Changes in endotoxin levels in T2DM subjects on anti-diabetic therapies

Introduction Chronic low-grade inflammation is a significant factor in the development of obesity associated diabetes. This is supported by recent studies suggesting endotoxin, derived from gut flora, may be key to the development of inflammation by stimulating the secretion of an adverse cytokine profile from adipose tissue. Aims The study investigated the relationship between endotoxin and various metabolic parameters of diabetic patients to determine if anti-diabetic therapies exerted a significant effect on endotoxin levels and adipocytokine profiles. Methods Fasting blood samples were collected from consenting Saudi Arabian patients (BMI: 30.2 ± (SD)5.6 kg/m2, n = 413), consisting of non-diabetics (ND: n = 67) and T2DM subjects (n = 346). The diabetics were divided into 5 subgroups based on their 1 year treatment regimes: diet-controlled (n = 36), metformin (n = 141), rosiglitazone (RSG: n = 22), a combined fixed dose of metformin/rosiglitazone (met/RSG n = 100) and insulin (n = 47). Lipid profiles, fasting plasma glucose, insulin, adiponectin, resistin, TNF-α, leptin, C-reactive protein (CRP) and endotoxin concentrations were determined. Results Regression analyses revealed significant correlations between endotoxin levels and triglycerides (R2 = 0.42; p < 0.0001); total cholesterol (R2 = 0.10; p < 0.001), glucose (R2 = 0.076; p < 0.001) and insulin (R2 = 0.032; p < 0.001) in T2DM subjects. Endotoxin showed a strong inverse correlation with HDL-cholesterol (R2 = 0.055; p < 0.001). Further, endotoxin levels were elevated in all of the treated diabetic subgroups compared with ND, with the RSG treated diabetics showing significantly lower endotoxin levels than all of the other treatment groups (ND: 4.2 ± 1.7 EU/ml, RSG: 5.6 ± 2.2 EU/ml). Both the met/RSG and RSG treated groups had significantly higher adiponectin levels than all the other groups, with the RSG group expressing the highest levels overall. Conclusion We conclude that sub-clinical inflammation in T2DM may, in part, be mediated by circulating endotoxin. Furthermore, that whilst the endotoxin and adipocytokine profiles of diabetic patients treated with different therapies were comparable, the RSG group demonstrated significant differences in both adiponectin and endotoxin levels. We confirm an association between endotoxin and serum insulin and triglycerides and an inverse relationship with HDL. Lower endotoxin and higher adiponectin in the groups treated with RSG may be related and indicate another mechanism for the effect of RSG on insulin sensitivity

Power changes of EEG signals associated with muscle fatigue: The root mean square analysis of EEG bands

The paper reports a research conducted to determine changes in the electrical activity of the contralateral motor cortex of the brain that drives the maximum voluntary contraction (MVC) of the right adductor pollicis muscle (APM) after fatigue. The power changes of EEG signals after muscle fatigue were computed. In twenty-five subjects, EEG signals from the left motor cortical area (C3, FC3) were recorded simultaneously with EMG signals from the right APM, before and after exercise-induced fatigue. The root mean square (RMS) of the EEG bands (alpha, beta, and gamma) was calculated to determine the power changes of the EEG signals after right APM fatigue. The mean RMS of the EEG bands were increased during MVC of the fatigued right APM compared to the RMS value during relaxation before fatigue (p&lt;0.05). The RMS value was seen to be greatest in the beta band, and lowest in the gamma band. The observed increase in the RMS of EEG bands during MVC of the fatigued right APM suggest an increase in the EEG signal power, which could reflect an increase in energy needed by the motor cortex to perform MVC in fatigued muscles, which might give an indication of neural fatigue in the motor cortex

Hydrogen bond network topology in liquid water and methanol: a graph theory approach

Networks are increasingly recognized as important building blocks of various systems in nature and society. Water is known to possess an extended hydrogen bond network, in which the individual bonds are broken in the sub-picosecond range and still the network structure remains intact. We investigated and compared the topological properties of liquid water and methanol at various temperatures using concepts derived within the framework of graph and network theory (neighbour number and cycle size distribution, the distribution of local cyclic and local bonding coefficients, Laplacian spectra of the network, inverse participation ratio distribution of the eigenvalues and average localization distribution of a node) and compared them to small world and Erdős–Rényi random networks. Various characteristic properties (e.g. the local cyclic and bonding coefficients) of the network in liquid water could be reproduced by small world and/or Erdős–Rényi networks, but the ring size distribution of water is unique and none of the studied graph models could describe it. Using the inverse participation ratio of the Laplacian eigenvectors we characterized the network inhomogeneities found in water and showed that similar phenomena can be observed in Erdős–Rényi and small world graphs. We demonstrated that the topological properties of the hydrogen bond network found in liquid water systematically change with the temperature and that increasing temperature leads to a broader ring size distribution. We applied the studied topological indices to the network of water molecules with four hydrogen bonds, and showed that at low temperature (250 K) these molecules form a percolated or nearly-percolated network, while at ambient or high temperatures only small clusters of four-hydrogen bonded water molecules exist

