Publications by authors named "Aaron Rendahl"

68 Publications

Retrospective evaluation of thrombocytopenia and tumor stage as prognostic indicators in dogs with splenic hemangiosarcoma.

J Am Vet Med Assoc 2021 Mar;258(6):630-637

Objective: To identify physical examination and perioperative CBC variables in dogs with splenic hemangiosarcoma (HSA) that could aid in predicting progression-free interval (PFI) and overall survival time (OST) in affected dogs.

Animals: 70 client-owned dogs with splenic HSA treated with splenectomy and chemotherapy between September 2004 and October 2016.

Procedures: A retrospective search of the University of Minnesota Veterinary Medical Center medical records database was performed to identify dogs with splenic HSA treated with splenectomy and with evidence in the medical records of intent to treat with chemotherapy. Data collection included dog signalment and body surface area, results from CBCs performed within 6 days before to 2 days after splenectomy, whether dogs had hemoabdomen or received transfusions, and tumor stage. Hematocrit, WBC count, and platelet count were treated as categorical variables (divided into terciles: above, within, or below reference limits) because of variation among reference intervals for the numerous analyzers used. Associations between variables and PFI or OST were investigated with Cox regression analyses, and hazard ratios (HRs) for a shorter PFI or OST were reported. Population Pearson correlation coefficient (ρ) analysis was performed to identify potential associations between variables of interest.

Results: Stage 3 HSA was identified as a negative prognostic indicator of PFI (HR, 6.6) and OST (HR, 4.5). Perioperative thrombocytopenia was similarly associated with shorter PFI (HR, 2.2) and OST (HR, 2.0). Results for Hct correlated (ρ = 0.58) with those for platelet count, and although our findings did not indicate a notable association between anemia and shorter PFI, such could not be ruled out.

Conclusions And Clinical Relevance: The prognostic value of thrombocytopenia warrants further substantiation to understand causal and mechanistic connections, and the presence of thrombocytopenia ultimately may prove valuable in guiding treatment recommendations for dogs with splenic HSA.
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http://dx.doi.org/10.2460/javma.258.6.630DOI Listing
March 2021

Proposed virulence-associated genes of Streptococcus suis isolates from the United States serve as predictors of pathogenicity.

Porcine Health Manag 2021 Feb 28;7(1):22. Epub 2021 Feb 28.

Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN, USA.

Background: There is limited information on the distribution of virulence-associated genes (VAGs) in U.S. Streptococcus suis isolates, resulting in little understanding of the pathogenic potential of these isolates. This lack also reduces our understanding of the epidemiology associated with S. suis in the United States and thus affects the efficiency of control and prevention strategies. In this study we applied whole genome sequencing (WGS)-based approaches for the characterization of S. suis and identification of VAGs.

Results: Of 208 S. suis isolates classified as pathogenic, possibly opportunistic, and commensal pathotypes, the genotype based on the classical VAGs (epf, mrp, and sly encoding the extracellular protein factor, muramidase-release protein, and suilysin, respectively) was identified in 9% (epf+/mrp+/sly+) of the pathogenic pathotype. Using the chi-square test and LASSO regression model, the VAGs ofs (encoding the serum opacity factor) and srtF (encoding sortase F) were selected out of 71 published VAGs as having a significant association with pathotype, and both genes were found in 95% of the pathogenic pathotype. The ofs+/srtF+ genotype was also present in 74% of 'pathogenic' isolates from a separate validation set of isolates. Pan-genome clustering resulted in the differentiation of a group of isolates from five swine production companies into clusters corresponding to clonal complex (CC) and virulence-associated (VA) genotypes. The same CC-VA genotype patterns were identified in multiple production companies, suggesting a lack of association between production company, CC, or VA genotype.

Conclusions: The proposed ofs and srtF genes were stronger predictors for differentiating pathogenic and commensal S. suis isolates compared to the classical VAGs in two sets of U.S. isolates. Pan-genome analysis in combination with metadata (serotype, ST/CC, VA genotype) was illustrated to be a valuable subtyping tool to describe the genetic diversity of S. suis.
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http://dx.doi.org/10.1186/s40813-021-00201-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917538PMC
February 2021

Retrospective analysis of the effects of Blastomyces antigen concentration in urine and radiographic findings on survival in dogs with blastomycosis.

J Vet Intern Med 2021 Mar 19;35(2):946-953. Epub 2021 Feb 19.

Veterinary Clinical Sciences Department, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA.

Background: The Blastomyces antigen concentration in urine (BACU) test is used to diagnose blastomycosis and monitor treatment in dogs. It is unknown if a higher BACU is associated with shorter survival.

Objectives: To determine if the magnitude of BACU before treatment is associated with survival in dogs with blastomycosis.

Animals: Fifty-two dogs with blastomycosis.

Methods: Retrospective case review. BACU, radiographic lung severity (RLS) score (0-4 scale), and survival time up to 1 year after diagnosis were obtained through medical record review of dogs with Blastomyces dermatitidis.

Results: The overall survival was: discharge, 87%; 1 week, 85%; 2 months, 74%; and 6 months, 69%. BACU correlated with RLS score (r = 0.33, P = .02). BACU and RLS scores were lower in survivors to 2 months than nonsurvivors (average BACU difference of 2.5 ng/mL, 95% confidence interval [CI]: 0.2-4.8 ng/mL, P = .04; median RLS difference of 2; range, 0-4, P = .02). Dogs with BACU <5 ng/mL and dogs with mild (0-1) RLS scores had a greater proportion surviving than those with BACU >5 ng/mL (P = .03) and dogs with severe (3-4) RLS scores (P = .04). All dogs with a BACU <5 ng/mL or mild RLS score were alive at last follow-up (median, 365 days; range, 44-365 days). In all, 68.1% of other dogs survived to 2 months (95% CI, 54.8%-84.8%).

Conclusions And Clinical Importance: Dogs with lower BACU and RLS scores have improved survival; however, it is unclear what specific cutoffs should be used for prognosis.
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http://dx.doi.org/10.1111/jvim.16041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995372PMC
March 2021

Indicators of Postoperative Pain in Syrian Hamsters ().

Comp Med 2021 Feb 26;71(1):76-85. Epub 2021 Jan 26.

Research Animal Resources, University of Minnesota, Twin Cities, Minnesota.

