Publications by authors named "Michael O'Neil"

Higher estrus-associated temperatures (HEAT) are a hallmark feature in sexually active females. The overarching aim of this study was to characterize the variability, magnitude, and persistence of HEAT in heifers and suckled beef cows as well as identify associated factors when occurring during thermoneutral conditions at the onset of the spring breeding season. In both heifers and cows, estrus was induced using a 7-d controlled internal drug release (CIDR)-PGF2α protocol.

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Objective: A series of novel, substituted tetracyclic benzothiazepines were designed and prepared in an effort to optimize the potency of this chemical class against drug-resistant strains of the malaria parasite.

Methods: Tetracyclic benzothiazepines bearing structural modification at seven distinct positions within the structure were synthesized in Knoevenagel condensation reactions followed by sequential intermolecular thio-Michael and then intramolecular imine formation reactions. Following purification and chemical characterization, the novel compounds were tested for in vitro efficacy against blood-stage P.

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Objective: This study aimed to evaluate the rescheduling of hydrocodone combination products (HCPs) from schedule III (CIII) to schedule II (CII) in patients receiving chronic HCP therapy.

Methods: This study was a retrospective cohort analysis of administrative pharmacy data from 118 statewide pharmacies from a retail chain in Tennessee. HCP filling histories were analyzed on patients meeting enrollment criteria from July 1, 2014, to October 1, 2015.

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A 44-year-old male with ongoing chest pain and left ventricular ejection fraction <20% was transferred from a peripheral hospital with intra-aortic balloon pump placement following a non-ST-elevation myocardial infarction (STEMI). The patient underwent emergent multi-vessel coronary artery bypass grafting requiring veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) on post-operative day (POD)#9 secondary to cardiogenic shock with biventricular failure. Due to clot formation, an oxygenator change-out was necessary shortly after initiation.

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Aims: Improvements in information technology have granted the recent development of rapid, cloud-enabled, onsite laboratory testing for rheumatoid arthritis (RA). This study aims to quantify the value to payers of such technologies.

Materials And Methods: To calculate the value of rapid, cloud-enabled, onsite laboratory testing to diagnose RA relative to traditional, centralized laboratory testing, an Excel-based decision tree model was created that simulated potential cost-savings to payers who cover routine evaluations of RA patients in the US.

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Article Synopsis
  • Pulsatile perfusion during cardiopulmonary bypass (CPB) may enhance microcirculation compared to traditional nonpulsatile methods, as evidenced by a study involving high-risk cardiac patients.
  • The study measured microcirculatory characteristics and tissue oxygen saturation at various time points during and after CPB, revealing that the pulsatile group maintained better blood flow and perfusion.
  • Overall, the findings suggest that pulsatile flow can lead to better recovery of microvascular function and potentially reduce complications related to systemic inflammation and reperfusion injury.
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In any drug discovery and development effort, a reduction in the time of the lead optimization cycle is critical to decrease the time to license and reduce costs. In addition, ethical guidelines call for the more ethical use of animals to minimize the number of animals used and decrease their suffering. Therefore, any effort to develop drugs to treat cutaneous leishmaniasis requires multiple tiers of testing that start with higher-throughput efficacy assessments and progress to lower-throughput models with the most clinical relevance.

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Background: Patients undergoing hybrid aortic arch reconstruction require careful protection of vital organs. We believe that whole body perfusion with tailored dual circuitry may help to achieve optimal patient outcomes.

Methods: Our circuit has evolved from a secondary circuit utilizing a cardioplegia delivery device for lower body perfusion to a dual-oxygenator circuit.

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Transformation of care delivery requires rethinking the relationship between the person and clinician. The model described provides a process to more fully engage patients in their care. Five encounters include assessing capacity for engagement, exchanging information and choices, planning, determining interventions, and evaluating the effectiveness of engagement interventions.

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A number of problems in probability and statistics can be addressed using the multivariate normal (Gaussian) distribution. In the one-dimensional case, computing the probability for a given mean and variance simply requires the evaluation of the corresponding Gaussian density. In the n-dimensional setting, however, it requires the inversion of an n ×n covariance matrix, C, as well as the evaluation of its determinant, det(C).

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Transformation of care delivery requires rethinking the relationship between the person and clinician. The model described provides a process to more fully engage patients in their care. Five encounters include assessing capacity for engagement, exchanging information and choices, planning, determining interventions, and evaluating the effectiveness of engagement interventions.

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Background And Objectives: Perfluorodecalin (PFD) has previously been shown to rapidly dissipate the opaque, white micro-bubble layer formed after exposure of tattoos to Q-switched lasers [1]. The current pilot study was conducted to qualitatively determine if the use of a transparent PFD-infused silicone patch would result in more rapid clearance of tattoos than conventional through-air techniques.

