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Total resection of glioblastoma (GB) tumors is nearly impossible, and systemic administration of temozolomide (TMZ) is often inadequate. This study presents a hybrid layered composite nanofiber mesh (LHN) designed for localized treatment in GB tumor bed. The LHN, consisting of polyvinyl alcohol and core-shell polylactic acid layers, was loaded with TMZ and rutin. In vitro analysis revealed that LHN TMZ and LHN rutin decelerated epithelial-mesenchymal transition and growth of stem-like cells, while the combination, LHN TMZ +rutin , significantly reduced sphere size compared to untreated and LHN TMZ -treated cells ( P therapy demonstrated a more pronounced tumor-reducing effect than LHN TMZ +rutin -treated rats compared to untreated controls. Structural changes in tumor mitochondria, reduced membrane potential, and decreased PARP expression indicated the activation of apoptotic pathways in tumor cells, which was further confirmed by a reduction in PHH3, indicating decreased mitotic activity of tumor cells. Additionally, the local application of LHNs in the GB model mitigated aggressive tumor features without causing local tissue inflammation or adverse systemic effects. This was evidenced by a decrease in the angiogenesis marker CD31, the absence of inflammation or necrosis in H&E staining of the cerebellum, increased production of IFN-γ, decreased levels of interleukin-4 in splenic T cells, and lower serum AST levels. Our findings collectively indicate that LHN TMZ is a promising biocompatible model for the local treatment of GB.TMZ +rutin -treated rats compared to untreated controls. Structural changes in tumor mitochondria, reduced membrane potential, and decreased PARP expression indicated the activation of apoptotic pathways in tumor cells, which was further confirmed by a reduction in PHH3, indicating decreased mitotic activity of tumor cells. Additionally, the local application of LHNs in the GB model mitigated aggressive tumor features without causing local tissue inflammation or adverse systemic effects. This was evidenced by a decrease in the angiogenesis marker CD31, the absence of inflammation or necrosis in H&E staining of the cerebellum, increased production of IFN-γ, decreased levels of interleukin-4 in splenic T cells, and lower serum AST levels. Our findings collectively indicate that LHN TMZ +rutin is a promising biocompatible model for the local treatment of GB., Competing Interests: The authors declare no conflicts of interest., (© 2024 Shenyang Pharmaceutical University. Published by Elsevier B.V.)

Introduction: To highlight the importance of hands-on experiences and mentorship in shaping the future workforce of specialized medical professionals via a Neurosurgery Training Camp., Methods: Responses of the questionnaire regarding the Neurosurgery Training Camp organized by Bursa Uludag University's Faculty of Medicine and the Turkish Neurosurgery Academy were reviewed retrospectively. A one-day program was organized to introduce neurosurgery to medical students. During the camp, the students participated in interactive presentations delivered by faculty members, had lunch together, became acquainted with neurosurgical tools and technologies, and performed interventions. With pre and postworkshop questionnaire, student's expectations and thoughts about camp was evaluated., Results: Forty-one students from 10 medical schools, spanning every year of study, attended the camp. Approximately 39% of the attendees ( n  = 16) were women and 61% ( n  = 25) were men. The post-workshop survey results demonstrated that 73% of the students ( n  = 30) were inclined to pursue a career in neurosurgery after the camp, 21.9% ( n  = 9) remained undecided, and 4.8% ( n  = 2) chose not to pursue neurosurgery. Feedback from the post-workshop questionnaire highlighted that all students perceived the camp as beneficial in providing insights into their future careers and aiding in making a decision regarding their career paths., Discussion: The neurosurgical training camp effectively inspired and educated medical students about the discipline of neurosurgery. Furthermore, the camp effectively altered the career aspirations and perceptions of neurosurgery among the participating students., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Unal, Aydin, Bilgic, Eser, Alper, Taskapılıoğlu, İlker Kafa, Kocaeli, Dogan, Yılmazlar, Bekar, Sekerci and Aksoy.)

Background: Various methods and techniques have been developed for extraforaminal decompression, particularly for far lateral lumbar disc herniation. Distinct anatomical differences are noticeable in the upper levels of the lumbar spine, which may complicate the related surgical approach. This study aimed to determine the safety and efficiency of the far lateral extraforaminal approach for the upper lumbar disc., Methods: L1-2 and L2-3 migrated lumbar disc herniations were defined as upper lumbar disc herniations. 31 consecutive patients with upper lumbar disk herniation who underwent extraforaminal lumbar microdiscectomy between January 2018 and March 2022 were retrospectively investigated. The patients were assessed using the interval history, follow-up lower back and leg pain visual analog scale scores (0-100 mm), the Oswestry Disability Index (%), and modified MacNab criteria., Results: 31 consecutive patients with upper lumbar disk herniation (20 men and 11 women) with a mean age of 52.8 ± 10.8 years (range 31-70 years) underwent extraforaminal lumbar microdiscectomy. The preoperative and postoperative visual analog scale scores and Oswestry Disability Index were significantly different (P < 0.001). According to the modified MacNab criteria, 23 patients showed excellent improvement, 5 showed good improvement, and 3 showed fair improvement; thus, the rate of satisfactory improvement was 90.3% at the 2-year follow-up. No patients required reoperation at the operative level during follow-up., Conclusions: Extraforaminal lumbar microdiscectomy is a safe and effective minimally invasive surgical technique for treating upper lumbar disc herniation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Parkinson's disease, a progressive neurodegenerative disorder, involves gradual degeneration of the nigrostriatal dopaminergic pathway, leading to neuronal loss within the substantia nigra pars compacta and dopamine depletion. Molecular factors, including neuroinflammation, impaired protein homeostasis, and mitochondrial dysfunction, contribute to the neuronal loss. Deep brain stimulation, a form of neuromodulation, applies electric current through stereotactically implanted electrodes, effectively managing motor symptoms in advanced Parkinson's disease patients. Deep brain stimulation exerts intricate effects on neuronal systems, encompassing alterations in neurotransmitter dynamics, microenvironment restoration, neurogenesis, synaptogenesis, and neuroprotection. Contrary to initial concerns, deep brain stimulation demonstrates antiinflammatory effects, influencing cytokine release, glial activation, and neuronal survival. This review investigates the intricacies of deep brain stimulation mechanisms, including insertional effects, histological changes, and glial responses, and sheds light on the complex interplay between electrodes, stimulation, and the brain. This exploration delves into understanding the role of neuroinflammatory pathways and the effects of deep brain stimulation in the context of Parkinson's disease, providing insights into its neuroprotective capabilities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Parkinson's disease, a progressive neurodegenerative disorder predominantly affecting elderly, is marked by the gradual degeneration of the nigrostriatal dopaminergic pathway, culminating in neuronal loss within the substantia nigra pars compacta (SNpc) and dopamine depletion. At the molecular level, neuronal loss in the SNpc has been attributed to factors including neuroinflammation, impaired protein homeostasis, as well as mitochondrial dysfunction and the resulting oxidative stress. This review focuses on the interplay between neuroinflammatory pathways and Parkinson's disease, drawing insights from current literature., Competing Interests: Declaration of Competing Interest Nothing to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim: To investigate the possible mediation of epigenetic mechanisms underlying the regenerative effect of uridine in a sciatic nerve transection rat model., Material and Methods: Fifty adult male rats were randomized to sham, control, and uridine groups. After unilateral transection and primary anastomosis of the right sciatic nerve, a single daily dose of saline (1 ml/kg; sham and control groups) or uridine (500 mg/kg; uridine group) was injected intraperitoneally for a week. The sciatic nerves were removed en bloc on the eighth day and levels of histone deacetylase 1 (HDAC1), acetylated histone-H3, and acetylated histone-H4 were analyzed in nerve homogenates. The number of myelinated axons in the sciatic nerve specimens was analyzed histomorphologically., Results: The HDAC1 levels were significantly greater in the control group than in the sham (p < 0.001) and uridine (p < 0.01) groups. Compared to the sham group, the acetylated histone-H3 and histone-H4 levels decreased in the control group (by 81.49% and 79.98%, respectively for both; p < 0.001) and increased significantly in the uridine group (by 62.54% and 51.68% respectively; p < 0.01, p < 0.05). The number of myelinated axons decreased significantly (p < 0.001) in the control group, which was enhanced significantly by uridine administration., Conclusion: Epigenetic mechanisms may partly mediate the regenerative effect of uridine treatment in a rat model of sciatic nerve injury. Our data provides novel insights in the management of peripheral nerve damage and suggests potential benefit of uridine for degenerative diseases in which epigenetic impairments are involved.

