Publications by authors named "Nicholas Frank"

88 Publications

Evidence-based Approach to Switching to a Pass-fail System for Clinical Year Veterinary Student Grading.

J Vet Med Educ 2021 Jan 25:e20190103. Epub 2021 Jan 25.

Veterinary schools have traditionally used letter grading systems to assess the performance of students on clinical rotations, but pass-fail grading may enhance the learning environment and student wellbeing. When a decision to switch grading systems is discussed, concerns are often raised about the effect of removing clinical year grades from final grade point average (GPA) calculations. In order to inform the decision-making at our institution, retrospective analysis of the effects of clinical year grades on final grade point average (GPA) was performed. The specific hypothesis tested was that clinical year GPA would not have a significant effect on cumulative GPA, as defined by a decrease or increase of 0.10 points on average. When data from two classes were examined, median (range) difference final GPA (0-4 scale) compared to GPA at the end of the preclinical curriculum (referred to as delta GPA) was 0.02 (-0.19 to 0.18) for the graduating class of 2016 after removal of two outliers and 0.03 (-0.10 to 0.18) for the class of 2017. Correlations between preclinical GPA and delta GPA (were -0.83 ( < 0.001) for both classes. The hypothesis was supported leading to the conclusion that the overall effect of clinical letter grades on final GPA was close to zero when whole classes were considered, and delta GPA ranged between -0.2 and 0.2 for all except two students. Data from this study were distributed prior to conducting a faculty vote to switch grading systems, and the motion was supported.
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http://dx.doi.org/10.3138/jvme.2019-0103DOI Listing
January 2021

Risk of adverse events due to high volumes of local anesthesia during Mohs micrographic surgery.

Arch Dermatol Res 2020 Oct 30. Epub 2020 Oct 30.

Department of Dermatology, Vanderbilt University Medical Center, Nashville, TN, USA.

General guidelines for the maximum amounts of locally injected lidocaine exist; however, there is a paucity of data in the Mohs micrographic surgery (MMS) literature. This study aimed to determine the safety and adverse effects seen in patients that receive larger amounts of locally injected lidocaine. A retrospective chart review of 563 patients from 1992 to 2016 who received over 30 mL of locally injected lidocaine was conducted. Patient records were reviewed within seven postoperative days for complications. The average amount of anesthesia received was 40 mL, and the average patient weight was 86.69 kg. 1.4% of patients had a complication on the day of surgery, and 4.4% of patients had a complication within 7 days of the surgery. The most common complications were excessive bleeding/hematoma formation and wound infection. Only two complications could be attributable to local anesthetics. Gender, heart disease, hypertension, diabetes, and smoking were not significant risk factors for the development of complications. MMS is a safe outpatient procedure for patients that require over 30 mL of locally injected anesthesia. The safety of high volumes of lidocaine extends to patients with risk factors such as heart disease, hypertension, diabetes, and smoking.
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http://dx.doi.org/10.1007/s00403-020-02155-1DOI Listing
October 2020

Effect of thyrotropin-releasing hormone stimulation testing on the oral sugar test in horses when performed as a combined protocol.

J Vet Intern Med 2019 Sep 20;33(5):2272-2279. Epub 2019 Aug 20.

School of Veterinary Medicine, University of Pennsylvania, Clinical Studies-New Bolton Center, Kennett Square, Chester, Pennsylvania.

Background: The use of parallel dynamic tests to identify insulin dysregulation (ID) and pituitary pars intermedia dysfunction (PPID) in horses could have better diagnostic utility than measuring baseline hormone concentrations, if the tests do not alter diagnostic interpretation of one another.

Hypothesis: Performing a thyrotropin-releasing hormone (TRH) stimulation test before an oral sugar test (OST) would not affect results of OST.

Animals: Twenty-six healthy university-owned horses.

Methods: A prospective randomized placebo-controlled, crossover design was used to evaluate 3 OST protocols: OST alone, TRH followed by OST (TRH + OST), and placebo followed by OST (placebo + OST). Agreement for plasma insulin concentrations and diagnostic interpretation were assessed with Bland-Altman and logistic regression analyses, respectively.

Results: Bland-Altman analysis of TRH + OST versus OST alone showed good agreement between testing protocols, with bias ± SD for insulin concentrations at baseline 0.4 ± 4.7 μIU/mL (95% limits of agreement [LOA], -8.8 to 9.7), 60 minute -0.5 ± 22.6 μIU/mL (95% LOA, -44.7 to 43.8), and 90 minute 1.9 ± 20.6 μIU/mL (95% LOA, -38.5 to 42.4) after OST, similar to placebo + OST versus OST alone. Diagnostic interpretation (positive/negative) was not different between protocols (TRH + OST versus OST alone [P = .78], placebo + OST versus OST alone [P = .77], or TRH + OST versus placebo + OST [P = .57]).

Conclusions And Clinical Importance: Concurrent testing for PPID and ID with a TRH stimulation test before an OST is an acceptable diagnostic tool for investigation of endocrinopathies in horses and allows accurate testing to be performed efficiently in 1 visit.
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http://dx.doi.org/10.1111/jvim.15601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766522PMC
September 2019

Response to letter to editor regarding ECEIM consensus statement on equine metabolic syndrome.

