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Background There is a need to evaluate the outcomes of patients who underwent brain tumor surgery with subsequent telemedicine or in-person follow-up during the COVID-19 pandemic. Methods We retrospectively included all patients who underwent surgery for brain tumor resection by a single neurosurgeon at our Institution from the beginning of the COVID-19 pandemic restrictions (March 2020) to August 2021. Outcomes were assessed by stratifying the patients using their preference for follow-up method (telemedicine or in-person). Results Three-hundred and eighteen (318) brain tumor patients who were included. The follow-up method of choice was telemedicine (TM) in 185 patients (58.17%), and in-person (IP) consults in 133 patients. We found that patients followed by TM lived significantly farther, with a median of 36.34 miles, compared to a median of 22.23 miles in the IP cohort (P = .0025). We found no statistical difference between the TM and the IP group, when comparing visits to the emergency department (ED) within 30 days after surgery (7.3% vs 6.01%, P = .72). Readmission rates, wound infections, and 30-day mortality were similar in both cohorts. These findings were also consistent after matching cohorts using a propensity score. The percentage of telemedicine follow-up consults was higher in the first semester (73.17%) of the COVID-19 pandemic, compared to the second (46.21%), and third semesters (47.86%). Conclusions Telehealth follow-up alternatives may be safely offered to patients after brain tumor surgery, thereby reducing patient burden in those with longer distances to the hospital or special situations as the COVID-19 pandemic.

INTRODUCTION Until recent decades, thalamic gliomas had been considered largely inoperable. These lesions are deep-seated and surrounded by vital structures. However, as technology and imaging modalities have improved, so have treatment modalities. Currently, a range of surgical approaches are used, partially dependent on the location of the lesion; although no consensus has been reached regarding optimal surgical management. OBJECTIVE To conduct a systematic review of the literature to describe the current surgical outcomes of adult thalamic gliomas. METHODS Four databases were searched with keywords “‘thalamic glioma’ AND ‘surgical intervention’ OR ‘thalamic glioma’ AND ‘surgical treatment’” for articles assessing surgical techniques of adult thalamic glioma resection. Our systematic review was reported in accordance with the PRISMA guidelines. 793 full-text studies were assessed for eligibility. Ultimately, 14 studies were included. RESULTS The mean age was of 33.57 years (18-83). In 479/507 cases the surgical strategy used was described. The transcortical approach was the most utilized (37.8% of cases). The remaining cases employed transventricular (23.8%), transcallosal (22.8%), and trans-sylvian transinsular (2.92%) approaches, among others. Gross total resection (GTR), subtotal resection (STR), and partial resection were achieved in 36.7%, 47.4%, and 15.9%, respectively. New temporary postoperative deficits were observed in 57/507 patients and new permanent deficits in 56/507 patients. There were 18 total perioperative deaths reported. The degree of morbidity across approaches was recorded in just one study, where no significant difference was found. The mean overall survival of adult patients after surgery ranged from 11.5 to 27.39 months across studies. CONCLUSION There is a lack of statistically strong data that addresses which surgical approach causes less morbidity and allows a better surgical resection for thalamic gliomas. Ultimately, surgical resection of adult thalamic gliomas can increase overall survival but at the risk of operative morbidity. Transcortical approaches appear to carry a greater overall survival

INTRODUCTION Adult midline gliomas are rare entities, with a scarcity of available clinical data. These patients have variable courses, with limited evidence to predict outcomes. Emerging evidence suggests that biomolecular profiles may play a significant role in outcomes, so tissue diagnosis is a key component of management. However, the role of cytoreductive therapy, such as Laser Interstitial Thermal Therapy (LITT) remains unknown. To date, only a few studies have described the use of MRI-guided LITT for managing midline gliomas. OBJECTIVE To present a retrospective analysis of a single-center two-surgeon experience treating adult midline gliomas with either biopsy/LITT or biopsy alone. METHODS Patients with midline intraxial tumors surgically treated at our tertiary care referral center were identified using our established database. Twenty-one patients managed either with biopsy/LITT or needle biopsy from 2015 to 2021 were included. Demographics and clinical records including, among others, length of hospital stay, preoperative lesion size, ablation volume, perioperative complications, adjuvant treatment, and stratified overall survival (OS) were collected. RESULTS The two cohorts were composed of 7 patients who underwent LITT, and 14 biopsies. The mean age was 60.95y (25-82). The average tumor volumes were 16.99 cm3 and 15.41 cm3 for LITT and biopsy, respectively. No post-surgical complications were found in the LITT group, one patient had a postsurgical hemorrhage after biopsy. The mean OS was 20.28 ± 9.63 months in the LITT group, which was greater but not statistically significant than in the biopsy group (11.05 ± 4.45 months) (p = 0.605). CONCLUSION Our results show that LITT is as safe as needle biopsy for the treatment of adult midline gliomas, and may offer a survival benefit given its cytoreductive properties.