Aim: To review our experience with patients presenting with recurrent trigeminal neuralgia (TN) and who have undergone repeat microvascular decompression surgery (rMVD)., Material and Methods: This retrospective observational study was conducted at the Department of Neurosurgery at a university hospital. Patients who initially experienced complete pain relief after the first MVD but later had a recurrence of TN symptoms which required an rMVD were included in the study. Pain control outcomes were evaluated based on the Barrow Neurological Institute (BNI) scale score., Results: Of the 375 patients who underwent MVD for TN over a 20-year period, 19 patients (6 females and 13 males) with a mean age of 57.68 ± 9.78 years developed symptom recurrence which necessitated an rMVD (5.06%). The average duration of the symptoms before the rMVD was 16.1 ± 19.36 months. The mean BNI score of the patients before the rMVD was 4.5 ± 0.5. Recurrence was primarily attributed to compression by a new offending vessel (n=9, 47.4%) or a Teflon granuloma (n=8, 42.1%). Two patients (10.5%) did not have any identifiable compression. During a follow-up period of 106.3 ± 58.3 months, excellent pain relief (BNI-I) was achieved in 10 patients (52.6%). Eight patients (42.1%) experienced a good outcome (BNI-III), and one patient (5.3%) experienced a poor outcome (BNI-IV)., Conclusion: Recurrence of TN symptoms can occur even after an initially successful MVD. Subsequent MVDs should be considered as the primary treatment option for recurrent TN, as it significantly controls pain with low morbidity.

Glioblastoma (GB) has susceptibility to post-surgical recurrence. Therefore, local treatment methods are required against recurrent GB cells in the post-surgical area. In this study, we developed a nanofiber-based local therapy against GB cells using Oleuropein (OL), and rutin and their combinations with Temozolomide (TMZ). The polylactic acid (PLA) core-shell nanofiber webs were encapsulated with OL (PLA OL ), rutin (PLA rutin ), and TMZ (PLA TMZ ) by an electrospinning process. A SEM visualized the morphology and the total immersion method determined the release characteristics of PLA webs. Real-time cell tracking analysis for cell growth, dual Acridine Orange/Propidium Iodide staining for cell viability, a scratch wound healing assay for migration capacity, and a sphere formation assay for tumor spheroid aggressiveness were used. All polymeric nanofiber webs had core-shell structures with an average diameter between 133 ± 30.7-139 ± 20.5 nm. All PLA webs promoted apoptotic cell death, suppressed cell migration, and spheres growth (p < 0.0001). PLA OL and PLA TMZ suppressed GB cell viability with a controlled release that increased over 120 h, while PLA rutin caused rapid cell inhibition (p < 0.0001). Collectively, our findings suggest that core-shell nano-webs could be a novel and effective therapeutic tool for the controlled release of OL and TMZ against recurrent GB cells., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Berrin Tunca reports financial support was provided by Scientific and Technological Research Council of Turkey (TUBITAK)., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background/aim: Awake craniotomy (AC) maximizes the resection of lesions in eloquent brain areas while preserving functionality. Tumor delineation with intraoperative use of sodium fluorescein (NaFl) facilitates total resection. When used with AC, it may allow for safe resection without increasing the risk of postoperative neurologic deficits. This study investigated the efficacy and safety of the combined use of NaFl and AC for maximum safe resection in patients with brain metastases., Material and Methods: Patients who underwent AC due to brain metastasis in the Department of Neurosurgery of Uludağ University's Faculty of Medicine between January 1, 2018 and August 1, 2022, were retrospectively analyzed. The study comprised 2 patient groups: plain AC (pAC) and NaFl-guided AC (NaFlg-AC). Surgical outcomes related to fluorescence intensity, degree of resection, perioperative complications, and postoperative neurological factors were evaluated., Results: The pAC group included 16 patients (12 males, 4 females), and the NaFlg-AC group comprised 21 (13 males, 7 females). The mean patient ages for males and females were 61.4 years (61.4 ± 9.5 years) and 60.4 years (60.6 ± 12 years), respectively. The most common origin of the metastatic lesion was the lung in both the pAC and NaFlg-AC groups (n = 12 vs. n = 14, respectively). Gross total resection (GTR) was achieved in 85.7% of the patients in the NaFlg-AC group, whereas the GTR rate was 68.7% in the pAC group. There was no significant difference in GTR rates between the 2 groups (p = 0.254). The mean duration of the resection time was significantly shorter in the NaFlg-AC group (45.95 ± 7.00 min vs. 57.5 ± 12.51 min; p = 0.002). The patients' Karnofsky Performance Status (KPS) score did not reach statistical significance at 6-month follow-up in either group compared to their preoperative baseline scores (p = 0.374). KPS did not show a significant difference between the 2 groups at any time., Conclusion: Fluorescence-guided resection in AC for metastatic tumors in sensory, motor, and cognitive areas is a feasible, safe, and convenient technique that significantly increases GTR rates and shortens operative time compared to conventional white light surgery without fluorescence guidance. It also does not increase the incidence of postoperative complications. With the combined use of AC and NaFl, ensuring clear and visible tumor margins during surgery and controlling patients' neurological function in real-time are possible., Competing Interests: Conflict of interest: The authors declare that there are no conflicts of interest., (© TÜBİTAK.)

Objective: Diabetes mellitus (DM)-mediated impaired glucose metabolism increase in the glioblastoma (GB) risk by inducing hyperglycemia and hyperinsulinemia. An integral membrane transport protein, glucose transporter 3 (GLUT3) facilitates glucose transport into GB tumor cells. We aimed to explore the regulation of GLUT3 in GB tumors of patients who were concurrently diagnosed with DM., Patients and Methods: Formalin-fixed paraffin-embedded (FFPE) tumor samples were collected from 93 GB patients and retrospectively analyzed. Of the total, 15 patients were concurrently diagnosed with DM (GB-DM). The role of GLUT3 in tumor aggressiveness was evaluated by analyzing its correlation with Ki67, P53 expression, MALAT1 expression, and peripheral blood hemoglobin A1C (HbA1c) level. T98G cells were treated with empagliflozin and metformin to modulate GLUT3. The RNA expression of GLUT3, SOX2, and MALAT1 was analyzed by real-time qPCR. The lactate levels of T98G cells were measured by Cobas c502 analyzer. A scratch wound assay was performed to investigate the migration rate of T98G cells., Results: GLUT3 expression was lower in GB-DM tumors than in GB-only tumors. In GB-DM, the expression of tumoral GLUT3 and peripheral blood glycated hemoglobin (HbA1c) levels were negatively correlated with P53 and Ki67. A decreased GLUT3 shortened the disease-free survival duration in GB-DM patients. Empagliflozin reduced GLUT3, while metformin-induced GLUT3 in T98G cells. The empagliflozin-mediated GLUT3 suppression induced SOX2 and MALAT1 expressions and influenced the migration capacity of T98G cells., Conclusions: Our findings suggest that the low GLUT3 expression of the tumors of GB-DM patients may induce the production of adenosine triphosphate (ATP) from cellular energy sources other than glucose metabolism. However, further studies are warranted to confirm these results.

Introduction and Objectives: Acute presentation with intracranial hemorrhage owing to a previously silent brain tumor (BT) is rare. Although any BT can bleed, the frequency and type of bleeding varies across tumor types., Materials and Methods: We aimed to retrospectively review our experience with 55 patients with BTs presenting with ICH., Results: Signs of increased intracranial pressure were the most common symptoms. The temporal lobe was the most common lesion site (n=22). Hemorrhages were mainly confined to the tumor margins (HCTs) (n=34). Extensive intraparenchymal hemorrhages (EIHs) were mainly associated with moderately/severely decreased levels of consciousness (LOCs) (n=15/16). High-grade glioma (HGGT) (n=25) was the leading pathological diagnosis followed by metastasis (MBT) (n=16/55). The hemorrhage type was associated with the pathological diagnosis of the tumor. Patients with HGGT (n=19/25) and MBT (n=9/16) mainly presented with HCTs, whereas low-grade gliomas (LGGT) primarily caused EIHs (n=6/7)., Conclusions: Hemorrhagic presentation is a rare occurrence in BTs. Among all, MBT and HGGT are responsible for majority of the cases. Importantly, despite their relatively benign characteristics, LGGTs mainly result in extensive parenchymal destruction once they bleed. Maximum surgical resection of hemorrhagic BTs and decompression of the affected brain regions followed by histological confirmation of the diagnosis should be the main goals of treatment in cases with hemorrhagic BTs., (Copyright © 2022. Published by Elsevier España, S.L.U.)

