Bench-to-bedside review: The gut as an endocrine organ in the critically ill

In health, hormones secreted from the gastrointestinal tract have an important role in regulating gastrointestinal motility, glucose metabolism and immune function. Recent studies in the critically ill have established that the secretion of a number of these hormones is abnormal, which probably contributes to disordered gastrointestinal and metabolic function. Furthermore, manipulation of endogenous secretion, physiological replacement and supra-physiological treatment (pharmacological dosing) of these hormones are likely to be novel therapeutic targets in this group. Fasting ghrelin concentrations are reduced in the early phase of critical illness, and exogenous ghrelin is a potential therapy that could be used to accelerate gastric emptying and/or stimulate appetite. Motilin agonists, such as erythromycin, are effective gastrokinetic drugs in the critically ill. Cholecystokinin and peptide YY concentrations are elevated in both the fasting and postprandial states, and are likely to contribute to slow gastric emptying. Accordingly, there is a rationale for the therapeutic use of their antagonists. So-called incretin therapies (glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide) warrant evaluation in the management of hyperglycaemia in the critically ill. Exogenous glucagon-like peptide-2 (or its analogues) may be a potential therapy because of its intestinotropic properties

Cortical oscillatory dysrhythmias in visual snow syndrome: a magnetoencephalography study

Visual Snow refers to the persistent visual experience of static in the whole visual field of both eyes. It is often reported by patients with migraine and co-occurs with conditions like tinnitus and tremor. The underlying pathophysiology of the condition is poorly understood. Previously we hypothesised, that visual snow syndrome may be characterised by disruptions to rhythmical activity within the visual system. To test this, data from 18 patients diagnosed with visual snow syndrome, and 16 matched controls, were acquired using magnetoencephalography. Participants were presented with visual grating stimuli, known to elicit decreases in alpha-band (8-13Hz) power and increases in gamma-band power (40-70Hz). Data were mapped to source-space using a beamformer. Across both groups, decreased alpha power and increased gamma power localised to early visual cortex. Data from the primary visual cortex were compared between groups. No differences were found in either alpha or gamma peak frequency or the magnitude of alpha power, p>0.05. However, compared with controls, our visual snow syndrome cohort displayed significantly increased primary visual cortex gamma power, p=0.035. This new electromagnetic finding concurs with previous functional MRI and PET findings suggesting that in visual snow syndrome, the visual cortex is hyper-excitable. The coupling of alpha-phase to gamma amplitude within the primary visual cortex was also quantified. Compared with controls, the visual snow syndrome group had significantly reduced alpha-gamma phase-amplitude coupling, p<0.05, indicating a potential excitation-inhibition imbalance in visual snow syndrome, as well as a potential disruption to top-down “noise-cancellation” mechanisms. Overall, these results suggest that rhythmical brain activity in primary visual cortex is both hyperexcitable and disorganised in visual snow syndrome, consistent with this being a condition of thalamocortical dysrhythmia

The effect of exogenous glucagon-like peptide-1 on the glycaemic response to small intestinal nutrient in the critically ill: a randomised double-blind placebo-controlled cross over study

IntroductionHyperglycaemia occurs frequently in the critically ill, affects outcome adversely, and is exacerbated by enteral feeding. Furthermore, treatment with insulin in this group is frequently complicated by hypoglycaemia. In healthy patients and those with type 2 diabetes, exogenous glucagon-like peptide-1 (GLP-1) decreases blood glucose by suppressing glucagon, stimulating insulin and slowing gastric emptying. Because the former effects are glucose-dependent, the use of GLP-1 is not associated with hypoglycaemia. The objective of this study was to establish if exogenous GLP-1 attenuates the glycaemic response to enteral nutrition in patients with critical illness induced hyperglycaemia.MethodsSeven mechanically ventilated critically ill patients, not previously known to have diabetes, received two intravenous infusions of GLP-1 (1.2 pmol/kg/min) and placebo (4% albumin) over 270 minutes. Infusions were administered on consecutive days in a randomised, double-blind fashion. On both days a mixed nutrient liquid was infused, via a post-pyloric feeding catheter, at a rate of 1.5 kcal/min between 30 and 270 minutes. Blood glucose and plasma GLP-1, insulin and glucagon concentrations were measured.ResultsIn all patients, exogenous GLP-1 infusion reduced the overall glycaemic response during enteral nutrient stimulation (AUC30-270 min GLP-1 (2077 +/- 144 mmol/l min) vs placebo (2568 +/- 208 mmol/l min); P = 0.02) and the peak blood glucose (GLP-1 (10.1 +/- 0.7 mmol/l) vs placebo (12.7 +/- 1.0 mmol/l); P ConclusionsAcute, exogenous GLP-1 infusion markedly attenuates the glycaemic response to enteral nutrition in the critically ill. These observations suggest that GLP-1 and/or its analogues have the potential to manage hyperglycaemia in the critically ill.Trial registrationAustralian New Zealand Clinical Trials Registry number: ACTRN12609000093280.Adam M. Deane, Marianne J. Chapman, Robert J.L. Fraser, Carly M. Burgstad, Laura K. Besanko and Michael Horowit