Despite the use of Syrian hamsters () in research, little is known about the evaluation of pain in this species. This study investigated whether the frequency of certain behaviors, a grimace scale, the treat-take-test proxy indicator, body weight, water consumption, and coat appearance could be monitored as signs of postoperative pain in hamsters in a research setting. Animals underwent no manipulation, anesthesia only or laparotomy under anesthesia. An ethogram was constructed and used to determine the frequencies of pain, active and passive behaviors by in-person and remote videorecording observation methods. The Syrian Hamster Grimace Scale (SHGS) was developed for evaluation of facial expressions before and after the surgery. The treat-take-test assessed whether surgery would affect the animals' motivation to take a high-value food item from a handler. The hypothesis was that behavior frequency, grimace scale, treat-take-test score, body weight, water consumption, and coat appearance would change from baseline in the surgery group but not in the no-intervention and anesthesia-only groups. At several time points, pain and passive behaviors were higher than during baseline in the surgery group but not the anesthesia-only and no-intervention groups. The SHGS score increased from baseline scores in 3 of the 9 animals studied after surgery. The frequency of pain behaviors and SHGS scores were highly specific but poorly sensitive tools to identify animals with pain. Behaviors in the pain category were exhibited by chiefly, but not solely, animals that underwent the laparotomy. Also, many animals that underwent laparotomy did not show behaviors in the pain category. Treat-take-test scores, body weight, water consumption, and coat appearance did not change from baseline in any of the 3 groups. Overall, the methods we tested for identifying Syrian hamsters experiencing postoperative pain were not effective. More research is needed regarding clinically relevant strategies to assess pain in Syrian hamsters.
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http://dx.doi.org/10.30802/AALAS-CM-20-990056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898174PMC
February 2021

Effect of Alternative Palatal Root Access Technique on Fracture Resistance of Root Canal Treated Maxillary Fourth Premolar Teeth in Dogs.

Front Vet Sci 2020 11;7:600145. Epub 2020 Dec 11.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, United States.

A biomechanical study was performed to identify the effect of different treatment methods for difficult to instrument palatal roots on the fracture resistance of root canal treated maxillary fourth premolar teeth in dogs. Forty maxillary fourth premolar teeth with surrounding alveolar bone were harvested from beagle cadavers. Inclusion criteria included maxillary fourth premolars with no evidence of disease and similar distal root canal volumes on radiographic evaluation. The teeth were randomly divided into a control group and three treatment groups based on the endodontic treatment technique for the palatal root. The control group had a single 2 mm transcoronal access on the mesiobuccal aspect of the tooth to allow instrumentation of both the mesiobuccal and palatal root through a single small access. Alternative treatment modalities that are described for difficult to instrument palatal roots investigated in this study included enlarging the transcoronal mesiobuccal access to 4 mm, making an additional access directly over the palatal root (2 mm), and hemisection with extraction of the palatal root. All teeth had the same distal root access size (2 mm) and relative location. After access, all teeth were filed, shaped, obturated, and restored in the same fashion. Axial compression testing was performed at an angle of 60 degrees to the long axis of the tooth using a universal materials testing machine. The maximum force prior to fracture was determined for each tooth based on a force vs. deflection curve. The mean maximum force prior to fracture for all teeth was 831 N. No significant difference in mean fracture resistance was identified between the control group and treatment groups or between the different treatment groups themselves. Thus, when faced with a difficult to instrument palatal root, the treatment method chosen should be based on operator preference and experience.
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http://dx.doi.org/10.3389/fvets.2020.600145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759647PMC
December 2020

Comparison of Semi-Cylindrical Recession Trochleoplasty and Trochlear Block Recession for the Treatment of Canine Medial Patellar Luxation: A Pilot Study.

Vet Comp Orthop Traumatol 2020 Nov 26. Epub 2020 Nov 26.

Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, United States.

Objective:  The aim of this study was to describe an alternative method for trochleoplasty, semi-cylindrical recession trochleoplasty (SCRT), and compare it to trochlear block recession (TBR) in regard to recessed trochlear depth, patellar depth, patellar articular contact with the trochlea, recessed trochlear surface area, procedure time, complications and functional outcome.

Study Design:  Ten dogs with bilateral grade II-III medial patellar luxations underwent bilateral simultaneous correction surgery including tibial tuberosity transposition, lateral imbrication and trochleoplasty with one stifle each undergoing TBR and SCRT. Patients received pre-and postoperative stifle computed tomography scans and pre- and 8-week postoperative pressure platform analysis and physical examinations. Recessed trochlear depth, patellar depth, trochlear surface area, patellar articular contact, procedure time, complications and functional outcomes as measured by gait analysis were compared between the two techniques.

Results:  There was no significant difference in measured outcome variables between techniques at any time point. At the time of the 8-week reassessment, no patella had reluxated.

Conclusion:  Short-term follow-up shows similar functional outcomes between both techniques regarding rate of reluxation and limb function. The SCRT was subjectively easier to perform than TBR, particularly in small patients. The SCRT is an acceptable method of trochleoplasty for the treatment of medial patellar luxation in dogs and further studies evaluating long-term outcomes are justified.
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http://dx.doi.org/10.1055/s-0040-1721107DOI Listing
November 2020

Changes in Matrix Components in the Developing Human Meniscus.

Am J Sports Med 2021 01 25;49(1):207-214. Epub 2020 Nov 25.

Department of Orthopedic Surgery, University of Minnesota, Minneapolis, Minnesota, USA.

Background: Treatment of meniscal tears is necessary to maintain the long-term health of the knee joint. Morphological elements, particularly vascularity, that play an important role in meniscal healing are known to change during skeletal development.

Purpose: To quantitatively evaluate meniscal vascularity, cellularity, collagen, and proteoglycan content by age and location during skeletal development.

Study Design: Descriptive laboratory study.

Methods: Medial and lateral menisci from 14 male and 7 female cadavers aged 1 month to 11 years were collected and evaluated. For each meniscus, histologic and immunohistologic techniques were used to establish the ratio of the area of proteoglycan (safranin O) positivity to the total area (proteoglycan ratio), collagen type I and type II immunostaining positivity, number of blood vessels, and cell density. These features were evaluated over the entire meniscus and also separately in 5 circumferential segments: anterior root, anterior horn, body, posterior horn, and posterior root. Additionally, cell density and number of blood vessels were examined in 3 radial regions: inner, middle, and periphery.

Results: Age was associated with a decrease in meniscal vessel count and cell density, while the proteoglycan ratio increased with skeletal maturity. Differences in vessel counts, cellular density, and proteoglycan ratio in different anatomic segments as well as in the inner, middle, and peripheral regions of the developing menisci were also observed. Collagen immunostaining results were inconsistent and not analyzed.

Conclusion: The cellularity and vascularity of the developing meniscus decrease with age and the proteoglycan content increases with age. All of these parameters are influenced by location within the meniscus.

Clinical Relevance: Age and location differences in meniscal morphology, particularly in the number of blood vessels, are expected to influence meniscal healing.
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http://dx.doi.org/10.1177/0363546520972418DOI Listing
January 2021

Influence of skull biometrics on cosmetic reconstruction after incisivectomy and nasal planectomy reconstruction in dogs.

Vet Surg 2021 Jan 23;50(1):89-103. Epub 2020 Nov 23.

VetSSMART, LLC, St Paul, Minnesota, USA.

Objective: To identify biometric skull measurements that are associated with tension and excess narrowing of the resultant nasal aperture during cosmetic nasal planectomy reconstruction.

Study Design: Ex vivo study.

Animals: Twenty cadavers of mesocephalic dogs.

