Beta-D-glucan in patients with haematological malignancies

(1-3)-beta-D-glucan (BDG) is an almost panfungal marker (absent in zygomycetes and most cryptococci), which can be successfully used in screening and diagnostic testing in patients with haematological malignancies if its advantages and limitations are known. The aim of this review is to report the data, particularly from the last 5 years, on the use of BDG in haematological population. Published data report mainly on the performance of the Fungitell™ assay, although several others are currently available, and they vary in method and cut-off of positivity. The sensitivity of BDG for invasive fungal disease (IFD) in haematology patients seems lower than in other populations, possibly because of the type of IFD (lower sensitivity was found in case of aspergillosis compared to candidiasis and pneumocystosis) or the use of prophylaxis. The specificity of the test can be improved by using two consecutive positive assays and avoiding testing in the case of the concomitant presence of factors associated with false positive results. BDG should be used in combination with clinical assessment and other diagnostic tests, both radiological and mycological, to provide maximum information. Good performance of BDG in cerebrospinal fluid (CSF) has been reported. BDG is a useful diagnostic method in haematology patients, particularly for pneumocystosis or initial diagnosis of invasive fungal infections

Regulatory T cells in the immunodiagnosis and outcome of kidney allograft rejection

Acute rejection (AR) is responsible for up to 12% of graft loss with the highest risk generally occurring during the first six months after transplantation. AR may be broadly classified into humoral as well as cellular rejection. Cellular rejection develops when donor alloantigens, presented by antigen-presenting cells (APCs) through class I or class II HLA molecules, activate the immune response against the allograft, resulting in activation of naive T cells that differentiate into subsets including cytotoxic CD8(+) and helper CD4(+) T cells type 1 (TH1) and TH2 cells or into cytoprotective immunoregulatory T cells (Tregs). The immune reaction directed against a renal allograft has been suggested to be characterized by two major components: a destructive one, mediated by CD4(+) helper and CD8(+) cytotoxic T cells, and a protective response, mediated by Tregs. The balance between these two opposite immune responses can significantly affect the graft survival. Many studies have been performed in order to define the role of Tregs either in the immunodiagnosis of transplant rejection or as predictor of the clinical outcome. However, information available from the literature shows a contradictory picture that deserves further investigation

Atherosclerosis, dyslipidemia, and inflammation: the significant role of polyunsaturated fatty acids

Phospholipids play an essential role in cell membrane structure and function. The length and number of double bonds of fatty acids in membrane phospholipids are main determinants of fluidity, transport systems, activity of membrane-bound enzymes, and susceptibility to lipid peroxidation. The fatty acid profile of serum lipids, especially the phospholipids, reflects the fatty acid composition of cell membranes. Moreover, long-chain n-3 polyunsatured fatty acids decrease very-low-density lipoprotein assembly and secretion reducing triacylglycerol production. N-6 and n-3 polyunsatured fatty acids are the precursors of signalling molecules, termed “eicosanoids,” which play an important role in the regulation of inflammation. Eicosanoids derived from n-6 polyunsatured fatty acids have proinflammatory actions, while eicosanoids derived from n-3 polyunsatured fatty acids have antiinflammatory ones. Previous studies showed that inflammation contributes to both the onset and progression of atherosclerosis: actually, atherosclerosis is predominantly a chronic low-grade inflammatory disease of the vessel wall. Several studies suggested the relationship between long-chain n-3 polyunsaturated fatty acids and inflammation, showing that fatty acids may decrease endothelial activation and affect eicosanoid metabolis

Ultra-rapid glutathionylation of chymotrypsinogen in its molten globule-like conformation: a comparison to archaeal proteins

Chymotrypsinogen, when reduced and taken to its molten globule-like conformation, displays a single cysteine with an unusual kinetic propensity toward oxidized glutathione (GSSG) and other organic thiol reagents. A single residue, identified by mass spectrometry like Cys1, reacts with GSSG about 1400 times faster than an unperturbed protein cysteine. A reversible protein-GSSG complex and a low pK(a) (8.1 +/- 0.1) make possible such astonishing kinetic property which is absent toward other natural disulfides like cystine, homocystine and cystamine. An evident hyper-reactivity toward 5,5 ' -dithiobis-(2-nitrobenzoic acid) (DTNB) and 1-chloro-2,4-dinitrobenzene (CDNB) was also found for this specific residue. The extraordinary reactivity toward GSSG is absent in two proteins of the thermophilic archaeon Sulfolobus solfataricus, an organism lacking glutathione: the Protein Disulphide Oxidoreductase (SsPDO) and the Bacterioferritin Comigratory Protein 1 (Bcp1) that displays Cys residues with an even lower pK(a) value (7.5 +/- 0.1) compared to chymotrypsinogen. This study, which also uses single mutants in Cys residues for Bcp1, proposes that this hyper-reactivity of a single cysteine, similar to that found in serum albumin, lysozyme, ribonuclease, may have relevance to drive the "incipit" of the oxidative folding of proteins from organisms where the glutathione/oxidized glutathione (GSH/GSSG) system is present

