Clinical Sciences Faculty Research and Publications

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Open Access
Cloning and characterization of feline islet glucokinase
(2014-06-10) Lindbloom-Hawley, Sara; LeCluyse, Michelle; Vandersande, Vanessa; Lushington, Gerald Henry; Schermerhorn, Thomas
Glucokinase (GK) is a metabolic enzyme encoded by the GCK gene and expressed in glucose-sensitive tissues, principally pancreatic islets cell and hepatocytes. The GK protein acts in pancreatic islets as a “glucose sensor” that couples fluctuations in the blood glucose concentration to changes in cellular function and insulin secretion. GCK and GK have proposed importance in the development and progression of diabetes mellitus and are potential therapeutic targets for diabetes treatment. The study was undertaken to determine the nucleotide sequence of feline pancreatic GK cDNA, predict the amino acid sequence and structure of the feline GK protein, and perform comparative bioinformatic analysis of feline cDNA and protein. Routine PCR techniques were used with cDNA from feline pancreas. Clones were assembled to obtain the full length cDNA. Protein prediction and modeling were performed using bioinformatic tools.
Open Access
Interpreting statistics from published research to answer clinical and management questions
(2016-11-01) White, Bradley J.; Larson, Robert L.; Theurer, Miles E.; whiteb; rlarson; White, Bradley J.; Larson, Robert L.
Appropriate statistical analysis is critical in interpreting results from published literature to answer clinical and management questions. Internal validity is an assessment of whether the study design and statistical analysis are appropriate for the hypotheses and study variables while controlling for bias and confounding. External validity is an assessment of the appropriateness of extrapolation of the study results to other populations. Knowledge about whether treatment or observation groups are truly different is unknown, but studies can be broadly categorized as exploratory or discovery, based on knowledge about previous research, biology, and study design, and this categorization affects interpretation. Confidence intervals, P-values, prediction intervals, credible intervals, and other decision aids are used singly or in combination to provide evidence for the likelihood of a given model but can be interpreted only if the study is internally valid. These decision aids do not test for bias, study design, or the appropriateness of applying study results to other populations dissimilar to the population tested. The biologic and economic importance of the magnitude of difference between treatment groups or observation groups as estimated by the study data and statistical interpretation is important to consider in clinical and management decisions. Statistical results should be interpreted in light of the specific question and production system addressed, the study design, and knowledge about pertinent aspects of biology to appropriately aid decisions.
Open Access
A mixed treatment comparison meta-analysis of metaphylaxis treatments for bovine respiratory disease in beef cattle
(2017-02-01) Abell, Kaitlynn M.; Theurer, Miles E.; Larson, Robert L.; White, Bradley J.; Apley, Michael D.; rlarson; whiteb; mapley; Larson, Robert L.; White, Bradley J.; Apley, Michael D.
The objective of this project was to evaluate the effects of antimicrobials approved for parenteral metaphylactic use in feeder and stocker calves on morbidity and mortality for bovine respiratory disease with the use of a mixed treatment comparison meta-analysis. An initial literature review was conducted in April 2016 through Pubmed, Agricola, and CAB (Commonwealth Agricultural Bureau) for randomized controlled trials for metaphylaxis antimicrobial administered parentally to incoming feedlot or stocker calves within 48 h of arrival. The final list of publications included 29 studies, with a total of 37 trials. There were 8 different metaphylactic antimicrobials. Final event outcomes were categorized into bovine respiratory disease (BRD) morbidity cumulative incidence d 1 to <= 60 of the feeding period, BRD morbidity cumulative incidence d 1 to closeout of the feeding period, BRD mortality cumulative incidence d 1 to closeout of the feeding period, and BRD retreatment cumulative incidence morbidity d 1 to closeout of the feeding period. Network meta-analysis combined direct and indirect evidence for all the event outcomes to determine mean odds ratio (OR) with 95% credibility intervals (CrIs) for all metaphylactic antimicrobial comparisons. The "upper tier" treatment arms for morbidity d 1 to <= 60 included tulathromycin, gamithromycin, and tilmicosin. For BRD mortality cumulative incidence d 1 to closeout and BRD retreatment morbidity d 1 to closeout, classifying the treatment arms into tiers was not possible due to overlapping 95% CrIs. The results of this project accurately identified differences between metaphylactic antimicrobials, and metaphylactic antimicrobial options appear to offer different outcomes on BRD morbidity and mortality odds in feedlot cattle.