Methods: Cosmetic reconstruction was performed after incisivectomy and nasal planectomy. Preoperative and intraoperative skull measurements included width of the nasal planum, rostral and caudal maxilla, labial flap, and maxilla at ostectomy site; the length of the nose, labial flap, and philtrum incision; lip thickness; and philtrum placement. Ratios of select width to length measurements were calculated. Correlation was tested between skull biometrics and tension during reconstruction as well as resulting opening of the nasal aperture.

Results: Breeds included golden retriever, pit bull, Labrador retriever, beagle, shepherd, basset hound, boxer mix, cocker spaniel, and Great Dane. No biometric ratios were predictive of procedural success. The most important objective measurements that were significantly correlated with inferior outcome included width of the nasal planum (>3 cm), width of the caudal maxilla (>6.2 cm), lip thickness (>0.5 cm), width of the labial flap (>2.9 cm), length of the incision created to make the cosmetic "philtrum" (longer incisions >2.8 cm), and philtrum placement (more dorsal placement).

Conclusion: Tension during reconstruction and decreased resultant nasal aperture were associated with wider facial features and thicker lips as well as directly impacted by cosmetic philtrum design and placement.

Clinical Significance: Standardized preoperative measurements may help guide clinical decision making in choosing and executing a nasal planectomy reconstructive technique.
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http://dx.doi.org/10.1111/vsu.13535DOI Listing
January 2021

Effects of the Administration of a Non-specific Immune Stimulant Around Transportation on Health and Performance of Jersey and Jersey-Cross Heifer Calves During the Rearing Period: Randomized Clinical Trial.

Front Vet Sci 2020 14;7:550202. Epub 2020 Oct 14.

NovaVive Inc., Napanee, ON, Canada.

Our objective was to evaluate the effects of a non-specific immune stimulant (IS) administered around transportation on health scores (HS), average daily gain (ADG), disease treatment and mortality of Jersey and Jersey-cross calves during the rearing period. Newborn calves (4 d ± 1) were randomly allocated to receive either 1 mL of saline (CON; = 438), 1 mL of IS before transport (BTIS; = 431), or 1 mL of IS immediately after transport (ATIS; = 436). Calves were health scored weekly for 3 weeks after transport. The data were analyzed using multivariable linear mixed models and multivariable logistic regression models. Kaplan-Meier survival analysis was performed for time to event analysis. Treatment, birth weight, breed, site of birth, serum total solids, dam parity, season of enrollment, and metaphylaxis were offered to models. Differences in respiratory and fecal HS, and ADG between treatment groups were not statistically significant. A total of 196 (15.0%) calves were treated at least once for any disease and 52 calves were treated multiple times. The proportion of calves treated for respiratory disease and/or diarrhea were 14.4, 14.4, and 16.2% for BTIS, ATIS and CON groups, respectively. Although the differences in the likelihood of treatment for both respiratory disease and/or diarrhea during the first 9 weeks of life was not statistically different between groups, we observed that more calves in the control group received disease treatments around 15 days of age compared with calves that received IS. The likelihood of treatment for respiratory diseases alone during the first 30 days of life was smaller in the calves that received IS before transportation when compared to the control group. Only 18 (1.4%) calves died within the study period. The calf mortality likelihood was not statistically different between study groups; however, fewer calves in the IS groups died when compared to CON. In conclusion, the use of IS around transportation did not influence weekly HS, ADG, and the number of disease treatments during the rearing period, but administering IS before transportation resulted in fewer treatments of respiratory diseases during the first 30 days post-transport and marginally lower mortality rates during the rearing period.
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http://dx.doi.org/10.3389/fvets.2020.550202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591452PMC
October 2020

Variability in Recommendations for Cervical Lymph Node Pathology for Staging of Canine Oral Neoplasia: A Survey Study.

Front Vet Sci 2020 13;7:506. Epub 2020 Aug 13.

Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN, United States.

There is no clear guideline regarding the indication for routine lymph node extirpation and pathologic evaluation during staging of canine oral tumors, despite a relatively high reported nodal metastatic rate for select tumor types. It is particularly unclear if clinicians recommend removal of lymph nodes only when there is confirmation of metastasis, defined as the N+ neck, or if elective neck dissection (END) is routinely recommended to confirm the true pathologic metastatic status of lymph nodes in the clinical N0 neck (no evidence of metastasis on clinical staging with diagnostic imaging or cytology). When clinicians are recommending END as a staging tool to confirm nodal status, there is also ambiguity regarding the surgical extent for subsequent histopathologic evaluation. The objective of this cross-sectional survey study was to determine the current recommendations given by practicing specialists regarding lymph node removal for dogs with oral tumors. Overall, 87 responses were obtained from 49 private practices (56%) and 38 academic institutions (44%). Respondents identified as oncologists (44%, = 38), soft tissue surgeons (40%, = 35), and dentists (16%, = 14). Regardless of tumor type and stage, extirpation and histopathology were most commonly recommended in the clinical N+ neck only. The recommendation to routinely perform END in the N0 neck was significantly associated with tumor type. Bilateral removal of the mandibular and retropharyngeal lymph nodes was recommended more often for oral malignant melanoma (OMM) than for oral squamous cell carcinoma (OSCC; ≤ 0.0039) or for oral fibrosarcoma (OFSA; ≤ 0.0007). The likelihood of recommending END increased with increasing tumor size. Academic clinicians were significantly ( < 0.01) more likely to recommend END compared to private practitioners for canine T1-T3 OMM, T3 OSCC, T2 OFSA, and MCT. This study highlights the variability in recommendations for lymph node pathology for dogs with oral tumors. While tumor type and size influenced the decision to pursue END, it was not routinely recommended, even for tumor types with a known propensity for metastasis. Prospective studies are warranted to determine the potential diagnostic and therapeutic value of END in the N0 neck in veterinary patients such that a consensus approach can be made.
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http://dx.doi.org/10.3389/fvets.2020.00506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438545PMC
August 2020

Volumetric tumor response assessment is inefficient without overt clinical benefit compared to conventional, manual veterinary response assessment in canine nasal tumors.

Vet Radiol Ultrasound 2020 Sep 23;61(5):592-603. Epub 2020 Jul 23.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, Minnesota, USA.

Accurate assessment of tumor response to therapy is critical in guiding management of veterinary oncology patients and is most commonly performed using response evaluation criteria in solid tumors criteria. This process can be time consuming and have high intra- and interobserver variability. The primary aim of this serial measurements, secondary analysis study was to compare manual linear tumor response assessment to semi-automated, contoured response assessment in canine nasal tumors. The secondary objective was to determine if tumor measurements or clinical characteristics, such as stage, would correlate to progression-free interval. Three investigators evaluated paired CT scans of skulls of 22 dogs with nasal tumors obtained prior to and following radiation therapy. The automatically generated tumor volumes were not useful for canine nasal tumors in this study, characterized by poor intraobserver agreement between automatically generated contours and hand-adjusted contours. The radiologist's manual linear method of determining response evaluation criteria in solid tumors categorization and tumor volume is significantly faster (P < .0001) but significantly underestimates nasal tumor volume (P < .05) when compared to a contour-based method. Interobserver agreement was greater for volume determination using the contour-based method when compared to response evaluation criteria in solid tumors categorization utilizing the same method. However, response evaluation criteria in solid tumors categorization and percentage volume change were strongly correlated, providing validity to response evaluation criteria in solid tumors as a rapid method of tumor response assessment for canine nasal tumors. No clinical characteristics or tumor measurements were significantly associated with progression-free interval.
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http://dx.doi.org/10.1111/vru.12895DOI Listing
September 2020

Comparison between smartphone electrocardiography and standard three-lead base apex electrocardiography in healthy horses.