Background The response to the global severe acute respiratory syndrome coronavirus 2 pandemic culminated in mandatory isolation throughout the world, with nationwide confinement orders issued to decrease viral spread. These drastic measures were successful in “flattening the curve” and maintaining the previous rate of coronavirus disease 2019 infections and deaths. To date, the effects of the coronavirus disease 2019 pandemic on neurotrauma has not been reported. Methods We retrospectively analyzed hospital admissions from Ryder Trauma Center at Jackson Memorial Hospital, during the months of March and April from 2016 to 2020. Specifically, we identified all patients who had cranial neurotrauma consisting of traumatic brain injury and/or skull fractures, as well as spinal neurotrauma consisting of vertebral fractures and/or spinal cord injury. We then performed chart review to determine mechanism of injury and if emergent surgical intervention was required. Results Compared with previous years, we saw a significant decline in the number of neurotraumas during the pandemic, with a 62% decline after the lockdown began. The number of emergent neurotrauma surgical cases also significantly decreased by 84% in the month of April. Interestingly, although the number of vehicular traumas decreased by 77%, there was a significant 100% increase in the number of gunshot wounds. Conclusions Population seclusion had a direct effect on the frequency of neurotrauma, whereas the change in relative proportion of certain mechanisms may be associated with the psychosocial effects of social distancing and quarantine.

INTRODUCTION: Current trends in surgical neuro-oncology have shown that early discharges are both safe and feasible with shorter lengths of stay (LOS) associated with fewer thromboembolic complications, less hospital-acquired infections, reduced costs, and greater patient satisfaction. Traditionally, infratentorial tumor resections have been associated with longer LOS and limited data exists evaluating predictors of early discharge in these patients. The objective was to assess patients undergoing posterior fossa craniotomies for tumor resection and identify variables associated with a postoperative day 1 (POD1) discharge and determine any differences in outcomes and readmission rates. METHODS: A retrospective review of posterior fossa craniotomies for tumor resection at our institution was performed from 2011 to 2020. Laser ablations, craniotomies for non-tumoral pathologies, and biopsies were excluded. Complete demographic, clinical, surgical and postoperative data was collected for each patient. RESULTS: 173 patients were identified and 25 (14.5%) were discharged on POD1. Median length of stay was 6 days. The POD1 discharges had significantly better preoperative Karnofsky performance scores (p

Background Large-scale brain networks and higher cognitive functions are frequently altered in neuro-oncology patients, but comprehensive non-invasive brain mapping is difficult to achieve in the clinical setting. The objective of our study is to evaluate traditional and non-traditional eloquent areas in brain tumor patients using a machine-learning platform. Methods We retrospectively included patients who underwent surgery for brain tumor resection at our Institution. Preoperative MRI with T1-weighted and DTI sequences were uploaded into the Quicktome platform. We categorized the integrity of nine large-scale brain networks: language, sensorimotor, visual, ventral attention, central executive, default mode, dorsal attention, salience and limbic. Network integrity was correlated with preoperative clinical data. Results One-hundred patients were included in the study. The most affected network was the central executive network (49%), followed by the default mode network (43%) and dorsal attention network (32%). Patients with preoperative deficits showed a significantly higher number of altered networks before the surgery (3.42 vs 2.19, P < .001), compared to patients without deficits. Furthermore, we found that patients without neurologic deficits had an average 2.19 networks affected and 1.51 networks at-risk, with most of them being related to non-traditional eloquent areas (P < .001). Conclusion Our results show that large-scale brain networks are frequently affected in patients with brain tumors, even when presenting without evident neurologic deficits. In our study, the most commonly affected brain networks were related to non-traditional eloquent areas. Integrating non-invasive brain mapping machine-learning techniques into the clinical setting may help elucidate how to preserve higher-order cognitive functions associated with those networks.

