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Find video protocols related to scientific articles indexed in Pubmed.
Design and evaluation of a new synthetic brain simulator for endoscopic third ventriculostomy.
J Neurosurg Pediatr
PUBLISHED: 11-01-2014
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OBJECT Endoscopic third ventriculostomy (ETV) is an effective but technically demanding procedure with significant risk. Current simulators, including human cadavers, animal models, and virtual reality systems, are expensive, relatively inaccessible, and can lack realistic sensory feedback. The purpose of this study was to construct a realistic, low-cost, reusable brain simulator for ETV and evaluate its fidelity. METHODS A brain silicone replica mimicking normal mechanical properties of a 4-month-old child with hydrocephalus was constructed, encased in the replicated skull, and immersed in water. Realistic intraventricular landmarks included the choroid plexus, veins, mammillary bodies, infundibular recess, and basilar artery. The thinned-out third ventricle floor, which dissects appropriately, is quickly replaceable. Standard neuroendoscopic equipment including irrigation is used. Bleeding scenarios are also incorporated. A total of 16 neurosurgical trainees (Postgraduate Years 1-6) and 9 pediatric and adult neurosurgeons tested the simulator. All participants filled out questionnaires (5-point Likert-type items) to rate the simulator for face and content validity. RESULTS The simulator is portable, robust, and sets up in minutes. More than 95% of participants agreed or strongly agreed that the simulator's anatomical features, tissue properties, and bleeding scenarios were a realistic representation of that seen during an ETV. Participants stated that the simulator helped develop the required hand-eye coordination and camera skills, and the training exercise was valuable. CONCLUSIONS A low-cost, reusable, silicone-based ETV simulator realistically represents the surgical procedure to trainees and neurosurgeons. It can help them develop the technical and cognitive skills for ETV including dealing with complications.
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Magnetoencephalography-guided resection of epileptogenic foci in children.
J Neurosurg Pediatr
PUBLISHED: 09-19-2014
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Object Resective surgery is increasingly used in the management of pediatric epilepsy. Frequently, invasive monitoring with subdural electrodes is required to adequately map the epileptogenic focus. The risks of invasive monitoring include the need for 2 operations, infection, and CSF leak. The aim of this study was to evaluate the feasibility and outcomes of resective epilepsy surgery guided by magnetoencephalography (MEG) in children who would have otherwise been candidates for electrode implantation. Methods The authors reviewed the records of patients undergoing resective epilepsy surgery at the Hospital for Sick Children between 2001 and 2010. They identified cases in which resections were based on MEG data and no intracranial recordings were performed. Each patient's chart was reviewed for presentation, MRI findings, MEG findings, surgical procedure, pathology, and surgical outcome. Results Sixteen patients qualified for the study. All patients had localized spike clusters on MEG and most had abnormal findings on MRI. Resection was carried out in each case based on the MEG data linked to neuronavigation and supplemented with intraoperative neuromonitoring. Overall, 62.5% of patients were seizure free following surgery, and 20% of patients experienced an improvement in seizures without attaining seizure freedom. In 2 cases, additional surgery was performed subsequently with intracranial monitoring in attempts to obtain seizure control. Conclusions MEG is a viable alternative to invasive monitoring with intracranial electrodes for planning of resective surgery in carefully selected pediatric patients with localization-related epilepsy. Good candidates for this approach include patients who have a well-delineated, localized spike cluster on MEG that is concordant with findings of other preoperative evaluations and patients with prior brain pathologies that make the implantation of subdural and depth electrodes somewhat problematic.
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Ventriculoperitoneal shunt 30-day failure rate: a retrospective international cohort study.
Neurosurgery
PUBLISHED: 09-05-2014
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With the need for transparency of surgical results, 30-day outcome measures have become increasingly important. Ventriculoperitoneal (VP) shunt failure is a substantial burden to patients and health care systems.
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Interictal high frequency oscillations correlating with seizure outcome in patients with widespread epileptic networks in tuberous sclerosis complex.
Epilepsia
PUBLISHED: 07-22-2014
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Multiple tubers in patients with tuberous sclerosis complex (TSC) often are responsible for drug-resistant epilepsy. The complexity of the epileptic network formed by multiple tubers complicates localization of the epileptogenic zone that is needed to design a surgical treatment strategy. High frequency oscillations (HFOs) on intracranial video-electroencephalography (IVEEG) may be a valuable surrogate marker for the localization of the epileptogenic zone. The purpose of this study was to test the hypothesis that high occurrence rate (OR) of interictal HFOs can guide the localization of the epileptogenic zone.
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Magnetoencephalography helps delineate the extent of the epileptogenic zone for surgical planning in children with intractable epilepsy due to porencephalic cyst/encephalomalacia.
J Neurosurg Pediatr
PUBLISHED: 07-11-2014
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Porencephalic cyst/encephalomalacia (PC/E) is a brain lesion caused by ischemic insult or hemorrhage. The authors evaluated magnetoencephalography (MEG) spike sources (MEGSS) to localize the epileptogenic zone in children with intractable epilepsy secondary to PC/E.
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Endoscopic third ventriculostomy and choroid plexus cauterization in infants with hydrocephalus: a retrospective Hydrocephalus Clinical Research Network study.
J Neurosurg Pediatr
PUBLISHED: 07-04-2014
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The use of endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC) has been advocated as an alternative to CSF shunting in infants with hydrocephalus. There are limited reports of this procedure in the North American population, however. The authors provide a retrospective review of the experience with combined ETV + CPC within the North American Hydrocephalus Clinical Research Network (HCRN).
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Pediatric awake craniotomy and intra-operative stimulation mapping.
J Clin Neurosci
PUBLISHED: 07-02-2014
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The indications for operating on lesions in or near areas of cortical eloquence balance the benefit of resection with the risk of permanent neurological deficit. In adults, awake craniotomy has become a versatile tool in tumor, epilepsy and functional neurosurgery, permitting intra-operative stimulation mapping particularly for language, sensory and motor cortical pathways. This allows for maximal tumor resection with considerable reduction in the risk of post-operative speech and motor deficits. We report our experience of awake craniotomy and cortical stimulation for epilepsy and supratentorial tumors located in and around eloquent areas in a pediatric population (n=10, five females). The presenting symptom was mainly seizures and all children had normal neurological examinations. Neuroimaging showed lesions in the left opercular (n=4) and precentral or peri-sylvian regions (n=6). Three right-sided and seven left-sided awake craniotomies were performed. Two patients had a history of prior craniotomy. All patients had intra-operative mapping for either speech or motor or both using cortical stimulation. The surgical goal for tumor patients was gross total resection, while for all epilepsy procedures, focal cortical resections were completed without any difficulty. None of the patients had permanent post-operative neurologic deficits. The patient with an epileptic focus over the speech area in the left frontal lobe had a mild word finding difficulty post-operatively but this improved progressively. Follow-up ranged from 6 to 27months. Pediatric awake craniotomy with intra-operative mapping is a precise, safe and reliable method allowing for resection of lesions in eloquent areas. Further validations on larger number of patients will be needed to verify the utility of this technique in the pediatric population.
