Genomics and Epigenomics of Gestational Diabetes Mellitus: Understanding the Molecular Pathways of the Disease Pathogenesis

One of the most common complications during pregnancy is gestational diabetes mellitus (GDM), hyperglycemia that occurs for the first time during pregnancy. The condition is multifactorial, caused by an interaction between genetic, epigenetic, and environmental factors. However, the underlying mechanisms responsible for its pathogenesis remain elusive. Moreover, in contrast to several common metabolic disorders, molecular research in GDM is lagging. It is important to recognize that GDM is still commonly diagnosed during the second trimester of pregnancy using the oral glucose tolerance test (OGGT), at a time when both a fetal and maternal pathophysiology is already present, demonstrating the increased blood glucose levels associated with exacerbated insulin resistance. Therefore, early detection of metabolic changes and associated epigenetic and genetic factors that can lead to an improved prediction of adverse pregnancy outcomes and future cardio-metabolic pathologies in GDM women and their children is imperative. Several genomic and epigenetic approaches have been used to identify the genes, genetic variants, metabolic pathways, and epigenetic modifications involved in GDM to determine its etiology. In this article, we explore these factors as well as how their functional effects may contribute to immediate and future pathologies in women with GDM and their offspring from birth to adulthood. We also discuss how these approaches contribute to the changes in different molecular pathways that contribute to the GDM pathogenesis, with a special focus on the development of insulin resistance.     

Measurement of anthocyanins and other phytochemicals in purple wheat

The major anthocyanin composition of normal purple wheat and heat stressed purple wheat were measured using HPLC, LC–MS/MS and the pH differential method. The lignan secoisolariciresinol diglucoside (SDG) and melatonin content were also measured. Total anthocyanin profile of normal purple wheat (491.3 mg/kg) was significantly (P < 0.05) lower than that of the heat stressed purple wheat (522.7 mg/kg). Thirteen major anthocyanins were isolated and cyanidin 3-glucoside was the predominant anthocyanin in purple wheat. Using the pH differential method, the total anthocyanin content of normal (500.6 mg/kg) and heat stressed (526.0 mg/kg) purple wheat were similar to those observed using HPLC. The SDG content of normal and heat stressed purple wheat were 770 and 520 μg/kg, while melatonin content was 4 and 2 μg/kg, respectively. The presence of SDG and melatonin in addition to anthocyanins may contribute to the health benefits associated with consumption of coloured cereal grains.     

Removal of aqueous Fe2+ using MnO2–clinoptilolite in a batch slurry reactor: Catalyst synthesis,characterization and modeling of catalytic behavior

An Iranian clinoptilolite has been modified with MnO₂ for the catalytic removal of Fe²⁺ cations from water in a batch slurry reactor. The modified zeolite was subjected to FESEM, XRD, WDX, XRF and specific surface area analysis. A correlation for the intrinsic catalytic reaction rate incorporating both Fe²⁺ and dissolved oxygen concentration as a function of reaction temperature has been presented. The effect of the modified zeolite aggregate particle size on the iron removal kinetics has been investigated. It was shown that for particles larger than 150 μm, diffusion through the mesopores of the zeolite aggregate is rate controlling. The effective diffusion coefficient through the particles at RT has been calculated as 2.3 × 10^?6 cm² s^?1. It is shown that liquid phase molecular diffusion within the mesopores is the dominating mass transfer mechanism.     

Differential Metabotypes in Synovial Fibroblasts and Synovial Fluid in Hip Osteoarthritis Patients Support Inflammatory Responses

