Browsing by Subject "Infection"

Now showing 1 - 8 of 8
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    Antibiotic use for treatment of acute sinusitis
    (2012-04-10) Martinson, Carin
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    The Facts About Sinusitis
    (2008-04-07) Wudel, Justin
    In acute uncomplicated sinusitis, intranasal corticosteroids have been shown to provide symptom relief and improve clinical outcomes. There is also no evidence that their use as monotherapy or as an adjuvant therapy would be detrimental in therapeutic doses, however, the data does not provide information regarding the optimal dose and/or duration of treatment.
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    Infection and Cardiovascular Disease: The Atherosclerosis Risk in Communities Study
    (2017-07) Cowan, Logan
    Infection has been identified as both a chronic and acute risk factor of cardiovascular disease (CVD). Despite the growing body of evidence, additional research elucidating the relationship between infection and CVD is needed. This dissertation employs longitudinal data from the Atherosclerosis Risk in Communities (ARIC) study, the Longitudinal Investigation of Thromboembolism Etiology (LITE) ancillary study, the Dental-ARIC (D-ARIC) ancillary study, and the corresponding ARIC study participant Centers for Medicare and Medicaid Services (CMS) data to examine the relationship between infection and CVD. In the first manuscript we assessed the longitudinal relationship between self-reported periodontal disease and clinical periodontal disease and incident venous thromboembolism (VTE). Self-reported periodontal disease was associated with 30% higher VTE risk that remained significant or borderline significant after adjustment. Crude associations between clinical periodontal disease classifications were attenuated with adjustment and were no longer significant. In the second manuscript we assessed the longitudinal relationship between history of endodontic therapy (ET) and incident coronary heart disease (CHD), ischemic stroke, heart failure, and VTE. We found no significant associations between self-reported history of ET and any of our outcomes of interest that remained after adjustment. In the final manuscript we used a case-crossover study design to evaluate infection as a potential trigger of CHD, ischemic stroke, and VTE. Infection was associated with higher odds of CHD, stroke, and VTE up to 90 days following the infection. The association between infection and CVD/VTE was graded such that the infection-CVD/VTE association was highest immediately following the infection and decreased as the time since the infection increased. Generally, outpatient infection was a weaker CVD/VTE trigger compared to all infections. Further research is needed to pinpoint if periodontal disease is independently associated with VTE risk and if periodontal prevention and treatment could reduce VTE risk. Our results do not support an independent association between endodontic therapy and CVD or VTE. The results of the third manuscript provide evidence in support of our hypothesis that infection is a CVD/VTE trigger. Patients with an infection who are at elevated risk of CVD should be considered potential candidates for CVD prophylaxis during and immediately after infection to reduce the otherwise elevated CVD/VTE risk.
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    Investigating Infection-Related Hospitalization as a Risk Factor for Incident Heart Failure and Mortality among Heart Failure Patients
    (2023-06) Molinsky, Rebecca
    HF is a growing epidemic with an estimated prevalence of 6.5 million individuals in the U.S., and poor outcomes persist despite recent therapeutic advancements. Studies have shown that an inflammatory response to infections may become dysregulated, thereby promoting collateral myocardial damage that may result in HF. Infection is also a common cause of hospitalization among HF patients and may lead to poor prognosis and high mortality. Limited data exist examining the relationship between infection-related hospitalization (IRH) and HF along with HF subtypes, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). Further, few studies have explored mortality rates following an IRH in HF patients or whether certain types of IRH are stronger predictors of mortality. This dissertation leveraged the strengths of large claims data (MarketScan) and a community-based study (ARIC) to address these limitations and parse out the dynamic relationship between infection-related hospitalization and HF with several manuscripts. The first manuscript, a case-crossover study of beneficiaries in the MarketScan databases, assessed the association between IRH and incident HF. IRH was associated with incident HF after both 1- and 3-months. The second manuscript investigated the association between IRH and long-term incident HF in the Atherosclerosis Risk in Communities study (ARIC). IRH was associated with a two-fold greater risk of incident HF, HFrEF, and HFpEF. Findings were stronger among those with HFpEF, for which treatment options are limited. Results from the first manuscript aligned with those of the second manuscript and both found respiratory, pneumonia, and blood/circulatory infections to have the strongest associations with incident HF. The third manuscript explored the relationship between IRH and mortality among HF patients in ARIC. IRH was associated with a two-fold greater risk of mortality among those with HFpEF, HFrEF, or unclassified HF. Respiratory, pneumonia, and other infections had the strongest associations with mortality. Our findings support prior literature linking IRH to HF risk and increased mortality among HF patients. These findings may have significant population-level implications given the high prevalence of IRH and the burden of HF on our aging society. Aim 1: Investigate the association between infection-related hospitalization and incident HF using U.S.-based claims data from MarketScan. Aim 2: Investigate the association between infection-related hospitalization and incident HF and HF subtypes (HFrEF or HFpEF) using a longitudinal community-based cohort study, ARIC. Aim 3: Among HF (HFrEF and HFpEF) patients, investigate the association between infection-related hospitalization and mortality using a longitudinal community-based cohort study, ARIC.
