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Local mRNA translation in axons is critical for the spatiotemporal regulation of the axonal proteome. A wide variety of mRNAs are localized and translated in axons; however, how protein synthesis is regulated at specific subcellular sites in axons remains unclear. Here, we establish that the axonal endoplasmic reticulum (ER) supports axonal translation in developing rat hippocampal cultured neurons. Axonal ER tubule disruption impairs local translation and ribosome distribution. Using nanoscale resolution imaging, we find that ribosomes make frequent contacts with axonal ER tubules in a translation-dependent manner and are influenced by specific extrinsic cues. We identify P180/RRBP1 as an axonally distributed ribosome receptor that regulates local translation and binds to mRNAs enriched for axonal membrane proteins. Importantly, the impairment of axonal ER-ribosome interactions causes defects in axon morphology. Our results establish a role for the axonal ER in dynamically localizing mRNA translation, which is important for proper neuron development., Competing Interests: Declaration of interests C.C.H. is an employee of Genentech, a member of the Roche group., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aims to investigate the impact of a short implant placed behind the mental foramen with the all-on-four treatment concept using the three-dimensional (3D) finite element stress analysis (FEA). Six different finite element analysis models were designed according to tilted implant angle (17° and 30°), presence of short implants, and short implant diameter (4.1 mm and 4.8 mm). A 100 N force was applied vertically from the central fossa of the lower right second premolar tooth. Maximum equivalent (von Mises) and Minimum/Maximum principal (Pmin/Pmax) stress values and distributions were evaluated by 3D-FEA. The highest stress value among tilted implants was in the T17 group. T30 was the group that caused the most stress in the cortical bone. Adding the short implant to the all-on-four design reduced von Mises stress on multi-unit abutments, abutment screws, and tilted implants in both the 17° and 30° groups. At the same time, it reduced Pmin/Pmax stresses in cortical bone. Similar behavior was observed in terms of stress values and distributions for the 4.1 and 4.8 mm short implant groups. The results show that short implant placement in the posterior region in the all-on-four concept reduces stress on the bone, implants, and prosthetic parts, regardless of the diameter of the short implant. In cases where biomechanical risks such as parafunctional habits and poor bone quality increase, we recommend increasing the number of implants with short implants.

(1) Background: Although the incidence of glioblastoma (GB) has a peak in patients aged 75-84 years, no standard treatment regimen for elderly patients has been established so far. The goal of this study was to analyze the outcome of GB patients ≥ 65 years to detect predictors with relevant impacts on overall survival (OS) and progression-free survival (PFS). (2) Methods: Medical records referred to our institution from 2006 to 2020 were analyzed. Adult GB patients with clinical data, postoperative MRI data, and ≥1 follow-up investigation after surgical resection were included. The complete cohort was divided into a younger (<65) and an elderly group (≥65 years). Multiple factors regarding OS and PFS were scanned using univariate and multivariable regression with p < 0.05. (3) Results: 1004 patients were included with 322 (61.0%) male individuals in the younger and 267 (56.1%) males in the older cohort. The most common tumor localization was frontal in both groups. Gross total resection (GTR) was the most common surgical procedure in both groups, followed by subtotal resection (STR) (145; 27.5%) in the younger group, and biopsy (156; 32.8%) in the elderly group. Multivariate analyses detected that in the younger cohort, MGMT promoter methylation and GTR were predictors for a longer OS, while MGMT methylation, GTR, and hypofractionated radiation were significantly associated with a longer OS in the elderly group. (4) Conclusions: Elderly patients benefit from surgical resection of GB when they show MGMT promoter methylation, undergo GTR, and receive hypofractionated radiation. Furthermore, MGMT methylation seems to be associated with a longer PFS in elderly patients. Further investigations are required to confirm these findings, especially within prospective radiation therapy studies and molecular examinations.

Study Design: A stereological and histopathological study in an animal model., Objective: This study explores the effects of the nerve growth factor and photobiomodulation therapy on the damaged nerve tissue and fracture healing., Methods: A total of 24 rabbits were divided into 4 groups: control group (n = 5), nerve growth factor (NGF) group (n = 7), photobiomodulation (PBMT) group (n = 6), and nerve growth factor and photobiomodulation therapy (NGF+PBMT) group (n = 6). The vertical fracture was performed between the mental foramen and the first premolar, and the mental nerve was crushed for 30 seconds with a standard serrated clamp with a force of approximately 50 N in all groups. The control group received an isotonic solution (.02 mL, .09% NaCl) to the operation site locally. The NGF group received 1 μg human NGF-β/.9% .2 mL NaCl solution for 7 days locally. The PBMT group received PBMT treatment (GaAlAs laser, 810 nm, .3 W, 18 J/cm 2 ) every 48 hours for 14 sessions following the surgery. The NGF+PBMT group received both NGF and PBMT treatment as described above. After 28 days, the bone tissues and mental nerves from all groups were harvested and histologically and stereologically analyzed., Results: According to the stereological results, the volume of the new vessel and the volume of the new bone were significantly higher in the PBMT group than in other groups (P < .001). According to the histopathological examinations, higher myelinated axons were observed in experimental groups than in the control group., Conclusions: As a result, PBMT has beneficial effects on bone regeneration. Based on the light microscopic evaluation, more regenerated axon populations were observed in the NGF group than in the PBMT and PBMT + NGF groups in terms of myelinated axon content., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Preoperative traction with the Gardner-Wells tongs (PTGWT) is a valuable option for cervical spine injuries with malalignment. The aim of this study was to analyze the factors related to the treatment success of PTGWT., Methods: All consecutive cases with PTGWT due to cervical spine injury with malalignment treated between 01/2010 and 09/2020 were included. Patients' records were reviewed for demographic and clinical characteristics. Treatment success was evaluated upon the angle correction in the sagittal plane using the computed tomography scans before and after the treatment., Results: Of 20 patients in the final analysis (median age: 77.5 years; 12 females [60%]), 14 individuals were treated for the type-II odontoid fracture, and six cases presented with subluxation fractures between C3 and C7. After PTGWT and subsequent intraoperative reposition, there was an improvement of the median deviation angle from initial 32° to 5.5°. PTGWT resulted in a significant improvement of the median deviation angle for the odontoid (17°, P<0.0001), but not for the subluxation (4°, P=0.10) fractures. The time interval between trauma and PTGWT was associated with the treatment success of subluxation (P=0.051) but not of odontoid (P=0.87) fractures. Older individuals aged ≥51 years showed better reposition results with PTGWT (17° vs. 7.5°, P=0.02). There were no PTGWT-related complications in the cohort., Conclusions: PTGWT is an effective and safe treatment for cervical spine injuries with malalignment. The patients with odontoid fractures might particularly profit from the PTGWT. Treatment delay seems more relevant for PTGWT success in subluxation than in odontoid fractures.

Purpose: Spinal cavernous malformations (SCM) present a risk for intramedullary hemorrhage (IMH), which can cause severe neurologic deficits. Patient selection and time of surgery have not been clearly defined., Methods: This observational study included SCM patients who underwent surgery in our department between 2003 and 2021. Inclusion required baseline clinical factors, magnetic resonance imaging studies, and follow-up examination. Functional outcome was assessed using the Modified McCormick scale score., Results: Thirty-five patients met the inclusion criteria. The mean age was 44.7 ± 14.5 years, and 60% of the patients were male. In univariate analysis, the unfavorable outcome was significantly associated with multiple bleeding events (p = .031), ventral location of the SCM (p = .046), and incomplete resection (p = .028). The time between IMH and surgery correlated with postoperative outcomes (p = .004), and early surgery within 3 months from IMH was associated with favorable outcomes (p = .033). This association remained significant in multivariate logistic regression analysis (p = .041)., Conclusions: Removal of symptomatic SCM should be performed within 3 months after IMH when gross total resection is feasible. Patients with ventrally located lesions might be at increased risk for postoperative deficits., (© 2023. The Author(s).)

