Effects of Prior Fasting on Fat Oxidation during Resistance Exercise

International Journal of Exercise Science 11(2): 827-833, 2018. Prior research has demonstrated that the percentage of fuel utilization contributed by CHO compared to fat rises with an increase in exercise intensity. The role of food intake prior to exercise has been well studied and fasting prior to exercise generally increases reliance on fat as fuel. However, data on the role of fasting prior to resistance exercise is limited. Therefore, the purpose of this study was to assess the effects of one bout of resistance training in a fasted state compared to ingestion of standardized meal on fat and carbohydrate utilization. Twelve female (n = 12, age = 20.1 ± 0.79 yrs, height = 67.0 ± 2.63 in, weight = 143 ± 21.8 lbs) NCAA Division 1 athletes participated in the study. Each participant completed one 10 hour fasted resistance training session and one postprandial resistance training session. The respiratory exchange ratio (RER) and METs were measured using a Cosmed K4b2portable metabolic cart (Cosmed, Rome, Italy) and heart rate was measured by a Polar H1 heart rate monitor. Participants consumed the prescribed food, waited 15 minutes, and then completed three sets of five repetitions of bench press, back squat, and military press at 60% of their 1-repetition maximum. The mean fasted RER was significantly lower than postprandial for back squat (p=0.01) and military press (p=0.02), but not bench press (p=0.19). There was no difference in METs, RPE, or HR between fasted and postprandial trials for any exercise. Results suggest that fasted resistance exercise relies more heavily on fat metabolism than carbohydrate

The Metal Dependence of Pyoverdine Interactions with Its Outer Membrane Receptor FpvA▿

To acquire iron, Pseudomonas aeruginosa secretes the fluorescent siderophore pyoverdine (Pvd), which chelates iron and shuttles it into the cells via the specific outer membrane transporter FpvA. We studied the role of iron and other metals in the binding and transport of Pvd by FpvA and conclude that there is no significant affinity between FpvA and metal-free Pvd. We found that the fluorescent in vivo complex of iron-free FpvA-Pvd is in fact a complex with aluminum (FpvA-Pvd-Al) formed from trace aluminum in the growth medium. When Pseudomonas aeruginosa was cultured in a medium that had been treated with a metal affinity resin, the in vivo formation of the FpvA-Pvd complex and the recycling of Pvd on FpvA were nearly abolished. The accumulation of Pvd in the periplasm of Pseudomonas aeruginosa was also reduced in the treated growth medium, while the addition of 1 μM AlCl3 to the treated medium restored the effects of trace metals observed in standard growth medium. Using fluorescent resonance energy transfer and surface plasmon resonance techniques, the in vitro interactions between Pvd and detergent-solubilized FpvA were also shown to be metal dependent. We demonstrated that FpvA binds Pvd-Fe but not Pvd and that Pvd did not compete with Pvd-Fe for FpvA binding. In light of our finding that the Pvd-Al complex is transported across the outer membrane of Pseudomonas aeruginosa, a model for siderophore recognition based on a metal-induced conformation followed by redox selectivity for iron is discussed

Validity of the Richmond Agitation-Sedation Scale (RASS) in critically ill children

Abstract Background The Richmond Agitation-Sedation Scale (RASS) is a single tool that is intuitive, is easy to use, and includes both agitation and sedation. The RASS has never been formally validated for pediatric populations. The objective of this study was to assess inter-rater agreement and criterion validity of the RASS in critically ill children. Methods To evaluate validity, the RASS score was compared to both a visual analog scale (VAS) scored by the patient’s nurse, and the University of Michigan Sedation Scale (UMSS), performed by a researcher. The nurse completed the VAS by drawing a single line on a 10-cm scale anchored by “unresponsive” and “combative.” The UMSS was used to validate the sedation portion of the RASS only, as it does not include grades of agitation. For inter-rater agreement, one researcher and the patient’s nurse simultaneously but independently scored the RASS. Results One hundred patient encounters were obtained from 50 unique patients, ages 2 months to 21 years. Of these, 27 assessments were on children who were mechanically ventilated and 73 were on children who were spontaneously breathing. In validity testing, the RASS was highly correlated with the nurse’s VAS (Spearman correlation coefficient 0.810, p < .0001) and with the UMSS (weighted kappa 0.902, p < .0001). Inter-rater agreement between nurse- and researcher-assessed RASS was excellent, with weighted kappa of 0.825 (p < .0001). Conclusions The RASS is a valid responsiveness tool for use in critically ill children. It allows for accurate assessment of awareness in mechanically ventilated and spontaneously breathing patients, and may improve our ability to titrate sedatives and assess for delirium in pediatrics

Feature Articles Pediatric Critical Care Medicine Pediatric Delirium and Associated Risk Factors: A Single-Center Prospective Observational Study*

