Exercise substantially improves metabolic health, making the elicited mechanisms important targets for novel therapeutic strategies. Uncoupling protein 3 (UCP3) is a mitochondrial inner membrane protein highly selectively expressed in skeletal muscle. Here we report that moderate UCP3 overexpression (roughly 3-fold) in muscles of UCP3 transgenic (UCP3 Tg) mice acts as an exercise mimetic in many ways. UCP3 overexpression increased spontaneous activity (∼40%) and energy expenditure (∼5-10%) and decreased oxidative stress (∼15-20%), similar to exercise training in wild-type (WT) mice. The increase in complete fatty acid oxidation (FAO; ∼30% for WT and ∼70% for UCP3 Tg) and energy expenditure (∼8% for WT and 15% for UCP3 Tg) in response to endurance training was higher in UCP3 Tg than in WT mice, showing an additive effect of UCP3 and endurance training on these two parameters. Moreover, increases in circulating short-chain acylcarnitines in response to acute exercise in untrained WT mice were absent with training or in UCP3 Tg mice. UCP3 overexpression had the same effect as training in decreasing long-chain acylcarnitines. Outcomes coincided with a reduction in muscle carnitine acetyltransferase activity that catalyzes the formation of acylcarnitines. Overall, results are consistent with the conclusions that circulating acylcarnitines could be used as a marker of incomplete muscle FAO and that UCP3 is a potential target for the treatment of prevalent metabolic diseases in which muscle FAO is affected.

AimThe aim of this study was to explore parental preparedness for discharge and their experiences of going home with their infant after the first-stage surgery for a functionally univentricular heart.BackgroundTechnological advances worldwide have improved outcomes for infants with a functionally univentricular heart over the last 3 decades; however, concern remains regarding mortality in the period between the first and second stages of surgery. The implementation of home monitoring programmes for this group of infants has improved this initial inter-stage survival; however, little is known about parents’ experiences of going home, their preparedness for discharge, and parents’ recognition of deterioration in their fragile infant.MethodThis study was conducted in 2011–2013; eight sets of parents were consulted in the research planning stage in September, 2011, and 22 parents with children aged 0–2 years responded to an online survey during November, 2012–March, 2013. Description of categorical data and deductive thematic analysis of the open-ended questions were undertaken.ResultsNot all parents were taught signs of deterioration or given written information specific to their baby. The following three themes emerged from the qualitative data:mixed emotions about going home,knowledge and preparedness, andsupport systems.ConclusionsParents are not adequately prepared for discharge and are not well equipped to recognise deterioration in their child. There is a role for greater parental education through development of an early warning tool to address the gap in parents’ understanding of signs of deterioration, enabling appropriate contact and earlier management by clinicians.

Interstitial cystitis (IC) is a chronic pain disorder of the bladder that is often underdiagnosed and mistreated. The difficulties in diagnosis stem from numerous theories regarding pathophysiology and etiology, including the breakdown of the glycosaminoglycan (GAG) layer, altered permeability of the urothelium, uroinflammation, and neural up-regulation. Dysfunction of the bladder increases the struggle for proper treatment and continues to prove difficult for health care providers to correctly diagnose and manage IC. If diagnosed and/or managed inappropriately, IC may contribute to increased symptom burden and decreased quality of life with respect to activities of daily living. When evaluating a patient's clinical presentation in combination with predefined risk factors, a health care provider can better establish a true diagnosis of IC, which, in turn, leads to better management of IC-associated symptoms. This review will help health care providers better understand the disease process by discussing pathophysiology, pain pathways, and common symptoms of IC, with the goal of better aiding them in the proper diagnosis and treatment of patients with IC.

Immune checkpoint inhibitors (ICIs) affect immunologic homeostasis, leading to immune-related adverse events (irAEs). Early irAE detection and management can prevent significant morbidity and mortality. A retrospective chart review was performed to characterize irAEs associated with nivolumab, ipilimumab, and nivolumab plus ipilimumab in adult medical oncology patients in Nova Scotia Health-Central Zone from 2013–2020, and to describe adherence to toxicity management guidelines. Diarrhea/colitis, hepatitis, pneumonitis, nephrotoxicity, and cardiotoxicity were studied. Of 129 charts reviewed, 67 patients (51.9%) experienced at least one irAE for a total of 98 irAEs and a 1.5% fatality rate. Of these irAEs, 33.7% led to an emergency room visit. Patients were admitted to hospital and steroids were used in 24.5% and 35.7% of cases, respectively. In 17.3% of irAEs, ICIs were permanently discontinued. In 20.4% of irAEs, ICIs were held, and patients were monitored; while in 18.4%, ICIs were held until the irAE was Grade 0–1 (and until steroids were tapered). Almost 47% of irAEs were managed according to guidelines (14.3% were not), and 38.8% had no documented management. Patients receiving immunotherapy frequently experience irAEs with half of irAEs having documented management adhering to guidelines. As immunotherapy indications expand, it is important to ensure irAEs are documented and managed appropriately.