Purpose: To histologically and radiographically investigate the effect of plasma rich in growth factor (PRGF) mixed with bone grafts on ossification in the early period., Materials and Methods: A total of 12 New Zealand male rabbits (weighing between approximately 2.5 to 3 kg) were included in this study. Subjects were randomly divided into two sets of groups: control and experiment. Autograft, DFDBA (demineralized freeze-dried bone allograft), and DBBM (deproteinized bovine bone mineral) were applied to different defects in the control groups, and autograft + PRGF, DFDBA + PRGF, and DBBM + PRGF were applied in the experimental groups. All subjects were euthanized 28 days after surgery. The volumes of the bone, new connective tissue, and new capillaries were evaluated stereologically, and the bone density in the defects was investigated radiographically., Results: Regarding the stereologic evaluation, the volumes of the bone and capillaries were significantly higher in the experimental groups than in the control groups. In contrast, the connective tissue volume was considerably lower ( P < .001, in all groups). Similarly, radiographic examinations showed that the bone density measurements in the experimental groups were higher than in the control groups. However, these differences were statistically significant only between the DFDBA + PRGF and DFDBA groups ( P < .011)., Conclusions: The present study provides evidence that the addition of PRGF to autograft, DFDBA, and DBBM enhances osteogenesis in the early period compared to using these grafts alone. It also accelerates the remodeling of connective tissue to bone in defects. Int J Oral Maxillofac Implants 2023;38:569-575. doi: 10.11607/jomi.9858.

Background: Platelet derived growth factors (PDGF)-D and the expression of its receptor increase in neoplastic progression of cancer. Co-silencing of growth factor and receptor can be suggested as an important strategy for effective cancer therapy. In the present study, we hypothesized that suppression of PDGF-D signaling pathway with small interfering RNAs (siRNAs) targeting both PDGF-D and PDGF receptor (PDGFR)-β is a promising strategy for anticancer therapy., Methods: Chitosan nanoplexes containing dual and single siRNA were prepared at different weight ratios and controlled by gel retardation assay. Characterization, cellular uptake, gene silencing and invasion studies were performed. The effect of nanoplexes on breast tumor growth, PDGF expression and apoptosis was investigated., Results: We have shown that downregulation of PDGF-D and PDGFR-β with chitosan/siRNA nanoplex formulations reduced proliferation and invasion in breast cancer cells. In the in vivo breast tumor model, it was determined that the intratumoral administration of chitosan/siPDGF-D/siPDGFR-β nanoplexes markedly decreased the tumor volume and PDGF-D and PDGFR-β mRNA and protein expression levels and increased apoptosis., Conclusions: According to the results obtained, we evaluated the effect of PDGF-D and PDGFR-β on breast tumor development and showed that RNAi-mediated inhibition of this pathway formulated with chitosan nanoplexes can be considered as a new breast cancer therapy strategy., (© 2022 John Wiley & Sons Ltd.)

Objective: The aim of this study was to investigate the functional outcome in spinal cavernous malformation (SCM) patients with single or multiple intramedullary hemorrhagic events., Methods: SCM patients who were conservatively treated between 2003 and 2021 and had complete clinical baseline characteristics, an MRI data set, at least one SCM-related intramedullary hemorrhage (IMH), and at least one follow-up examination were included in this study. Functional status was assessed using the modified McCormick Scale score at diagnosis, before and after each bleeding event, and at the last follow-up., Results: A total of 45 patients were analyzed. Univariate analysis identified multiple bleeding events as the only statistically significant predictor for an unfavorable functional outcome at the last follow-up (OR 15.28, 95% CI 3.22-72.47; p < 0.001). Patients significantly deteriorated after the first hemorrhage (29.0%, p = 0.006) and even more so after the second hemorrhage (84.6%, p = 0.002). Multiple bleeding events were significantly associated with functional deterioration at the last follow-up (76.9%, p = 0.003). The time between the last IMH and the last follow-up did not influence this outcome., Conclusions: IMH due to SCM is linked to functional worsening. Such outcomes tend to improve after each hemorrhage, but the probability of full recovery declines with each bleeding event.

Background and Objectives: Spinal meningiomas, which are well characterized and are most frequently intradural extramedullary tumors, represent 25% of all intradural spinal tumors. The goal of this study was to compare the outcomes of surgically treated patients with spinal meningiomas in two time intervals with special emphasis on postoperative functional outcomes. Methods: Patients with spinal meningiomas admitted to our department between 1990 and 2020 were enrolled and divided into a historic cohort (HC; treated 1990−2007) and a current cohort (CC; treated 2008−2020). Patients’ clinical data and surgical and radiological reports were retrospectively analyzed up to 5 years. Preoperative and postoperative neurological function were assessed using the modified McCormick Scale (mMCS). The Charlson Comorbidity Index (CCI) was used to evaluate the effect of comorbidities on the preoperative status and postoperative outcome. Results: We included 300 patients. Participants in the CC (n = 144) were significantly younger compared to those in the HC (n = 156), with twice as many patients <50 years of age (p < 0.001). The most common tumor location was the thoracic spine (n = 204). The median follow-up was 38.1 months (±30.3 standard deviation). A symptom duration until surgery <12 months was significantly associated with an earlier improvement in the mMCS (p = 0.045). In the CC, this duration was shorter and patients’ neurological function at the first and last follow-ups was significantly better than for those in the HC (p < 0.001 for both). Conclusions: Our study results suggested that the impact of surgical management and postoperative rehabilitation on spinal meningioma patients’ long-term neurological outcome has reached important milestones over the last decades. An earlier diagnosis led to earlier surgical treatment and improved patients’ postoperative neurological recovery. Our results exposed that surgical therapy for spinal meningioma should be performed within 12 months after appearance of symptoms to achieve a better recovery.

Strawberries are known for their high perishability and short shelf life. The effects of incorporating hydrogen gas into sealed packaging on the quality and shelf life of strawberries were evaluated. Fruits were packaged under reducing atmosphere [RAP1 (5% CO 2 , 4% H 2 , 91% N 2 ) and RAP2 (10% CO 2 , 4% H 2 , 86% N 2 )], modified atmosphere [MAP1 (5% CO 2 , 95% N 2 ) and MAP2 (10% CO 2 , 90% N 2 )], and control, followed by 12 weeks storage at 4 °C. At the end of storage, RAPs exhibited higher total soluble solids (TSS), firmness, L* and a*, phenolic and anthocyanin contents, and antioxidant activity followed by MAPs when compared with control. RAP2 was more potent in protecting the freshness indices than RAP1, and MAP2 outperformed MAP1, with the best protection characteristic attributed to RAP2. RAP technique extended the shelf life by 3-5 times the control, and 1.5-3.0 times the MAP. RAP should be recommended as a green and healthy preservation technique for the long storage of fresh fruits., Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05427-y., Competing Interests: Conflicts of interest/Competing interestsThe authors declare that they have no competing interests., (© Association of Food Scientists & Technologists (India) 2022.)

Background: Rosette-forming glioneuronal tumor (RGNT) is an extremely rare entity described for the first time in the WHO classification of tumors of the central nervous system in 2007. Predominantly, single case reports of RGNT in the pineal region have been published, and specific therapy concepts are pending., Methods: The study group comprised all patients with the RGNT (CNS WHO grade 1) in the pineal region that underwent microsurgical tumor removal in our center (August 2018-June 2021). Surgical strategy, histological findings, and clinical outcome are presented, and the results are evaluated and compared to published case reports., Results: Four male patients aged under 50 years (range between 20 and 48 years) and one female patient, 51 years old, were included in this study. Chronic headaches and generalized epileptic seizures were the main symptoms. Supra-cerebellar infratentorial gross total tumor resection (GTR) was performed in two cases, two patients underwent subtotal tumor resection, and an endoscopic biopsy was performed in case five., Conclusion: In cases where surgical resection seems feasible with a reasonable surgical risk, we advocate GTR. Regular and long-term MRI follow-up is essential to detect a slow tumor progression. The role of additional chemotherapy or radiotherapy remains unclear.

Background and Objectives: Spinal schwannomas are benign tumours that can present with various symptoms such as pain, radiculopathy and neurological deficit. Gross total resection (GTR) is of key importance for local recurrence. The aim of this study is to describe the clinical characteristics, resection rate, clinical outcome, as well as tumour recurrence, in patients with non-syndromic spinal schwannomas and to clarify which factors affect the resection rate. Materials and Methods: Patients with non-syndromic spinal schwannomas that underwent surgical resection between January 2009 and December 2018 at a single institution were included. Demographic parameters, clinical symptoms, tumour localisation and size, surgical approach and complications were noted. Factors influencing the extent of resection, the surgeon's decision regarding the approach and the occurrence of new postoperative deficits were evaluated. Results: Fifty patients (18 females) were included. The most common presenting symptom was radiculopathy (88%). The lumbar spine was the most commonly affected site (58%). Laminotomy (72%) was the preferred surgical approach overall and specifically for exclusively intraspinal schwannomas ( p = 0.02). GTR was achieved in 76.0% ( n = 38). In multivariate analysis, only tumour localisation within the spinal canal ( p = 0.014) independently predicted GTR, whereas the type of approach ( p = 0.50) and tumour volume ( p = 0.072) did not. New postoperative persisting deficits could not be predicted by any factor, including the use and alteration of intraoperative neuromonitoring. Recurrence was observed in four cases (8%) and was significantly higher in cases with STR ( p = 0.04). Conclusions: In this retrospective study, GTR was solely predicted by tumour localisation within the spinal canal. The decision regarding the utilisation of different surgical approaches was solely influenced by the same factor. No factor could predict new persisting deficits. Tumour recurrence was higher in STR.

