Virginia-Maryland College of Veterinary Medicine (VMCVM)

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https://hdl.handle.net/10919/5559

The Virginia-Maryland College of Veterinary Medicine is a two-state, three-campus professional school operated by the land-grant universities of Virginia Tech in Blacksburg and the University of Maryland at College Park. In addition to the main campus installation at Virginia Tech, the College also operates the Avrum Gudelsky Veterinary Center at College Park, and the Marion duPont Scott Equine Medical Center in Leesburg.

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2012-2018 Strategic Plan for the Virginia-Maryland Regional College of Veterinary Medicine
(Virginia Tech, 2012-09-30)
In order to maintain our excellence as one of the nation’s top veterinary colleges, we periodically revisit our goals and progress to formulate a strategic plan. The most recent of these plans was drafted on September 30, 2012 and lays out a road map for the college through the year 2018.
30th Annual Research Symposium: Chronic Disease and Aging
(Virginia-Maryland College of Veterinary Medicine, 2019-11-06)
Each year, the Virginia-Maryland College of Veterinary Medicine hosts this event to support the College’s mission of providing education to a diverse population of professional and post-graduate students in preparation for careers in the broad areas of veterinary medicine, biomedical sciences, and public health. The event serves to showcase the research of our graduate and training programs.
32nd Annual Graduate Research Symposium: Virginia-Maryland College of Veterinary Medicine
(Virginia Tech, 2023-03-14)
A program for the graduate research symposium held on March 14, 2023.
33rd Annual Graduate Research Symposium: Virginia-Maryland College of Veterinary Medicine
(Virginia Tech, 2024-03)
A program for the graduate research symposium held on March 18, 2024.
A 6-Nucleotide Regulatory Motif within the AbcR Small RNAs of Brucella abortus Mediates Host-Pathogen Interactions
Sheehan, Lauren M.; Caswell, Clayton C. (American Society for Microbiology, 2017-05)
In Brucella abortus, two small RNAs (sRNAs), AbcR1 and AbcR2, are responsible for regulating transcripts encoding ABC-type transport systems. AbcR1 and AbcR2 are required for Brucella virulence, as a double chromosomal deletion of both sRNAs results in attenuation in mice. Although these sRNAs are responsible for targeting transcripts for degradation, the mechanism utilized by the AbcR sRNAs to regulate mRNA in Brucella has not been described. Here, two motifs (M1 and M2) were identified in AbcR1 and AbcR2, and complementary motif sequences were defined in AbcR-regulated transcripts. Site-directed mutagenesis of M1 or M2 or of both M1 and M2 in the sRNAs revealed transcripts to be targeted by one or both motifs. Electrophoretic mobility shift assays revealed direct, concentration-dependent binding of both AbcR sRNAs to a target mRNA sequence. These experiments genetically and biochemically characterized two indispensable motifs within the AbcR sRNAs that bind to and regulate transcripts. Additionally, cellular and animal models of infection demonstrated that only M2 in the AbcR sRNAs is required for Brucella virulence. Furthermore, one of the M2-regulated targets, BAB2_0612, was found to be critical for the virulence of B. abortus in a mouse model of infection. Although these sRNAs are highly conserved among Alphaproteobacteria, the present report displays how gene regulation mediated by the AbcR sRNAs has diverged to meet the intricate regulatory requirements of each particular organism and its unique biological niche. IMPORTANCE Small RNAs (sRNAs) are important components of bacterial regulation, allowing organisms to quickly adapt to changes in their environments. The AbcR sRNAs are highly conserved throughout the Alphaproteobacteria and negatively regulate myriad transcripts, many encoding ABC-type transport systems. In Brucella abortus, AbcR1 and AbcR2 are functionally redundant, as only a double abcR1 abcR2 (abcR1/2) deletion results in attenuation in vitro and in vivo. In the present study, we confirmed that the AbcR sRNAs have redundant regulatory functions and defined two six-nucleotide motifs, M1 and M2, that the AbcR sRNAs utilize to control gene expression. Importantly, only M2 was linked to B. abortus virulence. Further investigation of M2-regulated targets identified BAB2_0612 as critical for colonization of B. abortus in mice, highlighting the significance of AbcR M2-regulated transcripts for Brucella infection. Overall, our findings define the molecular mechanism of the virulence-associated AbcR system in the pathogenic bacterium B. abortus.
