UW Neurological Surgery Recent PubMed Publications

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Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD...

Rett Syndrome is an X-linked neurological disorder characterized by behavioral and neurological regression, seizures, motor deficits, and dysautonomia. A particularly prominent presentation includes breathing abnormalities characterized by breathing irregularities, hyperventilation, repetitive breathholding during wakefulness, obstructive and central apneas during sleep, and abnormal responses to hypoxia and hypercapnia. The condition and pathology of the respiratory system is further...

Latent liver stages termed hypnozoites cause relapsing Plasmodium vivax malaria infection and represent a major obstacle in the goal of malaria elimination. Hypnozoites are clinically undetectable, and presently, there are no biomarkers of this persistent parasite reservoir in the human liver. Here, we have identified parasite and human proteins associated with extracellular vesicles (EVs) secreted from in vivo infections exclusively containing hypnozoites. We used P. vivax-infected human...

CONCLUSION: This study establishes the capacity to consistently infect NHPs with purified, vialed, cryopreserved PkSPZ, providing a foundation for future studies to probe protective immunological mechanisms elicited by PfSPZ vaccines that cannot be established in humans.

Microglia play a critical role in the neuroimmune response, but little is known about the role of microglia in sleep following an inflammatory trigger. Nevertheless, decades of research have been predicated on the assumption that an inflammatory trigger increases sleep through microglial activation. We hypothesized that mice (n = 30) with depleted microglia using PLX5622 (PLX) would sleep less following the administration of lipopolysaccharide (LPS) to induce inflammation. Brains were collected...

Cardiac rehabilitation (CR) after stroke has been proven to be a safe and feasible secondary prevention intervention. Limited qualitative data capture people's experiences and perceptions of attending CR following stroke, but with none addressing translational aspects when CR is delivered as routine clinical care. Using a phenomenological, qualitative approach, four semi-structured focus groups were conducted with 15 individuals (60% male) who had completed CR during their stroke care pathway....

YAP1 is a transcriptional coactivator regulated by the Hippo signaling pathway, including NF2. Meningiomas are the most common primary brain tumors; a large percentage exhibit heterozygous loss of chromosome 22 (harboring the NF2 gene) and functional inactivation of the remaining NF2 copy, implicating oncogenic YAP activity in these tumors. Recently, fusions between YAP1 and MAML2 have been identified in a subset of pediatric NF2 wild-type meningiomas. Here, we show that human...

Bouveret syndrome is a rare form of gallstone ileus in which a proximally lodged gallstone in the duodenum causes a gastric outlet obstruction. It is a rare condition that can be challenging to manage. Although endoscopic management remains first line, a surgical approach can be needed. We present two cases of Bouveret syndrome. A 65-year-old man with oral squamous cell carcinoma treated with endoscopic management and a 63-year-old woman treated with surgery.

Genetically engineered live Plasmodium falciparum sporozoites constitute a potential platform for creating consistently attenuated, genetically defined, whole-parasite vaccines against malaria through targeted gene deletions. Such genetically attenuated parasites (GAPs) do not require attenuation by irradiation or concomitant drug treatment. We previously developed a P. falciparum (Pf) GAP with deletions in P52, P36, and SAP1 genes (PfGAP3KO) and demonstrated its safety and immunogenicity in...

Lyophyllum decastes is a common mushroom that is prone to browning during prolonged storage. In this study, the effects of ultrasonic treatment on metabolic gene expression, enzyme activity, and metabolic compounds related to L. decastes browning were investigated. Treatment of the fruiting body at 35 kHz and 300 W for 10 min reduced the browning index of L. decastes by 21.0 % and increased the L* value by 11.1 %. Ultrasonic treatment of the fruiting body resulted in higher levels of total...

Body fat distribution is a major, heritable risk factor for cardiometabolic disease, independent of overall adiposity. Using exome-sequencing in 618,375 individuals (including 160,058 non-Europeans) from the UK, Sweden and Mexico, we identify 16 genes associated with fat distribution at exome-wide significance. We show 6-fold larger effect for fat-distribution associated rare coding variants compared with fine-mapped common alleles, enrichment for genes expressed in adipose tissue and causal...

CONCLUSIONS: Although rare, MT for AIS in the AYA demographic is both safe and effective. Even within this relatively young demographic, age remains significantly associated with improved functional outcomes. The implication of age-dependent stroke outcomes after MT within the AYA demographic needs greater validation to develop effective age-specific protocols for long-term care across both pediatric and adult centers.

CONCLUSIONS: Patient age is an important driver in technique selection, with surgeons selecting a more involved calvarial vault remodeling technique in older children. A variety of surgical techniques were analyzed, with the parietal reshaping technique being significantly associated with reduced length of stay; however, multiple perioperative factors may be contributory and require further analysis. When performed at high-volume centers by experienced pediatric neurosurgeons and craniofacial...

Mutations affecting isocitrate dehydrogenase (IDH) enzymes are prevalent in glioma, leukemia, and other cancers. Although mutant IDH inhibitors are effective against leukemia, they seem to be less active in aggressive glioma, underscoring the need for alternative treatment strategies. Through a chemical synthetic lethality screen, we discovered that IDH1-mutant glioma cells are hypersensitive to drugs targeting enzymes in the de novo pyrimidine nucleotide synthesis pathway, including...

Latrophilin-3 (LPHN3) is a brain specific G-protein coupled receptor associated with increased risk of attention deficit hyperactivity disorder (ADHD) and cognitive deficits. CRISPR/Cas9 was used to generate a constitutive knockout (KO) rat of Lphn3 by deleting exon 3, based on human data that LPHN3 variants are associated with some cases of ADHD. Lphn3 KO rats are hyperactive with an attenuated response to ADHD medication and have cognitive deficits. Here, we tested KO, heterozygous (HET), and...

Robotic-assisted gait training (RAGT) devices allow intensive high repetition of the gait cycle in individuals with locomotor disability, with reduced therapist effort. In addition to usual rehabilitation, RAGT post-stroke improves the likelihood of regaining independent walking, with maximum efficacy identified in the acute and subacute phases of stroke. This study explores the usability and acceptance of RAGT among persons with stroke in an acute hospital setting and examines users'...

The spatiotemporal representation of neural activity during rest and upon sensory stimulation in cortical areas is highly dynamic and may be predominantly governed by cortical state. On the mesoscale level, intrinsic neuronal activity ranges from a persistent state, generally associated with a sustained depolarization of neurons, to a bimodal, slow wave-like state with bursts of neuronal activation alternating with silent periods. These different activity states are prevalent under certain types...

CONCLUSIONS AND RELEVANCE: This study found that most participants with a GCS score of 15 and negative head CT scan reported incomplete recovery at 2 weeks and 6 months after their injury. The findings suggest that emergency department clinicians should recommend 2-week follow-up visits for these patients to identify those with incomplete recovery and to facilitate their rehabilitation.

Breathing is a critical, complex, and highly integrated behavior. Normal rhythmic breathing, also referred to as eupnea, is interspersed with different breathing related behaviors. Sighing is one of such behaviors, essential for maintaining effective gas exchange by preventing the gradual collapse of alveoli in the lungs, known as atelectasis. Critical for the generation of both sighing and eupneic breathing is a region of the medulla known as the preBötzinger Complex (preBötC). Efforts are...