Microbiology / Infectious Disease

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/30443


Recent Submissions

Now showing 1 - 4 of 4
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    ER-associated Regulation of Astrocyte Mitochondrial Function during HIV-1 Infection
    (2021) Proulx, Jessica; Borgmann, Kathleen
    Purpose: Astrocytes are key regulators of central nervous system (CNS) health and neuronal function. However, astrocyte mitochondrial dysfunction, such as induced by HIV-1, threatens the ability of astrocytes to provide the essential metabolic and antioxidant support to neurons. This study examined the endoplasmic reticulum (ER)-mitochondrial interface in response to HIV-1 infection to characterize changes in mitochondrial function, the unfolded protein response (UPR), and the regulation of mitochondria associated membranes (MAMs). We hypothesized that the ER regulates astrocyte mitochondrial function via UPR/MAM signaling during HIV-1 infection. Methods: The effects of chronic HIV-1 infection were examined using pseudotyped HIV-1 to infect primary human astrocytes. Astrocyte mitochondrial function and metabolic status were assessed using Seahorse extracellular flux analyzer while expression of UPR/MAM mediators was determined using protein expression assays. Pharmacological inhibition of the UPR pathways was used to delineate key regulatory mechanisms mediating changes on astrocyte mitochondrial function. Results: Our studies demonstrate increased astrocyte metabolic capacity in response to chronic HIV-1 infection which corresponded to increased expression of UPR/MAM mediators. Moreover, pharmacological inhibition of IRE1α impaired astrocyte mitochondrial activity. Conclusion: These findings illustrate the importance of ER-mitochondria communication in regulating astrocyte mitochondrial function and identify a novel possible mechanism to manipulate the metabolic and antioxidant coupling between astrocytes and neurons during HIV-1 pathogenesis.
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    A Case Report of Multisystem Inflammatory Syndrome in Children Presenting as Typhus
    (2021) Mahajan, Anisha; Murray, Celeste; Murray, Tyler; Shahin, Dani; Espino, Lynette; Jalfon, Rachel; Anvaripour, Navid
    Multisystem Inflammatory Syndrome in Children (MIS-C) is described as a set of life-threatening clinical symptoms arising secondary to an inflammatory response triggered by SARS-CoV-2 infection, typically manifesting 25 days after initial symptom onset. Considerations for diagnosis include age < 21, fever, laboratory evidence of inflammation, and previous SARS-CoV-2 exposure or infection. MIS-C presents similarly to endemic or murine Typhus caused by Rickettsia typhi. Both pathologies present with Kawasaki's Disease-like features of fever, rash, conjunctivitis, and lymphadenopathy. Additional shared non-specific symptoms include headache, pharyngitis, abdominal pain, and diarrhea. Furthermore, they share similar inflammatory markers and laboratory values, including elevated ESR, elevated ALT, and anemia. Here, we report a case of MIS-C initially misdiagnosed as murine Typhus. A 15-year-old male presented with symptoms of murine Typhus to a hospital in an endemic region. Due to a positive Rickettsia panel, doxycycline was initiated to treat suspected murine Typhus. The patient did not improve, and additional differential diagnoses were considered. Clinical suspicion for MIS-C was heightened due to self-reported history of COVID-19 infection one month prior. Anti-inflammatory treatment with intravenous immune globulin, methylprednisolone, and anakinra was initiated to symptomatically treat MIS-C. This therapeutic regimen resulted in patient stabilization and discharge, thus corroborating diagnosis of MIS-C. Due to the shared clinical manifestations of murine Typhus and MIS-C secondary to COVID-19, we recommend MIS-C as a differential for a patient presenting with characteristic symptoms.
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    Association of Prescription Opioid Use and Development of Infectious Diseases: A Systematic Review
    (2021) Ra, Jennifer
    Purpose: Recent studies have demonstrated an increased risk of infection associated with opioid use. The objective of this systematic review is to gather and compare evidence related to prescription opioids and development of infection. Methods The protocol for this systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) guidelines and was registered on PROSPERO (CRD42020205591). Studies about appropriate use of prescription opioids and subsequent development of infectious diseases were identified through an electronic search of PubMed, Embase, CINAHL complete, and Scopus databases. Inclusion criteria were adult patients with a prescription opioid who subsequently developed an infection. Exclusion criteria were studies related to pregnancy, human immunodeficiency virus (HIV), hepatitis C infection. Studies including prescription opioid misuse, overdose, or illicit or schedule I controlled substances were also ineligible. Results This systematic review yielded 25 studies that were highly variable in study design and target populations. Some studies included patients with immunocompromised states such as cancer and others included post-surgical populations or other disease states. The majority of studies established a correlation between prescription opioid use and risk of developing an infectious disease. Other trends associated with an increased risk of infection were current or recent use of opioids, extended-release opioid formulations, higher total daily morphine equivalents, and longer half-lives of opioids. Conclusion This systematic review showed a potential association between opioid use and acquirement of infectious diseases. Further randomized controlled trials are needed to validate these results.
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    An agent-based model for simulating viral infections
    (2021) Dobrovolny, Hana; Fain, Baylor
    As we have seen in the past year, new viruses can spread rapidly and cause outbreaks that need a quick response from researchers to develop or re-purpose treatments. While experiments and clinical studies form the basis of this response, the data generated by these studies can be further leveraged through the use of mathematical models. Properly calibrated and validated mathematical models can make predictions about scenarios that are difficult to test experimentally, but are also faster and cheaper when testing possible treatment regimens. We have developed a realistic agent-based model of viral infections that runs on graphical processing units (GPUs), so it runs fast enough to simulate typical in vitro viral studies in a few hours. We present here testing and validation of the model for influenza infections and show that it can be calibrated to simulate different viral infections.