Lipidomic Approaches to Study HDL Metabolism in Patients with Central Obesity Diagnosed with Metabolic Syndrome

The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors characterised by central obesity, atherogenic dyslipidaemia, and changes in the circulating lipidome; the underlying mechanisms that lead to this lipid remodelling have only been partially elucidated. This study used an integrated “omics” approach (untargeted whole serum lipidomics, targeted proteomics, and lipoprotein lipidomics) to study lipoprotein remodelling and HDL composition in subjects with central obesity diagnosed with MetS (vs. controls). Compared with healthy subjects, MetS patients showed higher free fatty acids, diglycerides, phosphatidylcholines, and triglycerides, particularly those enriched in products of de novo lipogenesis. On the other hand, the “lysophosphatidylcholines to phosphatidylcholines” and “cholesteryl ester to free cholesterol” ratios were reduced, pointing to a lower activity of lecithin cholesterol acyltransferase (LCAT) in MetS; LCAT activity (directly measured and predicted by lipidomic ratios) was positively correlated with high-density lipoprotein cholesterol (HDL-C) and negatively correlated with body mass index (BMI) and insulin resistance. Moreover, many phosphatidylcholines and sphingomyelins were significantly lower in the HDL of MetS patients and strongly correlated with BMI and clinical metabolic parameters. These results suggest that MetS is associated with an impairment of phospholipid metabolism in HDL, partially led by LCAT, and associated with obesity and underlying insulin resistance. This study proposes a candidate strategy to use integrated “omics” approaches to gain mechanistic insights into lipoprotein remodelling, thus deepening the knowledge regarding the molecular basis of the association between MetS and atherosclerosis.     

Analysis and neural network modeling of the nonlinear correlates of habituation in the vestibulo-ocular reflex

Through the process of habituation, continued exposure to low-frequency (0.01 Hz) rotation in the dark produced suppression of the low-frequency response of the vestibulo-ocular reflex (VOR) in goldfish. The response did not decay gradually, as might be expected from an error-driven learning process, but displayed several nonlinear and nonstationary features. They included asymmetrical response suppression, magnitude-dependent suppression for lower- but not higher-magnitude head rotations, and abrupt-onset suppressions suggestive of a switching mechanism. Microinjection of lidocaine into the vestibulocerebellum of habituated goldfish resulted in a temporary dishabituation. This suggests that the vestibulocerebellum mediates habituation, presumably through Purkinje cell inhibition of vestibular nuclei neurons. The habituated VOR data were simulated with a feed-forward, nonlinear neural network model of the VOR in which only Purkinje cell inhibition of vestibular nuclei neurons was varied. The model suggests that Purkinje cell inhibition may switch in to introduce nonstationarities, and cause asymmetry and magnitude-dependency in the VOR to emerge from the essential nonlinearity of vestibular nuclei neurons.     

Analysis of Clinic Layouts and Patient-Centered Procedural Innovations Using Discrete-Event Simulation

Abstract

Given that healthcare costs in the U.S. continue to climb, engineering managers can help address this situation by identifying designs for cost savings. Using discrete-event simulation, the layout of four different healthcare clinic scenarios considered in a redesign program named Patient Aligned Care Teams were studied. Model 1 is an existing layout in many clinics and Model 2 is staff-centered, while Models 3 and 4 provide additional space including common hallway(s). Our main conclusion is that Model 4 reduces patient travel distances and average queueing waits, while also providing the best privacy in accordance with HIPAA and the most security for the staff.     

Household Activity Pattern Problem with Autonomous Vehicles

Networks and Spatial Economics - The pace of changes in automating cars has sped up in the last few decades. Autonomous Vehicles (AVs) will dramatically change the future of transportation, and...     

The Role of Exosomal Epigenetic Modifiers in Cell Communication and Fertility of Dairy Cows

Abnormal uterine function affects conception rate and embryo development, thereby leading to poor fertility and reproduction failure. Exosomes are a nanosized subclass of extracellular vesicles (EV) that have important functions as intercellular communicators. They contain and carry transferable bioactive substances including micro RNA (miRNA) for target cells. Elements of the cargo can provide epigenetic modifications of the recipient cells and may have crucial roles in mechanisms of reproduction. The dairy industry accounts for a substantial portion of the economy of many agricultural countries. Exosomes can enhance the expression of inflammatory mediators in the endometrium, which contribute to various inflammatory diseases in transition dairy cows. This results in reduced fertility which leads to reduced milk production and increased cow maintenance costs. Thus, gaining a clear knowledge of exosomal epigenetic modifiers is critical to improving the breeding success and profitability of dairy farms. This review provides a brief overview of how exosomal miRNA contributes to inflammatory diseases and hence to poor fertility, particularly in dairy cows.     

Microstructure and elastic modulus of mixed gels of gelatin + oxidized starch: Effect of pH

The microstructure and elastic shear modulus of cold-set gels formed from high-sugar aqueous mixtures of gelatin (7 wt%) + oxidized starch (0-6 wt%) were investigated as a function of pH. Samples prepared at 90 °C, with citric acid added to adjust the pH, were rapidly quenched to ∼1 °C, subjected to a standard thermal treatment (40 °C for 10 min), and then investigated by confocal microscopy and small-deformation rheology at 24 °C. Under ‘natural’ conditions of pH ≈ 5.2 (no citric acid addition), the samples exhibited phase separation with a characteristic spinodal-type morphology. The spatial extent of the structural heterogeneity, expressed by a single length-scale parameter, was found to increase with starch concentration. Gradual acidification led to a reduction in this length-scale parameter, leading to complete inhibition of phase separation below a certain characteristic pH value in the range 4.5-4.9 (depending on starch content). Over the investigated pH range, the effect of starch addition was to reduce the storage modulus of the resulting gel. This reduction was more pronounced for the phase-separated samples. The pH of maximum rigidity was found to decrease from pH_max ≈ 4.6 for 0 wt% starch to pH_max ≈ 4.2 for 6 wt% starch. Taken all together, these observations can be understood in terms of the effects of pH on the cross-linking behaviour of the gelatin and the nature of the gelatin-starch electrostatic interactions. The microscopy results are consistent with a transition in behaviour from thermodynamic incompatibility (segregative interactions) at high pH to soluble complexation (associative interactions) at low pH.