CCND2 mutations in atypical chronic myeloid leukemia: a report of two cases.

Atypical chronic myeloid leukemia (aCML) is a rare MDS/MPN disease characterized by the absence of BCR::ABL1 rearrangement and well known typical mutations associated with myeloproliferative disorders. Mutational landscape associated with this disease was recently described with frequent involvement of SETBP1 and ETNK1 mutations. CCND2 mutations have not been frequently detected in MPN or MDS/MPN patients. We describe two cases of aCML with two CCND2 mutations in 280 and 281 codons which rapidly develop progressive characteristics, and we reviewed the literature about this unfavorable association, suggesting a role as a new possible marker of aggressive disease.

Rethinking of TEER measurement reporting for epithelial cells grown on permeable inserts.

Transepithelial electrical resistance (TEER) measures electrical resistance across epithelial tissue barriers involving confluent layer(s) of cells. TEER values act as a prerequisite for determining the barrier integrity of cells, which play a key role in evaluating the transport of drugs, materials or chemicals of interest across an epithelial barrier. The measurements can be performed non-invasively by measuring ohmic resistance across a defined area. Thus, the TEER values are reported in Ω·cm2. In vitro epithelial models are typically assembled on semi-permeable inserts providing two-chamber compartments, and the majority of the studies use inserts with polyethylene terephthalate (PET) membranes. Recently, new inserts with different membrane types and properties have been introduced. However, the TEER values presented so far did not allow a direct comparison. This study presents the characterization of selected epithelial tissues, i.e., lung, retina, and intestine, grown on an ultra-thin ceramic microporous permeable insert (SiMPLI) and PET membranes with different properties, i.e., thickness, material, and pore numbers. We verified the epithelial cell growth on both inserts via phase-contrast and confocal laser scanning microscope imaging. Barrier characteristics were assessed by TEER measurements and also by evaluating the permeability of fluorescein isothiocyanate through cell layers. The findings indicated that background TEER value calculations and the available surface area for cell growth must be thoroughly assessed when new inserts are introduced, as the values cannot be directly compared without re-calculations. Finally, we proposed electrical circuit models highlighting the contributors to TEER recordings on PET and SiMPLI insert membranes. This study paves the way for making the ohmic-based evaluation of epithelial tissues' permeability independent of the material and geometry of the insert membrane used for cell growth.

Assessment of clinical outcome of children with sepsis outside the intensive care unit.

In 2016, in order to identify adult patients with sepsis who are likely to have poor outcomes, the Third International Consensus Definitions Task Force introduced a new bedside index, called the quick Sepsis-related Organ Failure Assessment (qSOFA) score. However, these new criteria have not been validated in the pediatric population. In this study, we sought to assess the qSOFA score for children with sepsis, who are being treated outside the pediatric intensive care units. The qSOFA criteria were revised and applied to a study population of 89 pediatric patients with sepsis, admitted in a pediatric tertiary referral center from 2006 to 2016. The analysis of prognostic performance of qSOFA score for the prediction of severe sepsis showed a sensitivity of 46% (95% CI, 27-67%), a specificity of 74% (95% CI, 62-85%), a positive predictive value of 43% (95% CI, 34-52%), and a negative predictive value of 77% (95% CI, 71-82%). The area under ROC curve for qSOFA score ≥ 2 was 0.602 (95% CI 0.492-0.705).Conclusion: The qSOFA score showed a low accuracy to identify children in the pediatric ward at risk for severe sepsis. Clinical tools are needed to facilitate the diagnosis of impending organ dysfunction in pediatric infection outside of the ICU. What is Known: • One of the major challenges for clinicians is to identify and recognize children with sepsis and impending organ dysfunction, in the emergency and in the pediatric department. • In 2016, members of the Sepsis-3 task force proposed qSOFA, an empirically derived score using simple clinical criteria, to assist clinicians in identifying adult patients with sepsis at risk for poor outcome. What is New: • qSOFA demonstrated insufficient clinical value to be recommended as a screening tool for pediatric sepsis outside ICU. • D-dimer level and blood glucose may be useful biomarkers to identify children at risk for severe sepsis.

Data on some socio-economic parameters explaining the movement of extra-EU asylum seekers in Europe.

This article contains data concerning the movement of extra-EU asylum seekers in Europe. Data used in this paper were collected from the Eurostat database and the UNHCR database. The data consist of some socio-economic features related to 30 European countries where extra-EU asylum seekers have applied for protection. All variables were transformed into their natural logs. The degree of statistical correlation is evaluated from Pearson׳s coefficient, using the 0.05 level of significance. Regression analysis is conducted to identify some socio-economic predictors of countries attracting asylum migration. Six models are presented, where 'first time asylum applicants' in 2015 (1,324,215 individuals) in 30 European countries were regressed on 2014 predictors. The multilinear regression model was tested by using data on asylum seekers in 2014, regressed on the same predictors referred to 2013. The data here shared provide a resource for researchers working in the topical field of migration.

Ultrathin Ceramic Membranes as Scaffolds for Functional Cell Coculture Models on a Biomimetic Scale.