J Vet Intern Med 2019 05 16;33(3):1125-1126. Epub 2019 Apr 16.

Equine Clinic, Internal Medicine, Faculty of Veterinary Medicine, Justus-Liebig-University of Giessen, Giessen, Germany.

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http://dx.doi.org/10.1111/jvim.15503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524088PMC
May 2019

CT Fluoroscopic-Guided Coil Localization of Lung Nodules prior to Video-Assisted Thoracoscopic Surgical Resection Reduces Complications Compared to Hook Wire Localization.

J Vasc Interv Radiol 2019 03;30(3):453-459

Department of Radiology, Division of Vascular Interventional Radiology, University of Minnesota, 4600 Washington St. NE, Minneapolis, MN 55421.

Purpose: To compare the safety and efficacy of hook wire versus microcoil localization of pulmonary nodules prior to video-assisted thoracoscopic resection (VATS).

Materials And Methods: A retrospective comparative review was conducted of 46 patients (26 hook wire and 20 microcoil) who underwent computed tomography fluoroscopic-guided nodule localizations prior to VATS in a single center between January 2012 and August 2016. Nodule characteristics, procedural details, clinical outcomes, and pathologic findings were collected. Baseline characteristics and lung nodule distribution were not significantly different between the 2 groups. Nodule sizes ranged from 2 mm to 28 mm and were similar between groups. Twenty-nine patients (63%) were male, with mean (standard deviation) age of 61 (11) years. Adverse events were classified using standard criteria. Patients were followed for up to 90 days, and the clinical outcomes were compared.

Results: Successful resection of nodules was achieved in all patients. Twelve cases of displacement of the hook wire were observed compared to only 1 in the coil group (P < .01). The total complication rate was lower in the coil group (25% vs 54%, P = .04). Two patients required transition to thoracotomy in the hook wire group, compared to none in the coil group. Median blood loss was similar in both groups (median loss, 20-22 mL). One patient had positive margins in the hook wire group. There was a nonsignificant trend toward longer hospital stay and higher major complication rates after hook wire localization (P = .4).

Conclusions: Pulmonary nodule localization with coils prior to VATS resection demonstrated fewer displacements and fewer perioperative complications compared to hook wires.
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http://dx.doi.org/10.1016/j.jvir.2018.10.013DOI Listing
March 2019

ECEIM consensus statement on equine metabolic syndrome.

J Vet Intern Med 2019 Mar 6;33(2):335-349. Epub 2019 Feb 6.

Equine Clinic, Internal Medicine, Faculty of Veterinary Medicine, Justus-Liebig-University of Giessen, Giessen, Germany.

Equine metabolic syndrome (EMS) is a widely recognized collection of risk factors for endocrinopathic laminitis. The most important of these risk factors is insulin dysregulation (ID). Clinicians and horse owners must recognize the presence of these risk factors so that they can be targeted and controlled to reduce the risk of laminitis attacks. Diagnosis of EMS is based partly on the horse's history and clinical examination findings, and partly on laboratory testing. Several choices of test exist which examine different facets of ID and other related metabolic disturbances. EMS is controlled mainly by dietary strategies and exercise programs that aim to improve insulin regulation and decrease obesity where present. In some cases, pharmacologic aids might be useful. Management of an EMS case is a long-term strategy requiring diligence and discipline by the horse's carer and support and guidance from their veterinarians.
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http://dx.doi.org/10.1111/jvim.15423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430910PMC
March 2019

Local dynamic stability of the lower extremity in novice and trained runners while running intraditional and minimal footwear.

Gait Posture 2019 02 5;68:50-54. Epub 2018 Nov 5.

Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.

Background: Understanding how footwear cushioning influences movement stability may be helpful in reducing injuries related to repetitive loading.

Research Question: The purpose of this study was to identify the relationship between running experience and midsole cushioning on local dynamic stability of the ankle, knee and hip.

Methods: Twenty-four trained and novice runners were recruited to run on a treadmill for five minutes at the same relative intensity. Midsole thickness (thick/thin) and stiffness (soft / hard) were manipulated yielding four unique conditions. Lyapunov exponents were estimated using the Wolf algorithm from sagittal ankle, knee and hip kinematics.

Results: Trained runners had increased movement stability in all shoe conditions compared to their novice counterparts. Midsole thickness and stiffness, overall, did not affect movement stability within each of the running groups. Novice runners displayed decreased movement stability at the hip while running in the thick/soft running shoes. It was found that running experience has a greater influence on movement stability in the lower limbs compared to the midsole characteristics that were manipulated in this experiment. The hip was most stable followed by the knee and the ankle highlighting decreased stability in distal joints.

Conclusions: It appears that midsole design within current design ranges do not have the ability to influence movement stability.
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http://dx.doi.org/10.1016/j.gaitpost.2018.10.034DOI Listing
February 2019

Survey of human-horse relationships and veterinary care for geriatric horses.