The effects of Olea europaea leaf extract (OLE) phenolics, including oleuropein (OL), hydroxytyrosol (HT), tyrosol (TYR), and rutin against glioblastoma (GB), independently and in combination with temozolomide (TMZ), were investigated in T98G and A172 cells. Cell growth was assessed by WST-1, real-time cell analysis, colony formation, and cell cycle distribution assays. A dual acridine orange propidium iodide (AO/PI) staining and annexin V assay determined cell viability. A sphere-forming assay, an intracellular oxidative stress assay, and the RNA expression of CD133 and OCT4 investigated the GB stem-like cell (GSC) phenotype. A scratch wound-healing assay evaluated migration capacity. OL was as effective as OLE in terms of apoptosis promotion ( p < 0.001) and GSC inhibition ( p < 0.001). HT inhibited cell viability, GSC phenotype, and migration rate ( p < 0.001), but its anti-GB effect was less than the total effect of OLE alone. Rutin decreased reactive oxygen species production and inhibited colony formation and cell migration ( p < 0.001). TYR demonstrated the least effect. The additive effects of OL, HT, TYR and rutin with TMZ were significant ( p < 0.001). Our data suggest that OL may represent a novel therapeutic approach against GB cells, while HT and rutin show promise in increasing the efficacy of TMZ therapy.

Aim: To describe the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in glioblastoma (GB) progression in patients concurrently diagnosed with diabetes mellitus (DM)., Material and Methods: Formalin-fixed paraffin-embedded (FFPE) tumor samples of 47 patients diagnosed with GB only and 13 patients diagnosed with GB and DM (GB-DM) were enrolled in this study. Data for p53 and Ki67 immunohistochemical staining of the tumors and blood HbA1c levels of patients with DM were retrospectively collected. MALAT1 expression was assessed using quantitative real-time polymerase chain reaction., Results: The coexistence of GB and DM induced the nuclear expression of p53 and Ki67 compared with GB only. MALAT1 expression was higher in GB-DM tumors than in GB only tumors. The expression of MALAT1 and HbA1c levels were positively correlated. Additionally, MALAT1 was positively correlated with tumoral p53 and Ki67. The disease-free survival of patients with GB-DM with high MALAT1 expression was shorter than that of those diagnosed with GB only and with a lower MALAT1 expression., Conclusion: Our findings suggest that one of the mechanisms of the facilitating effect of DM on GB tumor aggressiveness is via MALAT1 expression.

Background: Gelastic seizures are extremely rare, short-lasting, unprovoked, and uncontrollable laughing attacks. We conducted this retrospective evaluation to determine whether these symptoms, manifesting in different forms, such as cheerful laughter, laughing, smiling, and sobbing had any value in terms of etiology or localization., Methods: A total of 31 patients who exhibited bouts of laughing or crying and who were under follow-up between 2000 and 2019 at tertiary epilepsy centers were included in the study. Laughing seizures were divided into three groups in terms of semiology (i.e., laughter with mirth, laughter without mirth, and smile). Dacrystic seizures were accompanied by some gelastic seizures and were divided into two groups in terms of semiology (i.e., weeping loudly [motor and voice-sobbing] and crying)., Results: Of the 27 patients with laughing seizures, 12 had seizures that manifested with smiling, 7 had seizures that manifested with laughing and mirth, and 8 had seizures that manifested with laughter without mirth. Dacrystic-gelastic seizures were observed in four patients, among whom 2 patients had crying and laughter without mirth and 2 patients had weeping loudly and laughter without mirth episodes., Conclusion: Gelastic and dacrystic seizures often suggest hypothalamic hamartomas, in the literature. This rare ictal behavior can originate from different cortical locations and lesions of a different nature. However, we found that gelastic seizures with smiling were a more homogenous group with regard to location in the temporal lobe, which we aimed to show by evaluating the patients included in this study., Competing Interests: The authors have no conflict of interests to declare., (Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

ObjectiveThe appropriate treatments for the different molecular subgroups of medulloblastomas are challenging to determine. Hence, this study aimed to examine the expression profiles of long non-coding RNAs (LncRNAs) to determine a marker that may be important for treatment selection in these subgroups.MethodsChanges in the expression of LncRNAs in the tissues of patients with medulloblastoma, which are classified into four subgroups according to their clinical characteristics and gene expression profiles, were examined via reverse transcription polymerase chain reaction. Moreover, there association with patient prognosis was evaluated.ResultsThe expression levels of MALAT1 and SNGH16 were significantly higher in patients with group 3 medulloblastoma than in those with other subtypes. Patients with high expression levels of MALAT1 and SNGH16 had a relatively shorter overall survival than those with low expression levels.ConclusionsPatients with group 3 medulloblastoma have a high MALAT1 level, which is associated with poor prognosis. Therefore, MALAT1 can be a new therapeutic target in medulloblastoma.

Introduction. Ulegyria results from perinatal hypoxic-ischemic brain injury in term infants. The specific mushroom-shaped configuration of ulegyria results from small atrophic circumvolutions at the bottom of a sulcus underlying an intact gyral apex. Clinically, ulegyria is generally associated with epilepsy. Here, we aimed to delineate the characteristics of patients with ulegyria and the epileptic seizures they experience. Material and methods . Medical records including radiology and pathology reports, video-electroencephalographic (EEG) analysis, operative notes, hospital progress and outpatient clinic notes were reviewed retrospectively in a total of 10 ulegyria patients. Results. Patients ages ranged between 24 and 58 years (mean, 32 ± 9.8 years). Past medical history was confirmed for neonatal asphyxia in 2 (20%). Neurological examination was remarkable for spastic hemiparesis in 1 (10%) patient with perisylvian ulegyria and for visual field deficits in 2 patients (20%) with occipital ulegyria. Ulegyria most commonly involved the temporoparietal region (n = 5, 50%) followed by the perisylvian area (n = 2, 20%). Except the one with bilateral perisylvian ulegyria, all patients had unilateral lesions (n = 9, 90%). Hippocampal sclerosis accompanied ulegyria in 2 patients (20%). All patients experienced epileptic seizures. Mean age at seizure onset was 8.8 ± 5.4 years (range, 2-20 years). Interictal scalp EEG and EEG-video monitoring records demonstrated temporoparietal and frontotemporal activities in 5 (50%) and 2 (20%) patients, respectively. The seizures were successfully controlled by antiepileptic medication in 8 patients (n = 8, 80%). The remaining 2 patients (%20) with concomitant hippocampal sclerosis required microsurgical resection of the seizure foci due to medically resistant seizures. Discussion. Ulegyria is easily recognized with its unique magnetic resonance imaging characteristics and clinical presentation in the majority of cases. It is highly associated with either medically resistant or medically controllable epileptic seizures. The treatment strategy depends on the age at onset and extends of the lesion that has a significant impact on the severity of the clinical picture.

Objective: Publications on vaccine hesitancy and the novel coronavirus disease 2019 in the scientific literature are increasing every day. An examination of their content will help to eliminate the existing negativity related to vaccine hesitancy through scientific methods. Hence, a systematic approach to the prevention of vaccine hesitancy worldwide can be developed. This article aims to survey how vaccine hesitancy is addressed in the PubMed articles about "vaccine hesitancy" over the novel coronavirus disease, for which the MeSH criteria have been published; to understand their recommendations for the prevention of vaccine hesitancy; to evaluate any related research described as "cross-sectional," "case-control," and "cohort" according to Strengthening the Reporting of Observational Studies in Epidemiology criteria; and to contribute to the current literature on the subject., Material and Methods: This study is planned to use a systematic review format and STROBE checklist was used to evaluate the articles accessed from PubMed database. Microsoft Excel was used as the data calculation tool., Results: Sixty-five (81.3%) of the 80 articles investigated in the scope of this study mention "vaccine." While 64 articles (80%) discuss the determination of vaccine hesitancy, 57 (71.3%) articles address its prevention. The keyword "COVID-19" is used in 61 articles (79.2%). The second most frequently used keyword is "vaccine hesitancy" (n = 37, 48.1%), followed by "vaccine" (n = 25, 32.5%). Twenty-nine (48%) of the reviewed articles originate from the WHO American Continents. The second most represented region of research is the European Region (n = 21, 35%), followed by the South East Asian Region (n = 5, 8%)., Conclusion: This study illustrates the recent situation for the coronavirus disease 2019 vaccine and reveals the presence of a vaccine hesitancy. Vaccine hesitancy is a risk factor that could prevent herd immunity. The systematic review of scientific articles should continue with improvements in order to tackle the problem as exemplified by the present study. Other checklists as well as STROBE checklist are recommended to be used in similar studies to have more objective conclusions.

