24 research outputs found

    Bacterial Isolates and Antimicrobial Susceptibility Phenotypes of Equine Specimens Submitted to the Oklahoma Animal Disease and Diagnostic Laboratory 2005-2007

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    Antimicrobial resistance is a topic of pervasive importance in both human and veterinary medicine. Increasingly, the zoonotic transfer of pathogens such as multi-drug resistance strains of Salmonella, methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus species is reported. The first step in responsible and effective use of antimicrobials in veterinary practice is to gain knowledge of the institutional and regional microbiologic environment. To this end, a large scale retrospective analysis was undertaken of all isolates from equine specimens submitted to the Oklahoma Animal Disease and Diagnostic Laboratory (OADDL) by the Boren Veterinary Medical Teaching Hospital, the College of Veterinary Health Sciences Ranch, and the regional veterinary community. Analysis was performed on pathogens identified, susceptibility phenotypes, and overall susceptibility patterns.The nature of bacterial isolates from equine specimens submitted to OADDL is similar to reported literature. Outbreaks of multi-drug resistant pathogens, particularly Staphylococcus aureus, have occurred at the BVMTH. These findings are supportive of real-time surveillance of major equine pathogens.Veterinary Pathobiolog

    Effective Treatment of Respiratory Alphaherpesvirus Infection Using RNA Interference

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    BACKGROUND: Equine herpesvirus type 1 (EHV-1), a member of the Alphaherpesvirinae, is spread via nasal secretions and causes respiratory disease, neurological disorders and abortions. The virus is a significant equine pathogen, but current EHV-1 vaccines are only partially protective and effective metaphylactic and therapeutic agents are not available. Small interfering RNAs (siRNA's), delivered intranasally, could prove a valuable alternative for infection control. siRNA's against two essential EHV-1 genes, encoding the viral helicase (Ori) and glycoprotein B, were evaluated for their potential to decrease EHV-1 infection in a mouse model. METHODOLOGY/PRINCIPAL FNDINGS: siRNA therapy in vitro significantly reduced virus production and plaque size. Viral titers were reduced 80-fold with 37.5 pmol of a single siRNA or with as little as 6.25 pmol of each siRNA when used in combination. siRNA therapy in vivo significantly reduced viral replication and clinical signs. Intranasal treatment did not require a transport vehicle and proved effective when given up to 12 h before or after infection. CONCLUSIONS/SIGNIFICANCE: siRNA treatment has potential for both prevention and early treatment of EHV-1 infections

    Risk of post-acute sequelae of SARS-CoV-2 infection associated with pre-coronavirus disease obstructive sleep apnea diagnoses: an electronic health record-based analysis from the RECOVER initiative

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    Obstructive sleep apnea (OSA) has been associated with more severe acute coronavirus disease-2019 (COVID-19) outcomes. We assessed OSA as a potential risk factor for Post-Acute Sequelae of SARS-CoV-2 (PASC).We assessed the impact of preexisting OSA on the risk for probable PASC in adults and children using electronic health record data from multiple research networks. Three research networks within the REsearching COVID to Enhance Recovery initiative (PCORnet Adult, PCORnet Pediatric, and the National COVID Cohort Collaborative [N3C]) employed a harmonized analytic approach to examine the risk of probable PASC in COVID-19-positive patients with and without a diagnosis of OSA prior to pandemic onset. Unadjusted odds ratios (ORs) were calculated as well as ORs adjusted for age group, sex, race/ethnicity, hospitalization status, obesity, and preexisting comorbidities.Across networks, the unadjusted OR for probable PASC associated with a preexisting OSA diagnosis in adults and children ranged from 1.41 to 3.93. Adjusted analyses found an attenuated association that remained significant among adults only. Multiple sensitivity analyses with expanded inclusion criteria and covariates yielded results consistent with the primary analysis.Adults with preexisting OSA were found to have significantly elevated odds of probable PASC. This finding was consistent across data sources, approaches for identifying COVID-19-positive patients, and definitions of PASC. Patients with OSA may be at elevated risk for PASC after SARS-CoV-2 infection and should be monitored for post-acute sequelae

    Researching COVID to Enhance Recovery (RECOVER) Adult Study Protocol: Rationale, Objectives, and Design

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    IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. METHODS: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. DISCUSSION: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options

    Invasion And Survival: Immunological Studies Of The Equine Chorionic Girdle

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    Successful mammalian pregnancy requires precise modulation of normal biological processes to ensure the survival of the feto-placental tissues while preserving the good health of the mother. The original research presented in this dissertation encompasses studies in both of these areas. The first part of this work addresses the long-standing question as to how feto-placental tissues, specifically invasive trophoblast, survive in the hostile environment of the maternal immune system. The Antczak laboratory previously developed an ectopic trophoblast transplant system to facilitate studies of the maternal immune response to invasive trophoblast in the horse. Single transplants of horse chorionic girdle into the vulvar mucosa of non-pregnant horse recipients were found to have lifespans and physiologic effects upon recipients similar to endometrial cups in a normal horse pregnancy. The current studies first expanded the trophoblast transplant system to include multiple rather than single transplants in individual recipients. The objective of this was to examine ectopic trophoblast survival in an immunologically primed as compared to naïve recipient. These serial transplants had lifespans similar to the single transplants, suggesting that the mechanisms protecting the trophoblast from immune destruction are initiated by the trophoblast itself. A series of transplants then was performed using Jenny donkeys as recipients. In each donkey recipient, primary transplants had lifespans of similar length to the horse-to-horse transplants, with second and subsequent transplants having progressively shorter lifespans. This pattern suggests that the horse-to-donkey transplants were subjected to a classic destructive memory response. The second body of work addresses the question as to how normal placentation disrupts maternal anatomy and physiology without causing adverse effects. This work was initiated with the discovery of interleukin 22 (IL22) mRNA in day 34 chorionic girdle using gene expression array analysis. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) then revealed that IL22 mRNA was rapidly upregulated in the chorionic girdle between days 32 and 35 of pregnancy. This represented the first identification of IL22 expression by a non-immune cell type. Interleukin 22 receptor RA1 (IL22RA1) mRNA was identified in pregnant endometrium, and in situ hybridization localized the mRNA to both the luminal and glandular epithelia. A monoclonal antibody was then generated against horse IL22. Mice were immunized with a fusion protein containing recombinant horse IL4 and IL22. Murine splenic cells were fused with SP 2/O myeloma cells to generate hybridoma cell lines. A monoclonal antibody to equine IL22 was identified. IL22 protein was then successfully detected in day 35 chorionic girdle. Knowing that IL22 in other biological systems has a role in preserving the integrity of mucosal surfaces and in epithelial cell proliferation, it was hypothesized that IL22 produced from the chorionic girdle binds receptor in the endometrium, repairing the damage caused by trophoblast invasion and initiating endometrial gland development
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