Similar glycaemic control and less hypoglycaemia during active titration after insulin initiation with glargine 300 units/mL and degludec 100 units/mL: A subanalysis of the BRIGHT study

Aim: To further investigate glycaemic control and hypoglycaemia in BRIGHT, focusing on the titration period. Materials and Methods: BRIGHT was a multicentre, open-label, randomized, active-controlled, two-arm, parallel-group, 24-week study in insulin-naïve patients with uncontrolled type 2 diabetes initiated on glargine 300 U/mL (Gla-300) (N = 466) or degludec (IDeg-100) (N = 463). Predefined efficacy and safety outcomes were investigated during the initial 12-week titration period. In addition, patients’ characteristics and clinical outcomes were assessed descriptively, stratified by confirmed (≤3.9 mmol/L) hypoglycaemia incidence during the initial titration period. Results: At week 12, HbA1c was comparable between Gla-300 (7.32%) and IDeg-100 (7.23%), with similar least squares (LS) mean reductions from baseline (−1.37% and − 1.39%, respectively; LS mean difference of 0.02; 95% confidence interval: −0.08 to 0.12). Patients who experienced hypoglycaemia during the initial titration period had numerically greater HbA1c reductions by week 12 than patients who did not (−1.46% vs. −1.28%), and higher incidence of anytime (24 hours; 73.3% vs. 35.7%) and nocturnal (00:00–06:00 hours; 30.0% vs. 11.9%) hypoglycaemia between weeks 13–24. Conclusions: The use of Gla-300 resulted in similar glycaemic control as IDeg-100 during the initial 12-week titration period of the BRIGHT study, when less anytime (24 hours) hypoglycaemia with Gla-300 versus IDeg-100 has been reported. Experiencing hypoglycaemia shortly after initiating Gla-300 or IDeg-100 may be associated with hypoglycaemia incidence in the longer term, potentially impacting glycaemic management

An Analysis by Synthesis Approach for Automatic Vertebral Shape Identification in Clinical QCT

Quantitative computed tomography (QCT) is a widely used tool for osteoporosis diagnosis and monitoring. The assessment of cortical markers like cortical bone mineral density (BMD) and thickness is a demanding task, mainly because of the limited spatial resolution of QCT. We propose a direct model based method to automatically identify the surface through the center of the cortex of human vertebra. We develop a statistical bone model and analyze its probability distribution after the imaging process. Using an as-rigid-as-possible deformation we find the cortical surface that maximizes the likelihood of our model given the input volume. Using the European Spine Phantom (ESP) and a high resolution \mu CT scan of a cadaveric vertebra, we show that the proposed method is able to accurately identify the real center of cortex ex-vivo. To demonstrate the in-vivo applicability of our method we use manually obtained surfaces for comparison.Comment: Presented on German Conference on Pattern Recognition (GCPR) 2018 in Stuttgar

Selection of Evolutionary Multicriteria Strategies: Application in Designing a Regional Water Restoration Management Plan

Sustainability of water resources has become a challenging problem worldwide, as the pollution levels of natural water resources (particularly of rivers) have increased drastically in the last decades. Nowadays, there are many Waste Water Treatment Plant (WWTP) technologies that provide different levels of efficiency in the removal of water pollutants, leading to a great number of combinations of different measures (PoM) or strategies. The management problem, then, involves finding which of these combinations are efficient, regarding the desired objectives (cost and quality). Therefore, decisions affecting water resources require the application of multi-objective optimization techniques which will lead to a set of tradeoff solutions, none of which is better or worse than the others, but, rather, the final decision must be one particular PoM including representative features of the whole set of solutions. Besides, there is not a universally accepted standard way to assess the water quality of a river. In order to consider simultaneously all these issues, we present in this work a hydroinformatics management tool, designed to help decision makers with the selection of a PoM that satisfies the WFD objectives. Our approach combines: 1) a Water Quality Model (WQM), devised to simulate the effects of each PoM used to reduce pollution pressures on the hydrologic network; 2) a Multi-Objective Evolutionary Algorithm (MOEA), used to identify efficient tradeoffs between PoMs’ costs and water quality; and 3) visualization of the Pareto optimal set, in order to extract knowledge from optimal decisions in a usable form. We have applied our methodology in a real scenario, the inner Catalan watersheds with promising results

Expression and functional activity of nucleoside transporters in human choroid plexus