Aim: Peripheral nerve regeneration remains an issue, and novel therapeutic approaches are required for functional recovery. This study investigated the regenerative potential and long-term functional effects of Uridine treatment in a rat model of sciatic nerve injury., Material and Methods: Male Sprague-Dawley rats were randomized to receive sham surgery plus saline (Sham group), right sciatic nerve transection and primary repair plus saline (Control group), right sciatic nerve transection, and primary repair plus 500 mg/kg Uridine (Uridine group). Saline or Uridine was injected intraperitoneally (i.p.) for seven days, and the rats were monitored for 12 weeks after surgery. We evaluated electrophysiological and functional recovery using electromyography (EMG) and sciatic functional index (SFI) at six and 12 weeks, respectively. At 12 weeks, rats were decapitated and their right sciatic nerves were examined in macroscopic and histomorphologic manners., Results: Functional evaluation by SFI and sciatic nerve conduction velocity analyzed by EMG both decreased in the Control group but recovered in the Uridine group 12 weeks after surgery. Additionally, upon experiment completion, Uridine treatment was observed to enhance nerve adherence, separability scores, and the number of myelinated axons., Conclusion: These results reveal that short-term Uridine treatment provides morphological and electrophysiological benefits, which are represented by long-term functional improvement in a rat model of sciatic nerve injury. These findings validate and extend our knowledge on Uridine's regenerative effects in peripheral nerve injuries.

Objective : This study was designed to conduct molecular classification based on IDH1/2, TERT, ATRX , and DAXX changes in pediatric and adult primary glioblastoma (GB) and to analyze the potential interaction of LncRNA MALAT1 in the determined homogeneous subgroups. Methods: We analyzed the expression profiles of ATRX/DAXX and MALAT1 using the qRT-PCR method and IDH and TERT mutation status using DNA sequencing analysis in 85 primary pediatric and adult GB patients. Results: IDH1 mutation was observed in 5 (5.88%) and TERT mutation in 65 (76.47%) primary pediatric and adult GB patients. ATRX and DAXX were detected in 18 (21.18%) and 7 (8.24%) patients. TERT mutation and loss of ATRX/DAXX C228T mutation had worse prognosis (p < 0.001). Six subgroups were obtained from the genetic analysis. Among the subgroups, MALAT1 was highly expressed in group A that had a single TERT C228T mutation had worse prognosis (p < 0.001). Six subgroups were obtained from the genetic analysis. Among the subgroups, MALAT1 was highly expressed in group A that had a single TERT mutation as compared to that in groups D and E (p = 0.001 and p < 0.001, respectively); further, high MALAT1 expression was associated with worse prognosis in patients with C228T mutation (p < 0.001). Conclusions: Our findings highlight that the presence of TERT C228T mutation and expression of MALAT1 can be used as primary targets during the follow-up of primary GB patients and in the development of new treatment strategies.

Aim: To determine the Wnt and SHH subtypes at the molecular level, and to compare them clinically by examining the changes in CTNNB1, AXIN, PTCH1, SMO, SUFU, and GLI1 mRNA expression in the medulloblastoma of a Turkish population determined according to patient selection criteria. In this context, the clinical distinction between Wnt and SHH groups are realized by considering the age, gender, survival time, location of the lesion, and radiological features of the patients., Material and Methods: Molecular separation was performed by RT-PCR analysis of CTNNB1, AXIN, PTCH1, SMO, SUFU, and GLI1 mRNA expression changes., Results: About 17.8% and 22.2% of the cases were included in the Wnt and the SHH group, respectively. When comparing group differences based on clinical and molecular data, 72.7% and 66.6% of matches were observed in the Wnt and the SHH group, respectively., Conclusion: It has been revealed that molecular analysis and grouping of patients with medulloblastoma can provide support for clinically determined subgroups.

Introduction: The noncoding RNAs (ncRNAs) play a role in biological processes of various cancers including gliomas. The majority of these transcripts are uniquely expressed in differentiated tissues or specific glioma types. Pediatric oligodendroglioma (POG) is a rare subtype of diffuse glioma and accounts for <1% of pediatric brain tumors. Because histologically POG resembles adult OG, the same treatment is applied as adults. However, the significance in predicting outcomes in POG patients is unclear. In this study, we aimed to investigate the prognostic significance of expression -profiles of microRNA (miRNA) and long noncoding RNA -(LncRNA) in POGs., Methods: We investigated the levels of 13 known miRNAs and 6 LncRNAs in tumor samples from 9 patients with primary POG by using RT-PCR and analyzed their association with outcomes., Results: The expression levels of miR-21, miR-106a, miR-10b, and LncRNA NEAT1 were higher, and the expression level of miR-143 was lower in POG tissues compared with normal brain tissues (p = 0.006, p = 0.032, p = 0.034, p = 0.002, and p = 0.001, respectively). High levels of NEAT1 and low expression of miR-143 were associated with decreased probability of short disease-free survival (p = 0.018 and p = 0.022, respectively)., Discussion: NEAT1 and miR-143 levels could serve as reciprocal prognostic predictors of disease progression in patients with POG. New treatment models to regulate the expression levels of NEAT1 and miR-143 will bring a new approach to the therapy of POG., (© 2021 S. Karger AG, Basel.)

Aim: To investigate the anti-apoptotic and anti-oxidant effects of systemic uridine treatment in a rat model of sciatic nerve injury., Material and Methods: Thirty-two adult male rats were equally randomized to Sham, Control, U100, and U500 groups. Sham rats received a sham operation by exposing the right sciatic nerve without transection, while those in the Control, U100, and U500 groups underwent right sciatic nerve transection followed by immediate primary anostomosis. Sham and Control groups received saline (0.9% NaCl) injections intraperitoneally (i.p.), while U100 and U500 groups received 100 mg/kg and 500 mg/kg uridine injections (i.p.), respectively, once a day for 7 days after the surgery. Rats in all the groups were sacrificed on the eighth day; sciatic nerve samples were analyzed for apoptosis by Western Blotting and for oxidation parameters including myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) by Enzyme-Linked Immunosorbent Assay (ELISA)., Results: Uridine treatment at the dose of 500 mg/kg significantly decreased as apoptosis determined by Caspase-3/Actin ratio and exhibited significant anti-oxidant effects as determined by decreased levels of MPO and MDA as well as increased levels of SOD, GPx, and CAT compared to controls. Uridine at 100 mg/kg was only found to decrease the Caspase-3/Actin ratio, although it significantly decreased MDA and increased CAT levels compared to controls., Conclusion: Treatment with uridine reduces apoptosis and oxidation in a rat model of sciatic nerve injury dose-dependently. Thus, uridine may be beneficial in peripheral nerve regeneration by exhibiting anti-apoptotic and anti-oxidant effects.

Aim: To investigate the effects of different radiation doses on the development of the neural tube defect in chick embryos using computed tomography (CT), and assess its correlation with survivin and Bcl-2 expressions., Material and Methods: A total of 150 chicken eggs were used and grouped into five categories. In Group 1 (n=30), the embryos were not exposed to radiation. In Group 2 (n=30), the embryos were irradiated using lung cancer screening chest CT protocol. In Groups 3 and 4 (n=30 each), the abdominopelvic and adult routine head CT protocols, respectively, were used to irradiate the embryos. In Group 5 (n=30), the embryos were irradiated using adult brain perfusion CT protocol. Subsequently, the embryos were examined under a stereomicroscope to assess the presence of neural tube developmental abnormalities. Moreover, immunohistochemical staining was performed to determine the survivin and Bcl-2 expression levels., Results: The risk of developing neural tube defect increased with the amount of exposed radiation. Moreover, no significant correlation was observed between the survivin and Bcl-2 expression levels and the radiation dose., Conclusion: Overall, the results of this study indicate that the radiation from CT may cause neural tube defect in chicken embryos.

