HIV-1 and recombinant gp120 affect the survival and differentiation of human vessel wall-derived mesenchymal stem cells

BAckground:HIV infection elicits the onset of a progressive immunodeficiency and also damages several other organs and tissues such as the CNS, kidney, heart, blood vessels, adipose tissue and bone. In particular, HIV infection has been related to an increased incidence of cardiovascular diseases and derangement in the structure of blood vessels in the absence of classical risk factors. The recent characterization of multipotent mesenchymal cells in the vascular wall, involved in regulating cellular homeostasis, suggests that these cells may be considered a target of HIV pathogenesis. This paper investigated the interaction between HIV-1 and vascular wall resident human mesenchymal stem cells (MSCs). RESULTS: MSCs were challenged with classical R5 and X4 HIV-1 laboratory strains demonstrating that these strains are able to enter and integrate their retro-transcribed proviral DNA in the host cell genome. Subsequent experiments indicated that HIV-1 strains and recombinant gp120 elicited a reliable increase in apoptosis in sub-confluent MSCs. Since vascular wall MSCs are multipotent cells that may be differentiated towards several cell lineages, we challenged HIV-1 strains and gp120 on MSCs differentiated to adipogenesis and endotheliogenesis. Our experiments showed that the adipogenesis is increased especially by upregulated PPAR\u3b3 activity whereas the endothelial differentiation induced by VEGF treatment was impaired with a downregulation of endothelial markers such as vWF, Flt-1 and KDR expression. These viral effects in MSC survival and adipogenic or endothelial differentiation were tackled by CD4 blockade suggesting an important role of CD4/gp120 interaction in this context. CONCLUSIONS: The HIV-related derangement of MSC survival and differentiation may suggest a direct role of HIV infection and gp120 in impaired vessel homeostasis and in genesis of vessel damage observed in HIV-infected patients

High-quality chest CT segmentation to assess the impact of COVID-19 disease

Purpose: COVID-19 has spread rapidly worldwide since its initial appearance, creating the need for faster diagnostic methods and tools. Due to the high rate of false-negative RT-PCR tests, the role of chest CT examination has been investigated as an auxiliary procedure. The main goal of this work is to establish a well-defined strategy for 3D segmentation of the airways and lungs of COVID-19 positive patients from CT scans, including detected abnormalities. Their identification and the volumetric quantification could allow an easier classification in terms of gravity, extent and progression of the infection. Moreover, these 3D reconstructions can provide a high-impact tool to enhance awareness of the severity of COVID-19 pneumonia. Methods: Segmentation process was performed utilizing a proprietary software, starting from six different stacks of chest CT images of subjects with and without COVID-19. In this context, a comparison between manual and automatic segmentation methods of the respiratory system was conducted, to assess the potential value of both techniques, in terms of time consumption, required anatomical knowledge and branch detection, in healthy and pathological conditions. Results: High-quality 3D models were obtained. They can be utilized to assess the impact of the pathology, by volumetrically quantifying the extension of the affected areas. Indeed, based on the obtained reconstructions, an attempted classification for each patient in terms of the severity of the COVID-19 infection has been outlined. Conclusions: Automatic algorithms allowed for a substantial reduction in segmentation time. However, a great effort was required for the manual identification of COVID-19 CT manifestations. The developed automated procedure succeeded in obtaining sufficiently accurate models of the airways and the lungs of both healthy patients and subjects with confirmed COVID-19, in a reasonable time

Validation of a rheological model for HDR based devices by tests on a full scale steel-concrete composite frame

High Damping Rubber (HDR), commonly used for seismic isolation devices, may also be used to produce passive dissipation devices. HDR-based devices have a number of advantages: they are recentering, they can withstanding a large number of cycle and moreover they can dissipate energy even under low excitations, such in the case of frequent earthquakes or wind actions. This paper presents a validation of a nonlinear viscoelastic model for HDR-based dampers already proposed by the same authors, by means of comparisons with experimental tests carried out on a full scale steel-concrete composite mock-up. The paper firstly describes the real scale mock-up and its characterization, in the elastic displacement range, carried out by means of free vibration tests. HDR devices were introduced in the frame by means of chevron-type braces and dynamic free vibration tests, force-controlled tests and displacement-controlled tests were performed. The coupled system is modelled as a nonlinear SDOF system consisting of an linear elastic element placed in parallel with HDR dampers. All experimental tests were numerically simulated with satisfactory results