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Background: It was found that the novel coronavirus disease 2019 (COVID-19) pandemic contributed to changes in the epidemiologic and symptomatic pattern of some neurologic disorders. Objectives: The present study investigated the frequency of seizures and their characteristics from February to August 2020 (the peak of the COVID-19 pandemic) compared to the same period the year before. Materials & Methods: This cross-sectional-analytical study was performed on patients with seizures in Poursina hospital in Guilan province, Iran, between February and August 2020 and the same period the year before. Patients with seizures at the beginning or during hospitalization with at least one seizure in the desired period were included in the study. Results: The increase in seizure frequency during the COVID-19 pandemic versus last year was statistically significant (P=0.014). It also observed a significant difference in seizure etiology (P=0.032), types (P<0.005), and history of seizure (P<0.001). The most prevalent causes of seizures and stroke before and during the COVID-19 pandemic are unknown. The convulsive status epilepticus increased during the COVID-19 pandemic period by 4-fold. Before the pandemic, the patients had a higher prevalence of seizure history. Conclusion: The frequency of seizures, their types, and etiology changed during the COVID-19 pandemic, signifying that COVID-19 can influence on hospital burden of the seizure population. [ABSTRACT FROM AUTHOR]

Insomnia is a serious problem after traumatic brain injury (TBI) and partially improves via sleeping pills. We investigated the efficacy of transcranial direct current stimulation (tDCS) with a focus on the role of age and gender. In a randomized double-blind clinical trial, 60 eligible TBI-induced insomnia patients were assigned to real and sham tDCS groups and were treated for three weeks. Sham but not real tDCS took sleeping pills for the first three weeks of the study and then used the placebo until the end of the study. The placebo was used by the real-tDCS group throughout the study. Sleep quality and insomnia severity were respectively evaluated by Pittsburg Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) at three time points. Real tDCS group reported lower mean ISI and PSQI scores at 3 weeks post treatment onset and maintained this decline for six weeks post treatment onset (P < 0.001). In younger participants and those identified as men, the treatment-induced attenuation of the mean PSQI score was reported higher and more lasting in real than sham tDCS groups. Gender and age-specific tDCS protocols may be warranted to optimize the therapeutic effect of tDCS. [ABSTRACT FROM AUTHOR]

Objectives: The role of combined presence of vitamin D deficiency and other risk factors of stroke in ischemic cerebrovascular accident (CVA) development in Iranian adults has been unclear, so far. The association of vitamin D status at admission with ischemic CVA severity and outcome in this community is not yet well elucidated. This study aimed to clarify these ambiguities. Methods: In a cross‐sectional study 104 hospitalized ischemic CVA patients and 104 healthy controls participated. The serum level of 25 (OH) D3 and baseline biochemical parameters were measured in ischemic patients within the first 24 h of admission, as well as healthy controls. The severity of CVA and clinical outcome were assessed using National Institutes Health Stroke Scale and Modified Rankin Scale, respectively. Data were analyzed using the Chi‐square test, independent t‐test, and multiple logistic regression. Results: There was a significant difference between patients and controls regarding the presence of vitamin D3 deficiency, hypertension, smoking, and baseline level of LDL and FBS. Vitamin D3 deficiency boosted the risk of ischemic in males and those having family history of CVA. A low serum level of 25 (OH) D3 was associated with more severity and poor outcome of CVA. The CVA severity, vitamin D3 deficiency, and hypertension were predictors of poor outcome. Conclusions: The study highlights the increased risk of ischemia in Iranians by cooccurrence of vitamin D3 deficiency and other risk factors of CVA. Clinical significance of vitamin D3 deficiency control may be suggested in those at risk of CVA and functional poor outcomes. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most malignant primary brain tumor and is characterized by vascular hyperplasia, necrosis, and high cell proliferation. Despite current standard therapies, including surgical resection and chemoradiotherapy, GBM patients survive for only about 15 months after diagnosis. Recently, the U.S. Food and Drug Administration (FDA) has approved an antiangiogenesis medication for recurrent GBM-bevacizumab-which has improved progression-free survival in GBM patients. Although bevacizumab has resulted in significant early clinical benefit, it inescapably predisposes tumor to relapse that can be represented as an infiltrative phenotype. Fundamentally, bevacizumab antagonizes the vascular endothelial growth factor A (VEGFA), which is consistently released on both endothelial cells (ECs) and GBM cells. Actually, VEGFA inhibition on the ECs leads to the suppression of vascular progression, permeability, and the vasogenic edema. However, the consequence of the VEGFA pathway blockage on the GBM cells remains controversial. Nevertheless, a piece of evidence supports the relationship between bevacizumab application and compensatory activation of kinase signaling within GBM cells, leading to a tumor cell invasion known as the main mechanism of bevacizumab-induced tumor resistance. A complete understanding of kinase responses associated with tumor invasion in bevacizumab-resistant GBMs offers new therapeutic opportunities. Thus, this study aimed at presenting a brief overview of preclinical and clinical data of the tumor invasion and resistance induced by bevacizumab administration in GBMs, with a focus on the kinase responses during treatment. The novel therapeutic strategies to overcome this resistance by targeting protein kinases have also been summarized. [ABSTRACT FROM AUTHOR]

