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Rasmussen encephalitis is a devastating progressive inflammatory disorder that leads to debilitating neurologic deficits and intractable epilepsy. Surgical treatment of the dominant hemisphere has been attempted with hesitation, given the lack of effective diagnostic tools to determine the potential functional deficits from disconnection procedures.

Background and Aim: Despite the anti-cancer and antimicrobial properties of licorice extract and lavender essential oil, some factors, such as low bioavailability and biodegradable, limit their therapeutic use. Using nanoparticles is a method to overcome these restrictions. This study aimed to investigate the anti-proliferative effects of nanoemulsion containing licorice extract and lavender essential oil on cancer cells; we also evaluated its antimicrobial properties in vitro. Methods & Materials: In this experimental study, nanoemulsions, containing licorice extract and lavender essential oil were developed by the spontaneous emulsion method. The anti-proliferative effect of nanoemulsion was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) colorimetric method on two cell lines HepG2 and SK-MEL-3. To measure the antimicrobial effect of 4 standard strains of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Minimum Inhibitory Concentration (MIC) method was used. Ethical Considerations: This study was approved by the Ethics Committee of Kashan University of Medical Sciences (Code: IR.KAUMS.MEDNT.REC.1396.106). Results: The results of MTT test on HepG2 cells indicated that the concentrations of 630, 1250, and 2500 μg/mL nanoemulsions caused toxicity to the cell and led to the death of >50% of the cells (IC50=401μg/mL; P50% of the cells (IC50 = 82 μg/mL; P

OBJECTIVE Drug-resistant epilepsy occurs in up to 40% of patients with epilepsy who may be considered for epilepsy surgery. For drug-resistant focal epilepsy, up to 50% of patients require invasive monitoring prior to surgery. Of the most common invasive monitoring strategies (subdural electrodes [SDEs] and stereo-electroencephalography [sEEG]), the most cost-effective strategy is unknown despite substantial differences in morbidity profiles. METHODS Using data collected from an internationally representative sample published in available systematic reviews and meta-analyses, this economic evaluation study employs a decision analysis model to simulate the risks and benefits of SDE and sEEG invasive monitoring strategies. In this model, patients faced differing risks of morbidity, mortality, resection, and seizure freedom depending on which invasive monitoring strategy they underwent. A range of cost values was obtained from a recently published single-center cost-utility analysis. The model considers a base case simulation of a characteristic patient with drug-resistant epilepsy using clinical parameters obtained from systematic reviews of invasive monitoring available in the literature. The main outcome measure was the probability of a positive outcome after invasive monitoring, which was defined as improvement in seizures without a complication. Cost-effectiveness was measured using an incremental cost-effectiveness ratio (ICER). RESULTS Invasive monitoring with sEEG had an increased cost of $274 and increased probability of effectiveness of 0.02 compared with SDEs, yielding an ICER of $12,630 per positive outcome obtained. Sensitivity analyses varied parameters widely and revealed consistent model results across the range of clinical parameters reported in the literature. One-way sensitivity analyses revealed that invasive monitoring strategy costs were the most influential parameter for model outcome. CONCLUSIONS In this analysis, based on available observational data and estimates of complication costs, invasive monitoring with either SDEs or sEEG was nearly equivalent in terms of cost-effectiveness.