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Factors associated with ventricular catheter movement and inaccurate catheter location: post hoc analysis of the hydrocephalus clinical research network ultrasound-guided shunt placement study.
J Neurosurg Pediatr
PUBLISHED: 06-13-2014
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Shunt survival may improve when ventricular catheters are placed into the frontal horn or trigone of the lateral ventricle. However, techniques for accurate catheter placement have not been developed. The authors recently reported a prospective study designed to test the accuracy of catheter placement with the assistance of intraoperative ultrasound, but the results were poor (accurate placement in 59%). A major reason for the poor accurate placement rate was catheter movement that occurred between the time of the intraoperative ultrasound image and the first postoperative scan (33% of cases). The control group of non-ultrasound using surgeons also had a low rate of accurate placement (accurate placement in 49%). The authors conducted an exploratory post hoc analysis of patients in their ultrasound study to identify factors associated with either catheter movement or poor catheter placement so that improved surgical techniques for catheter insertion could be developed.
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Development of a patient-specific surgical simulator for pediatric laparoscopic procedures.
Stud Health Technol Inform
PUBLISHED: 04-16-2014
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The purpose of this study is to develop and evaluate a pediatric patient-specific surgical simulator for the planning, practice, and validation of laparoscopic surgical procedures prior to intervention, initially focusing on the choledochal cyst resection and reconstruction scenario. The simulator is comprised of software elements including a deformable body physics engine, virtual surgical tools, and abdominal organs. Hardware components such as haptics-enabled hand controllers and a representative endoscopic tool have also been integrated. The prototype is able to perform a number of surgical tasks and further development work is under way to simulate the complete procedure with acceptable fidelity and accuracy.
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Differential transmembrane domain GXXXG motif pairing impacts major histocompatibility complex (MHC) class II structure.
J. Biol. Chem.
PUBLISHED: 03-11-2014
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Major histocompatibility complex (MHC) class II molecules exhibit conformational heterogeneity, which influences their ability to stimulate CD4 T cells and drive immune responses. Previous studies suggest a role for the transmembrane domain of the class II ?? heterodimer in determining molecular structure and function. Our previous studies identified an MHC class II conformer that is marked by the Ia.2 epitope. These Ia.2(+) class II conformers are lipid raft-associated and able to drive both tyrosine kinase signaling and efficient antigen presentation to CD4 T cells. Here, we establish that the Ia.2(+) I-A(k) conformer is formed early in the class II biosynthetic pathway and that differential pairing of highly conserved transmembrane domain GXXXG dimerization motifs is responsible for formation of Ia.2(+) versus Ia.2(-) I-A(k) class II conformers and controlling lipid raft partitioning. These findings provide a molecular explanation for the formation of two distinct MHC class II conformers that differ in their inherent ability to signal and drive robust T cell activation, providing new insight into the role of MHC class II in regulating antigen-presenting cell-T cell interactions critical to the initiation and control of multiple aspects of the immune response.
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Use of 3-dimensional printing technology and silicone modeling in surgical simulation: development and face validation in pediatric laparoscopic pyeloplasty.
J Surg Educ
PUBLISHED: 01-15-2014
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Pediatric laparoscopy poses unique training challenges owing to smaller workspaces, finer sutures used, and potentially more delicate tissues that require increased surgical dexterity when compared with adult analogs. We describe the development and face validation of a pediatric pyeloplasty simulator using a low-cost laparoscopic dry-laboratory model developed with 3-dimensional (3D) printing and silicone modeling.
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No significant improvement in the rate of accurate ventricular catheter location using ultrasound-guided CSF shunt insertion: a prospective, controlled study by the Hydrocephalus Clinical Research Network.
J Neurosurg Pediatr
PUBLISHED: 10-11-2013
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Object Cerebrospinal fluid shunt ventricular catheters inserted into the frontal horn or trigone are associated with prolonged shunt survival. Developing surgical techniques for accurate catheter insertion could, therefore, be beneficial to patients. This study was conducted to determine if the rate of accurate catheter location with intraoperative ultrasound guidance could exceed 80%. Methods The authors conducted a prospective, multicenter study of children (< 18 years) requiring first-time treatment for hydrocephalus with a ventriculoperitoneal shunt. Using intraoperative ultrasound, surgeons were required to target the frontal horn or trigone for catheter tip placement. An intraoperative ultrasound image was obtained at the time of catheter insertion. Ventricular catheter location, the primary outcome measure, was determined from the first postoperative image. A control group of patients treated by nonultrasound surgeons (conventional surgeons) were enrolled using the same study criteria. Conventional shunt surgeons also agreed to target the frontal horn or trigone for all catheter insertions. Patients were triaged to participating surgeons based on call schedules at each center. A pediatric neuroradiologist blinded to method of insertion, center, and surgeon determined ventricular catheter tip location. Results Eleven surgeons enrolled as ultrasound surgeons and 6 as conventional surgeons. Between February 2009 and February 2010, 121 patients were enrolled at 4 Hydrocephalus Clinical Research Network centers. Experienced ultrasound surgeons (> 15 cases prior to study) operated on 67 patients; conventional surgeons operated on 52 patients. Experienced ultrasound surgeons achieved accurate catheter location in 39 (59%) of 66 patients, 95% CI (46%-71%). Intraoperative ultrasound images were compared with postoperative scans. In 32.7% of cases, the catheter tip moved from an accurate location on the intraoperative ultrasound image to an inaccurate location on the postoperative study. This was the most significant factor affecting accuracy. In comparison, conventional surgeons achieved accurate location in 24 (49.0%) of 49 cases (95% CI [34%-64%]). The shunt survival rate at 1 year was 70.8% in the experienced ultrasound group and 66.9% in the conventional group (p = 0.66). Ultrasound surgeons had more catheters surrounded by CSF (30.8% vs 6.1%, p = 0.0012) and away from the choroid plexus (72.3% vs 58.3%, p = 0.12), and fewer catheters in the brain (3% vs 22.4%, p = 0.0011) and crossing the midline (4.5% vs 34.7%, p < 0.001), but they had a higher proportion of postoperative pseudomeningocele (10.1% vs 3.8%, p = 0.30), wound dehiscence (5.8% vs 0%, p = 0.13), CSF leak (10.1% vs 1.9%, p = 0.14), and shunt infection (11.6% vs 5.8%, p = 0.35). Conclusions Ultrasound-guided shunt insertion as performed in this study was unable to consistently place catheters into the frontal horn or trigone. The technique is safe and achieves outcomes similar to other conventional shunt insertion techniques. Further efforts to improve accurate catheter location should focus on prevention of catheter migration that occurs between intraoperative placement and postoperative imaging. Clinical trial registration no.: NCT01007786 ( ClinicalTrials.gov ).
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NOTES suction grasper for tubular viscera - characterization of gripping force when varying hole size, diameter, and number.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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This paper details the design and characterization of a novel suction grasper for Natural Orifice Transesophageal Surgery (NOTES). Axial gripping force was optimized by changing hole size, number, and spacing. A 10 kg pig and a rabbit esophagus were used to simulate a neonatal esophagus. Maximum axial forces of up to 7.2 N were achieved. Hole pattern spacing had little to no impact on force while suction area was very significant. Additionally, there was a preference for a greater number of holes versus larger holes for relatively large hole sizes. Lastly, smaller holes resulted in smoother loss of gripping force when beyond maximum holding force was applied.