Changes in cellular metabolism have been implicated in mediating the activated fibroblast phenotype in a number of chronic inflammatory disorders, including pulmonary fibrosis, renal disease and rheumatoid arthritis. The aim of this study was therefore to characterise the metabolic profile of synovial joint fluid and synovial fibroblasts under both basal and inflammatory conditions in a cohort of obese and normal-weight hip OA patients. Furthermore, we sought to ascertain whether modulation of a metabolic pathway in OA synovial fibroblasts could alter their inflammatory activity. Synovium and synovial fluid was obtained from hip OA patients, who were either of normal-weight or obese and were undergoing elective joint replacement surgery. The synovial fluid metabolome was determined by 1H NMR spectroscopy. The metabolic profile of isolated synovial fibroblasts in vitro was characterised by lactate secretion, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using the Seahorse XF Analyser. The effects of a small molecule pharmacological inhibitor and siRNA targeted at glutaminase-1 (GLS1) were assessed to probe the role of glutamine metabolism in OA synovial fibroblast function. Obese OA patient synovial fluid (n = 5) exhibited a different metabotype, compared to normal-weight patient fluid (n = 6), with significantly increased levels of 1, 3-dimethylurate, N-Nitrosodimethylamine, succinate, tyrosine, pyruvate, glucose, glycine and lactate, and enrichment of the glutamine–glutamate metabolic pathway, which correlated with increasing adiposity. In vitro, isolated obese OA fibroblasts exhibited greater basal lactate secretion and aerobic glycolysis, and increased mitochondrial respiration when stimulated with pro-inflammatory cytokine TNFα, compared to fibroblasts from normal-weight patients. Inhibition of GLS1 attenuated the TNFα-induced expression and secretion of IL-6 in OA synovial fibroblasts. These findings suggest that altered cellular metabolism underpins the inflammatory phenotype of OA fibroblasts, and that targeted inhibition of glutamine–glutamate metabolism may provide a route to reducing the pathological effects of joint inflammation in OA patients who are obese.     

Management of Multi-Queue Switches in QoS Networks

The concept of Quality of Service (QoS) networks has gained growing attention recently, as the traffic volume in the Internet constantly increases, and QoS guarantees are essential to ensure proper operation of most communication-based applications. A QoS switch serves m incoming queues by transmitting packets arriving to these queues through one output port, one packet per time step. Each packet is marked with a value indicating its priority in the network. Since the queues have bounded capacities and the rate of arriving packets can be much higher than the transmission rate, packets can be lost due to insufficient queue space. The goal is to maximize the total value of transmitted packets. This problem encapsulates two dependent questions: buffer management, namely which packets to admit into the queues, and scheduling, i.e. which queue to use for transmission in each time step. We use competitive analysis to study online switch performance in QoS-based networks. Specifically, we provide a novel generic technique that decouples the buffer management and scheduling problems. Our technique transforms any single-queue buffer management policy (preemptive or non-preemptive) to a scheduling and buffer management algorithm for our general m queues model, whose competitive ratio is at most twice the competitive ratio of the given buffer management policy. We use our technique to derive concrete algorithms for the general preemptive and non-preemptive cases, as well as for the interesting special cases of the 2-value model and the unit-value model. We also provide a 1.58-competitive randomized algorithm for the unit-value case. This case is interesting by itself since most current networks (e.g. IP networks) do not yet incorporate full QoS capabilities, and treat all packets equally.     

Combinatorial Algorithms for the Unsplittable Flow Problem

We provide combinatorial algorithms for the unsplittable flow problem (UFP) that either match or improve the previously best results. In the UFP we are given a (possibly directed) capacitated graph with n vertices and m edges, and a set of terminal pairs each with its own demand and profit. The objective is to connect a subset of the terminal pairs each by a single flow path subject to the capacity constraints such that the total profit of the connected pairs is maximized.We consider three variants of the problem. First is the classical UFP in which the maximum demand is at most the minimum edge capacity. It was previously known to have an O(√m) approximation algorithm; the algorithm is based on the randomized rounding technique and its analysis makes use of the Chernoff bound and the FKG inequality.We provide a combinatorial algorithm that achieves the same approximation ratio and whose analysis is considerably simpler. Second is the extended UFP in which some demands might be higher than edge capacities. Our algorithm for this case improves the best known approximation ratio. We also give a lower bound that shows that the extended UFP is provably harder than the classical UFP. Finally, we consider the bounded UFP in which the maximum demand is at most 1/K times the minimum edge capacity for some K > 1. Here we provide combinatorial algorithms that match the currently best known algorithms. All of our algorithms are strongly polynomial and some can even be used in the online setting.     