OBJECTIVECorpus callosotomy is a palliative procedure that is effective at reducing seizure burden in patients with medically refractory epilepsy. The procedure is traditionally performed via open craniotomy with interhemispheric microdissection to divide the corpus callosum. Concerns for morbidity associated with craniotomy can be a deterrent to patients, families, and referring physicians for surgical treatment of epilepsy. Laser interstitial thermal therapy (LITT) is a less invasive procedure that has been widely adopted in neurosurgery for the treatment of tumors. In this study, the authors investigated LITT as a less invasive approach for corpus callosotomy.METHODSThe authors retrospectively reviewed all patients treated for medically refractory epilepsy by corpus callosotomy, either partial or completion, with LITT. Chart records were analyzed to summarize procedural metrics, length of stay, adverse events, seizure outcomes, and time to follow-up. In select cases, resting-state functional MRI was performed to qualitatively support effective functional disconnection of the cerebral hemispheres.RESULTSTen patients underwent 11 LITT procedures. Five patients received an anterior two-thirds LITT callosotomy as their first procedure. One patient returned after LITT partial callosotomy for completion of callosotomy by LITT. The median hospital stay was 2 days (IQR 1.5–3 days), and the mean follow-up time was 1.0 year (range 1 month to 2.86 years). Functional outcomes are similar to those of open callosotomy, with the greatest effect in patients with a significant component of drop attacks in their seizure semiology. One patient achieved an Engel class II outcome after anterior two-thirds callosotomy resulting in only rare seizures at the 18-month follow-up. Four others were in Engel class III and 5 were Engel class IV. Hemorrhage occurred in 1 patient at the time of removal of the laser fiber, which was placed through the bone flap of a prior open partial callosotomy.CONCLUSIONSLITT appears to be a safe and effective means for performing corpus callosotomy. Additional data are needed to confirm equipoise between open craniotomy and LITT for corpus callosotomy.

OBJECTIVE Use of invasive stereoelectroencephalography (SEEG) has gained traction recently. However, scant research has investigated the costs and resource utilization of SEEG compared with subdural grid (SDG)–based techniques in pediatric patients. Here, the authors have presented a retrospective analysis of charges associated with SEEG and SDG monitoring at a single institution. METHODS The authors performed a retrospective case series analysis of pediatric patients with similar characteristics in terms of age, sex, seizure etiology, and epilepsy treatment strategy who underwent SEEG or SDG monitoring and subsequent craniotomy for resection of epileptogenic focus at St. Louis Children Hospital, St. Louis, Missouri, between 2013 and 2020. Financial data, including hospital charges, supplies, and professional fees (i.e., those related to anesthesia, neurology, neurosurgery, and critical care), were adjusted for inflation to 2020 US dollars. RESULTS The authors identified 18 patients (9 underwent SEEG and 9 underwent SDG) with similar characteristics in terms of age (mean [range] 13.6 [1.9–21.8] years for SDG patients vs 11.9 [2.4–19.6] years for SEEG patients, p = 0.607), sex (4 females underwent SDG vs 6 females underwent SEEG, p = 0.637), and presence of lesion (5 patients with a lesion underwent SDG vs 8 underwent SEEG, p = 0.294). All patients underwent subsequent craniotomy for resection of epileptogenic focus. SEEG patients were more likely to have a history of status epilepticus (p = 0.029). Across 1 hospitalization for each SDG patient and 2 hospitalizations for each SEEG patient, SEEG patients had a significantly shorter mean operating room time (288 vs 356 minutes, p = 0.015), mean length of stay in the ICU (1.0 vs 2.1 days, p < 0.001), and tended to have a shorter overall length of stay in the hospital (8.4 vs 10.6 days, p = 0.086). Both groups underwent invasive monitoring for similar lengths of time (5.2 days for SEEG patients vs 6.4 days for SDG patients, p = 0.257). Time to treatment from the initial invasive monitoring evaluation was significantly longer in SEEG patients (64.6 vs 6.4 days, p < 0.001). Neither group underwent readmission within the first 30 days after hospital discharge. Seizure outcomes and complication rates were similar. After adjustment for inflation, the average total perioperative charges were $104,442 for SDG and $106,291 for SEEG (p = 0.800). CONCLUSIONS Even though 2 hospitalizations were required for SEEG and 1 hospitalization was required for SDG monitoring, patients who underwent SEEG had a significantly shorter average length of stay in the ICU and operating room time. Surgical morbidity and outcomes were similar. Total perioperative charges for invasive monitoring and resection were approximately 2% higher for SEEG patients when corrected for inflation, but this difference was not statistically significant.

