UW Neurological Surgery Recent PubMed Publications

Non-synaptic Cell-Autonomous Mechanisms Underlie Neuronal Hyperactivity in a Genetic Model of <em>PIK3CA</em>-Driven Intractable Epilepsy

3 years 4 months ago
Patients harboring mutations in the PI3K-AKT-MTOR pathway-encoding genes often develop a spectrum of neurodevelopmental disorders including epilepsy. A significant proportion remains unresponsive to conventional anti-seizure medications. Understanding mutation-specific pathophysiology is thus critical for molecularly targeted therapies. We previously determined that mouse models expressing a patient-related activating mutation in PIK3CA, encoding the p110α catalytic subunit of...
Achira Roy

Robustness of Beta Desynchronization from Chronically Implanted Cortical Electrodes on Multiple Time Scales

3 years 4 months ago
Adaptive deep brain stimulation (aDBS) promises a significant improvement in patient outcomes, compared to existing deep brain stimulation devices. Fully implanted systems represent the next step to the clinical adoption of aDBS. We take advantage of a unique longitudinal data set formed as part of an effort to investigate aDBS for essential tremor to verify the long term reliability of electrocorticography strips over the motor cortex as a source of bio-markers for control of adaptive...
Tomasz M Fraczek

Arming Immune Cell Therapeutics with Polymeric Prodrugs

3 years 4 months ago
Engineered immune cells are an exciting therapeutic modality, which survey and attack tumors. Backpacking strategies exploit cell targeting capabilities for delivery of drugs to combat tumors and their immune-suppressive environments. Here, a new platform for arming cell therapeutics through dual receptor and polymeric prodrug engineering is developed. Macrophage and T cell therapeutics are engineered to express a bioorthogonal single chain variable fragment receptor. The receptor binds a...
Ciana L López

Probing Interplays between Human XBP1u Translational Arrest Peptide and 80S Ribosome

3 years 4 months ago
The ribosome stalling mechanism is a crucial biological process, yet its atomistic underpinning is still elusive. In this framework, the human XBP1u translational arrest peptide (AP) plays a central role in regulating the unfolded protein response (UPR) in eukaryotic cells. Here, we report multimicrosecond all-atom molecular dynamics simulations designed to probe the interactions between the XBP1u AP and the mammalian ribosome exit tunnel, both for the wild type AP and for four mutant variants...
Francesco Di Palma

Veterans with Traumatic Brain Injury-related Ocular Injury and Vision Dysfunction: Recommendations for Rehabilitation

3 years 4 months ago
CONCLUSIONS: Findings delineate service delivery models available to veterans with TBI-related vision impairment. The challenge these data address is the lack of clear paths from diagnosis of TBI to identification of vision dysfunction deficits to specialized vision rehabilitation, and finally to community reintegration and community based-vision rehabilitation.
Sandra L Winkler

Effect of CYP3A5 and CYP3A4 Genetic Variants on Fentanyl Pharmacokinetics in a Pediatric Population

3 years 4 months ago
Fentanyl is an anesthetic/analgesic commonly used in surgical and recovery settings. CYP3A4 and CYP3A5 encode enzymes, which metabolize fentanyl; genetic variants in these genes impact fentanyl pharmacokinetics in adults. Pharmacokinetic (PK) studies are difficult to replicate in children due to the burden of additional blood taken solely for research purposes. The aim of this study is to test the effect of CYP3A5 and CYP3A4 genetic variants on fentanyl PKs in children using opportunistically...
Michael L Williams

Reverse-transcription PCR increases sensitivity of broad-range fungal detection in bronchoalveolar lavage fluid

3 years 4 months ago
Broad-range PCR targeting 28S D1-D2 ribosomal DNA (rDNA) identifies numerous fungi but has limited sensitivity in clinical specimens. Ribosomal RNA (rRNA) vastly outnumbers rDNA, suggesting reverse transcription (RT)-PCR could improve detection. Among contrived samples, RT-PCR decreased 28S PCR cycle threshold values by 10--12 cycles and lowered the limit of detection > 2000-fold. Among 32 bronchoalveolar lavage specimens, RT-PCR detected 12/15 (80%) fungal PCR- or culture-positive specimens,...
Heather L Glasgow

