Search results for "Models"
showing 10 items of 8211 documents
Engineering approaches in siRNA delivery.
2017
siRNAs are very potent drug molecules, able to silence genes involved in pathologies development. siRNAs have virtually an unlimited therapeutic potential, particularly for the treatment of inflammatory diseases. However, their use in clinical practice is limited because of their unfavorable properties to interact and not to degrade in physiological environments. In particular they are large macromolecules, negatively charged, which undergo rapid degradation by plasmatic enzymes, are subject to fast renal clearance/hepatic sequestration, and can hardly cross cellular membranes. These aspects seriously impair siRNAs as therapeutics. As in all the other fields of science, siRNAs management ca…
Consequences of single-locus and tightly linked genomic architectures for evolutionary responses to environmental change
2020
AbstractGenetic and genomic architectures of traits under selection are key factors influencing evolutionary responses. Yet, knowledge of their impacts has been limited by a widespread assumption that most traits are controlled by unlinked polygenic architectures. Recent advances in genome sequencing and eco-evolutionary modelling are unlocking the potential for integrating genomic information into predictions of population responses to environmental change. Using eco-evolutionary simulations, we demonstrate that hypothetical single-locus control of a life history trait produces highly variable and unpredictable harvesting-induced evolution relative to the classically applied multi-locus mo…
New Therapeutic Implications of Endothelial Nitric Oxide Synthase (eNOS) Function/Dysfunction in Cardiovascular Disease
2019
The Global Burden of Disease Study identified cardiovascular risk factors as leading causes of global deaths and life years lost. Endothelial dysfunction represents a pathomechanism that is associated with most of these risk factors and stressors, and represents an early (subclinical) marker/predictor of atherosclerosis. Oxidative stress is a trigger of endothelial dysfunction and it is a hall-mark of cardiovascular diseases and of the risk factors/stressors that are responsible for their initiation. Endothelial function is largely based on endothelial nitric oxide synthase (eNOS) function and activity. Likewise, oxidative stress can lead to the loss of eNOS activity or even “uncoupli…
Type of chromosome abnormality affects embryo morphology dynamics.
2016
Objective To study the differences in the cleavage time between types of embryo chromosomal abnormalities and elaborate algorithm to exclude aneuploid embryos according to the likelihood to be euploid. Design Retrospective cohort study. Setting University affiliated private center. Patient(s) Preimplantational genetic screening patients (n = 112) including cases of advanced maternal age, repeated implantation failure, and recurrent miscarriage. A total of 485 embryos were analyzed. Intervention(s) None. Main Outcome Measure(s) All biopsied embryos were cultured in an incubator with time-lapse technology, cleavage timing from insemination to day 3 and all kinetic parameters that have been de…
Hepatitis delta virus infection in a large cohort of chronic hepatitis B patients in Ethiopia.
2017
Background Hepatitis D Virus (HDV)-infection is associated with a more severe outcome in patients with chronic hepatitis B (CHB); however, little is known about the presence of HDV in sub-Saharan Africa. We aimed to determine the prevalence of HDV-infection, as well as its clinical, biological and virological characteristics, in a large CHB cohort in Ethiopia. Methods In total, 1267 HIV-negative CHB patients at St. Paul's Hospital Millennium Medical College in Addis Ababa were screened for anti-HDV antibodies using ELISA assays. Confirmed positive samples were further tested for HDV RNA using a consensus commercial real-time RT-PCR assay. HDV genotypes were also determined for RNA positive …
Succinate receptor mediates intestinal inflammation and fibrosis.
2018
Succinate, an intermediate of the tricarboxylic acid cycle, is accumulated in inflamed areas and its signaling through succinate receptor (SUCNR1) regulates immune function. We analyze SUCNR1 expression in the intestine of Crohn's disease patients and its role in murine intestinal inflammation and fibrosis. We show that both serum and intestinal succinate levels and SUCNR1 expression in intestinal surgical resections were higher in CD patients than in controls. SUCNR1 co-localized with CD86, CD206, and alpha-SMA(+) cells in human intestine and we found a positive and significant correlation between SUCNR1 and alpha-SMA expression. In human isolated fibroblasts from CD patients SUCNR1 expres…
The torso integration hypothesis revisited in Homo sapiens: Contributions to the understanding of hominin body shape evolution.
2018
Objectives: Lower thoracic widths and curvatures track upper pelvic widths and iliac blades curvatures in hominins and other primates (torso integration hypothesis). However, recent studies suggest that sexual dimorphism could challenge this assumption in Homo sapiens. We test the torso integration hypothesis in two modern human populations, both considering and excluding the effect of sexual dimorphism. We further assess covariation patterns between different thoracic and pelvic levels, and we explore the allometric effects on torso shape variation. Material and Methods: A sex-balanced sample of 50 anatomically connected torsos (25 Mediterraneans, 25 Sub-Saharan Africans) was segmented fro…
Coffee consumption and total mortality in a Mediterranean prospective cohort
2018
Background The relation of coffee consumption with total mortality is controversial, because the available evidence is still inconsistent. Objective This study aimed to assess this association in a highly educated, middle-aged Mediterranean cohort. Design We analyzed data from 201,055 person-years of follow-up arising from 19,888 participants. Coffee consumption was obtained at baseline with the use of a previously validated semiquantitative food-frequency questionnaire. Information on mortality was ascertained by permanent contact with the "Seguimiento Universidad de Navarra" (SUN) participants and their families, postal authorities, and consultation of the National Death Index. We used Co…
Adjuvant chemotherapy and relative survival of patients with stage II colon cancer - A EURECCA international comparison between the Netherlands, Denm…
2016
BACKGROUND: The aim of the present EURECCA international comparison is to compare adjuvant chemotherapy and relative survival of patients with stage II colon cancer between European countries.METHODS: Population-based national cohort data (2004-2009) from the Netherlands (NL), Denmark (DK), Sweden (SE), England (ENG), Ireland (IE), and Belgium (BE) were obtained, as well as single-centre data from Lithuania. All surgically treated patients with stage II colon cancer were included. The proportion of patients receiving adjuvant chemotherapy was calculated and compared between countries. Besides, relative survival was calculated and compared between countries.RESULTS: Overall, 59,154 patients …
Rescuing Over-activated Microglia Restores Cognitive Performance in Juvenile Animals of the Dp(16) Mouse Model of Down Syndrome.
2020
Microglia are brain-resident immune cells and regulate mechanisms essential for cognitive functions. Down syndrome (DS), the most frequent cause of genetic intellectual disability, is caused by a supernumerary chromosome 21, containing also genes related to the immune system. In the hippocampus of the Dp(16) mouse model of DS and DS individuals, we found activated microglia, as assessed by their morphology; activation markers; and, for DS mice, electrophysiological profile. Accordingly, we found increased pro-inflammatory cytokine levels and altered interferon signaling in Dp(16) hippocampi. DS mice also showed decreased spine density and activity of hippocampal neurons and hippocampus-depe…