Iron corrosion in acidic media is a natural phenomenon that converts elemental iron to a more chemically-stable form, i.e. its oxide and hydroxide. In this study, the iron corrosion process is modeled as a completely implicit problem, solved by a novel finite difference model to provide insight into the ionic aspects of corrosion behavior. This new mathematical model eliminates the chemical potential parameters from the corrosion process equations, thereby reducing the need for experimental determination of chemical potentials. The eliminated-chemical-potential-parameters model predicts and quantifies key parameters (concentrations of conjugate base ion, iron (II) ion, hydrogen ion, anodic and cathodic potentials, and the electrical current density) associated with the iron corrosion process in acidic solutions. The rigorous derivation and novel application of the eliminated-chemical-potential-parameters model and its results provide new insights into the iron corrosion process. The present model is also applicable in any industrial process which is associated with metal corrosion. The model helps to guide the design of future corrosion resistant systems, and various experimental studies pertaining to corrosion inhibition techniques.

Background The blood–brain and blood–tumor barriers (BBB and BTB), which restrict the entry of most drugs into the brain and tumor, respectively, are a significant challenge in the treatment of glioblastoma. Laser interstitial thermal therapy (LITT) is a minimally invasive surgical technique increasingly used clinically for tumor cell ablation. Recent evidence suggests that LITT might locally disrupt BBB integrity, creating a potential therapeutic window of opportunity to deliver otherwise brain-impermeant agents. Methods We established a LITT mouse model to test if laser therapy can increase BBB/BTB permeability in vivo. Mice underwent orthotopic glioblastoma tumor implantation followed by LITT in combination with BBB tracers or the anticancer drug doxorubicin. BBB/BTB permeability was measured using fluorimetry, microscopy, and immunofluorescence. An in vitro endothelial cell model was also used to corroborate findings. Results LITT substantially disrupted the BBB and BTB locally, with increased permeability up to 30 days after the intervention. Remarkably, molecules as large as human immunoglobulin extravasated through blood vessels and permeated laser-treated brain tissue and tumors. Mechanistically, LITT decreased tight junction integrity and increased brain endothelial cell transcytosis. Treatment of mice bearing glioblastoma tumors with LITT and adjuvant doxorubicin, which is typically brain-impermeant, significantly increased animal survival. Conclusions Together, these results suggest that LITT can locally disrupt the BBB and BTB, enabling the targeted delivery of systemic therapies, including, potentially, antibody-based agents.

INTRODUCTION A central challenge in glioblastoma treatment is the presence of the blood-brain barrier (BBB) and blood-tumor barrier (BTB), which prevent access of drugs to the brain and tumor respectively. Recent evidence in patients suggests laser interstitial thermal therapy (LITT), used clinically for tumor ablation, locally disrupts BBB integrity, potentially creating a therapeutic window to deliver otherwise brain-impermeant agents. METHODS A mouse model for LITT, established using a Nd-YAG laser coupled to a 600 mm fiber optic and thermocouple probe, was inserted via burrhole to target the somatosensory cortex. Syngeneic GL261 tumor cells were stereotactically implanted prior to LITT. BBB and BTB permeability were assessed through measurement of fluorescein and doxorubicin after IV injection. Permeability of IV dextran (10 and 70 kDa) and human IgG was monitored by immunohistochemistry (IHC) analysis. Mechanisms of BBB breakdown in vivo were explored utilizing electron microscopy and IHC. RESULTS By fluorescein assay, LITT-induced BBB and BTB permeability began one day post-treatment and was sustained for at least 2 weeks. Additionally, both normal brain and brain tumors demonstrated an increase in Dextran 10 kDa, Dextran 70 kDa, and human IgG extravasation after IV injection in vivo. Mechanistically, we provide evidence that LITT triggers both a decrease in tight junction integrity and an increase in brain endothelial cell transcytosis. As proof-of-concept that LITT can enhance tumor delivery of systemic drugs, LITT increased IV doxorubicin permeability in brain in vivo. Moreover, LITT plus doxorubicin significantly increased survival in brain tumor-bearing mice compared to doxorubicin or LITT alone. CONCLUSIONS Our data suggest that LITT increases BBB and BTB permeability over a defined time window to large molecular weight agents, including antibodies, through multiple cellular mechanisms. Our preclinical results with LITT plus doxorubicin, which mirror a current clinical trial, indicate LITT can enhance the efficacy of systemically delivered drugs.

