Methylglyoxal, A Metabolite Increased in Diabetes is Associated with Insulin Resistance, Vascular Dysfunction and Neuropathies

The published manuscript is available at EurekaSelect via http://www.eurekaselect.com/openurl/content.php?genre=article&doi=10.2174/1389200217666151222155216 © 2018 Bentham Science PublishersBackground: Diabetes mellitus (DM) is a pandemic metabolic disease characterized by a chronically elevated blood glucose concentration (hyperglycemia) due to insulin dysfunction. Approximately 50% of diabetics show diabetes complications by the time they are diagnosed. Vascular dysfunction, nephropathy and neuropathic pain are common diabetes complications. Chronic hyperglycemia contributes to reactive oxygen species (ROS) generation such as methylglyoxal (MGO). Methods: Peer reviewed research papers were studied through bibliographic databases searching focused on review questions and inclusion/exclusion criteria. The reviewed papers were appraised according to the searching focus. The characteristics of screened papers were described, and a deductive qualitative content analysis methodology was applied to the included studies using a conceptual framework to yield this comprehensive systematic review. Results: Sixty-six papers were included in this review. Eleven papers related methylglyoxal generation to carbohydrates metabolism, ten papers related lipid metabolism to methylglyoxal and 5 papers showed the proteolytic pathways that contribute to methylglyoxal generation. Methylglyoxal metabolism was derived from 7 papers. Descriptive figure 1 was drawn to explain methylglyoxal sources and how diabetes increases methylglyoxal generation. Furthermore, twenty-six papers related methylglyoxal to diabetes complications from which 9 papers showed methylglyoxal ability to induce insulin dysfunction, an effect which was described in schematic figure 2. Additionally, fifteen papers revealed methylglyoxal contribution to vascular dysfunction and 3 papers showed methylglyoxal to cause neuropathic pain. Methylglyoxal-induced vascular dysfunction was drawn in a comprehensive figure 3. This review correlated methylglyoxal with diabetes and diabetes complications which were summarised in table 1. Conclusion: The findings of this review suggesting methylglyoxal as an essential therapeutic target for managing diabetes in the future.Peer reviewedFinal Accepted Versio

A comparison of handwritten and computer-assisted prescriptions in an intensive care unit

BACKGROUND: We conducted a prospective comparative study to evaluate the potential benefit of computer-assisted prescribing (CAP). We compared the accuracy, completeness and time use of CAP with that of conventional handwritten prescribing at the intensive care unit (ICU) of the John Radcliffe Hospital, Oxford, UK. RESULTS: Twenty-five clinicians and 2409 drug entries were evaluated for accuracy, completeness, legibility and time spent prescribing. One hundred and twenty-eight handwritten and 110 CAP charts were monitored. One hundred percent of CAP charts were complete compared to 47% of handwritten charts.Drug prescriptions were divided into three categories: intravenous fluids, intravenous infusions and intermittent drugs. Percentage of correct entries in each category were 64%, 47.5% and 90% for handwritten, compared to 48%, 32% and 90% for CAP charts, respectively.The mean time taken to prescribe was 20 s for hand written prescribing and 55 s for CAP. CONCLUSIONS: Computer-assisted prescriptions were more complete, signed and dated than handwritten prescriptions. Errors in prescribing, including failure to discontinue a drug were not reduced by CAP. Handwritten prescribing was quicker than CAP. Simple enhancements of the computer software could be introduced which might overcome these deficiencies. CAP was successfully integrated into clinical practice in the ICU

Synthesis and Spectral Characterization of Benzo[6,7] [1,5]diazocino[2,1-a]isoindol-12-(14H)-one Derivatives

© 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).A simple synthetic route to benzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one ring system is developed from readily available starting materials 3-(2-oxo-2-phenylethyl) isobenzofuran-1(3H)-ones and 2-(aminomethyl)aniline catalysed by para-toluenesulfonic acid in toluene in 27-85% yields. The 1H- and 13C-NMR spectra of the final products were assigned using a variety of one and two-dimensional NMR experiments. The distinction between the two potential isomers of the final products was made on the basis of heteronuclear multiple bond connectivity NMR spectra (HMBC).Peer reviewe