J Am Vet Med Assoc 2018 Aug;253(3):337-345

OBJECTIVE To assess relationships between horse owners (or lessees) and geriatric or nongeriatric horses and to investigate factors influencing veterinary care decision-making. DESIGN Descriptive, cross-sectional, survey-based study. SAMPLE 2,879 people who owned or leased ≥ 1 horse. PROCEDURES Participants were recruited through social media and online horse forums to participate in an online survey about their horses, including measures of attachment, veterinary care decision-making, and experiences surrounding the death of a horse. Data were collected for primary horses (those respondents interacted with most) and secondary horses. Horses were further categorized as geriatric (≥ 20 years of age) and nongeriatric. RESULTS Geriatric primary horses were considered companion animals, retired, or used as part of a business significantly more frequently, and described as competition horses significantly less frequently, than nongeriatric horses. Geriatric horses were owned or leased significantly longer than nongeriatric horses, but the degree of respondents' attachment did not differ for geriatric versus nongeriatric horses. When respondents reported the death of a horse in the previous year, euthanasia was associated with higher levels of bereavement than death by other means. Death of geriatric horses most commonly followed a chronic illness and was associated with significantly higher levels of bereavement than death of nongeriatric horses. Among factors influencing decisions regarding expensive or long-term medical care, the horse's ability to lead a comfortable life was ranked highest. Respondents with geriatric horses made numerous accommodations for their care. CONCLUSIONS AND CLINICAL RELEVANCE Results provided important initial information about the relationships people have with geriatric horses. Understanding how individuals perceive their horses and how they make decisions regarding complex veterinary care is critical in informing effective client communication.
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http://dx.doi.org/10.2460/javma.253.3.337DOI Listing
August 2018

Endocrine Disorders of the Equine Athlete.

Authors:
Nicholas Frank

Vet Clin North Am Equine Pract 2018 Aug 29;34(2):299-312. Epub 2018 May 29.

Department of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University, 200 Westboro Road, North Grafton, MA 01536, USA. Electronic address:

Equine athletes are affected by 2 major endocrine/metabolic disorders, insulin dysregulation (ID) and pituitary pars intermedia dysfunction. ID is a risk factor for laminitis in horses, which poses the greatest threat to performance because of the damage that it causes to hoof structures. This article includes an in-depth discussion of ID and other risk factors for laminitis that are grouped together as equine metabolic syndrome. As horses age, the risk of pituitary pars intermedia dysfunction increases, and this endocrine disorder may exacerbate preexisting ID and further increase the risk of laminitis.
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http://dx.doi.org/10.1016/j.cveq.2018.04.003DOI Listing
August 2018

Immunohistochemical expression of insulin, glucagon, and somatostatin in pancreatic islets of horses with and without insulin resistance.

Am J Vet Res 2018 Feb;79(2):191-198

OBJECTIVE To assess insulin, glucagon, and somatostatin expression within pancreatic islets of horses with and without insulin resistance. ANIMALS 10 insulin-resistant horses and 13 insulin-sensitive horses. PROCEDURES For each horse, food was withheld for at least 10 hours before a blood sample was collected for determination of serum insulin concentration. Horses with a serum insulin concentration < 20 μU/mL were assigned to the insulin-sensitive group, whereas horses with a serum insulin concentration > 20 μU/mL underwent a frequently sampled IV glucose tolerance test to determine sensitivity to insulin by minimal model analysis. Horses with a sensitivity to insulin < 1.0 × 10 L•min•mU were assigned to the insulin-resistant group. All horses were euthanized with a barbiturate overdose, and pancreatic specimens were harvested and immunohistochemically stained for determination of insulin, glucagon, and somatostatin expression in pancreatic islets. Islet hormone expression was compared between insulin-resistant and insulin-sensitive horses. RESULTS Cells expressing insulin, glucagon, and somatostatin made up approximately 62%, 12%, and 7%, respectively, of pancreatic islet cells in insulin-resistant horses and 64%, 18%, and 9%, respectively, of pancreatic islet cells in insulin-sensitive horses. Expression of insulin and somatostatin did not differ between insulin-resistant and insulin-sensitive horses, but the median percentage of glucagon-expressing cells in the islets of insulin-resistant horses was significantly less than that in insulin-sensitive horses. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that, in insulin-resistant horses, insulin secretion was not increased but glucagon production might be downregulated as a compensatory response to hyperinsulinemia.
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http://dx.doi.org/10.2460/ajvr.79.2.191DOI Listing
February 2018

Outcomes of Endovascular Management of Late Vascular Hemorrhage After Pancreatic Transplant.

AJR Am J Roentgenol 2018 Jan 18;210(1):201-206. Epub 2017 Oct 18.

1 Department of Diagnostic Radiology, University of Minnesota Twin Cities, 420 Delaware St SE, MMC 292, Minneapolis, MN 55455.

Objective: The aim of this retrospective study is to evaluate the endovascular treatment of hemorrhage in the nonperioperative setting in pancreas transplant recipients.

Materials And Methods: All angiograms performed between January 1, 1999, and June 1, 2016, to treat hemorrhage after pancreatic transplant at a single large-volume transplant center were reviewed. Fourteen patients who underwent 21 angiograms were identified. The patients' charts were reviewed for clinical indications, technical aspects of the endovascular interventions, outcomes, and complications.

Results: The mean number of angiograms was 1.5 per patient. The primary and primary assisted clinical success rates were 64.3% (9/14 patients) and 71.4% (10/14 patients), respectively. Five patients (35.7%) experienced complications. At presentation, eight patients had functioning grafts and seven of these eight patients (87.5%) maintained graft function.

