Isolation of feline islets of Langerhans by selective osmotic shock produces glucose responsive islets.

Introduction: Pancreatic islet isolation is essential for studying islet physiology, pathology, and transplantation, and feline islets could be an important model for human type II diabetes mellitus (T2D). Traditional isolation methods utilizing collagenases inflict damage and, in cats, may contribute to the difficulty in generating functional islets, as demonstrated by glucose-stimulated insulin secretion (GSIS). GLUT2 expression in ß cells may allow for adaptation to hyperosmolar glucose solutions while exocrine tissue is selectively disrupted. Methods: Here we developed a protocol for selective osmotic shock (SOS) for feline islet isolation and evaluated the effect of different hyperosmolar glucose concentrations (300 mmol/L and 600 mmol/L) and incubation times (20 min and 40 min) on purity, morphology, yield, and GSIS. Results: Across protocol treatments, islet yield was moderate and morphology excellent. The treatment of 600 mmol/L glucose solution with 20 min incubation resulted in the highest stimulation index by GSIS. Discussion: Glucose responsiveness was demonstrated, permitting future in vitro studies. This research opens avenues for understanding feline islet function and transplantation possibilities and enables an additional islet model for T2D.

Radiographic and ultrasonographic appearance of a jejunal torsion-volvulus in a dog.

A 1.5-year-old male neutered, 5 kg, Dachshund was referred for anorexia and vomiting for several days' duration. Radiographs revealed concern for a small intestinal obstruction. Ultrasonography revealed a severely distended segment of jejunum containing echogenic fluid that abruptly narrowed, twisted, and transitioned into normal jejunum, along with the presence of a distinct "whirl sign" that resulted from the intestinal segments twisting around themselves. This, in addition to the absence of flow on power Doppler interrogation, was compatible with a focal jejunal torsion-volvulus. The torsion-volvulus was surgically confirmed, a resection and anastomosis was performed, and the dog recovered uneventfully.

Geometric, landmark-guided technique reduces tissue trauma, surgery time, and subjective difficulty for canine peripheral lymphadenectomies: an educational crossover study.

OBJECTIVE: To compare the effect of a geometric, landmark-guided lymphadenectomy (LL) approach to peripheral lymph nodes (LNs) on successful LN identification, surgical time, tissue trauma, and ease of LN identification compared to standard lymphadenectomy (SL) and methylene blue-guided lymphadenectomy (MBL). SAMPLE: 18 adult, mixed-breed canine cadavers operated on by 7 veterinarians and 5 fourth-year veterinary students between July 23 and October 12, 2022. METHODS: Participants were provided standardized, publicly available materials regarding the anatomy and surgical techniques for SL of 3 peripheral lymphocentrums: superficial cervical, axillary (ALN), and superficial inguinal (SILN). Participants performed the 3 SLs unilaterally on canine cadavers. Thereafter, they were randomly assigned to 2 crossover groups: MBL and LL. All dissections were separated by at least 2 weeks for each participant. Primary outcome measures included successful LN identification, surgical time, tissue trauma scores, and subjective difficulty. RESULTS: Successful LN identification was highest with LL (86%) compared to SL (69%) and MBL (67%). Subjective difficulty scores were reduced with LL for SILN dissections. Tissue trauma scores were reduced when using LL for ALN and SILN compared to MBL and SL. Time to LN identification was reduced for ALN with LL. No significant differences were observed between MBL and SL, or for the superficial cervical dissections. CLINICAL RELEVANCE: Peripheral lymphadenectomies are time consuming and difficult for veterinarians in early stages of surgical training. Little surgical guidance is provided within current literature. Geometric, landmark-guided lymphadenectomies may improve LN identification success and reduce surgical time, tissue trauma, and procedure difficulty, which could encourage their clinical application.

Superficial anatomic landmarks can be used to triangulate the location of canine peripheral lymphocentrums: superficial cervical, axillary, and superficial inguinal.

