Size fractionation of microscopic protein aggregates using a preparative fluorescence-activated cell sorter.

Protein aggregation, which takes place both in vivo and in vitro, is an important degradative pathway for all proteins. Protein aggregates have distinct physicochemical and biological properties that are important to study and characterize from the perspective of both fundamental and applied sciences. The size of protein aggregates varies across a huge range, spanning several orders of magnitude.

Survivors versus nonsurvivors postburn: differences in inflammatory and hypermetabolic trajectories.

Objective: To evaluate whether a panel of common biomedical markers can be utilized as trajectories to determine survival in pediatric burn patients.

Background: Despite major advances in clinical care, of the more than 1 million people burned in the United States each year, more than 4500 die as a result of their burn injuries. The ability to predict patient outcome or anticipate clinical trajectories using plasma protein expression would allow personalization of clinical care to optimize the potential for patient survival.

Incidence of hot tap water scalds after the introduction of regulations in Ontario.

Hot water scalds can be quite debilitating for a prolonged period of time. It has been previously determined that the severity of hot water scalds increases in a logarithmic trend with water temperature, which has led to legislations requiring changes to the physical environment to reduce the temperature of hot water. In September 2004, Ontario changed its Building Code, requiring all new or renovated residential buildings to lower the maximum setting of their hot water heaters to 49°C (120°F).

Occurrence of multiorgan dysfunction in pediatric burn patients: incidence and clinical outcome.

Objective: To examine the incidence of single or multiple organ failure postburn and its resultant clinical outcomes during acute hospitalization.

Background: Patient outcomes are inherently dependent on intact organ function; however, burn injury affects the structure and function of almost every organ, but especially lung, liver, kidney, and heart. Therefore, single-organ failure and/or multiorgan failure (MOF) are thought to contribute significantly to postburn morbidity and mortality, but to date no large trial examining the effects of MOF on postburn outcomes exists.

XBP-1s is linked to suppressed gluconeogenesis in the Ebb phase of burn injury.

The first 24 h following burn injury is known as the ebb phase and is characterized by a depressed metabolic rate. While the postburn ebb phase has been well described, the molecular mechanisms underlying this response are poorly understood. The endoplasmic reticulum (ER) regulates metabolic rate by maintaining glucose homeostasis through the hepatic ER stress response.

Determination of burn patient outcome by large-scale quantitative discovery proteomics.

Objectives: Emerging proteomics techniques can be used to establish proteomic outcome signatures and to identify candidate biomarkers for survival following traumatic injury. We applied high-resolution liquid chromatography-mass spectrometry and multiplex cytokine analysis to profile the plasma proteome of survivors and nonsurvivors of massive burn injury to determine the proteomic survival signature following a major burn injury.

Design: Proteomic discovery study.

Genomic responses in mouse models poorly mimic human inflammatory diseases.

A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another.

Work-related burn injuries in Ontario, Canada: A follow-up 10-year retrospective study.

Work-related burn injuries contribute to a quarter of all burns in the USA. In 2009, the provincial Workplace Safety and Insurance Board reported 64,824 work-related injuries that resulted in time lost, 1188 injuries (2%) were a result of burns. There were two previous studies performed at a regional burn centre (1984-1990 and 1998-2000) that examined incidence and characteristics of work-related burns.

Effects of metformin on burn-induced hepatic endoplasmic reticulum stress in male rats.

Severe burn injury causes hepatic dysfunction that results in major metabolic derangements including insulin resistance and hyperglycemia and is associated with hepatic endoplasmic reticulum (ER) stress. We have recently shown that insulin reduces ER stress and improves liver function and morphology; however, it is not clear whether these changes are directly insulin mediated or are due to glucose alterations. Metformin is an antidiabetic agent that decreases hyperglycemia by different pathways than insulin; therefore, we asked whether metformin affects postburn ER stress and hepatic metabolism.

Hepatic apoptosis postburn is mediated by c-Jun N-terminal kinase 2.

The trauma of a severe burn injury induces a hypermetabolic response that increases morbidity and mortality. Previously, our group showed that insulin resistance after burn injury is associated with endoplasmic reticulum (ER) stress. Evidence suggests that c-Jun N-terminal kinase (JNK) 2 may be involved in ER stress-induced apoptosis.

Enteral nutrition support in burn care: a review of current recommendations as instituted in the Ross Tilley Burn Centre.

Failure to adequately address the increased levels of inflammatory mediators, catecholamines and corticosteroids central to the hypermetabolic response post burn injury can lead to catastrophic results. One of the most important perturbations is provision of adequate and early nutrition. The provision of the right balance of macro and micronutrients, along with additional antioxidants is essential to mitigating the hypermetabolic and hypercatabolic state that results following a burn injury.

Association of postburn fatty acids and triglycerides with clinical outcome in severely burned children.