Vet Rec 2020 10 15;187(9):e70. Epub 2020 May 15.

Veterinary Population Medicine, The University of Minnesota, St. Paul, Minnesota, USA.

Background: Cardiac arrhythmias are commonly auscultated during routine physical examinations in horses and determining the underlying electrical abnormality using an ECG is important. The most commonly used device is a three-lead base apex system (Televet), however few practitioners carry this for routine visits. With recognition of the utility of smartphone-based ECGs in humans, dogs and ruminants, the AliveCor single-lead bipolar smartphone-based ECG has gained popularity. The objective of this study was to determine if AliveCor and Televet ECG measurements were comparable in healthy horses using multiple observers.

Methods: ECGs were performed on 15 healthy horses simultaneously using the AliveCor and Televet.

Results: There was very good to perfect interdevice and interobserver agreement for heart rate and RR interval measurement, and moderate-to-good interdevice and interobserver agreement for detection of non-pathological arrhythmias. Interdevice agreement for measurement of P-wave and QRS duration, QT, PR and T-peak to T-end interval was poor to fair. Interestingly, interobserver agreement for P-wave and QRS duration, QT, PR, and T-peak to T-end interval measurements was fair to good.

Conclusion: Overall, the AliveCor is comparable to the Televet for heart rate and RR measurement, and for the detection of non-pathogenic arrhythmias with acceptable agreement between observers.
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http://dx.doi.org/10.1136/vr.105759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606555PMC
October 2020

Prevalence and trend analysis of antimicrobial resistance in clinical Escherichia coli isolates collected from diseased pigs in the USA between 2006 and 2016.

Transbound Emerg Dis 2020 Feb 25. Epub 2020 Feb 25.

Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.

Antimicrobial resistance (AMR) is an emerging threat to both human and animal health. Antimicrobial use and resistance in food animal production, including swine, has received increased scrutiny as a source of resistant foodborne pathogens. Continuous surveillance of AMR in bacterial isolates of swine origin can guide in conservation of antimicrobials used in both human and swine medicine. The objective of this study was to evaluate the prevalence and trends of the phenotypic AMR in Escherichia coli of swine origin isolated from clinical samples at the Minnesota Veterinary Diagnostic laboratory between 2006 and 2016. The prevalence of resistance to ampicillin, tetracyclines and sulphadimethoxine remained greater than 50% throughout the period. There was a drastic change in enrofloxacin resistance, increasing from less than 1% to more than 20% between 2006 and 2016 (annual relative increase of 57% between 2006 and 2013 and 16% between 2013 and 2016). The prevalence of resistance to other antimicrobials remained constant (ceftiofur, oxytetracycline and chlortetracycline) or changed significantly (annual relative changes of less than 10%) for at least some time-period between 2006 and 2016 (ampicillin, florfenicol, gentamicin, neomycin, sulphadimethoxine, trimethoprim-sulphamethoxazole and spectinomycin). Rarefaction analysis revealed an increase in the number of unique combinations of AMRs per year. Network analysis was performed by estimating and plotting partial correlations between minimum inhibitory concentrations (MICs) of various antimicrobials. An increase in strength of these networks was observed, particularly in networks created after 2010, which can be indicative of increased multiple AMR in these isolates. These results provide valuable insight into the trends in AMR in E. coli of swine origin in the USA and act as supplementary information to the existing active AMR surveillance systems.
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http://dx.doi.org/10.1111/tbed.13528DOI Listing
February 2020

Comparison of immediate versus delayed streak plate inoculation on urine bacterial culture and susceptibility testing in dogs and cats.

J Vet Intern Med 2020 Mar 31;34(2):783-789. Epub 2020 Jan 31.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota.

Background: Quantitative bacterial culture and susceptibility testing is the gold standard diagnostic for determining bacterial urinary tract infection. Transport of samples to external reference laboratories is common practice in veterinary medicine.

Objective: To compare bacterial culture and susceptibility results from clinical urine samples when streak plate inoculation is performed immediately after sample collection versus after transport to a reference laboratory. To determine the clinical implications of discrepant culture results.

Animals: One hundred and ninety-four canine and 45 feline urine samples that were submitted for urinalysis and urine culture and susceptibility testing.

Methods: This was a prospective, cross-sectional study. Streak plate inoculations were performed on urine samples immediately after collection and also after transport to a reference laboratory. Samples were stored in plain sterile tubes and refrigerated up to 24 hours before transport. Culture results were compared, and discordant results were evaluated for clinical relevance. Signalment, comorbidities, lower urinary tract signs, and antimicrobial history were recorded.

Results: Kappa coefficient for agreement between plating methods was 0.884. Twenty-two (71%) of 31 discrepant results were determined to have no clinical impact. Though 35% of clean midstream samples had discrepant culture results, only 8% of these had clinical impact. Conversely, 8.6% from cystocentesis were discrepant, but 41% of these had clinical impact.

Conclusions And Clinical Importance: Provided urine samples are stored and transported appropriately, the immediate preplating of urine for culture and susceptibility testing is unnecessary in the majority of cases. Despite more discrepancies in plating methods for midstream samples, the minority were of clinical importance.
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http://dx.doi.org/10.1111/jvim.15719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096614PMC
March 2020

Prevalence and time trend analysis of antimicrobial resistance in respiratory bacterial pathogens collected from diseased pigs in USA between 2006-2016.

Res Vet Sci 2020 Feb 21;128:135-144. Epub 2019 Nov 21.

Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, USA; VISAVET Health Surveillance Center, Universidad Complutense, Madrid, Spain; Department of Animal Health, Facultad de Veterinaria, Universidad Complutense, Madrid, Spain. Electronic address:

Swine respiratory disease complex (SRDC) causes massive economic losses to the swine industry and is a major animal welfare concern. Antimicrobials are mainstay in treatment and control of SRDC. However, there is a lack of data on the prevalence and trends in resistance to antimicrobials in bacterial pathogens associated with SRDC. The objective of this study was to estimate the prevalence and changes in resistance to 13 antimicrobials in swine bacterial pathogens (Streptococcus suis, Pasteurella multocida, Actinobacillus suis and Haemophilus parasuis) in the U.S.A using data collected at University of Minnesota Veterinary Diagnostic Laboratory between 2006 and 2016. For antimicrobials for which breakpoints were available, prevalence of resistance remained below 10% except for tetracycline in S. suis and P. multocida isolates, and these prevalence estimates remained consistently low over the years despite statistical significance (p < .05) in trend analysis. For antimicrobial-bacterial combinations without available breakpoints, the odds of isolates being resistant increased by >10% annually for 7 and 1 antimicrobials in H. parasuis and S. suis isolates respectively, and decreased >10% annually for 4 and 1 antimicrobials in A. suis and H. parasuis isolates, respectively, according to the ordinal regression models. Clinical implications of changes in AMR for A. suis and H. parasuis should be interpreted cautiously due to the lack of interpretive criteria and challenges in antimicrobial susceptibility tests in the case of H. parasuis. Future studies should focus on surveillance of antimicrobial resistance and establishment of standardized susceptibility testing methodologies and interpretive criteria for these animal pathogens of critical importance.
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http://dx.doi.org/10.1016/j.rvsc.2019.11.010DOI Listing
February 2020

Determination of a serum total calcium concentration threshold for accurate prediction of ionized hypercalcemia in dogs with and without hyperphosphatemia.

