modality for the treatment of trigeminal neuralgia (TN). Outcome prediction of this modality is very important for proper case selection. The aim of this study was to create artificial neural networks (ANN) to predict the clinical outcomes after gamma knife radiosurgery (GKRS) in patients with TN, based on preoperative clinical factors. PATIENTS AND METHODS: We used the clinical findings of 155 patients who were underwent GKRS (from March 2000 to march 2015) at Iran Gamma Knife center, Teheran, Iran. Univariate analysis was performed for a long list of risk factors, and those with P-Value < 0.2 were used to create back-propagation ANN models to predict pain reduction and hypoesthesia after GKRS. Pain reduction was defined as BNI score 3a or lower and hypoesthesia was defined as BNI score 3 or 4. RESULTS: Typical trigeminal neuralgia (TTN) (P-Value = 0.018) and age>65 (P-Value = 0.040) were significantly associated with successful pain reduction and three other variables including radiation dosage >85 (P-Value = 0.098), negative history of diabetes mellitus (P-Value = 0.133) and depression (P-Value = 0.190). On the other hand, radio dosage>85 (P-Value = 0.008) was significantly associated with hypoesthesia, other related risk factors (with p-Value<0.2), were history of multiple sclerosis (P-Value = 0.106), pain duration more than 10 years before GKRS (P-Value = 0.115), history of depression (P-Value = 0.139), history of percutaneous ablative procedures (P-Value = 0.148) and history of diabetes mellitus (P-Value = 0.169).ANN models could predict pain reduction and hypoesthesia with the accuracy of 84.5% and 91.5% respectively. By mutual elimination of each factor in this model we could also evaluate the contribution of each factor in the predictive performance of ANN. CONCLUSIONS: The findings show that artificial neural networks can predict post operative outcomes in patients who underwent GKRS with a high level of accuracy. Also the contribution of each factor in the prediction of outcomes can be determined using the trained network.

Transportation mode and timing of spinal cord decompression and stabilization in patients with traumatic spinal cord injury in Iran.

STUDY DESIGN: Cross-sectional retrospective study. OBJECTIVE: To describe the transportation mode to hospital and timing of spinal cord decompression and stabilization (D&S), length of hospital stay, frequency of pressure injuries, and sepsis during hospitalization. SETTING: Brain and Spinal Injury Research Center, Tehran, Iran. METHODS: Eight hundred and thirty patients with traumatic spinal cord injury (TSCI) were enrolled. Mode of transportation and length of time to reach the first hospital, length of hospital stay (LOS), and the time span between hospital arrival and decompression and stabilization (D&S) were recorded. RESULTS: Fifty-nine percent of the enrolled individuals were transported to the first hospital by ambulance, while 41% were transferred by vehicles without medical equipment and personnel. Median length of time to reach the first hospital was 1 h for both ambulance and non-equipped car groups, with no statistically significant difference (p = 0.1). Median LOS, frequencies of pressure injuries, and sepsis based on the injury levels were not significantly different between two transportation modalities. One hundred and seventy-seven individuals had early surgery, and 254 had late surgery. Median LOS was 13 days in the early surgery group and 20 days in the late surgery group (p = 0.002). Frequencies of pressure injuries and sepsis were not significantly different between the late and early surgery groups for various injury levels. CONCLUSION: About 59% of our patients had been transported to a hospital by non-medical personnel. Those with late surgery had significantly longer LOS. Improving TSCI patients' transportation method and early surgical interventions, if possible, may be considered.

Survival Analysis in Patients with Chronic Traumatic Spinal Cord Injury.

BACKGROUND: The goal of this study was to determine hazard rate of death rate and the causes of death in Iranian patients with Traumatic spinal cord injury (TSCI). METHODS: Overall, 1024 patients with chronic traumatic spinal cord injury referred to Brain and Spinal Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran from Jan 2013-2017 were enrolled. Epidemiological and neurological data, along with secondary complications were recorded for all participants. In the case of death, the cause, and the date of death were recorded. The Kaplan-Meier method was used for survival analysis. A log-rank test was carried out to compare survival due to different risk factors. Risk factors and relative risk estimates associated with death were assessed by means of a Cox regression model. RESULTS: Nineteen percent were lost to follow up. During the follow-up period, 22 out of 830 remaining cases (2.6%) died. Deaths were only observed in patients with cervical injuries (59% in C1-C4 level and 41% in C5-C7 level). Kaplan-Meier Log-rank test showed that probability of survival was significantly less in females, complete injury cases, patients with cervical spine injury, depression, and ADR (Autonomic dysreflexia). Controlling for age, sex and education level, Cox regression model showed that hazard rate of death was significantly affected by the categorical variables such as level of injury (HR=0.2, 95% CI=0.12-0.39), severe ADR. CONCLUSION: Probability of survival is lower in female individuals, cases with complete injuries, patients with cervical spine injury, individuals with depression (BDI>10), and clients who experience ADR.

