Nonhuman primates (NHPs) have been and remain a highly valuable animal model with an essential role in translational research and pharmaceutical drug development. Based on current regulatory guidelines, the nonclinical safety of novel therapeutics should be evaluated in relevant nonclinical species, which commonly includes NHPs for biotherapeutics. Given the practical and ethical limitations on availability and/or use of NHPs and in line with the widely accepted guiding "3Rs" (replace, reduce, and refine) principles, many approaches have been considered to optimize toxicity study designs to meaningfully reduce the number of NHPs used.
View Article and Find Full Text PDFThe adoption of digital measures in pharmaceutical research and development (R&D) presents an opportunity to enhance the efficiency and effectiveness of discovering and developing new therapeutics. For clinical measures, the Digital Medicine Society's (DiMe) V3 Framework is a comprehensive validation framework that encompasses verification, analytical validation, and clinical validation. This manuscript describes collaborative efforts to adapt this framework to ensure the reliability and relevance of digital measures for a preclinical context.
View Article and Find Full Text PDFHemotropic mycoplasmas are unculturable bacteria that infect the surface of red blood cells of several mammalian species including cattle. The importance of hemoplasmas in cattle remains unclear and limited information is available about biological routes of transmission. The objective of this cross-sectional study was to determine the prevalence of transplacental transmission of hemoplasmas and to determine if colostrum of infected cows contained DNA from hemoplasma organisms.
View Article and Find Full Text PDFIntroduction: For general surgeons practising in rural areas, multiple factors influence care beyond skills learned in residency. The British Columbia Privileging Dictionary (BCPD) defines core and non-core procedures that shape the scope of general surgeons. Moreover, the Royal College has adopted a Competence by Design (CBD) curriculum which employs entrustable professional activities (EPAs) that list surgical skill residents must be proficient in by graduation.
View Article and Find Full Text PDFHospital-acquired falls are a continuing clinical concern. The emergence of advanced analytical methods, including NLP, has created opportunities to leverage nurse-generated data, such as clinical notes, to better address the problem of falls. In this nurse-driven study, we employed an iterative process for expert manual annotation of RNs clinical notes to enable the training and testing of an NLP pipeline to extract factors related to falls.
View Article and Find Full Text PDFMore than 3 years into the global pandemic, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a significant threat to public health. Immunities acquired from infection or current vaccines fail to provide long term protection against subsequent infections, mainly due to their fast-waning nature and the emergence of variants of concerns (VOCs) such as Omicron. To overcome these limitations, SARS-CoV-2 Spike protein receptor binding domain (RBD)-based epitopes are investigated as conjugates with a powerful carrier, the mutant bacteriophage Qβ (mQβ).
View Article and Find Full Text PDFBackground: Rural general surgeons perform many procedures outside the conventional scope of the specialty. Unique to British Columbia, the Rural Practice Subsidiary Agreement (RSA) formally defines rurality in the province. Our goal is to understand the scope of practice for BC's rural general surgeons and whether it has been affected over time by changing privileging guidelines.
View Article and Find Full Text PDFThe bovine hemoplasmas include Mycoplasma wenyonii and Candidatus Mycoplasma haemobos, which are increasingly recognized as infecting cattle throughout the world. Infection with hemotropic mycoplasma has been reported to be widespread in mature dairy cows, but little is known about its prevalence in calves and heifers. The objective of this study was to investigate the prevalence and dynamics of infection with M.
View Article and Find Full Text PDFCaused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19) has shown extensive lung manifestations in vulnerable individuals, putting lung imaging and monitoring at the forefront of early detection and treatment. Magnetic particle imaging (MPI) is an imaging modality, which can bring excellent contrast, sensitivity, and signal-to-noise ratios to lung imaging for the development of new theranostic approaches for respiratory diseases. Advances in MPI tracers would offer additional improvements and increase the potential for clinical translation of MPI.
View Article and Find Full Text PDFObjective: Reduced left ventricular ejection fraction (LVEF) is common in hemodialysis (HD) patients. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is considered an important determinant of cardiovascular events. The aim of the study was to evaluate the relationship between Lp-PLA2 and LVEF in HD patients.
View Article and Find Full Text PDFUnlabelled: Relapse is the leading cause of death in patients with medulloblastoma, the most common malignant pediatric brain tumor. A better understanding of the mechanisms underlying recurrence could lead to more effective therapies for targeting tumor relapses. Here, we observed that SOX9, a transcription factor and stem cell/glial fate marker, is limited to rare, quiescent cells in high-risk medulloblastoma with MYC amplification.
View Article and Find Full Text PDFCerebrospinal fluid (CSF) microcirculation refers to CSF flow through brain or spinal parenchyma. CSF enters the tissue along the perivascular spaces of the penetrating arteries where it mixes with the interstitial fluid circulating through the extracellular space. The potential of harnessing CSF microcirculation for drug delivery to deep areas of the brain remains an area of controversy.
