Publications by authors named "David Kimball"

Background: Neurointerventional robotic systems have potential to reduce occupational radiation, improve procedural precision, and allow for future remote teleoperation. A limited number of single institution case reports and series have been published outlining the safety and feasibility of robot-assisted diagnostic cerebral angiography.

Methods: This is a multicenter, retrospective case series of patients undergoing diagnostic cerebral angiography at three separate institutions - University of California, Davis (UCD); University of California, Los Angeles (UCLA); and University of California, San Francisco (UCSF).

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Background: The inferolateral triangle is a surgical skull base triangle used as a neurosurgical landmark. There are few reports of its measurements with little attention paid to anatomic variations.

Methods: The inferolateral triangle was measured in 10 adult human cadaveric heads via dissection then direct measurement and 5 participants undergoing neuroimaging using tracing features.

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We identified a set of thiosemicarbazone (TSC) metal ion chelators that reactivate specific zinc-deficient p53 mutants using a mechanism called zinc metallochaperones (ZMCs) that restore zinc binding by shuttling zinc into cells. We defined biophysical and cellular assays necessary for structure-activity relationship studies using this mechanism. We investigated an alternative class of zinc scaffolds that differ from TSCs by substitution of the thiocarbamoyl moiety with benzothiazolyl, benzoxazolyl, and benzimidazolyl hydrazones.

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Understanding variation in physiological traits across taxa is a central question in evolutionary biology that has wide-ranging implications in biomedicine, disease ecology, and environmental protection. Sialic acid (Sia), and in particular, 5-N-acetylneuraminic acid (Neu5Ac), is chemically bound to galactose and the underlying glycan via α2-3 or α2-6 glycosidic linkage (i.e.

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Lupus panniculitis (LP), also referred to as lupus erythematosus profundus (LEP), is a chronic recurrent inflammation condition of the subcutaneous fat. It occurs in 1 to 3% of patients with systemic lupus erythematosus (SLE) and in 10% of patients with discoid lupus erythematosus (DLE), but can also occur as an entity of its own. Patients with lupus panniculitis usually present with persistent, often tender and painful skin lesions, or subcutaneous nodules, that range from 1 to 5 cm in diameter.

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Chemotherapy and radiation are more effective in wild-type (WT) p53 tumors due to p53 activation. This is one rationale for developing drugs that reactivate mutant p53 to synergize with chemotherapy and radiation. Zinc metallochaperones (ZMC) are a new class of mutant p53 reactivators that restore WT structure and function to zinc-deficient p53 mutants.

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Triple negative breast cancer (TNBC) is an aggressive subset for which effective therapeutic approaches are needed. A significant proportion of TNBC patients harbor either germline or somatic mutations in , or epigenetic silencing of , which renders them deficient in DNA repair. Virtually all deficient breast cancers harbor mutations in suggesting that inactivation of p53 is a requirement for tumor progression in the setting of deficiency.

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Zinc metallochaperones (ZMC) are a new class of anticancer drugs that reactivate zinc-deficient mutant p53 by raising and buffering intracellular zinc levels sufficiently to restore zinc binding. pharmacodynamics of ZMCs indicate that p53-mutant activity is ON by 4-6 hours and is OFF by 24. We sought to understand the mechanism of this regulation and to translate these findings preclinically.

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The anterolateral triangle is one of 10 surgical triangles of the cavernous sinus and serves as an important anatomic landmark for the skull base surgeon. There are few studies in the English literature that have precisely defined and measured the borders of the anterolateral triangle and little agreement has been made regarding the nomenclature within the English literature. A total of 12 midsagittally hemisected adult human cadaveric head halves were dissected to expose the anterolateral triangle.

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Background: Recent studies show that human placenta, processed and encapsulated for postpartum consumption, contains a host of trace minerals and hormones that could conceivably affect maternal physiology. Our objective was to investigate whether salivary hormone concentrations of women ingesting their own encapsulated placenta during the early postpartum differed from those of women consuming a placebo.

Methods: Randomly assigned participants (N=27) were given a supplement containing either their dehydrated and homogenized placenta (n=12), or placebo (n=15).

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Background: Human maternal placentophagy is gaining popularity among a growing number of women who believe it provides maternal benefits, including prevention of postpartum blues/depression, improved maternal bonding, and reduced fatigue.

