Arene oxidation with malonoyl peroxides

Malonoyl peroxide 7, prepared in a single step from the commercially available diacid, is an effective reagent for the oxidation of aromatics. Reaction of an arene with peroxide 7 at room temperature leads to the corresponding protected phenol which can be unmasked by aminolysis. An ionic mechanism consistent with the experimental findings and supported by isotopic labeling, Hammett analysis, EPR investigations and reactivity profile studies is proposed

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Assessing glycemia in type 1 diabetic patients using a microdialysis system for continuous glucose monitoring

Background: Continuous glucose monitoring systems can monitor moment-to-moment changes in blood glucose concentration, which cannot be detected by intermittent self-monitoring. Continuing monitoring sys--tems may lead to improved glycemic control. We evaluated a microdialysis technique for improving glycemic control in type 1 diabetes patients treated by different means of basal insulin substitution. Patients and Methods: Fifty-two type 1 diabetic patients on twice daily NPH and pre-meal aspart insulin were randomized in two groups: the continuation of NPH (n=26) (group 1) or once daily glargine (n=26) (group 2). 48-hour GlucoDay registrations were started at the beginning and after 4 months. Results: At baseline, time spent in the euglycemic range (glucose between 3.9 and 8.0mmol/L) was 37.96±6.81% for the NPH group and 35.83±6.24% for the glargine group. At endpoint, time in the euglyce--mic range increased in both groups (51.02±7.22% and 57.29±10.27%, P< 0.001 vs. before treatment for both groups). Time spent in the hypoglycemic range (glucose < 3.9 mmol/L) was 9.98±2.57% for the first group and 10.24±3.55% for the second group at baseline. At endpoint, time in the hypoglycemic range decreased in both groups (8.00±2.13% and 6.59±2.04%, P< 0.001 vs. before treatment for both groups). Conclusion: The analysis of the GlucoDay data gave us information about glycemia other than HbA1c and self-monitoring of blood glucose, such us a peakless activity profile and the lower percentage of time spent in the hypoglycemic range in the glargine-treated group

Characterization of PicoGreen Interaction with dsDNA and the Origin of Its Fluorescence Enhancement upon Binding

PicoGreen is a fluorescent probe that binds dsDNA and forms a highly luminescent complex when compared to the free dye in solution. This unique probe is widely used in DNA quantitation assays but has limited application in biophysical analysis of DNA and DNA-protein systems due to limited knowledge pertaining to its physical properties and characteristics of DNA binding. Here we have investigated PicoGreen binding to DNA to reveal the origin and mode of PicoGreen/DNA interactions, in particular the role of electrostatic and nonelectrostatic interactions in formation of the complex, as well as demonstrating minor groove binding specificity. Analysis of the fluorescence properties of free PicoGreen, the diffusion properties of PG/DNA complexes, and the excited-state lifetime changes upon DNA binding and change in solvent polarity, as well as the viscosity, reveal that quenching of PicoGreen in the free state results from its intramolecular dynamic fluctuations. On binding to DNA, intercalation and electrostatic interactions immobilize the dye molecule, resulting in a >1000-fold enhancement in its fluorescence. Based on the results of this study, a model of PicoGreen/DNA complex formation is proposed

Baseline level of platelet-leukocyte aggregates, platelet CD63 expression, and soluble P-selectin concentration in patients with posttraumatic stress disorder: a pilot study

Platelets may have an important role in the development of cardiovascular disease (CVD) as a result of chronic stress. We conducted a pilot study to evaluate the effect of posttraumatic stress disorder (PTSD) on baseline platelet activation. Platelet-leukocyte aggregates (PLA) and CD63 expression were measured by flow cytometry, and soluble (s)P-selectin concentration was determined in sera of 20 Croatian male combat veterans with PTSD and 20 healthy civilians. Groups were matched in sex, age, body mass index (BMI) and traditional CVD risk factors. Our data showed no differences in measured parameters. Other platelet activation markers should be determined and a larger sample size used in future studies

Past, present, and future of informed consent in pain and genomics research: Challenges facing global medical community

In recent decades, there has been a revision of the role of institutional review boards with the intention of protecting human subjects from harm and exploitation in research. Informed consent aims to protect the subject by explaining all of the benefits and risks associated with a specific research project. To date, there has not been a review published analyzing issues of informed consent in research in the field of genetic/Omics in subjects with chronic pain, and the current review aims to fill that gap in the ethical aspects of such investigation. Despite the extensive discussion on ethical challenges unique to the field of genetic/Omics, this is the first attempt at addressing ethical challenges regarding Informed Consent Forms for pain research as the primary focus. We see this contribution as an important one, for while ethical issues are too often ignored in pain research in general, the numerous arising ethical issues that are unique to pain genetic/Omics suggest that researchers in the field need to pay even greater attention to the rights of subjects/patients. This article presents the work of the Ethic Committee of the Pain-Omics Group (www.painomics.eu), a consortium of 11 centers that is running the Pain-Omics project funded by the European Community in the 7th Framework Program theme (HEALTH.2013.2.2.1-5—Understanding and controlling pain). The Ethic Committee is composed of 1 member of each group of the consortium as well as key opinion leaders in the field of ethics and pain more generally