UW Neurological Surgery Recent PubMed Publications

Post-traumatic epilepsy (PTE) is a recurrent and often drug-refractory seizure disorder caused by traumatic brain injury (TBI). No single drug treatment prevents PTE, but preventive drug combinations that may prophylax against PTE have not been studied. Based on a systematic evaluation of rationally chosen drug combinations in the intrahippocampal kainate (IHK) mouse model of acquired epilepsy, we identified two multi-targeted drug cocktails that exert strong antiepileptogenic effects. The...

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Understanding of newborn immune ontogeny in the first week of life will enable age-appropriate strategies for safeguarding vulnerable newborns against infectious diseases. Here we conducted an observational study exploring the immunological profile of infants longitudinally throughout their first week of life. Our Expanded Program on Immunization - Human Immunology Project Consortium (EPIC-HIPC) studies the epigenetic regulation of systemic immunity using small volumes of peripheral blood...

Program death 1 (PD-1) inhibitors such as nivolumab are immune checkpoint inhibitors that have revolutionized the treatment of metastatic melanoma. Despite its success in treating melanoma, immune activation can lead to immune-related adverse effects, which are experienced by half of melanoma patients treated with PD-1 inhibitors. Despite the common frequency of immune-mediated adverse events, the development of a secondary lymphoma is exceedingly rare. We present the case of a 53-year-old woman...

Cutaneous mycobacterial infections cause substantial morbidity and are challenging to diagnose and treat. An improved understanding of the dermal immune response to mycobacteria may inspire new therapeutic approaches. We conducted a controlled human infection study with 10 participants who received 2 × 106 CFUs of Mycobacterium bovis bacillus Calmette-Guérin (Tice strain) intradermally and were randomized to receive isoniazid or no treatment. Peripheral blood was collected at multiple time...

CONCLUSIONS: These observations highlight the capacity of omental adipocytes to generate a pro-tumorigenic and chemoprotective microenvironment in ovarian cancer and other adipose-related malignancies.

CONCLUSIONS: Assessment of gross motor function reflected a consistent pattern of significantly slower performances for blast and nonblast TBI groups compared to controls, over all follow-up intervals. Fine motor function performance reflected a similar significant difference pattern at 1- and 5-year follow-up intervals, with a reduced difference from control groups at the 10-year follow-up. Maintenance of high-level motor functions, including overall motor speed, coordination, and reaction...

With the development and characterization of biomarkers that may reflect neural network state as well as a patient's clinical deficits, there is growing interest in more complex stimulation designs. While current implantable neuromodulation systems offer pathways to expand the design and application of adaptive stimulation paradigms, technological drawbacks of these systems limit adaptive neuromodulation exploration. In this paper, we discuss the implementation of a phase-triggered stimulation...

Traumatic brain injury (TBI), a global leading cause of mortality and disability, lacks effective treatments to enhance recovery. Synaptic remodeling has been postulated as one mechanism that influences outcomes after TBI. We sought to investigate whether common mechanisms affecting synapse maintenance are shared between TBI and other neuropsychiatric conditions using pathway enrichment tools and genome-wide genotype data, with the goal of highlighting novel treatment targets. We leveraged an...

CONCLUSIONS: IVT is associated with improved functional outcomes in AIS patients with LVO despite unsuccessful MT.

Oligodendroglioma, IDH-mutant and 1p/19q-codeleted has highly variable outcomes that are strongly influenced by patient age. The distribution of oligodendroglioma age is non-Gaussian and reportedly bimodal, which motivated our investigation of age-associated molecular alterations that may drive poorer outcomes. We found that elevated HOXD12 expression was associated with both older patient age and shorter survival in the TCGA (FDR < 0.01, FDR = 1e-5) and the CGGA (p = 0.03, p < 1e-3). HOXD12...

CONCLUSION: Our findings validate GRP78 as a target of OLN anti-cancer and anti-viral activities. These proof-of-principle studies support further investigation of OLN as a readily accessible compound to dually combat cancer and COVID-19.

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Inhibition of Hepatitis B Virus (HBV) replication by small molecules that modulate capsid assembly and the encapsidation of pgRNA and viral polymerase by HBV core protein is a clinically validated approach toward the development of new antivirals. Through definition of a minimal pharmacophore, a series of isoquinolinone-based capsid assembly modulators (CAMs) was identified. Structural biology analysis revealed that lead molecules possess a unique binding mode, exploiting electrostatic...

CONCLUSIONS: Findings illustrate the nature and rates of distinct neuropsychiatric symptom trajectories and their relationship to traumatic injuries. Providers may use these results as a referent for gauging typical v. atypical recovery in the first 12 months post-injury.

CONCLUSIONS: Together these data reveal a role for microenvironment Cav3 in promoting GBM tumor progression through regulating neuronal and glial processes particularly associated with the OPC-cell state. Targeting both intrinsic and microenvironment Cav3 with the inhibitor mibefradil significantly enhanced the anti-GBM effects of TMZ and radiation.

Nascent polypeptide chains (NCs) are extruded from the ribosome through an exit tunnel (ET) traversing the large ribosomal subunit. The ET's irregular and chemically complex wall allows for various NC-ET interactions. Translational arrest peptides (APs) bind in the ET to induce translational arrest, a property that can be exploited to study NC-ET interactions by Force Profile Analysis (FPA). We employed FPA and molecular dynamics (MD) simulations to investigate how individual residues placed in...

Laboratory benchmarking allows objective analysis of the analytical performance of malaria rapid diagnostic tests (RDTs). We present the analytical detection limits of the Rapigen BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH), the Rapigen BIOCREDIT Malaria Ag Pf (pLDH/HRPII), and two best-in-class WHO-prequalified comparator RDTs, generated using standardized panels containing recombinant antigen, in vitro cultured parasites, international standards, and clinical samples. Detection limit antigen...

CONCLUSION: Higher morning and daylight exposure levels were associated with various positive objective and subjective sleep measures in professional team sport athletes, supporting the need for education on optimising light exposure to improve circadian function, sleep, and health.

Lettuce is an established food commodity in the UK increasingly facing supply challenges in winter due to adverse weather events and rising energy costs. We investigate whether an agroecologically grown salad mix of lettuce and underutilised leafy greens produced in the Azores, Portugal, could be part of a sustainable solution. We performed a Life Cycle Assessment to compare the environmental impacts of this salad mix with four other value chains for winter salad supply to the UK: conventional...