Saturated fatty acid concentrations are predictive of insulin sensitivity and beta cell compensation in dogs.

Chronic feeding of a high fat diet (HFD) in preclinical species induces broad metabolic dysfunction characterized by body weight gain, hyperinsulinemia, dyslipidemia and impaired insulin sensitivity. The plasma lipidome is not well characterized in dogs with HFD-induced metabolic dysfunction. We therefore aimed to describe the alterations that occur in the plasma lipid composition of dogs that are fed a HFD and examine the association of these changes with the clinical signs of metabolic dysfunction. Dogs were fed a normal diet (ND) or HFD for 12 weeks. Insulin sensitivity (SI) and beta cell compensation (AIRG) were assessed through an intravenous glucose tolerance test (IVGTT) and serum biochemistry was analyzed before the introduction of HFD and again after 12 weeks of continued ND or HFD feeding. Plasma lipidomics were conducted prior to the introduction of HFD and again at week 8 in both ND and HFD-fed dogs. 12 weeks of HFD feeding resulted in impaired insulin sensitivity and increased beta cell compensation measured by SI (ND mean: 11.5 [mU/l]-1 min-1, HFD mean: 4.7 [mU/l]-1 min-1) and AIRG (ND mean: 167.0 [mU/l]min, HFD mean: 260.2 [mU/l]min), respectively, compared to dogs fed ND over the same duration. Chronic HFD feeding increased concentrations of plasma lipid species and deleterious fatty acids compared to dogs fed a ND. Saturated fatty acid (SFA) concentrations were significantly associated with fasting insulin (R2 = 0.29), SI (R2 = 0.49) and AIRG (R2 = 0.37) in all dogs after 12 weeks, irrespective of diet. Our results demonstrate that chronic HFD feeding leads to significant changes in plasma lipid composition and fatty acid concentrations associated with metabolic dysfunction. High SFA concentrations may be predictive of deteriorated insulin sensitivity in dogs.

Feeding dogs a high-fat diet induces metabolic changes similar to natural aging, including dyslipidemia, hyperinsulinemia, and peripheral insulin resistance.

OBJECTIVE: The goal of this study was to characterize changes induced by a high-fat diet in body composition, insulin levels and sensitivity, blood lipids, and other key biomarkers also associated with the metabolic dysfunction that occurs with natural aging. ANIMALS: 24 male Beagle dogs, 3 to 7 years of age, of mixed castration status. METHODS: Dogs were randomly assigned to continue twice daily feeding of the commercial adult maintenance diet (n = 12, including 2 intact) that they were previously fed or to a high-fat diet (12, including 2 intact) for 17 weeks between December 1, 2021, and April 28, 2022. Assessments included body composition (weight, body condition score, and adipose mass determined by deuterium enrichment), clinical chemistries, plasma fatty acid quantification, oral glucose tolerance test, and histology of subcutaneous and visceral adipose biopsy samples. RESULTS: The high-fat diet led to increased body weight, body condition score, fat mass and adipocyte size, hyperinsulinemia and peripheral insulin resistance, and elevations in serum lipids, including cholesterol, triglycerides, and several species of free fatty acids. Leptin levels increased in dogs fed a high-fat diet but not in control dogs. There were no significant changes in routine clinical chemistry values in either group. CLINICAL RELEVANCE: Feeding a high-fat diet for 17 weeks led to potentially deleterious changes in metabolism similar to those seen in natural aging in dogs, including hyperinsulinemia, insulin resistance, and dyslipidemia. A high-fat diet model may provide insights into the similar metabolic dysfunction that occurs during natural aging.

Accelerating the Global Workforce Demand for Nurse Informaticians: Advanced Health Informatics Certification (AHIC).

Advances in professional recognition of nursing informatics vary by country but examples exist of training programs moving from curriculum-based education to competency based frameworks to produce highly skilled nursing informaticians. This panel will discuss a significant credentialing project in the United States that should further enhance professional recognition of highly skilled nurses matriculating from NI programs as well as nurses functioning in positions where informatics-induced transformation is occurring. The panel will discuss the professionalization of health informatics by describing core content, training requirements, education needs, and administrative framework applicable for the creation of an Advanced Health Informatics Certification (AHIC).

IL-31-induced pruritus in dogs: a novel experimental model to evaluate anti-pruritic effects of canine therapeutics.