Conclusion: It is critical to recognize transplant-related hemorrhage after pancreas transplant. Endovascular management is associated with high clinical success and rarely results in loss of graft function, suggesting that it should be a consideration for first-line therapy in this patient population.
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http://dx.doi.org/10.2214/AJR.17.18171DOI Listing
January 2018

Philosophy: Religion's openness towards science.

Authors:
Frank W Nicholas

Nature 2017 06;546(7659):474

University of Sydney, Australia.

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http://dx.doi.org/10.1038/546474bDOI Listing
June 2017

Relationship of skeletal muscle inflammation with obesity and obesity-associated hyperinsulinemia in horses.

Can J Vet Res 2016 Jul;80(3):217-24

Department of Physiological Sciences (Banse, McFarlane) and Department of Veterinary Clinical Sciences (Holbrook), Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma 74078, USA; Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts 01536, USA (Frank).

Local (skeletal muscle and adipose) and systemic inflammation are implicated in the development of obesity-associated insulin resistance in humans. In horses, obesity is neither strongly nor consistently associated with systemic inflammation. The role of skeletal muscle inflammation in the development of insulin dysregulation (insulin resistance or hyperinsulinemia) remains to be determined. We hypothesized that skeletal muscle inflammation is related to obesity-associated hyperinsulinemia in horses. Thirty-five light-breed horses with body condition scores (BCSs) of 3/9 to 9/9 were studied, including 7 obese, normoinsulinemic (BCS ≥ 7, resting serum insulin < 30 μIU/mL) and 6 obese, hyperinsulinemic (resting serum insulin ≥ 30 μIU/mL) horses. Inflammatory biomarkers were evaluated in skeletal muscle biopsies and plasma. Relationships between markers of inflammation and BCS were evaluated. To assess the role of inflammation in obesity-associated hyperinsulinemia, markers of inflammation were compared among lean or ideal, normoinsulinemic (L-NI); obese, normoinsulinemic (O-NI); and obese, hyperinsulinemic (O-HI) horses. Skeletal muscle and plasma tumor necrosis factor alpha (TNFα) concentrations were negatively correlated with BCS. When comparing inflammatory markers among groups, skeletal muscle TNFα was lower in the O-HI group than in the O-NI or L-NI groups. In horses, neither skeletal muscle nor systemic inflammation appears to be positively related to obesity or obesity-associated hyperinsulinemia.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924556PMC
July 2016

Hybrid vigour in dogs?

Vet J 2016 Aug 30;214:77-83. Epub 2016 May 30.

School of Life and Environmental Sciences, Faculty of Veterinary Science, University of Sydney, Sydney, NSW 2006, Australia.

Evidence from other species justifies the hypotheses that useful hybrid vigour occurs in dogs and that it can be exploited for improved health, welfare and fitness for purpose. Unfortunately, most of the relevant published canine studies do not provide estimates of actual hybrid vigour because of inadequate specification of the parentage of mixed-bred dogs. To our knowledge, only three published studies have shed any light on actual hybrid vigour in dogs. There are two reports of actual hybrid vigour between Labrador and Golden retrievers, the first ranging from +2.5% to -6.0% for components of a standardised applied-stimulus behavioural test, and the second being at least +12.4% for chance of graduating as a guide dog. The third study provides a minimum estimate of negative actual hybrid vigour: crossbreds between Labrador retrievers and poodles had a higher prevalence of multifocal retinal dysplasia than the average prevalence in their purebred parent breeds. The lack of estimates of actual hybrid vigour can be overcome by including the exact nature of the cross (e.g. F1, F2 or backcross) and their purebred parental breeds in the specification of mixed-bred dogs. Even if only F1 crossbreds can be categorised, this change would enable researchers to conduct substantial investigations to determine whether hybrid vigour has any utility for dog breeding.
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http://dx.doi.org/10.1016/j.tvjl.2016.05.013DOI Listing
August 2016

Effects of withholding feed on thyrotropin-releasing hormone stimulation test results and effects of combined testing on oral sugar test and thyrotropin-releasing hormone stimulation test results in horses.

Am J Vet Res 2016 Jul;77(7):738-48

OBJECTIVE To assess effects of withholding feed on thyrotropin-releasing hormone (TRH) stimulation test results used in diagnosis of pituitary pars intermedia dysfunction in horses and determine effects of combined testing on results of the TRH stimulation test and the oral sugar test (OST) used in diagnosis of equine metabolic syndrome. ANIMALS 30 adult horses. PROCEDURES All horses underwent TRH stimulation tests under fed and nonfed conditions, an OST alone, and an OST combined with TRH stimulation testing. For TRH stimulation tests, plasma ACTH concentrations were measured before (baseline) and 10 minutes after (poststimulation) IV TRH administration. For the OST, plasma glucose and insulin concentrations were measured before (baseline) and 60 and 90 minutes after oral corn syrup administration. For combined testing, the TRH stimulation test was initiated immediately after 60-minute posttreatment sample collection for the OST. Results were compared among methods by Wilcoxon matched-pairs, signed rank tests, paired t tests, and Bland-Altman analysis. RESULTS Feeding conditions did not affect median ACTH concentrations when TRH stimulation tests were performed alone. Median baseline ACTH concentration did not differ between TRH stimulation tests performed alone (under fed or nonfed conditions) and those combined with OSTs. Median poststimulation ACTH concentration was significantly lower for combined tests than for solitary TRH stimulation tests. Mean 60-minute plasma glucose concentration was significantly lower for solitary OSTs than for combined tests, but this difference could not be attributed to TRH administration. CONCLUSIONS AND CLINICAL RELEVANCE Combined testing in the manner described impacted ACTH concentrations during TRH stimulation tests and is not recommended at this time.
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http://dx.doi.org/10.2460/ajvr.77.7.738DOI Listing
July 2016

Relationship of oxidative stress in skeletal muscle with obesity and obesity-associated hyperinsulinemia in horses.