INTRODUCTION Ovarian cancer is a rare cause of brain metastasis requiring neurosurgical intervention. Management strategies vary and prognostic factors are not well known. OBJECTIVE We aim to systematically review the literature on management and outcomes of ovarian cancer brain metastasis and compare it with our experience. METHODS Systematic review was performed using PRISMA guidelines. Databases were sourced from inception to April 2022. Study selection was based on predetermined inclusion/exclusion criteria. A simultaneous retrospective analysis was performed on patients from our institution who underwent evaluation and treatment for metastatic intracranial lesions of ovarian origin. RESULTS Literature search generated 214 articles. Twelve were ultimately selected, representing 428 brain metastasis (BM) patients from ovarian cancer. Patients age from 27-80 years. The interval from cancer diagnosis to BM ranged from 0 – 226.2 months. Surgical resection (SR), stereotactic radiosurgery (SRS), and whole-brain radiotherapy were the most frequently used treatment modalities. Individual patients’ overall survival following BM diagnosis ranged from 0 – 173 months. For our institutional analysis, 9 patients were included with median age of 56 years. Median interval from diagnosis to BM was 51 months. Four patients were treated with SR and adjuvant SRS. Two patients had SR and SRS with additional extraventricular drain placement. Two patients had SR only, and one received only SRS. Median radiation dose received was 20 Gy. For those who experienced progression, median progression-free survival was 14 months. One patient exhibited no progression at the time of analysis. Three patients were alive at the time of analysis with two others lost to follow-up. CONCLUSION brain metastases following ovarian cancer are a rare outcome carrying a poor prognosis. Multimodal therapies, specifically SR and SRS, correlate with increased survival. Further study is needed to better guide optimal management, with particular attention to the benefits of resection with targeted adjuvant radiation.

BACKGROUND There is a need to evaluate the outcomes of patients who underwent brain tumor surgery and were followed by telemedicine or in-person consults during the COVID-19 pandemic. METHODS We retrospectively included all patients who underwent surgery for brain tumor resection by a single neurosurgeon at our Institution from the beginning of the COVID-19 pandemic restrictions (March 2020) to August 2021. Outcomes were assessed by stratifying the patients using their preference for follow-up method (telemedicine or in-person). RESULTS Three-hundred and eighteen (318) brain tumor patients who were included. The follow-up method of choice was telemedicine in 185 patients (58.17%), and in-person consults in 133 patients. We found that patients followed by telemedicine lived significantly farther, with a median of 22.23 miles, compared to a median of 36.34 miles in the TM cohort (p = 0.0025). When comparing visits to the emergency department (ED) within 30 days after surgery, and we found no statistical difference between the TM and the IP group (7.3% vs 6.01%, p=0.72). Readmission rates, wound infections and 30-day mortality were similar in both cohorts. These findings were also consistent after matching cohorts using a propensity score. The percentage of telemedicine follow-up consults was higher in the first semester (73.17%) of the COVID-19 pandemic, compared to the second (46.21%) and third semesters (47.86%). CONCLUSIONS Telehealth follow-up alternatives may be safely offered to patients after brain tumor surgery, thereby reducing patient burden in those with longer distances to the hospital or special situations as the COVID-19 pandemic.

INTRODUCTION Cranial neurosurgery confers psychological stress, as well as the stress of being in the hospital rather than in one’s preferred surroundings. Compared with inpatient admissions, same-day discharges reduce patient exposure to nosocomial infection, thromboembolic complications, and medical error. Also, it reduces costs to the health care system. OBJECTIVE To report the results of a pilot study that prospectively evaluated for the first time in a United States hospital, the outcomes of patients that underwent brain tumor surgery and are discharged home the same day as surgery. METHODS A quality intervention study including patients who underwent outpatient craniotomy for brain tumors by a single neurosurgeon (R.J.K) at the University of Miami from August 2020 to August 2021 was performed. Patients included were between 16 to 85 years old, with a Karnofsky Performance Status score of ≥ 70, and with supratentorial tumors with a maximum diameter of 4 cm. Complete demographic and clinical data were collected prospectively for each patient. In all patients, the minimum observation period was 6 h after surgery. RESULTS 37 of 334 patients met the inclusion criteria for the outpatient protocol. Thirty-two patients were discharged on the same day as surgery. Five patients (14%) were considered eligible for outpatient surgery but were ultimately admitted to the hospital postoperatively and were discharged after overnight observation. No postoperative complications were noted at two-week follow-up. CONCLUSION With appropriate selection and postoperative monitoring, same-day discharge can be considered a safe and feasible option for certain craniotomy cases. Establishing a multidisciplinary team of physicians, nurses, radiologists, and physical therapists is critical to achieving this aim. Physicians should have a low threshold to admit a patient with concerning exam findings, complications, or complicated past medical history