BACKGROUND: Pruritus is a characteristic clinical sign of allergic skin conditions including atopic dermatitis (AD) in the dog. IL-31 is a cytokine found in the serum of some dogs with AD and can induce pruritic behaviours in laboratory beagle dogs. HYPOTHESIS/OBJECTIVES: The objectives were to characterize an IL-31-induced pruritus model by evaluating the efficacy of prednisolone, dexamethasone and oclacitinib, and to compare the speed of anti-pruritic effects of oclacitinib against those of prednisolone and dexamethasone. ANIMALS: Purpose-bred beagle dogs were used in all studies. METHODS: Randomized, blinded, placebo-controlled studies were designed to evaluate and compare the anti-pruritic properties of prednisolone, dexamethasone and oclacitinib following a single intravenous injection of recombinant canine IL-31. Video surveillance was used to monitor and score pruritic behaviours in study animals. RESULTS: Prednisolone [0.5 mg/kg, per os (p.o.)] reduced IL-31-induced pruritus when given 10 h prior to observation. When the time interval between drug treatment and observation was shortened to 1 h, dexamethasone (0.2 mg/kg, intramuscular) but not prednisolone (0.25 or 0.5 mg/kg, p.o.) reduced IL-31-induced pruritus. Oclacitinib (0.4 mg/kg, p.o.) reduced pruritus when given 1, 6, 11 and 16 h prior to the observation period, and the anti-pruritic activity of oclacitinib was greater when compared to prednisolone and dexamethasone at all time points assessed. CONCLUSION AND CLINICAL IMPORTANCE: The efficacy of prednisolone, dexamethasone and oclacitinib in the IL-31-induced pruritus model gives confidence that this may be a relevant model for acute pruritus associated with allergic dermatitis including AD and can be used to evaluate novel compounds or formulations.

Receptor-based discovery strategies for insecticides and parasiticides: a review.

Drug discovery is an iterative process with high risks and low chance of success. New genomics technologies allow veterinary medicine and agrochemical companies to validate and functionally screen new receptor-based targets, including neuropeptide G-protein coupled receptors, which were previously not amenable to high throughput screening. However this is just the first step in a long process to translate a mechanistic assay hit into a drug on the market. In addition to effectively eradicating pests on crops and parasites on their host, the molecules must also be safe, cheap to synthesise, formulatable and patentable. This is a costly process in which early attrition of unsuitable molecules is key to any successful program. Although first principle discovery is risky the ultimate benefits are considerable and future genomics resources will help to generate higher quality hits to strengthen the discovery pipeline.

Don E. Detmer and the American Medical Informatics Association: an appreciation.

Don E. Detmer has served as President and Chief Executive Officer of the American Medical Informatics Association (AMIA) for the past five years, helping to set a course for the organization and demonstrating remarkable leadership as AMIA has evolved into a vibrant and influential professional association. On the occasion of Dr. Detmer's retirement, we fondly reflect on his professional life and his many contributions to biomedical informatics and, more generally, to health care in the U.S. and globally.

A Drosophila systems approach to xenobiotic metabolism.

Insecticide resistance is a major problem for both medicine and agriculture and is frequently associated with overexpression of metabolic enzymes that catalyze the breakdown of pesticides, leading to broad-spectrum resistance. However, the insect tissues within which these metabolic enzymes normally reside remain unclear. Microarray analysis of nine adult tissues from Drosophila melanogaster reveals that cytochrome P-450s and glutathione-S-transferases show highly tissue-specific expression patterns; most were confined to one or more epithelial tissues, and half showed dominant expression in a single tissue. The particular detoxifying enzymes encountered by a xenobiotic thus depend critically on the route of administration. In particular, known insecticide metabolism genes are highly enriched in insect Malpighian (renal) tubules, implicating them in xenobiotic metabolism. The tubules thus display, with the fat body, roles analogous to the vertebrate liver and immune system, as well as its acknowledged renal function. To illustrate this, when levels of a single gene, Cyp6g1, were manipulated in just the Malpighian tubules of adult Drosophila, the survival of the whole insect after 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT) challenge was altered, whereas corresponding manipulations in the nervous system or the fat body were without effect. This shows that, although detoxification enzymes are widely distributed, baseline protection against DDT resides primarily in the insect excretory system, corresponding to less than 0.1% of the mass of the organism.