Subcutaneous granulocyte colony-stimulating factor administration for subacute traumatic spinal cord injuries, report of neurological and functional outcomes: a double-blind randomized controlled clinical trial.

In BriefSpinal cord injury is among the most devastating neurological conditions affecting humans. The authors assessed the therapeutic efficacy of subcutaneous recombinant granulocyte colony-stimulating factor as an adjunct to classic surgical and rehabilitative treatments for subacute traumatic spinal cord injuries. This safe and noninvasive treatment may be helpful for better care and satisfaction of patients with this devastating condition throughout the world.

The Anti-Angiogenic Effect of Atorvastatin in Glioblastoma Spheroids Tumor Cultured in Fibrin Gel: in 3D in Vitro Model

Purpose: Glioblastoma multiform (GBM) is the most aggressive glial neoplasm. Researchers have exploited the fact that GBMs are highly vascularized tumors. Anti-angiogenic strategies including those targeting VEGF pathway have been emerged for treatment of GBM. Previously, we reported the anti-inflammatory effect of atorvastatin on GBM cells. In this study, we investigated the anti-angiogenesis and apoptotic activity of atorvastatin on GBM cells. Methods: Different concentrations of atorvastatin (1, 5, 10µM) were used on engineered three-dimensional (3D) human tumor models using glioma spheroids and Human Umbilical Vein Endothelial cells (HUVECs) in fibrin gel as tumor models. To reach for these aims, angiogenesis as tube-like structures sprouting of HUVECs were observed after 24 hour treatment with different concentrations of atorvastatin into the 3-D fibrin matrix and we focused on it by angiogenesis antibody array. After 48 hours exposing with different concentrations of atorvastatin, cell migration of HUVECs were investigated. After 24 and 48 hours exposing with different concentrations of atorvastatin VEGF, CD31, caspase-3 and Bcl-2 genes expression by real time PCR were assayed. Results: The results showed that atorvastatin has potent anti-angiogenic effect and apoptosis inducing effect against glioma spheroids. Atorvastatin down-regulated the expression of VEGF, CD31 and Bcl-2, and induced the expression of caspase-3 especially at 10µM concentration. These effects are dose dependent. Conclusion: These results suggest that this biomimetic model with fibrin may provide a vastly applicable 3D culture system to study the effect of anti-cancer drugs such as atorvastatin on tumor malignancy in vitro and in vivo and atorvastatin could be used as agent for glioblastoma treatment.

Development of Persian version of the Spinal Cord Independence Measure III assessed by interview: a psychometric study.

STUDY DESIGN: Cross-sectional psychometric study. OBJECTIVES: To translate the Spinal Cord Independence Measure III (SCIM-III) into Persian, to evaluate it culturally and to analyze the validity and reliability of the Persian version of the SCIM-III (P-SCIM). SETTING: Brain and Spinal Injury Research Center (BASIR), Tehran, Iran. METHODS: The P-SCIM was developed by forward translation, back-translation, and cultural equivalence assessment procedure. The authors studied: (a) correlation of P-SCIM with the Functional Independence Measure (FIM™) for determining convergence validity, (b) P-SCIM scores in neurological categories for comparison and evaluating discriminative validity, (c) Inter-rater reliability of P-SCIM, (d) Cronbach's alpha for measuring internal consistency of P-SCIM-III. RESULTS: The validity of the scale was supported by a Pearson correlation coefficient of > 0.9 (p < 0.001) between FIM™ and P-SCIM. The Persian SCIM was found to be valid in discriminating different neurological categories. The Inter-rater reliability was concluded by Intraclass correlations of a coefficient > 0.9. Bland-Altman analysis demonstrated good agreement between our raters (mean difference: 0.7, limit of agreement: - 8.09-9.58). Also internal consistency of the scale was shown by Cronbach's alpha to be > 0.7 (0.86). CONCLUSION: P-SCIM-III is a valid and consistent tool for determining functionality in Persian speaking people with spinal cord injury.