J Vet Intern Med 2020 Jan 6;34(1):74-82. Epub 2019 Nov 6.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota.

Background: Total serum calcium (tCa) concentrations are poorly predictive of ionized calcium (iCa) status in dogs.

Hypothesis: There is an optimal threshold of tCa concentration that is highly predictive of ionized hypercalcemia and this threshold is higher in hyperphosphatemic dogs as compared to nonhyperphosphatemic dogs.

Animals: Nonhyperphosphatemic (n = 1593) and hyperphosphatemic (n = 250) adult dogs.

Methods: Retrospective medical record review of paired tCa and iCa concentration measurements in dogs presented to a university teaching hospital over a 5-year period. Positive and negative predictive values, sensitivity, and specificity were calculated for tCa concentration thresholds of 11.0-15.0 mg/dL (upper limit of laboratory reference interval = 11.5 mg/dL) in nonhyperphosphatemic and hyperphosphatemic groups.

Results: In nonhyperphosphatemic dogs, an optimal tCa concentration threshold of 12.0 mg/dL resulted in a positive predictive value of 93% (95% confidence interval [CI], 84%-98%) and sensitivity of 52% (95% CI, 43%-61%) for ionized hypercalcemia. An optimal tCa concentration threshold was not identified for hyperphosphatemic dogs. The nonhyperphosphatemic dogs had a higher prevalence of ionized hypercalcemia than the hyperphosphatemic dogs (7 versus 3%, P = .04) and a lower prevalence of ionized hypocalcemia (23 versus 62%, respectively; P < .001).

Conclusions And Clinical Importance: High tCa concentrations are strongly predictive of ionized hypercalcemia in nonhyperphosphatemic adult dogs and should prompt further diagnostic testing to determine the underlying cause of hypercalcemia. In this population, dogs without increased tCa concentrations rarely had ionized hypercalcemia, but iCa concentrations still should be evaluated in patients with tCa concentrations within the reference interval if there is clinical suspicion for calcium abnormalities.
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http://dx.doi.org/10.1111/jvim.15654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979110PMC
January 2020

Rapid Transduction and Expansion of Transduced T Cells with Maintenance of Central Memory Populations.

Mol Ther Methods Clin Dev 2020 Mar 30;16:1-10. Epub 2019 Sep 30.

Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USA.

Chimeric antigen receptor (CAR)-T cells show great promise in treating cancers and viral infections. However, most protocols developed to expand T cells require relatively long periods of time in culture, potentially leading to progression toward populations of terminally differentiated effector memory cells. Here, we describe in detail a 9-day protocol for CAR gene transduction and expansion of primary rhesus macaque peripheral blood mononuclear cells (PBMCs). Cells produced and expanded with this method show high levels of viability, high levels of co-expression of two transduced genes, retention of the central memory phenotype, and sufficient quantity for immunotherapeutic infusion of 1-2 × 10 cells/kg in a 10 kg rhesus macaque. This 9-day protocol may be broadly used for CAR-T cell and other T cell immunotherapy approaches to decrease culture time and increase maintenance of central memory populations.
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http://dx.doi.org/10.1016/j.omtm.2019.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6816036PMC
March 2020

An in-home intervention of parent-implemented strategies to increase child vegetable intake: results from a non-randomized cluster-allocated community trial.

BMC Public Health 2019 Jul 4;19(1):881. Epub 2019 Jul 4.

Department of Food Science and Nutrition, University of Minnesota, 1334 Eckles Ave, St. Paul, MN, 55108, USA.

Background: Less than 2% of children in the U.S., ages 9-13, meet the minimum dietary recommendations for vegetable intake. The home setting provides potential opportunities to promote dietary behavior change among children, yet limited trials exist with child vegetable intake as a primary outcome. Strategies to increase vegetable intake grounded in behavioral economics are no/low cost and may be easily implemented in the home by parents.

Methods: This non-randomized, controlled study tested whether an intervention of parent-led strategies informed by behavioral economics and implemented within a series of 6 weekly parent-child vegetable cooking skills classes, improved dietary outcomes of a diverse sample of low-income children (ages 9-12) more than the vegetable cooking skills classes alone. The primary outcomes were total vegetable intake, dietary quality (HEI scores), total energy intake, vegetable liking, variety of vegetables tried, child BMI-z score, and home availability of vegetables. Outcome measures were collected at baseline, immediate post-treatment, 6 and 12 months follow-up. Mixed model regression analyses with fixed independent effects (treatment condition, time point and treatment condition x time interaction) were used to compare outcomes between treatment conditions.

Results: A total of 103 parent/child pairs (intervention = 49, control = 54) were enrolled and 91 (intervention = 44, control = 47) completed the weekly cooking skills program. The intervention did not improve child total vegetable intake. Intervention children increased dark green vegetable intake from immediate post-treatment to 12 months. The number of vegetables children tried increased and mean vegetable liking decreased over time for both control and intervention children.

Conclusions: Findings from this study suggest that the strategies and the manner in which they were implemented may not be effective in low-income populations. The burden of implementing a number of strategies with potentially higher food costs may have constrained the ability of families in the current study to use the strategies as intended.

Trial Registration: This trial has been retrospectively registered at : # NCT03641521 on August 21, 2018.
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http://dx.doi.org/10.1186/s12889-019-7079-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610910PMC
July 2019

Serotype and Genotype (Multilocus Sequence Type) of Streptococcus suis Isolates from the United States Serve as Predictors of Pathotype.

J Clin Microbiol 2019 09 26;57(9). Epub 2019 Aug 26.