Context: Free fatty acids (FFAs) and triglycerides (TGs) are altered postburn, but whether these alterations are associated with postburn outcomes is not clear.

Objective: The aim of the present study was to analyze lipid metabolic profiles in pediatric burn patients and to correlate these profiles with patient outcomes and hospital courses.

Design And Setting: We conducted a prospective cohort study at an academic pediatric hospital burn center.

Albumin supplementation for hypoalbuminemia following burns: unnecessary and costly!

Following fluid resuscitation, patients with major burns frequently develop prolonged hypoalbuminemia. It is not known whether this should be corrected by albumin supplementation. The purpose of this study was to determine whether there are any benefits associated with albumin supplementation to correct hypoalbuminemia in burned adults.

Long-term propranolol use in severely burned pediatric patients: a randomized controlled study.

Objective: To determine the safety and efficacy of propranolol given for 1 year on cardiac function, resting energy expenditure, and body composition in a prospective, randomized, single-center, controlled study in pediatric patients with large burns.

Background: Severe burns trigger a hypermetabolic response that persists for up to 2 years postburn. Propranolol given for 1 month postburn blunts this response.

Optimized fluid management improves outcomes of pediatric burn patients.

Background: One of the major determinants for survival of severely burned patients is appropriate fluid resuscitation. At present, fluid resuscitation is calculated based on body weight or body surface area, burn size, and urinary output. However, recent evidence suggests that fluid calculation is inadequate and that over- and under-resuscitations are associated with increased morbidity and mortality.

Proteomics improves the prediction of burns mortality: results from regression spline modeling.

Prediction of mortality in severely burned patients remains unreliable. Although clinical covariates and plasma protein abundance have been used with varying degrees of success, the triad of burn size, inhalation injury, and age remains the most reliable predictor. We investigated the effect of combining proteomics variables with these three clinical covariates on prediction of mortality in burned children.

The effect of ketoconazole on post-burn inflammation, hypermetabolism and clinical outcomes.

Background: Hypercortisolemia has been suggested as a primary hormonal mediator of whole-body catabolism following severe burn injury. Ketoconazole, an anti-fungal agent, inhibits cortisol synthesis. We, therefore, studied the effect of ketoconazole on post-burn cortisol levels and the hyper-catabolic response in a prospective randomized trial (block randomization 2:1).

Insulin therapy improves protein metabolism in the critically ill.

Critical illness, trauma and burns are associated with profound metabolic abnormalities, of which protein catabolism, hyperglycemia and insulin resistance are hallmarks of these conditions. Increased protein breakdown and loss results in muscle wasting, weakness and diminished functioning. Interestingly, hyperglycemia and insulin resistance augment catabolic responses.

Hyperglycemia exacerbates burn-induced liver inflammation via noncanonical nuclear factor-κB pathway activation.

Hyperglycemia and inflammation are hallmarks of burn injury. In this study, we used a rat model of hyperglycemia and burn injury to investigate the effects of hyperglycemia on inflammatory responses in the liver. Hyperglycemia was induced in male Sprague-Dawley rats with streptozotocin (STZ) (35-40 mg/kg), followed by a 60% third-degree scald burn injury.

The properties of an "ideal" burn wound dressing--what do we need in daily clinical practice? Results of a worldwide online survey among burn care specialists.

Objective: Using Internet polling to classify characteristics of a burn wound dressing considered as "ideal" by burn care specialists for small sized burns (<20% TBSA).

Methods: Open, voluntary Internet-based cross-sectional survey with twenty non-compulsory questions and collection of information related to profession, staff grade, work location.

Results: In total one-hundred and twenty-one participants from 39 countries were included (response rate: 121/1000=12.

Propranolol improves impaired hepatic phosphatidylinositol 3-kinase/akt signaling after burn injury.

Severe burn injury is associated with induction of the hepatic endoplasmic reticulum (ER) stress response. ER stress leads to activation of c-Jun N-terminal kinase (JNK), suppression of insulin receptor signaling via phosphorylation of insulin receptor substrate 1 and subsequent insulin resistance. Marked and sustained increases in catecholamines are prominent after a burn.

Impaired ability of burn patient neutrophils to stimulate β-defensin production by keratinocytes.

Immunosuppressive neutrophils (PMN-II) appearing in association with burn injury have a role on the increased susceptibility of burn patients to various infections. In the present study, the role of PMN-II on the production of human β-defensins (HBDs), important molecules on host antimicrobial innate immunities, by human keratinocytes was studied. Normal human epidermal keratinocytes (NHEKs) were cultured with neutrophils (PMNs) isolated from burn patients or healthy volunteers in dual-chamber transwells.

Three components of education in burn care: surgical education, inter-professional education, and mentorship.

Education in burn care can be divided into three main components: surgical education, inter-professional education, e.g. critical care education and mentorship.