Transcranial direct current stimulation: estimation of the electric field and of the current density in an anatomical human head model

This paper investigates the spatial distribution of the electric field and of the current density in the brain tissues induced by transcranial direct current stimulation of the primary motor cortex. A numerical method was applied on a realistic human head model to calculate these field distributions in different brain structures, such as the cortex, the white matter, the cerebellum, the hippocampus, the medulla oblongata, the pons, the midbrain, and the thalamus. The influence of varying the anode area, the cathode area, and the injected current was also investigated. An electrode area as the one typically used in clinical practice (i.e., both electrodes equal to 35 cm(2)) resulted into complex and diffuse amplitude distributions over all the examined brain structures, with the region of maximum induced field being below or close to the anode. Variations in either the anode or cathode area corresponded to changes in the field amplitude distribution in all the brain tissues, with the former variation producing more diffuse effects. Variations in the injected current resulted, as could be expected, in linearly correlated changes in the field amplitudes.     

In vitro degradability of three forages: fermentation kinetics and gas production of NDF and neutral detergent‐soluble fraction of forages

The fermentation of the neutral detergent‐soluble (NDS) fraction of three forages (alfalfa hay, Italian ryegrass + oats hay and corn silage) was measured using a curve subtraction technique with in vitro gas production data from the whole forage (WF) and the isolated neutral detergent fibre (NDF). NDF disappearance and volatile fatty acid (VFA) production were determined. There was no significant difference between the VFA patterns from the whole forage and the isolated NDF. There were significant (P < 0.001) linear correlations between the volume of gas and moles of VFA produced and the mass of fibre digested in the NDF samples. Using the monophasic curve model, maximum gas production rates (R_M) for the whole forages and the isolated NDF and NDS fractions can be calculated. For all three forages we obtained R_M‐NDS > R_M‐WF > R_M‐NDF. Trends in the rates of gas and VFA production were similar in the whole forages. The NDF showed a high superimposition between substrate degradability and VFA production. Our experiment confirmed the curve subtraction technique as a simple method to obtain information on the size and digestion kinetics of the NDS fraction, which helps in understanding the nutritional significance of this important fraction of the forages studied. © 2001 Society of Chemical Industry     

Molecular Alterations in Gastric Preneoplastic Lesions and Early Gastric Cancer

Prognosis of gastric cancer is dramatically improved by early diagnosis. Correa’s cascade correlates the expression of some molecular markers with the progression of preneoplastic lesions toward carcinoma. This article reviews the diagnostic and prognostic values of molecular markers in complete (MUC2) and incomplete (MUC2, MUC5AC, and MUC6) intestinal metaplasia, gastric dysplasia/intra-epithelial neoplasia, and early gastric cancer. In particular, considering preinvasive neoplasia and early gastric cancer, some studies have demonstrated a correlation between molecular alterations and prognosis, for example, mucins phenotype in gastric dysplasia, and GATA6, TP53 mutation/LOH and MUC6 in early gastric cancer. Moreover, this review considers novelties from the literature regarding the (immuno)histochemical characterization of diffuse-type/signet ring cell gastric cancer, with particular attention to clinical outcomes of patients. The aim of this review is the evaluation of the state of the art regarding suitable biomarkers used in the pre-surgical phase, which can distinguish patients with different prognoses and help decide the best therapeutic strategy.     

The Design of Web Games for Helping Young High-Functioning Autistics in Learning How to Manage Money

Mobile Networks and Applications - We describe the design of a Web-based game application aimed to support high-functioning individuals affected by Autism Spectrum Disorder in gaining skills that...     

A Quantitative Assay for Ca2+ Uptake through Normal and Pathological Hemichannels

Connexin (Cx) hemichannels (HCs) are large pore hexameric structures that allow the exchange of ions, metabolites and a variety of other molecules between the cell cytoplasm and extracellular milieu. HC inhibitors are attracting growing interest as drug candidates because deregulated fluxes through HCs have been implicated in a plethora of genetic conditions and other diseases. HC activity has been mainly investigated by electrophysiological methods and/or using HC-permeable dye uptake measurements. Here, we present an all-optical assay based on fluorometric measurements of ionized calcium (Ca²⁺) uptake with a Ca²⁺-selective genetically encoded indicator (GCaMP6s) that permits the optical tracking of cytosolic Ca²⁺ concentration ([Ca²⁺]_cyt) changes with high sensitivity. We exemplify use of the assay in stable pools of HaCaT cells overexpressing human Cx26, Cx46, or the pathological mutant Cx26G45E, under control of a tetracycline (Tet) responsive element (TRE) promoter (Tet-on). We demonstrate the usefulness of the assay for the characterization of new monoclonal antibodies (mAbs) targeting the extracellular domain of the HCs. Although we developed the assay on a spinning disk confocal fluorescence microscope, the same methodology can be extended seamlessly to high-throughput high-content platforms to screen other kinds of inhibitors and/or to probe HCs expressed in primary cells and microtissues.     

KRAS-Mutant Non-Small-Cell Lung Cancer: From Past Efforts to Future Challenges

KRAS is the most frequently mutated oncogene identified in human cancers. Despite the numerous efforts to develop effective specific inhibitors against KRAS, this molecule has remained “undruggable” for decades. The development of direct KRAS inhibitors, such as sotorasib, the first FDA-approved drug targeting KRAS G12C, or adagrasib, was made possible with the discovery of a small pocket in the binding switch II region of KRAS G12C. However, a new challenge is represented by the necessity to overcome resistance mechanisms to KRAS inhibitors. Another area to be explored is the potential role of co-mutations in the selection of the treatment strategy, particularly in the setting of immune checkpoint inhibitors. The aim of this review was to analyze the state-of-the-art of KRAS mutations in non-small-cell lung cancer by describing the biological structure of KRAS and exploring the clinical relevance of KRAS as a prognostic and predictive biomarker. We reviewed the different treatment approaches, focusing on the novel therapeutic strategies for the treatment of KRAS-mutant lung cancers.     

Characterization of 22q12 Microdeletions Causing Position Effect in Rare NF2 Patients with Complex Phenotypes

Neurofibromatosis type 2 is an autosomal dominant tumor-prone disorder mainly caused by NF2 point mutations or intragenic deletions. Few individuals with a complex phenotype and 22q12 microdeletions have been described. The 22q12 microdeletions’ pathogenic effects at the genetic and epigenetic levels are currently unknown. We here report on 22q12 microdeletions’ characterization in three NF2 patients with different phenotype complexities. A possible effect of the position was investigated by in silico analysis of 22q12 topologically associated domains (TADs) and regulatory elements, and by expression analysis of 12 genes flanking patients’ deletions. A 147 Kb microdeletion was identified in the patient with the mildest phenotype, while two large deletions of 561 Kb and 1.8 Mb were found in the other two patients, showing a more severe symptomatology. The last two patients displayed intellectual disability, possibly related to AP1B1 gene deletion. The microdeletions change from one to five TADs, and the 22q12 chromatin regulatory landscape, according to the altered expression levels of four deletion-flanking genes, including PIK3IP1, are likely associated with an early ischemic event occurring in the patient with the largest deletion. Our results suggest that the identification of the deletion extent can provide prognostic markers, predictive of NF2 phenotypes, and potential therapeutic targets, thus overall improving patient management.