Open Access
Genomic signatures of Mannheimia haemolytica that associate with the lungs of cattle with respiratory disease, an integrative conjugative element, and antibiotic resistance genes
(2016-11-29) Clawson, M. L.; Murray, R. W.; Sweeney, M. T.; Apley, Michael D.; DeDonder, Keith D.; Capik, Sarah F.; Larson, Robert L.; Lubbers, Brian V.; White, Bradley J.; Kalbfleisch, T. S.; Schuller, G.; Dickey, A. M.; Harhay, G. P.; Heaton, M. P.; Chitko-McKown, C. G.; Brichta-Harhay, D. M.; Bono, J. L.; Smith, T. P. L.; mapley; whiteb; rlarson; blubbers; Apley, Michael D.; White, Bradley J.; Larson, Robert L.; Lubbers, Brian V.
Background: Mannheimia haemolytica typically resides in cattle as a commensal member of the upper respiratory tract microbiome. However, some strains can invade their lungs and cause respiratory disease and death, including those with multi-drug resistance. A nucleotide polymorphism typing system was developed for M. haemolytica from the genome sequences of 1133 North American isolates, and used to identify genetic differences between isolates from the lungs and upper respiratory tract of cattle with and without clinical signs of respiratory disease. Results: A total of 26,081 nucleotide polymorphisms were characterized after quality control filtering of 48,403 putative polymorphisms. Phylogenetic analyses of nucleotide polymorphism genotypes split M. haemolytica into two major genotypes (1 and 2) that each were further divided into multiple subtypes. Multiple polymorphisms were identified with alleles that tagged genotypes 1 or 2, and their respective subtypes. Only genotype 2 M. haemolytica associated with the lungs of diseased cattle and the sequence of a particular integrative and conjugative element (ICE). Additionally, isolates belonging to one subtype of genotype 2 (2b), had the majority of antibiotic resistance genes detected in this study, which were assorted into seven combinations that ranged from 1 to 12 resistance genes. Conclusions: Typing of diverse M. haemolytica by nucleotide polymorphism genotypes successfully identified associations with diseased cattle lungs, ICE sequence, and antibiotic resistance genes. Management of cattle by their carriage of M. haemolytica could be an effective intervention strategy to reduce the prevalence of respiratory disease and supplemental needs for antibiotic treatments in North American herds.
Open Access
The impact of item-writing flaws and item complexity on examination item difficulty and discrimination value
(2016-09-29) Rush, Bonnie R.; Rankin, David C.; White, Bradley J.; brush; drankin; whiteb; Rush, Bonnie R.; Rankin, David C.; White, Bradley J.; Mahmudiono, Trias
Background: Failure to adhere to standard item-writing guidelines may render examination questions easier or more difficult than intended. Item complexity describes the cognitive skill level required to obtain a correct answer. Higher cognitive examination items promote critical thinking and are recommended to prepare students for clinical training. This study evaluated faculty-authored examinations to determine the impact of item-writing flaws and item complexity on the difficulty and discrimination value of examination items used to assess third year veterinary students. Methods: The impact of item-writing flaws and item complexity (cognitive level I-V) on examination item difficulty and discrimination value was evaluated on 1925 examination items prepared by clinical faculty for third year veterinary students. Results: The mean (± SE) percent correct (83.3 % ± 17.5) was consistent with target values in professional education, and the mean discrimination index (0.18 ± 0.17) was slightly lower than recommended (0.20). More than one item-writing flaw was identified in 37.3 % of questions. The most common item-writing flaws were awkward stem structure, implausible distractors, longest response is correct, and responses are series of true-false statements. Higher cognitive skills (complexity level III-IV) were required to correctly answer 38.4 % of examination items. As item complexity increased, item difficulty and discrimination values increased. The probability of writing discriminating, difficult examination items decreased when implausible distractors and all of the above were used, and increased if the distractors were comprised of a series of true/false statements. Items with four distractors were not more difficult or discriminating than items with three distractors. Conclusion: Preparation of examination questions targeting higher cognitive levels will increase the likelihood of constructing discriminating items. Use of implausible distractors to complete a five-option multiple choice question does not strengthen the discrimination value. © 2016 The Author(s).
