UW Neurological Surgery Recent PubMed Publications

Machine learning identifies molecular regulators and therapeutics for targeting SARS-CoV2-induced cytokine release

3 years 9 months ago
Although 15-20% of COVID-19 patients experience hyper-inflammation induced by massive cytokine production, cellular triggers of this process and strategies to target them remain poorly understood. Here, we show that the N-terminal domain (NTD) of the SARS-CoV-2 spike protein substantially induces multiple inflammatory molecules in myeloid cells and human PBMCs. Using a combination of phenotypic screening with machine learning-based modeling, we identified and experimentally validated several...
Marina Chan

Noncanonical Notch signals have opposing roles during cardiac development

3 years 9 months ago
The Notch pathway is an ancient intercellular signaling system with crucial roles in numerous cell-fate decision processes across species. While the canonical pathway is activated by ligand-induced cleavage and nuclear localization of membrane-bound Notch, Notch can also exert its activity in a ligand/transcription-independent fashion, which is conserved in Drosophila, Xenopus, and mammals. However, the noncanonical role remains poorly understood in in vivo processes. Here we show that increased...
Matthew Miyamoto

Targeting community-based naloxone distribution using opioid overdose death rates: A descriptive analysis of naloxone rescue kits and opioid overdose deaths in Massachusetts and Rhode Island

3 years 9 months ago
CONCLUSIONS: We identified variations in spatial patterns of opioid overdose fatalities and naloxone availability, and these disparities appeared to be widening in some areas over time. Data on the spatial distribution of naloxone distribution and opioid overdose deaths can inform targeted, community-based naloxone distribution strategies that optimize resources to prevent opioid overdose fatalities.
Xiao Zang

Thiamine increases resident endoglin positive cardiac progenitor cells and atrial contractile force in humans: A randomised controlled trial

3 years 9 months ago
CONCLUSION: Thiamine does not improve proliferation ability of CPC in patients undergoing CABG, but increases the proportion of CD34^(-)/CD105^(+) cells. Having not met its primary endpoint, this study provides the impetus to re-examine CPC biology prior to any clinical outcome-based trial examining potential beneficial cardiovascular effects of thiamine.
Sean Coffey

Hypoglossal Nerve Schwannoma With Severe Brainstem Compression: Microsurgical Excision by Extreme Lateral Approach: 2-Dimensional Operative Video

3 years 9 months ago
A 37-yr-old male presented with a history of left-sided tongue atrophy and fasciculations and weakness of upper limbs for 3 mo. Magnetic resonance imaging (MRI) revealed a large, partially cystic tumor with severe compression of the brainstem and spinal cord, with expansion and erosion of the hypoglossal canal. Computed tomography (CT) angiography showed the left vertebral artery to be anteriorly displaced by the tumor. A retrosigmoid craniotomy and craniectomy were performed followed by...
Qazi Zeeshan

Extrinsic interactions in the microenvironment in vivo activate an antiapoptotic multidrug-resistant phenotype in CLL

3 years 9 months ago
The Bcl-2 inhibitor venetoclax has yielded exceptional clinical responses in chronic lymphocytic leukemia (CLL). However, de novo resistance can result in failure to achieve negative minimal residual disease and predicts poor treatment outcomes. Consequently, additional proapoptotic drugs, such as inhibitors of Mcl-1 and Bcl-xL, are in development. By profiling antiapoptotic proteins using flow cytometry, we find that leukemic B cells that recently emigrated from the lymph node (CD69+/CXCR4Low)...
Kallesh D Jayappa

An assessment of executive function in two different rat models of attention-deficit hyperactivity disorder: Spontaneously hypertensive versus Lphn3 knockout rats

3 years 9 months ago
Attention-deficit/hyperactivity disorder (ADHD) a common neurodevelopmental disorder of childhood and often comorbid with other externalizing disorders (EDs). There is evidence that externalizing behaviors share a common genetic etiology. Recently, a genome-wide, multigenerational sample linked variants in the Lphn3 gene to ADHD and other externalizing behaviors. Likewise, limited research in animal models has provided converging evidence that Lphn3 plays a role in EDs. This study examined the...
Helen J K Sable