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Outcomes of CSF shunting in children: comparison of Hydrocephalus Clinical Research Network cohort with historical controls: clinical article.
J Neurosurg Pediatr
PUBLISHED: 08-02-2013
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The Hydrocephalus Clinical Research Network (HCRN), which comprises 7 pediatric neurosurgical centers in North America, provides a unique multicenter assessment of the current outcomes of CSF shunting in nonselected patients. The authors present the initial results for this cohort and compare them with results from prospective multicenter trials performed in the 1990s.
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Fc?R-driven release of IL-6 by macrophages requires NOX2-dependent production of reactive oxygen species.
J. Biol. Chem.
PUBLISHED: 07-15-2013
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Activation of the Fc?R via antigen containing immune complexes can lead to the generation of reactive oxygen species, which are potent signal transducing molecules. However, whether ROS contribute to Fc?R signaling has not been studied extensively. We set out to elucidate the role of NADPH oxidase-generated ROS in macrophage activation following Fc?R engagement using antigen-containing immune complexes. We hypothesized that NOX2 generated ROS is necessary for propagation of downstream Fc?R signaling and initiation of the innate immune response. Following exposure of murine bone marrow-derived macrophages (BMDMs) to inactivated Francisella tularensis (iFt)-containing immune complexes, we observed a significant increase in the innate inflammatory cytokine IL-6 at 24 h compared with macrophages treated with Ft LVS-containing immune complexes. Ligation of the Fc?R by opsonized Ft also results in significant ROS production. Macrophages lacking the gp91(phox) subunit of NOX2 fail to produce ROS upon Fc?R ligation, resulting in decreased Akt phosphorylation and a reduction in the levels of IL-6 compared with wild type macrophages. Similar results were seen following infection of BMDMs with catalase deficient Ft that fail to scavenge hydrogen peroxide. In conclusion, our findings demonstrate that ROS participate in elicitation of an effective innate immune in response to antigen-containing immune complexes through Fc?R.
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Major histocompatibility complex (MHC) class II-peptide complexes arrive at the plasma membrane in cholesterol-rich microclusters.
J. Biol. Chem.
PUBLISHED: 03-26-2013
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Antigen-specific CD4 T cells are activated by small numbers of antigenic peptide-MHC class II (pMHC-II) complexes on dendritic cells (DCs).
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Access to surgery for paediatric patients with medically refractory epilepsy: A systems analysis.
Epilepsy Res.
PUBLISHED: 03-07-2013
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A systems analysis perspective was undertaken to evaluate access to surgery for children with medically refractory epilepsy (MRE) in Ontario, the largest province in Canada. The analysis focused on the assessment of referral patterns, healthcare utilization, time intervals and patient flow to determine surgical candidacy in children with MRE. The purpose of this systems analysis study was to identify rate limiting steps that may lead to delayed surgical candidacy decision and surgery.
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Neurosurgical management of neurenteric cysts in children.
J Neurosurg Pediatr
PUBLISHED: 03-01-2013
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Neurenteric cysts (NCs) are endothelium-lined structures of presumed endodermal origin. There have been few pediatric series of intracranial NCs reported previously. The authors present their experience in the management of these lesions.
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Nanotechnology in corneal neovascularization therapy--a review.
J Ocul Pharmacol Ther
PUBLISHED: 02-20-2013
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Nanotechnology is an up-and-coming branch of science that studies and designs materials with at least one dimension sized from 1-100 nm. These nanomaterials have unique functions at the cellular, atomic, and molecular levels. The term "nanotechnology" was first coined in 1974. Since then, it has evolved dramatically and now consists of distinct and independent scientific fields. Nanotechnology is a highly studied topic of interest, as nanoparticles can be applied to various fields ranging from medicine and pharmacology, to chemistry and agriculture, to environmental science and consumer goods. The rapidly evolving field of nanomedicine incorporates nanotechnology with medical applications, seeking to give rise to new diagnostic means, treatments, and tools. Over the past two decades, numerous studies that underscore the successful fusion of nanotechnology with novel medical applications have emerged. This has given rise to promising new therapies for a variety of diseases, especially cancer. It is becoming abundantly clear that nanotechnology has found a place in the medical field by providing new and more efficient ways to deliver treatment. Ophthalmology can also stand to benefit significantly from the advances in nanotechnology research. As it relates to the eye, research in the nanomedicine field has been particularly focused on developing various treatments to prevent and/or reduce corneal neovascularization among other ophthalmologic disorders. This review article aims to provide an overview of corneal neovascularization, currently available treatments, and where nanotechnology comes into play.
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Nonhybrid, finished microbial genome assemblies from long-read SMRT sequencing data.
Nat. Methods
PUBLISHED: 01-31-2013
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We present a hierarchical genome-assembly process (HGAP) for high-quality de novo microbial genome assemblies using only a single, long-insert shotgun DNA library in conjunction with Single Molecule, Real-Time (SMRT) DNA sequencing. Our method uses the longest reads as seeds to recruit all other reads for construction of highly accurate preassembled reads through a directed acyclic graph-based consensus procedure, which we follow with assembly using off-the-shelf long-read assemblers. In contrast to hybrid approaches, HGAP does not require highly accurate raw reads for error correction. We demonstrate efficient genome assembly for several microorganisms using as few as three SMRT Cell zero-mode waveguide arrays of sequencing and for BACs using just one SMRT Cell. Long repeat regions can be successfully resolved with this workflow. We also describe a consensus algorithm that incorporates SMRT sequencing primary quality values to produce de novo genome sequence exceeding 99.999% accuracy.
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Cis and trans regulatory mechanisms control AP2-mediated B cell receptor endocytosis via select tyrosine-based motifs.
PLoS ONE
PUBLISHED: 01-23-2013
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Following antigen recognition, B cell receptor (BCR)-mediated endocytosis is the first step of antigen processing and presentation to CD4+ T cells, a crucial component of the initiation and control of the humoral immune response. Despite this, the molecular mechanism of BCR internalization is poorly understood. Recently, studies of activated B cell-like diffuse large B cell lymphoma (ABC DLBCL) have shown that mutations within the BCR subunit CD79b leads to increased BCR surface expression, suggesting that CD79b may control BCR internalization. Adaptor protein 2 (AP2) is the major mediator of receptor endocytosis via clathrin-coated pits. The BCR contains five putative AP2-binding YxxØ motifs, including four that are present within two immunoreceptor tyrosine-based activation motifs (ITAMs). Using a combination of in vitro and in situ approaches, we establish that the sole mediator of AP2-dependent BCR internalization is the membrane proximal ITAM YxxØ motif in CD79b, which is a major target of mutation in ABC DLBCL. In addition, we establish that BCR internalization can be regulated at a minimum of two different levels: regulation of YxxØ AP2 binding in cis by downstream ITAM-embedded DCSM and QTAT regulatory elements and regulation in trans by the partner cytoplasmic domain of the CD79 heterodimer. Beyond establishing the basic rules governing BCR internalization, these results illustrate an underappreciated role for ITAM residues in controlling clathrin-dependent endocytosis and highlight the complex mechanisms that control the activity of AP2 binding motifs in this receptor system.