Open Access
Left Displacement of the Abomasum in 4 Beef Calves
(2016-06-01) Oman, R. E.; Streeter, R. N.; Reppert, Emily J.; Chako, C. Z.; erepper; Reppert, Emily J.
BackgroundLittle is known about the occurrence rate, underlying etiology or treatment of left displacement of the abomasum in beef calves. ObjectiveDescribe the clinical presentation, diagnosis and treatment of left displacement of the abomasum in 4 beef calves. AnimalsFour client-owned beef breed calves with left displaced abomasum (LDA). MethodsRetrospective case series. Hospital medical records were reviewed to identify all beef breed cattle under the age of 6 months diagnosed with LDA. ResultsFour beef calves were treated for left displacement of the abomasum. All four had a history of decreased appetite and left-sided abdominal distention. Two had recently been treated for necrotic laryngitis and one was being treated for clostridial abomasitis. Ultrasonography confirmed the abomasum to be displaced between the rumen and the left body wall in all calves. The calves were initially treated by rolling to correct the abomasal displacement. The abomasum redisplaced in 3 of 4 calves within 1 hour to 6 days; 1 calf developed a mesenteric volvulus. A right paramedian abomasopexy was performed in all cases. Three of 4 calves grew well and remained in the herd 6-18 months later; 1 calf was euthanized because of complications associated with necrotic laryngitis. Conclusions and clinical importanceLeft displacement of the abomasum should be considered as a differential diagnosis for beef calves with abdominal distention. Concurrent necrotic laryngitis can increase the risk of abomasal displacement in beef calves. Treatment should include surgical correction as rolling is not curative and might be associated with mesenteric volvulus.
Open Access
Large genomic differences between Moraxella bovoculi isolates acquired from the eyes of cattle with infectious bovine keratoconjunctivitis versus the deep nasopharynx of asymptomatic cattle
(2016-02-13) Dickey, A. M.; Loy, J. D.; Bono, J. L.; Smith, T. P. L.; Apley, Michael D.; Lubbers, Brian V.; DeDonder, K. D.; Capik, S. F.; Larson, Robert L.; White, Bradley J.; Blom, J.; Chitko-McKown, C. G.; Clawson, M. L.; mapley; blubbers; rlarson; whiteb
Moraxella bovoculi is a recently described bacterium that is associated with infectious bovine keratoconjunctivitis (IBK) or "pinkeye" in cattle. In this study, closed circularized genomes were generated for seven M. bovoculi isolates: three that originated from the eyes of clinical IBK bovine cases and four from the deep nasopharynx of asymptomatic cattle. Isolates that originated from the eyes of IBK cases profoundly differed from those that originated from the nasopharynx of asymptomatic cattle in genome structure, gene content and polymorphism diversity and consequently placed into two distinct phylogenetic groups. These results suggest that there are genetically distinct strains of M. bovoculi that may not associate with IBK.