A 7-week-old male Golden Retriever with extreme leukocytosis: A case report
Bingham, Emily; Conner, Bobbi; Stern, Jere; Vitalo, Amber; Schaer, Michael (Wiley, 2020-09-27)
Although neoplasia should be a top concern for extreme leukocytosis in dogs, infectious causes must also be considered to avoid delays in treatment or undue recommendations for humane euthanasia. Blood film review is of paramount importance.
Abdominal ultrasonographic findings at diagnosis of osteosarcoma in dogs and association with treatment outcome
Sacornrattana, O.; Dervisis, Nikolaos G.; McNiel, E. A. (Wiley-Blackwell, 2013-09-01)
The purpose of this study was to describe abdominal ultrasonographic findings present at diagnosis of osteosarcoma (OSA) in dogs and to investigate for associations with treatment outcome. Medical records from 118 dogs diagnosed with OSA that had abdominal ultrasonography performed as part of their initial evaluation were reviewed. Fifty-seven percent had ultrasonographic abnormalities identified. The organ with the highest frequency of ultrasonographic changes was the spleen. While most sonographic changes were considered to be either benign or of unknown clinical consequences, metastases were identified in three dogs (2.5%), two of which (1.7%) did not have other evidence of metastasis. Dogs with any ultrasonographic abnormality were less likely to receive definitive therapy (P = 0.005) and exhibited shorter survival, although the latter observation was not statistically significant (P = 0.071). However, the identification of lesions in either the liver (P = 0.021) or the kidney (P = 0.003) was statistically associated with shorter survival.
Ablative and Immunostimulatory Effects of Histotripsy Ablation in a Murine Osteosarcoma Model
Hay, Alayna N.; Imran, Khan Mohammad; Hendricks-Wenger, Alissa; Gannon, Jessica M.; Sereno, Jacqueline; Simon, Alex; Lopez, Victor A.; Coutermarsh-Ott, Sheryl; Vlaisavljevich, Eli; Allen, Irving C.; Tuohy, Joanne L. (MDPI, 2023-10-09)
Background: Osteosarcoma (OS) is the most frequently occurring malignant bone tumor in humans, primarily affecting children and adolescents. Significant advancements in treatment options for OS have not occurred in the last several decades, and the prognosis remains grim with only a 70% rate of 5-year survival. The objective of this study was to investigate the focused ultrasound technique of histotripsy as a novel, noninvasive treatment option for OS. Methods: We utilized a heterotopic OS murine model to establish the feasibility of ablating OS tumors with histotripsy in a preclinical setting. We investigated the local immune response within the tumor microenvironment (TME) via immune cell phenotyping and gene expression analysis. Findings: We established the feasibility of ablating heterotopic OS tumors with ablation characterized microscopically by loss of cellular architecture in targeted regions of tumors. We observed greater populations of macrophages and dendritic cells within treated tumors and the upregulation of immune activating genes 72 h after histotripsy ablation. Interpretation: This study was the first to investigate histotripsy ablation for OS in a preclinical murine model, with results suggesting local immunomodulation within the TME. Our results support the continued investigation of histotripsy as a novel noninvasive treatment option for OS patients to improve clinical outcomes and patient prognosis.