Purpose: Degenerative cervical myelopathy (DCM) is the most common non-traumatic cause of spinal cord dysfunction. Prediction of the neurological outcome after surgery is important. The aim of this study was to analyze the relationship between first symptoms of DCM and the neurological outcome after surgery., Methods: A retrospective analysis over a period of 10 years was performed. First symptoms such as cervicobrachial neuralgia, sensory and motor deficits and gait disturbances were evaluated regarding the postoperative neurological outcome. The modified Japanese Orthopedic Association Score (mJOA Score) was used to evaluate neurological outcome., Results: In total, 411 patients (263 males, 64%) with a median age of 62.6 ± 12.1 years were included. Cervicobrachial neuralgia was described in 40.2%, gait disturbance in 31.6%, sensory deficits in 19% and motor deficits in 9.2% as first symptom. Patients with cervicobrachial neuralgia were significantly younger (median age of 58 years, p = 0.0005) than patients with gait disturbances (median age of 68 years, p = 0.0005). Patients with gait disturbances and motor deficits as first symptom showed significantly lower mJOA Scores than other patients (p = 0.0005). Additionally, motor deficits and gait disturbance were negative predictors for postoperative outcome according to the mJOA Score., Conclusion: Motor deficits and gait disturbances as the first symptom of DCM are negative predictors for postoperative neurological outcome. Nevertheless, patients with motor deficits and gait disturbance significantly profit from the surgical treatment despite poor preoperative mJOA Score., (© 2021. The Author(s).)

Objective: Cavernous spinal cord malformations (SCMs) are believed to have a high rate of bleeding. The risk of intramedullary hemorrhage (IMH) or recurrent IMH and the neurological impact of bleeding events are important for clinical decision-making and could impact current treatment strategies., Methods: The authors screened their institutional database for patients with cavernous SCM treated between 2003 and 2020. Patients with complete MRI data sets and clinical baseline characteristics were included. Surgically treated patients were censored after cavernous SCM removal. Neurological functional status was obtained using the modified McCormick (MMcC) scale at diagnosis, first IMH, and second IMH. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for hemorrhage or rehemorrhage., Results: Seventy-one patients with cavernous SCM were analyzed. Cox regression analysis identified previous IMH (hazard ratio 7.86, 95% confidence interval 1.01-61.47, p = 0.049) as an independent predictor for rehemorrhage during the 5-year follow-up. The cumulative 5-year risk of bleeding or rebleeding was 41.3% for cavernous SCM. The MMcC score significantly deteriorated in 75% of patients after recurrent hemorrhage (p = 0.012)., Conclusions: During untreated 5-year follow-up, a considerably increased risk for hemorrhage or rehemorrhage was found in cavernous malformations of the spinal cord compared to cerebral cavernous malformations. Neurological function significantly deteriorates after the second bleeding. The probability of recurrent IMH increased significantly after initial presentation with hemorrhage.

This study aimed to compare the effectiveness of different graft materials using induced membrane technique for reconstruction of mandibular segmental bone defects. New Zealand rabbits were used as the experimental animal. As first-stage surgical procedure, segmental bone defects were created at the lower border of the mandibula in all groups. Polymethylmethacrylate (PMMA) cement was inserted into the defects. After 6 weeks, PMMA cement was removed in all groups. In the Control group, defect areas were left empty. Defects were filled with autogenous graft in the Autograft group, xenograft in the Xenograft group, and a mixture of autogenous graft and xenograft in the Autograft + Xenograft group. Histopathological, stereological, and immunohistochemical analyses were performed. A total of 40 New Zealand rabbits were used. Rabbits were randomly divided into four subgroups as Control, Autograft, Xenograft and Autograft + Xenograft groups (n = 10). When the groups were compared in terms of newly formed bone tissue volumes, significant difference was found between the Control group and Autograft group, Xenograft group and Autograft + Xenograft group (p < 0.001, p < 0.001, p = 0.003). The results of immunohistochemical examination were consistent with this finding. Stereological and immunohistochemical results can be used as a justification to adopt the induced membrane technique on an experimental basis in humans when it comes to the reconstruction of small segmental mandibular defects., Competing Interests: Declaration of competing interest The authors declared that they have no conflict of interest in regard to this work., (Copyright © 2021 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: Spinal cord ependymomas account for 3-6% of all central nervous system tumors and around 60% of all intramedullary tumors. The aim of this study was to analyze the neurological outcome after surgery and to determine prognostic factors for functional outcome., Patients and Methods: Patients treated surgically due to a spinal cord ependymoma between 1990 and 2018 were retrospectively included. Demographics, neurological symptoms, radiological parameters, histopathology, and neurological outcome (using McCormick Score [MCS]) were analyzed. Possible prognostic factors for neurological outcome were evaluated., Results: In total, 148 patients were included (76 males, 51.4%). The mean age was 46.7 ± 15.3 years. The median follow-up period was 6.8 ± 5.4 years. The prevalence was mostly in the lumbar spine (45.9%), followed by the thoracic spine (28.4%) and cervical spine (25.7%). Gross-total resection was achieved in 129 patients (87.2%). The recurrence rate was 8.1% and depended on the extent of tumor resection ( p  = 0.001). Postoperative temporary neurological deterioration was observed in 63.2% of patients with ependymomas of the cervical spine, 50.0% of patients with ependymomas of the thoracic spine, and 7.4% of patients with ependymomas of the lumbosacral region. MCS 1-2 was detected in nearly two-thirds of patients with cervical and thoracic spinal cord ependymoma 36 months after surgery. Neurological recovery was superior in thoracic spine ependymomas compared with cervical spine ependymomas. Poor preoperative functional condition (MCS >2), cervical and thoracic spine location, and tumor extension >2 vertebrae were independent predictors of poor neurological outcome., Conclusion: Neurological deterioration was seen in the majority of cervical and thoracic spine ependymomas. Postoperative improvement was less in thoracic cervical spine ependymomas compared with thoracic spine ependymomas. Poor preoperative status and especially tumor extension >2 vertebrae are predictors of poor neurological outcome (MCS >2)., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2021.)

