Search results for "Life Sciences & Biomedicine"
showing 10 items of 253 documents
DNA Methylation and Non-Coding RNAs during Tissue-Injury Associated Pain.
2022
While about half of the population experience persistent pain associated with tissue damages during their lifetime, current symptom-based approaches often fail to reduce such pain to a satisfactory level. To provide better patient care, mechanism-based analgesic approaches must be developed, which necessitates a comprehensive understanding of the nociceptive mechanism leading to tissue injury-associated persistent pain. Epigenetic events leading the altered transcription in the nervous system are pivotal in the maintenance of pain in tissue injury. However, the mechanisms through which those events contribute to the persistence of pain are not fully understood. This review provides a summar…
Epidemiology of intra-abdominal infection and sepsis in critically ill patients: "AbSeS", a multinational observational cohort study and ESICM Trials…
2019
Pardo-Oviedo, Juan Mauricio/0000-0003-0084-3449; Lopez-Delgado, Juan Carlos/0000-0003-3324-1129; Corradi, Francesco/0000-0002-5588-2608; De Backer, Daniel/0000-0001-9841-5762; POTA, VINCENZO/0000-0001-9999-3388; Tomescu, Dana/0000-0001-9673-5754; Sabetian, Golnar/0000-0001-8764-2150; Girardis, Massimo/0000-0002-2453-0829; Brazzi, Luca/0000-0001-7059-0622; Leone, Marc/0000-0002-3097-758X; Zabolotskikh, Igor Borisovich/0000-0002-3623-2546; De Lange, Dylan/0000-0002-0191-7270; ALMEKHLAFI, GHALEB A./0000-0002-0323-7025; Elke, Gunnar/0000-0002-4948-1605; Grigoras, Ioana/0000-0001-9412-9574; Czuczwar, Miroslaw/0000-0002-9025-6717; Nora, David/0000-0002-1133-7368; Masjedi, Mansoor/0000-0001-6175-9…
Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes.
2017
BACKGROUND Degludec is an ultralong-Acting, once-daily basal insulin that is approved for use in adults, adolescents, and children with diabetes. Previous open-label studies have shown lower day-To-day variability in the glucose-lowering effect and lower rates of hypoglycemia among patients who received degludec than among those who received basal insulin glargine. However, data are lacking on the cardiovascular safety of degludec. METHODS We randomly assigned 7637 patients with type 2 diabetes to receive either insulin degludec (3818 patients) or insulin glargine U100 (3819 patients) once daily between dinner and bedtime in a double-blind, treat-To-Target, event-driven cardiovascular outco…
Pliocene colonization of the Mediterranean by Great White Shark inferred from fossil records, historical jaws, phylogeographic and divergence time an…
2020
Aim: Determine the evolutionary origin of the heretofore poorly characterized contemporary Great White Shark (GWS; Carcharodon carcharias) of the Mediterranean Sea, using phylogenetic and dispersal vicariance analyses to trace back its global palaeo-migration pattern. Location: Mediterranean Sea. Taxon: Carcharodon carcharias. Methods: We have built the largest mitochondrial DNA control region (CR) sequence dataset for the Mediterranean GWS from referenced historical jaws spanning the 19th and 20th centuries. Mediterranean and global GWS CR sequences were analysed for genetic diversity, phylogenetic relationships and divergence time. A Bayes factor approach was used to assess two scenarios …
eNOS S-nitrosylates β-actin on Cys374 and regulates PKC-θ at the immune synapse by impairing actin binding to profilin-1.
2017
The actin cytoskeleton coordinates the organization of signaling microclusters at the immune synapse (IS); however, the mechanisms involved remain poorly understood. We show here that nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) controls the coalescence of protein kinase C-¿ (PKC-¿) at the central supramolecular activation cluster (c-SMAC) of the IS. eNOS translocated with the Golgi to the IS and partially colocalized with F-actin around the c-SMAC. This resulted in reduced actin polymerization and centripetal retrograde flow of ß-actin and PKC-¿ from the lamellipodium-like distal (d)-SMAC, promoting PKC-¿ activation. Furthermore, eNOS-derived NO S-nitrosylated ß-…
An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs.
2021
[BACKGROUND & AIMS] Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intra-hepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. [METHODS] We combined new and existing genotype data for 10, 516 cases and 20, 77…
The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017 : a systematic analysis for the Global Bu…
2020
Background\ud \ud Cirrhosis and other chronic liver diseases (collectively referred to as cirrhosis in this paper) are a major cause of morbidity and mortality globally, although the burden and underlying causes differ across locations and demographic groups. We report on results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 on the burden of cirrhosis and its trends since 1990, by cause, sex, and age, for 195 countries and territories.\ud \ud \ud \ud Methods\ud \ud We used data from vital registrations, vital registration samples, and verbal autopsies to estimate mortality. We modelled prevalence of total, compensated, and decompensated cirrhosis on the bas…
Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000-17: analysis for th…
2020
Background: Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods: We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuri…
Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
2020
AbstractThere are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of …
Prognostic Factors in Childhood Anaplastic Large Cell Lymphoma: Long Term Results of the International ALCL99 Trial
2020
With the aim of describing the long-term follow-up and to define the prognostic role of the clinical/pathological/molecular characteristics at diagnosis for childhood, adolescent and young adults affected by anaplastic large cell lymphoma (ALCL), we analyzed 420 patients aged up to 22 years homogeneously treated within the international ALCL99 trial. The 10-year progression free survival (PFS) was 70% and overall survival was 90%, rare late relapses occurred but no secondary malignancies were reported. Among clinical/pathological characteristics, only patients presenting a small cell/lymphohistiocytic (SC/LH) pattern were independently associated with risk of failure (hazard ratio = 2.49). …