INTRODUCTION Classical prefrontal approaches exposed the lateral surface of the frontal lobe. Minimally invasive (MI) approaches achieved to reduce soft tissue damage and craniotomy size without affecting tumor resection grade. This is associated with shorter hospital stays and faster return to preoperative daily activities. OBJECTIVE To describe the MI prefrontal glioma resection technique developed in our department and to analyze our surgical results. METHODS We performed a retrospective review of patients who underwent prefrontal lobe glioma (WHO grade II-IV) resection using an MI approach in 2016-2021 at the University of Miami Hospital. Re-surgery, biopsy-only patients, multicentric tumors, and patients with less than four months of follow-up were excluded. Demographic and clinical data were collected. A 4-5 cm linear incision is done, starting at 1 cm lateral to the sagittal suture and extending towards the superior temporal line. An ellipsoidal-shaped mini-craniotomy is performed. RESULTS Thirty-four patients were included. The mean age was 50.2 years old, with 20 male subjects. Twenty-two patients had high-grade gliomas (HGG) and 12 patients had low-grade gliomas (LGG). On average, patients were discharged 1.97 days after surgery. The mean craniotomy area was 15,5 cm2 (7-43 cm2). The mean tumor volume was 64,5 cm2 ( 9 -165.8 cm2). Two wound infections and one case of aseptic meningitis were observed in patients with craniotomies > 15 cm2, while the group with craniotomies < 15 cm2 had no perioperative complications. In the HGG group, a supramaximal resection (SMR) was achieved in 8 patients, 9 HGG patients had gross total resection (GTR) or near-total resection (NTR), and 5 patients had subtotal resection (STR). In the LGG, GTR was achieved in 10 patients and STR in 2 patients. CONCLUSION MI prefrontal approach for frontal gliomas is safe and feasible with minor complications, short hospital stay, and without sacrificing tumor resection volume.

INTRODUCTION The concept of enhanced recovery after surgery (ERAS) due to standardized interventions has been gaining more relevance within neurosurgery. Advances were made both in protocols for spine and cranial surgery. These experiences described many benefits such as less psychological stress, reduction in hospitalization days, and lower hospital costs, without increasing the incidence of complications. However, no experience has described to date the applicability of an ERAS program for laser ablation thermal therapy (LITT). OBJECTIVE To describe our initial experience with the first enhanced recovery program reported for laser ablation for brain tumors. Secondly, to summarize the perioperative clinical outcomes of ERAS applied to LITT. METHODS We performed a retrospective analysis of all adult patients who underwent LITT for oncological lesions from 2013 to 2021. A multidisciplinary program was created by protocolizing interventions carried out along the path of the patient's hospitalization. Each recommendation was individually assessed for its appropriateness for enhancing recovery and for its validity with a focused literature review process. RESULTS A total of 184 patients were included, with a mean age of 60.7 ± 13.5 years, 35% males. 167 tumors were located in the supratentorial compartment, and 17 were infratentorial; the mean tumor diameter was 1.84 ± 1.04 cm. Among the pathologies treated 50.0% were metastasis, and 36.9% were glioblastomas. The mean postoperative day discharge was 1.2 ± 0.8 days. The readmission rate due to surgical complications within 30 days of surgery was 2.7%. These readmission rates fall into what is expected according to published literature without an ERAS program and longer hospital admissions. One death was recorded in the perioperative period. CONCLUSION Clinical interventions that could constitute an ERAS program are feasible in laser ablation of brain tumors. This study could be useful as a preliminary framework for the development of future guidelines.