OBJECTIVE: To utilize the geometry of superficial anatomic landmarks to guide incisional location and orientation for peripheral lymphadenectomy, document deep anatomic landmarks for lymphocentrum identification, and develop novel surgical approaches to the superficial cervical, axillary, and superficial inguinal lymphocentrums in dogs. ANIMALS: 12 canine cadavers. PROCEDURES: 2 cadavers were used for a pilot investigation to determine optimal body positioning, select superficial anatomic landmarks for lymphocentrum identification, and evaluate novel surgical approaches to the 3 lymphocentrums. These lymphocentrums were then dissected in 10 additional cadavers using these novel surgical approaches. Measurements of the distances from lymphocentrum to landmark and between landmarks were obtained for each lymphocentrum. Deep anatomic landmarks were recorded for each dissection. The mean and SD were calculated for each measurement and used to develop geometric guidelines for estimating the location of each lymphocentrum for these surgical approaches. RESULTS: Each peripheral lymphocentrum was found in the same location relative to the respective, predetermined, superficial, anatomic boundaries in all cadavers. Briefly, the superficial landmarks to each lymphocentrum were as follows: (1) superficial cervical: wing of atlas, acromion process of scapula, greater tubercle of humerus; (2) axillary: caudal border of transverse head of superficial pectoral muscle, caudal triceps muscle, ventral midline; and (3) superficial inguinal: origin of pectineus muscle, ipsilateral inguinal mammary gland, ventral midline. The proposed superficial and deep surgical landmarks were identified within every cadaver. The previously undescribed surgical approaches were effective for lymphocentrum identification. CLINICAL RELEVANCE: Anatomic landmarks provided in this study may help reduce surgical time and tissue trauma during peripheral lymphadenectomy in dogs. This study was also the first to describe a surgical approach to the superficial inguinal lymphocentrum and ventral approaches to the superficial cervical and axillary lymphocentrums and provided previously unpublished anatomic landmarks for a lateral approach to the superficial cervical lymphocentrum.

Assessment of Burnout, Professional Fulfillment, and Strategies for Improvement in Veterinary Faculty at a Large Academic Department.

Retention and recruitment of clinical faculty is crucial for the success of quality veterinary education. Clinical faculty in busy teaching hospital environments have the potential to experience significant burnout, though few studies have focused on identifying stressors in this group. The objective of this study was to measure burnout and professional fulfillment in clinical faculty using a recently validated instrument, the Stanford Professional Fulfillment Index (PFI). The survey was distributed to faculty in July 2020, a time that coincided with the COVID-19 pandemic. The survey was completed by 80% (52/65) of survey recipients. Scores for Overall Burnout were significantly higher (p = .027) and Professional Fulfillment scores significantly lower (p < .001) for veterinary faculty when compared with a reference group of academic physicians; 61.7% (29/47) of the faculty met the criteria for burnout, and 20.4% (10/49) met the criteria for professional fulfillment. Overall Burnout and Professional Fulfillment scores were not affected by faculty rank or gender, although interpersonal disengagement was greater in faculty who had worked > 6 years at the institution (p = .032). Responses indicated that faculty valued their work and their patients but faced an excessive workload and lacked autonomy to make changes. Faculty proposed improving efficiency, increasing staffing, and distributing work to technical staff. The PFI is a brief, no-cost instrument validated for measuring burnout and fulfillment in health care workers that can be used to assess well-being among veterinary faculty. Involving faculty in suggesting interventions may yield a variety of creative and actionable options.

Glomerulotubular pathology in dogs with subclinical ehrlichiosis.

