Phosphoramidates and phosphonamidates (ProTides) with antiviral activity

Following the first report on the nucleoside phosphoramidate (ProTide) prodrug approach in 1990 by Chris McGuigan, the extensive investigation of ProTide technology has begun in many laboratories. Designed with aim to overcome limitations and the key resistance mechanisms associated with nucleoside analogues used in the clinic (poor cellular uptake, poor conversion to the 5′-monophosphate form), the ProTide approach has been successfully applied to a vast number of nucleoside analogues with antiviral and anticancer activity. ProTides consist of a 5′-nucleoside monophosphate in which the two hydroxyl groups are masked with an amino acid ester and an aryloxy component which once in the cell is enzymatically metabolized to deliver free 5′-monophosphate, which is further transformed to the active 5′-triphosphate form of the nucleoside analogue. In this review, the seminal contribution of Chris McGuigan’s research to this field is presented. His technology proved to be extremely successful in drug discovery and has led to two Food and Drug Administration-approved antiviral agents

Fire mediated geochemical alterations in Andosol’s SOM under Canarian Pine (Pinus canariensis) forest

4 páginas, 1 figura, 2 tablas, 26 referencias.-- FUEGORED 2010.-- Jornadas Internacionales celebradas del 6-10 de octubre 2010, en Santiago de Compostela, España.Peer reviewe

ERODIBILITY OF FOREST ANDOSOLS AND SOIL PROPERTIES

Abstract The sensitivity of Andosols to water erosion in a forest environment (Garajonay National Park, Gomera, Canary Islands) has been studied by evaluating USLE's erodibility factor (K), the actual susceptibility of soil to separation by means of two tests for measuring the stability of aggregates, and its relationship with relevant physicochemical properties. The results show the limited validity of the conventional estimation of erodibility in andic soils, where the sensitivity towards erosion is mostly related to their content in organometallic compounds

Ablation Strategies for Different Types of Atrial Fibrillation in Europe: Results of the ESC-EORP EHRA Atrial Fibrillation Ablation Long-Term Registry

Aims: The ESC EORP EHRA Atrial Fibrillation (AF) Ablation Long-Term registry was designed to assess management and outcomes of AF catheter ablation procedures in Europe. To investigate the current ablation approaches and their outcomes for patients with paroxymal AF (PAF) and non-PAF in Europe. Methods and results: Data from index ablations were collected in 27 European countries at 104 centres in a prospective fashion. Pre-procedural, procedural, and 1-year follow-up data were captured on a web-based electronic case record form. Data on the ablation procedure were available for 3446 patients. Of these, 2513 patients and 933 patients underwent pulmonary vein isolation (PVI) or PVI plus (PVIplus) additional ablation, respectively. The ablation strategy was limited to PVI in 81% and 56% of patients in the PAF and non-PAF group, respectively (P < 0.001). In the non-PAF group, left atrial linear ablation and ablation of complex fragmented atrial electrograms were more commonly performed. Arrhythmias recurrence after PVI was 29% and 39% in the PAF and non-PAF group, respectively (P < 0.001) and 42% after PVIplus in both groups. Atrial fibrillation related hospital admissions were more common in the PVIplus group (20% vs. 14%). A very low procedural complication rate was observed. No relevant differences were observed with regard to repeat ablation (PVI 9% and PVIplus 11%). Conclusion: In patients with PAF and non-PAF, the ablation strategies of PVI and PVIplus led to similar arrhythmia-free survival rates after 1 year. A considerable hospital readmission rate was noted.info:eu-repo/semantics/publishedVersio

Sudden Cardiac Death and Copy Number Variants: What Do We Know after 10 Years of Genetic Analysis?

Over the last ten years, analysis of copy number variants has increasingly been applied to the study of arrhythmogenic pathologies associated with sudden death, mainly due to significant advances in the field of massive genetic sequencing. Nevertheless, few published reports have focused on the prevalence of copy number variants associated with sudden cardiac death. As a result, the frequency of these genetic alterations in arrhythmogenic diseases as well as their genetic interpretation and clinical translation has not been established. This review summarizes the current available data concerning copy number variants in sudden cardiac death-related diseases

HRS/EHRA/APHRS/LAHRS/ACC/AHA worldwide practice update for telehealth and arrhythmia monitoring during and after a pandemic

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), started in the city of Wuhan late in 2019. Within a few months, the disease spread toward all parts of the world and was declared a pandemic on March 11, 2020. The current health care dilemma worldwide is how to sustain the capacity for quality services not only for those suffering from COVID-19 but also for non-COVID-19 patients, all while protecting physicians, nurses, and other allied health care workers

World Heart Federation Roadmap on Atrial Fibrillation - A 2020 Update

The World Heart Federation (WHF) commenced a Roadmap initiative in 2015 to reduce the global burden of cardiovascular disease and resultant burgeoning of healthcare costs. Roadmaps provide a blueprint for implementation of priority solutions for the principal cardiovascular diseases leading to death and disability. Atrial fibrillation (AF) is one of these conditions and is an increasing problem due to ageing of the world’s population and an increase in cardiovascular risk factors that predispose to AF. The goal of the AF roadmap was to provide guidance on priority interventions that are feasible in multiple countries, and to identify roadblocks and potential strategies to overcome them. Since publication of the AF Roadmap in 2017, there have been many technological advances including devices and artificial intelligence for identification and prediction of unknown AF, better methods to achieve rhythm control, and widespread uptake of smartphones and apps that could facilitate new approaches to healthcare delivery and increasing community AF awareness. In addition, the World Health Organisation added the non-vitamin K antagonist oral anticoagulants (NOACs) to the Essential Medicines List, making it possible to increase advocacy for their widespread adoption as therapy to prevent stroke. These advances motivated the WHF to commission a 2020 AF Roadmap update. Three years after the original Roadmap publication, the identified barriers and solutions were judged still relevant, and progress has been slow. This 2020 Roadmap update reviews the significant changes since 2017 and identifies priority areas for achieving the goals of reducing death and disability related to AF, particularly targeted at low-middle income countries. These include advocacy to increase appreciation of the scope of the problem; plugging gaps in guideline management and prevention through physician education, increasing patient health literacy, and novel ways to increase access to integrated healthcare including mHealth and digital transformations; and greater emphasis on achieving practical solutions to national and regional entrenched barriers. Despite the advances reviewed in this update, the task will not be easy, but the health rewards of implementing solutions that are both innovative and practical will be great