Open Access
Pathologies of acute interstitial pneumonia in feedlot cattle
(2016-03-30) Valles, J. A.; Apley, Michael D.; Reinhardt, Christopher D.; Bartle, Steven J.; Thomson, Daniel U.; mapley; cdr3; sjbartle; thomson
Acute Interstitial Pneumonia (AIP) is a costly issue that affects feedlot cattle. Research has yet to elucidate the etiology of AIP; therefore a case-control study was conducted to evaluate possible management and physiological factors that contribute to AIP in feedlot cattle. The experiment was conducted during the summer of 2011 in a commercial feedyard in Kansas. Animals exhibiting clinical signs of AIP and a control animal from the same pen were selected for ante-mortem examination. Post-mortem AIP cases were also selected for additional examination. Ante-mortem measurements included rumen gas cap hydrogen sulfide and pH, rectal temperature and body weight. Post-mortem examination added histological examination of lung tissue. Rectal temperature was greater in the AIP cattle (40.6±0.16°C) than controls (39.7±0.16°C; p<0.001). Body weight (499±56 Vs. 506±60 kg), hydrogen sulfide (136±133 vs. 269.8±311 ppm) and rumen pH (6.4±0.5 Vs. 6.2±0.6) were similar between AIP and control cattle (p>0.10). Post-mortem rumen pH values were 6.3±0.4 and 5.7±0.6 for AIP and control cattle, respectively. Histological evaluation of lung samples showed that bronchiolitis was present in about 90% of the cattle affected with AIP. About 75% of the cattle with AIP also had bronchopneumonia. No relationships between feed intake patterns, or serum amylase or lipase levels were noted between treatments (p>0.20). This study generally confirms that AIP tends to occur more in heifers relative to steers, occurs in cattle at heavier weights or later in the feeding period and tends to be associated pathologically with bronchio’ litis and bronchopneumonia. The lack of differences in rumen measures and the feed intake data between AIP and control cattle suggest that feed intake patterns and rumen fermentation may not impact AIP in feedlot cattle and that it may be more directly related to bronchiolitis/bronchopneumonia due to chronic irritation or infection. © 2016 Jose A. Valles, Michael D. Apley, Chris D. Reinhardt, Steven J. Bartle and Daniel U. Thomson.
Open Access
Determination of value of bovine respiratory disease control using a remote early disease identification system compared with conventional methods of metaphylaxis and visual observations
(2015-08-01) White, Bradley J.; Amrine, D. E.; Goehl, D. R.; whiteb
Open Access
Bayesian Geostatistical Analysis and Ecoclimatic Determinants of Corynebacterium pseudotuberculosis Infection among Horses
(2015-10-16) Boysen, C.; Davis, Elizabeth G.; Beard, Laurie A.; Lubbers, Brian V.; Raghavan, Ram K.; egdavis; labeard; blubbers; rkraghavan
Open Access
Spatial-Temporal Dynamics of High-Resolution Animal Networks: What Can We Learn from Domestic Animals?
(2015-06-24) Chen, S.; Ilany, A.; White, Bradley J.; Sanderson, Michael W.; Lanzas, C.; whiteb; sandersn
Open Access
Effect of Sucralfate on the Relative Bioavailability of Enrofloxacin and Ciprofloxacin in Healthy Fed Dogs
(2015-12-09) KuKanich, Katherine; KuKanich, Butch; Guess, S.; Heinrich, E.; kstenske; kukanich
Open Access
In vitro increase of mean corpuscular volume difference (dMCV) as a marker for serum hypertonicity in dogs.
(2014-12-03) Reinhart, Jennifer M.; Yancey, Misty R.; Pohlman, Lisa M.; Schermerhorn, Thomas; pohlman; tscherme
Spurious increase in erythrocyte mean corpuscular volume (MCV) on automated cell analyzers is a well-characterized lab error in hypertonic patients. A difference between automated and manual MCV (dMCV) greater than 2 fl has been shown to predict hypertonicity in humans. The purpose of this study was to investigate dMCV as a marker for serum hypertonicity in dogs and to examine the relationship between dMCV and three methods of estimating serum tonicity: measured (OsM_M), calculated (OsM_C), and calculated effective (OsM_CE) osmolalities. OsM_C, OsM_CE, and dMCV were calculated from routine blood values and OsM_M was directly measured in 121 dogs. The dMCV of hypertonic dogs was significantly larger than that of normotonic dogs for all three osmolality methods. dMCV predicted hypertonicity as estimated by OsM_M better than it predicted hypertonicity as estimated by OsM_C and OsM_CE. A cutoff of 2.96 fl yielded the best sensitivity (76%) and specificity (71%) for hypertonicity estimated by OsMM.