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Surgical outcomes in craniosynostosis reconstruction: The use of prefabricated templates in cranial vault remodelling.
J Plast Reconstr Aesthet Surg
PUBLISHED: 01-03-2013
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Cranio-orbital reshaping for anterior cranial-vault deformities associated with craniosynostosis traditionally relies on the surgeons subjective estimate of the shape and appearance of a normal forehead. Computer-aided design/computer-aided manufacture (CAD/CAM) bandeau templates to guide reconstruction were introduced in our centre to eliminate this subjectivity and to effect more reproducible surgical results. The aim of this study was to compare two groups of patients (template, n = 14 vs. no template, n = 23) to measure surgical outcomes. The virtual, computational version of the template was used as an outcome assessment tool. It was used to calculate an intervening area under the curve (AUC) between the normative template and the patients reconstructed supra-orbital bar on a representative computed tomography (CT) axial section. A comprehensive chart review was conducted of patients in both groups to examine the preoperative and postoperative variables. Based on the analysis performed on the immediate postoperative CT scans, in the template group - as compared to the control, no-template group - the use of the bandeau template led to a greater reduction in AUC (74% vs. 56%, p = 0.016), indicating a better conformity between the reconstructed supra-orbital bar and the ideal, normal bandeau shape. The duration of operation was significantly reduced with the use of the template (212 vs. 258 min, p < 0.001). The application of prefabricated templates in cranio-orbital reshaping is highly useful for accurate preoperative planning; reproducible and efficient intra-operative correction of dysmorphology; and objective surgical outcomes assessment.
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Pre- and post-shunting observations in adult sheep with kaolin-induced hydrocephalus.
Fluids Barriers CNS
PUBLISHED: 01-01-2013
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The objective of this study was to examine host-shunt interactions in sheep with kaolin-induced hydrocephalus.
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Hydrocephalus status in spina bifida: an evaluation of variations in neuropsychological outcomes.
J Neurosurg Pediatr
PUBLISHED: 09-03-2011
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The effect of hydrocephalus status on neuropsychological outcomes in children with spina bifida (SB) has not been carefully evaluated. The authors hypothesized a stepwise progression of outcomes related to hydrocephalus status (shunt-treated, arrested, or no hydrocephalus) and that motor, spatial, and executive function tasks would be more sensitive to hydrocephalus status than vocabulary and reading tasks.
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Focal resection of fast ripples on extraoperative intracranial EEG improves seizure outcome in pediatric epilepsy.
Epilepsia
PUBLISHED: 07-29-2011
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High-frequency oscillations (HFOs), termed ripples at 80-200 Hz and fast ripples (FRs) at >200/250 Hz, recorded by intracranial electroencephalography (EEG), may be a valuable surrogate marker for the localization of the epileptogenic zone. We evaluated the relationship of the resection of focal brain regions containing high-rate interictal HFOs and the seizure-onset zone (SOZ) determined by visual EEG analysis with the postsurgical seizure outcome, using extraoperative intracranial EEG monitoring in pediatric patients and automated HFO detection.
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Lateralized interictal epileptiform discharges during rapid eye movement sleep correlate with epileptogenic hemisphere in children with intractable epilepsy secondary to tuberous sclerosis complex.
Epilepsia
PUBLISHED: 07-29-2011
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We assessed lateralization of interictal epileptiform discharges (IEDs) in children with intractable epilepsy secondary to tuberous sclerosis complexes (TSCs) during rapid eye movement sleep (R), compared with non-rapid eye movement sleep (NR) and wakefulness (W), to determine epileptogenicity of R-IEDs.
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A standardized protocol to reduce cerebrospinal fluid shunt infection: the Hydrocephalus Clinical Research Network Quality Improvement Initiative.
J Neurosurg Pediatr
PUBLISHED: 07-05-2011
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Quality improvement techniques are being implemented in many areas of medicine. In an effort to reduce the ventriculoperitoneal shunt infection rate, a standardized protocol was developed and implemented at 4 centers of the Hydrocephalus Clinical Research Network (HCRN).
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Ethical issues in surgical decision making concerning children with medically intractable epilepsy.
Epilepsy Behav
PUBLISHED: 06-20-2011
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The widespread inclusion of surgical strategies in the treatment of medically intractable epilepsy is largely justified by the medical and psychosocial burden of the illness. Performing these procedures in pediatric populations is associated with distinct challenges ranging from unique seizure etiologies to issues surrounding brain development and functional plasticity. As the trend toward more aggressive surgical intervention continues, the ethical foundation of current and emerging practices must be increasingly scrutinized. Here, we present the first article discussing ethical issues in the surgical management of medically intractable epilepsies in children. We discuss principles of informed consent, harm reduction, and justice in this vulnerable patient population. We also highlight the unique ethical challenge of surgical decision making concerning developmentally delayed children. The recognition of these issues is essential to providing patient-centered, responsible, and ethical care.
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The Ia.2 epitope defines a subset of lipid raft-resident MHC class II molecules crucial to effective antigen presentation.
J. Immunol.
PUBLISHED: 05-04-2011
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Previous work established that binding of the 11-5.2 anti-I-A(k) mAb, which recognizes the Ia.2 epitope on I-A(k) class II molecules, elicits MHC class II signaling, whereas binding of two other anti-I-A(k) mAbs that recognize the Ia.17 epitope fail to elicit signaling. Using a biochemical approach, we establish that the Ia.2 epitope recognized by the widely used 11-5.2 mAb defines a subset of cell surface I-A(k) molecules predominantly found within membrane lipid rafts. Functional studies demonstrate that the Ia.2-bearing subset of I-A(k) class II molecules is critically necessary for effective B cell-T cell interactions, especially at low Ag doses, a finding consistent with published studies on the role of raft-resident class II molecules in CD4 T cell activation. Interestingly, B cells expressing recombinant I-A(k) class II molecules possessing a ?-chain-tethered hen egg lysosome peptide lack the Ia.2 epitope and fail to partition into lipid rafts. Moreover, cells expressing Ia.2(-) tethered peptide-class II molecules are severely impaired in their ability to present both tethered peptide or peptide derived from exogenous Ag to CD4 T cells. These results establish the Ia.2 epitope as defining a lipid raft-resident MHC class II conformer vital to the initiation of MHC class II-restricted B cell-T cell interactions.
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Neurosurgical management of extraaxial central nervous system infections in children.
J Neurosurg Pediatr
PUBLISHED: 05-03-2011
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Extraaxial infections of the CNS, including subdural empyema and epidural abscess, are rare but potentially life-threatening conditions. Symptoms are usually progressive, and early diagnosis is therefore important. Early intervention with appropriate treatment offers the best opportunity for eradicating the infection and promoting maximal neurological recovery.
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High kurtosis of intracranial electroencephalogram as a marker of ictogenicity in pediatric epilepsy surgery.