Veterinary Diagnostic Laboratory, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA

is a significant cause of mortality in piglets and growing pigs worldwide. The species contains pathogenic and commensal strains, with pathogenic strains causing meningitis, arthritis, endocarditis, polyserositis, and septicemia. Serotyping and multilocus sequence typing (MLST) are primary methods to differentiate strains, but the information is limited for strains found in the United States. The objective of this study was to characterize the diversity of 208 isolates collected between 2014 and 2017 across North America (mainly the United States) by serotyping and MLST and to investigate associations between subtype and pathotype classifications (pathogenic, possibly opportunistic, and commensal), based on clinical information and site of isolation. Twenty serotypes were identified, and the predominant serotypes were 1/2 and 7. Fifty-eight sequence types (STs) were identified, and the predominant ST was ST28. Associations among serotypes, STs, and pathotypes were investigated using odds ratio and clustering analyses. Evaluation of serotype and ST with pathotype identified a majority of isolates of serotypes 1, 1/2, 2, 7, 14, and 23 and ST1, ST13, ST25, ST28, ST29, ST94, ST108, ST117, ST225, ST373, ST961, and ST977 as associated with the pathogenic pathotype. Serotypes 21 and 31, ST750, and ST821 were associated with the commensal pathotype, which is composed of isolates from farms with no known history of -associated disease. Our study demonstrates the use of serotyping and MLST to differentiate pathogenic from commensal isolates and establish links between pathotype and subtype, thus increasing the knowledge about strains circulating in the United States.
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http://dx.doi.org/10.1128/JCM.00377-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711919PMC
September 2019

Canine Pruritus Visual Analog Scale: how does it capture owners' perception of their pet's itching level?

Vet Dermatol 2019 Oct 29;30(5):377-e111. Epub 2019 May 29.

Veterinary and Biomedical Sciences, University of Minnesota, 1988 Finch Ave, Saint Paul, MN, 55108, USA.

Background: Accurate measurement of pruritus severity is difficult in veterinary medicine.

Objectives: To determine how the changes in Pruritus Visual Analog Scale (PVAS) scores at follow-up visits agree with the owners' perceptions of improvement of their pet's pruritus.

Animals: One hundred and ninety two pruritic dogs were included in the prospective study and 196 in the retrospective study.

Methods And Materials: Owners were randomly assigned into five groups and PVAS scores were recorded during two consecutive visits. Group A: previous scores were shown before completing the PVAS; Group B: PVAS was completed then owners were shown previous scores and asked to repeat the PVAS; Group C: PVAS was completed as reported previously; Group D: PVAS and a 0-10 verbal scale (VS) were completed. Retrospectively, PVAS scores were analysed during at least three consecutive visits. The average percentage and kappa agreements were calculated for all groups. In addition, PVAS and VS scores were compared in Group D.

Results: The average percentage and kappa agreements were higher in groups A (96%; 0.81), B [before (80%; 0.54), after (82%; 0.59) previous score] and D (85%; 0.47). Group C (79%; 0.37) had the lowest agreement. PVAS and VS scores were not significantly different (P = 0.56) in Group D. The average percentage and kappa agreements for the retrospective study were 50.8% and 0.25. The highest values (63%; 0.355) were noted at 30-60 day visit intervals.

Conclusions And Clinical Importance: Showing owners previous scores could improve how PVAS captures the owner's perception of their dog's itching level.
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http://dx.doi.org/10.1111/vde.12761DOI Listing
October 2019

Environmental Sampling Survey of H5N2 Highly Pathogenic Avian Influenza-Infected Layer Chicken Farms in Minnesota and Iowa.

Avian Dis 2018 12;62(4):373-380

College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108,

Respiratory secretions, feces, feathers, and eggs of avian influenza-infected hens provide ample sources of virus which heavily contaminate barn and farm environments during a disease outbreak. Environmental sampling surveys were conducted in the Midwestern United States on affected farms during the 2015 H5N2 highly pathogenic avian influenza (HPAI) outbreak to assess the degree of viral contamination. A total of 930 samples were obtained from various sites inside and outside layer barns housing infected birds and tested with real-time reverse transcriptase PCR. The distribution and load of viral RNA in barns in which most birds were dead at the onset of depopulation efforts (high-mortality barns) were compared with those of barns in which birds were euthanatized before excess mortality occurred (normal-mortality barns). A statistically significant difference was seen between cycle threshold (Ct) values for samples taken of fans, feed troughs, barn floors, barn walls, cages, manure-associated locations, barn doors, egg belts, and the exterior of high-mortality . normal-mortality barns. In high-mortality barns, sample sites were found to be the most to least contaminated in the following order: cages, manure-associated locations, barn floors, egg belts, feed troughs, barn doors, barn walls, fans, exterior, and egg processing. Significant changes in Ct values over time following HPAI detection in a barn and depopulation of birds on an infected farm were observed for the manure-associated, barn floor, barn wall, and fan sampling sites. These results show that high mortality in a flock as a result of HPAI will increase contamination of the farm environment. The results also suggest optimal sampling locations for detection of virus; however, the persistence of RNA on highmortality farms may delay the determination that adequate sanitization has been performed for restocking to take place.
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http://dx.doi.org/10.1637/11891-050418-Reg.1DOI Listing
December 2018

Molecular and Physiological Characterization of Fluoroquinolone-Highly Resistant Enteritidis Strains.

Front Microbiol 2019 9;10:729. Epub 2019 Apr 9.

Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN, United States.

Four clinical isolates of Enteritidis, susceptible to ciprofloxacin, and their spontaneous ciprofloxacin resistant (MICs from 8 to 16 μg/mL) and highly resistant (MIC 2048 μg/mL) mutants were used to gain an insight into the dynamics of development of fluoroquinolone (FQs) resistance in Enteritidis serovar. The first two high-frequency (i.e., mutations that occurred in each tested strain) mutations occurred in the , resulting in amino acid substitutions S83Y and S83F as well as D87G. Amino acid substitution D87G was significantly associated with the highly resistant mutants. Another high-frequency mutation, deletion in the intergenic region, was determined among the same group of highly resistant mutants. More importantly, each of these deletion mutations affected the RamR binding site. The effect of one 41 bp deletion mutation was empirically tested. The results showed that the deletion was responsible for resistance to ceftiofur and amoxicillin/clavulanic acid and decreased susceptibility to azithromycin and tetracycline. Performing gene expression assays across all ciprofloxacin susceptible groups, we found a consistent and significant upregulation of the , , and (efflux pump associated genes) and downregulation of (porin), clearly illustrating the importance of not only efflux but also porin-mediated permeability in the development of FQs resistance. Our data also showed that . Enteritidis could acquire multiple mutations in QRDR region, further resulting in no up regulation of the genes. These QRDR mutations and no activation of the AcrAB efflux pump seem to preserve the fitness of this organism compared to the . Enteritidis strains that did not acquire multiple QRDR mutations. This report describes the dynamics of FQ-associated mutations in the highly resistant in FQ mutants in . Enteritidis. In addition, we characterized a deletion in the integenic region, demonstrating that this frequent mutation in the highly resistant FQ mutants provide resistance or reduce susceptibility to multiple families of antibiotics.
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http://dx.doi.org/10.3389/fmicb.2019.00729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465633PMC
April 2019

Retrospective evaluation of the route and timing of nutrition in dogs with septic peritonitis: 68 cases (2007-2016).

J Vet Emerg Crit Care (San Antonio) 2019 May 25;29(3):288-295. Epub 2019 Apr 25.

Veterinary Medical Center, University of Minnesota, St Paul, MN.