Primary glioblastoma (GB) is the most aggressive type of brain tumors. While mutations in isocitrate dehydrogenase (IDH) genes are frequent in secondary GBs and correlate with a better prognosis, most primary GBs are IDH wild-type. Recent studies have shown that the long noncoding RNA metastasis associated lung adenocarcinoma transcript-1 (MALAT1) is associated with aggressive tumor phenotypes in different cancers. Our aim was to clarify the prognostic significance of MALAT1 in IDH1/2 wild-type primary GB tumors. We analyzed IDH1/2 mutation status in 75 patients with primary GB by DNA sequencing. The expression of MALAT1 was detected in the 75 primary GB tissues and 5 normal brain tissues using reverse transcription quantitative PCR (RT-qPCR). The associations between MALAT1 expression, IDH1/2 mutation status, and clinicopathological variables of patients were determined. IDH1 (R132H) mutation was observed in 5/75 primary GBs. IDH2 (R172H) mutation was not detected in any of our cases. MALAT1 expression was significantly upregulated in primary GB vs. normal brain tissues (p = 0.025). Increased MALAT1 expression in IDH1/2 wild-type primary GBs correlated with patient age and tumor localization (p = 0.032 and p = 0.025, respectively). A multivariate analysis showed that high MALAT1 expression was an unfavorable prognostic factor for overall survival (p = 0.034) in IDH1/2 wild-type primary GBs. High MALAT1 expression may have a prognostic role in primary GBs independent of IDH mutations.

Object: In this report, we aimed to analyze the outcome results of our patients who underwent percutaneous trigeminal tractotomy (TR) and nucleotomy (NC) procedures, which are defined as destructive procedures targeting the descending trigeminal tractus and nucleus caudalis of the spinal trigeminal nucleus, respectively, for intractable craniofacial pain., Methods: The medical records of a total of 12 patients who underwent a total of 14 computed tomography (CT)-guided TR-NC procedures at our clinics between 2005 and 2017 were retrospectively reviewed., Results: A significant increase in patients' performance status (p = 0.015) as well as a significant decrease in the VAS score (p < 0.001) were achieved. Grade I pain relief (VAS = 0, no pain) was established in 66.7% of the patients, whereas grade II pain relief was observed in the remaining patients. Two of the patients suffered from recurrent pain after the initial procedure. Both patients underwent a second trigeminal TR-NC procedure, and grade I pain relief was re-established. The mean VAS score at 3-month follow-up was 1.4 ± 1.1, whereas this score at 6-month follow-up was 2 ± 1.3. The trigeminal TR-NC procedure resulted in a significant decrease in patients' VAS scores at 3- and 6-month follow-up visits compared with preoperative VAS scores (p < 0.001). Transient ataxia was noted in only one patient (8.3%) early after the procedure., Conclusions: The results presented in the current study support the efficacy of the percutaneous CT-guided trigeminal TR-NC procedure in the management of intractable facial pain in selected patients. The use of CT guidance allows direct visualization of the target area, thereby enhancing the safety and success of the procedure., (© 2020 S. Karger AG, Basel.)

Aim: To determine the efficacy and safety of microvascular decompression (MVD) for hemifacial spasm (HFS) by retrospectively reviewing our results., Material and Methods: A total of 55 patients who underwent MVD in our clinic between 2003 and 2017 were retrospectively analyzed. Clinical outcome results, recurrence rates, and surgical complications were noted., Results: Thirty-six patients were female (65%). The mean age of the patients was 51.3 years. The mean duration of the complaint was 46.4 months. In 45 patients (82%), HFS was completely resolved within the first 6 months after the surgery. Five patients (9%) with recurrent symptoms were reoperated within the first year of the surgery. HFS symptoms of five patients (9%) completely ceased initially, but started again and reoperation was required due to failure of alternative treatments. Delayed facial nerve palsy and hearing loss were noted in one patient for each (2%). Cerebrospinal fluid leak was observed in two patients (4%). No mortality was observed in this series., Conclusion: MVD is a safe and effective option for patients with HFS that is resistant to medical treatment.

Glioblastoma (GBM) is the most prevalent and deadliest subtype of glioma. Despite current innovations in existing therapeutic modalities, GBM remains incurable, and alternative therapies are required. Previously, we demonstrated that Olea europaea leaf extract (OLE) kills GBM cells by modulating miR-181b, miR-137, miR-153 and Let-7d expression. However, although oleuropein (OL) is the main compound in OLE, its role in the antitumour effect of OLE remains unknown. This study determined the effect of OL on GBM cell line T98G and compared the results with our previous findings regarding the effect of OLE on the same cell line. The antiproliferative activity of OL and its effect on temozolomide (TMZ) response were tested inT98G cells using WST-1 assay. OL inhibition was evaluated using one-way analysis of variance with Tukey's post hoc test. The effect of OL on miR-181b, miR-137, miR-153 and Let-7d expression was assessed using quantitative reverse transcription polymerase chain reaction. Fold differences in expression between untreated, OL or OL + TMZ-treated samples were calculated using 2 -ΔCt method. Significance was evaluated using an independent sample t -test. Treatment with 277.5 and 555 µM OL resulted in 39.51% and 75.40% reductions in T98G cells within 24 h. Coadministration of 325 µM TMZ and 277.5 or 555 µM, OL caused 2.08- and 2.83-fold increases, respectively, in the therapeutic effect of TMZ. OL + TMZ significantly increased microRNA expression, particularly Let-7d, than OLE. In conclusion, OL has an antitumour effect on GBM cells mainly via regulation of Let-7d expression. The present results also indicate other minor compounds in OLE play important anticancer roles.

Spinal paragangliomas are rarely-observed neuroendocrine benign tumors in the extra-adrenal paraganglionic system. Primary spinal involvement is even rarer. Radiologic differential diagnosis is not easy. This paper presents 2 lumbar paraganglioma cases and focuses on nuances to provide ideas for radiological differential diagnosis.

Unmethylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter leads to Temozolomide (TMZ) resistance in most of the glioblastoma multiforme (GBM) patients. We previously investigated the synergistic effect of Olea europaea leaf extract (OLE) on TMZ cytotoxicity through modulating microRNA expression. To date, knowledge about the effect of OLE on MGMT methylation is insufficient. The aim of the current study was to evaluate the potential modulating effect of OLE on the TMZ response of GBM tumors through MGMT methylation. Exposure to 1 mg/mL OLE caused a significant induction of CpG island methylation in the MGMT gene using Methyl quantitative PCR assay (P < 0.001). In WST-1 analysis, the use of 350 µM TMZ plus 1 mg/mL OLE significantly increased the TMZ response of MGMT unmethylated cells (P = 0.003). Using the comet assay, the impact of 1 mg/mL OLE plus 350 µM TMZ on the formation of DNA strand breaks was significantly higher than that of 450 µM TMZ alone (P < 0.001) and Western blot analysis revealed that, when cells are treated with 1-mg/mL OLE, the total p53 protein levels tended to decrease. The results presented in this study uniquely demonstrated that OLE synergistically increased the TMZ response of GBM tumors by regulating MGMT gene methylation and p53 expression. However, further studies to validate our findings are required.

Patients with glioblastoma multiforme (GBM) that are cancer stem-cell-positive (GSC [+]) essentially cannot benefit from anti-angiogenic or anti-invasive therapy. In the present study, the potential anti-angiogenic and anti-invasive effects of Olea europaea (olive) leaf extract (OLE) were tested using GSC (+) tumours. OLE (2mg/mL) caused a significant reduction in tumour weight, vascularisation, invasiveness and migration (p=0.0001, p<0.001, p=0.004; respectively) that was associated with reducing the expression of VEGFA, MMP-2 and MMP-9. This effect was synergistically increased in combination with bevacizumab. Therefore, our current findings may contribute to research on drugs that inhibit the invasiveness of GBM., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Aim: To evaluate the safety and effectiveness of computed tomography-guided high-level percutaneous selective cervical cordotomy (CT-guided HPSCC)., Material and Methods: CT-guided percutaneous procedures were performed in fifty-nine patients between the years 2004- 2013 for cancer pain. Forty-eight patients with cancer-related body pain were treated with CT-guided HPSCC was evaluated retrospectively., Results: CT-guided HPSCC was performed in 33 male and 15 female patients. The mean age was 49.93 years. The distance between skin-dura, anteroposterior diameter and mediolateral diameter was measured as 40 to 71.1 mm, 8 to 88 mm and 8 to 99 mm respectively. The mean postoperative Karnofsky Performance Score (KPS) was 95. Mean preoperative Visual Analog Scale (VAS) score was 9.6, and 3.6 on postoperative day 1. The 6 < sup > th < /sup > month follow-up VAS score was 6.8. Preoperative total sleeping hours in a 24-hour period were 5.5 hours, which increased in the immediate postoperative period to 8.5 hours. The most common pathology treated was bronchogenic carcinoma. Six of the procedures were bilateral and there were no permanent complication due to the procedure., Conclusion: CT-guided HPSCC is still very effective, cheap and repetitive procedure for cancer pain. The procedure should be performed by experienced surgeons and although there is a hegemony of opioids, the number of surgeons that perform the procedure must be increased.