Objective: Microsurgical resection of spinal ependymomas is associated with a considerable risk of postoperative neurological deterioration. We aimed to develop a risk score for outcome prediction after surgery for spinal ependymoma., Materials and Methods: All patients who underwent microsurgical resection of spinal ependymoma between 1980 and 2015 were included. Different perioperative parameters were collected for the score construction. Poor outcome was defined as the modified McCormick Scale (MMCS) >2 at 6 months after surgery., Results: Of 131 patients (mean age: 45.6 ± 16.7 years; 63 females), 38 cases (29%) showed poor outcome. Based on the univariate analysis, preoperative MMCS, subtotal tumor resection, proximal tumor level on the spinal cord, tumor extension, intramedullary location, and WHO grading were included in the multivariate analysis. The final risk score consisted of the following independent predictors: preoperative MMCS > 1 (1 point), proximal tumor level at Th 10 and higher (1 point), and tumor extension ≥ 3 vertebrae (1 point). The constructed score (0-3 points; Score for OUtcome after Resection of Spinal Ependymoma [SOURSE]) showed high diagnostic accuracy (area under the curve [AUC] = 0.883), which was superior to preoperative MMCS (AUC = 0.798) and Karnofsky Performance Status (AUC = 0.794). Patients scoring 0, 1, 2, and 3 points showed poor outcome in 0%, 12.9%, 54.6%, and 76.2% of the cases respectively., Conclusion: The presented SOURSE score based on preoperative neurologic condition, tumor location, and tumor extension could accurately predict the postoperative outcome in patients undergoing microsurgery of spinal ependymoma. Our data should be validated in a prospective trial., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Hormone and human epidermal growth factor receptor 2 (HER2/neu) receptor status is prognostic and predictive in breast cancer (BC) and guides the choice of therapy. However, owing to receptor conversion, the receptor status can differ in metastases compared with that of the primary tumor. The aim of the present study was to analyze the prognostic value of receptor status, receptor conversion, and clinical parameters in patients with resected BC brain metastases (BMs)., Methods: Patients with BCBMs treated at our institution from July 2007 to December 2019 were eligible for the present study. The receptor status of the BC and corresponding BMs and the occurrence of receptor conversion were separately recorded for 3 common receptors: HER2/neu, estrogen receptor, and progesterone receptor. The association between the receptor status or receptor conversion and clinical parameters was adjusted for outcome-relevant patient and tumor characteristics., Results: The final analysis included 78 patients. HER2/neu receptor status in BMs was associated with overall survival (P = 0.033). Receptor conversion was identified in 39 patients (50.0%): HER2/neu, n = 9 (11.5%); estrogen receptor, n = 22 (28.2%); and progesterone receptor, n = 25 (32.1%). In the final multivariate Cox regression analysis, HER2/neu receptor conversion (adjusted hazard ratio [aHR], 3.58; P = 0.006), Karnofsky performance status score <70% (aHR, 3.11; P = 0.048), infratentorial BM location (aHR, 2.49; P = 0.007), and age ≥55 years at BM diagnosis (aHR, 2.20; P = 0.046) were independently associated with poorer survival., Conclusions: Of the 3 common BC receptors, only HER2/neu receptor conversion was strongly associated with the prognosis of patients with surgically treated BCBMs. The clinical relevance of the reevaluation of receptor status in BMs favors surgical treatment of patients with noneloquent BCBMs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Neuronal function relies on careful coordination of organelle organization and transport. Kinesin-1 mediates transport of the endoplasmic reticulum (ER) and lysosomes into the axon and it is increasingly recognized that contacts between the ER and lysosomes influence organelle organization. However, it is unclear how organelle organization, inter-organelle communication and transport are linked and how this contributes to local organelle availability in neurons. Here, we show that somatic ER tubules are required for proper lysosome transport into the axon. Somatic ER tubule disruption causes accumulation of enlarged and less motile lysosomes at the soma. ER tubules regulate lysosome size and axonal translocation by promoting lysosome homo-fission. ER tubule - lysosome contacts often occur at a somatic pre-axonal region, where the kinesin-1-binding ER-protein P180 binds microtubules to promote kinesin-1-powered lysosome fission and subsequent axonal translocation. We propose that ER tubule - lysosome contacts at a pre-axonal region finely orchestrate axonal lysosome availability for proper neuronal function., (© 2021. The Author(s).)

Abstract: The aim of this study is to analyze the effects of autogenous dentin graft and mixture of autogenous dentin graft and platelet-rich fibrin (PRF) applied to the tooth extraction sockets on bone healing process. A total of 57 extraction sockets in 9 patients who were planned to be treated with dental implant after tooth extraction were evaluated in this study. Extraction sockets were divided randomly into 3 groups for each patient. In the first group, sockets were filled with autogenous dentin graft (Group D). In the second group, sockets were filled with the mixture of PRF and autogenous dentin graft (Group DP). In the third group, sockets were left empty as the control group (Group C). After 3 months, histological and immunohistochemical evaluations were performed on the samples taken during the implant surgery. Additionally, samples obtained from each group were examined by scanning electron microscopy. According to the histopathological findings, when the groups were compared in terms of new bone formation there was a significant difference between Group DP, both Group C, and Group D (P = 0.00), (P = 0.001). These findings supported by immunohistochemical results that showing increased bone morphogenetic protein-2 and Runt-related transcription factor-2 expression in Group DP. It has been concluded that undemineralized autogenous dentin graft has bone formation capacity on early period of bone healing. It can be used as bone graft material in augmentation procedures and its combined use with PRF accelerates new bone formation., Competing Interests: The author reports no conflicts of interest., (Copyright © 2020 by Mutaz B. Habal, MD.)

Cholestasis is associated with the accumulation of bile acids and bilirubin in the hepatocytes and leads to liver injury. Pregnane X Receptor (PXR) coordinates protective hepatic responses to toxic stimuli, and this receptor was reported to stimulate bile secretion by increasing MRP2 expression. Since PXR activators were reported to be anti-inflammatory in the liver, PXR was proposed as a drug target for the treatment of chronic inflammatory liver diseases. We investigated the potential protective effect of spironolactone (SPL), an enzyme inducer, in hepatotoxicity induced by bile duct ligation in rats. Wistar Albino (250-300 g) rats were divided into the control group and the bile duct ligated (BDL) group. BDL group was divided into three subgroups; following BDL, for 3 days, the first group received propylene glycol (vehicle of SPL) (blinded), the second subgroup received spironolactone (SPL) (200 mg/kg oral), and the third subgroup received SPL for 3 days, starting 3 days after the bile duct ligation, in order to investigate if it has a healing effect after hepatitis had developed. The control group was sham-operated and received saline. At the end of the experiment, blood and tissue samples were collected. Serum TNF-α, NF-ĸB, bilirubin, IL-6 levels, ALT, AST, ALP activities and tissue MPO activity and oxidant damage increased after the bile duct ligation was significantly decreased following SPL administration. PXR and MRP2 activity showed an increase in the hepatocytes as a result of the treatment. In conclusion, it was observed that SPL administration significantly decreases liver inflammation and damage related to BDL.

Study Design: Retrospective study (data analysis)., Objective: The purpose of this study was to assess the role of different factors on postoperative outcome of patients with degenerative cervical myelopathy (DCM)., Summary of Background Data: Ongoing degenerative changes of DCM lead to progressive neurological deficits. The optimal timing of surgical treatment is still unclear, especially in patients with mild DCM., Methods: Patients with DCM treated in our clinic between 2007 and 2016 were retrospectively analyzed. Pre- and postoperative neurological function was assessed by the modified Japanese Orthopaedic Association Score (mJOA Score) at different stages. The minimum clinically important difference (MCID) was used to evaluate the improvement after surgery. The comorbidities were recorded using the Charlson Comorbidity Index (CCI). Possible associations between age, sex, CCI, preoperative symptoms duration, high signal intensity (SI) on T2-weighted magnetic resonance imaging (MRI) with mJOA Score and MCID were analyzed using univariate analysis and multivariate regression models. Additionally, subgroup analysis was performed according to the severity of DCM (mild: mJOA Score ≥15 points; moderate: mJOA Score of 12-14 points; and severe: mJOA Score <12 points)., Results: The mean age of the final cohort (n = 411) was 62.6 years (range: 31-96 years), 36.0% were females. High SI on T2-weighted MRI was detected in 60.3% of the cases. In the multivariate analysis, patients' age (P = 0.005), higher CCI (P = 0.001), and presence of high SI on T2-weighted MRI (P = 0.0005) were associated independently with lower pre- and postoperative mJOA Score and postoperative MCID. Subgroup analysis revealed age and high SI on T2-weighted MRI as predictors of pre- and postoperative mJOA. However, symptom duration did not influence neurological outcome according to the severity of DCM., Conclusion: Surgery for DCM leads to significant functional improvement. However, better outcome was observed in younger individuals with lower CCI and absence of radiographic myelopathy signs. Therefore, DCM surgery, particularly before occurrence of high SI on MRI, seems to be essential for postoperative functional improvement regardless the above-mentioned confounders.Level of Evidence: 3., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Intuitive eating and mindful eating are new approach eating behaviors. Assessing the relationship of some anthropometric measurements to intuitive eating and mindful eating., Methods: Cross-sectional descriptive study. Adults aged 19-45 living in the center of Ankara the capital of Turkey. 250 volunteers (68 men and 182 women) aged 19-45 years. Data were collected through face-to-face interviews using a questionnaire contained the Intuitive Eating Scale (IES-2), Mindful Eating Questionnaire (MEQ-30) and Eating Attitudes Test (EAT-26). Anthropometric measurements were performed by the researchers themselves. Between-group analyses were performed to test statistical differences and relationships., Results: There was a positive correlation between IES-2 and MEQ-30 scores (r = 0.477; p = 0.000), indicating that the higher the IES-2 scores, the higher the MEQ-30 scores. IES-2 scores and BMI were negatively correlated (p < 0.05) and also MEQ-30 scores were negatively correlated with waist-to-height ratio and BMI (r = - 0.143; p = 0.024, r = - 0.159; p = 0.012). The higher the "disinhibition" and "control of eating," the lower the body weight, waist circumference, waist-to-height ratio and BMI was found., Conclusions: It was concluded that the more the intuitive eating, the more the mindful eating. And also it is suggested that anthropometric measurements might be an indicator of intuitive eating and mindful eating., Level of Evidence: Level V, cross-sectional descriptive study.