Fasting and nutrient-stimulated plasma peptide-YY levels are elevated in critical illness and associated with feed intolerance: an observational, controlled study

INTRODUCTION: Delayed gastric emptying and feed intolerance occur frequently in the critically ill. In these patients, gastric motor responses to nutrients are disturbed. Peptide YY (PYY) slows gastric emptying. The aim of this study was to determine fasting and nutrient-stimulated plasma PYY concentrations and their relationship to cholecystokinin (CCK) in critically ill patients. METHODS: Studies were performed in 19 unselected mechanically ventilated critically ill patients (12 males; 48 ± 7 years old) in a randomised, single-blind fashion. Subjects received a 60-minute duodenal infusion of Ensure(® )at either 1 or 2 kcal/minute. Blood samples were collected at baseline and at 20, 40, 60, and 180 minutes following commencement of the nutrient infusion for the measurement of plasma PYY and CCK concentrations (using radioimmunoassay). Patient data were compared to 24 healthy subjects (17 males; 43 ± 2 years old). RESULTS: Fasting PYY concentration was higher in patients (P < 0.05), particularly in those with feed intolerance (P < 0.05). Plasma PYY concentrations were higher in patients during nutrient infusion (area under the curve [AUC] at 1 kcal/minute: 2,265 ± 718 versus 1,125 ± 138 pmol/l.min, P < 0.05; at 2 kcal/minute: 2,276 ± 303 versus 1,378 ± 210 pmol/l.min, P = 0.01) compared to healthy subjects. The magnitude of PYY elevation was greater in patients during the 1 kcal/minute infusion (AUC: 441 ± 153 versus 186 ± 58 pmol/l.min, P < 0.05), but not the 2 kcal/minute infusion. Fasting and nutrient-stimulated plasma CCK concentrations were higher in patients (P < 0.05). There was a relationship between plasma PYY and CCK concentrations during fasting (r = 0.52, P < 0.05) and nutrient infusion (r = 0.98, P < 0.0001). CONCLUSION: In critical illness, both fasting and nutrient-stimulated plasma PYY concentrations are elevated, particularly in patients with feed intolerance, in conjunction with increased CCK concentrations

Learning environments research in English classrooms

Although learning environments research has thrived for decades in many countries and school subjects, English classroom environment research is still in its infancy. This article paves the way for expanding research on English classroom environments by (1) reviewing the limited past research in English classrooms and (2) reporting the first study of English learning environments in Singaporean primary schools. For a sample of 441 grade 6 students, past research in other subjects was replicated in that a modified version of the What Is Happening In this Class? questionnaire was cross-validated, classroom environment was found to vary with the determinants of student sex and ethnicity, and associations emerged between students’ attitudes and the nature of the classroom environment

Trauma as counter-revolutionary colonisation: narratives from (post)revolutionary Egypt

We argue that multiple levels of trauma were present in Egypt before, during and after the 2011 revolution. Individual, social and political trauma constitute a triangle of traumatisation which was strategically employed by the Egyptian counter-revolutionary forces – primarily the army and the leadership of the Muslim Brotherhood – to maintain their political and economic power over and above the social, economic and political interests of others. Through the destruction of physical bodies, the fragmentation and polarisation of social relations and the violent closure of the newly emerged political public sphere, these actors actively repressed the potential for creative and revolutionary transformation. To better understand this multi-layered notion of trauma, we turn to Habermas’ ‘colonisation of the lifeworld’ thesis which offers a critical lens through which to examine the wider political and economic structures and context in which trauma occurred as well as its effects on the personal, social and political realms. In doing so, we develop a novel conception of trauma that acknowledges individual, social and political dimensions. We apply this conceptual framing to empirical narratives of trauma in Egypt’s pre- and post-revolutionary phases, thus both developing a non-Western application of Habermas’ framework and revealing ethnographic accounts of the revolution by activists in Cairo