Abrogation of atypical neurogenesis and vascular-derived EphA4 prevents repeated mild TBI-induced learning and memory impairments
Greer, Kisha; Gudenschwager-Basso, Erwin K.; Kelly, Colin; Cash, Alison; Kowalski, Elizabeth A.; Cerna, Steven; Ocampo, Collin Tanchanco; Wang, Xia; Theus, Michelle H. (2020-09-21)
Brain injury resulting from repeated mild traumatic insult is associated with cognitive dysfunction and other chronic co-morbidities. The current study tested the effects of aberrant neurogenesis in a mouse model of repeated mild traumatic brain injury (rmTBI). Using Barnes Maze analysis, we found a significant reduction in spatial learning and memory at 24 days post-rmTBI compared to repeated sham (rSham) injury. Cell fate analysis showed a greater number of BrdU-labeled cells which co-expressed Prox-1 in the DG of rmTBI-injured mice which coincided with enhanced cFos expression for neuronal activity. We then selectively ablated dividing neural progenitor cells using a 7-day continuous infusion of Ara-C prior to rSham or rmTBI. This resulted in attenuation of cFos and BrdU-labeled cell changes and prevented associated learning and memory deficits. We further showed this phenotype was ameliorated in EphA4f.(/f)/Tie2-Cre knockout compared to EphA4f.(/f) wild type mice, which coincided with altered mRNA transcript levels of MCP-1, Cx43 and TGF beta. These findings demonstrate that cognitive decline is associated with an increased presence of immature neurons and gene expression changes in the DG following rmTBI. Our data also suggests that vascular EphA4-mediated neurogenic remodeling adversely affects learning and memory behavior in response to repeated insult.
Achromobacter xylosoxidans in extended semen causes reproductive failure in artificially inseminated sows and gilts
Clark, Sherrie G. (2008)
Achromobacter xylosoxidans, a Pseudomonas-like bacterium, contaminated a boar stud laboratory’s water distillation and delivery system that was used for extension of raw semen for artificial insemination. In sow herds that used the contaminated semen, conception rates decreased and vulvar discharges, culled sows, and nonproductive sow days increased. Thorough diagnostic testing revealed that A xylosoxidans was the etiological agent of endometritis and subsequent reproductive failure in these sows and gilts. This is the first known report of female reproductive failure attributed to A xylosoxidans. Routine cleaning and control measures to reduce bacterial growth in the extender ultimately failed to eliminate A xylosoxidans. Following short-term elimination of A xylosoxidans from the extended semen, reproductive parameters in the sow herds returned to their previous levels.
The activation of the IFN beta induction/signaling pathway in porcine alveolar macrophages by porcine reproductive and respiratory syndrome virus is variable
Overend, Christopher C.; Cui, Junru; Grubman, Marvin J.; Garmendia, Antonio E. (2017-03)
Background It has been recognized that the expression of type I interferon (IFN alpha/beta) may be suppressed during infection with porcine reproductive, respiratory syndrome virus (PRRSV). This causes profound negative effects on both the innate and adaptive immunity of the host resulting in persistence of infection. Objective Test the effects of PRRSV infection of porcine alveolar macrophages (PAMs), the main target cell, on the expression of interferon beta (IFN beta) and downstream signaling events. Methods In order to examine those effects, PAMs harvested from lungs of healthy PRRSV-free animals were infected with virulent, attenuated, infectious clone-derived chimeric viruses, or field PRRS virus strains. Culture supernatants from the infected PAMs were tested for IFN beta protein expression by means of indirect ELISA and for bioactivity by a vesicular stomatitis virus plaque reduction assay. The expression of the Mx protein was assayed to ascertain signaling events. Results These experiments demonstrated that PRRSV does induce variably, the expression of bioactive IFN beta protein in the natural host cell. To further elucidate the effects of PRRSV infection on IFN beta signaling, Mx-1 an interferon stimulated gene (ISG), was also tested for expression. Interestingly, Mx-1 expression by infected PAMs generally correlated with IFN beta production. Conclusion The results of this study demonstrate that the induction of IFN beta and signaling in PAMs after PRRSV infection is variable.
ACVIM small animal consensus statement on safe use of cytotoxic chemotherapeutics in veterinary practice
Smith, Annette N.; Klahn, Shawna L.; Phillips, Brenda; Parshley, Lisa; Bennett, Peter; Flory, Andi; Calderon, Rosemary (American College of Veterinary Internal Medicine, 2018-05)
The purpose of this report is to offer a consensus opinion of ACVIM oncology diplomates and technicians on the safe use of cytotoxic chemotherapeutics in veterinary practice. The focus is on minimizing harm to the personnel exposed to the drugs: veterinary practitioners, veterinary technicians, veterinary staff, and pet owners. The safety of the patient receiving these drugs is also of paramount importance, but is not addressed in this statement. Much of the information presented is based on national recommendations by Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, United States Pharmacopeia, and other published regulations. These directives reflect an abundance of caution to minimize exposure to medical personnel, but large-scale studies about the consequences of long-term occupational exposure are not available in veterinary medicine. Challenges in the delivery of optimal treatment safely and economically to veterinary patients in general practice without access to a veterinary oncologist or other specialist, because of costs or proximity, remain.
