Chronic Hyperkaliemia in Chronic Kidney Disease: An Old Concern with New Answers

Increasing potassium intake ameliorates blood pressure (BP) and cardiovascular (CV) prognoses in the general population; therefore the World Health Organization recommends a high-potassium diet (90–120 mEq/day). Hyperkalaemia is a rare condition in healthy individuals due to the ability of the kidneys to effectively excrete dietary potassium load in urine, while an increase in serum K⁺ is prevalent in patients with chronic kidney disease (CKD). Hyperkalaemia prevalence increases in more advanced CKD stages, and is associated with a poor prognosis. This scenario generates controversy on the correct nutritional approach to hyperkalaemia in CKD patients, considering the unproven link between potassium intake and serum K⁺ levels. Another concern is that drug-induced hyperkalaemia leads to the down-titration or withdrawal of renin-angiotensin system inhibitors (RASI) and mineralocorticoids receptors antagonists (MRA) in patients with CKD, depriving these patients of central therapeutic interventions aimed at delaying CKD progression and decreasing CV mortality. The new K⁺-binder drugs (Patiromer and Sodium-Zirconium Cyclosilicate) have proven to be adequate and safe therapeutic options to control serum K⁺ in CKD patients, enabling RASI and MRA therapy, and possibly, a more liberal intake of fruit and vegetables.     

A Novel Morphological Parameter Predicting Fibrotic Evolution in Myeloproliferative Neoplasms: New Evidence and Molecular Insights

Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) represent a group of hematological disorders that are traditionally considered as indistinct slow progressing conditions; still, a subset of cases shows a rapid evolution towards myelofibrotic bone marrow failure. Specific abnormalities in the megakaryocyte lineage seem to play a central role in this evolution, especially in the bone marrow fibrosis but also in the induction of myeloproliferation. In this review, we analyze the current knowledge of prognostic factors of MPNs related to their evolution to myelofibrotic bone marrow failure. Moreover, we focused the role of the megakaryocytic lineage in the various stages of MPNs, with updated examples of MPNs in vitro and in vivo models and new therapeutic implications.     

TRPA1 Role in Inflammatory Disorders: What Is Known So Far?

The transient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily of channels, is primarily localized in a subpopulation of primary sensory neurons of the trigeminal, vagal, and dorsal root ganglia, where its activation mediates neurogenic inflammatory responses. TRPA1 expression in resident tissue cells, inflammatory, and immune cells, through the indirect modulation of a large series of intracellular pathways, orchestrates a range of cellular processes, such as cytokine production, cell differentiation, and cytotoxicity. Therefore, the TRPA1 pathway has been proposed as a protective mechanism to detect and respond to harmful agents in various pathological conditions, including several inflammatory diseases. Specific attention has been paid to TRPA1 contribution to the transition of inflammation and immune responses from an early defensive response to a chronic pathological condition. In this view, TRPA1 antagonists may be regarded as beneficial tools for the treatment of inflammatory conditions.     

Fighting the Huntington’s Disease with a G-Quadruplex-Forming Aptamer Specifically Binding to Mutant Huntingtin Protein: Biophysical Characterization,In Vitro and In Vivo Studies

A set of guanine-rich aptamers able to preferentially recognize full-length huntingtin with an expanded polyglutamine tract has been recently identified, showing high efficacy in modulating the functions of the mutated protein in a variety of cell experiments. We here report a detailed biophysical characterization of the best aptamer in the series, named MS3, proved to adopt a stable, parallel G-quadruplex structure and show high nuclease resistance in serum. Confocal microscopy experiments on HeLa and SH-SY5Y cells, as models of non-neuronal and neuronal cells, respectively, showed a rapid, dose-dependent uptake of fluorescein-labelled MS3, demonstrating its effective internalization, even in the absence of transfecting agents, with no general cytotoxicity. Then, using a well-established Drosophila melanogaster model for Huntington’s disease, which expresses the mutated form of human huntingtin, a significant improvement in the motor neuronal function in flies fed with MS3 was observed, proving the in vivo efficacy of this aptamer.     

Targeting CD10 on B-Cell Leukemia Using the Universal CAR T-Cell Platform (UniCAR)

Chimeric antigen receptor (CAR)-expressing T-cells are without a doubt a breakthrough therapy for hematological malignancies. Despite their success, clinical experience has revealed several challenges, which include relapse after targeting single antigens such as CD19 in the case of B-cell acute lymphoblastic leukemia (B-ALL), and the occurrence of side effects that could be severe in some cases. Therefore, it became clear that improved safety approaches, and targeting multiple antigens, should be considered to further improve CAR T-cell therapy for B-ALL. In this paper, we address both issues by investigating the use of CD10 as a therapeutic target for B-ALL with our switchable UniCAR system. The UniCAR platform is a modular platform that depends on the presence of two elements to function. These include UniCAR T-cells and the target modules (TMs), which cross-link the T-cells to their respective targets on tumor cells. The TMs function as keys that control the switchability of UniCAR T-cells. Here, we demonstrate that UniCAR T-cells, armed with anti-CD10 TM, can efficiently kill B-ALL cell lines, as well as patient-derived B-ALL blasts, thereby highlighting the exciting possibility for using CD10 as an emerging therapeutic target for B-cell malignancies.     

Reusing back-propagation artificial neural networks for land cover classification in tropical savannahs

This paper focuses on a method to overcome some of the disadvantages that are related with the use of artificial neural networks (ANNs) as supervised classifiers. The proposed method aims at speeding up network learning, improving classification accuracies and reducing variability on classification performance due to random weight initialization. This can be realized by transferring implicit knowledge from a previously learned source task to a new target task using the proposed algorithm, Discriminality Based Transfer (DBT). The presented approach is compared with conventional network training and a literal transfer method in a 13-class tropical savannah classification experiment using Landsat Thematic Mapper (TM) data. Knowledge was extracted from a network trained on the Kara experimental site in Togo. This information was used to classify the Savanes-L'Oti area which differs in terms of geographical position, image acquisition date, climatological condition and land cover. It was possible to speed up network learning 5.2, 4.3 and 1.8 times using, respectively, 5-, 10- and 20-pixels-per-class training sets. Larger training sets showed less speed improvement. After applying DBT, average classification accuracies were not significantly different from accuracies obtained after training random initialized networks, although DBT tended to show better performance on smaller training sets. It was possible to explain differences in individual class accuracies by analysing Bhattacharyya (BH) distances calculated between all Kara and Savanes-L'Oti classes. Finally, variability on classification performance decreased significantly when training with 5-, 10- and 20-pixels-per-class training sets after DBT application.     

Characterizing landscape changes in central Rondonia using Landsat TM imagery

An analysis of landscape changes in a region of pioneer settlements in central Rondonia, western Brazilian Amazon, was derived from Landsat TM data. Total deforested area increased from 206 x 103 ha in 1977, to 565 x 103 ha in 1985 and to 1210 x 103 ha, or 35.5% of the region, in 1995. Eighty-one per cent of the total 1995 deforestation had occurred in regions within 12.5km from areas of pioneer colonization deforested by 1977. Deforested area exceeded 79% in regions within 12.5km from the region's first road.     

Silicon-on-Insulator Spectral Filters Fabricated With CMOS Technology

We give an overview of recent progress in passive spectral filters and demultiplexers based on silicon-on-insulator photonic wire waveguides: ring resonators, interferometers, arrayed waveguide gratings, and echelle diffraction gratings, all benefit from the high-index contrast possible with silicon photonics. We show how the current generation of devices has improved crosstalk levels, insertion loss, and uniformity due to an improved fabrication process based on 193 nm lithography.