Spiritual well-being and quality of life in patients with spinal cord injury: A study from Iran.

Objective To assess the relationship between spiritual well-being and health-related quality of life (QOL) among patients with spinal cord injury (SCI). Setting Brain and SCI Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. Methods This was a cross-sectional study. A sample of patients with SCI participated in the study and completed two questionnaires: the Short-Form 36-Item Health Survey (SF-36) in order to collect data on vitality, social functioning, mental health and role emotional and the Spiritual Well-Being Scale (SWBS) to measure religious and existential well-being. The association between spiritual well-being and health-related QOL was then assessed. Results In all 213 patients were studied. The mean age of patients was 43.5 (SD = 10.8) years, and most were male (77.5%). The results obtained from generalized linear regression analysis indicated that religious well-being and existential well-being were significant contributing factors to improved vitality, social functioning, mental health and role emotional. Conclusion The findings suggest that having higher levels of spiritual well-being might improve quality of life in people with spinal cord injury.

Granulocyte-colony stimulating factor administration for neurological improvement in patients with postrehabilitation chronic incomplete traumatic spinal cord injuries: a double-blind randomized controlled clinical trial.

OBJECTIVE Granulocyte-colony stimulating factor (G-CSF) is a major growth factor for activation and differentiation of granulocyte colonies in the bone marrow. This cytokine has been widely and safely employed in different conditions over many years. The purpose of this study was to investigate the efficacy of G-CSF administration for traumatic spinal cord injury (TSCI). METHODS This double-blind parallel randomized, placebo-controlled, clinical trial, a phase III study, was performed from June 2013 to June 2016 in the Brain and Spinal Cord Injury Research (BASIR) center at Tehran University of Medical Sciences (TUMS). It included 120 patients with incomplete chronic TSCI, American Spinal Injury Association (ASIA) Impairment Scale (AIS) B, C, or D, of at least 6 months' duration. Sixty patients were allocated into the treatment group and 60 patients into the control group. All the patients had completed an outpatient rehabilitation program in the postacute period and were in a neurological and functional plateau. Patients were assessed with the ASIA grading system, the Spinal Cord Independence Measure (SCIM-III), and the International Association of Neurorestoratology-Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS) just before intervention and at 1, 3, and 6 months after 7 subcutaneous administrations of 300 µg/day of G-CSF in the treatment group and placebo in the control group (administered once per day over the course of 1 week). Randomization was performed with randomized block design, and the patients and evaluators were blinded regarding the treatment groups. One patient did not receive the entire allocated intervention and 5 patients were lost to follow-up. Thus data from 114 patients were included in the analysis. RESULTS One hundred twenty patients were randomized and allocated into the study groups. Among them, 56 patients (93.3%) in the G-CSF group and 58 patients (96.6%) in the placebo group completed the study protocol. After 6 months of follow-up, AIS in the placebo group remained unchanged, whereas in the G-CSF group, 1 patient improved from AIS B to C, and 4 patients improved from AIS C to D. The mean (± SE) improvement in ASIA motor score in the G-CSF group was 5.5 ± 0.62, which was significantly more than in the placebo group (0.77 ± 0.20) (p < 0.001). The mean light touch and pinprick sensory scores, respectively, increased by 6.1 ± 1.1 and 8.7 ± 1.5 in the G-CSF group and by 1.3 ± 0.52 and 0.89 ± 0.44 scores in the placebo group (p < 0.001). Evaluation of functional improvement by the IANR-SCIFRS instrument revealed significantly more improvement in the G-CSF group (3.5 ± 0.37) than in the placebo group (0.41 ± 0.12) (p < 0.001). Also, a significant difference was observed in functional improvement between the 2 groups as measured by SCIM-III instrument (7.5 ± 0.95 vs 2.1 ± 0.51, p < 0.001). CONCLUSIONS Administration of G-CSF for incomplete chronic spinal cord injuries is associated with significant motor, sensory, and functional improvement. Clinical trial registration no.: IRCT201108297441N1 ( www.irct.ir ).

Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017).

Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version "Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)". The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility.

Anti-differentiation non-coding RNA, ANCR, is differentially expressed in different types of brain tumors.

Long non-coding RNAs (lncRNAs) are important modulators of various cellular and molecular events, including cancer-associated pathways. The Anti-differentiation ncRNA (ANCR) is a key regulator of keratinocyte differentiation, where its expression is necessary to maintain epidermal progenitor's cells. Herein, we investigated the expression pattern of ANCR in the course of neural differentiation. Moreover, we used published RNAseq data and clinical samples to evaluate the alteration of ANCR expression in different cell types and brain tumors. Furthermore, we manipulated ANCR expression in glioma cell lines to clarify a potential functional role for ANCR in tumorigenesis. Our qRT-PCR results revealed a significant upregulation of ANCR in more malignant and less differentiated types of brain tumors (P = 0.03). This data was in accordance with down regulation of ANCR during neural differentiation. ANCR suppression caused an elevation in apoptosis rate, as well as a G1 cell cycle arrest in glioblastoma cell line. Altogether, our data demonstrated that ANCR may play a role in glioma genesis and that it could be considered as a potential diagnostic and therapeutic target to combat brain cancers.

Predictive Value of Braden Risk Factors in Pressure Ulcers of Outpatients With Spinal Cord Injury.

Pressure Ulcers (PUs) remain among the most common complications after traumatic spinal cord Injuries (SCIs). The main goal of risk factor assessment with different tools has been to provisionally estimate the chance of developing pressure ulcers in patients with Spinal Cord Injury (SCI). Braden tool has been of good predictive value and most commonly employed in hospital communities for risk assessment of pressure sore development. The objective of this study was to determine the Braden risk factors as well as the prevalence of pressure injuries in SCI patients. This cross-sectional study was performed from June 2013 to December 2015 on 163 consecutive referred outpatients with chronic traumatic SCI in our tertiary SCI rehabilitation clinic. We assessed pressure induced skin injuries as well as their Braden risk factors and analyzed their association with stage and location of Pressure Ulcer (PU) and calculated prevalence of PU. One hundred and sixty-three patients out of 580 were found to have active pressure sores, with a prevalence of 28.1%. In the multiple models, only the Braden scale had significant association with the presence of active pressure sore. Patients with severe and moderate Braden scores were 2.36 and 1.82 times, more at risk of pressure sore development, as compared with those having mild scores (P≤0.01). It may be deduced that in various stages of SCI rehabilitation, the Braden scale may be calculated, and patients with moderate and severe risks (according to Braden sale) may need more attention and/or inpatient care for PU prevention.

Anti-inflammatory Effects of Atorvastatin in Human Glioblastoma Spheroids Cultured in a Three-dimensional Model: Possible Relevance to Glioblastoma Treatment.

Glioblastoma multiform (GBM) is a primary malignant brain tumor with a few therapeutic targets available for it. The interaction between the immune system and glioma is an important factor that could lead to novel therapeutic approaches to fight glioma. In this study, we investigated in vitro anti-inflammatory and apoptotic activity of atorvastatin in different concentrations 1, 5, and 10 µM on glioma spheroid cells cultured in a three-dimensional model in fibrin gel that indicate the complex in vivo microenvironment better than a simple two-dimensional cell culture. A mechanistic insight into the role of IL-17RA, TRAF3IP2, and apoptotic genes in progression of glioma could provide an important way for therapy of malignant tumors with manipulation of this inflammatory axis. To reach for these aims, after 24 and 48 h exposure with different concentrations of atorvastatin, caspase-8, caspase-3, Bcl-2, TRAF3IP2, and IL-17RA gene expression were assayed. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and cell cycle assay were used for evaluating the cell apoptosis and proliferation. The results showed that atorvastatin has anti-inflammatory and apoptotic effects against glioma spheroids. Atorvastatin induced the expression of caspase-3 and caspase-8 and downregulated the expression of Bcl-2, TRAF3IP2, and IL-17RA especially at 10 µM concentration. These effects are dose dependent. The most likely mechanisms are the inhibition of inflammation by IL-17RA interaction with TRAF3IP2 and NF-κB signaling pathway. Finally, these results suggest that atorvastatin could be used as an anti-cancer agent for glioblastoma treatment.