Open Access
Use of PCR to identify Leptospira in kidneys of big brown bats (Eptesicus fuscus) in Kansas and Nebraska, USA
(2014-11-04) Harkin, Kenneth R.; Hays, Michael P.; Davis, Rolan D.; Moore, Michael C.; harkin; mhays; rdd8889; mcmoore
Bats have been implicated as potential carriers of Leptospira as a result of surveys, mostly in Australia and South America. We measured the prevalence of pathogenic leptospires in kidneys of bats from Kansas and Nebraska. From 7 August 2012 to 21 August 2012, we extracted DNA from kidneys of 98 big brown bats (Eptesicus fuscus) submitted and found negative for rabies. The DNA was processed in a two-step, seminested PCR assay with a dual-labeled Taqman probe specific for pathogenic leptospires. As a negative control, we used a saprophytic leptospire (Leptospira biflexa Patoc) and, as a pathogenic control, Leptospira interrogans Canicola. All bat kidneys were negative for pathogenic leptospires, suggesting that it is unlikely that the big brown bat, one of the most prevalent bat species in North America, is a reservoir for transmission of leptospires to dogs or humans.
Open Access
Cloning and characterization of feline islet glucokinase
(2014-06-10) Lindbloom-Hawley, Sara; LeCluyse, Michelle; Vandersande, Vanessa; Lushington, Gerald Henry; Schermerhorn, Thomas; tscherme
Background: Glucokinase (GK) is a metabolic enzyme encoded by the GCK gene and expressed in glucose-sensitive tissues, principally pancreatic islets cell and hepatocytes. The GK protein acts in pancreatic islets as a “glucose sensor” that couples fluctuations in the blood glucose concentration to changes in cellular function and insulin secretion. GCK and GK have proposed importance in the development and progression of diabetes mellitus and are potential therapeutic targets for diabetes treatment. The study was undertaken to determine the nucleotide sequence of feline pancreatic GK cDNA, predict the amino acid sequence and structure of the feline GK protein, and perform comparative bioinformatic analysis of feline cDNA and protein. Routine PCR techniques were used with cDNA from feline pancreas. Clones were assembled to obtain the full length cDNA. Protein prediction and modeling were performed using bioinformatic tools. Results: Full-length feline pancreatic GK cDNA contains a 1398 nucleotide coding sequence with high identity to other pancreatic GK cDNAs. The deduced 465 amino acid feline protein has 15 amino acid substitutions not found in other mammalian GK proteins but maintains high structural homology with human GK. Feline pancreatic GK is highly conserved at nucleotide and protein levels. Residues crucial for substrate binding and catalysis are completely conserved in the feline protein. Conclusion: Molecular analysis predicts that feline pancreatic GK functions similarly to other mammalian GK proteins.
Open Access
Normal glucose metabolism in carnivores overlaps with diabetes pathology in non-carnivores
(2014-08-04) Schermerhorn, Thomas; tscherme
Carnivores, such as the dolphin and the domestic cat, have numerous adaptations that befit consumption of diets with high protein and fat content, with little carbohydrate content. Consequently, nutrient metabolism in carnivorous species differs substantially from that of non-carnivores. Important metabolic pathways known to differ between carnivores and non-carnivores are implicated in the development of diabetes and insulin resistance in non-carnivores: (1) the hepatic glucokinase (GCK) pathway is absent in healthy carnivores yet GCK deficiency may result in diabetes in rodents and humans, (2) healthy dolphins and cats are prone to periods of fasting hyperglycemia and exhibit insulin resistance, both of which are risk factors for diabetes in non-carnivores. Similarly, carnivores develop naturally occurring diseases such as hemochromatosis, fatty liver, obesity, and diabetes that have strong parallels with the same disorders in humans. Understanding how evolution, environment, diet, and domestication may play a role with nutrient metabolism in the dolphin and cat may also be relevant to human diabetes.