Clin Neurophysiol
PUBLISHED: 03-21-2011
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We determined whether kurtosis analysis of intracranial electroencephalogram (EEG) can estimate the localization of the epileptogenic zone.
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Topographic movie of intracranial ictal high-frequency oscillations with seizure semiology: epileptic network in Jacksonian seizures.
Epilepsia
PUBLISHED: 11-10-2010
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We developed a technique to produce images of dynamic changes in ictal high-frequency oscillations (HFOs) >40 Hz recorded on subdural electroencephalography (EEG) that are time-locked to the ictal EEG and ictal semiology video. We applied this technique to Jacksonian seizures to demonstrate ictal HFO propagation along the homunculus in the primary sensory-motor cortex to visualize the underlying epileptic network.
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Intraoperative angiography during microsurgical removal of arteriovenous malformations in children.
J Neurosurg Pediatr
PUBLISHED: 11-03-2010
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Confirming the successful management of pediatric arteriovenous malformations (AVMs) requires high-quality postoperative digital subtraction angiography. Although the role of intraoperative angiography during the microsurgical removal of AVMs is well established in adults, the technique has several limitations including poor image quality, uniplanar image acquisition, and absent full heparin protection. Here, the authors report on their experience with high-quality intraoperative angiography during the surgical management of pediatric AVMs in their image-guided therapy (IGT) facility.
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Predicting who will benefit from endoscopic third ventriculostomy compared with shunt insertion in childhood hydrocephalus using the ETV Success Score.
J Neurosurg Pediatr
PUBLISHED: 10-05-2010
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The authors recently developed and internally validated the ETV Success Score (ETVSS)--a simplified means of predicting the 6-month success rate of endoscopic third ventriculostomy (ETV) for a child with hydrocephalus, based on age, etiology of hydrocephalus, and presence of a previous shunt. A high ETVSS predicts a high chance of early ETV success. In this paper, they assess the clinical utility of the ETVSS by determining whether long-term survival outcomes for ETV versus shunt insertion are different within strata of ETVSS (low, moderate, and high scores).
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Physiological-range temperature changes modulate cognate antigen processing and presentation mediated by lipid raft-restricted ubiquitinated B cell receptor molecules.
J. Immunol.
PUBLISHED: 09-24-2010
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BCR-mediated Ag processing and presentation is critical to the initiation and control of a humoral immune response. Trafficking of internalized Ag-BCR complexes to intracellular Ag processing compartments is driven by ubiquitination of the cytoplasmic domain of the BCR. Using a biochemical approach, it is here established that ubiquitinated Ag-BCR complexes are formed via a signaling-dependent mechanism and restricted to plasma membrane lipid rafts. Because the structure of lipid rafts is temperature sensitive, the impact of physiological-range temperature changes (PRTCs; 33-39°C) on lipid raft-dependent and -independent BCR functions was investigated. Whereas the kinetics of lipid raft-independent BCR internalization is unaffected by temperature changes within this range, raft-dependent BCR signaling and ubiquitination as well as BCR-mediated Ag processing are significantly affected. The extent and duration of Ag-BCR ubiquitination is increased and prolonged at 37-39°C (normal to febrile temperature) compared with that at 33°C (peripheral body temperature). As might be expected, increased temperature also accelerates the overall kinetics of Ag-BCR degradation. Notably, at 33°C the expression of peptide-MHC class II complexes derived from the BCR-mediated processing of cognate Ag is profoundly slowed, whereas the kinetics of expression of peptide-MHC class II complexes derived from fluid-phase Ag processing remains unchanged. These results establish the effect of PRTCs on multiple lipid raft-dependent BCR functions including the processing and presentation of cognate Ag, suggesting one mechanism by which PRTCs, such as fever, may impact the initiation and/or maturation of a humoral immune response.
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Endoscopic third ventriculostomy vs cerebrospinal fluid shunt in the treatment of hydrocephalus in children: a propensity score-adjusted analysis.
Neurosurgery
PUBLISHED: 07-22-2010
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Endoscopic third ventriculostomy (ETV) has preferentially been offered to patients with more favorable prognostic features compared with shunt.
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Prospective surveillance of complications in a pediatric neurosurgery unit.
J Neurosurg Pediatr
PUBLISHED: 06-03-2010
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Complications of specific pediatric neurosurgical procedures are well recognized. However, focused surveillance on a specific neurosurgical unit, for all procedures, may lead to better understanding of the most important complications, and allow targeted strategies for quality improvement.
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Ventriculocystostomy and endoscopic third ventriculostomy/shunt placement in the management of hydrocephalus secondary to giant retrocerebellar cysts in infancy.
J Neurosurg Pediatr
PUBLISHED: 04-07-2010
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Hydrocephalus secondary to giant retrocerebellar cysts in infancy is a challenging condition and many treatment options exist. The authors report on 3 consecutive cases involving infants under the age of 6 months treated successfully with ventriculocystostomy in combination with direct hydrocephalus treatment (endoscopic third ventriculostomy or shunt placement). They describe the operative procedure, the surgical morbidity, and outcome in each case and review the literature regarding surgical approaches to this condition.
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Do baclofen pumps influence the development of scoliosis in children?
J Neurosurg Pediatr
PUBLISHED: 02-04-2010
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Intrathecal baclofen is an effective treatment for spasticity in patients with cerebral palsy. There has been increasing concern, however, that intrathecal baclofen may accelerate the development of scoliosis in this population. To this end, the authors reviewed their population of pediatric patients with baclofen pumps to assess the incidence of scoliosis.
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Palmitic Acid Is a Novel CD4 Fusion Inhibitor That Blocks HIV Entry and Infection.
AIDS Res. Hum. Retroviruses
PUBLISHED: 12-17-2009
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The high rate of HIV-1 mutation and the frequent sexual transmission highlight the need for novel therapeutic modalities with broad activity against both CXCR4 (X4) and CCR5 (R5)-tropic viruses. We investigated a large number of natural products, and from Sargassum fusiforme we isolated and identified palmitic acid (PA) as a natural small bioactive molecule with activity against HIV-1 infection. Treatment with 100 microM PA inhibited both X4 and R5 independent infection in the T cell line up to 70%. Treatment with 22 microM PA inhibited X4 infection in primary peripheral blood lymphocytes (PBL) up to 95% and 100 microM PA inhibited R5 infection in primary macrophages by over 90%. Inhibition of infection was concentration dependent, and cell viability for all treatments tested remained above 80%, similar to treatment with 10(-6)M nucleoside analogue 2, 3-dideoxycytidine (ddC). Micromolar PA concentrations also inhibited cell-to-cell fusion and specific virus-to-cell fusion up to 62%. PA treatment did not result in internalization of the cell surface CD4 receptor or lipid raft disruption, and it did not inhibit intracellular virus replication. PA directly inhibited gp120-CD4 complex formation in a dose-dependent manner. We used fluorescence spectroscopy to determine that PA binds to the CD4 receptor with K(d) approximately 1.5 +/- 0.2 microM, and we used one-dimensional saturation transfer difference NMR (STD-NMR) to determined that the PA binding epitope for CD4 consists of the hydrophobic methyl and methelene groups located away from the PA carboxyl terminal, which blocks efficient gp120-CD4 attachment. These findings introduce a novel class of antiviral compound that binds directly to the CD4 receptor, blocking HIV-1 entry and infection. Understanding the structure-affinity relationship (SAR) between PA and CD4 should lead to the development of PA analogs with greater potency against HIV-1 entry.