EC02-179 Managing Livestock Manure to Protect Environmental Quality

This book covers the land application part of manure management. With increasing regulations, the livestock producer needs to understand the scientific principles that affect manure transformations and how to use these principles to manage the manure for maximum fertilizer value with minimal environmental impact. Improved land application of manure is one part of the solution, but we suggest that the producer evaluate the quantity of nutrients arriving on the farm as feed, animals, and fertilizer compared to the total that is exported. Achieving a nutrient balance will reduce potential environmental hazards often associated with animal agriculture

Contribution of a mutational hot spot to hemoglobin adaptation in high-altitude Andean house wrens

A key question in evolutionary genetics is why certain mutations or certain types of mutation make disproportionate contributions to adaptive phenotypic evolution. In principle, the preferential fixation of particular mutations could stem directly from variation in the underlying rate of mutation to function-altering alleles. However, the influence of mutation bias on the genetic architecture of phenotypic evolution is difficult to evaluate because data on rates of mutation to function-altering alleles are seldom available. Here, we report the discovery that a single point mutation at a highly mutable site in the βA-globin gene has contributed to an evolutionary change in hemoglobin (Hb) function in high-altitude Andean house wrens (Troglodytes aedon). Results of experiments on native Hb variants and engineered, recombinant Hb mutants demonstrate that a nonsynonymous mutation at a CpG dinucleotide in the βA-globin gene is responsible for an evolved difference in Hb–O2 affinity between high- and low-altitude house wren populations. Moreover, patterns of genomic differentiation between high- and low-altitude populations suggest that altitudinal differentiation in allele frequencies at the causal amino acid polymorphism reflects a history of spatially varying selection. The experimental results highlight the influence of mutation rate on the genetic basis of phenotypic evolution by demonstrating that a large-effect allele at a highly mutable CpG site has promoted physiological differentiation in blood O2 transport capacity between house wren populations that are native to different elevations

Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study.

Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (Emax ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes

Intentional and unintentional medication non-adherence in psoriasis: The role of patients’ medication beliefs and habit strength

Medication non-adherence is a missed opportunity for therapeutic benefit. We assessed “real-world” levels of self-reported non-adherence to conventional and biologic systemic therapies used for psoriasis and evaluated psychological and biomedical factors associated with non-adherence using multivariable analyses. Latent profile analysis was used to investigate whether patients can be categorized into groups with similar medication beliefs. Latent profile analysis categorizes individuals with similar profiles on a set of continuous variables into discrete groups represented by a categorical latent variable. Eight hundred and eleven patients enrolled in the British Association of Dermatologists Biologic Interventions Register were included. Six hundred and seventeen patients were using a self-administered systemic therapy; 22.4% were classified as “non-adherent” (12% intentionally and 10.9% unintentionally). Patients using an oral conventional systemic agent were more likely to be non-adherent compared to those using etanercept or adalimumab (29.2% vs. 16.4%; P ≤ 0.001). Latent profile analysis supported a three-group model; all groups held strong beliefs about their need for systemic therapy but differed in levels of medication concerns. Group 1 (26.4% of the sample) reported the strongest concerns, followed by Group 2 (61%), with Group 3 (12.6%) reporting the weakest concerns. Group 1 membership was associated with intentional non-adherence (odds ratio = 2.27, 95% confidence interval = 1.16−4.47) and weaker medication-taking routine or habit strength was associated with unintentional non-adherence (odds ratio = 0.92, 95% confidence interval = 0.89−0.96). Medication beliefs and habit strength are modifiable targets for strategies to improve adherence in psoriasis

Different applications of concept maps in Higher Education

Purpose: The aim of this work is to show different applications of concept maps in higher education, concretely in qualifications of the Polytechnic University of Valencia. Design/methodology/approach: Different methodologies have been used depending on the application of concept maps: as evaluation tool, as knowledge organizing tool, and as meaningful learning tool. Findings: Students consider the concept maps useful principally to select key ideas, to achieve a comprehensive view of the lesson, and to bring up the subject. Moreover, concept maps promote the meaningful and active learning, help students to understand, follow-up, and learn subjects with a high load of contents. Research limitations/implications: The most important limitation is the use of the concept maps in subjects with a high number of students. Practical implications: The realization of concept maps allows the student to develop generic competences. Originality/value: The originality of this work is to show how a same tool can be used in different subjects of different qualifications. © Journal of Industrial Engineering and Management, 2011.Bes Piá, A.; Blasco-Tamarit, E.; Muñoz Portero, MJ. (2011). Different applications of concept maps in Higher Education. Journal of Industrial Engineering and Management. 4(1):81-102. doi:10.3926/jiem.2011.v4n1.p81-102Senia811024