Changes in plasma levels of N-arachidonoyl ethanolamine and N-palmitoylethanolamine following bariatric surgery in morbidly obese females with impaired glucose homeostasis

Aim: We examined endocannabinoids (ECs) in relation to bariatric surgery and the association between plasma ECs and markers of insulin resistance. Methods: A study of 20 participants undergoing bariatric surgery. Fasting and 2-hour plasma glucose, lipids, insulin, and C-peptide were recorded preoperatively and 6 months postoperatively with plasma ECs (AEA, 2-AG) and endocannabinoid-related lipids (PEA, OEA). Results: Gender-specific analysis showed differences in AEA, OEA, and PEA preoperatively with reductions in AEA and PEA in females postoperatively. Preoperatively, AEA was correlated with 2-hour glucose (r = 0.55, P = 0.01), HOMA-IR (r = 0.61, P = 0.009), and HOMA %S (r = -0.71, P = 0.002). OEA was correlated with weight (r = 0.49, P = 0.03), waist circumference (r = 0.52, P = 0.02), fasting insulin (r = 0.49, P = 0.04), and HOMA-IR (r = 0.48, P = 0.05). PEA was correlated with fasting insulin (r = 0.49, P = 0.04). 2-AG had a negative correlation with fasting glucose (r = -0.59, P = 0.04). Conclusion: Gender differences exist in circulating ECs in obese subjects. Females show changes in AEA and PEA after bariatric surgery. Specific correlations exist between different ECs and markers of obesity and insulin and glucose homeostasis

Impending Hyperglycemia in Normoglycemic Renal Transplant Recipients—An Experimental Predictive Surrogate

Background. β-Cell dysfunction and insulin resistance combine to cause new-onset diabetes after transplantation. The product of these two parameters, quantitatively measured as disposition index (DI), is a mathematical constant in normoglycemia and declines in advance of impending hyperglycemia. The aim of this study was to derive a simple surrogate for the DI to expose predysglycemic abnormalities posttransplantation. Methods. First-phase insulin secretion and sensitivity were determined by mathematical minimal model analysis of 58 frequently sampled, intravenous glucose tolerance tests in 58 non-diabetic renal transplant recipients and correlated against surrogate indexes based on fasting blood samples. Products of insulin secretion/resistance indexes were correlated against calculated DI, regression analysis performed for hyperbolic compatibility, autocorrelation studies conducted, and surrogates tested in various subgroups of renal transplant recipients to ensure robustness in a heterogeneous group. Results. The best correlation was achieved with “HOMAsec (first-phase insulin secretion)×McAuley's index (insulin resistance)” (r=0.594, P<0.001). Regression analysis was consistent with a mathematical hyperbola (ln HOMAsec vs. ln McAuley's index, r=−0.639 [95% confidence interval, −1.772 to −0.950]), statistical autocorrelation was excluded (in a subset of 20 patients with repeat metabolic investigations), and the surrogate remained valid in different subgroups of transplant recipients. Conclusions. Our surrogate “HOMAsec×McAuley's index,” requiring only fasting glucose, insulin, and triglycerides, is a simple and noninvasive surrogate for the DI. Its predictive utility for identifying impending hyperglycemia posttransplantation should be investigated further to ascertain whether its experimental nature can translate to clinical validity

Effects of Nutritional Supplementation during Pregnancy on Early Adult Disease Risk: Follow Up of Offspring of Participants in a Randomised Controlled Trial Investigating Effects of Supplementation on Infant Birth Weight

<div><p>Background</p><p>Observational evidence suggests that improving fetal growth may improve adult health. Experimental evidence from nutritional supplementation trials undertaken amongst pregnant women in the less developed world does not show strong or consistent effects on adult disease risk and no trials from the more developed world have previously been reported. </p> <p>Objective</p><p>To test the hypothesis that nutritional supplementation during pregnancy influences offspring disease risk in adulthood </p> <p>Design</p><p>Clinical assessment of a range of established diseases risk markers in young adult offspring of 283 South Asian mothers who participated in two trials of nutritional supplementation during pregnancy (protein/energy/vitamins; energy/vitamins or vitamins only) at Sorrento Maternity Hospital in Birmingham UK either unselected or selected on the basis of nutritional status. </p> <p>Results</p><p>236 (83%) offspring were traced and 118 (50%) of these were assessed in clinic. Protein/energy/vitamins supplementation amongst undernourished mothers was associated with increased infant birthweight. Nutritional supplementation showed no strong association with any one of a comprehensive range of markers of adult disease risk and no consistent pattern of association with risk across markers in offspring of either unselected or undernourished mothers. </p> <p>Conclusions</p><p>We found no evidence that nutritional supplements given to pregnant women are an important influence on adult disease risk however our study lacked power to estimate small effects. Our findings do not provide support for a policy of nutritional supplementation for pregnant women as an effective means to improve adult health in more developed societies.</p> </div