Is visual imagery really visual? Overlooked evidence from neuropsychology.

Does visual imagery engage some of the same representations used in visual perception? The evidence collected by cognitive psychologists in support of this claim has been challenged by three types of alternative explanation: Tacit knowledge, according to which subjects use nonvisual representations to simulate the use of visual representations during imagery tasks, guided by their tacit knowledge of their visual systems; experimenter expectancy, according to which the data implicating shared representations for imagery and perception is an artifact of experimenter expectancies; and nonvisual spatial representation, according to which imagery representations are partially similar to visual representations in the way they code spatial relations but are not visual representations. This article reviews previously overlooked neuropsychological evidence on the relation between imagery and perception, and discusses its relative immunity to the foregoing alternative explanations. This evidence includes electrophysiological and cerebral blood flow studies localizing brain activity during imagery to cortical visual areas, and parallels between the selective effects of brain damage on visual perception and imagery. Because these findings cannot be accounted for in the same way as traditional cognitive data using the alternative explanations listed earlier, they can play a decisive role in answering the title question. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Laser in situ keratomileusis: literature review of a developing technique

We reviewed papers published in peer-reviewed journals describing techniques and results of laser in situ keratomileusis (LASIK) and summarized the instruments used, nomograms, preoperative and postoperative refractions, predictability, outcome, safety, and complications. We performed a similar review of abstracts published in the abstract books of the 1996 meeting of the International Society of Refractive Surgery, the 1997 meeting of the Association for Research in Vision and Ophthalmology, and the 1997 meeting of the American Society of Cataract and Refractive Surgery. The number of LASIK and photorefractive keratectomy (PRK) patients described in the abstracts were sorted by city. Mean weighted latitudes were calculated and compared for each procedure. The mean preoperative refraction in the papers was -12.59 diopters (D), which was statistically higher than that in the abstracts, -8.71 D (P < .001), and the mean postoperative refraction, -1.10 and + 0.93 D, respectively. The mean percentage of cases within +/- 1.00 D was 67.0% in the papers and 82.5% in the abstracts. Uncorrected visual acuity (UCVA) of 20/40 or better was achieved in 49.2% of eyes in the papers and 83.2% of those in the abstracts; a UCVA of 20/20 or better was achieved in 22.0 and 56.6%, respectively. The portion of eyes that lost two or more lines of best corrected visual was 8.0% in the papers and 0.9% in the abstracts. Complications in the papers included irregular flap (4.0%), incomplete cut (2.5%), free cap (4.9%), perforated lenticule (2.6%), short flap (3.0%), sliding flap (1.4%), interface debris (6.8%), central island (5.3%), decentration (4.7%), epithelial ingrowth (4.3%), induced astigmatism (5.1%), wrinkles (5.9%), haze (8.7%), night vision problems (14.0%), and reoperation (8.2%), Mean latitude for LASIK cases (27.00 degrees +/- 13.73 [SD] was significantly lower than that for PRK cases (42.85 +/- 11.7 degrees). Visual outcomes of LASIK surgery show significant improvements when recent abstracts are compared with published papers. This may reflect continued improvement in the surgical techniques, surgeons' skills, and visual outcomes.     

Recurrent polymorphic ventricular tachycardia complicating radiofrequency catheter ablation of the atrioventricular junction

Recurrent ventricular tachycardia and ventricular fibrillation were observed immediately after RF ablation of the AV junction in a 64-year-old man. This arrhythmia was preceded by ventricular bigeminy and a long-short sequence. It was not associated with prolongation of the QT interval compared to baseline, and recurred 3 months later despite ventricular pacing at 90 beats/min. This is the first reported case of sustained ventricular arrhythmia complicating RF AV junction ablation despite rapid ventricular pacing, and recurring 3 months after discharge. It may explain the rare cases of sudden death complicating this procedure.