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Localization of epileptic foci in children with intractable epilepsy secondary to multiple cortical tubers by using synthetic aperture magnetometry kurtosis.
J Neurosurg Pediatr
PUBLISHED: 12-03-2009
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Magnetoencephalography (MEG) has been typically used to localize epileptic activity by modeling interictal activity as equivalent current dipoles (ECDs). Synthetic aperture magnetometry (SAM) is a recently developed adaptive spatial filtering algorithm for MEG that provides some advantages over the ECD approach. The SAM-kurtosis algorithm (also known as SAM[g2]) additionally provides automated temporal detection of spike sources by using excess kurtosis value (steepness of epileptic spike on virtual sensors). To evaluate the efficacy of the SAM(g2) method, the authors applied it to readings obtained in children with intractable epilepsy secondary to tuberous sclerosis complex (TSC), and compared them to localizations obtained with ECDs.
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Management of pediatric brainstem cavernous malformations: experience over 20 years at the hospital for sick children.
J Neurosurg Pediatr
PUBLISHED: 11-03-2009
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Because of their location and biological behavior, brainstem cavernous malformations (CMs) pose a formidable clinical challenge to the neurosurgeon. The optimal management of these lesions requires considerable neurosurgical judgment. Accordingly, the authors reviewed their experience with the management of pediatric brainstem CMs at the Hospital for Sick Children.
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Management of osteoblastoma and osteoid osteoma of the spine in childhood.
J Neurosurg Pediatr
PUBLISHED: 11-03-2009
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Osteoid osteomas and osteoblastoma of the spine are rare lesions in childhood, and management strategies have changed. The authors reviewed their recent experience with these 2 types of lesions to elucidate current treatment modalities and outcomes.
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Neurosurgical implications of achondroplasia.
J Neurosurg Pediatr
PUBLISHED: 10-03-2009
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Achondroplasia is the most common form of human short-limbed dwarfism. The pediatric neurosurgeon is frequently required to treat children with achondroplasia who have hydrocephalus, cervicomedullary compression (CMD), and spinal canal stenosis. Accordingly, the authors have reviewed the experience of neurosurgery in children with achondroplasia at The Hospital for Sick Children.
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Technique for drilling instrument monitoring electrical conductivity in pediatric cervical spine screw insertion: a preliminary report.
J Pediatr Orthop
PUBLISHED: 09-29-2009
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To detail a technique of assisted screw placement in pediatric patients with cervical spine disorders. The use of a recently produced wireless electronic freehand drilling instrument is documented.
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Neurosurgical management of intractable rolandic epilepsy in children: role of resection in eloquent cortex. Clinical article.
J Neurosurg Pediatr
PUBLISHED: 09-24-2009
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The authors undertook this study to review their experience with cortical resections in the rolandic region in children with intractable epilepsy.
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Francisella tularensis induces ubiquitin-dependent major histocompatibility complex class II degradation in activated macrophages.
Infect. Immun.
PUBLISHED: 08-24-2009
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The intracellular bacterium Francisella tularensis survives and replicates within macrophages, ultimately killing the host cell. Resolution of infection requires the development of adaptive immunity through presentation of F. tularensis antigens to CD4+ and CD8+ T cells. We have previously established that F. tularensis induces macrophage prostaglandin E2 (PGE2) production, leading to skewed T-cell responses. PGE2 can also downregulate macrophage major histocompatibility complex (MHC) class II expression, suggesting that F. tularensis-elicited PGE2 may further alter T-cell responses via inhibition of class II expression. To test this hypothesis, gamma interferon (IFN-gamma)-activated reporter macrophages were exposed to supernatants from F. tularensis-infected macrophages, and the class II levels were measured. Exposure of macrophages to infection supernatants results in essentially complete clearance of surface class II and CD86, compromising the macrophages ability to present antigens to CD4 T cells. Biochemical analysis revealed that infection supernatants elicit ubiquitin-dependent class II downregulation and degradation within intracellular acidic compartments. By comparison, exposure to PGE2 alone only leads to a minor decrease in macrophage class II expression, demonstrating that a factor distinct from PGE2 is eliciting the majority of class II degradation. However, production of this non-PGE2 factor is dependent on macrophage cyclooxygenase activity and is induced by PGE2. These results establish that F. tularensis induces the production of a PGE2-dependent factor that elicits MHC class II downregulation in IFN-gamma-activated macrophages through ubiquitin-mediated delivery of class II to lysosomes, establishing another mechanism for the modulation of macrophage antigen presentation during F. tularensis infection.
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Neurosurgical management of intracranial epidermoid tumors in children. Clinical article.
J Neurosurg Pediatr
PUBLISHED: 08-04-2009
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Epidermoid tumors are benign lesions representing 1% of all intracranial tumors. There have been few pediatric series of intracranial epidermoid tumors reported previously. The authors present their experience in the management of these lesions.
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A multicenter retrospective comparison of conversion from temporary to permanent cerebrospinal fluid diversion in very low birth weight infants with posthemorrhagic hydrocephalus.
J Neurosurg Pediatr
PUBLISHED: 07-03-2009
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The purpose of this study was to define the incidence of permanent shunt placement and infection in patients who have undergone the 2 most commonly performed temporizing procedures for posthemorrhagic hydrocephalus (PHH) of prematurity: ventriculosubgaleal (VSG) shunt placement and ventricular reservoir placement for intermittent tapping.
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Predicting postresection hydrocephalus in pediatric patients with posterior fossa tumors.
J Neurosurg Pediatr
PUBLISHED: 05-05-2009
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Approximately 30% of children with posterior fossa tumors exhibit hydrocephalus after tumor resection. Recent literature has suggested that prophylactic endoscopic third ventriculostomy diminishes the risk of this event. Because the majority of patients will not have postoperative hydrocephalus, a preoperative clinical prediction rule that identifies patients at high or low risk for postresection hydrocephalus would be helpful to optimize the care of these children.
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Use of axial and subaxial translaminar screw fixation in the management of upper cervical spinal instability in a series of 7 children.
Neurosurgery
PUBLISHED: 04-08-2009
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The management of upper cervical spinal instability in children continues to represent a technical challenge. Traditionally, a number of wiring techniques followed by halo orthosis have been applied; however, they have been associated with a high rate of nonunion and poor tolerance for the halo. Alternatively, C1-C2 transarticular screws and C2 pars/pedicle screws allow more rigid fixation, but they are technically demanding and associated with vertebral artery injuries. Recently, C2 translaminar screws have been added to the armamentarium of the pediatric spine surgeon as a technically simple and biomechanically efficient method of fixation. However, subaxial translaminar screws have not been described in the pediatric population. We describe our experience with axial and subaxial translaminar screws in 7 pediatric patients.
