Search results for "Nous"

Determinants of the Quality of Warfarin Control after Venous Thromboembolism and Validation of the SAMe-TT2-R2 Score: An Analysis of Hokusai-VTE.

2019

Background Time in therapeutic range (TTR) measures the quality of vitamin K antagonist (VKA) anticoagulation. In patients with atrial fibrillation, the dichotomized SAMe-TT2-R2 score (≥2 vs. < 2 points) can predict if adequate TTR is unlikely to be achieved. Aims We validated the SAMe-TT2-R2 score in patients with venous thromboembolism (VTE) randomized to the warfarin arm of the Hokusai-VTE trial. Patients and Methods A total of 3,874 patients were included in the primary analysis (day 31–180 from randomization). The efficacy and safety outcomes were symptomatic recurrent VTE and major or clinically relevant non-major bleeding. Results The rates of recurrent VTE and bleeding events we…

Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo chronic myelogenous Leukemia cell growth

2017

Despite Imatinib (IM), a selective inhibitor of Bcr-Abl, having led to improved prognosis in Chronic Myeloid Leukemia (CML) patients, acquired resistance and long-term adverse effects is still being encountered. There is, therefore, urgent need to develop alternative strategies to overcome drug resistance. According to the molecules expressed on their surface, exosomes can target specific cells. Exosomes can also be loaded with a variety of molecules, thereby acting as a vehicle for the delivery of therapeutic agents. In this study, we engineered HEK293T cells to express the exosomal protein Lamp2b, fused to a fragment of Interleukin 3 (IL3). The IL3 receptor (IL3-R) is overexpressed in CML…

Methanotrophy under Versatile Conditions in the Water Column of the Ferruginous Meromictic Lake La Cruz (Spain)

2016

Lakes represent a considerable natural source of methane to the atmosphere compared to their small global surface area. Methanotrophs in sediments and in the water column largely control methane fluxes from these systems, yet the diversity, electron accepting capacity, and nutrient requirements of these microorganisms have only been partially identified. Here, we investigated the role of electron acceptors alternative to oxygen and sulfate in microbial methane oxidation at the oxycline and in anoxic waters of the ferruginous meromictic Lake La Cruz, Spain. Active methane turnover in a zone extending well below the oxycline was evidenced by stable carbon isotope-based rate measurements. We o…

Photoferrotrophy: Remains of an Ancient Photosynthesis in Modern Environments

2017

Photoferrotrophy, the process by which inorganic carbon is fixed into organic matter using light as an energy source and reduced iron [Fe(II)] as an electron donor, has been proposed as one of the oldest photoautotrophic metabolisms on Earth. Under the iron-rich (ferruginous) but sulfide poor conditions dominating the Archean ocean, this type of metabolism could have accounted for most of the primary production in the photic zone. Here we review the current knowledge of biogeochemical, microbial and phylogenetic aspects of photoferrotrophy, and evaluate the ecological significance of this process in ancient and modern environments. From the ferruginous conditions that prevailed during most …

Pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant, recurrent, pre-treated ovarian cancer - Results of the PACOVAR-trial.

2017

Abstract Purpose The prognosis is poor for patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC). Evidence suggests that antiangiogenic treatment modalities could play a major role in EOC. A combined therapy consisting of the investigational oral antiangiogenic agent pazopanib and metronomic oral cyclophosphamide may offer a well-tolerable treatment option to patients with recurrent, previously treated EOC. Patients and methods This study was designed as a multicenter phase I trial evaluating the optimal dose as well as activity and tolerability of pazopanib with metronomic cyclophosphamide in the treatment of patients with recurrent, platinum-resistant, previously tre…

Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma.

2016

Daratumumab, a human IgGκ monoclonal antibody that targets CD38, induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma.In this phase 3 trial, we randomly assigned 498 patients with relapsed or relapsed and refractory multiple myeloma to receive bortezomib (1.3 mg per square meter of body-surface area) and dexamethasone (20 mg) alone (control group) or in combination with daratumumab (16 mg per kilogram of body weight) (daratumumab group). The primary end point was progression-free survival.A prespecifie…

A targeted proteomics investigation of the obesity paradox in venous thromboembolism

2021

Abstract The obesity paradox, the controversial finding that obesity promotes disease development but protects against sequelae in patients, has been observed in venous thromboembolism (VTE). The aim of this investigation was to identify a body mass–related proteomic signature in VTE patients and to evaluate whether this signature mediates the obesity paradox in VTE patients. Data from the Genotyping and Molecular Phenotyping in Venous ThromboEmbolism Project, a prospective cohort study of 693 VTE patients, were analyzed. A combined end point of recurrent VTE or all-cause death was used. Relative quantification of 444 proteins was performed using high-throughput targeted proteomics technolo…

Acute deep vein thrombosis suppresses peripheral T cell effector function

2018

Hypertrophic pachymeningitis and cerebral venous thrombosis in myeloperoxidase-ANCA associated vasculitis

2019

Hypertrophic pachymeningitis (HP) is a circumscribed inflammatory process that thickens meninges with fibrous adhesions. Among the causes of HP, vasculitis and autoimmune disease should be considered; myeloperoxidase (MPO)-antinuclear cytoplasmatic antibodies (ANCA)-positivity can be the only

Small endogenous molecules as moiety to improve targeting of CNS drugs.

2016

A major challenge in the development of novel neuro-therapeutic agents is to effectively overcome the blood-brain barrier (BBB), which acts as a 'working dynamic barrier'. The core problem in the treatment of neurodegenerative diseases is failed delivery of potential medicines due to their inadequate permeation rate. Areas covered: The present review gives a summary of endogenous moieties used in synthesizing prodrugs, derivatives and bioisosteric drugs appositely designed to structurally resemble physiological molecular entities able to be passively absorbed or carried by specific carrier proteins expressed at BBB level. In particular, this overview focuses on aminoacidic, glycosyl, purine…