Open Access
Comparison of classification algorithms to predict outcomes of feedlot cattle identified and treated for Bovine Respiratory Disease
(2014-07-01) Amrine, David E.; White, Bradley J.; Larson, Robert L.; whiteb; rlarson
Bovine respiratory disease (BRD) continues to be the primary cause of morbidity and mortality in feedyard cattle. Accurate identification of those animals that will not finish the production cycle normally following initial treatment for BRD would provide feedyard managers with opportunities to more effectively manage those animals. Our objectives were to assess the ability of different classification algorithms to accurately predict an individual calf’s outcome based on data available at first identification of and treatment for BRD and also to identify characteristics of calves where predictive models performed well as gauged by accuracy. Data from 23 feedyards in multiple geographic locations within the U.S. from 2000 to 2009 representing over one million animals were analyzed to identify animals clinically diagnosed with BRD and treated with an antimicrobial. These data were analyzed both as a single dataset and as multiple datasets based on individual feedyards and partitioned into training, testing, and validation datasets. Classifiers were trained and optimized to identify calves that did not finish the production cycle with their cohort. Following classifier training, accuracy was evaluated using validation data. Analysis was also done to identify sub-groups of calves within populations where classifiers performed better compared to other sub-groups. Accuracy of individual classifiers varied by dataset. The accuracy of the best performing classifier by dataset ranged from a low of 63% in one dataset up to 95% in a different dataset. Sub-groups of calves were identified within some datasets where accuracy of a classifiers were greater than 98%; however these accuracies must be interpreted in relation to the prevalence of the class of interest within those populations. We found that by pairing the correct classifier with the data available, accurate predictions could be made that would provide feedlot managers with valuable information.
Open Access
What is your diagnosis?
(2013-09-01) Delk, Katie W.; Carpenter, James W.; Pennick, Kate; Pohlman, Lisa M.; Nietfeld, Jerome C.; carpentr; pohlman; jcnietfe
Open Access
Evaluating group housing strategies for the ex-situ conservation of harlequin frogs (Atelopus spp.) using behavioral and physiological indicators
(2014-02-25) Cikanek, Shawna J.; Nockold, Simon; Brown, Janine L.; Carpenter, James W.; Estrada, Angie; Guerrel, Jorge; Hope, Katharine; Ibáñez, Roberto; Putman, Sarah B.; Gratwicke, Brian; carpentr
We have established ex situ assurance colonies of two endangered Panamanian harlequin frogs, Atelopus certus and Atelopus glyphus, but observed that males fought with each other when housed as a group. Housing frogs individually eliminated this problem, but created space constraints. To evaluate the potential stress effects from aggressive interactions when grouping frogs, we housed male frogs in replicated groups of one, two, and eight. We measured aggressive behavioral interactions and fecal glucocorticoid metabolite (GC) concentrations as indicators of stress in each tank. In both small and large groups, frogs initially interacted aggressively, but aggressive interactions and fecal GCs declined significantly after the first 2 weeks of being housed together, reaching the lowest levels by week 4. We conclude that aggressive interactions in same-sex groups of captive Atelopus may initially cause stress, but the frogs become habituated within a few weeks and they can safely be housed in same-sex groups for longer periods of time.
Open Access
Highly dynamic animal contact network and implications on disease transmission
(2014-03-26) Chen, Shi; White, Bradley J.; Sanderson, Michael W.; Amrine, David E.; Ilany, Amiyaal; Lanzas, Cristina; whiteb; sandersn
Contact patterns among hosts are considered as one of the most critical factors contributing to unequal pathogen transmission. Consequently, networks have been widely applied in infectious disease modeling. However most studies assume static network structure due to lack of accurate observation and appropriate analytic tools. In this study we used high temporal and spatial resolution animal position data to construct a high-resolution contact network relevant to infectious disease transmission. The animal contact network aggregated at hourly level was highly variable and dynamic within and between days, for both network structure (network degree distribution) and individual rank of degree distribution in the network (degree order). We integrated network degree distribution and degree order heterogeneities with a commonly used contact-based, directly transmitted disease model to quantify the effect of these two sources of heterogeneity on the infectious disease dynamics. Four conditions were simulated based on the combination of these two heterogeneities. Simulation results indicated that disease dynamics and individual contribution to new infections varied substantially among these four conditions under both parameter settings. Changes in the contact network had a greater effect on disease dynamics for pathogens with smaller basic reproduction number (i.e. R[subscript 0] < 2).