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Open Access Publications from the University of California

Scholarly Works (59 results)

  • Thesis
  • Peer Reviewed
UC Davis Electronic Theses and Dissertations (2021)

Cholesterol, a major lipid component of animal plasma membranes (PM) and a small component in some plants, has been associated with the development of various diseases and infections, like Alzheimer’s disease (AD), Parkinson’s diseases (PD), H. pylori infection, etc., through an imbalance in cholesterol homeostasis or cholesterol modification. In addition to the bioactivity of lipids like cholesterol, glycolipids (glycosylceramides and sterol glycosides) have been reported to influence the release of T-helper 1 (TH1) and T-helper 2 (TH2) cytokines in mammals. Also, cholesterol has been reported to undergo a sugar exchange with glucosyl ceramides. In previous studies, cholesterol analogues with intrinsic or extrinsic fluorescent groups were used as probes to monitor biodistribution of cholesterol and the sugar exchange with glucosyl ceramides. However, problems arose with these cholesterol probes from disrupting plasma membranes to difficult extraction for metabolite characterization. Recently, a dehydroepiandrosterone (DHEA) probe with a primary alkoxyl-azido group mimicked cholesterol well while providing efficient extraction via copper(I)-catalyzed azide/alkyne cycloaddition (CuAAC) with 4-N-methylamino-1,8-napthalimidopropyne (MAN) for metabolite characterization and minimal disruption of plasma membranes. Currently, there are no azido-glycolipid probes available to monitor the metabolism of glycolipids during TH1 and TH2 cytokine release in addition to the sugar exchange with ceramides. In this project, two secondary C17 azido-DHEA (5 and 8) probes were prepared and six azido-glycolipid (14, 15, 16, 17, 22, and 24) probes were proposed to study the metabolism of lipids and glycolipids in various environments. Chapter 1 will focus on the bioactivity of sterols/sterol glycosides and previous sterol probes. Chapter 2 will discuss the total synthesis of the two secondary C17 azido-DHEA probes (5 and 8). Chapter 3 will cover the NMR characterization of various DHEA derivatives while Chapter 4 will describe previous glycosylceramide derivatives, the bioactivity of glycosylceramides, and the future synthesis of six azido-glycolipid probes (14, 15, 16, 17, 22, and 24).

    Cover page: Design and Synthesis of “Clickable” Azido-Lipid/Glycolipid Probes
    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2023)
    Since the publication of seminal work demonstrating ablation of AF triggers within the pulmonary veins, significant focus has been placed upon finding adjunctive AF mapping and ablation strategies to improve the targeted treatment of this arrhythmia. Presently, wide-area circumferential ablation to achieve pulmonary vein isolation has become the standard of care for catheter-based management. However, despite significant work, a comprehensive mechanistic understanding of the sustaining mechanisms of AF remains elusive. The present study from Nagase and colleagues provides important insight derived from a multielectrode catheter-based mapping algorithm regarding the spatial relationships between identified targets, regions of low voltage, and complex fractionated atrial electrograms. Being spatially distinct and distributed in both atria, they may represent novel targets for ablation therapy. Additional studies are required to better assess the impact of elimination of such foci.
      Cover page: Mapping for nonpulmonary vein atrial fibrillation sources: The road to improved ablation outcomes.
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2021)
      A 32-year-old woman with a history of symptomatic supraventricular tachycardia, inappropriate sinus tachycardia, and hyperadrenergic POTS was treated with ivabradine and metoprolol. She then presented with bradycardia and Mobitz II second-degree AV block on event monitoring six weeks after COVID-19 infection. Her post-viral workup revealed normalization of catecholamine levels and significant symptomatic improvement in heart rate. To the authors' knowledge, this is the first reported case of improvement in POTS after COVID-19 infection. As our understanding of COVID-19 continues to improve, it will be vital to better understand the impact of COVID-19 dysautonomia on cardiac patients.
        Cover page: Clinical and Laboratory Improvement in Hyperadrenergic Postural Orthostatic Tachycardia Syndrome (POTS) after COVID-19 Infection
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2021)

        Background

        Evidence to support use of cardiac resynchronization therapy (CRT) among patients with both heart failure (HF) and atrial fibrillation (AF) is largely limited to retrospective or post hoc subanalyses. Data from a prospectively enrolled and contemporary cohort are needed.

        Objective

        We aim to better characterize the changes from baseline in HF patients with concomitant AF subsequently implanted with a 2-lead CRT-DX system capable of sensing in the atrium, aggregating diagnostics, and delivering CRT therapy. The primary objective of this study is to evaluate the percentage of all HF subjects with an improvement in a clinical composite score from pre-CRT implant to 12 months.

        Methods

        The study is a US-based, prospective, observational multicenter clinical trial conducted at up to 50 sites and enrolling approximately 400 subjects with a follow-up period of 1 year. Multiple subject assessments, atrial rhythm status, and device interrogation will be collected at follow-up visits occurring at 3, 6, and 12 months postimplant.

        Results

        A Clinical Events Committee will adjudicate subject HF events, arrhythmia events, death events, and all device-classified ventricular tachycardia and ventricular fibrillation episodes with treatment that are collected throughout the follow-up period. Their decisions are based on independent physician review of the data from sites and device interrogation.