Subclinical stage of ehrlichiosis is characterized by absence of clinical or laboratory alterations; however, it could lead to silent glomerular/tubular changes and contribute significantly to renal failure in humans and animals. The aim of this study was to evaluate glomerular and tubular alterations in dogs with subclinical ehrlichiosis. We evaluated renal biopsies of 14 bitches with subclinical ehrlichiosis and 11 control dogs. Samples were obtained from the left kidney, and the tissue obtained was divided for light microscopy, immunofluorescence, and transmission electron microscopy. Abnormalities were identified by light microscopy in 92.9% of dogs with ehrlichiosis, but not in any of the dogs of the control group. Mesangial cell proliferation and synechiae (46.1%) were the most common findings, but focal segmental glomerulosclerosis and ischemic glomeruli (38.4%), focal glomerular mesangial matrix expansion (30.7%), mild to moderate interstitial fibrosis and tubular atrophy (23%), and glomerular basement membrane spikes (23%) were also frequent in dogs with ehrlichiosis. All animals with ehrlichiosis exhibited positive immunofluorescence staining for immunoglobulins. Transmission electron microscopy from dogs with ehrlichiosis revealed slight changes such as sparse surface projections and basement membrane double contour. The subclinical phase of ehrlichiosis poses a higher risk of development of kidney damage due to the deposition of immune complexes.

Bilirubin as a Therapeutic Molecule: Challenges and Opportunities.

There is strong evidence that serum free bilirubin concentration has significant effects on morbidity and mortality in the most significant health conditions of our times, including cardiovascular disease, diabetes, and obesity/metabolic syndrome. Supplementation of bilirubin in animal and experimental models has reproduced these protective effects, but several factors have slowed the application bilirubin as a therapeutic agent in human patients. Bilirubin is poorly soluble in water, and is a complex molecule that is difficult to synthesize. Current sources of this molecule are animal-derived, creating concerns regarding the risk of virus or prion transmission. However, recent developments in nanoparticle drug delivery, biosynthetic strategies, and drug synthesis have opened new avenues for applying bilirubin as a pharmaceutical agent. This article reviews the chemistry and physiology of bilirubin, potential clinical applications and summarizes current strategies for safe and efficient drug delivery.

Addressing Unsatisfactory Performance in Employees.

Veterinarians are placed in a leadership role over various teams, and delivering performance feedback is an essential part of being a good leader. Evaluation of underperforming employees is especially challenging, but it is important to recognize that poor performance almost never resolves without active input and support from the team leader. Although it seems counterintuitive, honest and specific performance evaluations can improve work satisfaction and enhance the relationship between the employee and supervisor. This article provides veterinarians with the tools to structure an evaluation system in their practice that will turn a dreaded task into a mechanism to improve workplace culture and performance.

Leading and Influencing Culture Change.

Veterinary practices must continuously change to meet the needs of their clients, maintain the standard of patient care, and remain profitable. Ultimately, all changes boil down to the incorporation of new behaviors by the practice employees. However, human nature tends to resist change and most of the change initiatives will fail unless they are guided by a well-defined process of generating a sense of urgency, recruiting a team of opinion leaders, involving the employees, and removing barriers to change. This chapter reviews the barriers to change and will outline a proven process for enacting change in your team.

Safety, Tolerability, and Proof-Of-Concept Study of OKV-119, a Novel Exenatide Long-Term Drug Delivery System, in Healthy Cats.

Background: Glucagon-like peptide-1 (GLP-1) is an incretin hormone that plays an important role in glucose homeostasis and food intake. In people, GLP-1 receptor agonists (GLP-1RAs) are commonly used for the treatment of type 2 diabetes mellitus (DM) and obesity; however, non-adherence to injectable medications is common. OKV-119 is an investigational drug delivery system intended for subdermal implantation and delivery of the GLP-1RA exenatide for up to 6 months. Hypothesis/Objectives: Develop protocols for the subcutaneous (SC) insertion and removal of OKV-119 and to evaluate its tolerability, in vivo drug-releasing characteristics, and weight-loss effects in cats. Animals: Two cadaveric and 19 purpose-bred cats. Methods: In cadavers, OKV-119 insertion protocol and imaging were performed at three SC locations. The safety and tolerability of OKV-119 implants were assessed in a small (n = 4 cats) 62-day study. Weekly plasma exenatide concentrations and body weight were measured in a 42-day proof-of-concept study designed to evaluate OKV-119 prototypes implanted in cats (n = 15). Results: In anesthetized cats, the duration of insertion and removal procedures was 1-2 min. OKV-119 was easily identified on radiographs, and well-tolerated without any apparent implant site reactions. Following implantation, exanatide plasma concentrations were observed for up to 35 days. Plasma exenatide concentrations were correlated to weight loss. Conclusion and clinical importance: Our findings suggest that OKV-119 could be easily inserted and removed during a routine clinic visit and can be used to safely and effectively deliver exenatide. Future studies of OKV-119, configured to release exenatide for a longer extended months-long duration, are warranted to determine whether the combination of metabolic improvements and beneficial weight-loss, coupled with minimal impact on pet-owner's lifestyle, lead to improved outcomes for obese cats and feline DM patients.

