44 research outputs found
Prognostic implications of mean nuclear diameter in breast cancer.
The mean nuclear diameter of 100 breast cancers was measured on tissue sections, to evaluate its importance for early prognosis. The cases were subdivided into 3 subgroups: small (25.5% of cases), medium (63.3%) and large (11.2%) nuclei. Early recurrence and mortality rates were investigated in each of the categories. Increasing nuclear size was shown to be related to mortality from metastatic disease. However, large-nucleus tumours had an inverse relationship with lymphnode involvement and possibly with recurrence rate. Hence, in our material nuclear size as a sole criterion was not a good indicator of the early behaviour of operable breast cancer
An Image-Based High-Content Screening Assay for Compounds Targeting Intracellular Leishmania donovani Amastigotes in Human Macrophages
Leishmaniasis is a tropical disease threatening 350 million people from endemic regions. The available drugs for treatment are inadequate, with limitations such as serious side effects, parasite resistance or high cost. Driven by this need for new drugs, we developed a high-content, high-throughput image-based screening assay targeting the intracellular amastigote stage of different species of Leishmania in infected human macrophages. The in vitro infection protocol was adapted to a 384-well-plate format, enabling acquisition of a large amount of readouts by automated confocal microscopy. The reading method was based on DNA staining and required the development of a customized algorithm to analyze the images, which enabled the use of non-modified parasites. The automated analysis generated parameters used to quantify compound activity, including infection ratio as well as the number of intracellular amastigote parasites and yielded cytotoxicity information based on the number of host cells. Comparison of this assay with one that used the promastigote form to screen 26,500 compounds showed that 50% of the hits selected against the intracellular amastigote were not selected in the promastigote screening. These data corroborate the idea that the intracellular amastigote form of the parasite is the most appropriate to be used in primary screening assay for Leishmania
Screening out irrelevant cell-based models of disease
The common and persistent failures to translate promising preclinical drug candidates into clinical success highlight the limited effectiveness of disease models currently used in drug discovery. An apparent reluctance to explore and adopt alternative cell-and tissue-based model systems, coupled with a detachment from clinical practice during assay validation, contributes to ineffective translational research. To help address these issues and stimulate debate, here we propose a set of principles to facilitate the definition and development of disease-relevant assays, and we discuss new opportunities for exploiting the latest advances in cell-based assay technologies in drug discovery, including induced pluripotent stem cells, three-dimensional (3D) co-culture and organ-on-a-chip systems, complemented by advances in single-cell imaging and gene editing technologies. Funding to support precompetitive, multidisciplinary collaborations to develop novel preclinical models and cell-based screening technologies could have a key role in improving their clinical relevance, and ultimately increase clinical success rates
Sinusoidal heart rate pattern: Reappraisal of its definition and clinical significance
Equilibrium potential-pH diagram for the system Mn-H2O at 25°Câ
info:eu-repo/semantics/publishe
Caesarean section or symphysiotomy for obstructed labour for developing countries? Need to ascertain women's preferences
Guidance on interpretation of the COVID-19 vaccine impact on infections in the Sciensano weekly report
El Correo gallego : diario polĂtico de la mañana: Ano LIX NĂșmero 20384 - 1937 xuño 15
NiP
alloys are very often used in industry, due to their outstanding
performance in corrosion and wear. Alloys with high phosphorus content
(â„16 atom % P) are amorphous and show high corrosion resistance
in both neutral and acidic solutions irrespective of the presence
of chloride ions. The reason for this behavior is attributed to the
formation of a âP-enriched surface layerâ whose exact
nature is still under debate. In this work, an iterative algorithm
based on the application of maximum entropy method on nondestructive
angle-resolved X-ray photoelectron spectroscopy data has been applied
to the investigation of the surface layer grown on Ni18P alloys following
mechanical polishing and anodic polarization in sulfate solutions.
The results show that the outermost region of the examined alloy has
a complex layered structure: (1) an uppermost hydrocarbon contamination
layer about 1 nm thick, which includes also adsorbed water; (2) a
nickel (poly)Âphosphate layer of about 1 nm; (3) a highly phosphorus-enriched
interface being about 2 nm thick with a marked phosphorus concentration
gradient, from 70 to 20 atom %; and (4) bulk alloy with the stoichiometric
composition. These findings, together with the chemical state of the
different phosphorus compounds, allow us to conclude that the high
corrosion and wear resistance of NiP alloys might be ascribed to the
presence of a thin, self-repairing nickel (poly)Âphosphate layer grown
on a strongly P-enriched interface. Because the Auger parameter of
P at the interface is similar to that of elemental P, it might be
also concluded that the interface is enriched in elemental phosphorus