Membrane-bound and membraneless organelles/biomolecular condensates ensure compartmentalization into functionally distinct units enabling proper organization of cellular processes. Membrane-bound organelles form dynamic contacts with each other to enable the exchange of molecules and to regulate organelle division and positioning in coordination with the cytoskeleton. Crosstalk between the cytoskeleton and dynamic membrane-bound organelles has more recently also been found to regulate cytoskeletal organization. Interestingly, recent work has revealed that, in addition, the cytoskeleton and membrane-bound organelles interact with cytoplasmic biomolecular condensates. The extent and relevance of these complex interactions are just beginning to emerge but may be important for cytoskeletal organization and organelle transport and remodeling. In this review, we highlight these emerging functions and emphasize the complex interplay of the cytoskeleton with these organelles. The crosstalk between membrane-bound organelles, biomolecular condensates and the cytoskeleton in highly polarized cells such as neurons could play essential roles in neuronal development, function and maintenance., 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., (Copyright © 2020 Koppers, Özkan and Farías.)

Objectives: Bisphosphonate-related osteonecrosis of the jaw is potential side effect of long-term bisphosphonate therapy. Different treatment modalities have been used in this and investigate the effects of low-level laser therapy (LLLT) and extracorporeal shockwave therapy (ESWT) on socket healing after tooth extraction in rats given long-term bisphosphonates., Methods: Forty male Wistar-Albino rats were used in this experimental study. About 0.1 mg/kg zoledronic acid was administered intraperitoneally to all animals 3 times per week for 8 weeks. Four groups were made which were control, LLLT, ESWT, and ESWT+LLLT. Upper right first molar teeth extraction was performed in all groups; no treatment was given to the control group after molar tooth extraction. About 810 nm wavelength GaAlAs laser was used in LLLT group. In ESWT group, 1000 pulses, 0.21 mJ/mm ESWT was applied, and the 2 treatment methods were applied to the last ESWT+LLLT group at the same time. All the 4 groups were divided into 2 subgroups according to sacrification time 4 and 8 weeks. Steorologic, histologic, and immunohistochemical examinations were performed., Results: The highest new bone volume was observed in the early LLLT+ESWT. New vessel volume and CD31 expression were found to be high in the LLLT group. matrixmetalloproteinaze (MMP)-2 expression was found increased by the application of LLLT and ESWT., Conclusion: The LLLT and ESWT have similar effect on socket healing in the early period and that co-use is more effective upon healing. The LLLT has been shown to increase CD31 expression and increase vascularization and soft-tissue healing.

Background: Visual impairment (VI) due to neoplastic infiltration of the optic canal (OC) is frequently seen in skull base meningiomas representing a significant restriction in patients` quality of life. However, the delicate anatomy of this region often prevents gross total tumor resection. The aim of the present study was to evaluate the impact of intradural OC decompression and postoperative oncological procedure on preservation of visual acuity in subtotal resected skull base meningiomas., Methods: A retrospective analysis of 31 consecutive patients (19 females, 12 males; mean age 53 [range 18-78]), treated in our institution between 01/2011- 09/2014 was performed. Patients` charts were analyzed with special respect to operative procedure, postoperative treatment and procedural impact on late visual function., Results: Most patients (74.2%) had VI prior to surgery. A pterional craniotomy (97%) facilitated subtotal tumor removal in 71% of the patients with no intraoperative and a low rate (6.4%) of postoperative complications. Adjunctive radiotherapy was performed in 19.3% of the patients. Preoperative visual acuity was preserved or improved in 92% of the patients. Substantial tumor regrowth occurred in only 11.2% of the patients., Conclusions: Intradural decompression of the OC stabilizes visual function in subtotally resected skull base meningiomas. Moreover, adjuvant radiotherapy seems to further benefit visual outcome which has to be evaluated in further prospective studies.

Background: There is evidence on deficits in facial emotion recognition (FER) in patients with bipolar disorder (BD), and these deficits may be present in individuals with genetic risk for BD. This study investigated facial emotion identification and discrimination abilities in patients with BD, their parents, and healthy controls., Materials and Methods: This study included 38 patients with bipolar I disorder and 30 healthy controls for patients as well as 30 healthy mothers and 30 healthy fathers of these patients and 30 healthy controls who matched the mothers and fathers for age, gender, and education (total 188 participants). Facial Emotion Identification and Discrimination Tests were applied to all participants; the Hamilton Depression Rating Scale and Young Mania Rating Scale were applied to patients and their control group., Results: Facial Emotion Identification and Discrimination Test scores of patients and their parents were reasonably lower than their matching control groups. Moreover, we found that difficulty in FER affected more emotions in mothers than in fathers and mothers performed significantly worse than patients in the identification of angry and embarrassed faces., Conclusion: These findings indicate that parents of patients with BD have impairment with recognizing facial emotions and suggest that there may be an association between FER of patients with BD and that of their mothers., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Ruptured middle cerebral artery (MCA) aneurysms are one of the causes of subarachnoid (SAH) or intracerebral hemorrhage (ICH) but the factors associated with the bleeding type are unknown. The aim of the study was to analyze the association of the morphological variations of the Sylvian fissure (SF) and vascular parameters on occurrence of different bleeding patterns in patients with ruptured MCA aneurysms., Patients and Methods: The data of consecutive 202 patients with ruptured MCA aneurysm of two centers were included for analysis. Patients were divided into three groups: Group 1 with SAH, Group 2 with accompanying ICH and Group 3 with intrasylvian hemorrhage (ISH). The SF was divided into five types according to the previously described classification. Analyzed vascular parameters were aneurysm size, localization, presence of a daughter aneurysm, shape, and angulation of the aneurysm sac., Results: A total of 202 patients (141 female, 61 male, mean age 52.4 yr) were included in this study. 67 patients (33.2%) had a SAH, 122 (60.4%) an ICH and 13 (6.4%) presented with ISH. Statistical analysis showed a significant association of narrow and twisted SF types 4 and 5 (p < 0.001) and temporal angulation of the aneurysm (p = 0.030) for occurrence of ICH. All other vascular parameters showed no significant association for any kind of hemorrhage., Conclusion: Our results allow the conclusion that the complex SF types 4 and 5, as well as the temporal angulation of the aneurysm sac are associated with the occurrence of ICH in ruptured MCA aneurysms., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2019. Published by Elsevier B.V.)

Background: Degenerative cervical myelopathy (DCM) is the most common reason for spinal cord disease in elderly patients. This study analyzes the preoperative status and postoperative outcome of higher-aged patients in comparison to young and elderly patients in order to determine the benefit to those patients from DCM surgery., Methods: A retrospective analysis of the clinical data, radiological findings, and operative reports of 411 patients treated surgically between 2007 and 2016 suffering from DCM was performed. The preoperative and postoperative neurological functions were evaluated using the modified Japanese Orthopedic Association Score (mJOA Score), the postoperative mJOA Score improvement, the neurological recovery rate (NRR) of the mJOA Score, and the minimum clinically important difference (MCID). The Charlson Comorbidity Index (CCI) was used to evaluate the impact of comorbidities on the preoperative and postoperative mJOA Score. The comparisons were performed between the following age groups: G1: ≤50 years, G2: 51-70 years, and G3: >70 years., Results: The preoperative and postoperative mJOA Score was significantly lower in G3 than in G2 and G1 ( p < 0.0001). However, the mean mJOA Score's improvement did not differ significantly ( p = 0.81) between those groups six months after surgery (G1: 1.99 ± 1.04, G2: 2.01 ± 1.04, G: 2.00 ± 0.91). Furthermore, the MCID showed a significant improvement in every age-group. The CCI was evaluated for each age-group, showing a statistically significant group effect ( p < 0.0001). Analysis of variance revealed a significant group effect on the delay (weeks) between symptom onset and surgery ( p = 0.003). The duration of the stay at the hospital did differ significantly between the age groups ( p < 0.0001)., Conclusion: Preoperative and postoperative mJOA Scores, but not the extent of postoperative improvement, are affected by the patients' age. Therefore, patients should be considered for DCM surgery regardless of their age.

