Developmental Timing of High-Fat Diet Exposure Impacts Glucose Homeostasis in Mice in a Sex-Specific Manner.

We previously demonstrated that male, but not female, Swiss Webster mice are susceptible to diabetes, with incidence increased by early overnutrition and high-fat diet (HFD). In this study, we investigated how HFD in Swiss Webster males and females during preweaning, peripubertal, and postpubertal periods alters glucose homeostasis and diabetes susceptibility. In males, HFD throughout life resulted in the highest diabetes incidence. Notably, switching to chow postpuberty was protective against diabetes relative to switching to chow at weaning, despite the longer period of HFD exposure. Similarly, HFD throughout life in males resulted in less liver steatosis relative to mice with shorter duration of postpubertal HFD. Thus, HFD timing relative to weaning and puberty, not simply exposure length, contributes to metabolic outcomes. Females were protected from hyperglycemia regardless of length or timing of HFD. However, postpubertal HFD resulted in a high degree of hepatic steatosis and adipose fibrosis, but glucose regulation and insulin sensitivity remained unchanged. Interestingly, peri-insulitis was observed in the majority of females but was not correlated with impaired glucose regulation. Our findings reveal critical periods of HFD-induced glucose dysregulation with striking sex differences in Swiss Webster mice, highlighting the importance of careful consideration of HFD timing relative to critical developmental periods.

Early overnutrition in male mice negates metabolic benefits of a diet high in monounsaturated and omega-3 fats.

Overconsumption of saturated fats promotes obesity and type 2 diabetes. Excess weight gain in early life may be particularly detrimental by promoting earlier diabetes onset and potentially by adversely affecting normal development. In the present study we investigated the effects of dietary fat composition on early overnutrition-induced body weight and glucose regulation in Swiss Webster mice, which show susceptibility to high-fat diet-induced diabetes. We compared glucose homeostasis between a high-fat lard-based (HFL) diet, high in saturated fats, and a high-fat olive oil/fish oil-based (HFO) diet, high in monounsaturated and omega-3 fats. We hypothesized that the healthier fat profile of the latter diet would improve early overnutrition-induced glucose dysregulation. However, early overnutrition HFO pups gained more weight and adiposity and had higher diabetes incidence compared to HFL. In contrast, control pups had less weight gain, adiposity, and lower diabetes incidence. Plasma metabolomics revealed reductions in various phosphatidylcholine species in early overnutrition HFO mice as well as with diabetes. These findings suggest that early overnutrition may negate any beneficial effects of a high-fat diet that favours monounsaturated and omega-3 fats over saturated fats. Thus, quantity, quality, and timing of fat intake throughout life should be considered with respect to metabolic health outcomes.

In-hospital usability and feasibility evaluation of Panda, an app for the management of pain in children at home.

BACKGROUND: Postoperative pain in children is often poorly managed at home, leading to slower functional recovery, poor oral intake, sleep disturbances, and behavioral changes. Panda is a smartphone application (app) designed to support parents in assessing their child's pain and managing medications. AIMS: The aim of this study was to evaluate the Panda app's usability and feasibility in hospital prior to testing the app at home. METHODS: The study comprised two phases. Phase I evaluated Panda's usability with nurses, parents, and adolescents using simulated scenarios. Usability was measured by task completion rate, user error rates, and the Computer Systems Usability Questionnaire. Phase II evaluated Panda's feasibility by observing parents/guardians of pediatric patients using the app on the postsurgical ward. Feasibility was measured using response frequency and delay following app notifications from an audit trail of app function, and parental satisfaction from an interview. Feedback was used to guide iterative app improvements. RESULTS: In Phase I, 13 nurses, 12 parents, and 5 adolescents evaluated the app. A total of 103 usability issues were identified, analyzed, and addressed. In Phase II, 29 parents responded to a total of 151 app notifications, with 84% responding within 1 hour in the final round of testing; 93% of participants reported the app was easy to use, and rated the app with a median [interquartile range] Computer Systems Usability Questionnaire score of 2 [1-4]. Significant barriers to use included lack of flexibility in the medication scheduling, low volume of alert sounds, and the extra time spent on medication safety checks. CONCLUSION: Panda's usability was improved and its feasibility demonstrated in the controlled hospital environment. The next step is to evaluate its feasibility for use at home.