UW Neurological Surgery Recent PubMed Publications

Sleep timing and the circadian clock in mammals: Past, present and the road ahead

4 years ago
Nearly all mammals display robust daily rhythms of physiology and behavior. These approximately 24-h cycles, known as circadian rhythms, are driven by a master clock in the suprachiasmatic nucleus (SCN) of the hypothalamus and affect biological processes ranging from metabolism to immune function. Perhaps the most overt output of the circadian clock is the sleep-wake cycle, the integrity of which is critical for health and homeostasis of the organism. In this review, we summarize our current...
Raymond E A Sanchez

GABA<sub>A</sub> Alpha 2,3 Modulation Improves Select Phenotypes in a Mouse Model of Fragile X Syndrome

4 years ago
Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability. FXS is caused by functional loss of the Fragile X Protein (FXP), also known as Fragile X Mental Retardation Protein (FMRP). In humans and animal models, loss of FXP leads to sensory hypersensitivity, increased susceptibility to seizures and cortical hyperactivity. Several components of the GABAergic system, the major inhibitory system in the brain, are dysregulated in FXS, and thus modulation of GABAergic...
Tori L Schaefer

Radiation Necrosis from Stereotactic Radiosurgery-How Do We Mitigate?

4 years ago
Intracranial stereotactic radiosurgery (SRS) is an effective and convenient treatment for many brain conditions. Data regarding safety come mostly from retrospective single institutional studies and a small number of prospective studies. Variations in target delineation, treatment delivery, imaging follow-up protocols and dose prescription limit the interpretation of this data. There has been much clinical focus on radiation necrosis (RN) in particular, as it is being increasingly recognized on...
Balamurugan A Vellayappan

Ligand Conjugate Structure Activity Relationships and Enhanced Endosomal Escape with a Targeted Polymer Micelle in Non-Human Primates

4 years ago
N-Acetylgalactosamine (GalNAc) conjugated small interfering RNA (siRNA) are a leading RNA interference (RNAi) platform allowing targeted inhibition of disease-causing genes in hepatocytes. More than a decade of development has recently resulted in the first approvals for this class of drugs. While substantial effort has been made to improve nucleic acid modification patterns for better payload stability and efficacy, relatively little attention has been given to the GalNAc targeting ligand. In...
Richard James Holland

Dibutyl phthalate disrupts conserved circadian rhythm in Drosophila and human cells

4 years ago
People are constantly exposed to phthalates, due to their common use in the production of plastics, pharmaceuticals, cosmetics and skin care products. The ability of phthalates to disrupt endocrine signaling, leading to developmental, reproductive and metabolic defects, has been studied, yet how phthalates interfere with these biological functions is still unclear. To uncover DBP interacting molecular pathways, we raised Drosophila melanogaster on food containing dibutyl phthalate (DBP) at...
Wen Liu

Long-chain acylcarnitine 18:1 acutely increases human atrial myocardial contractility and arrhythmia susceptibility

4 years ago
Long-chain acylcarnitines (LCACs) are known to directly alter cardiac contractility and electrophysiology. However, the acute effect of LCACs on human cardiac function is unknown. We aimed to determine the effect of LCAC 18:1, which has been associated with cardiovascular disease, on the contractility and arrhythmia susceptibility of human atrial myocardium. Additionally, we aimed to assess how LCAC 18:1 alters Ca^(2+) influx and spontaneous Ca^(2+) release in vitro. Human right atrial...
Hamish M Aitken-Buck

The <em>Drosophila melanogaster</em> Levodopa-Induced Depression Model Exhibits Negative Geotaxis Deficits and Differential Gene Expression in Males and Females

4 years ago
More than 320 million people live with depression in the world, a disorder that severely limits psychosocial functioning and diminishes quality of life. The prevalence of major depression is almost two times higher in women than in men. However, the molecular mechanisms of its sex-specific pathophysiology are still poorly understood. Drosophila melanogaster is an established model for neurobiological research of depression-like states, as well as for the study of molecular and genetic sex...
Thiago C Moulin

The Chemistry of the Ketogenic Diet: Updates and Opportunities in Organic Synthesis