Exogenous glucagon-like peptide-1 attenuates the glycaemic response to postpyloric nutrient infusion in critically ill patients with type-2 diabetes

Extent: 11p.Introduction: Glucagon-like peptide-1 (GLP-1) attenuates the glycaemic response to small intestinal nutrient infusion in stress-induced hyperglycaemia and reduces fasting glucose concentrations in critically ill patients with type-2 diabetes. The objective of this study was to evaluate the effects of acute administration of GLP-1 on the glycaemic response to small intestinal nutrient infusion in critically ill patients with pre-existing type-2 diabetes. Methods: Eleven critically ill mechanically-ventilated patients with known type-2 diabetes received intravenous infusions of GLP-1 (1.2 pmol/kg/minute) and placebo from t = 0 to 270 minutes on separate days in randomised double-blind fashion. Between t = 30 to 270 minutes a liquid nutrient was infused intraduodenally at a rate of 1 kcal/min via a naso-enteric catheter. Blood glucose, serum insulin and C-peptide, and plasma glucagon were measured. Data are mean ± SEM. Results: GLP-1 attenuated the overall glycaemic response to nutrient (blood glucose AUC30-270 min: GLP-1 2,244 ± 184 vs. placebo 2,679 ± 233 mmol/l/minute; P = 0.02). Blood glucose was maintained at < 10 mmol/l in 6/11 patients when receiving GLP-1 and 4/11 with placebo. GLP-1 increased serum insulin at 270 minutes (GLP-1: 23.4 ± 6.7 vs. placebo: 16.4 ± 5.5 mU/l; P < 0.05), but had no effect on the change in plasma glucagon. Conclusions: Exogenous GLP-1 in a dose of 1.2 pmol/kg/minute attenuates the glycaemic response to small intestinal nutrient in critically ill patients with type-2 diabetes. Given the modest magnitude of the reduction in glycaemia the effects of GLP-1 at higher doses and/or when administered in combination with insulin, warrant evaluation in this group.Adam M Deane, Matthew J Summers, Antony V Zaknic, Marianne J Chapman, Robert JL Fraser, Anna E Di Bartolomeo, Judith M Wishart, Michael Horowit

Glucose absorption and gastric emptying in critical illness

Introduction: Delayed gastric emptying occurs frequently in critically ill patients and has the potential to adversely affect both the rate, and extent, of nutrient absorption. However, there is limited information about nutrient absorption in the critically ill, and the relationship between gastric emptying (GE) and absorption has hitherto not been evaluated. The aim of this study was to quantify glucose absorption and the relationships between GE, glucose absorption and glycaemia in critically ill patients. Methods: Studies were performed in nineteen mechanically ventilated critically ill patients and compared to nineteen healthy subjects. Following 4 hours fasting, 100 ml of Ensure, 2 g 3-Omethyl glucose (3-OMG) and ⁹⁹mTc sulphur colloid were infused into the stomach over 5 minutes. Glucose absorption (plasma 3- OMG), blood glucose levels and GE (scintigraphy) were measured over four hours. Data are mean ± SEM. A P-value 0.51; P < 0.05). Conclusions In critically ill patients; (i) the rate and extent of glucose absorption are markedly reduced; (ii) GE is a major determinant of the rate of absorption, but does not fully account for the extent of impaired absorption; (iii) blood glucose concentration could be one of a number of factors affecting GE.Marianne J Chapman, Robert JL Fraser, Geoffrey Matthews, Antonietta Russo, Max Bellon, Laura K Besanko, Karen L Jones, Ross Butler, Barry Chatterton and Michael Horowit

Fast fluorescence microscopy for imaging the dynamics of embryonic development

Live imaging has gained a pivotal role in developmental biology since it increasingly allows real-time observation of cell behavior in intact organisms. Microscopes that can capture the dynamics of ever-faster biological events, fluorescent markers optimal for in vivo imaging, and, finally, adapted reconstruction and analysis programs to complete data flow all contribute to this success. Focusing on temporal resolution, we discuss how fast imaging can be achieved with minimal prejudice to spatial resolution, photon count, or to reliably and automatically analyze images. In particular, we show how integrated approaches to imaging that combine bright fluorescent probes, fast microscopes, and custom post-processing techniques can address the kinetics of biological systems at multiple scales. Finally, we discuss remaining challenges and opportunities for further advances in this field