Although using Dynamic Assessment especially in educational setting has been revealed to be a useful approach in helping learners to achieve higher levels of learning, not much consideration has been given to the role of teacher mediation through Dynamic Assessment in teaching writing literacy (Persian language). This study aimed to explore possible effects of teacher mediation on Iranian students' Persian writing skills. To this end 30 Iranian Persian students were selected as participants of the study. The treatment group was taught writing skill through DA by using Flexible mediation, but the control group without receiving any mediation. A non-dynamic pre- and post-test writings were given to both groups to determine any differences in their writing performance. At the end of the treatment a semi-structured interview was used to know the experimental group's opinion about their teacher's assistance. The data was subjected to the statistical procedure of t-test and the results indicated that not only all the students of experimental group outperformed the students of control group but according the semi-structured interview, DA acted as low affective filter for them since they saw teacher as an assistant during their writing and their improvement increased their motivation. [ABSTRACT FROM AUTHOR]

Introduction: The mechanism of putative cytotoxicity of 4-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidone (rolipram), a specific phosphodiesterase-4 (PDE4) inhibitor, on glioblastoma multiforme (GBM) is almost unknown. This study aimed to investigate the role of protein kinase B (Akt) pathway in the cytotoxic effect of rolipram on human GBM U87 MG cell line and Tumor-Initiating Cells (TICs) isolated from patient's GBM specimen. Methods: TICs were characterized by using flow cytometry and quantitative real-time PCR. The cells were treated with rolipram at inhibitory concentration of 50% (IC50) in the presence or absence of SC79 (4µg/mL), a specific AKT activator, for 48 hours. The cell viability and apoptosis were measured by MTT assay and TUNEL staining, respectively. The relative expression of Phospho-Akt (Ser473), matrix metalloproteinase 2 (MMP2), and vascular endothelial growth factor A (VEGFA) were detected using Western blotting. Results: The findings showed that rolipram could suppress cell viability in both U87MG and TICs, dose-dependently. Interestingly, the rolipram-induced cytotoxicity was significantly reduced in the presence of SC79. Nevertheless, in rolipram-treated cells, the pretreatment with SC79 significantly led to increase in U87 MG cells and TICs apoptosis and decrease in viability of U87 MG cells but not TICs relative to corresponding control. In U87 MG and TICs, rolipram-induced reduction of Phospho-Akt (Ser473) and MMP2 levels were significantly suppressed by SC79. Conclusion: There is a cell type-specific mechanism of anti-proliferative action of rolipram on GBM cells. The reduction of intracellular level of MMP2 but not VEGFA by rolipram is conducted through the inhibition of Akt signal. Rolipram-induced apoptosis is mediated via Akt dependent/independent mechanisms. [ABSTRACT FROM AUTHOR]