In Vitro Evaluation of a Novel Synthetic Bilirubin Analog as an Antioxidant and Cytoprotective Agent for Pancreatic Islet Transplantation.

Bilirubin is a natural cytoprotective agent and physiologic doses have proven to be beneficial in various models of organ and cellular transplantation. Recently, we showed that bilirubin has protective effects in models of pancreatic islet transplantation, preventing cell death associated with islet stress and suppressing the release of damage-associated molecular patterns. Despite these promising therapeutic attributes, the natural bilirubin used in these research studies is animal-derived (porcine), making it unsuitable for clinical application. In the current study, we synthesized two bilirubin analogs that can be produced without the use of animal-derived products. Antioxidant activity for the analogs was measured using the ferric-reducing-ability-of-plasma (FRAP) and 2,2V-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) assays. Dose-dependent cytotoxicity and cytoprotective effects were then demonstrated in isolated rat islets. Compound 1 showed similar antioxidant activity to natural bilirubin. Dose-dependent cytotoxicity was seen following treatment with Compound 1 and natural bilirubin at doses >40 µM, resulting in significantly increased cell death when compared to control islets (P < 0.05) or islets treated with doses ≤20 µM (P < 0.05). Following hypoxic challenge, islet cell death was reduced in islets treated with Compound 1 at 10 µM (17.27% ± 0.26%) compared to natural bilirubin at 10 µM (51.36% ± 0.71%; P < 0.0001) or 20 µM (59.02% ± 0.83%; P < 0.0001) and control islets (36.51% ± 0.44%; P < 0.0001). Compound 1 was found to have promising antioxidant and cytoprotective effects, limiting islet cell death in a model of islet transplantation hypoxic stress. Compound 1 may serve as a synthetic drug lead for clinical islet transplantation and further evaluation of this molecule and its analogs is warranted.

Cross-Sectional Assessment of the Emotional Intelligence of Fourth-Year Veterinary Students and Veterinary House Officers in a Teaching Hospital.

Emotional intelligence (EI) is the recognition and management of emotions. This skill set is important to work relationships and professional success. In this cross-sectional, observational study, we investigated EI scores of 4th-year veterinary students, interns, and residents in a teaching hospital, using a psychometric tool with professional population norms. Participants' EI scores were compared with professional norms and between the sample groups. Scores were examined on the basis of demographics and residency program type. Twenty-four 4th-year students and 43 interns and residents completed the survey. Total, composite, and subscale scores for all groups were lower than professional means. We noted no statistically significant differences in EI scores between training levels, but evaluation of effect sizes showed a medium negative effect of higher training levels on Self-Perception Composite, Self-Regard, Emotional Expression, Interpersonal Composite, Flexibility, and Optimism and a medium positive effect of higher training levels on Impulse Control. Medium effects for residency type were found for Stress Tolerance, Flexibility, and Stress Management, with higher scores for residencies with heavy inpatient loads. Medium effects for residency type were found on Flexibility scores, with higher scores for residents in disciplines with a perceived high stress level. We found that baseline EI scores of 4th-year veterinary students, interns, and residents at a teaching hospital were similar to, but uniformly lower than, those of other professionals and did not increase with training level. These results may be used to build on strengths and address weaknesses associated with EI of students and house officers at this institution.

Thermogenic crosstalk occurs between adipocytes from different species.