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    Optimizing Metal Complexes as Bacteria-Specific Tracers for in vivo Nuclear Molecular Imaging and Modulators of the Nuclease Resistance of DNA Nanostructures
    (2023-05) Joaqui Joaqui, Michel Andrey
    Infectious diseases caused by bacteria remain one of the major global threats to human health. Rapid and precise diagnosis is thus crucial for preventing the propagation of these bacterial pathogens and achieving favorable treatment results for impacted patients. To achieve this, diagnostic methods must possess the ability to accurately detect the bacterial pathogen with high selectivity, while also being prompt to facilitate rapid containment and informed treatment decisions. In vivo nuclear molecular imaging modalities such as PET and SPECT have gained importance as alternative diagnostics techniques, especially in scenarios where the site of infection is unknown, or the extraction of sample is anatomically challenging rendering well-established in vitro diagnostic techniques impractical. The effectiveness of these in vivo imaging techniques heavily relies on the utilization of proper radiolabeled probes that target bacteria. Currently, there are no radiotracers available that can be swiftly and easily prepared and that exhibit the necessary selectivity for bacterial cells to enable clear and definitive diagnosis. The first part of this dissertation presents an investigation regarding the use of artificial siderophore analogs of enterobactin, a bacterial virulence factor, as promising scaffolds for the development of metal-based radiopharmaceutical agents suitable for the detection of bacteria in vivo. The study covers the rationale behind the design of the artificial enterobactin analogs, the study of the in vitro and in vivo stability of the 68Ga and 45Ti-labeled enterobactin analogs, their suitability as nuclear imaging agents, as well as the evaluation of their abilities to image a bacterial infection in vivo.The second part of this dissertation, on the other hand, is dedicated to exploring the stability challenges faced by DNA nanotechnology in biologically relevant environments, particularly the instability of DNA-based nanomaterials. DNA nanostructures exhibit unique properties and hold great potential in areas such as biotechnology, nanoelectronics, and nanomedicine. However, these materials encounter numerous hurdles, such as degradation by nucleases and enzymes when introduced into biological environments like blood, tissues, or cells. Such degradation significantly impairs the stability and performance of DNA nanomaterials, curtailing their effectiveness in biological and biomedical applications. Hence, the field of DNA nanotechnology is currently grappling with the critical challenge of devising techniques to enhance the stability and performance of DNA nanomaterials under such conditions. The second section of this dissertation describes a methodical exploration of the modulation of the degradation of DNA nanocages through reversible supramolecular functionalization with metal complexes. The study encompasses the development and synthesis of several coordination compounds featuring metal centers such as EuIII, TbIII, PtII, CuII, CoII, and RuII, as well as a diversity of ligands. Further, the binding affinities of these metal complexes for DNA nanostructures are assessed, and their ability to mitigate the degradation of DNA nanostructures in biologically relevant media is evaluated.
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    The role of antigen receptor signaling in activation and development of invariant Natural Killer T cells
    (2014-05) Holzapfel, Keli Lee
    CD1d-reactive invariant Natural Killer T cells (iNKT) are a T cell subset that have characteristics of both innate immune cells and adaptive immune cells. As a result, they are considered a bridge between the innate and the adaptive immune response. iNKT cells can rapidly secrete a variety of cytokines after activation, and therefore have an important immunomodulatory role during the immune response in many different diseases, such as cancer, asthma, autoimmune disease, and infection. During infections, there are three models of iNKT cell activation: activation requiring microbial antigen, cytokine driven activation, and activation requiring self-antigen. However, how iNKT cells become activated during some infections remains controversial, as activation requiring self-antigen has only been indirectly shown. Therefore, I addressed this controversy using an antigen receptor signal strength reporter mouse, in which Nur77gfp reports stimulation of the T cell receptor (TCR). Although the sensitivity of this reporter mouse was initially observed in conventional T cells, I showed that Nur77gfp is also a sensitive readout for TCR stimulation in iNKT cells. Therefore, several bacterial and viral infections were examined for the role of antigen-dependent versus antigen-independent activation. These experiments showed that Nur77gfp was upregulated during infections with a microbial antigen, and was not upregulated during an infection previously considered to activate iNKT cells by the cytokine driven model. Unexpectedly, the infectious contexts reported to require self-antigen for iNKT cell activation did not upregulate Nur77gfp, indicating that the main driver of iNKT cell activation is cytokine, and thus activation is antigen-independent. Additionally, as a result of the immunomodulatory capabilities of iNKT cells, iNKT cells have great potential for use in new therapeutics. However, for these therapies to be effective, an exogenous source of iNKT cells is needed. Therefore, I adapted the OP9-DL1 culture system to derive iNKT cells from hematopoietic progenitor cells in vitro. I showed that the frequency of cells expressing the iNKT TCR needed to be increased in order to detect iNKT cells using this system. Furthermore, I showed that the addition of IL-15 can enhance the percentage of cells expressing the NKT1 subset transcription factor Tbet. Therefore, this iNKT cell adapted OP9-DL1 culture system can be used as a new method to examine factors that influence iNKT cell development and to identify factors that can skew iNKT cell subset differentiation. Ultimately, these experiments aided in advancing the understanding of iNKT cell activation and development, as well as how to harness the power of iNKT cells to artificially orchestrate an immune response for therapeutic use.
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    Urinary Tract Infection (UTI)
    (2011-08-01) Osborne, Sarah
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    What is a Urinary Tract Infection (UTI)?
    (2011-08-03) Day, Emily