Abstract Background Human equilibrative nucleoside transporters (hENTs) 1-3 and human concentrative nucleoside transporters (hCNTs) 1-3 in the human choroid plexus (hCP) play a role in the homeostasis of adenosine and other naturally occurring nucleosides in the brain; in addition, hENT1, hENT2 and hCNT3 mediate membrane transport of nucleoside reverse transcriptase inhibitors that could be used to treat HIV infection, 3'-azido-3'-deoxythymidine, 2'3'-dideoxycytidine and 2'3'-dideoxyinosine. This study aimed to explore the expression levels and functional activities of hENTs 1-3 and hCNTs 1-3 in human choroid plexus. Methods Freshly-isolated pieces of lateral ventricle hCP, removed for various clinical reasons during neurosurgery, were obtained under Local Ethics Committee approval. Quantification of mRNAs that encoded hENTs and hCNTs was performed by the hydrolysis probes-based reverse transcription real time-polymerase chain reaction (RT-qPCR); for each gene of interest and for 18 S ribosomal RNA, which was an endogenous control, the efficiency of PCR reaction (E) and the quantification cycle (Cq) were calculated. The uptake of [3H]inosine by the choroid plexus pieces was investigated to explore the functional activity of hENTs and hCNTs in the hCP. Results RT-qPCR revealed that the mRNA encoding the intracellularly located transporter hENT3 was the most abundant, with E-Cq value being only about 40 fold less that the E-Cq value for 18 S ribosomal RNA; mRNAs encoding hENT1, hENT2 and hCNT3 were much less abundant than mRNA for the hENT3, while mRNAs encoding hCNT1 and hCNT2 were of very low abundance and not detectable. Uptake of [3H]inosine by the CP samples was linear and consisted of an Na+-dependent component, which was probably mediated by hCNT3, and Na+-independent component, mediated by hENTs. The latter component was not sensitive to inhibition by S-(4-nitrobenzyl)-6-thioinosine (NBMPR), when used at a concentration of 0.5 μM, a finding that excluded the involvement of hENT1, but it was very substantially inhibited by 10 μM NBMPR, a finding that suggested the involvement of hENT2 in uptake. Conclusion Transcripts for hENT1-3 and hCNT3 were detected in human CP; mRNA for hENT3, an intracellularly located nucleoside transporter, was the most abundant. Human CP took up radiolabelled inosine by both concentrative and equilibrative processes. Concentrative uptake was probably mediated by hCNT3; the equilibrative uptake was mediated only by hENT2. The hENT1 transport activity was absent, which could suggest either that this protein was absent in the CP cells or that it was confined to the basolateral side of the CP epithelium.</p

Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action

In the present study, upon showing sexual dimorphism in dimethyl fumarate (DMF) efficacy to moderate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats, cellular and molecular substrate of this dimorphism was explored. In rats of both sexes, DMF administration from the day of immunization attenuated EAE severity, but this effect was more prominent in males leading to loss of the sexual dimorphism observed in vehicle-administered controls. Consistently, in male rats, DMF was more efficient in diminishing the number of CD4+ T lymphocytes infiltrating spinal cord (SC) and their reactivation, the number of IL-17+ T lymphocytes and particularly cellularity of their highly pathogenic IFN-gamma+GM-CSF+IL-17+ subset. This was linked with changes in SC CD11b+CD45+TCR alpha beta- microglia/proinflammatory monocyte progeny, substantiated in a more prominent increase in the frequency of anti-inflammatory phygocyting CD163+ cells and the cells expressing high surface levels of immunoregulatory CD83 molecule (associated with apoptotic cells phagocytosis and implicated in downregulation of CD4+ T lymphocyte reactivation) among CD11b+CD45+TCR alpha beta- cells in male rat SC. These changes were associated with greater increase in the nuclear factor (erythroid-derived 2)-like 2 expression in male rats administered with DMF. In accordance with the previous findings, DMF diminished reactive nitrogen and oxygen species generation and consistently, SC level of advanced oxidation protein products, to the greater extent in male rats. Overall, our study indicates sex-specificity in the sensitivity of DMF cellular and molecular targets and encourages sex-based clinical research to define significance of sex for action of therapeutic agents moderating autoimmune neuroinflammation-/oxidative stress-related nervous tissue damage

Comparative molecular biological analysis of membrane transport genes in organisms

Comparative analyses of membrane transport genes revealed many differences in the features of transport homeostasis in eight diverse organisms, ranging from bacteria to animals and plants. In bacteria, membrane-transport systems depend mainly on single genes encoding proteins involved in an ATP-dependent pump and secondary transport proteins that use H+ as a co-transport molecule. Animals are especially divergent in their channel genes, and plants have larger numbers of P-type ATPase and secondary active transporters than do other organisms. The secondary transporter genes have diverged evolutionarily in both animals and plants for different co-transporter molecules. Animals use Na+ ions for the formation of concentration gradients across plasma membranes, dependent on secondary active transporters and on membrane voltages that in turn are dependent on ion transport regulation systems. Plants use H+ ions pooled in vacuoles and the apoplast to transport various substances; these proton gradients are also dependent on secondary active transporters. We also compared the numbers of membrane transporter genes in Arabidopsis and rice. Although many transporter genes are similar in these plants, Arabidopsis has a more diverse array of genes for multi-efflux transport and for response to stress signals, and rice has more secondary transporter genes for carbohydrate and nutrient transport