Addressing opioid misuse through community-engaged strategy development: study protocol of a randomized controlled trial
Zimmerman, Emily B.; Rafie, Carlin; Wenzel, Sophie G.; Hosig, Kathryn; Villani, Domenique; Dance, Jon; Lee, Samantha S. (2024-07-19)
Background: Involving stakeholders in the research process facilitates collaboration, increasing understanding of factors influencing their wellbeing and motivating community action. Currently, there is a need for randomized controlled trials to evaluate the effectiveness of community-engaged research approaches for health, well-being, and engagement outcomes. In this study, we evaluate the effectiveness of both the SEED Method and a modified Delphi method in a participatory project to develop local strategies to address the opioid epidemic in three rural communities. The purpose of this study is to increase the level of evidence for community-engaged research methods through a randomized controlled trial. Methods: Two communities will use the SEED Method and one will use a modified Delphi method. We aim to recruit a total of 144 participants (48 per community). The evaluation team will randomize participants to an intervention group or a control group. In addition, we will collect outcome data from the participatory research team members leading the projects in each county (n = 18) and from additional community members who participate in focus groups (n = 32). The primary outcome for all participants will be the change in self-reported civic engagement as measured by the total score on the Individual Mobilization Scale. Discussion: In the context of participatory action to address opioid misuse in rural counties, this study will provide an understanding of the effectiveness of two community engagement methods for increasing civic engagement, as well as the extent to which participants successfully create locally tailored action strategies. The study will also explore how the observed effects differ depending on the participant’s role in the project (stakeholder participant, community research team member, or focus group participant), which is an important consideration for participatory research.
Adenovirus transduction to express human ACE2 causes obesity-specific morbidity in mice, impeding studies on the effect of host nutritional status on SARS-CoV-2 pathogenesis
Rai, Pallavi; Chuong, Christina; LeRoith, Tanya; Smyth, James W.; Panov, Julia; Levi, Moshe; Kehn-Hall, Kylene; Duggal, Nisha K.; Weger-Lucarelli, James (Elsevier, 2021-11-01)
The COVID-19 pandemic has paralyzed the global economy and resulted in millions of deaths globally. People with co-morbidities like obesity, diabetes and hypertension are at an increased risk for severe COVID-19 illness. This is of overwhelming concern because 42% of Americans are obese, 30% are pre-diabetic and 9.4% have clinical diabetes. Here, we investigated the effect of obesity on disease severity following SARS-CoV-2 infection using a well-established mouse model of diet-induced obesity. Diet-induced obese and lean control C57BL/6 N mice, transduced for ACE2 expression using replication-defective adenovirus, were infected with SARS-CoV-2, and monitored for lung pathology, viral titers, and cytokine expression. No significant differences in tissue pathology or viral replication was observed between AdV transduced lean and obese groups, infected with SARS-CoV-2, but certain cytokines were expressed more significantly in infected obese mice compared to the lean ones. Notably, significant weight loss was observed in obese mice treated with the adenovirus vector, independent of SARS-CoV-2 infection, suggesting an obesity-dependent morbidity induced by the vector. These data indicate that the adenovirus-transduced mouse model of SARS-CoV-2 infection, as described here and elsewhere, may be inappropriate for nutrition studies.