Can J Vet Res 2015 Oct;79(4):329-38

Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma 74078, USA (Banse, McFarlane); Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts 01536, USA (Frank); Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta T2N 4Z6 (Kwong).

In horses, hyperinsulinemia and insulin resistance (insulin dysregulation) are associated with the development of laminitis. Although obesity is associated with insulin dysregulation, the mechanism of obesity-associated insulin dysregulation remains to be established. We hypothesized that oxidative stress in skeletal muscle is associated with obesity-associated hyperinsulinemia in horses. Thirty-five light breed horses with body condition scores (BCS) of 3/9 to 9/9 were studied, including 7 obese, normoinsulinemic (BCS ≥ 7, resting serum insulin < 30 μIU/mL) and 6 obese, hyperinsulinemic (resting serum insulin ≥ 30 μIU/mL) horses. Markers of oxidative stress (oxidative damage, mitochondrial function, and antioxidant capacity) were evaluated in skeletal muscle biopsies. A Spearman's rank correlation coefficient was used to determine relationships between markers of oxidative stress and BCS. Furthermore, to assess the role of oxidative stress in obesity-related hyperinsulinemia, markers of antioxidant capacity and oxidative damage were compared among lean, normoinsulinemic (L-NI); obese, normoinsulinemic (O-NI); and obese, hyperinsulinemic (O-HI) horses. Increasing BCS was associated with an increase in gene expression of a mitochondrial protein responsible for mitochondrial biogenesis (estrogen-related receptor alpha, ERRα) and with increased antioxidant enzyme total superoxide dismutase (TotSOD) activity. When groups (L-NI, O-NI, and O-HI) were compared, TotSOD activity was increased and protein carbonyls, a marker of oxidative damage, decreased in the O-HI compared to the L-NI horses. These findings suggest that a protective antioxidant response occurred in the muscle of obese animals and that obesity-associated oxidative damage in skeletal muscle is not central to the pathogenesis of equine hyperinsulinemia.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581679PMC
October 2015

Evaluation of a thyrotropin-releasing hormone solution stored at room temperature for pituitary pars intermedia dysfunction testing in horses.

Am J Vet Res 2015 May;76(5):437-44

Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536.

Objective: To determine whether plasma ACTH concentrations vary following administration of a thyrotropin-releasing hormone (TRH) solution prepared for research purposes and stored at -20°C (rTRH) or prepared by a compounding pharmacy and stored at room temperature (approx 22°C; cTRH).

Animals: 34 adult horses.

Procedures: The study consisted of 2 experiments. In experiment 1, each horse underwent 2 TRH stimulation tests separated by 24 hours; 10 horses were administered cTRH for the first test and rTRH for the second test (group 1), 10 horses were administered rTRH for the first test and cTRH for the second test (group 2), and 10 horses were administered rTRH for both tests (group 3). Plasma ACTH concentrations were measured at 0 (baseline) and 30 minutes after TRH administration and the delta ACTH responses (change in ACTH concentration after TRH administration) were calculated. In experiment 2, the design was the same as that for experiment 1 except there were 14 days between tests, ACTH was measured at 0 and 10 minutes after TRH administration, and 11, 9, and 10 horses were assigned to groups 1, 2, and 3, respectively.

Results: Adverse effects associated with TRH administration included transient coughing and yawning. In experiment 1, the median delta ACTH response for the second test was significantly lower than that for the first test for all groups. In experiment 2, the median delta ACTH response did not differ significantly between the first and second tests for any group, ACTH concentrations after rTRH administration were positively correlated (rs = 0.95) with those after cTRH administration, and the mean ± SD bias in post-TRH ACTH concentration between rTRH and cTRH was 2.9 ± 12.4 pg/mL.

Conclusions And Clinical Relevance: Results indicated that the TRH stimulation test should not be repeated within 24 hours, and cTRH solution stored at room temperature could be used to effectively perform TRH stimulation testing in horses.
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http://dx.doi.org/10.2460/ajvr.76.5.437DOI Listing
May 2015

Understanding genetics: why should vets care?

J Feline Med Surg 2015 Mar;17(3):201-2

University of California, Davis, USA.

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http://dx.doi.org/10.1177/1098612X15571877DOI Listing
March 2015

Canine hip dysplasia - towards more effective selection.

N Z Vet J 2015 Mar 27;63(2):67-8. Epub 2015 Jan 27.

a Faculty of Veterinary Science , University of Sydney , NSW 2006 , Australia.