The Intersection of Type 2 Myocardial Infarction and Heart Failure

3 years 9 months ago
Background Type 2 myocardial infarction (T2MI) is common and associated with high cardiovascular event rates. However, the relationship between T2MI and heart failure (HF) is uncertain. Methods and Results We identified patients with T2MI at a large tertiary hospital between October 2017 and May 2018. Patient characteristics, causes of T2MI, and subsequent HF hospitalizations were determined by physician chart review. We identified 359 patients with T2MI over the study period; 184 patients had a...
Cian P McCarthy

Genomic insights into the diversity, virulence and resistance of <em>Klebsiella pneumoniae</em> extensively drug resistant clinical isolates

3 years 9 months ago
Klebsiella pneumoniae has been implicated in wide-ranging nosocomial outbreaks, causing severe infections without effective treatments due to antibiotic resistance. Here, we performed genome sequencing of 70 extensively drug resistant clinical isolates, collected from Brasília's hospitals (Brazil) between 2010 and 2014. The majority of strains (60 out of 70) belonged to a single clonal complex (CC), CC258, which has become distributed worldwide in the last two decades. Of these CC258 strains, 44...
Amy H Y Lee

Tuberous Sclerosis Complex (TSC) Inactivation Increases Neuronal Network Activity by Enhancing Ca<sup>2+</sup> Influx via L-Type Ca<sup>2+</sup> Channels

3 years 9 months ago
Tuberous sclerosis complex (TSC) is a multisystem developmental disorder characterized by hamartomas in various organs, such as the brain, lungs, and kidneys. Epilepsy, along with autism and intellectual disability, is one of the neurologic impairments associated with TSC that has an intimate relationship with developmental outcomes and quality of life. Sustained activation of the mammalian target of rapamycin (mTOR) via TSC1 or TSC2 mutations is known to be involved in the onset of epilepsy in...
Chihiro Hisatsune

Colchicine for prevention of vascular inflammation in Non-CardioEmbolic stroke (CONVINCE) - study protocol for a randomised controlled trial

3 years 9 months ago
BACKGROUND: Inflammation contributes to unstable atherosclerotic plaque and stroke. In randomised trials in patients with coronary disease, canukinumab (an interleukin-1B antagonist) and colchicine (a tubulin inhibitor with pleiotropic anti-inflammatory effects) reduced recurrent vascular events.Hypothesis: Anti-inflammatory therapy with low-dose colchicine plus usual care will reduce recurrent vascular events in patients with non-severe, non-cardioembolic stroke and TIA compared with usual care...
Peter Kelly

RNase III and RNase E Influence Posttranscriptional Regulatory Networks Involved in Virulence Factor Production, Metabolism, and Regulatory RNA Processing in Bordetella pertussis

3 years 9 months ago
Bordetella pertussis has been shown to encode regulatory RNAs, yet the posttranscriptional regulatory circuits on which they act remain to be fully elucidated. We generated mutants lacking the endonucleases RNase III and RNase E and assessed their individual impact on the B. pertussis transcriptome. Transcriptome sequencing (RNA-Seq) analysis showed differential expression of ∼25% of the B. pertussis transcriptome in each mutant, with only 28% overlap between data sets. Both endonucleases...
Gyles Ifill

Dual mechanisms of opioid-induced respiratory depression in the inspiratory rhythm-generating network

3 years 9 months ago
The analgesic utility of opioid-based drugs is limited by the life-threatening risk of respiratory depression. Opioid-induced respiratory depression (OIRD), mediated by the μ-opioid receptor (MOR), is characterized by a pronounced decrease in the frequency and regularity of the inspiratory rhythm, which originates from the medullary preBötzinger Complex (preBötC). To unravel the cellular- and network-level consequences of MOR activation in the preBötC, MOR-expressing neurons were optogenetically...
Nathan A Baertsch

Understanding loss to follow-up in a longitudinal study of people with traumatic brain injury

3 years 9 months ago
CONCLUSIONS: The findings suggest a need to understand sociodemographic variables and their influence on participant attrition in longitudinal TBI research. With a better understanding of these predictors, procedures can be developed to address retention of participants who are identified as being at increased risk for study drop out.
Leia Vos

Practical Assessment of Alcohol Use Disorder in Routine Primary Care: Performance of an Alcohol Symptom Checklist

3 years 9 months ago
CONCLUSIONS: Alcohol Symptom Checklists used in routine care discriminated AUD severity consistently with current definitions of AUD and performed equitably across age, sex, race, and ethnicity. Integrating symptom checklists into routine care may help inform clinical decision-making around diagnosing and managing AUD.
Kevin A Hallgren
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