Adrenocortical Challenge Response and Genomic Analyses in Scottish Terriers With Increased Alkaline Phosphate Activity
Zimmerman, Kurt L.; Panciera, David L.; Hoeschele, Ina; Monroe, William E.; Todd, S. Michelle; Werre, Stephen R.; LeRoith, Tanya; Fecteau, Kellie; Lake, Bathilda B. (Frontiers, 2018-10-09)
Scottish terriers (ST) frequently have increased serum alkaline phosphatase (ALP) of the steroid isoform. Many of these also have high serum concentrations of adrenal sex steroids. The study’s objective was to determine the cause of increased sex steroids in ST with increased ALP. Adrenal gland suppression and stimulation were compared by low dose dexamethasone (LDDS), human chorionic gonadotropin (HCG) and adrenocorticotropic hormone (ACTH) response tests. Resting plasma pituitary hormones were measured. Steroidogenesis-related mRNA expression was evaluated in six ST with increased ALP, eight dogs of other breeds with pituitary-dependent hyperadrenocorticism (HAC), and seven normal dogs. The genome-wide association of single nucleotide polymorphisms (SNP) with ALP activity was evaluated in 168 ST. ALP (reference interval 8–70 U/L) was high in all ST (1,054 U/L) and HAC (985 U/L) dogs. All HAC dogs and 2/8 ST had increased cortisol post-ACTH administration. All ST and 2/7 Normal dogs had increased sex steroids post-ACTH. ST and Normal dogs had similar post-challenge adrenal steroid profiles following LDDS and HCG. Surprisingly, mRNA of hydroxysteroid 17-beta dehydrogenase 2 (HSD17B2) was lower in ST and Normal dogs than HAC. HSD17B2 facilities metabolism of sex steroids. A SNP region was identified on chromosome 5 in proximity to HSD17B2 that correlated with increased serum ALP. ST in this study with increased ALP had a normal pituitary-adrenal axis in relationship to glucocorticoids and luteinizing hormone.We speculate the identified SNP and HSD17B2 gene may have a role in the pathogenesis of elevated sex steroids and ALP in ST.
Advanced breeding techniques of small ruminants and camelids
Clark-Deener, Sherrie (2015-05-14)
After a producer has gained knowledge and experience with the breeding management of their herd or flock, they may decide to attempt a variety of assisted reproductive techniques. What exactly is included in the category of assisted reproductive techniques? The author has included timed artificial insemination – both transcervical and laparoscopic, embryo transfer, and semen collection and freezing as the techniques to be discussed in this manuscript. In technical terms, the use of various pharmaceuticals for manipulation of the estrous cycle is assisted reproductive technology, but most authors will include this material when discussing the breeding management of groups as was done in this series of proceedings articles.
Advanced sequencing approaches detected insertions of viral and human origin in the viral genome of chronic hepatitis E virus patients
Papp, C-Patrick; Biedermann, Paula; Harms, Dominik; Wang, Bo; Kebelmann, Marianne; Choi, Mira; Helmuth, Johannes; Corman, Victor M.; Thuermer, Andrea; Altmann, Britta; Klink, Patrycja; Hofmann, Joerg; Bock, C-Thomas (Nature Portfolio, 2022-02-02)
The awareness of hepatitis E virus (HEV) increased significantly in the last decade due to its unexpectedly high prevalence in high-income countries. There, infections with HEV-genotype 3 (HEV-3) are predominant which can progress to chronicity in immunocompromised individuals. Persistent infection and antiviral therapy can select HEV-3 variants; however, the spectrum and occurrence of HEV-3 variants is underreported. To gain in-depth insights into the viral population and to perform detailed characterization of viral genomes, we used a new approach combining long-range PCR with next-generation and third-generation sequencing which allowed near full-length sequencing of HEV-3 genomes. Furthermore, we developed a targeted ultra-deep sequencing approach to assess the dynamics of clinically relevant mutations in the RdRp-region and to detect insertions in the HVR-domain in the HEV genomes. Using this new approach, we not only identified several insertions of human (AHNAK, RPL18) and viral origin (RdRp-derived) in the HVR-region isolated from an exemplary sample but detected a variant containing two different insertions simultaneously (AHNAK- and RdRp-derived). This finding is the first HEV-variant recognized as such showing various insertions in the HVR-domain. Thus, this molecular approach will add incrementally to our current knowledge of the HEV-genome organization and pathogenesis in chronic hepatitis E.