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http://dx.doi.org/10.1080/00480169.2015.985562DOI Listing
March 2015

The sheep genome illuminates biology of the rumen and lipid metabolism.

Science 2014 Jun;344(6188):1168-1173

Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.

Sheep (Ovis aries) are a major source of meat, milk, and fiber in the form of wool and represent a distinct class of animals that have a specialized digestive organ, the rumen, that carries out the initial digestion of plant material. We have developed and analyzed a high-quality reference sheep genome and transcriptomes from 40 different tissues. We identified highly expressed genes encoding keratin cross-linking proteins associated with rumen evolution. We also identified genes involved in lipid metabolism that had been amplified and/or had altered tissue expression patterns. This may be in response to changes in the barrier lipids of the skin, an interaction between lipid metabolism and wool synthesis, and an increased role of volatile fatty acids in ruminants compared with nonruminant animals.
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http://dx.doi.org/10.1126/science.1252806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157056PMC
June 2014

Mutation discovery for Mendelian traits in non-laboratory animals: a review of achievements up to 2012.

Anim Genet 2014 Apr 26;45(2):157-70. Epub 2013 Dec 26.

Faculty of Veterinary Science, University of Sydney, Sydney, NSW, 2006, Australia.

Within two years of the re-discovery of Mendelism, Bateson and Saunders had described six traits in non-laboratory animals (five in chickens and one in cattle) that show single-locus (Mendelian) inheritance. In the ensuing decades, much progress was made in documenting an ever-increasing number of such traits. In 1987 came the first discovery of a causal mutation for a Mendelian trait in non-laboratory animals: a non-sense mutation in the thyroglobulin gene (TG), causing familial goitre in cattle. In the years that followed, the rate of discovery of causal mutations increased, aided mightily by the creation of genome-wide microsatellite maps in the 1990s and even more mightily by genome assemblies and single-nucleotide polymorphism (SNP) chips in the 2000s. With sequencing costs decreasing rapidly, by 2012 causal mutations were being discovered in non-laboratory animals at a rate of more than one per week. By the end of 2012, the total number of Mendelian traits in non-laboratory animals with known causal mutations had reached 499, which was half the number of published single-locus (Mendelian) traits in those species. The distribution of types of mutations documented in non-laboratory animals is fairly similar to that in humans, with almost half being missense or non-sense mutations. The ratio of missense to non-sense mutations in non-laboratory animals to the end of 2012 was 193:78. The fraction of non-sense mutations (78/271 = 0.29) was not very different from the fraction of non-stop codons that are just one base substitution away from a stop codon (21/61 = 0.34).
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http://dx.doi.org/10.1111/age.12103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225684PMC
April 2014

Genetic correlations among canine hip dysplasia radiographic traits in a cohort of Australian German Shepherd Dogs, and implications for the design of a more effective genetic control program.

PLoS One 2013 7;8(11):e78929. Epub 2013 Nov 7.

Faculty of Veterinary Science, The University of Sydney, Sydney, New South Wales, Australia.

Canine hip dysplasia (CHD) is a common musculoskeletal disease in pedigree dog populations. It can cause severe pain and dysfunction which may require extensive medication and/or surgical treatment and often ultimately requires humane euthanasia. CHD has been found to be moderately heritable and, given its impact on welfare, should be considered an imperative breeding priority. The British Veterinary Association/Kennel Club scoring method is one of several measures used to assess the genetic propensity of potential breeding stock for dysplastic changes to the hips based on radiographic examination. It is a complex measure composed of nine ordinal traits, intended to evaluate both early and late dysplastic changes. It would be highly desirable if estimated breeding values (EBVs) for these nine traits were consolidated into a simpler, EBV-based, selection index more easily usable by breeders. A multivariate analysis on the phenotype scores from an Australian cohort of 13,124 German Shepherd Dogs (GSDs) returned genetic correlations between 0.48-0.97 for the nine traits which fell into two trait groups, Group 1 reflecting early changes ("laxity") and Group 2 reflecting late changes ("osteoarthritis"). Principal components analysis of the ordinal EBVs suggested the same pattern, with strong differentiation between "laxity" and "osteoarthritis" traits in the second component. Taking account of all results, we recommend interim use of two selection indexes: the first being the average of ordinal EBVs for "laxity" traits and the second being the average of ordinal EBVs for "osteoarthritis" traits. The correlation between these two selection indexes (0.771-0.774) is sufficiently less than unity enabling the selection of dogs with different genetic propensity for laxity and for osteoarthritic CHD changes in GSDs; this may also be applicable in other breeds. Dogs with low propensity for severe osteoarthritic change in the presence of laxity may be of interest both in molecular research and breeding programs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0078929PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820674PMC
August 2014

Estimated breeding values for canine hip dysplasia radiographic traits in a cohort of Australian German Shepherd dogs.

PLoS One 2013 29;8(10):e77470. Epub 2013 Oct 29.

Faculty of Veterinary Science, The University of Sydney, Sydney, New South Wales, Australia.