        Conclusion

        The BIO-AffectDX study aims to provide further insight into the expected outcomes from CRT treatment in patients with HF and AF.
          Cover page: Atrial fibrillation associated with heart failure treated by a 2-lead CRT-DX system (BIO-AffectDX): Study design and clinical protocol
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2013)

          Background

          Atrial fibrillation (AF) is common after open-chest procedures, but the etiology remains poorly understood. Lung transplant procedures allow for the study of novel contributing factors.

          Methods

          Records of lung transplant procedures performed at a single center between 2002 and 2009 were reviewed.

          Results

          Of 174 patients, 27 (16%) had AF a median 6 days post-surgery. Post-operative AF patients less often had right ventricular hypertrophy (RVH) by either electrocardiogram (0 versus 14%, P=.042) or echocardiography (19% versus 47%, P=.006), and had lower pulmonary artery systolic pressures (PASP) (39 ± 12 versus 51 ± 22, P=.005). After multivariable adjustment, every 10-mm Hg increase in PASP was associated with a 31% reduction in the odds of post-operative AF (OR 0.69, 95% CI 0.49-0.98, P=.035). A higher pulmonary pressure was the only predictor independently associated with less post-operative AF.

          Conclusions

          Higher PASP was associated with a lower risk of AF after lung transplantation.
            Cover page: Elevated pulmonary artery systolic pressures are associated with a lower risk of atrial fibrillation following lung transplantation
            • Article
            • Peer Reviewed
            UC San Diego Previously Published Works (2018)
              Cover page: Successful ventricular tachycardia ablation in a patient with a biventricular ventricular assist device and heparin-induced thrombocytopenia using bivalirudin.
              • Article
              • Peer Reviewed
              UC San Diego Previously Published Works (2020)
              A 67-year-old man presented with dizziness secondary to ventricular tachycardia (VT) originating from the moderator band. The VT was refractory to multiple antiarrhythmic medications requiring extracorporeal membrane oxygenation and eventual curative ablation. We highlight a malignant form of idiopathic VT, unique electrocardiogram characteristics, and ablation considerations. (Level of Difficulty: Intermediate.).
                Cover page: Ventricular Tachycardia Storm Originating From Moderator Band Requiring Extracorporeal Membrane Oxygenation
                • Article
                • Peer Reviewed
                UC San Diego Previously Published Works (2017)
                  Cover page: A surgeon with symptomatic ventricular tachycardia while operating and exacerbated by left lateral decubitus position: Too much of a stretch?
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2015)

                  Background

                  Patients with paroxysmal and persistent atrial fibrillation experience a similar risk of thromboembolism. Therefore, consensus guidelines recommend anticoagulant therapy in those at risk for thromboembolism irrespective of atrial fibrillation classification. We sought to examine whether there are differences in rates of appropriate oral anticoagulant treatment among patients with paroxysmal vs persistent atrial fibrillation in real-world cardiology practices.

                  Methods

                  We studied 71,316 outpatients with atrial fibrillation and intermediate to high thromboembolic risk (CHADS2 score ≥2) enrolled in the American College of Cardiology PINNACLE Registry between 2008 and 2012. Using hierarchical modified Poisson regression models adjusted for patient characteristics, we examined whether anticoagulant treatment rates differed between patients with paroxysmal vs persistent atrial fibrillation.

                  Results

                  The majority of outpatients (78.4%, n = 55,905) had paroxysmal atrial fibrillation. In both unadjusted and multivariable adjusted analyses, patients with paroxysmal atrial fibrillation were less frequently prescribed oral anticoagulant therapy than those with persistent atrial fibrillation (50.3% vs 64.2%; adjusted risk ratio [RR] 0.74; 95% confidence interval [CI], 0.72-0.76). Instead, patients with paroxysmal atrial fibrillation were prescribed more frequently only antiplatelet therapy (35.1% vs 25.0%; adjusted RR 1.77; 95% CI, 1.69-1.86) or neither antiplatelet nor anticoagulant therapy (14.6% vs 10.8%; adjusted RR 1.35; 95% CI, 1.26-1.44; P < .0001 for differences across all 3 comparisons).

                  Conclusions

                  In a large, real-world cardiac outpatient population, patients with paroxysmal atrial fibrillation with a moderate to high risk of stroke were less likely to be prescribed appropriate oral anticoagulant therapy and more likely to be prescribed less effective or no therapy for thromboembolism prevention.
                    Cover page: Differences in Anticoagulant Therapy Prescription in Patients with Paroxysmal Versus Persistent Atrial Fibrillation
                    • Article
                    • Peer Reviewed
                    UC San Diego Previously Published Works (2020)
                    We present a rare complication of spontaneous thrombus formation on the WATCHMAN delivery system, on both the right- and left-sided systemic circulation. We also describe the multidisciplinary team approach and the use of percutaneous vacuum-assisted aspiration system (AngioVac, AngioDynamics, Latham, New York) for successful thrombus removal. (Level of Difficulty: Intermediate.).
                      Cover page: Spontaneous Left Atrial Thrombus Formation on the Catheter Delivery System During WATCHMAN Implantation
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