Objectives: In the present study, it was aimed to study the antioxidant effects of spironolactone (SPL) to determine its possible protective effects in hepatic ischemia reperfusion injury., Material and Methods: Hepatic artery, portal vein, and bile duct of Wistar albino rats were clamped for 45 minutes under anesthesia to form an ischemia period. Then reperfusion was allowed and the rats were decapitated 60 minutes later. SPL (20 mg/kg, p.o.) or SF was orally administered for 30 minutes before ischemia. Rats in the control arm underwent sham surgery and were administered isotonic saline. Liver function was studied by measuring aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-alpha (TNF-α), and interleukin 1beta (IL-1β) levels. Malondialdehyde (MDA), glutathione (GSH), luminol, and lucigenin levels, myeloperoxidase (MPO) and Na+-K+-ATPase enzyme activities were analyzed to study tissue injury under light microscope., Results: While IR increased AST, ALT, TNF-α, and IL-1β levels and MDA, luminol, and lusigenin levels and MPO activities, it caused a decrease in GSH levels and Na+K+-ATPase activity. Spironolactone administration significantly improved these values., Conclusion: Protective effects of SPL against ischemia/reperfusion injury via various mechanisms suggest that this agent may become a novel treatment agent in clinical practice., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (Copyright © 2019, Turkish Surgical Society.)

Objectives: Since publication of the ISAT study, the majority of neurovascular centers adhere to "coil first" policy for patients with subarachnoid hemorrhage (SAH). However, final allocation in favor of coiling or clipping is based on anatomic features of ruptured intracranial aneurysms with respect to clinical characteristics of SAH. In this study, we analyzed the parameters relevant for treatment allocation of ruptured anterior communicating artery aneurysms (AComAA)., Patients and Methods: From our institutional SAH database, all cases with ruptured AComAA, which underwent diagnostic subtraction angiography (DSA) with subsequent treatment allocation, were included. The radiographic features of AComAA were collected from pre-treatment DSA. In addition, demographic, clinical and radiographic parameters of SAH were recorded. The variables selected through univariate analyses were subsequently evaluated using multivariate regression analysis., Results: Of 300 SAH patients in the final analysis, the majority of the cases underwent endovascular coiling (n = 221, 73.7%). The following aneurysm features were associated with treatment modality in the univariate analysis: maximal sack size (p = 0.034), perpendicular height (p = 0.007), aspect ratio (p < 0.001) and sack/neck-ratio (p = 0.001). Accordingly, the following cutoffs for these variables were defined upon the receiver operating characteristics curves: 5 mm for sack size, 6 mm for perpendicular height, 1.6 for aspect ratio and sack/neck-ratio. In the multivariate analysis, aspect ratio of 1.6 was the only independent predictor of treatment allocation (p = 0.005; aOR = 2.57; 95% CI 1.33-4.96), which remained significant (p = 0.003; aOR = 2.77; 95% CI 1.41-5.45) after adjusting for patients' age, WFNS & Fisher grades, as well as intracerebral hematoma volume., Conclusion: Although not-routinely assessed during initial allocation treatment, our retrospective analysis proved that aspect ratio is a reliable predictor of treatment allocation of ruptured AComAA. Except for large space-occupying ICH commonly obligating the microsurgical treatment, other clinical and radiographic characteristics of SAH do not seem to be of clinical relevance for the selection of treatment modality., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Tuberous sclerosis complex (TSC) is a rare multisystem genetic disease. Arterial wall developmental disorders, such as aneurysms, in association with TSC have been well described for extracranial vasculature. The characteristics of intracranial aneurysms (IAs) in TSC have not previously been addressed in the literature. This systematic review was performed to identify and assess the distinct characteristics of IAs in patients with TSC., Methods: The authors searched PubMed, Scopus, and Web of Science for publications describing cases of TSC and IA reported before August 7, 2018. They also report 2 cases of IAs in TSC patients treated at their own institution., Results: Thirty-three TSC patients with a total of 42 IAs were included in this review. Three individuals presented with subarachnoid hemorrhage. The IAs were large or giant in 57.1% and fusiform in 45.2% of the cases. Most of the IAs (61.9%, 26 of 42) originated from the internal carotid artery. There was a higher prevalence of pediatric cases (66.7%) and male patients (63.6%, 21 of 32 individuals with known sex) among the collected series., Conclusions: TSC patients with IAs are characterized with a higher proportion of large/giant and fusiform IAs and young age, suggesting rapid aneurysmal growth. Furthermore, there is a distinct location pattern of IAs and an inverse sex ratio than in the healthy population. Large population-based patient registers are required to improve the understanding of epidemiology and pathophysiology of IA formation in TSC.

Our propose is to evaluate CT-guided biopsies in suspected spondylodiscitis with respect to puncture site, microbiology findings, histopathology findings and impact on antibiotic therapy. 86 CT-guided spine interventions in suspected spondylodiscitis comprising 201 biopsy procedures were analyzed. Medical records of all patients were screened for microbiology and histopathology reports as well as date, duration and kind of antibiotic therapy. Statistical analyses included calculation of Chi 2 -tests and logistic regression analyses. Locations of biopsies were intervertebral disc (48.3%), paravertebral soft-tissue (38.3%) and vertebral body (10.9%). Positive microbiological findings were found altogether in 33.8% of cases, positive histopathological findings in 53.6%. Significant associations between positive microbiological findings, positive histopathological findings and antibiotic therapy, respectively, were found. Location of biopsies did not significantly influence rate of positive findings. From the variables age, white blood cell count, serum creatinine and puncture site, none were found to be an independent predictor for a positive microbiological result. We concluded that CT-guided biopsy of intervertebral disc and paravertebral soft tissue yields positive microbiologic findings in a significant proportion of cases. Puncture site is not associated with positive results of microbiology or histopathology., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest.

Objective: Several parameters like extent of resection and MGMT promotor methylation in glioblastoma (GBM) are known to influence survival. Other elements like multifocality and proliferation indices are not commonly used. The aim of the present study was to analyze routinely and not routinely assessed prognostic markers for survival of patients suffering from GBM in a single center., Methods: Adult cases with GBM operated at our institution were included in this survey. The association of age, Karnofsky performance status (KPS), MGMT promotor methylation, Ki67 proliferation index, IDH1/2 mutational status, and multifocality on overall survival (OS) was analyzed in univariate and multivariate cox regression models., Results: We analyzed 565 patients with a mean age of 62.2 (18-84) years. Median OS was 12.5 months. MGMT promoter methylation and IDH 1/2 mutation were associated with significant better OS (P < 0.01). In 48 cases (8.5%), the tumor was localized in both hemispheres, which was associated with a significant worse OS than tumor infiltration of 1 hemisphere (P = 0.039). Mean Ki67 proliferation index increased to 18% when both hemispheres were infiltrated. Multivariate analysis for OS revealed IDH 1/2 wildtype (adjusted odds ratio [aOR] 4.3), higher age (aOR 4.2), unmethylated MGMT promotor (aOR 3.5), preoperative KPS score <70 (aOR 1.9), and multifocality (aOR 2.1) as independent parameters for worse survival., Conclusions: This study confirms well-known parameters like MGMT promoter methylation, IDH 1/2 mutational status, KPS, and age as independent prognostic factors for survival and reveals multifocality as further independent prognostic marker for survival. The dismal prognosis of multifocal involvement is associated with an increasing Ki67 proliferation index., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To investigate the association of the BRAFV600E mutation with papillary thyroid carcinoma using clinical, morphological and prognostic parameters. We also intend to assess the utility of the BRAFV600E immunohistochemistry and compare it with BRAF polymerase chain reaction (RT-PCR)., Material and Method: We applied BRAFV600E immunohistochemistry in a cohort of 107 papillary carcinomas, 19 adenomas and 13 normal thyroid tissues that was chosen retrospectively between 2011 and 2015. Statistical analysis was based on semiquantitative immunohistochemistry findings. We also applied BRAF RT-PCR in a subgroup of 14 papillary carcinomas, 13 metastatic lymph nodes and 4 adenomas that was chosen randomly., Results: In regard to the comparison of BRAFV600E immunohistochemistry and BRAF RT-PCR, a 3+ nuclear and cytoplasmic immunoexpression was considered 'positive'. The BRAFV600E mutation was most frequently observed in classic variant cases. No mutation was detected in follicular variant cases. The mutational status of the primary tumour and the lymph node metastasis was consistent. A significant relationship of the BRAFV600E mutation was found with prognostic factors such as higher pT stage, classic variant, lymphatic invasion, perineural invasion, lower mitotic index, lack of tumour capsule, intrathyroidal spread and extrathyroidal extension., Conclusion: Immunohistochemistry, using the VE1 clone, is a reliable technique for detection of the BRAFV600E mutation. Our results with immunohistochemistry are consistent with a previous effort. In our study, despite the correlation between some pathological prognostic parameters and the BRAFV600E mutation; poor prognosis was found to be irrelevant overall. Morphological parameters seem to be keener than the BRAFV600E mutation. Nevertheless, different series display different results, possibly due to environmental factors. Considering this and the proven success of targeted therapies against the BRAFV600E mutation a thorough assessment would be important.