Background Choroid plexus carcinoma (CPC) is a rare, malignant tumor occurring more commonly in children than adults. This case report describes the clinical course of a 3-year-old boy with a rare case of metastatic CPC with a novel TP53 mutation. Case Description A 3-year-old boy presented with postconcussive symptoms after a fall. Computed tomography and magnetic resonance imaging revealed lesions in the suprasellar cistern, left lateral ventricle, and cauda equina. The tumor was diagnosed as choroid plexus carcinoma with a novel TP53 V216M somatic mutation. The patient underwent resection of the left lateral ventricle lesion. Conclusion We describe a case of CPC with highly metastatic characteristics and a novel TP53 mutation. Our report implicates TP53 in the pathogenesis of pediatric CPC, and we emphasize that CPC in children should prompt careful consideration of TP53 status to inform prognosis and clinical treatment.

Aneurysmal subarachnoid hemorrhage (SAH) is rare in neonates. The authors present a unique report of a neonate with SAH from anterior inferior cerebellar artery (AICA) aneurysm rupture that was successfully treated with Onyx embolization. This case report demonstrates the utility of Onyx embolization for posterior circulation aneurysms in neonates and the successful management of SAH in this population.

Asphaltene precipitation in reservoirs during production and Enhanced Oil Recovery (EOR) can cause serious problems that lead to reduction of reservoir fluid production. In order to study asphaltene tendency to precipitate and change in flow rate as a function of distance from wellbore, an equation of state (Peng-Robinson) based model namely Nghiem et al.’s model has been employed in this study. The heaviest components of crude oil are separated into two parts: The first portion is considered as non-precipitating component (C31A+) and the second one is considered as precipitating component (C31B+) and the precipitated asphaltene is considered as pure solid. For determination of the acentric factor and critical properties, Lee-Kesler and Twu correlations are employed, respectively. In this study, a multiphase flow (oil, gas and asphaltene) model for an asphaltenic crude oil for which asphaltene is considered as solid particles (precipitated, flocculated and deposited particles), has been developed. Furthermore, effect of asphaltene precipitation on porosity and permeability reduction has been studied. Results of this study indicate that asphaltene tendency to precipitate increases and permeability of porous medium decreases by increasing oil flow rate in under-saturated oil reservoirs and dropping reservoir pressure under bubble point pressure. On the other hand, asphaltene tendency to precipitate decreases with pressure reduction to a level lower than bubble point pressure where asphaltene starts to dissolve back into oil phase. Moreover, it is observed that precipitation zone around the wellbore develops with time as pressure declines to bubble point pressure (production rate increases up). Also, there is an equilibrium area near wellbore region at which reservoir fluid properties such as UAOP (Upper Asphaltene Onset Pressure) and LAOP (Lower Asphaltene Onset Pressure) are constant and independent of the distance from wellbore.

OBJECTIVEThe ROSA device is a robotic stereotactic arm that uses a laser system to register the patient’s head or spine with MR or CT images. In this study, the authors analyze their experience with this system in pediatric neurosurgical applications and present selected cases that exemplify the usefulness of this system.METHODSThe authors reviewed all cases that utilized the ROSA system at their institution. Patient demographics, pathology, complications, electrode placement, laser ablation, and biopsy accuracy were analyzed. Patient disposition and condition at follow-up were also analyzed.RESULTSSeventeen patients underwent 23 procedures using the ROSA system. A total of 87 electroencephalography electrodes were placed, with 13% deviating more than 3 mm from target. Six patients underwent stereotactic needle biopsy, and 9 underwent laser interstitial thermotherapy (LITT). One patient who underwent LITT required a subsequent craniotomy for tumor resection. Another patient experienced an asymptomatic extraaxial hematoma that spontaneously resolved. No patient suffered neurological complications during follow-up. Follow-up from the last procedure averaged 180 days in epilepsy patients and 309 days in oncology patients.CONCLUSIONSThe precision, ease of use, and versatility of the ROSA system make it well suited for pediatric neurosurgical practice. Further work, including long-term analysis of results and cost-effectiveness, will help determine the utility of this system and if its applications can be expanded.