Methods: We conducted a randomized, double-blind, placebo-controlled pilot study (N=27) in which participants consumed either their processed, encapsulated placenta (n=12), or similarly prepared placebo (n=15). Maternal mood, bonding, and fatigue were assessed via validated scales across four time points during late pregnancy and early postpartum.

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A lung cancer survivor reflects on facing an uncertain future and beating the odds, on lessons learned, on planning, and especially, on hope.

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Background: Hepatocellular carcinoma (HCC) represents one of the most lethal cancers worldwide due to therapy resistance and disease recurrence. Tumor relapse following treatment could be driven by the persistence of liver cancer stem-like cells (CSCs). The protein BMI1 is a member of the polycomb epigenetic factors governing cellular self-renewal, proliferation, and stemness maintenance.

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Small-molecule restoration of wild-type structure and function to mutant p53 (so-called mutant reactivation) is a highly sought-after goal in cancer drug development. We previously discovered that small-molecule zinc chelators called (ZMCs) reactivate mutant p53 by restoring zinc binding to zinc-deficient p53 mutants. The lead compound identified from the NCI-60 human tumor cell lines screen, NSC319726 (ZMC1), belongs to the thiosemicarbazone (TSC) class of metal ion chelators that bind iron, copper, magnesium, zinc, and other transition metals.

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Oligosaccharides, such as starch, cellulose, and hemicelluloses, are abundant and easily obtainable bio-derived materials that can potentially be used as precursors for fuels and chemical feedstocks. To access the pertinent molecular building blocks (i.e.

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Human maternal placentophagy is a rare but growing practice in several industrialized countries among postpartum mothers seeking a variety of purported health benefits attributed to the practice. These postpartum mothers typically consume their placenta as a processed, encapsulated supplement. To determine whether free (unconjugated) steroid hormones and melatonin in placenta can survive the encapsulation process (namely steaming and dehydration), we analyzed 28 placenta samples processed for encapsulation using liquid chromatography tandem-mass spectrometry (LC-MS/MS) to evaluate the concentration of 17 hormones.

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Objective: The existing literature regarding preoperative cervical spinal tumor embolization is sparse, with few discussions on the indications, risks, and best techniques. We present our experience with the preoperative endovascular management of hypervascular cervical spinal tumors.

Methods: We performed a retrospective review of all patients who underwent preoperative spinal angiography (regardless of whether tumor embolization was performed) at our institution (from 2002 to 2012) for primary and metastatic cervical spinal tumors.

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Cerebral artery fenestrations are usually detected incidentally during angiography, have a reported incidence ranging from of 0.03% to 1%, and rarely cause neurological symptoms. They can, however, be associated with aneurysmal dilatation at the proximal or distal end of the fenestration, cerebral arteriovenous malformations, or (rarely) ischemic symptoms.

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The synthesis, SAR, and in vivo activity of inhibitors of delta-5 desaturase are described. Ring-constraint of the initial series provided access to a variety of in vitro active chemotypes, from which the indazole was selected. Examples from the indazole series displayed in vivo activity in reducing the enzymatic activity of liver delta-5 desaturase.

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Objectives The roof of the porus trigeminus, composed of the posterior petroclinoid dural fold, is an important landmark to the skull base surgeon. Ossification of the posterior petroclinoid dural fold is an anatomical variation rarely mentioned in the literature. Such ossification results in the trigeminal nerve traversing a bony foramen as it enters Meckel cave.

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Modulating GPR88 activity is suggested to have therapeutic utility in the treatment of CNS disorders, such as schizophrenia. This Letter will describe the discovery and SAR development of a class of potent GPR88 agonists.

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p53 is a Zn(2+)-dependent tumor suppressor inactivated in >50% of human cancers. The most common mutation, R175H, inactivates p53 by reducing its affinity for the essential zinc ion, leaving the mutant protein unable to bind the metal in the low [Zn(2+)]free environment of the cell. The exploratory cancer drug zinc metallochaperone-1 (ZMC1) was previously demonstrated to reactivate this and other Zn(2+)-binding mutants by binding Zn(2+) and buffering it to a level such that Zn(2+) can repopulate the defective binding site, but how it accomplishes this in the context of living cells and organisms is unclear.

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Small molecule modulators of GPR88 activity (agonists, antagonists, or modulators) are of interest as potential agents for the treatment of a variety of psychiatric disorders including schizophrenia. A series of phenylglycinol and phenylamine analogs have been prepared and evaluated for their GPR88 agonist activity and pharmacokinetic (PK) properties.

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