UW Neurological Surgery Recent PubMed Publications

CONCLUSIONS: Primary care clinics that implement office-based addiction treatment by nurses increase patient-years of opioid use disorder (OUD) treatment in male but not female patients. Exploratory findings suggest that differences in the proportion of patients treated for OUD, rather than differences in the duration of OUD treatment, account for observed differences across groups.

Somatosensory perception largely emerges from diverse peripheral sensory neurons whose cell bodies reside in dorsal root ganglia (DRG). Damage or dysfunction of DRG neurons is a major cause of chronic pain and sensory loss. In mice, deep single-cell transcriptomic profiling and genetically defined models have offered important clues into DRG function, but in humans, the cellular and molecular landscape of DRG neurons remains less understood. Here, we constructed a reference cell atlas of the...

The ribosome is the highly conserved molecular machine that decodes mRNAs during protein synthesis. While traditionally thought to consist of a uniform set of proteins, here we discover that ribosome composition is reprogrammed to adapt to intrinsic and external cellular perturbations. During infection by non-segmented negative-sense viruses, viral entry into cells recruits the large ribosomal subunit protein rpL40 to a noncanonical site on the small subunit of 80S ribosomes near the mRNA entry...

Glioblastoma (GBM) quiescent (Q) cell populations are hypothesized to contain cancer stem-like cells (CSC) that drive tumor growth, cellular heterogeneity, and recurrence. However, GBM tumors do not neatly resolve into developmental hierarchies and Q stem-like activities are difficult to assess. Here, we evaluated tumor Q subpopulations in patient-derived GBM xenograft tumors using live cell reporters, DNA label retention assays, and single cell genomics. Compared to adult neural stems cells...

Cognitive decline with aging, and some neurodegenerative conditions like Alzheimer's disease, disproportionately affects females yet few mechanisms beyond steroid hormone signaling fully explain this sex-specific vulnerability. The chromatin-remodeling DEK protein, upregulated by estrogen and progesterone and broadly expressed in the brain, including the hippocampus, may be one such mechanism. We have previously linked DEK loss with indices of neuronal dysfunction, including increased DNA...

Alzheimer's disease (AD) is the most common cause of dementia, with global case numbers projected to reach 153 million in 2050 ¹ . AD is highly heritable, with twin-based heritability estimates of 60-80% ² . While 1,200 causal loci are predicted to exist for AD ³ , approximately 80 have been associated with AD in two recent studies ^(4,5) , suggesting that many loci remain to be discovered ⁶ . Here, we analyzed data from 183,620 AD cases and 2.6 million controls from diverse ancestries,...

Pediatric Inflammatory Bowel Disease (IBD) remains challenging to treat and difficult to prognosticate. Although multiple immune cell types coordinate pathology in both Crohn's disease (CD) and ulcerative colitis (UC), specifying which cell types and cell states portend better or worse response to major IBD treatment strategies, including anti-TNF therapies (the only FDA-approved therapy for pediatric IBD), remains challenging. Here, we present the results of the PREDICT study, which enrolled 79...

After a traumatic brain injury, around 12% of patients require surgical interventions during their index hospitalization due to delayed or progressive intracranial hemorrhage or complications such as elevated intracranial pressure (ICP)¹. Compiling data from four harmonized studies with 288 patients that have high-frequency physiological measurements, including ICP, we aimed to determine factors associated with those surgeries and whether longitudinal physiological measurements could be used to...

CONCLUSIONS: Our data place TNFR2 signaling as a potential upstream regulator of TOX expression in T cells and propose TNFR2 antagonism as a novel immunotherapeutic strategy.

In contrast to living organisms, viruses were long thought to lack protein synthesis machinery and instead depend on host factors to translate viral transcripts. Here, we discover that giant DNA viruses encode a distinct and functional IF4F translation initiation complex to drive protein synthesis, thereby blurring the line between cellular and acellular biology. During infection, eukaryotic IF4F on host ribosomes is replaced by an essential viral IF4F that regulates viral translation, virion...

Acute traumatic spinal cord injury (tSCI) often results in devastating neurological dysfunction for affected individuals and imposes a substantial financial burden on society worldwide. Current treatment approaches have limited ability to counteract secondary injury expansion and additional cell death. The extent of secondary damage is a result of posttraumatic tissue swelling, edema, vascular damage, and hematoma and these factors contribute to pathological intraspinal pressure (ISP) elevations...

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We have developed a low-cost (30 USD), simple do-it-yourself (DIY) potentiostat with cyclic voltammetry (CV), open circuit potential (OCP) and electrochemical impedance spectroscopy (EIS) capability. The HunStat2 potentiostat is based on Analog Devices' AD5941 Analog Front End chip, which significantly simplifies the construction of potentiostats for both direct and alternating current (DC and AC, respectively) techniques. Interested readers are provided with circuit diagrams and a bill of...

Tractometry of diffusion-weighted magnetic resonance imaging (dMRI) non-invasively quantifies tissue properties of brain connections. It is widely used in aging studies but could be less reliable in aging brains due to increased white matter free water. We demonstrate that computational free water elimination (FWE) and multi-shell multi-tissue (MSMT) modeling both increase the reliability and accuracy of tractometry in a large (n = 396) cohort of older adults (65-103 y.o.). We found substantial...

Meta-analysis of gene-based tests using single-variant summary statistics is a powerful strategy for genetic association studies. However, current approaches require sharing the covariance matrix between variants for each study and trait of interest. For large-scale studies with many phenotypes, these matrices can be cumbersome to calculate, store and share. Here, to address this challenge, we present REMETA-an efficient tool for meta-analysis of gene-based tests. REMETA uses a single sparse...

Insomnia and depression are common co-morbidities associated with mild traumatic brain injury (mTBI). Data from Transforming Research and Clinical Knowledge in TBI, a longitudinal cohort study of TBI and orthopedic controls (OTC), were used to examine insomnia trajectories and the temporal relationship between insomnia and depressive symptoms during recovery. mTBI (n = 1,557) and OTC (n = 226) adult patients with no psychiatric or sleep disorder history were assessed at 2 weeks and 3, 6, and 12...

CONCLUSION: This Delphi study specifically addresses the gap in clinical guidance for danazol management in HAE patients. The resulting consensus document provides a valuable tool to aid the standardization of danazol discontinuation protocols and ensures that patients can access the safest and most effective treatment options available.

CONCLUSIONS: Despite varying levels of formal knowledge of pain management, individuals with TBI reported utilizing a wide array of strategies to self-manage pain - often informed by "trial-and-error." Guided self-management training may enhance the effectiveness of their approach as well as possibly increase the efficiency in which they develop an effective approach and make subsequent adjustments.

Mpox re-emerged globally in 2022 with atypical clinical features and efficient human-to-human transmission, which underscores the need to better understand host immune responses. We conducted an integrative transcriptomic analysis of mpox virus (MPXV) infection in nonhuman primates by leveraging RNA-Seq datasets from whole-blood and skin. We applied the Generalized Linear Model with Quasi-Likelihood F-test and Magnitude-Altitude Score (GLMQL-MAS), a method that combines rigorous statistical...