Saliva, a bodily fluid with recognized and potential diagnostic applications

Human whole saliva is a bodily fluid that can be obtained easily by noninvasive techniques. Specimens can be collected by the patient also at home in order to monitor health status and variations of several analytes of clinical interest. The contributions to whole saliva include secretions from salivary glands and, among others, from the gingival crevicular fluid that derives from the epithelial mucosa. Therefore, saliva is currently a relevant diagnostic fluid for many substances, including steroids, nonpeptide hormones, therapeutic drugs, and drugs of abuse. This review at first briefly describes the different contributions to whole saliva. A section illustrates the procedures for the collection, handling, and storage of salivary specimens. Another section describes the present use of whole saliva for diagnostic purposes and its specific utilization for the diagnosis of several local and systemic diseases. The final sections illustrate the future opportunities offered by various not conventional techniques with a focus on the most recent –omic investigations. It describes the various issues that have to be taken into account to avoid false positives and negatives, such as the strength of the experimental plan, the adequacy of the number of samples under study, and the proper choice of controls

Graphene Nanoflake Uptake Mediated by Scavenger Receptors

The biological interactions of graphene have been extensively investigated over the last 10 years. However, very little is known about graphene interactions with the cell surface and how the graphene internalization process is driven and mediated by specific recognition sites at the interface with the cell. In this work, we propose a methodology to investigate direct molecular correlations between the biomolecular corona of graphene and specific cell receptors, showing that key protein recognition motifs, presented on the nanomaterial surface, can engage selectively with specific cell receptors. We consider the case of apolipoprotein A-I, found to be very abundant in the graphene protein corona, and observe that the uptake of graphene nanoflakes is somewhat increased in cells with greatly elevated expression of scavenger receptors B1, suggesting a possible mechanism of endogenous interaction. The uptake results, obtained by flow cytometry, have been confirmed using Raman microspectroscopic mapping, exploiting the strong Raman signature of graphene

A microfluidic approach for synthesis and kinetic profiling of branched gold nanostructures

Automatized approaches for nanoparticle synthesis and characterization represent a great asset to their applicability in the biomedical field by improving reproducibility and standardization, which help to meet the selection criteria of regulatory authorities. The scaled-up production of nanoparticles with carefully defined characteristics, including intrinsic morphological features, and minimal intra-batch, batch-to-batch, and operator variability, is an urgent requirement to elevate nanotechnology towards more trustable biological and technological applications. In this work, microfluidic approaches were employed to achieve fast mixing and good reproducibility in synthesizing a variety of gold nanostructures. The microfluidic setup allowed exploiting spatial resolution to investigate the growth evolution of the complex nanoarchitectures. By physically isolating intermediate reaction fractions, we performed an advanced characterization of the shape properties during their growth, not possible with routine characterization methods. Employing an in-house developed method to assign a specific identity to shapes, we followed the particle growth/deformation process and identified key reaction parameters for more precise control of the generated morphologies. Besides, this investigation led to the optimization of a one-pot multi-size and multi-shape synthesis of a variety of gold nanoparticles. In summary, we describe an optimized platform for highly controlled synthesis and a novel approach for the mechanistic study of shape-evolving nanomaterials

Juegos serios aplicados a niños con discapacidades

La discapacidad intelectual o retardo mental es una afección que produce un funcionamiento intelectual general por debajo del promedio y una carencia de las destrezas necesarias para la vida diaria. Esta patología afecta alrededor del 1 al 3% de la población y las personas que la padecen tienen una adquisición lenta e incompleta de las habilidades cognitivas. En el presente trabajo se presenta la metodología utilizada en la implementación de un entorno lúdico desarrollado para un centro educativo terapéutico donde se tratan pacientes con retraso mental, Síndrome de Down, parálisis cerebral, etc.Sociedad Argentina de Informática e Investigación Operativa (SADIO