OBJECTIVE The goal of this study was to identify the rate of neosuture formation in patients with craniosynostosis treated with endoscope-assisted strip craniectomy and investigate whether neosuture formation in sagittal craniosynostosis has an effect on postoperative calvarial shape. METHODS The authors retrospectively reviewed 166 cases of nonsyndromic craniosynostosis that underwent endoscope-assisted repair between 2006 and 2014. Preoperative and 1-year postoperative head CT scans were evaluated, and the rate of neosuture formation was calculated. Three-dimensional reconstructions of the CT data were used to measure cephalic index (CI) (ratio of head width and length) of patients with sagittal synostosis. Regression analysis was used to calculate significant differences between patients with and without neosuture accounting for age at surgery and preoperative CI. RESULTS Review of 96 patients revealed that some degree of neosuture development occurred in 23 patients (23.9%): 16 sagittal, 2 bilateral coronal, 4 unilateral coronal, and 1 lambdoid synostosis. Complete neosuture formation was seen in 14 of those 23 patients (9 of 16 sagittal, 1 of 2 bilateral coronal, 3 of 4 unilateral coronal, and 1 of 1 lambdoid). Mean pre- and postoperative CI in the complete sagittal neosuture group was 67.4% and 75.5%, respectively, and in the non-neosuture group was 69.8% and 74.4%, respectively. There was no statistically significant difference in the CI between the neosuture and fused suture groups preoperatively or 17 months postoperatively in patients with sagittal synostosis. CONCLUSIONS Neosuture development can occur after endoscope-assisted strip craniectomy and molding helmet therapy for patients with craniosynostosis. Although the authors did not detect a significant difference in calvarial shape postoperatively in the group with sagittal synostosis, the relevance of neosuture formation remains to be determined. Further studies are required to discover long-term outcomes comparing patients with and without neosuture formation.

Background: Insecticide resistance is one of the serious problems for German cockroach control program. This study was conducted to determine the bendiocarb and Carbaryl resistance mechanisms in German cockroaches using the piperonyl butoxide (PBO). Methods: Bioassay tests were conducted with 4 to 6 different concentrations of both insecticides with four replicates of 10 susceptible strain cockroaches per concentration to determine of discriminative concentration. After determining discriminative concentration, the result was compared to wild strain. The levels of susceptibility and resistance ratio (RR) and synergism ratio (SR) were calculated for each five wild strains. Moreover resistance mechanisms in wild strains were determined using PBO synergist in vivo. Results: Hospital strains showed different levels of resistance to bendiocarb and carbaryl compared to susceptible strain. The bendiocarb and carbaryl resistance ratios ranged from 2.11 to 7.97 and 1.67 to 2 at LD50 levels, respectively. The synergist PBO significantly enhanced the toxicity of bendiocarb and carbaryl to all strains with different degrees of synergist ratio, 1.31, 1.39, 3.61, 1.78, 1.62 and 2.1 fold for bendiocarb, 1.19, 1.18, 1.12. 1.29, 1.45 and 1.11-fold for carbaryl, suggesting monooxygenase involvement in bendiocarb and carbaryl resistance. Conclusion: The synergetic effect of PBO had the highest effect on bendiocarb and resistance level was significantly reduced, which indicates the important role of monoxidase enzyme in creating resistance to Bendiocarb. Piperonyl butoxide did not have a significant synergistic effect on carbaryl and did not significantly break the resistance.

A paucity of effective treatments exists for glioblastoma, the most malignant form of brain cancer. However, novel therapies are in active development, including therapies based on the use of virus...

Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that is selectively and abundantly expressed in the brain, and its activity is required for normal synaptic function. Here, we show that UCH-L1 functions in maintaining normal synaptic structure in hippocampal neurons. We found that UCH-L1 activity is rapidly upregulated by NMDA receptor activation, which leads to an increase in the levels of free monomeric ubiquitin. Conversely, pharmacological inhibition of UCH-L1 significantly reduces monomeric ubiquitin levels and causes dramatic alterations in synaptic protein distribution and spine morphology. Inhibition of UCH-L1 activity increases spine size while decreasing spine density. Furthermore, there is a concomitant increase in the size of presynaptic and postsynaptic protein clusters. Interestingly, however, ectopic expression of ubiquitin restores normal synaptic structure in UCH-L1-inhibited neurons. These findings point to a significant role of UCH-L1 in synaptic remodeling, most likely by modulating free monomeric ubiquitin levels in an activity-dependent manner.