Canine hip dysplasia (CHD) is a serious and common musculoskeletal disease of pedigree dogs and therefore represents both an important welfare concern and an imperative breeding priority. The typical heritability estimates for radiographic CHD traits suggest that the accuracy of breeding dog selection could be substantially improved by the use of estimated breeding values (EBVs) in place of selection based on phenotypes of individuals. The British Veterinary Association/Kennel Club scoring method is a complex measure composed of nine bilateral ordinal traits, intended to evaluate both early and late dysplastic changes. However, the ordinal nature of the traits may represent a technical challenge for calculation of EBVs using linear methods. The purpose of the current study was to calculate EBVs of British Veterinary Association/Kennel Club traits in the Australian population of German Shepherd Dogs, using linear (both as individual traits and a summed phenotype), binary and ordinal methods to determine the optimal method for EBV calculation. Ordinal EBVs correlated well with linear EBVs (r = 0.90-0.99) and somewhat well with EBVs for the sum of the individual traits (r = 0.58-0.92). Correlation of ordinal and binary EBVs varied widely (r = 0.24-0.99) depending on the trait and cut-point considered. The ordinal EBVs have increased accuracy (0.48-0.69) of selection compared with accuracies from individual phenotype-based selection (0.40-0.52). Despite the high correlations between linear and ordinal EBVs, the underlying relationship between EBVs calculated by the two methods was not always linear, leading us to suggest that ordinal models should be used wherever possible. As the population of German Shepherd Dogs which was studied was purportedly under selection for the traits studied, we examined the EBVs for evidence of a genetic trend in these traits and found substantial genetic improvement over time. This study suggests the use of ordinal EBVs could increase the rate of genetic improvement in this population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0077470PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812223PMC
August 2014

Effects of intravenous lipopolysaccharide infusion on glucose and insulin dynamics in horses with equine metabolic syndrome.

Am J Vet Res 2013 Jul;74(7):1020-9

Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.

Objective: To test the hypothesis that glucose and insulin dynamics during endotoxemia differ between healthy horses and horses with equine metabolic syndrome (EMS).

Animals: 6 healthy adult mares and 6 horses with EMS.

Procedures: Each horse randomly received an IV infusion of lipopolysaccharide (20 ng/kg [in 60 mL of sterile saline {0.9% NaCl} solution]) or saline solution, followed by the other treatment after a 7-day washout period. Baseline insulin-modified frequently sampled IV glucose tolerance tests were performed 27 hours before and then repeated at 0.5 and 21 hours after infusion. Results were assessed via minimal model analysis and area under the curve values for plasma glucose and serum insulin concentrations.

Results: Lipopolysaccharide infusion decreased insulin sensitivity and increased area under the serum insulin concentration curve (treatment × time) in both healthy and EMS-affected horses, compared with findings following saline solution administration. The magnitude of increase in area under the plasma glucose curve following LPS administration was greater for the EMS-affected horses than it was for the healthy horses. Horses with EMS that received LPS or saline solution infusions had decreased insulin sensitivity over time.

Conclusions And Clinical Relevance: Glucose and insulin responses to endotoxemia differed between healthy horses and horses with EMS, with greater loss of glycemic control in EMS-affected horses. Horses with EMS also had greater derangements in glucose and insulin homeostasis that were potentially stress induced. It may therefore be helpful to avoid exposure of these horses to stressful situations.
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http://dx.doi.org/10.2460/ajvr.74.7.1020DOI Listing
July 2013

Effects of equine metabolic syndrome on inflammatory responses of horses to intravenous lipopolysaccharide infusion.

Am J Vet Res 2013 Jul;74(7):1010-9

Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.

Objective: To test the hypothesis that inflammatory responses to endotoxemia differ between healthy horses and horses with equine metabolic syndrome (EMS). Animals-6 healthy horses and 6 horses with EMS.

Procedures: Each horse randomly received an IV infusion of lipopolysaccharide (20 ng/kg [in 60 mL of sterile saline {0.9% NaCl} solution]) or saline solution, followed by the other treatment after a 7-day washout period. Baseline data were obtained 30 minutes before each infusion. After infusion, a physical examination was performed hourly for 9 hours and at 15 and 21 hours; a whole blood sample was collected at 30, 60, 90, 120, 180, and 240 minutes for assessment of inflammatory cytokine gene expression. Liver biopsy was performed between 240 and 360 minutes after infusion. Results-Following lipopolysaccharide infusion in healthy horses and horses with EMS, mean rectal temperature, heart rate, and respiratory rate increased, compared with baseline findings, as did whole blood gene expression of interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α. The magnitude of blood cytokine responses did not differ between groups, but increased expression of IL-6, IL-8, IL-10, and tumor necrosis factor-α persisted for longer periods in EMS-affected horses. Lipopolysaccharide infusion increased liver tissue gene expressions of IL-6 in healthy horses and IL-8 in both healthy and EMS-affected horses, but these gene expressions did not differ between groups.

Conclusions And Clinical Relevance: Results supported the hypothesis that EMS affects horses' inflammatory responses to endotoxin by prolonging cytokine expression in circulating leukocytes. These findings are relevant to the association between obesity and laminitis in horses with EMS.
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http://dx.doi.org/10.2460/ajvr.74.7.1010DOI Listing
July 2013

Characterization of blood lipoproteins and validation of cholesterol and triacylglycerol assays for free-ranging polar bears (Ursus maritimus).

J Vet Diagn Invest 2013 May 30;25(3):423-7. Epub 2013 Apr 30.