Background: CDP-choline (cytidine-5'-diphosphocholine) improves functional recovery, promotes nerve regeneration, and decreases perineural scarring in rat peripheral nerve injury. The aim of the present study was to investigate the mechanism of action of CDP-choline with regard to matrix metalloproteinase (MMP) activity in the rat-transected sciatic nerve injury model., Materials and Methods: Male Wistar rats were randomized into Sham, Saline, and CDP-choline groups. Rats in Sham group received Sham surgery, whereas rats in Saline and CDP-choline groups underwent right sciatic nerve transection followed by immediate primary saturation and injected intraperitoneally with 0.9% NaCl (1 mL/kg) and CDP-choline (600 μg/kg), respectively. Sciatic nerve samples were obtained 1, 3, and 7 d after the surgery and analyzed for levels and activities of MMP-2 and MMP-9, levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) and TIMP-3, and axonal regeneration., Results: CDP-choline treatment decreased the levels and activities of MMP-2 and MMP-9, whereas increasing levels of TIMP-1 and TIMP-3 significantly on the third and seventh day after injury compared to Saline group. In addition, CDP-choline administration resulted in new axon formation and formation and advancement of myelination on newly formed islets (compartments) of axonal regrowth., Conclusions: Our data show, for the first time, that CDP-choline modulates MMP activity and promotes the expression of TIMPs to stimulate axonal regeneration. These data help to explain one mechanism by which CDP-choline provides neuroprotection in peripheral nerve injury., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: To demonstrate the effect of glatiramer acetate (GA) in chick embryos on neural tube (NT) development, and to explore its effects of Foxp1, apoptosis, and N-cadherin., Material and Methods: One hundred fertile, specific pathogen free eggs were divided into 5 groups for this study. The eggshell was windowed specifically at 24 hours of incubation. The embryos in Group 1 (n=20) were treated with 10 μl physiological saline; in Group 2 the embryos (n=20) were given 10 μl GA (equal to daily human therapeutic dose); 20 μl GA (equal to twice daily human therapeutic dose) was injected to embryos in Group 3 (n=20); in Group 4 and 5, 30 μl and 40 μl GA were administered to the embryos (n=20) (equal to x3 and x4 daily human therapeutic dose, respectively). Each egg was re-incubated for 24 hours more. Then, histological and immunohistochemical evaluation of the subjects were done., Results: The embryos with NT defect showed FOXP1 expression without N- cadherin or staining with N-cadherin in another location in our study. We interpreted this result as GA leading to an NT closure defect by increasing FOXP expression. Moreover, we also showed the reverse relation between FOXP1 and N-cadherin at the immunohistochemical level for the first time., Conclusion: GA affects the spinal cord development through FOXP in the chick embryo model at high doses.

Background and Objective: The hepatitis C virus (HCV) which infects 3% of the world's population is a global challenge. Recently, genome-wide association studies (GWAS) have identified that the IL28B gene rs8099917 polymorphism was associated with the response to the pegylated-interferon alpha/ribavirin (PegIFNα/RBV) combination therapy in patients infected with HCV genotype 1. IL28B gene rs8099917 polymorphism should be determined before beginning treatment of HCV-infected patients to predict an individual's response. The aims of this study were to analyze the correlation between IL28B gene rs8099917 (T/G) polymorphism and PegIFNα/RBV therapy outcome in the Turkish population., Methods: Genotypes of the IL28B gene rs8099917 (T/G) single nucleotide polymorphism (SNP) were determined in 308 patients with HCV infection by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. One group consisted of 148 patients with a sustained virological response (SVR), whereas the second group consisted of 160 nonresponders (non-SVR)., Results: Allele and genotype associations of IL28B gene rs8099917 polymorphism with a sustained virological response were observed in comparisons between the SVR and non-SVR groups (P<0.001). In addition, the characteristics of the subjects did not differ between these two groups except for age and fibrosis stage (P<0.05). Additionally, neither SVR nor rs80999917 genotypes were associated by HCV RNA levels., Conclusions: In conclusion, the rs8099917 polymorphism was thus found strongly associated with a sustained virological response to therapy in Turkish patients infected with HCV genotype 1. Consequently, we suggest determining IL28B gene rs8099917 polymorphism of patients with HCV genotype 1 before onset of treatment., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background: Surgery is regarded as a common treatment option for patients with mesial temporal lobe epilepsy due to hippocampal sclerosis but sometimes deciding this diagnosis can be very difficult. We aim to investigate the shape differences in the temporal lobe of mesial temporal sclerosis epilepsy patients compared with healthy controls, investigating the side difference and, if present, assessing the clinical application of this situation., Method: The MRI scans of mesial TLE patients and controls were retrospectively reviewed. Temporal lobe data were collected from the two-dimensional digital images. Standard anthropometric landmarks were selected and marked on each digital image using TPSDIG 2.04 software. Eight anatomic landmarks were marked on images. A generalized Procrustes analysis was used to evaluate the shape difference. The shape deformation of the temporal lobe from control to patient was evaluated using the TPS method., Results: There were statistically significant TL shape differences between groups. High level deformations for the left and right side from the control to patient group were seen in the TPS graphic. The highest deformation was determined at the inferior lateral temporal midpoint of the middle temporal gyri and superior temporal landmark points of both the right and left sides., Conclusion: Our study for the first time demonstrated temporal shape differences in TLE patients using a landmark-based geometrical morphometric method by taking into consideration the topographic distribution of TL.

Programmed cell death-1 (PD-1) plays a critical role in regulating T-cell function during hepatitis B virus (HBV) infection. This study investigated the relationship between the polymorphisms of PD-1 gene and the susceptibility to HBV infection. Single nucleotide polymorphisms (SNPs) in PD-1 gene at positions +7146 G>A (guanine to adenine substitution) and +7209 C>T (cytosine to thymine substitution) were analysed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 220 subjects with chronic hepatitis B infection and 165 spontaneous clearance of HBV subjects. However, no statistically significant differences were found in the genotype distributions of the PD-1 +7146 G>A and PD-1 +7209 C>T polymorphisms among chronic hepatitis B and spontaneous clearance subjects. According to stratified analyses, borderline significance was observed between PD-1 +7146 GA genotype and risk of HBV chronicity in the subgroup of male gender (OR = 1.88, 95% 0.95-3.71; P = 0.07). Our findings demonstrate for the first time that the PD-1 +7146 G>A and PD-1 +7209 C>T polymorphisms have not been any major role in genetic susceptibility to chronicity of HBV infection, at least in the population studied here. Independent studies are needed to validate our findings in a larger series, as well as in patients of different ethnic origins., (© 2015 John Wiley & Sons Ltd.)

Glioblastoma multiforme (GBM) is one of the deadliest human malignancies. A cure for GBM remains elusive, and the overall survival time is less than 1 year. Thus, the development of more efficient therapeutic approaches for the treatment of these patients is required. Induction of tumor cell death by certain phytochemicals derived from medicinal herbs and dietary plants has become a new frontier for cancer therapy research. Although the cancer suppressive effect of Ficus carica (fig) latex (FCL) has been determined in a few cancer types, the effect of this latex on GBM tumors has not been investigated. Therefore, in the current study, the anti-proliferative activity of FCL and the effect of the FCL-temozolomide (TMZ) combination were tested in the T98G, U-138 MG, and U-87 MG GBM cell lines using the WST-1 assay. The mechanism of cell death was analyzed using Annexin-V/FITC and TUNEL assays, and the effect of FCL on invasion was tested using the chick chorioallantoic membrane assay. To determine the effect of FCL on GBM progression, the expression levels of 40 GBM associated miRNAs were analyzed in T98G cells using RT-qPCR. According to the obtained data, FCL causes cell death in GBM cells with different responses to TMZ, and this effect is synergistically increased in combination with TMZ. In addition, the current study is the first to demonstrate the effect of FCL on modulation of let-7d expression, which may be an important underlying mechanism of the anti-invasive effect of this extract.