Background RNA from exosomes and other microvesicles contain transcripts of tumour origin. In this study we sought to identify biomarkers of glioblastoma multiforme in microvesicle RNA from serum of affected patients. Methods Microvesicle RNA from serum from patients with de-novo primary glioblastoma multiforme (N = 9) and normal controls (N = 7) were analyzed by microarray analysis. Samples were collected according to protocols approved by the Institutional Review Board. Differential expressions were validated by qRT-PCR in a separate set of samples (N = 10 in both groups). Results Expression profiles of microvesicle RNA correctly separated individuals in two groups by unsupervised clustering. The most significant differences pertained to down-regulated genes (121 genes > 2-fold down) in the glioblastoma multiforme patient microvesicle RNA, validated by qRT-PCR on several genes. Overall, yields of microvesicle RNA from patients was higher than from normal controls, but the additional RNA was primarily of size < 500 nt. Gene ontology of the down-regulated genes indicated these are coding for ribosomal proteins and genes related to ribosome production. Conclusions Serum microvesicle RNA from patients with glioblastoma multiforme has significantly down-regulated levels of RNAs coding for ribosome production, compared to normal healthy controls, but a large overabundance of RNA of unknown origin with size < 500 nt.

Background: Recent studies have shown that RNA isolated from exosomes and other microvesicles (exoRNA) contain diagnostically relevant transcripts of tumor origin. In this study we sought to identify specific biomarkers of glioblastoma multiforme (GBM) and malignant ovarian cancer in the ribonucleic acid fraction extracted from microvesicles (exoRNA) isolated from the serum of affected patients. Methods: All samples were collected following informed consent in accordance with the appropriate protocols approved by the MGH Institutional Review Board (GBM) and the Umeå University ethics committee (ovarian tumors). Patients with primary GBM (N=9), normal controls (N=7); and pathologically proven benign (N=16), borderline (N=19), and malignant (N=29, stage I-IV, grade 1–3) neoplastic transformation of the ovaries were included. ExoRNA isolated from patient serum was amplified and analyzed by microarray analysis on Agilent 4×44K arrays (GBM) and Agilent 8×60K arrays (ovarian tumors). Differential expressions between control and GBM samples were validated by qRT-PCR in a separate set of samples (N=10 in both groups). Results: Array analysis of the amplified exoRNA yielded significant signals from at least 10,000 genes on the array for all samples. The expression profiles of the exoRNA from GBM patients were shown to be different from those of normal healthy volunteers. The most significant expression differences observed in the array analysis pertained to down-regulated genes (121 genes >2-fold down) in the GBM patient exoRNA, which was validated by qRT-PCR on several genes. Gene ontology analysis of the down-regulated genes indicated these are primarily mRNAs coding for ribosomal proteins and other genes related to ribosome production. Supervised analysis showed no significant differential gene expression between the benign, borderline, and malignant ovarian tumors. However, unsupervised Consensus Clustering yielded a clear segregation of the patients into two new groups (100% resampling consensus for 61 samples). Gene Set Enrichment Analysis (GSEA) showed a strong association of one of the two groups with genes linked to translation initiation (FDR q-value 0.04), and mRNA processing (FDR q-value 0.032). GSEA also confirmed a strong overlap of the genes separating the ovarian cancer samples into two groups with those discriminating GBM from healthy control individuals. Conclusions: Microvesicle isolated RNA from patients with GBM is significantly different from that of normal control individuals. The same genes support a binary classification of ovarian tumors suggesting that common biological processes may be in effect for these different tumor types. The common signature is hallmarked by messenger RNAs coding for ribosome production, which are significantly downregulated in GBM exoRNA and in one of two novel subgroups of ovarian tumors. While the biological role of this signature remains to be elucidated, we conclude that exosomal RNA expression profiling has the potential to serve as a clinically relevant diagnostic source of information about the biology, malignancy, and state of tumors. This underlines the diagnostic potential of exosomes not only in early diagnosis, but also in directing therapies, evaluating response and in situations where biopsy samples are difficult to access. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C140.