Background Proximal junctional kyphosis is a kyphotic deformity following spine instrumentation, predominantly seen in scoliosis patients. There have been previous attempts to develop classification schema of PJK. We analyzed the factors contributing to PJK based upon our own clinical experience with the goal of developing a clinical guidance tool which took into account both etiology and mechanism of failure. Methods: We performed a retrospective analysis of all re-operation thoracolumbar surgeries at a single institution over a 14-year period. Patients with PJK were identified and categorized based upon the etiology, mechanism of failure, and an indication of revision. Next, we conducted a systematic review on articles emphasizing a classification system for PJK. Results: Fourteen PJK patients were identified out of 121 patients who required revision spine surgery. The average age was 64.9 ± 10.2 years, with 10 males (71%) and 4 females (29%). Three primary etiologies were identified: 6/14 (47%) overcorrection, 6/14 (47%) osteopenia, and 2/14 (14%) ligamentous disruption. The mechanism of failure was likewise divided into three categories: 9/14 (64%) compression fracture, 1/14 (7%) hardware failure, and 4/14 (29%) disc degeneration. The relationship between osteopenia and the development of a compression fracture leading to PJK was statistically significant (p = 0.031). Conclusion: There are multiple current classification systems for PJK. Our study findings were in line with previously published literature and suggest the need for a future classification system combining both etiology, mechanism of failure, and severity of disease.

Laser interstitial thermal therapy is a minimally invasive surgical alternative to craniotomy that uses laser light through a fiber optic probe placed within a target lesion to create thermal tissue damage, resulting in cellular death. It is used in neuro-oncology to treat inaccessible lesions and obviate morbidity in high-risk patients. Overall complication rates and outcome measures are comparable with those seen in radiation and/or craniotomy. Laser interstitial thermal therapy can be an effective option for recurrent brain metastases. Prospective, randomized trials must be performed to evaluate the efficacy of laser interstitial thermal therapy as a primary treatment for brain metastases.

Patients who present with traumatic brain injury (TBI) combined with blunt cerebrovascular injuries (BCVI) are difficult to manage, in part because treatment for each entity may exacerbate the other. It is necessary to develop a treatment paradigm that ensures maximum benefit while mitigating the opposing risks. A cohort of 150 patients from 2015 to present, with either internal carotid artery (ICA) and/or vertebral artery (VA) dissections or pseudoaneurysms, was cross-referenced with those who had sustained TBI. Of the 38 patients identified with both TBI and BCVI, 25 suffered ICA injuries, 10 had VA injuries and 3 had combined ICA/VA injuries. Unilateral BCVI occurred in 30 patients, while 8 had bilateral BCVI. Two patients required surgical intervention for TBI, and 5 patients required endovascular intervention for BCVI. Positive emboli detection studies (EDS) on transcranial dopplers (TCD) were demonstrated in 19 patients, with 9 patients having radiographic evidence of stroke. Anti-platelet therapy was initiated in 32 patients, and anti-coagulation in 10 patients, without new or worsening intracranial hemorrhages (ICH). Overall, 76% of patients were able to be discharged home or to rehabilitation, with good recovery demonstrated in 73% of the patients who had appropriate follow-up. In the setting of concurrent TBI and BCVI, use of anti-platelet/coagulation to prevent stroke can be safe if monitored closely. Here we describe a treatment paradigm which weighs the risk and benefits of therapies based on severity of ICH and stroke prevention, which tended to result in good disposition and recovery.

Background Glioma is a family of primary brain malignancies with limited treatment options and in need of novel therapies. We previously demonstrated that the adhesion G protein-coupled receptor GPR133 (ADGRD1) is necessary for tumor growth in adult glioblastoma, the most advanced malignancy within the glioma family. However, the expression pattern of GPR133 in other types of adult glioma is unknown. Methods We used immunohistochemistry in tumor specimens and non-neoplastic cadaveric brain tissue to profile GPR133 expression in adult gliomas. Results We show that GPR133 expression increases as a function of WHO grade and peaks in glioblastoma, where all tumors ubiquitously express it. Importantly, GPR133 is expressed within the tumor bulk, as well as in the brain-infiltrating tumor margin. Furthermore, GPR133 is expressed in both isocitrate dehydrogenase (IDH) wild-type and mutant gliomas, albeit at higher levels in IDH wild-type tumors. Conclusion The fact that GPR133 is absent from non-neoplastic brain tissue but de novo expressed in glioma suggests that it may be exploited therapeutically.