Outcomes of Mechanical Thrombectomy for Patients With Stroke Presenting With Low Alberta Stroke Program Early Computed Tomography Score in the Early and Extended Window

3 years 4 months ago
CONCLUSIONS AND RELEVANCE: In this cohort study, more than 1 in 5 patients presenting with an ASPECTS of 2 to 5 achieved 90-day functional independence after MT. A favorable outcome was nearly 5 times more likely for patients with low ASPECTS who had successful recanalization. The association of a low ASPECTS with 90-day outcomes did not differ for patients presenting in the early vs extended MT window.
Eyad Almallouhi

Machine learning modeling of genome-wide copy number alteration signatures reliably predicts IDH mutational status in adult diffuse glioma

3 years 4 months ago
Knowledge of 1p/19q-codeletion and IDH1/2 mutational status is necessary to interpret any investigational study of diffuse gliomas in the modern era. While DNA sequencing is the gold standard for determining IDH mutational status, genome-wide methylation arrays and gene expression profiling have been used for surrogate mutational determination. Previous studies by our group suggest that 1p/19q-codeletion and IDH mutational status can be predicted by genome-wide somatic copy number alteration...
Nicholas Nuechterlein

Characteristics and Growth Rate of Lung Metastases in Patients With Primary Gastrointestinal Malignancies and Lung-dominant Metastatic Disease: A Retrospective Cohort Analysis

3 years 4 months ago
CONCLUSIONS: Lung metastases from primary GI cancers have a variable but overall indolent natural history and are generally associated with prolonged survival outcomes. Further efforts to define patterns of growth of lung metastases, informed by size, number, and clinical/molecular features, are needed to guide appropriate timing and selection of therapy as well as surveillance strategies.
Shohei Burns

Androgen receptor regulates eIF5A2 expression and promotes prostate cancer metastasis via EMT

3 years 4 months ago
Androgen receptor (AR) is an androgen-activated transcription factor of the nuclear receptor superfamily. AR plays a role in the development and progression of prostate cancer (PCa). However, the exact role of AR in PCa metastasis remains unclear. In the present study, we aimed to elucidate the function of AR in PCa. We found that eukaryotic translation initiation factor (EIF) 5A2, an elongation factor that induces epithelial-to-mesenchymal transition (EMT) in PCa cells, was significantly...
Yuancai Zheng

Socioeconomic and demographic factors in the diagnosis and treatment of Chiari malformation type I and syringomyelia

3 years 4 months ago
CONCLUSIONS: Socioeconomic and demographic factors appear to influence the presentation and management of patients with CM-I and SM. Race is associated with age and timing of diagnosis as well as operating room time, estimated blood loss, and length of hospital stay. This exploration of socioeconomic and demographic barriers to care will be useful in understanding how to improve access to pediatric neurosurgical care for patients with CM-I and SM.
Syed Hassan A Akbari

Concurrent decompression and resection versus decompression with delayed resection of acutely ruptured brain arteriovenous malformations

3 years 4 months ago
CONCLUSIONS: Ruptured bAVM rarely presents in clinical herniation requiring surgical decompression and hematoma evacuation. Concurrent surgical decompression and resection of a ruptured bAVM can be performed on low-grade lesions without compromising LOS or long-term functional outcome; however, the surgeon may encounter a more challenging surgical environment.
Rajeev D Sen

Ultrasound-guided core biopsy in the diagnosis of parotid neoplasia: an overview and update with a review of the literature

3 years 4 months ago
CONCLUSIONS: USCB can be considered as the optimum tool of choice for the diagnosis of parotid neoplasia. This would particularly be the case in centres utilizing FNAC with high non-diagnostic rates or reduced diagnostic accuracy when compared to USCB published data, or in centres establishing a new service.
Katharine Julia Hurry

Review of rodent models of attention deficit hyperactivity disorder

3 years 4 months ago
Attention deficit hyperactivity disorder (ADHD) is a polygenic neurodevelopmental disorder that affects 8-12 % of children and >4 % of adults. Environmental factors are believed to interact with genetic predispositions to increase susceptibility to ADHD. No existing rodent model captures all aspects of ADHD, but several show promise. The main genetic models are the spontaneous hypertensive rat, dopamine transporter knock-out (KO) mice, dopamine receptor subtype KO mice, Snap-25 KO mice, guanylyl...
Samantha L Regan
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