Publications by authors named "David Dennis"

Article Synopsis
  • Water-soluble prodrug technology has potential for improving the oral bioavailability of insoluble small molecule drugs, but it's not widely used due to rapid breakdown in the gastrointestinal tract that leads to ineffective drug absorption.
  • Researchers developed a new water-soluble promoiety (Sol-moiety) technology aimed at slowing the hydrolysis of prodrugs, enhancing drug absorption instead of causing precipitation.
  • The effectiveness of this technology was shown by significantly improving the pharmacokinetics of drugs like enzalutamide, vemurafenib, and paclitaxel, including a successful study on a paclitaxel prodrug in a mouse model for pancreatic tumors.
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Importance: Ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) are the most treatable causes of out-of-hospital cardiac arrest (OHCA). Yet, it remains unknown if defibrillator pad position, placement in the anterior-posterior (AP) or anterior-lateral (AL) locations, impacts patient outcomes in VF or pVT OHCA.

Objective: To determine the association between initial defibrillator pad placement position and OHCA outcomes for patients presenting with VF or pVT.

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High temperature requirement A serine peptidase 1 (HTRA1) is a serine protease involved in an array of signaling pathways. It is also responsible for the regulation of protein aggregates via refolding, translocation, and degradation. It has subsequently been found that runaway proteolytic HTRA1 activity plays a role in a variety of diseases, including Age-Related Macular Degeneration (AMD), osteoarthritis, and Rheumatoid Arthritis.

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The phytocannabinoid cannabigerol (CBG) is the central biosynthetic precursor to many cannabinoids, including Δ-tetrahydrocannabinol (THC) and cannabidiol (CBD). Though the use of CBG has recently witnessed a widespread surge because of its beneficial health effects and lack of psychoactivity, its metabolism by human cytochrome P450s is largely unknown. Herein, we describe comprehensive and cytochrome P450 (CYP)-mediated metabolic studies of CBG, ranging from liquid chromatography tandem mass spectrometry-based primary metabolic site determination, synthetic validation, and kinetic behavior using targeted mass spectrometry.

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Despite centuries-long use of in human culture and the now ubiquitous claims of its medicinal value, only a small handful of phytocannabinoids have been rigorously evaluated for pharmacological properties. While more than 100 distinct minor cannabinoids have been documented to date, a paucity of studies on their biological activities have been conducted due to a lack of routine access to sufficient quantities for testing. Herein, we report a strategy to prepare several structurally diverse minor cannabinoids deriving synthetically from readily available cannabidiol.

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Dabbing and vaping cannabis extracts have gained large popularity in the United States as alternatives to cannabis smoking, but diversity in both available products and consumption habits make it difficult to assess consumer exposure to psychoactive ingredients and potentially harmful components. This work studies the how relative ratios of the two primary components of cannabis extracts, Δ-tetrahydrocannabinol (THC) and terpenes, affect dosage of these and exposure to harmful or potentially harmful components (HPHCs). THC contains a monoterpene moiety and has been previously shown to emit similar volatile degradation products to terpenes when vaporized.

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Recent direct numerical simulations (DNS) and experiments in turbulent channel flow have found intermittent low- and high-drag events in Newtonian fluid flows, at Reτ=uτh/ν between 70 and 100, where uτ, and ν are the friction velocity, channel half-height and kinematic viscosity, respectively. These intervals of low-drag and high-drag have been termed "hibernating" and "hyperactive", respectively, and in this paper, a further investigation of these intermittent events is conducted using experimental and numerical techniques. For experiments, simultaneous measurements of wall shear stress and velocity are carried out in a channel flow facility using hot-film anemometry (HFA) and laser Doppler velocimetry (LDV), respectively, for Reτ between 70 and 250.

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Objective: While emphasized in clinical practice, the association between advanced airway insertion first-pass success (FPS) and patient outcomes is incompletely understood. We sought to determine the association of airway insertion FPS with adult out-of-hospital cardiac arrest (OHCA) outcomes in the Pragmatic Airway Resuscitation Trial (PART).

Methods: We performed a secondary analysis of PART, a multicenter clinical trial comparing LT and ETI upon adult OHCA outcomes.

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Heat stress occurring at reproductive stages can result in significant and permanent damage to crop yields. However, previous genetic studies in understanding heat stress response and signaling were performed mostly on seedling and plants at early vegetative stages. Here we identify, using a developmentally defined, gain-of-function genetic screen with approximately 18 000 Arabidopsis thaliana activation-tagged lines, a mutant that maintained productive seed set post-severe heat stress during flowering.