Objectives: Intraoperative aneurysm rupture (IOAR) is a common complication during intracranial aneurysm (IA) surgery. In light of the paradigm shift regarding IA selected for clipping in the post-International Subarachnoid Aneurysm Trial (ISAT) era, we aimed to evaluate the risk factors and effects of IOAR in an institutional series of clipped ruptured IA (RIA) and unruptured IA (UIA)., Material and Methods: All IAs treated with microsurgical clipping at our institution between 2003 and 2016 were eligible for this study. Demographic, clinical, and radiographic factors were correlated with occurrence of IOAR in univariate and multivariate analyses. The effect on outcome was analyzed for RIA and UIA separately., Results: Nine hundred and three clipped IAs were included in the final analysis (538 UIA and 365 RIA). IOAR occurred in 163 cases (18.1%), mostly during clipping of RIA (37.5% vs. 4.8%) In multivariate analysis, ruptured status (adjusted odds ratio [aOR], 10.46; P < 0.001), sack size (aOR, 1.05 per mm increase; P = 0.038) and IA location in the anterior communicating artery (aOR, 2.31; P < 0.001) independently predicted IOAR. For RIA cases, IOAR was also independently predicted by rebleeding before therapy (aOR, 3.11; P = 0.033) and clinical severity of subarachnoid hemorrhage (aOR, 1.18 per WFNS grade increase; P = 0.049). IOAR independently predicted poor outcome (aOR, 1.83; P = 0.042) after RIA surgery. In turn, IOAR affected only the risk for cerebral infarct (OR, 3.75; P = 0.003) and incomplete IA occlusion (OR, 3.45; P = 0.003) for UIA cases, but not the outcome (P = 0.263)., Conclusions: IOAR was independently predicted by the ruptured status, location, and size of IA and by initial severity of aneurysmal bleeding and pretreatment rebleeding. The influence of IOAR differed between RIA and UIA cases., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Distraction osteogenesis (DO) is widely used treatment for the bone deformities. In addition extracorporeal shock wave therapy (ESWT) is a new perspective on noninvasive modalities of management of the bone regeneration. We examined the effects of 2 different single doses of ESWT on the consolidation period of DO of the rabbit mandible using stereological, radiological and immunohistochemical methods in the present study., Methods: DO was performed unilaterally in the mandible of 18 New Zealand rabbits (6 months' old, weighing between 2.5 and 3 kg). The distraction zone of the mandible has received no treatment as controls. Group 2 (ESWT 500) received ESWT (single dose of 500 impulses 0.19 mJ/mm energy flux intensity and 2155 mJ totally) were applied on the first day of the consolidation. Group 3 (ESWT 1000) treated with ESWT (single dose of 1000 impulses0.19 mJ/mm energy flux intensity and 4310 mJ totally) were applied on the first day of the consolidation period. After the sacrification, radiologically bone mineral density, new bone formation, new fibrous tissue, and new vessel formation were analyzed using unbiased stereological methods., Results: It was found a statistically significant difference between the study groups and control group in the bone mineral density measurements and the highest values were in the ESWT1000 group. In terms of stereological analysis, there was a significant difference between the study groups and control group (P = 0.00). The new capillary volume was highest in the E1000 group. Additionally, significant differences were found in point of the capillary volumes between the groups control and ESWT500 (P = 0.001), control and ESWT1000 (P = 0.000), ESWT500 and ESWT1000 (P = 0.040), respectively., Conclusions: A total of 1000 impulses ESWT may induce the growth factors to enhance the newly formed bone regeneration.

Objectives: The purpose of this study was to investigate possible protective effects of St. John's wort in the hepatic ischemia/reperfusion injury., Material and Methods: The hepatic artery, portal vein, and bile duct were all clamped for 45 minutes to induce ischemia in rats, and after that reperfusion for 1 hour. SJW was administrated orally, once a day for 3 days before ischemia/reperfusion. The aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor, and interleukin levels were measured in the serum samples. Luminol chemiluminescence, lucigenin luminol chemiluminescence levels; myeloperoxidase. The sodium-potassium ATPase (Na+/K+ ATPase) activity was determined in the liver tissue, and caspase-3 and caspase-9 activity with the bcl-2/bax ratio were measured by the western blot analysis., Results: The St. John's wort administration recovered the aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor, and IL-1β levels serum parameters meaningfully, while ischemia/reperfusion caused an increase in luminol chemiluminescence, lucigenin luminol chemiluminescence, myeloperoxidase, caspase-3, and caspase-9 activity and led to a decrease in the B-cell lymphoma-2/bcl-2-associated X protein (bcl-2/bax) ratio and the Na+/K+ ATPase activity., Conclusion: The obtained results indicate protective effects of St. John's wort on the ischemia/reperfusion injury through various mechanisms, and we are able to suggest that St. John's wort can clinically create a new therapeutic principle.

Objective: We aimed to investigate the effect of 10 mg/kg sildenafil on the structure and function of the liver in a rat model of obstructive jaundice., Material and Methods: Sixty-two male Wistar albino rats were distributed into six different groups. Obstructive jaundice was performed by legating the common bile duct. 10 mg/kg sildenafil citrate in drinking water was delivered orally after the operation before sacrificing them. Rats were sacrificed either after 10 or 28 days according to the study design. The blood and tissue samples from the liver were obtained to perform a biochemical and histopathological analysis to study functional and structural changes in the liver., Results: At the 10th day, there was no difference between the sildenafil-treated and control groups with regard to the aspartate aminotransferase and alanine aminotransferase levels (p=0.423, p=0.661). The alkaline phosphatase total bilirubin levels among the groups were statistically different (p<0.001). At the 28th day, liver function tests except alanine aminotransferase showed significant differences among the groups (p<0.001). Liver function tests did not changed significantly between the 10th and 28th day in sildenafil-treated rats (p>0.05). Significant differences were observed among the groups with regard to cholestasis, fibrosis, inflammation, and necrosis (p<0.001). However, edema increased in the sildenafil-treated group (p<0.001). On the 28th day, the severity of structural changes in the liver after obstructive jaundice, except edema, reduced significantly (p<0.001). The sildenafil-treated groups at different time points didn't show any statistical difference in histopathological changes (p>0.05)., Conclusion: Oral administration of 10 mg/kg sildenafil citrate dramatically reverses the biochemical and histopathological liver changes induced by obstructive jaundice in rats., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare.

Objective: The aim of this study was to evaluate the efficacy of the local application of vancomycin hydrochloride (HCl)-ceftriaxone disodium hemiheptahydrate onto implants before using them to prevent postoperative infection., Methods: The study included 239 patients (153 women and 86 men; mean age: 48.23 ± 16.77 years) who had thoracolumbar stabilization with transpedicular screws. All surgeries were performed by the same surgeon. Patients were divided into two groups. In the group 1 (n = 104), implants were bathed in a solution of local prophylactic antibiotics for 5 seconds just before implantation. In the group 2 (n = 135), implants were not bathed before implantation. Local antibiotics used in the study was effective against gram positive bacteria (including methicillin resistant Staphylococcus aureus) and gram negative bacteria. The rate of surgical site infection and wound healing time were compared between the groups., Results: A total of 10 patients (4.1%) had deep wound infection and 20 (8.4%) had superficial infection. The most common bacteria was Staphylococcus aureus. One patient died 21 days after the surgery because of sepsis. The wound healed in a mean of 9.66 ± 2.04 days in patients who had no infection and in 32.33 ± 19.64 days in patients with infection (p < 0.001). The patients in group 1 had significantly less deep infection than the patients in group 2 (p < 0.05). However, there was no statistically significant difference between the groups for superficial infection. Patients with vertebral fracture had significantly lower deep infection rate in group 1. The deep infection rate of group 1 patients with diabetes, with bleeding of more than 2000 mL, transfused with blood transfusions above 3 units and with dural injury was significantly lower than those in the group 2. None of the patients had allergic reactions to the drugs used for local prophylaxis., Conclusions: This study shown that bathing implants in antibiotics solution was an effective local prophylactic method to prevent deep infections in spinal surgeries with instrumentation., Level of Evidence: Level III, Therapeutic study., (Copyright © 2018 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.)