Objective: To describe a single-institution pilot study regarding prevalence and risk factors for delirium in critically ill children. Design: A prospective observational study, with secondary analysis of data collected during the validation of a pediatric delirium screening tool, the Cornell Assessment of Pediatric Delirium. Setting: This study took place in the PICU at an urban academic medical center. Patients: Ninety-nine consecutive patients, ages newborn to 21 years. Intervention: Subjects underwent a psychiatric evaluation for delirium based on the Diagnostic and Statistical Manual IV criteria. Measurements and Main Results: Prevalence of delirium in this sample was 21%. In multivariate analysis, risk factors associated with the diagnosis of delirium were presence of developmental delay, need for mechanical ventilation, and age 2-5 years. Conclusions: In our institution, pediatric delirium is a prevalent problem, with identifiable risk factors. Further large-scale prospective studies are required to explore multi-institutional prevalence, modifiable risk factors, therapeutic interventions, and effect on long-term outcomes. (Pediatr Crit Care Med 2015; 16:303-309) Key Words: critical care; delirium; pediatric critical care; pediatrics; prevalence; risk factor D elirium is the behavioral manifestation of acute cerebral dysfunction associated with serious underlying medical illness. It presents as an acute and fluctuating change in mental status, with disordered attention and cognition (1). It is a well-known and prevalent problem in adult intensive care, linked to short-and long-term morbidity (2), increased mortality (3), and astronomical healthcare costs (4). The pathophysiology of ICU delirium is complex and multifactorial. It is the end result of diffuse cerebral metabolic abnormality. Broadly, alterations in neurotransmission, cerebral blood flow, energy metabolism, and disordered cellular homeostasis all play a role (5-7). Although it can occasionally be traced to a single etiology (e.g., alcohol toxicity or delirium tremens), in the ICU, it is frequently a result of three synergistic events: the underlying disease process, side-effects of treatment, and the highly abnormal critical care unit environment (8, 9). As an example, let us consider the patient admitted to the ICU with pneumonia and associated acute hypoxemic respiratory failure. The inflammatory process associated with the infection and hypoxia predisposes the patient to delirium. The benzodiazepine prescribed to facilitate patient-ventilator synchrony is itself deliriogenic. The prolonged period of immobilization in the ICU bed, the presence of invasive catheters and monitors, and the disruption of the patient&apos;s sleep-wake cycle all contribute to the evolving delirium (9, 10). It is important to recognize that delirium is a medical diagnosis and not simply a constellation of symptoms. Delirium is not untreated pain, oversedation, sleep deprivation, or withdrawal (although any of these may contribute to the development of delirium) Epidemiology and risk factors for pediatric delirium are not yet well described, due in part to the absence of widespread screening, underrecognition, and lack of evidence-based dat

Delirium in critically ill children: an international point prevalence study∗

Objectives: To determine prevalence of delirium in critically ill children and explore associated risk factors. Design: Multi-institutional point prevalence study. Setting: Twenty-five pediatric critical care units in the United States, the Netherlands, New Zealand, Australia, and Saudi Arabia. Patients: All children admitted to the pediatric critical care units on designated study days (n = 994). Intervention: Children were screened for delirium using the Cornell Assessment of Pediatric Delirium by the bedside nurse. Demographic and treatment-related variables were collected. Measurements and Main Results: Primary study outcome measure was prevalence of delirium. In 159 children, a final determination of mental status could not be ascertained. Of the 835 remaining subjects, 25% screened positive for delirium, 13% were classified as comatose, and 62% were delirium-free and coma-free. Delirium prevalence rates varied significantly with reason for ICU admission, with highest delirium rates found in children admitted with an infectious or inflammatory disorder. For children who were in the PICU for 6 or more days, delirium prevalence rate was 38%. In a multivariate model, risk factors independently associated with development of delirium included age less than 2 years, mechanical ventilation, benzodiazepines, narcotics, use of physical restraints, and exposure to vasopressors and antiepileptics. Conclusions: Delirium is a prevalent complication of critical illness in children, with identifiable risk factors. Further multi-institutional, longitudinal studies are required to investigate effect of delirium on long-term outcomes and possible preventive and treatment measures. Universal delirium screening is practical and can be implemented in pediatric critical care units

PPM1D mutations are oncogenic drivers of de novo diffuse midline glioma formation

Abstract The role of PPM1D mutations in de novo gliomagenesis has not been systematically explored. Here we analyze whole genome sequences of 170 pediatric high-grade gliomas and find that truncating mutations in PPM1D that increase the stability of its phosphatase are clonal driver events in 11% of Diffuse Midline Gliomas (DMGs) and are enriched in primary pontine tumors. Through the development of DMG mouse models, we show that PPM1D mutations potentiate gliomagenesis and that PPM1D phosphatase activity is required for in vivo oncogenesis. Finally, we apply integrative phosphoproteomic and functional genomics assays and find that oncogenic effects of PPM1D truncation converge on regulators of cell cycle, DNA damage response, and p53 pathways, revealing therapeutic vulnerabilities including MDM2 inhibition