648 research outputs found

    Clinical, Laboratory and Lung Ultrasound Assessment of Congestion in Patients with Acute Heart Failure

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    Congestion is the main cause of hospitalization in patients with acute heart failure (AHF), however its precise assessment by simple clinical evaluation remains elusive. The recent introduction of the lung ultrasound scan (LUS) allowed to physicians to more precisely quantify pulmonary congestion. The aim of this study was to compare clinical congestion (CC) with LUS and B-type natriuretic peptide (BNP) in order to achieve a more complete evaluation and to evaluate the prognostic power of each measurement. Methods: All patients were submitted to clinical evaluation for blood sample analysis and LUS at admission and before discharge. LUS protocol evaluated the number of B-lines for each chest zone by standardized eight site protocol. CC was measured following ESC criteria. The mean difference between admission and discharge congestion logBNP and B-lines values were calculated. Combined end points of death and rehospitalization was calculated over 180 days. Results: 213 patients were included in the protocol; 133 experienced heart failure with reduced ejection fraction (HFrEF), and 83 presented with heart failure with preserved ejection fraction (HFpEF). Patients with HFrEF had a more increased level of BNP (1150 (812-1790) vs. 851 (694-1196); p = 0.002) and B lines total number (32 (27-38) vs. 30 (25-36); p = 0.05). A positive correlation was found between log BNP and Blines number in both HFrEF (r = 0.57; p < 0.001) and HFpEF (r = 0.36; p = 0.001). Similarly, dividing B-lines among tertiles the upper group (B-lines >= 36) had an increased clinical congestion score. Among three variables at admission only B-lines were predictive for outcome (AUC 0.68 p < 0.001) but not LogBNP and CC score. During 180 days of follow-up, univariate analysis showed that persistent Delta B-lines <-32.3% (HR 6.54 (4.19-10.20); p < 0.001), persistent Delta BNP < -43.8% (HR 2.48 (1.69-3.63); p < 0.001) and persistent Delta CC < 50% (HR 4.25 (2.90-6.21); p < 0.001) were all significantly related to adverse outcome. Multivariable analysis confirmed that persistent Delta B-lines (HR 4.38 (2.64-7.29); p < 0.001), Delta BNP (HR 1.74 (1.11-2.74); p = 0.016) and Delta CC (HR 3.38 (2.10-5.44); p < 0.001 were associated with the combined end point. Conclusions: a complete clinical laboratory and LUS assessment better recognized different congestion occurrence in AHF. The difference between admission and discharge B-lines provides useful prognostic information compared to traditional clinical evaluation. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

    Role of Microenvironment in Glioma Invasion. What We Learned from In Vitro Models

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    The invasion properties of glioblastoma hamper a radical surgery and are responsible for its recurrence. Understanding the invasion mechanisms is thus critical to devise new therapeutic strategies. Therefore, the creation of in vitro models that enable these mechanisms to be studied represents a crucial step. Since in vitro models represent an over-simplification of the in vivo system, in these years it has been attempted to increase the level of complexity of in vitro assays to create models that could better mimic the behaviour of the cells in vivo. These levels of complexity involved: 1. The dimension of the system, moving from two-dimensional to three-dimensional models; 2. The use of microfluidic systems; 3. The use of mixed cultures of tumour cells and cells of the tumour micro-environment in order to mimic the complex cross-talk between tumour cells and their micro-environment; 4. And the source of cells used in an attempt to move from commercial lines to patient-based models. In this review, we will summarize the evidence obtained exploring these different levels of complexity and highlighting advantages and limitations of each system used

    Gradient catastrophe and flutter in vortex filament dynamics

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    Gradient catastrophe and flutter instability in the motion of vortex filament within the localized induction approximation are analyzed. It is shown that the origin if this phenomenon is in the gradient catastrophe for the dispersionless Da Rios system which describes motion of filament with slow varying curvature and torsion. Geometrically this catastrophe manifests as a rapid oscillation of a filament curve in a point that resembles the flutter of airfoils. Analytically it is the elliptic umbilic singularity in the terminology of the catastrophe theory. It is demonstrated that its double scaling regularization is governed by the Painlev\'e-I equation.Comment: 11 pages, 3 figures, typos corrected, references adde

    Systemic T Cells Immunosuppression of Glioma Stem Cell-Derived Exosomes Is Mediated by Monocytic Myeloid-Derived Suppressor Cells