Background: The objective was to determine the predictors of posttraumatic psychiatric disorders (PTPD) during the first 6 months following traumatic brain injury (TBI) focusing on neuroimaging, clinical and neuropsychological appraisements during acute and discharge phase of TBI. Materials and Methods: We designed a prospective, longitudinal study in which 150 eligible TBI patients were entered. Postresuscitation brain injury severity and discharged functional outcome were evaluated by standard clinical scales. First neuroimaging was done at a maximum of 24 h after head trauma. Early posttraumatic (PT) neuropsychological outcomes were assessed using Persian neuropsychological tasks at discharge. The standardized psychiatric assessments were carefully implemented 6 months postinjury. A total of 133 patients returned for follow-up assessment at 6 months. They were divided into two groups according to the presence of PTPD. Results: Apparently, aggression was the most prevalent type of PTPD (31.48%). There was no significant difference between groups regarding functional outcome at discharge. Diffuse axonal injury (12.96%) and hemorrhages (40.74%) within the cortex (42.59%) and sub-cortex (33.33) significantly occurred more prevalent in PTPD group than non-PTPD ones. Primary postresuscitation TBI severity, early PT lingual deficit and subcortical lesion on first scan were able to predict PTPD at 6 months follow-up. Conclusion: Almost certainly, the expansive dissociation risk of cortical and subcortical pathways related to linguistic deficits due to severe intracranial lesions over a period of time can augment possibility of subsequent conscious cognitive-emotional processing deficit, which probably contributes to latter PTPD. Hence, early combined therapeutic supplies including neuroprotective pharmacotherapy and neurofeedback for neural function reorganization can dampen the lesion expansion and latter PTPD. [ABSTRACT FROM AUTHOR]