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Patient with postcentral gyrectomy demonstrates reliable localization of hand motor area using magnetoencephalography.
Pediatr Neurosurg
PUBLISHED: 03-03-2009
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Magnetoencephalography (MEG) data analyzed with novel spatial filtering methods, namely event-related beamforming (ERB), have shown success in localizing hand motor areas in healthy adults and in a group of pediatric patients with peri-Rolandic tumors. The validity of this method to localize the primary motor field in a pediatric tumor case was confirmed by intraoperative direct cortical stimulation. Currently, the reliability of this method has not been demonstrated. We report on a 16-year-old boy with localization-related epilepsy originating from his right hemisphere sensory cortex. Hand motor and sensory areas were identified preoperatively by ERB analysis of MEG data. The patient underwent invasive monitoring which localized the epileptic focus to right postcentral gyrus, immediately posterior to the MEG motor area and adjacent to the MEG sensory area. The patient received a gyrectomy of sensory cortex guided by intraoperative direct cortical stimulation to ensure sparing of hand motor cortex. Replication of the MEG motor mapping protocol postoperatively demonstrated reliable localization of the motor and sensory areas. We also discuss caveats for future applications of this protocol.
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Presurgical localization of primary motor cortex in pediatric patients with brain lesions by the use of spatially filtered magnetoencephalography.
Neurosurgery
PUBLISHED: 02-26-2009
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The objective of this study was to confirm the efficacy of spatially filtered magnetoencephalography for the preoperative localization of primary motor cortex in pediatric patients with focal lesions in the region of the sensorimotor cortex.
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Endoscopic third ventriculostomy in the treatment of childhood hydrocephalus.
J. Pediatr.
PUBLISHED: 02-25-2009
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To develop a model to predict the probability of endoscopic third ventriculostomy (ETV) success in the treatment for hydrocephalus on the basis of a childs individual characteristics.
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A new porcine skull base model: fibrin glue improves strength of cerebrospinal fluid leak repairs.
Otolaryngol Head Neck Surg
PUBLISHED: 01-14-2009
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Fibrin glue is used in addition to grafts and flaps to repair cerebrospinal (CSF) leaks. We designed a porcine model to test the hypothesis that fibrin glue increases biomechanical strength.
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Interictal epileptogenic fast oscillations on neonatal and infantile EEGs in hemimegalencephaly.
Epilepsy Res.
PUBLISHED: 01-03-2009
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Hemimegalencephaly is an epileptic encephalopathy which presents during the neonatal period. Our aims are to analyze interictal fast oscillations and EEG patterns in neonates and infants with hemimegalencephaly.
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3D curve constrained deformable registration using a neuro-fuzzy transformation model.
Conf Proc IEEE Eng Med Biol Soc
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Image registration of abdominal organs and soft tissues is considered daunting due to large organ shift and tissue deformation caused by patient motion, respiration, etc. In this study, we propose a novel neuro-fuzzy deformable registration technique that is constrained by 3D curves of vessel centerlines and point marks while minimizing strain energy. We present an analytical global optimal solution in the case when 3D curves, strain energy and point marks are considered, which will provide fast and robust deformable match for internal structures such as blood vessels, and significantly reduce the chance to get trapped in local minima. We have demonstrated the effectiveness of our deformable technique in registering liver MR images. Validation shows a target registration error of 1.98 mm and an average centerline distance error of 1.65 mm. This technique has the potential to significantly improve registration capability and the quality of intra-operative image guidance.
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Extraction of liver vessel centerlines under guidance of patient-specific models.
Conf Proc IEEE Eng Med Biol Soc
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Fast extraction of blood vessels of abdominal organs is still a challenging task especially in intra-procedural treatments due to large tissue deformation. In this study, we propose a novel joint vessel extraction and registration framework. This vessel extraction technique is under the guidance of prior knowledge patient specific models. The proposed technique automatically provides correspondence between extracted vessels and pre-procedural vessels, which is important for image guidance such as labeled vessels from pre-procedural models, improves the quality of disease diagnosis using multiple images and follow-up, and provides important information for nonrigid image registration. Another key component in our framework is to dynamically update mapped pre-procedural models by rapidly registering the patient model to the current image based on strain energy, point marks and 3D extracted vessels currently available. We have demonstrated the effectiveness of our technique in extraction of vessels from liver MR images. Validation shows a extraction error of 3.99 mm. This technique has the potential to significantly improve the quality of intra-procedural image guidance, diagnosis of disease and treatment planning.
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Multiple mechanisms mediate enhanced immunity generated by mAb-inactivated F. tularensis immunogen.
Immunol. Cell Biol.
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We have previously demonstrated that immunization with the inactivated Francisella tularensis, a Category A intracellular mucosal pathogen, combined with IgG2a anti-F. tularensis monoclonal antibody (Ab), enhances protection against subsequent F. tularensis challenge. To understand the mechanism(s) involved, we examined the binding, internalization, presentation, and in vivo trafficking of inactivated F. tularensis in the presence and absence of opsonizing monoclonal Ab. We found that when inactivated F. tularensis is combined with anti-F. tularensis monoclonal Ab, presentation to F. tularensis-specific T cells is enhanced. This enhancement is Fc receptor (FcR)-dependent, and requires a physical linkage between the monoclonal Ab and the inactivated F. tularensis immunogen. This enhanced presentation is due, in part, to enhanced binding and internalization of inactivated F. tularensis by antigen(Ag)-presenting cells, and involves interactions with multiple FcR types. Furthermore, targeting inactivated F. tularensis to FcRs enhances dendritic cell maturation and extends the time period over which Ag-presenting cells stimulate T cells. In vivo trafficking studies reveal enhanced transport of inactivated F. tularensis immunogen to the nasal-associated lymphoid tissue in the presence of monoclonal Ab, which is FcRn-dependent. In summary, these are the first comprehensive studies using a single-vaccine protection model/immunogen to establish the array of mechanisms involved in enhanced immunity/protection mediated by an FcR-targeted mucosal immunogen. These results demonstrate that multiple cellular/immune mechanisms contribute to FcR-enhanced immunity.
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Needs assessment for simulation training in neuroendoscopy: a Canadian national survey.
J. Neurosurg.
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In recent years, dramatic changes in surgical education have increased interest in simulation-based training for complex surgical skills. This is particularly true for endoscopic third ventriculostomy (ETV), given the potential for serious intraoperative errors arising from surgical inexperience. However, prior to simulator development, a thorough assessment of training needs is essential to ensure development of educationally relevant platforms. The purpose of this study was to conduct a national needs assessment addressing specific goals of instruction, to guide development of simulation platforms, training curricula, and assessment metrics for ETV.
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The use of high frequency oscillations to guide neocortical resections in children with medically-intractable epilepsy: how do we ethically apply surgical innovations to patient care?
Seizure
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Resective surgical strategies are increasingly applied to treat medically-intractable epilepsy in children as uncontrolled seizures are associated with poor cognitive, developmental and behavioral outcomes. Innovative surgical strategies are, however, needed to improve outcomes and minimize the morbidity of such procedures.
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Neurosurgical management of frontal lobe epilepsy in children.
