Decrease in hepatic very‐low‐density lipoprotein–triglyceride secretion after weight loss is inversely associated with changes in circulating leptin

Aim: Although weight loss usually decreases very‐low‐density lipoprotein–triglyceride (VLDL‐TG) secretion rate, the change in VLDL‐TG kinetics is not directly related to the change in body weight. Circulating leptin also declines with weight loss and can affect hepatic lipid metabolism. The aim of this study was to determine whether circulating leptin is associated with weight loss‐induced changes in VLDL‐TG secretion. Methods: Ten extremely obese subjects were studied. VLDL‐TG secretion rate and the contribution of systemic (derived from lipolysis of subcutaneous adipose tissue TG) and non‐systemic fatty acids (derived primarily from lipolysis of intrahepatic and intraperitoneal TG, and de novo lipogenesis) to VLDL‐TG production were determined by using stable isotopically labelled tracer methods before and 1 year after gastric bypass surgery. Results: Subjects lost 33 ± 12% of body weight, and VLDL‐TG secretion rate decreased by 46 ± 23% (p = 0.001), primarily because of a decrease in the secretion of VLDL‐TG from non‐systemic fatty acids (p = 0.002). Changes in VLDL‐TG secretion rates were not significantly related to reductions in body weight, body mass index, plasma palmitate flux, free fatty acid or insulin concentrations. The change in VLDL‐TG secretion was inversely correlated with the change in plasma leptin concentration (r = ?0.72, p = 0.013), because of a negative association between changes in leptin and VLDL‐TG secretion from non‐systemic fatty acids (r = ?0.95, p < 0.001). Conclusions: Weight loss‐induced changes in plasma leptin concentration are inversely associated with changes in VLDL‐TG secretion rate. Additional studies are needed to determine whether the correlation between circulating leptin and VLDL‐TG secretion represents a cause‐and‐effect relationship.     

Pre-obese and obese agouti mice are sensitive to the anorectic effects of peptide YY(3-36) but resistant to ghrelin

OBJECTIVE: The role of the melanocortin system in the feeding effects of peripheral peptide YY(3-36) (PYY(3-36)) and ghrelin was investigated using the agouti (A(y)/a) mouse as a model of abnormal melanocortin signalling. Furthermore, we examined whether the ectopic expression of agouti protein in A(y)/a mice results in complete MC4-R inhibition, by studying the effects of peripheral alpha-melanocyte-stimulating hormone (alpha-MSH) and leptin on food intake. DESIGN: Adult A(y)/a mice were studied in the pre-obese state (7-8 weeks) and obese state (14-15 weeks). Animals received PYY(3-36) (0.02 micromol/kg), NDP-alpha-MSH (0.2 micromol/kg), leptin (2 micromol/kg) (all 24 h fasted state) and ghrelin (0.2 micromol/kg) (fed state) by intraperitoneal (i.p.) injection. Age-matched A(y)/a controls received i.p. saline. A separate cohort of wild-type (WT), age-matched controls received the same peptide dose or saline. Food intake was measured at 1, 2, 4, 8 and 24 h post-injection and compared in all four groups. Plasma leptin-, ghrelin- and PYY-like immunoreactivity (IR) were measured using radioimmunoassay (RIA). RESULTS: At 2 h post-injection, PYY(3-36) reduced food intake in pre-obese and obese A(y)/a mice, whereas ghrelin had no effect. Plasma ghrelin levels were significantly reduced in pre-obese and obese A(y)/a mice compared to WT controls. Peripheral administration of NDP-alpha-MSH and leptin acutely suppressed feeding (0-2 h) in pre-obese and obese A(y)/a mice. CONCLUSIONS: Responsiveness of pre-obese and obese A(y)/a mice to PYY(3-36) suggests that the melanocortin system may not be essential for the anorectic effects of this peptide. Melanocortinergic antagonism by agouti protein in A(y)/a mice may be sufficient to block the effects of endogenous, but not exogenous PYY(3-36), alpha-MSH and leptin. The mechanism underlying ghrelin resistance in A(y)/a mice may result from antagonism of hypothalamic melanocortin receptors-4 by agouti protein, supporting a role for the melanocortin system in mediating ghrelin's actions.     

Overcoming all obstacles: a framework for embedding interprofessional education into a large, multisite Bachelor of Science Nursing program

As the delivery of health care becomes more complex and challenging, the need for all health care professionals to collaborate as a team has been identified. Nurses are an integral part of the health care team, so it is critical that their education prepare them for interprofessional collaborative practice. Although many academic settings are currently offering interprofessional education (IPE) in the form of compulsory and elective activities and courses, it may not be enough nor an option for programs with large volumes of students who are distributed across a variety of sites and locations. This article outlines a framework that has been successfully adopted by one large school of nursing that chose to integrate interprofessional competencies throughout its curriculum. This IPE agenda is cost-effective, sustainable, and accessible, and it can be adapted to meet the needs of other prelicensure programs that face similar obstacles or challenges with offering IPE.     