4 years ago
The high-fat, low-carbohydrate (ketogenic) diet has grown in popularity in the last decade as a weight loss tool. Research into the diet's effects on the body have revealed a variety of other health benefits. The use of exogenous ketone supplements to confer the benefits of the diet without strict adherence to it represents an exciting new area of focus. Synthetic ketogenic compounds are of particular interest that has received very little emphasis and is an untapped area of focus for chemical...
Michael Scott Williams

Incidence of Immune-Mediated Pseudoprogression of Lymphoma Treated with Immune Checkpoint Inhibitors: Systematic Review and Meta-Analysis

4 years ago
We evaluated the incidence of pseudoprogression and indeterminate response (IR) in patients with lymphoma treated with immune checkpoint inhibitors (ICIs). A systematic search of PubMed and EMBASE was performed up to 6 February 2021, using the keywords "lymphoma," "immunotherapy," and "pseudoprogression." Random-effects models were used to calculate both pooled incidence of pseudoprogression patients with lymphoma and an IR according to LYRIC criteria, while the Higgins inconsistency index (I2)...
Amy Junghyun Lee

Patient Activation, Depressive Symptoms, and Self-Rated Health: Care Management Intervention Effects among High-Need, Medically Complex Adults

4 years ago
The purpose of this randomized controlled trial (n = 268) at a Federally Qualified Health Center was to evaluate the outcomes of a care management intervention versus an attention control telephone intervention on changes in patient activation, depressive symptoms and self-rated health among a population of high-need, medically complex adults. Both groups had similar, statistically significant improvements in patient activation and self-rated health. Both groups had significant reductions in...
Cynthia F Corbett

Characterizing initiation, use, and discontinuation of extended-release buprenorphine in a nationally representative United States commercially insured cohort

4 years ago
CONCLUSIONS: Across all treatment groups, medication discontinuation was high, and in this sample of early adopters with limited follow-up time, we found no evidence that extended-release buprenorphine offered a retention advantage compared to other MOUD in real-world settings. Retention continues to represent a major obstacle to treatment effectiveness, and interventions are needed to address this challenge even as new MOUD formulations become available.
Jake R Morgan

The jaw-dropping costs of oral cavity cancer malpractice

4 years ago
CONCLUSIONS: There has been a significant rise in allegations of failure to biopsy and failure to refer (p < 0.05). In addition, while award amounts appear different between decades, the difference is not statistically significant (p = 0.248). Education should focus on early diagnosis, biopsy, and referral to physicians who routinely care for this patient population.
Amanda Wong

PfSPZ-CVac efficacy against malaria increases from 0% to 75% when administered in the absence of erythrocyte stage parasitemia: A randomized, placebo-controlled trial with controlled human malaria infection

4 years ago
PfSPZ-CVac combines 'PfSPZ Challenge', which consists of infectious Plasmodium falciparum sporozoites (PfSPZ), with concurrent antimalarial chemoprophylaxis. In a previously-published PfSPZ-CVac study, three doses of 5.12x104 PfSPZ-CVac given 28 days apart had 100% vaccine efficacy (VE) against controlled human malaria infection (CHMI) 10 weeks after the last immunization, while the same dose given as three injections five days apart had 63% VE. Here, we conducted a dose escalation trial of...
Sean C Murphy

Synthesis and biological evaluation of novel 2-alkoxycarbonylallylester phosphonium derivatives as potential anticancer agents

4 years ago
Several phosphonium derivatives have been synthesized from Baylis-Hillman (BH) reaction derived allyl bromides and aryl phosphines as mitochondria targeting anticancer agents. In vitro cell proliferation inhibition studies on various solid tumor cell lines indicate that most of the compounds exhibit IC(50) values in µM concentrations. Further studies reveal that β-substituted BH bromide derived phosphonium derivatives enhance the biological activity to low µM IC(50) values. In vitrometabolic...
Zachary S Gardner

Hybrid microcatheter angioplasty for refractory cerebral vasospasm

4 years ago
Cerebral vasospasm is a significant cause of morbidity and mortality associated with aneurysmal subarachnoid hemorrhage (aSAH). Intra-arterial chemical and mechanical angioplasty, performed alone or in combination, have been shown to ameliorate cerebral vasospasm and improve patient outcomes. Few options exist for patients who fail these traditional endovascular tactics. We propose a hybrid microcatheter technique that combines the mechanical benefit of transient high pressure induced by...
Melanie Walker
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