Adventitious viruses persistently infect three commonly used mosquito cell lines
Weger-Lucarelli, James; Rückert, Claudia; Grubaugh, Nathan D.; Misencik, Michael J.; Armstrong, Philip M.; Stenglein, Mark D.; Ebel, Gregory D.; Brackney, Doug E. (2018-08)
Mosquito cell lines have been used extensively in research to isolate and propagate arthropod-borne viruses and understand virus-vector interactions. Despite their utility as an in vitro tool, these cell lines are poorly defined and may harbor insect-specific viruses. Accordingly, we screened four commonly-used mosquito cell lines, C6/36 and U4.4 cells from Aedes albopictus, Aag2 cells from Aedes aegypti, and Hsu cells from Culex quinquefasciatus, for the presence of adventitious (i.e. exogenous) viruses. All four cell lines stained positive for double-stranded RNA, indicative of RNA virus replication. We subsequently identified viruses infecting Aag2, U4.4 and Hsu cell lines using untargeted next-generation sequencing, but not C6/36 cells. PCR confirmation revealed that these sequences stem from active viral replication and/or integration into the cellular genome. Our results show that these commonly-used mosquito cell lines are persistently-infected with several viruses. This finding may be critical to interpreting data generated in these systems.
Adverse Health Outcomes Following Hurricane Harvey: A Comparison of Remotely-Sensed and Self-Reported Flood Exposure Estimates
Ramesh, Balaji; Callender, Rashida; Zaitchik, Benjamin F.; Jagger, Meredith; Swarup, Samarth; Gohlke, Julia M. (American Geophysical Union, 2023-04)
Remotely sensed inundation may help to rapidly identify areas in need of aid during and following floods. Here we evaluate the utility of daily remotely sensed flood inundation measures and estimate their congruence with self-reported home flooding and health outcomes collected via the Texas Flood Registry (TFR) following Hurricane Harvey. Daily flood inundation for 14 days following the landfall of Hurricane Harvey was acquired from FloodScan. Flood exposure, including number of days flooded and flood depth was assigned to geocoded home addresses of TFR respondents (N = 18,920 from 47 counties). Discordance between remotely-sensed flooding and self-reported home flooding was measured. Modified Poisson regression models were implemented to estimate risk ratios (RRs) for adverse health outcomes following flood exposure, controlling for potential individual level confounders. Respondents whose home was in a flooded area based on remotely-sensed data were more likely to report injury (RR = 1.5, 95% CI: 1.27-1.77), concentration problems (1.36, 95% CI: 1.25-1.49), skin rash (1.31, 95% CI: 1.15-1.48), illness (1.29, 95% CI: 1.17-1.43), headaches (1.09, 95% CI: 1.03-1.16), and runny nose (1.07, 95% CI: 1.03-1.11) compared to respondents whose home was not flooded. Effect sizes were larger when exposure was estimated using respondent-reported home flooding. Near-real time remote sensing-based flood products may help to prioritize areas in need of assistance when on the ground measures are not accessible.
Agreement between Electrical Cardiometry and Pulmonary Artery Thermodilution for Measuring Cardiac Output in Isoflurane-Anesthetized Dogs
Paranjape, Vaidehi V.; Henao-Guerrero, Natalia; Menciotti, Giulio; Saksena, Siddharth; Agostinho, Manuela (MDPI, 2023-04-21)
In animals, invasive pulmonary artery thermodilution (PATD) is a gold standard for cardiac output (CO) monitoring, but it is impractical in clinical settings. This study evaluates the agreement between PATD and noninvasive electrical cardiometry (EC) for measuring CO and analyzes the other EC-derived hemodynamic variables in six healthy anesthetized dogs subjected to four different hemodynamic events in a sequential order: (1) euvolemia (baseline); (2) hemorrhage (33% blood volume loss); (3) autologous blood transfusion; and (4) 20 mL/kg colloid bolus. The CO measurements obtained using PATD and EC are compared using Bland–Altman analysis, Lin’s concordance correlation (LCC), and polar plot analysis. Values of p < 0.05 are considered significant. The EC measurements consistently underpredict the CO values as compared with PATD, and the LCC is 0.65. The EC’s performance is better during hemorrhage, thus indicating its capability in detecting absolute hypovolemia in clinical settings. Even though the percentage error exhibited by EC is 49.4%, which is higher than the standard (<30%), EC displays a good trending ability. Additionally, the EC-derived variables display a significant correlation with the CO measured using PATD. Noninvasive EC may have a potential in monitoring trends in hemodynamics in clinical settings.

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