Isomaltulose Improves Postexercise Glycemia by Reducing CHO Oxidation in T1DM

Purpose: Individuals with type 1 diabetes mellitus (T1DM) are encouraged to consume CHO to prevent hypoglycemia during or after exercise. However, the research comparing specific types of CHO is limited. This study compared the alterations in metabolism and fuel oxidation in response to running after preexercise ingestion of isomaltulose or dextrose in T1DM. Methods: After preliminary testing, on two occasions, eight T1DM individuals consumed 75 g of either dextrose (DEX; GI = 96) or isomaltulose (ISO; GI = 32), 2 h before performing 45 min of treadmill running at 80% perpendicular to 1% (V) over dotO(2peak). Blood glucose (BG) was measured for 2 h before and 3 h after exercise. Cardiorespiratory parameters were collected at rest and during exercise. Data (mean +/- SEM) were analyzed using repeated-measures ANOVA. Results: There was a smaller increase in BG in the preexercise period under ISO with peak BG occurring at 120 min after ingestion compared with 90 min under DEX (Delta+4.5 +/- 0.4 vs Delta+9.1 +/- 0.6 mmol.L(-1), P < 0.01). During the final 10 min of exercise, there were lower CHO (ISO 2.85 perpendicular to 0.07 vs DEX 3.18 perpendicular to 0.08 g.min(-1), P < 0.05) and greater lipid oxidation rates (ISO 0.33 perpendicular to 0.03 vs DEX 0.20 +/- 0.03 g.min(-1), P < 0.05) under ISO. After exercise, ISO BG was lower than DEX for the entire 180-min period, with BG area under the curve and mean BG concentrations being 21% +/- 3% and 3.0 +/- 0.4 mmol.L(-1) lower, respectively (P < 0.05). Conclusions: Consumption of ISO improves BG responses during and after exercise through reduced CHO and improved lipid oxidation during the later stages of exercise

Deep Underground Neutrino Experiment (DUNE), Far Detector Technical Design Report, Volume II: DUNE Physics

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay -- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. DUNE is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. Volume II of this TDR, DUNE Physics, describes the array of identified scientific opportunities and key goals. Crucially, we also report our best current understanding of the capability of DUNE to realize these goals, along with the detailed arguments and investigations on which this understanding is based. This TDR volume documents the scientific basis underlying the conception and design of the LBNF/DUNE experimental configurations. As a result, the description of DUNE's experimental capabilities constitutes the bulk of the document. Key linkages between requirements for successful execution of the physics program and primary specifications of the experimental configurations are drawn and summarized. This document also serves a wider purpose as a statement on the scientific potential of DUNE as a central component within a global program of frontier theoretical and experimental particle physics research. Thus, the presentation also aims to serve as a resource for the particle physics community at large

Reconstruction of interactions in the ProtoDUNE-SP detector with Pandora

International audienceThe Pandora Software Development Kit and algorithm libraries provide pattern-recognition logic essential to the reconstruction of particle interactions in liquid argon time projection chamber detectors. Pandora is the primary event reconstruction software used at ProtoDUNE-SP, a prototype for the Deep Underground Neutrino Experiment far detector. ProtoDUNE-SP, located at CERN, is exposed to a charged-particle test beam. This paper gives an overview of the Pandora reconstruction algorithms and how they have been tailored for use at ProtoDUNE-SP. In complex events with numerous cosmic-ray and beam background particles, the simulated reconstruction and identification efficiency for triggered test-beam particles is above 80% for the majority of particle type and beam momentum combinations. Specifically, simulated 1 GeV/$c$ charged pions and protons are correctly reconstructed and identified with efficiencies of 86.1$\pm0.6$% and 84.1$\pm0.6$%, respectively. The efficiencies measured for test-beam data are shown to be within 5% of those predicted by the simulation

Reconstruction of interactions in the ProtoDUNE-SP detector with Pandora

International audienceThe Pandora Software Development Kit and algorithm libraries provide pattern-recognition logic essential to the reconstruction of particle interactions in liquid argon time projection chamber detectors. Pandora is the primary event reconstruction software used at ProtoDUNE-SP, a prototype for the Deep Underground Neutrino Experiment far detector. ProtoDUNE-SP, located at CERN, is exposed to a charged-particle test beam. This paper gives an overview of the Pandora reconstruction algorithms and how they have been tailored for use at ProtoDUNE-SP. In complex events with numerous cosmic-ray and beam background particles, the simulated reconstruction and identification efficiency for triggered test-beam particles is above 80% for the majority of particle type and beam momentum combinations. Specifically, simulated 1 GeV/$c$ charged pions and protons are correctly reconstructed and identified with efficiencies of 86.1$\pm0.6$% and 84.1$\pm0.6$%, respectively. The efficiencies measured for test-beam data are shown to be within 5% of those predicted by the simulation