Objective: To determine the impact of route of nutrition on length of hospitalization and survival to discharge in dogs with septic peritonitis.

Design: Retrospective study from 2007 to 2016.

Setting: University teaching hospital.

Animals: Sixty-eight dogs with septic peritonitis that survived ≥48 hours.

Interventions: None.

Measurements And Main Results: Nutritional strategy was categorized into 1 of 4 groups: voluntary, feeding tube, parenteral (PN), and combined feeding tube and PN. Body weight, body condition score, time without caloric intake before and during hospitalization, length of hospitalization, and percentage of resting energy requirements provided during the first 3 days of nutritional support were recorded. Overall, 54/68 dogs survived (79%). Survival Prediction Index 2 scores were not significantly different between groups. Dogs receiving PN only were less likely to survive than those receiving any enteral nutrition (OR 9.7; 95CI 1.84-58.75). Compared to dogs not receiving PN, dogs receiving any PN were significantly less likely to survive (OR 9.66; 95% CI 1.7-105.8), and were in hospital significantly longer (P = 0.025). Metabolic complications associated with PN were frequent but not associated with increased length of hospitalization or survival to discharge.

Conclusions: Dogs with septic peritonitis that received any PN were in hospital longer and less likely to survive but may have been sicker than those receiving other forms of nutritional support. Further studies are warranted to evaluate reasons for worse outcomes in dogs with septic peritonitis receiving PN.
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http://dx.doi.org/10.1111/vec.12841DOI Listing
May 2019

Cytology and the cell block method in diagnostic characterization of canine lymphadenopathy and in the immunophenotyping of nodal lymphoma.

Vet Comp Oncol 2019 Sep 13;17(3):365-375. Epub 2019 Jun 13.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota.

Minimally invasive techniques used to evaluate canine peripheral lymphadenopathy (PLN), including fine needle aspiration biopsy with cytological evaluation (FNAB-C) and flow cytometry (FC), have benefits and limitations. The cell block (CB) method is an alternate processing technique in which fine needle aspirate biopsy samples are concentrated, fixed, and embedded in paraffin for routine histological processing/staining. Utilizing three observers, we determined the diagnostic value of the CB in evaluating canine PLN across six categories (non-diagnostic, reactive, inflammatory/infectious, probable lymphoma and lymphoma, metastatic neoplasia) and correlated findings to immunophenotypic and clonal antigen receptor rearrangement results in canine nodal lymphoma. Eighty-five paired FNAB-C and CB samples were evaluated from canine patients presenting to the University of Minnesota Veterinary Oncology or Internal Medicine services. Diagnostic quality samples were obtained in 55/85 (65%) CB and 81/85 (95%) FNAB-C samples, respectively, and nodal pathology impacted CB diagnostic yield. Overall percent agreement between diagnostic-quality FNAB-C and CB samples was 86%, but increased to 95% if the categories of lymphoma and probable lymphoma were combined. There was 100% agreement for both the diagnoses of metastatic neoplasia and reactive lymph nodes and 92% agreement for the diagnosis of lymphoma/probable lymphoma. Using immunohistochemistry (IHC), CB samples correctly immunophenotyped 22/23 (96%) cases of B-cell lymphoma, but only 1/6 (17%) cases of T-cell lymphoma. IHC was not completed on nine cases of lymphoproliferative disease because of insufficient cellularity. When the CB method (CBM) yielded diagnostic quality samples there was good to excellent agreement with FNAB-C samples and CB samples were suitable for some IHC tests.
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http://dx.doi.org/10.1111/vco.12484DOI Listing
September 2019

Monitoring the Curriculum through the Student Perspective.

J Vet Med Educ 2020 Apr 22;47(2):177-192. Epub 2019 Apr 22.

Department of Veterinary Population Medicine, University of Minnesota College of Veterinary Medicine.

Student input was deliberately included as part of the curriculum implementation and assessment plan at the University of Minnesota College of Veterinary Medicine. The new curriculum included design features to encourage deeper learning such as a spiral curriculum with cross-course integration, increased open time, and more active learning. Student well-being was seen as a simultaneous need. To gather overall perceptions of workload and well-being, student volunteers from each cohort were surveyed weekly starting in 2013. Survey questions asked about out-of-class work time, level of integration, extracurricular activities, student well-being habits, paid employment, and other factors. Survey questions were combined with course data to get a full picture of week quality, total course work time, extracurricular activities, and the effects of integration. Many of our hypotheses about curricular and extracurricular impacts on week quality were disproven. Week quality was most positively affected by student factors of sleep and exercise, whereas the curricular factors of out-of-class work time, total course work time, and examination hours had the strongest negative effects. A surprising finding was that open time, in-class hours, and paid employment hours had a minimal effect on week quality. Students identified excessively heavy semesters and uneven semester workloads that resulted in early revisions to the new curriculum. Student feedback provided a view of the curriculum that was not otherwise available and resulted in early and significant impacts on the new curriculum, and they provided insight into whether planned changes had occurred and how effective various factors were in reaching the curricular goals.
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http://dx.doi.org/10.3138/jvme.0418-038r1DOI Listing
April 2020

DLA class II haplotypes show sex-specific associations with primary hypoadrenocorticism in Standard Poodle dogs.

Immunogenetics 2019 05 9;71(5-6):373-382. Epub 2019 Apr 9.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, 55108, USA.

Addison's disease (AD) is a life-threatening endocrine disorder that occurs spontaneously in both humans and dogs. Associations between MHC class II genes and AD have been shown in several human studies. Our goal was to identify MHC class II associations with AD in a large population of Standard Poodles, a breed highly predisposed to AD. We sequenced exon 2 of the class II genes DLA-DRB1, DLA-DQA1, and DLA-DQB1 in 110 affected and 101 unaffected Standard Poodles and tested for association with AD. After correcting for population structure, two haplotypes were found to confer risk of developing AD in a sex-specific manner: DLA-DRB1*015:01-DQA1*006:01-DQB1*023:01 in males (xp = 0.03, OR 2.1) and DLA-DRB1*009:01-DQA1*001:01-DQB1*008:01:1 in females (xp = 0.02, OR 8.43). Sex-specific associations have been previously described in human populations, but this is the first report of this kind in dogs. Consistent with findings in other studies, we found the DLA-DQA1*006:01 allele (xp = 0.04) to be associated with AD in males independent of haplotype. In females, the haplotype DLA-DRB1*009:01-DQA1*001:01-DQB1*008:01:1 confers a very high risk for developing AD, although its frequency was rare (9 of 124 females) in our study population. Further studies are warranted to validate the findings of this exploratory dataset and to assess the usefulness of this haplotype as a risk marker for AD in female Standard Poodles. Our results highlight the importance of evaluating MHC class II disease associations in large populations, and accounting for both biological sex and population structure.
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http://dx.doi.org/10.1007/s00251-019-01113-0DOI Listing
May 2019

Low levels of SIV-specific CD8+ T cells in germinal centers characterizes acute SIV infection.

PLoS Pathog 2019 03 21;15(3):e1007311. Epub 2019 Mar 21.

Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota, United States of America.

CD8+ T cells play an important role in controlling of HIV and SIV infections. However, these cells are largely excluded from B cell follicles where HIV and SIV producing cells concentrate during chronic infection. It is not known, however, if antigen-specific CD8+ T cells are excluded gradually as pathogenesis progresses from early to chronic phase, or this phenomenon occurs from the beginning infection. In this study we determined that SIV-specific CD8+ T cells were largely excluded from follicles during early infection, we also found that within follicles, they were entirely absent in 60% of the germinal centers (GCs) examined. Furthermore, levels of SIV-specific CD8+ T cells in follicular but not extrafollicular areas significantly correlated inversely with levels of viral RNA+ cells. In addition, subsets of follicular SIV-specific CD8+ T cells were activated and proliferating and expressed the cytolytic protein perforin. These studies suggest that a paucity of SIV-specific CD8+ T cells in follicles and complete absence within GCs during early infection may set the stage for the establishment of persistent chronic infection.
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http://dx.doi.org/10.1371/journal.ppat.1007311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445460PMC
March 2019

Preliminary Evaluation of Sustained-release Compared with Conventional Formulations of Meloxicam in Sheep ().

J Am Assoc Lab Anim Sci 2019 05 7;58(3):339-345. Epub 2019 Mar 7.

Preclinical Research Center, Department of Surgery, University of Minnesota, St Paul, Minnesota; Veterinary Population Medicine Department, University of Minnesota, St Paul, Minnesota.

Sustained-release (SR) drugs refine current analgesic regimens by alleviating the need for multiple sessions of handling and restraint and by reducing the local tissue irritation that can occur due to repeated injections. Although a variety of SR drugs are already used in lab animal medicine, no studies exist that evaluate the suitability of an SR NSAID in sheep. This study used HPLC-MS to measure the plasma concentrations of 2 formulations of meloxicam-conventional and SRM- after subcutaneous administration in 6 adult ewes. Blood was collected at 0, 4, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, and 168 h after injection. In addition, physical exams, urinalysis, and biochemical analysis were performed at 0, 24, 48, and 120 h after dosage. Peak plasma concentrations were 1057 ± 433 ng/mL at 4 ± 0 h for conventional meloxicam and 3238 ± 1480 ng/mL at 6.7 ± 4.1 h for SR meloxicam (SRM). Elimination half-lives were 12.1 4.2 for CM and 15.2 ± 2.4 h for SRM. One sheep had an episode of acute renal azotemia starting 24 h after SRM administration; the episode resolved over time, and the definitive relationship to SRM administration was not determined. Plasma levels of SRM were higher than CM throughout the initial 24 h, remained variably elevated until 60 h after injection, but failed to sustain presumed therapeutic levels of 400 ng/mL for the full 72 h across all animals in this study. Further investigation is warranted to determine the safety and clinical efficacy of SRM in sheep. Currently, when SRM is used in sheep, we recommend the combination of a preemptive and multimodal analgesia regimen with clinical assessments throughout the postoperative period.
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http://dx.doi.org/10.30802/AALAS-JAALAS-18-000076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526501PMC
May 2019

Urinary neutrophil gelatinase-associated lipocalin in dogs with stable or progressive kidney disease.

J Vet Intern Med 2019 Mar 14;33(2):654-661. Epub 2019 Feb 14.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, Minnesota.

Background: Active kidney injury may play a role in chronic kidney disease (CKD) progression in dogs. Neutrophil gelatinase-associated lipocalin (NGAL), a novel tubular kidney injury biomarker, may help differentiate progressive CKD from stable CKD in dogs.

Objectives: To determine if urinary NGAL : creatinine ratio (UNCR) differentiates stable and progressive CKD in dogs. We hypothesized that UNCR would be higher in dogs with progressive CKD versus stable CKD.

Animals: Twenty-one healthy control dogs, 22 with prerenal azotemia, 19 with stable CKD, 30 with progressive CKD, and 27 with acute kidney injury (AKI).

Methods: Prospective study. Azotemic (serum creatinine concentration >1.6 mg/dL) dogs or nonazotemic AKI dogs were enrolled and classified into 4 groups: (1) prerenal azotemia, (2) stable CKD, (3) progressive CKD, and (4) AKI. Urinary NGAL was measured by ELISA and UNCR compared among groups. Urine protein : creatinine ratio (UPC) in dogs with stable and progressive CKD was compared to UNCR for differentiating CKD groups.

Results: UNCR was significantly higher in dogs with progressive CKD than stable CKD. UNCR of the prerenal azotemia group was significantly lower than that of the progressive CKD and AKI groups. No significant difference was found in UNCR between stable CKD and prerenal azotemia groups. ROC curve analysis of UNCR for differentiating progressive CKD from stable CKD resulted in an AUC of 0.816 (95% confidence interval [CI], 0.673-0.959), greater than that of UPC (0.696; 95% CI, 0.529-0.863).

Conclusions And Clinical Importance: Urinary NGAL could be helpful to predict the risk of progression in dogs with CKD.
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http://dx.doi.org/10.1111/jvim.15428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430932PMC
March 2019

Mycoplasma hyorhinis and Mycoplasma hyosynoviae dual detection patterns in dams and piglets.

PLoS One 2019 3;14(1):e0209975. Epub 2019 Jan 3.

Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, United States of America.

Mycoplasma hyorhinis and M. hyosynoviae are agents associated with arthritis in pigs. This study investigated the tonsillar detection patterns of M. hyorhinis and M. hyosynoviae in a swine population with a history of lameness. The plausibility of dual PCR detection of these agents in dams at one and three weeks post-farrowing and their offspring at the same time was determined. The association between M. hyorhinis and M. hyosynoviae detection in piglets and potential development of lameness in wean-to-finish stages was evaluated by correlating individual piglet lameness scores and PCR detection in tonsils. Approximately 40% of dams were detected positive for M. hyorhinis and M. hyosynoviae at both one and three weeks post-farrowing. In first parity dams, M. hyorhinis was detected in higher proportions (57.1% and 73.7%) at both weeks of sampling compared to multi-parity dams. A lower proportion of first parity dams (37.5%) were detected positive at week one with M. hyosynoviae and an increase in this proportion to 50% was identified in week three. Only 8.3% of piglets were detected positive for M. hyorhinis in week one compared to week three (50%; p<0.05). The detection of M. hyosynoviae was minimal in piglets at both weeks of sampling (0% and 0.9%). Lameness was scored in pigs 5-22 weeks of age, with the highest score observed at week 5. The correlation between PCR detection and lameness scores revealed that the relative risk of developing lameness post-weaning was significantly associated with detection of M. hyorhinis in piglets at three weeks of age (r = 0.44; p<0.05).The detection pattern of M. hyorhinis and M. hyosynoviae in dams did not reflect the detection pattern in piglets. Results of this study suggest that positive detection of M. hyorhinis in piglets pre-weaning could act as a predictor for lameness development at later production stages.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209975PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317828PMC
September 2019