Creutzfeldt-Jakob disease is a very rare, progressive neurodegenerative disorder that is incurable and always fatal. It is one of the transmissible spongiform encephalopathies caused by prions. Multiple vacuoles in neuropil and neuronal loss in the gray matter gives the classical sponge-like appearance of brain and are responsible for the typical clinical symptoms. In this report, we present 4 cases referred to the neurology department of Uludağ University with neurological symptoms. Patients were evaluated with electroencephalogram and magnetic resonance imaging, and performed brain biopsies for further investigation. For definitive diagnosis of Creutzfeldt-Jakob disease, accumulation of prion protein in brain was detected immunohistochemically. Patients died within weeks in consequence of rapid progression of the disease. Although Creutzfeldt-Jakob disease is an infrequent disorder, when a patient presents with characteristic clinical symptoms such as rapidly progressive dementia with myoclonus, the diagnosis of Creutzfeldt-Jakob disease should be taken into consideration.

Background and Aim: Multiple risk factors lead to hepatocellular carcinoma (HCC) including viral infections, mutation and single nucleotide polymorphisms (SNPs). Interleukin 28B (IL28B) gene rs12979860 polymorphism has been shown to be associated with HCC in the different populations, but its association with HCC has not been investigated in the Turkish population. We investigated whether the rs12979860 polymorphism of IL28B gene affects the risk of HCC., Material and Method: We performed genotyping analysis using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a hospital-based case-control study of 187 confirmed HCC patients and 208 healthy subjects (cancer and viral infection negative) in the Turkish population., Results: The allele and genotype analysis showed no significant differences between the risk of HCC and IL28B gene rs12979860 polymorphism (OR = 1.10; 95% 0.59-2.08 P = 0.76 for genotype). However, in the HBV-related HCC subgroup, the TT genotype increased a 1.46-fold the risk of developing HCC, but not statistically significant (OR = 1.46; 95% 0.71-2.97 P = 0.30). Furthermore, no significant differences were found between clinical findings, and sex in comparison with the IL28B genotypes in HCC group (P > 0.05)., Conclusion: Our results suggest, for the first time, that no significant association were found between IL28B rs12979860 genotypes with the risk of developing HCC in Turkish patients. Further independent investigations are required to clarify the possible role of IL28B gene rs12979860 polymorphism on the risk of developing HCC in a larger series and also in patients of different ethnic origins.

Purpose: Arterial spin labeling perfusion imaging (ASL-PI) is a non-invasive perfusion imaging method that can be used for evaluation and quantification of cerebral blood flow (CBF). Aim of our study was to evaluating the efficiency of ASL in histopathological grade estimation of glial tumors and comparing findings with dynamic susceptibility contrast perfusion imaging (DSC-PI) method., Methods: This study involved 33 patients (20 high-grade and 13 low-grade gliomas). Multiphase multislice pulsed ASL MRI sequence and a first-passage gadopentetate dimeglumine T2*-weighted gradient-echo single-shot echo-planar sequence were acquired for all the patients. For each patient, perfusion relative signal intensity (rSI), CBF and relative CBF (rCBF) on ASL-PI and relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) values on DSC-PI were determined. The relative signal intensity of each tumor was determined as the maximal SI within the tumor divided by SI within symetric region in the contralateral hemisphere on ASL-PI. rCBV and rCBF were calculated by deconvolution of an arterial input function. Relative values of the lesions were obtained by dividing the values to the normal appearing symmetric region on the contralateral hemisphere. For statistical analysis, Mann-Whitney ranksum test was carried out. Receiver operating characteristic curve (ROC) analysis was performed to assess the relationship between the rCBF-ASL, rSI-ASL, rCBV and rCBF ratios and grade of gliomas. Their cut-off values permitting best discrimination was calculated. The correlation between rCBV, rCBF, rSI-ASL and rCBF-ASL and glioma grade was assessed using Spearman correlation analysis., Results: There was a statistically significant difference between low and high-grade tumors for all parameters. Correlation analyses revealed significant positive correlations between rCBV and rCBF-ASL (r=0.81, p<0.001). However correlation between rCBF and rCBF-ASL was weaker (r=0.64, p<0.001)., Conclusion: Arterial spin labeling is an employable imaging technique for evaluating tumor perfusion non-invasively and may be useful in differentiating high and low grade gliomas., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The stem-like cells of Glioblastoma multiforme (GBM) tumors (GSCs) are one of the important determinants of recurrence and drug resistance. The aims of the current study were to evaluate the anticancer effect of Olea europaea leaf extract (OLE) on GBM cell lines, the association between OLE and TMZ responses, and the effect of OLE and the OLE-TMZ combination in GSCs and to clarify the molecular mechanism of this effect on the expression of miRNAs related to cell death. The anti-proliferative activity of OLE and the effect of the OLE-TMZ combination were tested in the T98G, U-138MG and U-87MG GBM cell lines using WST-1 assay. The mechanism of cell death was analyzed with Annexin V/FITC and TUNEL assays. The effects of OLE on the expression levels of miR-181b, miR-153, miR-145 and miR-137 and potential mRNA targets were analyzed in GSCs using RT-qPCR. OLE exhibited anti-proliferative effects via apoptosis and necrosis in the GBM cell lines. In addition, OLE significantly induced the expression of miR-153, miR-145, and miR-137 and decreased the expression of the target genes of these miRNAs in GSCs (p < 0.05). OLE causes cell death in GBM cells with different TMZ responses, and this effect is synergistically increased when the cells are treated with a combination of OLE and TMZ. This is the first study to indicate that OLE may interfere with the pluripotency of GSCs by modulating miRNA expression. Further studies are required, but we suggest that OLE may have a potential for advanced therapeutic cancer drug studies in GBM.

Temozolomide (TMZ) is widely used to treat glioblastoma multiforme (GBM). Although the MGMT gene methylation status is postulated to correlate with TMZ response, some patients with a methylated MGMT gene still do not benefit from TMZ therapy. Cancer stem cells (CSCs) may be one of the causes of therapeutic resistance, but the molecular mechanism underlying this resistance is unclear. microRNA (miRNA) deregulation has been recognized as another chemoresistance modulating mechanism. Thus, we aimed to evaluate the miRNA expression patterns associated with chemoresistance that is dependent on the CSC status in GBM tumors to identify therapeutic biomarkers. CSCs were identified in 5 of 20 patients' tumor tissues using magnetic separation. CSC (+) tumors displayed a significant induction of CpG island methylation in the MGMT gene promoter (p = 0.009). Using real-time reverse transcription polymerase chain reaction (qRT-PCR), 9 miRNAs related to GBM (mir-181b, miR-153, miR-137, miR-145, miR-10a, miR-10b, let-7d, miR-9, and miR-455-3p), which are associated with cell cycle and invasion was analyzed in tumor samples. Low miR-181b and high miR-455-3p expression levels were detected (p = 0.053, p = 0.004; respectively) in CSC (+) tumors. Analysis revealed a significant correlation between miR-455-3p expression and Smad2 protein levels as analyzed by immunohistochemistry in CSC (+) tumors (p = 0.002). Thus, miR-455-3p may be involved in TMZ resistance in MGMT methylated CSC (+) GBM patients. Further studies and evaluations are required, but this miRNA may provide novel therapeutic molecular targets for GBM treatment and new directions for the development of anticancer drugs.

Purpose: While bupivacaine is the most frequently used local anesthetic for spinal anesthesia, use of levobupivacaine in clinical practice has advanced recently. The aim of our study was to compare the clinical and anesthetic effects of isobaric bupivacaine and isobaric levobupivacaine when administered intrathecally in patients undergoing lumbar disc surgery., Methods: ASA I-III, 60 patients were enrolled in this study. Only patients with unilateral single-level (L4-5) lumbar disc hernia were selected and operated in each group and all were operated by the same surgeon. Patients were randomized into two groups, as group B (n = 30): 15 mg 0.5% isobaric bupivacaine, or group L (n = 30): 15 mg 0.5% isobaric levobupivacaine received intrathecally. The level of sensory block dermatome, degree of motor block, intraoperative sensory and motor block characteristics, and postoperative recovery times of spinal anesthesia were evaluated. The satisfaction scores of the surgeon and patients, intraoperative hemodynamic changes, intraoperative and postoperative complications were recorded., Results: The maximum level of sensory blockade was significantly higher in the levobupivacaine group (group L 7 ± 1.63, group B 8.6 ± 1.76 thoracic dermatome, p < 0.05). There was no significant difference in the onset time of sensory (group L 6 ± 3 min, group B 9 ± 4 min) and motor (in group L 7 ± 3 min, in group B 10 ± 4 min) blockade (p > 0.05). There was no significant difference between the groups regarding duration of operation (group L 49 ± 7.3 min, group B 52 ± 8.1, p > 0.05). Recovery times of sensory (175 ± 57 min) and motor (216 ± 59 min) blockade were significantly shorter in the levobupivacaine group (p < 0.05). Mobilization was also earlier in the levobupivacaine group (339 ± 90 min, p < 0.05). Patients' satisfaction and intraoperative, postoperative complications were similar between the two groups., Conclusions: Our results showed that block recovery time was shorter in the levobupivacaine group, this may be a disadvantage for longer operative procedures. But with proper patient selection this can be eliminated. Recovery time was shorter in levobupivacaine group. Therefore, postoperative neurological examination can be done earlier. In addition, early mobilization can be an advantage for postoperative recovery.