Visceral obesity increases risks for all-cause mortality worldwide. A small population of thermogenic adipocytes expressing uncoupling protein-1 (Ucp1) regulates energy dissipation in white adipose tissue (WAT) depots. Thermogenic adipocytes subsets decrease obesity in mice, but their efficacy has not been tested in obese large animals. Here we enclosed murine subcutaneous adipocytes with and without engineered thermogenic response in biocompatible microcapsules and implanted them into the left and right side of the visceral falciform depot in six obese dogs. After 28 days of treatment, dogs have markedly reduced waist circumference, body weight, and fat mass. Ucp1 expression in canine WAT was increased at sites implanted with thermogenic vs. wild type murine adipocytes. This site-specific thermogenic remodeling of canine tissue by thermogenic murine adipocytes suggests evolutionary conserved paracrine regulation of energy dissipation across species. These findings have translational potential aimed to reduce deleterious WAT depots in humans and pets.

Hydrogen peroxide plasma sterilization of a waterproof, high-definition video camera case for intraoperative imaging in veterinary surgery.

OBJECTIVE: To evaluate the safety and usability of a wearable, waterproof high-definition camera/case for acquisition of surgical images by sterile personnel. STUDY DESIGN: An in vitro study to test the efficacy of biodecontamination of camera cases. Usability for intraoperative image acquisition was assessed in clinical procedures. METHODS: Two waterproof GoPro Hero4 Silver camera cases were inoculated by immersion in media containing Staphylococcus pseudointermedius or Escherichia coli at ≥5.50E+07 colony forming units/mL. Cases were biodecontaminated by manual washing and hydrogen peroxide plasma sterilization. Cultures were obtained by swab and by immersion in enrichment broth before and after each contamination/decontamination cycle (n = 4). The cameras were then applied by a surgeon in clinical procedures by using either a headband or handheld mode and were assessed for usability according to 5 user characteristics. RESULTS: Cultures of all poststerilization swabs were negative. One of 8 cultures was positive in enrichment broth, consistent with a low level of contamination in 1 sample. Usability of the camera was considered poor in headband mode, with limited battery life, inability to control camera functions, and lack of zoom function affecting image quality. Handheld operation of the camera by the primary surgeon improved usability, allowing close-up still and video intraoperative image acquisition. CONCLUSION: Vaporized hydrogen peroxide sterilization of this camera case was considered effective for biodecontamination. Handheld operation improved usability for intraoperative image acquisition. CLINICAL SIGNIFICANCE: Vaporized hydrogen peroxide sterilization and thorough manual washing of a waterproof camera may provide cost effective intraoperative image acquisition for documentation purposes.

Selective Osmotic Shock for Islet Isolation in the Cadaveric Canine Pancreas.

Currently, islet isolation is performed using harsh collagenases that cause nonspecific injury to both islets and exocrine tissue, negatively affecting the outcome of cell transplantation. We evaluated a novel islet isolation protocol utilizing high concentrations of glucose to cause selective osmotic shock (SOS). Islets have a membrane glucose transporter that allows adaptation to changes in glucose concentrations while exocrine tissue can be selectively destroyed by these osmolar shifts. Canine pancreata were obtained within 15 min after euthanasia from animals ( n = 6) euthanized for reasons unrelated to this study. Each pancreas was divided into 4 segments that were randomized to receive 300 mOsm glucose for 20 min (group 1), 600 mOsm for 20 min (group 2), 300 mOsm for 40 min (group 3), or 600 mOsm for 40 min (group 4). Islet yield, purity, and viability were compared between groups. Mean ± standard error of the mean islet yield for groups 1 to 4 was 428 ± 159, 560 ± 257, 878 ± 443, and 990 ± 394 islet equivalents per gram, respectively. Purity ranged from 37% to 45% without the use of density gradient centrifugation and was not significantly different between groups. Islet cell viability was excellent overall (89%) and did not differ between treatment protocol. Islet function was best in groups treated with 300 mOsm of glucose (stimulation index [SI] = 3.3), suggesting that the lower concentration of glucose may be preferred for use in canine islet isolation. SOS provides a widely available means for researchers to isolate canine islets for use in islet transplantation or in studies of canine islet physiology.