Summary: Low-grade astrocytomas (LGAs) carry neomorphic mutations in isocitrate dehydrogenase (IDH) concurrently with P53 and ATRX loss. To model LGA formation, we introduced R132H IDH1, P53 shRNA, and ATRX shRNA into human neural stem cells (NSCs). These oncogenic hits blocked NSC differentiation, increased invasiveness in vivo, and led to a DNA methylation and transcriptional profile resembling IDH1 mutant human LGAs. The differentiation block was caused by transcriptional silencing of the transcription factor SOX2 secondary to disassociation of its promoter from a putative enhancer. This occurred because of reduced binding of the chromatin organizer CTCF to its DNA motifs and disrupted chromatin looping. Our human model of IDH mutant LGA formation implicates impaired NSC differentiation because of repression of SOX2 as an early driver of gliomagenesis. : In a human neural stem cell model of low-grade astrocytoma, Modrek et al. show that mutant IDH1 and loss of P53 and ATRX together block differentiation via disassociation of SOX2 from putative enhancers. This occurs because of disruption of chromatin looping secondary to hypermethylation at CTCF motifs. Keywords: low-grade glioma, astrocytoma, IDH, P53, ATRX, neural stem cells, SOX2, chromatin looping, CTCF, DNA methylation

Patient-derived xenografts (PDX) provide in vivo glioblastoma (GBM) models that recapitulate actual tumors. Orthotopic tumor xenografts within the mouse brain are obtained by injection of GBM stem-like cells derived from fresh surgical specimens. These xenografts reproduce GBM's histologic complexity and hallmark biological behaviors, such as brain invasion, angiogenesis, and resistance to therapy. This method has become essential for analyzing mechanisms of tumorigenesis and testing the therapeutic effect of candidate agents in the preclinical setting. Here, we describe a protocol for establishing orthotopic tumor xenografts in the mouse brain with human GBM cells.

Background While effective for the repair of large skull base defects, the Hadad-Bassagasteguy nasoseptal flap increases operative time and can result in a several-week period of postoperative crusting during re-mucosalization of the denuded nasal septum. Endoscopic transsphenoidal surgery for pituitary adenoma resection is generally not associated with large dural defects and high-flow cerebrospinal fluid (CSF) leaks requiring extensive reconstruction. Here, we present the posterior nasoseptal flap as a novel technique for closure of skull defects following endoscopic resection of pituitary adenomas. This flap is raised in all surgeries during the transnasal exposure using septal mucoperiosteum that would otherwise be discarded during the posterior septectomy performed in binostril approaches. Methods We present a retrospective, consecutive case series of 43 patients undergoing endoscopic transsphenoidal resection of a pituitary adenoma followed by posterior nasoseptal flap placement and closure. Main outcome measures were extent of resection and postoperative CSF leak. Results The mean extent of resection was 97.16 ± 1.03%. Radiographic measurement showed flap length to be adequate. While a defect in the diaphragma sellae and CSF leak were identified in 21 patients during surgery, postoperative CSF leak occurred in only one patient. Conclusions The posterior nasoseptal flap provides adequate coverage of the surgical defect and is nearly always successful in preventing postoperative CSF leak following endoscopic transsphenoidal resection of pituitary adenomas. The flap is raised from mucoperiosteum lining the posterior nasal septum, which is otherwise resected during posterior septectomy. Because the anterior septal cartilage is not denuded, raising such flaps avoids the postoperative morbidity associated with the larger Hadad-Bassagasteguy nasoseptal flap.

This paper presents the findings from a proof-of-concept study that was conducted to examine whether engines and vehicles equipped with onboard diagnostic systems could provide data for optimizing fleet preventive maintenance practices. The study investigated the development of a statistical approach for recommending oil changes in the Texas Department of Transportation's fleet, based on engine data collection and oil sampling analysis for a sample of heavy-duty dump trucks. The study also investigated whether predictive intervals could improve preventive maintenance practices and save money. The engine parameters that were logged included engine speed, oil temperature, engine load, coolant temperature, and engine oil pressure; and the oil parameters tested included viscosity, oxidation, nitration, total acid number, total base number, wear metals, soot, and fuel dilution. The findings indicated that there were very low levels of oil degradation, attributable to the engine operations, which were observed to be predominantly low-load operations with a lot of idling. The findings support potential changes to fleet maintenance and management practices from an economic and environmental perspective.

