Search results for "Genesis"
showing 10 items of 12136 documents
Inflammatory cytokines shape a changing DNA methylome in monocytes mirroring disease activity in rheumatoid arthritis
2019
Objective: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that mainly targets joints. Monocytes and macrophages are critical in RA pathogenesis and contribute to inflammatory lesions. These extremely plastic cells respond to extracellular signals which cause epigenomic changes that define their pathogenic phenotype. Here, we interrogated how DNA methylation alterations in RA monocytes are determined by extracellular signals. Methods: High-throughput DNA methylation analyses of patients with RA and controls and in vitro cytokine stimulation were used to investigate the underlying mechanisms behind DNA methylation alterations in RA as well as their relationship with clinic…
Rho GTPases are over-expressed in human tumors.
1999
Small GTPases of the Rho family are involved in the regulation of a variety of cellular processes, such as the organization of the microfilamental network, cell-cell contact and malignant transformation. To address the question of whether Rho proteins are involved in carcinogenesis in man, we compared their expression in tumors from colon, breast and lung with that of the corresponding normal tissue originating from the same patient. As shown by Rho-specific 32P-ADP-ribosylation, as well as Western-blot analysis, the amount of RhoA protein was largely increased in all 3 types of tumors tested. The most dramatic differences in the expression of Rho GTPases were observed in breast tissue. All…
Road network characterization to understand city evolution
2021
International audience; Cities combine different kind of processes that drive their evolution. It is of a great interest to understand the effects of different kinds of spatial patterns on those processes, to be able to minimize space consumption and optimize mobility and transportation.In this research, we aim to contribute to the understanding of city evolution by a focus on the road network of the Eastern French city of Dijon’s. Firstly, we select three network indicators that can be used to characterize the city structure as it grows. We apply these indicators to Dijon’s historical road networks from 1650 until 2019. Finally, we discuss how we can use computational simulations of city g…
Fosildiagénesis del anélido Rotularia spirulaea (Lamarck, 1818) (Polychaeta, Serpulidae) en el Eoceno del dominio pirenaico occidental
2018
The presence of the fossil polychaete Rotularia spirulaea (Lamarck, 1818) in Eocene deposits (middle Lutecian – upper Bartonian and (?) Priabonian) belonging to the western Pyrenean Domain is verified. In this paper, a fossildiagenetic study has been carried out. Fossils from three areas, corresponding to diff erent depositional settings, have been analysed. In area 1, sediments of the Ardanatz Sandstone and Ilundain Marls formations [Pamplona Basin and adjoining areas (Navarre)], were sampled. Here, the specimens of R. spirulaea were not substantially affected by taphonomic reworking and the original microstructure of the carbonate tube is preserved. The test consists of a thick external …
Study of the Strengths and Weaknesses of Nursing Work Environments in Primary Care in Spain
2021
Background: Nursing work environments are defined as the characteristics of the workplace that promote or hinder the provision of professional care by nurses. Positive work environments lead to better health outcomes. Our study aims to identify the strengths and weaknesses of primary health care settings in Spain. Methods: Cross-sectional study carried out from 2018 to 2019. We used the Practice Environment Scale of the Nursing Work Index and the TOP10 Questionnaire of Assessment of Environments in Primary Health Care for data collection. The associations between sociodemographic and professional variables were analyzed. Results: In total, 702 primary care nurses participated in the study. …
Long-term safety of nine systemic medications for psoriasis: A cohort study using the Spanish Registry of Adverse Events for Biological Therapy in De…
2020
Background: Registry studies broadly describing the safety of systemic drugs in psoriasis are needed. Objective: To describe the safety findings of the systemic drugs acitretin, adalimumab, apremilast, cyclosporine, etanercept, infliximab, methotrexate, secukinumab, and ustekinumab used for the treatment of moderate to severe psoriasis in patients included in the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry. Methods: The incidence rate ratio (IRR) and adjusted IRR (including propensity scores) of identified adverse events for each drug, using methotrexate as reference, were determined by means of a prospective cohort. Results: O…
Abemaciclib: safety and effectiveness of a unique cyclin-dependent kinase inhibitor
2020
Introduction: The discovery and the clinical availability of novel cyclin-dependent kinases 4 and 6 inhibitors have profoundly changed the therapeutic scenario of metastatic hormone receptor-positive breast carcinoma. Among these inhibitors, abemaciclib can induce potent and sustained cell cycle arrest and immune system stimulation. Areas covered: This review summarizes the safety profile and clinical efficacy data on abemaciclib alone or in combination with aromatase inhibitors or fulvestrant in metastatic hormone receptor-positive breast carcinoma. The management of patients treated with abemaciclib is the object of this paper. Expert opinion: As shown in phase 2 and 3 clinical trials on …
Safety and immunogenicity of the PRAME cancer immunotherapeutic in metastatic melanoma: results of a phase I dose escalation study
2016
Purpose The PRAME tumour antigen is expressed in several tumour types but in few normal adult tissues. A dose-escalation phase I/II study (NCT01149343) assessed the safety, immunogenicity and clinical activity of the PRAME immunotherapeutic (recombinant PRAME protein (recPRAME) with the AS15 immunostimulant) in patients with advanced melanoma. Here, we report the phase I dose-escalation study segment. Patients and methods Patients with stage IV PRAME-positive melanoma were enrolled to 3 consecutive cohorts to receive up to 24 intramuscular injections of the PRAME immunotherapeutic. The RecPRAME dose was 20, 100 or 500 µg in cohorts 1, 2 and 3, respectively, with a fixed dose of AS15. Advers…
Polyphenols and Pharmacological Screening of a Monarda fistulosa L. dry Extract Based on a Hydrodistilled Residue By-Product
2021
This study aimed to determine the composition and content of polyphenols in the dry extract obtained from the hydrodistilled residue by-product of the wild bergamot (Monarda fistulosa L., Lamiaceae Martinov family) herb (MFDE) and to evaluate its safety and pharmacological properties. The total phenolic content (TPC) in the MFDE was 120.64 mg GAE/g. The high-performance liquid chromatography (HPLC) analysis showed the presence of a plethora of phenolic compounds, including hydroxycinnamic acids and flavone derivatives in the MFDE, with rosmarinic acid and luteolin-7-O-glucoside being the main components. With an IC50 value of 0.285 mg/mL, it was found to be a strong DPPH radical scavenger. …
Tenapanor for the treatment of irritable bowel syndrome with constipation.
2020
Introduction: Irritable bowel syndrome with constipation is associated with higher rates of functional impairment, as compared to other subtypes of the syndrome. Conventional laxative-based pharmacologic therapy of IBS-C, which is mostly symptom-based, is often unsatisfactory. Tenapanor represents a first-in-class orally available inhibitor of NHE3, which is minimally absorbed in the GI tract, what constitutes a significant therapeutic benefit, as it may act on the drug target. Areas covered: Aim of this article is to sum up the evidences about pharmacodynamics and pharmacokinetics of tenapanor, focusing on animal models and in vitro studies, but also discuss clinical trials on tenapanor's …