Background and Aims: Because the outcome of glioblastoma multiforme (GBM) remains dismal, there is an urgent need for a better molecular characterization of this malignancy. The aim of this prospective study was to investigate the prognostic impact of the expression of c-mesenchymal-epithelial transition (c-Met) a receptor tyrosine kinase implicated in expression growth, survival, motility/migration, and invasion in GMB patients managed according to the established diagnostic and therapeutic protocols., Methods: Between May 2003 and March 2011, a total of 69 patients (33 males and 36 females; mean age: 52.2 ± 12.9 years, age range: 23-81 years) referred to our Department for the surgical removal of GBM were evaluated immunohistochemically for c-Met expression. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures., Results: Compared with c-Met- subjects (n = 38), c-Met+ subjects (n = 31) had both a significantly lower OS (15.3 ± 2.3 vs. 22.6 ± 2.5 months, respectively, p < 0.01) and PFS (12.3 ± 2.1 vs. 19.1 ± 2.6 months, respectively, p < 0.05). After allowance for potential confounders, multivariate Cox regression analysis identified c-Met+ as an independent predictor of both OS (hazard ratio = 1.7; 95 % confidence interval = 1.2-1.9, p < 0.01) and PFS (hazard ratio = 1.6; 95 % confidence interval = 1.1-2.3, p < 0.05)., Conclusions: Our findings suggest that c-Met immunohistochemical expression is an independent predictor of outcomes in patients with GBM treated by standard of care.

Aim: The aim of this study was to investigate the dose dependence of citicoline's previously-reported effects on recovery of peripheral nerve injury., Material and Methods: Right sciatic nerves of sixty adult female Wistar Albino rats were incised and primary anastomosis was performed. Rats were then divided into four groups: Control group received 2 ml of saline intraperitoneally, while rats in C-300, C-600 and C-900 groups received 300 μmol/kg, 600 μmol/kg and 900 μmol/kg citicoline dissolved in 2 ml saline, respectively. Rats were tested for sciatic functional index (SFI) on the 4th, 8th and 12th weeks and electrophysiological recordings were obtained on the 12th week. Rats were then sacrificed to investigate nerve adhesions and perform histomorphological examinations., Results: Our results showed that rats in C-600 and C-900 groups had significantly lesser neural adhesion and greater SFI and electrophysiological score than those in the Control and C-300 groups (p < 0.05). Mean density and total number of functionally myelinated axons were significantly increased in C-900 group, while perineural scar tissue formation was reduced in all citicoline-treated groups., Conclusion: We conclude that citicoline exhibits dose-dependent effects on axonal regeneration and recovery without scar formation in a rat model of peripheral nerve incision and primary anastomosis.

Intracranial chondroma is a rare benign neoplasm that occurs most often at the skull base. In extremely rare instances, it arises from the dura mater of the convexity or from the falx cerebri. The tumor cells are thought to originate from meningeal fibroblasts, perivascular mesenchymal tissue, or ectopic chondrocytes. Because the clinical presentation of such cases is nonspecific and because neuroimaging findings are not pathognomonic, intracranial chondromas mimic other intracranial tumors. Herein, we report a chondroma originating from the dura mater in the frontal region. The patient had been followed-up radiologically for 3 years after a preliminary diagnosis of meningioma until the correct diagnosis of chondroma was established with postoperative histological examination.

Aim: Patients usually suffer significant pain after lumbar laminectomy. Wound infiltration with local anesthetics is a useful method for postoperative pain control. Our aim was to compare the efficacies of preemptive wound infiltration with bupivacaine and levobupivacaine., Material and Methods: 60 patients were randomized three groups as follows: Group L wound infiltration with 20 mL 0.25% levobupivacaine and 40 mg methylprednisolone just before wound closure; Group B wound infiltration with 20 mL 0.25% bupivacaine and 40 mg methylprednisolone before closure; Group C had this region infiltrated with 20 ml physiological saline. Demographic data, vital signs, postoperative pain scores and morphine usage were recorded., Results: First analgesic requirement time was significantly shorter in the control group compared to other two groups (p < 0.001). Group B had the lowest cumulative morphine consumption at the end of 24 hours within 0-4, 4-12 and 12-24 hours time intervals and the values were not significant when compared with Group L, however the consumption of both groups was significantly lower compared to the control group (p < 0.001)., Conclusion: Our data suggest that preoperative infiltration of the wound site with bupivacaine or levobupivacaine provides similarly effective pain control with reduced opiate dose after unilateral lumbar laminectomy.

Background: Reactive oxygen species (ROS) can oxidize biological molecules that mediate carcinogenesis by causing metabolic malfunction and damage to DNA. Human serum paraoxonases (PON1, PON2 and PON3) play a role in antioxidant defense and protect the cell against ROS. PON1 polymorphisms Q192R and L55M have been shown to be associated with several human cancers, but their association with hepatocellular carcinoma (HCC) has yet to be investigated., Methods: We performed genotyping analysis using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a hospital-based case-control study of 217 confirmed HCC patients and 217 age-, gender-, smoking- and alcohol consumption-matched cancer-free controls in Turkish population., Results: Q192R and L55M polymorphisms were in significant linkage disequilibrium (LD) (D' = 0.77). However, allele, genotype and haplotype analysis showed no significant differences between the risks of HCC and PON1 polymorphisms. Moreover, no significant differences were found between clinical findings, clinicopathological features and sex in comparison with the PON1 genotypes in HCC group., Conclusion: Our results suggest for the first time that neither the Q192R polymorphism nor the L55M polymorphism has relationship with the risk of developing HCC. Further independent studies are required to clarify the possible role of PON1 gene Q192R and L55M polymorphisms on the risk of developing HCC in a larger series and also in patients of different ethnic origins.

Glioblastoma represents extreme anaplasia in astrocytic tumors. In spite of this aggressiveness, extracranial metastasis of glioblastoma is very rare and has been documented in only a few patients in the literature. In this article, a 30-year-old woman with secondary glioblastoma associated with extracranial distant metastasis was presented. In September 2008, an intracranial lesion in the left frontal region was diagnosed by magnetic resonance imaging (MRI) after admission to the hospital by headache and seizure and subsequently resected. The histology of the lesion revealed an anaplastic astrocytoma (grade III). Upon recurrence of the tumor 7 months later, the patient underwent a second craniotomy for recurrence tumor resection. The histological diagnosis was glioblastoma. After radiotherapy and chemotherapy, cranial computerized tomography (CT) and whole body scintigraphy revealed metastatic lesions in the right cervical lymph nodes and the left ischium. A neck dissection and parathyroidectomy on the right side was performed. The cytomorphological and histological features of the tumor supported the diagnosis of metastatic glioblastoma.

Aim: The programmed cell death-1 (PD-1) is a potent immunoregulatory molecule which is responsible for the negative regulation of T-cell activation and peripheral tolerance. Recently, overexpression of PD-1 has been reported to contribute to immune system evasion and poor survival of hepatocellular carcinoma (HCC). A common single nucleotide polymorphism in intron 4 of PD-1 gene called PD-1.3 has been reported to influence PD-1 expression, but its association with HCC has yet to be investigated. The aim of the present study was to investigate whether this polymorphism could be involved in the risk of HCC susceptibility., Methods: The genotype frequency of PD-1.3 polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 236 subjects with HCC and 236 cancer-free control subjects matched on age, gender, smoking and alcohol status., Results: No statistically significant differences were found in the genotype distributions of the PD-1.3 polymorphism among HCC and cancer-free control subjects (P=0.22)., Conclusion: Our results demonstrate for the first time that the PD-1.3 polymorphism has not been in any major role in genetic susceptibility to hepatocellular carcinogenesis, at least in the population studied here. Independent studies are needed to validate our findings in a larger series, as well as in patients of different ethnic origins., (Copyright © 2012 Elsevier B.V. All rights reserved.)