To model low-grade astrocytoma (LGA) formation, we introduced R132H IDH1, P53 shRNA and ATRX shRNA in human neural stem cells (NSCs). These oncogenic hits blocked NSC differentiation, increased invasiveness in vivo and led to an epigenetic and transcriptional profile resembling IDH1-mutant human LGAs. The differentiation block was caused by transcriptional silencing of transcription factor SOX2. Ectopic expression of SOX2 was sufficient to rescue the differentiation block. We found that SOX2 down-regulation was secondary to disassociation of its promoter from a putative long-range enhancer ~700kb downstream of SOX2. This occurred due to reduced binding of the chromatin organizer CTCF to its methylated DNA motifs and disrupted chromatin looping. Our human model of IDH-mutant LGA implicates impaired NSC differentiation due to epigenetic repression of SOX2 as an early driver of gliomagenesis.

Background: Previous reports have proposed an association between traumatic brain injury (TBI) and subsequent glioblastoma (GBM) formation. Methods: We used literature searches and radiographic evidence from two patients to assess the possibility of a link between TBI and GBM. Results: Epidemiological studies are equivocal on a possible link between brain trauma and increased risk of malignant glioma formation. We present two case reports of patients with GBM arising at the site of prior brain injury. Conclusion: The hypothesis that TBI may predispose to gliomagenesis is disputed by several large-scale epidemiological studies, but supported by some. Radiographic evidence from two cases presented here suggest that GBM formed at the site of brain injury. We propose a putative pathogenesis model that connects post-traumatic inflammation, stem and progenitor cell transformation, and gliomagenesis.

The (CGG)n-repeat in the 5′-untranslated region of the fragile X mental retardation gene ( FMR1) gene is polymorphic and may become unstable on transmission to the next generation. In fragile X syndrome, CGG repeat lengths exceed 200, resulting in silencing of FMR1 and absence of its protein product, fragile X mental retardation protein (FMRP). CGG repeat lengths between 55 and 200 occur in fragile X premutation (FXPM) carriers and have a high risk of expansion to a full mutation on maternal transmission. FXPM carriers have an increased risk for developing progressive neurodegenerative syndromes and neuropsychological symptoms. FMR1 mRNA levels are elevated in FXPM, and it is thought that clinical symptoms might be caused by a toxic gain of function due to elevated FMR1 mRNA. Paradoxically, FMRP levels decrease moderately with increasing CGG repeat length in FXPM. Lowered FMRP levels may also contribute to the appearance of clinical problems. We previously reported increases in regional rates of cerebral protein synthesis (rCPS) in the absence of FMRP in an Fmr1 knockout mouse model and in a FXPM knockin (KI) mouse model with 120 to 140 CGG repeats in which FMRP levels are profoundly reduced (80%–90%). To explore whether the concentration of FMRP contributes to the rCPS changes, we measured rCPS in another FXPM KI model with a similar CGG repeat length and a 50% reduction in FMRP. In all 24 brain regions examined, rCPS were unaffected. These results suggest that even with 50% reductions in FMRP, normal protein synthesis rates are maintained.

Background: Fragile X syndrome (FXS) is the most common known inherited form of intellectual disability and the single genomic cause of autism spectrum disorders. It is caused by the absence of a fragile X mental retardation gene ( Fmr1 ) product, FMRP, an RNA-binding translation suppressor. Elevated rates of protein synthesis in the brain and an imbalance between synaptic signaling via glutamate and γ-aminobutyric acid (GABA) are both considered important in the pathogenesis of FXS. In a mouse model of FXS ( Fmr1 knockout [KO]), treatment with R-baclofen reversed some behavioral and biochemical phenotypes. A remaining crucial question is whether R-baclofen is also able to reverse increased brain protein synthesis rates. Methods: To answer this question, we measured regional rates of cerebral protein synthesis in vivo with the L-[1-14C]leucine method in vehicle- and R-baclofen–treated wildtype and Fmr1 KO mice. We further probed signaling pathways involved in the regulation of protein synthesis. Results: Acute R-baclofen administration corrected elevated protein synthesis and reduced deficits on a test of social behavior in adult Fmr1 KO mice. It also suppressed activity of the mammalian target of rapamycin pathway, particularly in synaptosome-enriched fractions, but it had no effect on extracellular-regulated kinase 1/2 activity. Ninety min after R-baclofen treatment, we observed an increase in metabotropic glutamate receptor 5 expression in the frontal cortex, a finding that may shed light on the tolerance observed in human studies with this drug. Conclusions: Our results suggest that treatment via activation of the GABA (GABA receptor subtype B) system warrants further study in patients with FXS.