Epithelial tissue serves as an interface between biological compartments. Many in vitro epithelial cell models have been developed as an alternative to animal experiments to answer a range of research questions. These in vitro models are grown on permeable two-chamber systems; however, commercially available, polymer-based cell culture inserts are around 10 µm thick. Since the basement membrane found in biological systems is usually less than 1 µm thick, the 10-fold thickness of cell culture inserts is a major limitation in the establishment of realistic models. In this work, an alternative insert, accommodating an ultrathin ceramic membrane with a thickness of only 500 nm (i.e., the Silicon nitride Microporous Permeable Insert [SIMPLI]-well), was produced and used to refine an established human alveolar barrier coculture model by both replacing the conventional inserts with the SIMPLI-well and completing it with endothelial cells. The structural-functional relationship of the model was evaluated, including the translocation of gold nanoparticles across the barrier, revealing a higher translocation if compared to corresponding polyethylene terephthalate (PET) membranes. This study demonstrates the power of the SIMPLI-well system as a scaffold for epithelial tissue cell models on a truly biomimetic scale, allowing construction of more functionally accurate models of human biological barriers.

Transfer of ultrasmall iron oxide nanoparticles from human brain-derived endothelial cells to human glioblastoma cells.

Nanoparticles (NPs) are being used or explored for the development of biomedical applications in diagnosis and therapy, including imaging and drug delivery. Therefore, reliable tools are needed to study the behavior of NPs in biological environment, in particular the transport of NPs across biological barriers, including the blood-brain tumor barrier (BBTB), a challenging question. Previous studies have addressed the translocation of NPs of various compositions across cell layers, mostly using only one type of cells. Using a coculture model of the human BBTB, consisting in human cerebral endothelial cells preloaded with ultrasmall superparamagnetic iron oxide nanoparticles (USPIO NPs) and unloaded human glioblastoma cells grown on each side of newly developed ultrathin permeable silicon nitride supports as a model of the human BBTB, we demonstrate for the first time the transfer of USPIO NPs from human brain-derived endothelial cells to glioblastoma cells. The reduced thickness of the permeable mechanical support compares better than commercially available polymeric supports to the thickness of the basement membrane of the cerebral vascular system. These results are the first report supporting the possibility that USPIO NPs could be directly transferred from endothelial cells to glioblastoma cells across a BBTB. Thus, the use of such ultrathin porous supports provides a new in vitro approach to study the delivery of nanotherapeutics to brain cancers. Our results also suggest a novel possibility for nanoparticles to deliver therapeutics to the brain using endothelial to neural cells transfer.

Dynamic perspective on the function of thermoresponsive nanopores from in situ AFM and ATR-IR investigations.

This article describes the morphological and chemical characterization of stimuli-responsive functionalized silicon surfaces provided in parallel by atomic force spectroscopy (AFM) and Fourier transform infrared spectroscopy (FT-IR) enhanced by the single-beam sample reference attenuated total reflection method (SBSR-ATR). The stimuli-responsive behavior of the surfaces was obtained by grafting-to in melt carboxyl-terminated poly-N-isopropylacryl amides (PNIPAAM) with different degree of polymerization (DP) on epoxide-functionalized silicon substrates. The unprecedented real time and in situ physicochemical insight into the temperature-triggered response of the densely packed superficial brushes allowed for the selection of a PNIPAAM with a specific DP as a suitable polymer for the fabrication of silicon membranes exhibiting switchable nanopores. The fabrication process combines the manufacture of nanoporous silicon surfaces and their subsequent chemical functionalization by the grafting-to in melt of the selected polymer. Then, relevant information was obtained in what concerns the chemical modifications behind the topographical changes that drive the functioning of PNIPAAM-based hybrid nanovalves as well as the timescale on which the opening and closing of the nanopores occur.

Integrated optical biosensor for in-line monitoring of cell cultures.

An analytical detection platform was developed to evaluate the induced toxicity in cell cultures exposed to foreign agents like growth factors or nanoparticles. Connecting a biosensing detection device to the cell culture flasks allows analyzing the composition of cell medium in real-time. The analysis relies on the quantification of inflammatory cytokines released by cells into the cell culture medium, by means of solid-phase immunoassays analyzed with the wavelength interrogated optical sensing (WIOS) instrument. A fluidic system for in situ measurements allows detecting cytokines in real-time, with a sensitivity of 1-100 ng/mL depending on the cytokine. In addition, integration of an in-line optical absorbance measurement unit, in combination with the standard AB cell proliferation assay, provides information on the cell viability in the culture. Fluidic connections between the cell culture flasks, the optical biosensor and the absorbance measurement unit simultaneously allow quantifying up to three cytokines (interleukin 8, interleukin 6 and the monocyte chemotactic protein), assessing cellular proliferation, and thus discriminating between naïve cells and cells exposed to foreign agents such as growth factors (tumor necrosis factor alpha) or nanoparticles. This analytical tool presents a high potential for assessing the cytotoxicity of nanoparticles and other chemicals in vitro.