Objectives: We investigated the therapeutic effect of transcranial direct current stimulation (tDCS) combined with routine physiotherapy on the neurological and upper limb motor function in ischemic stroke patients with hemiplegia., Methods: In a Randomized double-blind controlled trial study, 52 eligible stroke patients were assigned to real tDCS receiving bihemispheric electrical current with 1.5 mA for 30 minutes over the primary motor cortex, and sham tDCS with a current intensity of 0.5 mA for 30 seconds. Both groups received routine physiotherapy, 5 sessions per week for two weeks. The National Institute of Health Stroke Scale (NIHSS) and the Medical Research Council Scale for Muscle Strength were used to assess the neurological and upper limb motor functions, respectively., Results: Both therapeutic approaches begot a significant improvement in upper limb motor function and neurological impairment at the last session of therapy and follow-up study. However, the treatment-induced neurological amelioration at the last session of therapy in real tDCS was significantly more than sham, especially in those identified as female and under 60 years old., Conclusions: A gender and age-specific protocol of real tDCS combined with routine physiotherapy might be beneficial to improve neurological impairment but not upper limb motor dysfunction after stroke., Competing Interests: Conflict of interest statement: All authors declare that they have no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Type 2 diabetes mellitus (T2DM) is recognized as a complex metabolic which has affected the lives of millions of people around the world. Vitamin D receptor (VDR) gene polymorphisms have been suggested to be a vital contributor to the development of T2DM. However, the association between VDR gene polymorphisms and T2DM remains controversial. We have investigated the association between two VDR gene polymorphisms (rs731236 and rs1544410) and T2DM in an Iranian population., Methods: A total of 148 T2DM patients and 100 normal controls were recruited in this study. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis to perform genotyping., Results: The results of the present research revealed that the frequency of the rs731236 C allele was significantly higher in T2DM patients than in normal controls (p = 0.044). The CC genotype of rs731236 was connected with an increased risk of T2DM (OR = 2.85, 95% CI = 1.06-7.69, p = 0.039). However, no significant difference in the frequency of the rs1544410 C allele between T2DM patients and normal controls was observed (p = 0.918)., Conclusion: Our findings were suggestive of the rs731236 polymorphism of the VDR as a risk factor for developing T2DM in the Iranian population, while rs1544410 polymorphism may not be associated with T2DM susceptibility. Further research is needed to approve these findings in other populations and to clarify the underlying mechanisms involved in such an association., Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01323-0., Competing Interests: Competing of interestThere are no conflicts of interest declared by the authors., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Cell therapy is an important strategy for the treatment of incurable diseases including those that occur in the Central Nervous System (CNS). Among different strategies, the method of delivering or transplantation of cells into the brain has shown significant effects on regeneration. In this study, a new protocol has been developed for the transplantation of adipose tissuederived stem cells into the brain through Cerebrospinal Fluid (CSF) in rat models., Methods: For this purpose, a wide range of ages (7-30 days old) of male neonates of Wistar rats was used. Moreover, human adipose tissue was obtained from a superficial layer of abdomen through liposuction surgery. The size of the inserted part of needle to access middle cranial fossa and subarachnoid space in animals with an average weight of 10-80 g was determined. In addition, to confirm the entrance of needle into the subarachnoid space, CSF was aspirated slowly and then injection was done within two minutes., Results: The findings showed the presence of transplanted human Adipose-Derived Stem Cells (hADSC) in the cerebellum and basal ganglia following three days and also after two months that confirmed the entrance of transplanted cells into the cerebrospinal fluid and migration of them into the brain tissue. All the animals survived after the transplantation process, with the lowest side effects compared to the available conventional methods., Conclusion: It can be concluded that the cells could be efficiently transplanted into CSF through subarachnoid space by injection via superior orbital fissure with a minimally invasive technique., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: The mechanism of putative cytotoxicity of 4-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidone (rolipram), a specific phosphodiesterase-4 (PDE4) inhibitor, on glioblastoma multiforme (GBM) is almost unknown. This study aimed to investigate the role of protein kinase B (Akt) pathway in the cytotoxic effect of rolipram on human GBM U87 MG cell line and Tumor-Initiating Cells (TICs) isolated from patient's GBM specimen., Methods: TICs were characterized by using flow cytometry and quantitative real-time PCR. The cells were treated with rolipram at inhibitory concentration of 50% (IC50) in the presence or absence of SC79 (4μg/mL), a specific AKT activator, for 48 hours. The cell viability and apoptosis were measured by MTT assay and TUNEL staining, respectively. The relative expression of Phospho-Akt (Ser473), matrix metalloproteinase 2 (MMP2), and vascular endothelial growth factor A (VEGFA) were detected using Western blotting., Results: The findings showed that rolipram could suppress cell viability in both U87MG and TICs, dose-dependently. Interestingly, the rolipram-induced cytotoxicity was significantly reduced in the presence of SC79. Nevertheless, in rolipram-treated cells, the pretreatment with SC79 significantly led to increase in U87 MG cells and TICs apoptosis and decrease in viability of U87 MG cells but not TICs relative to corresponding control. In U87 MG and TICs, rolipram-induced reduction of Phospho-Akt (Ser473) and MMP2 levels were significantly suppressed by SC79., Conclusion: There is a cell type-specific mechanism of anti-proliferative action of rolipram on GBM cells. The reduction of intracellular level of MMP2 but not VEGFA by rolipram is conducted through the inhibition of Akt signal. Rolipram-induced apoptosis is mediated via Akt dependent/independent mechanisms., Competing Interests: Conflict of Interest The authors declared no conflicts of interest.

Background: Head injury (HI) is preventable and knowledge of the epidemiology of children's HI is essential for developing preventive strategies., Objectives: The aim of this study was to survey pediatric HI patients admitted to emergency wards at Poursina Hospital in Rasht, Iran, from 2009 to 2010, and to identify the cause of HI in these children., Patients and Methods: In this retrospective study, all HI patients under the age of 18 who were admitted to emergency wards between March 2009 and March 2010 were enrolled in the study. Demographic, etiologic, and injury data were collected and a descriptive analysis was performed., Results: A total of 668 patients were included in this study. The mean age was 10.4 ± 5.3 years. The most frequent cause of HI was traffic accidents. The mean Glasgow Coma Scale (GCS) score was 14.5 ± 1.6. The ratio of boys to girls was approximately 3 to 1. The ratio of boys to girls increased with increasing age (P < 0.01). Moreover, an association was found between age at injury and etiology of HI as well as a significant association between age at injury and the place of event (P < 0.01)., Conclusions: The incidence of childhood HI due to traffic accidents is high (81% of pediatric trauma cases). Thus, motorcyclist education and improvement in traffic engineering for pedestrians and bicyclists should be included in prevention programs.