Excessive Daytime Sleepiness and Obstructive Sleep Apnea in Patients With Sarcoidosis

BackgroundSystemic symptoms are common in sarcoidosis and are associated with a decreased quality of life. Excessive daytime sleepiness (EDS) often is associated with obstructive sleep apnea (OSA) but may be a systemic symptom independently associated with sarcoidosis. The aim of this study was to assess the relationship between sarcoidosis and EDS.MethodsIn a retrospective analysis, we used Epworth Sleepiness Scale scores to compare sleepiness in 62 patients with sarcoidosis with 1,005 adults without sarcoidosis referred for polysomnography for suspicion of OSA. Linear regression models controlled for covariates. In a subgroup analysis of patients with sarcoidosis, sleepiness scores and polysomnograms were compared between those with normal and those with abnormal pulmonary function based on total lung capacity.ResultsEDS was more common in patients with sarcoidosis than in those without, and sarcoidosis remained an independent predictor of increased sleepiness after controlling for covariates. Compared with control patients referred for polysomnography, fewer patients with sarcoidosis had clinically significant OSA. However, among patients with sarcoidosis, OSA was more severe in those with abnormal lung function.ConclusionsSarcoidosis is independently associated with EDS. Sleepiness may contribute to the morbidity of sarcoidosis and should be followed even after treating for potentially coexisting OSA or depression. Abnormal lung function in sarcoidosis may contribute to OSA, although the mechanisms for this are not known.     

Handheld Point-of-Care Cerebrospinal Fluid Lactate Testing Predicts Bacterial Meningitis in Uganda

We validated a handheld point-of-care lactate (POCL) monitor''s ability to measure lactate in cerebrospinal fluid (CSF) and diagnose bacterial meningitis in Uganda. There was a strong linear correspondence between POCL and standard laboratory lactate test results (R² = 0.86; P < 0.001). For 145 patients with clinical meningitis, the area under the receiver operating characteristic curve for the prediction of bacterial meningitis by CSF POCL was 0.92 (95% confidence interval = 0.85–0.99, P < 0.001). A CSF POCL concentration of 7.7 mmol/L provided 88% sensitivity and 90% specificity for the diagnosis of bacterial meningitis. CSF POCL testing had excellent use in the diagnosis of bacterial meningitis, and it may be useful where CSF analyses are delayed or laboratory infrastructure is limited.     

Odor representations in the olfactory bulb evolve after the first breath and persist as an odor afterimage

Rodents can discriminate odors in one breath, and mammalian olfaction research has thus focused on the first breath. However, sensory representations dynamically change during and after stimuli. To investigate these dynamics, we recorded spike trains from the olfactory bulb of awake, head-fixed mice and found that some mitral cells’ odor representations changed following the first breath and others continued after odor cessation. Population analysis revealed that these postodor responses contained odor- and concentration-specific information—an odor afterimage. Using calcium imaging, we found that most olfactory glomerular activity was restricted to the odor presentation, implying that the afterimage is not primarily peripheral. The odor afterimage was not dependent on odorant physicochemical properties. To artificially induce aftereffects, we photostimulated mitral cells using channelrhodopsin and recorded centrally maintained persistent activity. The strength and persistence of the afterimage was dependent on the duration of both artificial and natural stimulation. In summary, we show that the odor representation evolves after the first breath and that there is a centrally maintained odor afterimage, similar to other sensory systems. These dynamics may help identify novel odorants in complex environments.Sensory systems, even when presented with fixed stimuli, use dynamic neural representations that change over time. These changes range from simple potentiation or adaptation to more complex temporal patterns (1, 2). These dynamics can persist even after the cessation of stimulus, which can take the form of an off-response or prolonged aftereffect. Aftereffects have been intensely studied in vision (1, 3) and also observed in audition (4, 5), touch (6, 7), taste (here the afterimages may be due to persistent ligand binding) (8, 9), and insect olfaction (10, 11). In mammalian olfaction, the only reported aftereffect is a “persistent afterdischarge” following high concentration odors (12).Olfaction is an active process that is coordinated by breathing (2, 13). Odorants bind to odorant receptor neurons (ORNs) in the epithelium, which synapse onto mitral/tufted (M/T) cells in the olfactory bulb (OB) at precisely defined glomeruli. Direct recordings of ORNs in rats show that ORNs are excited by odors and that activity can last for seconds after odor cessation (14). Others have measured the output of ORNs, by imaging glomeruli, and found that the response is gated by each breath and that the amplitude decreases with time (13, 15). The importance of breath segmentation for M/T cells has recently been shown in awake subjects, where neurons respond with precise, phasic firing patterns (16–18). However, these recordings have focused on how information is represented during the first breath, as rodents can identify odors in a single breath (19–21). Activity in piriform cortex is also segmented by breaths, and neurons there respond sparsely (22, 23), and with adaptation (24, 25). To date, no one has addressed, in the OB of awake rodents, how the odor representation evolves with each breath and how the odor representation changes after odor offset. Answering these questions will yield insight into how odor identity is maintained and how the olfactory network represents odors.To investigate olfactory dynamics, we recorded from M/T cells in awake, head-fixed mice. We found that, during the odor, the odor representation shifts significantly after the first breath and not via simple attenuation. Furthermore, we observed a subset of cells that responded in an odor-specific manner after odor cessation—an olfactory afterimage. We performed calcium imaging on sensory neuron terminals, photostimulated channelrhodopsin-expressing M/T cells, and determined that the afterimage is primarily maintained centrally rather than peripherally. In conclusion, we have found that the odor response is dynamic and that one must consider all breaths of the response during an odor and afterward to characterize a cell''s “odor receptive field.” The existence of an odor afterimage shows that afterimages may be a general, useful property of all sensory systems.