Mapping 6D N = 1 supergravities to F-theory

We develop a systematic framework for realizing general anomaly-free chiral 6D supergravity theories in F-theory. We focus on 6D (1, 0) models with one tensor multiplet whose gauge group is a product of simple factors (modulo a finite abelian group) with matter in arbitrary representations. Such theories can be decomposed into blocks associated with the simple factors in the gauge group; each block depends only on the group factor and the matter charged under it. All 6D chiral supergravity models can be constructed by gluing such blocks together in accordance with constraints from anomalies. Associating a geometric structure to each block gives a dictionary for translating a supergravity model into a set of topological data for an F-theory construction. We construct the dictionary of F-theory divisors explicitly for some simple gauge group factors and associated matter representations. Using these building blocks we analyze a variety of models. We identify some 6D supergravity models which do not map to integral F-theory divisors, possibly indicating quantum inconsistency of these 6D theories.Comment: 37 pages, no figures; v2: references added, minor typos corrected; v3: minor corrections to DOF counting in section

Adhesive stresses in axially-loaded tubular bonded joints - Part II: development of an explicit closed-form solution for the Lubkin and Reissner model

The literature presents several analytical models and solutions for single- and double-lap bonded joints, whilst the joint between circular tubes is less common. For this geometry the pioneering model is that of Lubkin and Reissner (Trans. ASME 78, 1956), in which the tubes are treated as cylindrical thin shells subjected to membrane and bending loading, whilst the adhesive transmits shear and peel stresses which are a function of the axial coordinate only. Such assumptions are consistent with those usually adopted for the flat joints. A former investigation has shown that the L-R model agrees with FE results for many geometries and gives far better results than other models appeared later in the literature. The aim of the present work is to obtain and present an explicit closed-form solution, not reported by Lubkin and Reissner, which is achieved by solving the governing equations by means of the Laplace transform. The correctness of the findings, assessed by the comparison with the tabular results of Lubkin and Reissner, and the features of this solution are commente

The use of buffer pellets to pseudo hot seed (RE)-Ba-Cu-O-(Ag) single grain bulk superconductors

Reliable seeding of the superconducting (RE)Ba₂Cu₃O₇-δ (RE-123) phase is a critical step in the melt growth of large, single grain, (RE)BaCuO [(RE)BCO] bulk superconductors. Recent improvements to the top seeded melt growth (TSMG) processing technique, which is an established method of fabricating bulk (RE)BCO superconductors, based on the use of a buffer layer between the seed and green body preform, has improved significantly the reliability of the single grain growth process. This technique has been used successfully for the primary TSMG and infiltration melt growth (IG) of all compositions within the [(RE)BCO-Ag] family of materials (where RE = Sm, Gd and Y), and in recycling processes. However, the mechanism behind the improved reliability of the melt process is not understood fully and its effect on the superconducting properties of the fully processed single grains is not clear. In this paper, we investigate the effect of the use of a buffer pellet between the seed and green body on the microstructure, critical current, critical temperature and trapped field of the bulk superconductor. We conclude that the introduction of the buffer pellet evolves the melt growth process towards that observed in the technologically challenging hot seeding technique, but has the potential to yield high quality single grain samples but by a commercially viable melt process.This work was supported by the Engineering and Physical Sciences Research Council [EPSRC, grant number EP/K02910X/1] and King Abdulaziz City for Science and Technology [KACST].This is the final version of the article. It was first available from IOP Publishing via http://dx.doi.org/10.1088/0953-2048/29/1/015010 Additional data related to this publication is available at the University of Cambridge data repository [https://www.repository.cam.ac.uk/handle/1810/249091]. All other data accompanying this publication are directly available within the publication

Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines in patients with cardiovascular disease

Introduction: Inflammation contributes to cardiovascular disease and is exacerbated with increased adiposity, particularly omental adiposity; however, the role of epicardial fat is poorly understood. Methods: For these studies the expression of inflammatory markers was assessed in epicardial fat biopsies from coronary artery bypass grafting (CABG) patients using quantitative RT-PCR. Further, the effects of chronic medications, including statins, as well as peri-operative glucose, insulin and potassium infusion, on gene expression were also assessed. Circulating resistin, CRP, adiponectin and leptin levels were determined to assess inflammation. Results: The expression of adiponectin, resistin and other adipocytokine mRNAs were comparable to that in omental fat. Epicardial CD45 expression was significantly higher than control depots (p < 0.01) indicating significant infiltration of macrophages. Statin treated patients showed significantly lower epicardial expression of IL-6 mRNA, in comparison with the control abdominal depots (p < 0.001). The serum profile of CABG patients showed significantly higher levels of both CRP (control: 1.28 ± 1.57 μg/mL vs CABG: 9.11 ± 15.7 μg/mL; p < 0.001) and resistin (control: 10.53 ± 0.81 ng/mL vs CABG: 16.8 ± 1.69 ng/mL; p < 0.01) and significantly lower levels of adiponectin (control: 29.1 ± 14.8 μg/mL vs CABG: 11.9 ± 6.0 μg/mL; p < 0.05) when compared to BMI matched controls. Conclusion: Epicardial and omental fat exhibit a broadly comparable pathogenic mRNA profile, this may arise in part from macrophage infiltration into the epicardial fat. This study highlights that chronic inflammation occurs locally as well as systemically potentially contributing further to the pathogenesis of coronary artery disease

Normality and smoothness of simple linear group compactifications

If G is a complex semisimple algebraic group, we characterize the normality and the smoothness of its simple linear compactifications, namely those equivariant GxG-compactifications which possess a unique closed orbit and which arise in a projective space of the shape P(End(V)), where V is finite dimensional rational G-module. Both the characterizations are purely combinatorial and are expressed in terms of the highest weights of V. In particular, we show that Sp(2r) (with r > 0) is the unique non-adjoint simple group which admits a simple smooth compactification.Comment: v2: minor changes, final version. To appear in Math.