Materials And Methods: Black or dark blue tattoos were divided into two halves in a single-site IRB-approved study with 17 subjects with Fitzpatrick skin types I-III.

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This study applies recent advances in 3D virtual imaging for application in the prediction planning of dentofacial deformities. Stereo-photogrammetry has been used to create virtual and physical models, which are creatively combined in planning the surgical correction of anterior open bite. The application of these novel methods is demonstrated through the surgical correction of a case.

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Background: As anti-malarial drug resistance escalates, new safe and effective medications are necessary to prevent and treat malaria infections. The US Army is developing tafenoquine (TQ), an analogue of primaquine (PQ), which is expected to be more effective in preventing malaria in deployed military personnel.

Methods: To compare the prophylactic efficacy of TQ and PQ, a transgenic Plasmodium berghei parasite expressing the bioluminescent reporter protein luciferase was utilized to visualize and quantify parasite development in C57BL/6 albino mice treated with PQ and TQ in single or multiple regimens using a real-time in vivo imaging system (IVIS).

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Background: Immunization with genetically engineered, attenuated malaria parasites (GAP) that arrest during liver infection confers sterile protection in mouse malaria models. A first generation Plasmodium falciparum GAP (Pf p52(-)/p36(-) GAP) was previously generated by deletion of two pre-erythrocytic stage-expressed genes (P52 and P36) in the NF54 strain.

Methods: A first-in-human, proof-of-concept, safety and immunogenicity clinical trial in six human volunteers was conducted.

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Anti-malarial 8-aminoquinolines drugs cause acute hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDD). Efforts to develop non-hemolytic 8-aminoquinolines have been severely limited caused by the lack of a predictive in vivo animal model of hemolytic potential that would allow screening of candidate compounds. This report describes a G6PDD mouse model with a phenotype closely resembling the G6PDD phenotype found in the African A-type G6PDD human.

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Three empirical studies and one analysis of pre-existing data were performed to determine the everyday meanings of time, a major component of phenomenological analyses of human experience. To this end, participants in Studies 1 and 2 sorted time related words into groups having similar meanings, with these groups then evaluated by hierarchical clustering procedures. Results of Studies 1 and 2 produced similar clustering patterns suggesting it was possible to define the everyday meanings of time in terms of experiences of change and continuity, linear organization, tempo, and boundaries.

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Background: Controversy exists regarding the optimal perfusion modality during cardiopulmonary bypass (CPB). Here we compare the effects of pulsatile versus nonpulsatile perfusion on microvascular blood flow during and after CPB.

Methods: High-risk cardiac surgical patients were randomly assigned to have pulsatile (n=10) or nonpulsatile (n=10) flow during CPB.

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Mechanisms of drug resistance in Plasmodium vivax have been difficult to study partially because of the difficulties in culturing the parasite in vitro. This hampers monitoring drug resistance and research to develop or evaluate new drugs. There is an urgent need for a novel method to study mechanisms of P.

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Ketotifen is known to exhibit antimalarial activity in mouse and monkey malaria models. However, the low plasma levels and short half life of the drug do not adequately explain its in vivo efficacy. We synthesized most of the known metabolites of ketotifen and evaluated their antimalarial activity and pharmacokinetics in mice.

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A series of new guanidylimidazole derivatives was prepared and evaluated in mice and Rhesus monkeys infected with malarial sporozoites. The majority of the new compounds showed poor metabolic stability and weak in vitro activities in three clones of Plasmodium falciparum. Compounds 8a, 8h, 9a, 16a, and 16e cured the mice infected with sporozoites of P.

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Background: Opioids are analgesics that have potential for misuse, abuse or addiction. Up to an estimated 23 percent of prescribed doses are used nonmedically. As prescribers of 12 percent of immediate-release (IR) opioids in the United States, dentists can minimize the potential for misuse or abuse.

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A series of 2-guanidino-4-oxoimidazoline (deoxo-IZ) derivatives was prepared and showed potent antimalarial activities in rodent and Rhesus models. Compound 8e, the most potent analogues of this series, is the first non-8-aminoqinoline antimalarial that demonstrated radical curative activity in non-human primate by oral route and showed causal prophylactic activity comparable to that of the commonly used clinical drugs in Rhesus monkeys infected with sporozoites of Plasmodium cynomolgi. The metabolic stability and metabolites profile indicated that the new deoxo-IZ derivatives (8) may act as prodrugs of the corresponding IZ (1 and 2) derivatives.

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Effective acute pain management is an essential but sometimes challenging component of dental practice. Numerous studies have examined the efficacy of various analgesic agents in dental postoperative models. This article combines an evaluation of the available evidence with current prescribing patterns to provide dental practitioners prescribing recommendations for acute pain, based on the anticipated severity of post-procedural pain.

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