J Neurosurg Pediatr
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Pediatric frontal lobe epilepsy (FLE) remains a challenging condition for neurosurgeons and epileptologists to manage. Postoperative seizure outcomes remain far inferior to those observed in temporal lobe epilepsies, possibly due to inherent difficulties in delineating and subsequently completely resecting responsible epileptogenic regions. In this study, the authors review their institutional experience with the surgical management of FLE and attempt to find predictors that may help to improve seizure outcome in this population.
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Consensus definitions of complications for accurate recording and comparisons of surgical outcomes in pediatric neurosurgery.
J Neurosurg Pediatr
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Monitoring and recording of complications in pediatric neurosurgery are important for quality assurance and in particular for improving outcomes. Lack of accurate or mutually agreed upon definitions hampers this process and makes comparisons between centers, which is an important method to improve outcomes, difficult. Therefore, the Canadian Pediatric Neurosurgery Study Group created definitions of complications in pediatric neurosurgery with consensus among 13 Canadian pediatric neurosurgical centers.
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Intracystic therapies for cystic craniopharyngioma in childhood.
Front Endocrinol (Lausanne)
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Introduction: Craniopharyngioma of childhood are commonly cystic in nature. An intracystic catheter insertion and subsequent instillation of substances inducing cyst shrinkage seems a beneficial strategy avoiding additional morbidity in a highly vulnerable brain location. Methods: A systematic review of the medical literature was performed to identify potentially relevant, all languages articles using Ovid MEDLINE and EMBASE from inception to July 2011 and Cochrane Central Register of Controlled Trials to third quarter 2011. All references were examined for relevancy. Results: Of 142 unique references, 71 referred to substances used for intracystic craniopharyngioma treatment. General aspects of intracystic catheter insertion as well as response rates, risks, and outcomes of children treated with intracystic radioisotopes, bleomycin, and interferon (IFN) are critically reviewed and an outline for potential future endeavors provided. Conclusion: IFN seems currently the intracystic substance with the best benefit risk ratio. The authors advocate for consensus on prospective data collection and standardized intracystic treatment strategies to allow reliable comparisons and herewith optimize treatment and outcome.
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Francisella tularensis elicits IL-10 via a PGE?-inducible factor, to drive macrophage MARCH1 expression and class II down-regulation.
PLoS ONE
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Francisella tularensis is a bacterial pathogen that uses host-derived PGE? to subvert the hosts adaptive immune responses in multiple ways. Francisella-induced PGE? acts directly on CD4 T cells to blunt production of IFN-?. Francisella-induced PGE? can also elicit production of a >10 kDa soluble host factor termed FTMØSN (F. tularensismacrophage supernatant), which acts on IFN-? pre-activated MØ to down-regulate MHC class II expression via a ubiquitin-dependent mechanism, blocking antigen presentation to CD4 T cells. Here, we report that FTMØSN-induced down-regulation of MØ class II is the result of the induction of MARCH1, and that MØ expressing MARCH1 "resistant" class II molecules are resistant to FTMØSN-induced class II down-regulation. Since PGE? can induce IL-10 production and IL-10 is the only reported cytokine able to induce MARCH1 expression in monocytes and dendritic cells, these findings suggested that IL-10 is the active factor in FTMØSN. However, use of IL-10 knockout MØ established that IL-10 is not the active factor in FTMØSN, but rather that Francisella-elicited PGE? drives production of a >10 kDa host factor distinct from IL-10. This factor then drives MØ IL-10 production to induce MARCH1 expression and the resultant class II down-regulation. Since many human pathogens such as Salmonella typhi, Mycobacterium tuberculosis and Legionella pneumophila also induce production of host PGE?, these results suggest that a yet-to-be-identified PGE?-inducible host factor capable of inducing IL-10 is central to the immune evasion mechanisms of multiple important human pathogens.
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Center effect and other factors influencing temporization and shunting of cerebrospinal fluid in preterm infants with intraventricular hemorrhage.
J Neurosurg Pediatr
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There is little consensus regarding the indications for surgical CSF diversion (either with implanted temporizing devices [reservoir or subgaleal shunt] or shunt alone) in preterm infants with posthemorrhagic hydrocephalus. The authors determined clinical and neuroimaging factors associated with the use of surgical CSF diversion among neonates with intraventricular hemorrhage (IVH), and describe variations in practice patterns across 4 large pediatric centers.
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The Syk-binding ubiquitin ligase c-Cbl mediates signaling-dependent B cell receptor ubiquitination and B cell receptor-mediated antigen processing and presentation.
J. Biol. Chem.
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B cell receptor (BCR)-mediated antigen (Ag) processing and presentation lead to B cell-T cell interactions, which support affinity maturation and immunoglobulin class switching. These interactions are supported by generation of peptide-MHC class II complexes in multivesicular body-like MIIC compartments of B cells. Previous studies have shown that trafficking of Ag·BCR complexes to MVB-like MIIC occurs via an ubiquitin-dependent pathway and that ubiquitination of Ag·BCR complexes occurs by an Src family kinase signaling-dependent mechanism that is restricted to lipid raft-resident Ag·BCR complexes. This study establishes that downstream Syk-dependent BCR signaling is also required for BCR ubiquitination and BCR-mediated antigen processing and presentation. Knockdown studies reveal that of the two known Syk-binding E3 ubiquitin ligases c-Cbl and Cbl-b, only c-Cbl appears to have a central role in BCR ubiquitination, trafficking to MIIC, and ubiquitin-dependent BCR-mediated antigen processing and presentation. These results establish the novel role for Syk signaling and the Syk-binding ubiquitin ligase c-Cbl in the BCR-mediated processing and presentation of cognate antigen and define one mechanism by which antigen-induced BCR ubiquitination is modulated to impact the initiation and maturation of the humoral immune response.
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Angioarchitectural features associated with hemorrhagic presentation in pediatric cerebral arteriovenous malformations.
J Neurointerv Surg
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To date, there have been few published studies examining the relationship between arteriovenous malformation (AVM) angioarchitecture and hemorrhagic presentation among children with cerebral AVMs. This study examines this relationship in this unique population, in whom symptomatic presentation of cerebral AVM is the norm rather than the exception.
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Inequities in access to pediatric epilepsy surgery: a bioethical framework.
Neurosurg Focus
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Epilepsy is a common childhood condition associated with a considerable medical and psychosocial burden. Children in whom medical treatment fails to reduce seizure burden represent an especially vulnerable patient population because prolonged, uncontrolled seizures are associated with poor developmental and neurocognitive outcomes. Surgical treatment in the form of cortical resection, functional disconnection, or neuromodulation may alleviate or significantly reduce the disease burden for a subset of these patients. However, there remains a dichotomy between the perceived benefits of surgery and the implementation of surgical strategies in the management of medically intractable epilepsy. The current paper presents an analysis of the bioethical implications of existing inequities in access to pediatric epilepsy surgery that result from inconsistent referral practices and discrepant evaluation techniques. The authors provide a basic bioethical framework composed of 5 primary expectations to inform public, institutional, and personal policies toward the provision of epilepsy surgery to afflicted children.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.