Department of Zoology and Physiology, University of Wyoming, 1000 East University Avenue, Laramie, WY, USA.

Blood triacylglycerol (TG) and lipoproteins are important variables for evaluating nutritional status of wildlife, but measurements are often expensive and difficult. Performance of a small, portable blood analyzer intended for human medical diagnostics was evaluated in measuring these variables in plasma and serum from free-ranging polar bears (Ursus maritimus), which are experiencing nutritional stress related to sea ice loss. The analyzer accurately tracked changes in concentration of total cholesterol (Ctotal), cholesterol associated with high-density lipoprotein (CHDL), and TG during a validation protocol of diluting samples and spiking them with exogenous cholesterol and glycerol. Values of Ctotal and TG agreed well with values obtained by other methods (ultracentrifugation followed by colorimetric assays); agreement was variable for values of cholesterol associated with specific lipoproteins. Similar to a study of captive polar bears, ultracentrifugation methods revealed greater TG in very low-density lipoproteins than in low-density lipoprotein, which is unusual and merits additional study.
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http://dx.doi.org/10.1177/1040638713486114DOI Listing
May 2013

Effects of a "two-hit" model of organ damage on the systemic inflammatory response and development of laminitis in horses.

Vet Immunol Immunopathol 2012 Nov 7;150(1-2):90-100. Epub 2012 Sep 7.

Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.

The role of endotoxemia in the development of laminitis remains unclear. Although systemic inflammation is a risk factor for laminitis in hospitalized horses, experimental endotoxin administration fails to induce the disease. While not sufficient to cause laminitis by itself, endotoxemia might predispose laminar tissue to damage from other mediators during systemic inflammation. In "two-hit" models of organ damage, sequential exposure to inflammatory stimuli primes the immune system and causes exaggerated inflammatory responses during sepsis. Acute laminitis shares many characteristics with sepsis-associated organ failure, therefore an equine "two-hit" sepsis model was employed to test the hypothesis that laminitis develops with increased frequency and severity when repeated inflammatory events exacerbate systemic inflammation and organ damage. Twenty-four light breed mares (10) and geldings (14) with chronic disease conditions or behavioral abnormalities unrelated to laminitis that warranted euthanasia were obtained for the study. Horses were randomly assigned to receive an 8-h intravenous infusion of either lipopolysaccharide (5 ng/kg/h) or saline beginning at -24h, followed by oligofructose (OF; 5 g/kg) via nasogastric tube at 0 h. Euthanasia and tissue collection occurred at Obel grade 2 laminitis, or at 48 h if laminitis had not developed. Liver biopsies were performed at 24h in laminitis non-responders. Blood cytokine gene expression was measured throughout the study period. Lipopolysaccharide and OF administration independently increased mean rectal temperature (P<0.001), heart rate (P=0.003), respiratory rate (P<0.001), and blood interleukin (IL)-1β gene expression (P<0.0016), but responses to OF were not exaggerated in endotoxin-pretreated horses. The laminitis induction rate did not differ between treatment groups and was 63% overall. When horses were classified as laminitis responders and non-responders, area under the blood IL-1β expression curve (P=0.010) and liver and lung gene expression of IL-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α (P<0.05) were higher in responders following OF administration. The results indicate that endotoxin pretreatment did not enhance responses to OF. However, systemic inflammation was more pronounced in laminitis responders compared to non-responders, and tissue-generated inflammatory mediators could pose a greater risk than those produced by circulating leukocytes.
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http://dx.doi.org/10.1016/j.vetimm.2012.09.002DOI Listing
November 2012

Effects of continuous or intermittent lipopolysaccharide administration for 48 hours on the systemic inflammatory response in horses.

Am J Vet Res 2012 Sep;73(9):1394-402

Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.

Objective: To determine whether the method of lipopolysaccharide (LPS) administration (intermittent vs continuous) affects the magnitude and duration of the systemic inflammatory response in horses and whether prolonged (48 hours) endotoxemia induces laminitis.

Animals: 12 healthy adult horses (10 mares and 2 geldings).

Procedures: Horses were randomly assigned to receive LPS (total dose, 80 μg; n = 4) or saline (0.9% NaCl) solution (80 mL/h; 4) via constant rate infusion or 8 bolus IV injections of LPS (10 μg, q 6 h;4) during a 48-hour period. Physical examinations were performed every 4 hours, inflammatory cytokine gene expression was determined for blood samples obtained every 8 hours, and IV glucose tolerance tests were performed.

Results: All LPS-treated horses had signs of depression and mild colic; those signs abated as the study progressed. Administration of LPS increased expression of interleukin-1β, interleukin-6, and interleukin-8, but results were not significantly different between LPS treatment groups. Cytokine expression was significantly higher on the first day versus the second day of LPS treatment. Interleukin-1β expression was positively correlated with rectal temperature and expression of other cytokines. Glucose and insulin dynamics for both LPS groups combined did not differ significantly from those of the saline solution group. Signs of laminitis were not detected in any of the horses.

Conclusions And Clinical Relevance: Horses developed LPS tolerance within approximately 24 hours after administration was started, and the method of LPS administration did not affect the magnitude or duration of systemic inflammation. Laminitis was not induced in horses.
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http://dx.doi.org/10.2460/ajvr.73.9.1394DOI Listing
September 2012