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Rapid and reproducible access to a series of unique porphyrin and bacteriochlorin glycoconjugates, including meso-glycosylated porphyrins and bacteriochlorins, and beta-glycosylated porphyrins, via copper catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) is reported for the first time. The work presented highlights the system-dependent reaction conditions required for glycosylation to porphyrins and bacteriochlorins based on the unique electronic properties of each ring system. Attenuated reaction conditions were used to synthesize fifteen new glycosylated porphyrin and bacteriochlorin analogs in 74 - 99% yield, and were extended to solid support to produce the first oligo(amidoamine)-based porphyrin glycoconjugate.

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Anthracyclines are archetypal representatives of the tetracyclic type II polyketide natural products that are widely used in cancer chemotherapy. Although the synthesis of this class of compounds has been a subject of several investigations, all known approaches are based on annulations, relying on the union of properly prefunctionalized building blocks. Herein, we describe a conceptually different approach using a polynuclear arene as a starting template, ideally requiring only functional decorations to reach the desired target molecule.

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Background: Rigid interspinous process fixation (ISPF) has received consideration as an efficient, minimally disruptive technique in supporting lumbar interbody fusion. However, despite advantageous intraoperative utility, limited evidence exists characterizing midterm to long-term clinical outcomes with ISPF. The objective of this multicenter study was to prospectively assess patients receiving single-level anterior (ALIF) or lateral (LLIF) lumbar interbody fusion with adjunctive ISPF.

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Background: The Luke Commission, a provider of comprehensive mobile health outreach in rural Swaziland, focuses on human immunodeficiency virus testing and prevention, including the performance of over 100 circumcisions weekly. Educational objectives for medical student global health electives are essential. Learning research methodology while engaging in clinical activities reinforces curriculum goals.

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Inadvertent knotting of infant feeding tubes used for clean intermittent catheterisation (CIC) is a rare complication in paediatric patients. The small flexible tubes used in infants if advanced too far into the bladder may form a knot as the bladder empties. Surgical intervention is required especially if it is lodged in the urethra.

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Early-phase transmission (EPT) of Yersinia pestis by unblocked fleas is a well-documented, replicable phenomenon with poorly defined mechanisms. We review evidence demonstrating EPT and current knowledge on its biological and biomechanical processes. We discuss the importance of EPT in the epizootic spread of Y.

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The inherent difficulty of understanding turbulence has led to researchers attacking the topic in many different ways over the years of turbulence research. Some approaches have been more successful than others, but most only deal with part of the problem. One approach that has seen reasonable success (or at least popularity) is that of attempting to deconstruct the complex and disorganised turbulent flow field into to a set of motions that are in some way organised.

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Organizational states of turbulence are identified through novel analysis of large scale pipe flow experiments at a Reynolds number of 35 000. The distinct states are revealed by an azimuthal decomposition of the two-point spatial correlation of the streamwise velocity fluctuation. States with dominant azimuthal wave numbers corresponding to k_{θ}=2,3,4,5,6 are discovered and their structure revealed as a series of alternately rotating quasistreamwise vortices.

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Influenza virus infections result in considerable morbidity and mortality both in the temperate and tropical world. Influenza surveillance over multiple years is important to determine the impact and epidemiology of influenza and to develop a national vaccine policy, especially in countries developing influenza vaccine manufacturing capacity, such as Vietnam. We conducted surveillance of influenza and influenza-like illness in Vietnam through the National Influenza Surveillance System during 2006-2010.

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Background: Vietnam is currently developing domestic capability to manufacture influenza vaccines but information on the genetic and antigenic characteristics of locally circulating seasonal influenza viruses is limited. To assess the relevance of WHO recommended vaccine strains to the situation in Vietnam, we analyzed the genetic relatedness of the hemagglutinin (HA) gene of seasonal influenza A viruses circulating in Vietnam from 2001 to 2009 to WHO recommended vaccine strains over the same period.

Methods And Principal Findings: We sequenced the HA gene of 32 H1N1 and 44 H3N2 seasonal influenza A isolates from laboratory-based sentinel surveillance sites in Hanoi from 2001 to 2005 and from a national influenza surveillance system from 2005 to 2009.

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In 2006, national influenza surveillance was implemented in Vietnam. Epidemiologic and demographic data and a throat swab for influenza testing were collected from a subset of outpatients with influenza-like illness (ILI). During January 1, 2006 through December 31, 2007, of 184,521 ILI cases identified at surveillance sites, 11,082 were tested and 2112 (19%) were positive for influenza by reverse transcription polymerase chain reaction.

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Protecting crop yield under drought stress is a major challenge for modern agriculture. One biotechnological target for improving plant drought tolerance is the genetic manipulation of the stress response to the hormone abscisic acid (ABA). Previous genetic studies have implicated the involvement of the beta-subunit of Arabidopsis farnesyltransferase (ERA1) in the regulation of ABA sensing and drought tolerance.

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Wild-type tobacco (Nicotiana tabacum L.) seed development was characterized with respect to architecture and carbohydrate metabolism. Tobacco seeds accumulate oil and protein in the embryo, cellular endosperm and inner layer of the seed coat.

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