View Article and Find Full Text PDFTwo captive vulturine guineafowl () were presented with lethargy, hyporexia, weight loss, and progressive neurologic signs. One of the guineafowl was seropositive for (1:50 dilution). Both guineafowl died within 5 d of presentation.
View Article and Find Full Text PDFChronic wasting disease (CWD) is a transmissible prion disorder, primarily affecting free-ranging and captive cervids in North America (United States and Canada), South Korea, and Europe (Finland, Norway, and Sweden). Current diagnostic methods used in the United States for detection of CWD in hunter harvested deer involve demonstration of the causal misfolded prion protein (PrP) in the obex or retropharyngeal lymph nodes (RLNs) using an antigen detection ELISA as a screening tool, followed by a confirmation by the gold standard method, immunohistochemistry (IHC). Real-time quaking-induced conversion (RT-QuIC) assay is a newer approach that amplifies misfolded CWD prions and has facilitated CWD prion detection in a variety of tissues, body fluids, and excreta.
View Article and Find Full Text PDFEastern equine encephalomyelitis (EEE) is a mosquito-borne viral disease that is an emerging public health concern in the state of Michigan. Although Michigan has one of the highest incidence rates of EEE in the United States, much of the information known about cases in humans, equines, and other animals residing in Michigan is unpublished. This article summarizes such information and explores spatial trends in the historic distribution of EEE in Michigan.
View Article and Find Full Text PDFBackground: Rates of detecting ≥1 potential enteric pathogens (PEP) or toxins (PEP-T) in feces, blood, or both of horses ≥6 months of age with enteric disease and impact of multiple detections on outcome of horses with colitis has not been reported.
Objective: To determine detection rates of PEP/PEP-T in feces, blood, or both of horses with enteric disease and effect of detecting multiple agents on outcome of horses with colitis.
Animals: Thirty-seven hundred fifty-three fecal samples submitted to IDEXX Laboratories and 239 fecal and blood samples submitted to Michigan State University's Veterinary Diagnostic Laboratory (MSUVDL).
Background: AKI is a complication of coronavirus disease 2019 (COVID-19) that is associated with high mortality. Despite documented kidney tropism of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are no consistent reports of viral detection in urine or correlation with AKI or COVID-19 severity. Here, we hypothesize that quantification of the viral load of SARS-CoV-2 in urine sediment from patients with COVID-19 correlates with occurrence of AKI and mortality.
View Article and Find Full Text PDFEastern equine encephalitis virus (EEEV) infects many avian species but has rarely been described in Ruffed Grouse (Bonasa umbellus). Between September and December 2019, 40 Ruffed Grouse, most in poor physical condition, were submitted to the Michigan, Wisconsin, and Minnesota (US) Departments of Natural Resources; eight were positive for EEEV.
View Article and Find Full Text PDF(formerly ) is a hemotrophic, epicellular bacterial parasite of cattle that has been associated with clinical disorders, including hemolytic anemia, decreased milk yield, and peripheral edema. and a related organism, , have been detected in both ill and apparently healthy cattle, but little is known about their prevalence in US dairy cattle. The objective of this prospective, cross-sectional study was to determine herd-level apparent prevalence of and in dairy cattle located in Wisconsin and Michigan compared with seroprevalence of bovine leukemia virus (BLV) in the same herds.
View Article and Find Full Text PDFThe exquisite sensitivity of in vitro amplification assays such as real-time polymerase chain reaction (rtPCR) requires the establishment of thorough and robust laboratory practices. To this end, an American Association of Veterinary Laboratory Diagnosticians (AAVLD) committee of subject matter experts was convened to develop a set of best practices for performance of nucleic acid amplification assays. Consensus advice for the performance of preanalytical, analytical, and postanalytical steps is presented here, along with a review of supporting literature.
View Article and Find Full Text PDFThis consensus document presents the suggested guidelines developed by the Laboratory Technology Committee (LTC) of the American Association of Veterinary Laboratory Diagnosticians (AAVLD) for development, validation, and modification (methods comparability) of real-time PCR (rtPCR) assays. These suggested guidelines are presented with reference to the World Organisation for Animal Health (OIE) guidelines for validation of nucleic acid detection assays used in veterinary diagnostic laboratories. Additionally, our proposed practices are compared to the guidelines from the Foods Program Regulatory Subdivision of the U.
View Article and Find Full Text PDFRetinoic acid receptor-related orphan receptor γ (RORγ) is a transcription factor regulating the expression of the pro-inflammatory cytokine IL-17 in human T helper 17 (Th17) cells. Activating RORγ can induce multiple IL-17-mediated autoimmune diseases but may also be useful for anticancer therapy. Its deep immunological functions make RORɣ an attractive drug target.
View Article and Find Full Text PDFGlioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. Patients usually undergo surgery followed by aggressive radio- and chemotherapy with the alkylating agent temozolomide (TMZ). Still, median survival is only 12-15 months after diagnosis.
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