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    A major contributing factor to glioma development and progression is its ability to evade the immune system. Nano-meter sized vesicles, exosomes, secreted by glioma-stem cells (GSC) can act as mediators of intercellular communication to promote tumor immune escape. Here, we investigated the immunomodulatory properties of GCS-derived exosomes on different peripheral immune cell populations. Healthy donor peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3, anti-CD28 and IL-2, were treated with GSC-derived exosomes. Phenotypic characterization, cell proliferation, Th1/Th2 cytokine secretion and intracellular cytokine production were analysed by distinguishing among effector T cells, regulatory T cells and monocytes. In unfractionated PBMCs, GSC-derived exosomes inhibited T cell activation (CD25 and CD69 expression), proliferation and Th1 cytokine production, and did not affect cell viability or regulatory T-cell suppression ability. Furthermore, exosomes were able to enhance proliferation of purified CD4+ T cells. In PBMCs culture, glioma-derived exosomes directly promoted IL-10 and arginase-1 production and downregulation of HLA-DR by unstimulated CD14+ monocytic cells, that displayed an immunophenotype resembling that of monocytic myeloid-derived suppressor cells (Mo-MDSCs). Importantly, the removal of CD14+ monocytic cell fraction from PBMCs restored T-cell proliferation. The same results were observed with exosomes purified from plasma of glioblastoma patients. Our results indicate that glioma-derived exosomes suppress T-cell immune response by acting on monocyte maturation rather than on direct interaction with T cells. Selective targeting of Mo-MDSC to treat glioma should be considered with regard to how immune cells allow the acquirement of effector functions and therefore counteracting tumor progression

    The mirna content of exosomes released from the glioma microenvironment can affect malignant progression

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    Low-grade gliomas (LGG) are infiltrative primary brain tumors that in 70% of the cases undergo anaplastic transformation, deeply affecting prognosis. However, the timing of progression is heterogeneous. Recently, the tumor microenvironment (TME) has gained much attention either as prognostic factor or therapeutic target. Through the release of extracellular vesicles, the TME contributes to tumor progression by transferring bioactive molecules such as microRNA. The aim of the study was to take advantage of glioma-associated stem cells (GASC), an in vitro model of the glioma microenvironment endowed with a prognostic significance, and their released exosomes, to investigate the possible role of exosome miRNAs in favoring the anaplastic transformation of LGG. Therefore, by deep sequencing, we analyzed and compared the miRNA profile of GASC and exosomes obtained from LGG patients characterized by different prognosis. Results showed that exosomes presented a different signature, when compared to their cellular counterpart and that, although sharing several miRNAs, exosomes of patients with a bad prognosis, selectively expressed some miRNAs possibly responsible for the more aggressive phenotype. These findings get insights into the value of TME and exosomes as potential biomarkers for precision medicine approaches aimed at improving LGG prognostic stratification and therapeutic strategies

    Design of Multicationic Copper-Bearing Layered Double Hydroxides for Catalytic Application in Biorefinery

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    Ethanol has been used as a renewable hydrogen-donor in the conversion of a lignin model molecule in subcritical conditions. Noble metal-free porous mixed oxides, obtained by activation of Cu-Ni-Al and Cu-Ni-Fe layered double hydroxide (LDH) precursors, have been used as heterogeneous catalysts for Meerwein-Ponndorf-Verley (MPV) hydrogen transfer and further hydrogenation by ethanol dehydrogenation products. Both the Cu/(Cu+Ni) ratio and the nature of the trivalent cation (Al or Fe) affect the activity of the catalysts, as well as the selectivity towards the different steps of the hydrogenation reactions and the cleavage of lignin-like phenylether bonds. Accounting for the peculiar behaviour of Cu2+ and M(III) cations in the synthesis of LDHs, the coprecipitation of the precursors has been monitored by titration experiments. Structural and textural properties of the catalysts are closely related to the composition of the LDH precursors

    Classification of integrable Weingarten surfaces possessing an sl(2)-valued zero curvature representation

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    In this paper we classify Weingarten surfaces integrable in the sense of soliton theory. The criterion is that the associated Gauss equation possesses an sl(2)-valued zero curvature representation with a nonremovable parameter. Under certain restrictions on the jet order, the answer is given by a third order ordinary differential equation to govern the functional dependence of the principal curvatures. Employing the scaling and translation (offsetting) symmetry, we give a general solution of the governing equation in terms of elliptic integrals. We show that the instances when the elliptic integrals degenerate to elementary functions were known to nineteenth century geometers. Finally, we characterize the associated normal congruences
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