Objectives: The purpose of the present study was to evaluate the effects of sildenafil on mandibular fracture healing in animals treated with zoledronic acid by using histologic, histomorphometric, immunohistochemical, and radiodensitometric methods., Materials and Methods: A total of 36 Sprague-Dawley rats (3 months old) were used. All animals were treated intraperitoneally with 0.1 mg/kg zoledronate three times per week, for a total of 8 weeks. Postoperatively, the animals were divided into two groups: zoledronate group (Z), which had no treatment applied (n = 18), and zoledronate + sildenafil (ZS), which were treated daily with 10 mg/kg sildenafil (n = 18). Each group was divided into two subgroups and the animals were sacrificed at the end of week 1 (Z1 and ZS1, n = 9) and week 4 (Z4 and ZS4, n = 9) after the operation. Histologic, histomorphometric, immunohistochemical analysis, and radiodensitometry were performed on the test subjects., Results: Sildenafil-treated groups showed a significant increase in fracture healing scores. This result was supported by the densitometric, histologic, histomorphometric, and immunohistochemical findings., Conclusions: Sildenafil may have positive effects on accelerating and improving fracture healing, and it may be used as a supporting factor in bone healing in patients treated with bisphosphonate (BP) to prevent negative effects of BP's., Competing Interests: There are no conflicts of interest.

Background: The aim of this study was to investigate the effects of melatonin on intestinal anastomosis after intestinal ischemia/ reperfusion injury (IRI)., Methods: Thirty Wistar albino rats of both sexes were divided into 3 groups: sham, control, and treatment. IRI was performed by clamping the superior mesenteric artery (SMA) for 30 minutes, followed by reperfusion. The sham rats received only manipulation of the SMA. Melatonin (10 mg/kg) was administered to the treatment group, and the control group was given a vehicle injection. Both the treatment group and the control group further underwent ileal resection of a 1-cm segment and anastomosis. On the postoperative seventh day, the anastomotic burst pressure, hydroxyproline level, histological indices of wound healing, and oxidative parameters of catalase (CAT), superoxide dismutase (SOD), total glutathione (T-GSH), and glutathione peroxidase (GSH-Px) levels were measured. A one-way analysis of variance and chi-square test were used for the categorical data., Results: Melatonin treatment led to a significantly higher burst pressure (p=0.027 and p<0.001, respectively). The 2 antioxidant enzymes, CAT and SOD, were at the highest level in the sham and melatonin groups and the lowest level in the control group (p=0.001 and p=0.002, respectively). Melatonin treatment resulted in a significantly higher level of both enzymes compared with the control group (p=0.026 and 0.003, respectively). The GSHpx and total GSH levels were slightly elevated in the treated rats, but the difference was not statistically significant (p=0.205 and 0.216, respectively). Fibroblast infiltration, capillary formation, and epithelialization were significantly better in the melatonin-treated animals. The granulocyte and mononuclear infiltration scores were similar between all groups., Conclusion: It was concluded that melatonin had marked effects on intestinal anastomotic healing during intestinal IRI.

Background and Objective:  We present a treatment approach for a rare condition of patients with a ventral C1 fracture and a congenital cleft in the posterior arch (half-ring Jefferson fracture) with an intact transverse atlantal ligament. Our technique aims to achieve stability of the atlanto-occipital and atlantoaxial joints while preserving mobility of the upper cervical spine., Patients and Methods:  Two male patients, 43 years and 29 years of age, respectively, were admitted to our hospital due to a fracture of the ventral arch of the atlas with no damage of the transverse atlantal ligament. Both men also presented a congenital cleft of the posterior arch. Initial conservative management with a halo-thoracic vest was performed in one case and failed. As a result, surgical treatment was performed in both cases using bilateral C1 mass screws and a transverse connector., Results:  The patients showed no neurologic deficits on follow-up examination 4 weeks after surgery with a full range of head and neck motion. Computed tomography (CT) showed no dislocation of the implanted material with good dorsal alignment and a stable ventral fracture distance. Follow-up CT showed osseous stability in both cases with the beginning of bony ossification of the bone graft., Conclusion:  Isolated instable fractures of the ventral arch of the atlas with a congenital cleft of the posterior arch with no damage of the transverse atlantal ligament can be stabilized using bilateral C1 mass screws and a transverse connector preserving upper cervical spine mobility., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Georg Thieme Verlag KG Stuttgart · New York.)

Bioactive glass has been demonstrated as a biocompatible bone substitute. However bone healing process can be prolonged due to late resorption of the material. Adipose derived stem cells (ASC) have osteogenic differentiation potential and hence can be a cell source for bone regeneration. The aim of this study was to test whether combination of bioactive glass with ASCs would enhance bone regeneration. Following creation of critical sized defects on the calvaria of 32 Wistar rats, the animals were randomly divided into four groups: Group C (control): Defects were left untreated; Group G: Defects were covered with autologous bone graft; Group BG: Defects were filled with bioactive glass; Group BG/ASC: Defects were filled with bioactive glass seeded with ASCs. The defect size was significantly greater in Group C compared to all other groups. Bone density was significantly lower in Group C compared to Group G and Group BG/ASC. Bone regeneration score of Group C was significantly lower than other groups. Group BG/ASC demonstrated lamellar bone and havers canal formation. The results of this study demonstrated that bioactive glass implanted with ASC is a biocompatible construct stimulating radiologically and histologically evident bone regeneration similar to autologous bone grafting. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1002-1008, 2017., (© 2016 Wiley Periodicals, Inc.)

Our aim was to investigate the probable protective effects of aerobic, resistance and combined exercise methods on ovariectomy and d-galactose induced Alzheimer's Disease (AD)-like model. d-galactose (100mg/kg) or saline were administered intraperitoneally for 6 weeks to ovariectomized or sham-operated rats (n=8/group). Aerobic (AE), resistance (RE) and combined exercises (CE) (aerobic+resistance) were performed for 3 times a week for 6 weeks. Anxiety level and cognitive functions were evaluated via hole-board and object recognition tests. Brain myeloperoxidase, malondialdehyde, nitric oxide activity, lucigenin-enhanced chemiluminescence, glutathione and serum insulin like growth factor-I (IGF-I) assays were done. Hippocampal mRNA levels of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and amyloid precursor protein 695 (APP695) were measured. Amyloid Beta (Aβ), NGF, BDNF, IGF-I immunoreactive neurons were evaluated. Freezing time were increased in AD-like model and decreased back with AE (p<0.05). Deteriorated working memory in AD-like model was improved with all exercise types (p<0.05-0.001). Reduced glutathione levels in AD-like model were increased and increased malondialdehyde levels were reduced and serum IGF-I levels were increased by all exercises (p<0.05-0.001). Increased APP mRNA levels in AD-like model were decreased via CE (p<0.05). Elevated Aβ scores in AD-like model were decreased by RE and CE (p<0.01) in hippocampus and by all exercise types in cortex (p<0.05-0.01). Decreased cortical NGF immunocytochemical scores of AD-like model were increased by CE (p<0.05). Different exercise models may have protective effects in development stage of AD via reducing oxidative stress and Aβ scores, and by improving antioxidant system and brain plasticity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

OBJECTIVE The aim of this study was to determine seizure outcome, functional outcome, and the withdrawal of antiepileptic drugs (AEDs) after conservative or surgical treatment of patients with new-onset cavernoma-related epilepsy (CRE). METHODS The authors conducted a retrospective comparative observational study of 79 consecutive patients, each with a single sporadic cerebral cavernous malformation (CCM) and new-onset CRE. RESULTS Forty-one patients underwent initial surgery (IS), and 38 patients underwent initial conservative (IC) treatment. Of those in the latter group, 19 underwent delayed surgical (DS) treatment. At the last follow-up, 88%, 32%, and 79% of patients in the respective groups had been seizure free for at least 2 years (International League Against Epilepsy [ILAE] Class 1; IS vs IC, p < 0.0001) and 78%, 8%, and 58%, respectively, had been off AEDs (IS vs IC, p < 0.0001). The cumulative probability of staying seizure free (ILAE Class 1) during a 5-year period was 73% (mean seizure-free follow-up 49.8 ± 2.7 months, 95% CI 44.4-55.1 months) for the IS group, 22% (mean 31.8 ± 3.6 months, 95% CI 24.8-38.8 months) for the IC group, and 68% (mean 48.6 ± 4.3 months, 95% CI 40.1-57.1 months) for the DS group (IS vs IC p < 0.001). Long-term operative morbidity was 3%, and long-term morbidity in the conservatively treated group was also 3%. CONCLUSIONS Patients with CCM and new-onset CRE who underwent IS treatment showed better results in seizure control and the discontinuation of AEDs than the conservatively treated patients. Operative morbidity was comparable to the morbidity from symptomatic CCM hemorrhage in the conservative group. Half of the patients who started with conservative treatment underwent subsequent surgical treatment; however, a longer duration of epilepsy prior to surgery did not worsen postoperative seizure outcome.