The development of innovative diagnostic tests is fundamental in the route towards malaria eradication. Here, we discuss the sorting capabilities of an innovative test for malaria which allows the ...quantitative and rapid detection of all malaria species. The physical concept of the test exploits the paramagnetic property of infected erythrocytes and hemozoin crystals, the magnetic fingerprints of malaria common to all species, which allows them to undergo a selective magnetophoretic separation driven by a magnetic field gradient in competition with gravity. Upon separation, corpuscles concentrate at the surface of a silicon microchip where interdigitated electrodes are placed in close proximity to magnetic concentrators. The impedance variation proportional to the amount of attracted particles is then measured. The capability of our test to perform the selective detection of infected erythrocytes and hemozoin crystals has been tested by means of capture experiments on treated bovine red blood cells, mimicking the behavior of malaria-infected ones, and suspensions of synthetic hemozoin crystals. Different configuration angles of the chip with respect to gravity force and different thicknesses of the microfluidic chamber containing the blood sample have been investigated experimentally and by multiphysics simulations. In the paper, we describe the optimum conditions leading to maximum sensitivity and specificity of the test.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Upon cardiac pathological conditions such as ischemia, microenvironmental changes instruct a series of cellular responses that trigger cardiac fibroblasts-mediated tissue adaptation and inflammation. ...A comprehensive model of how early environmental changes may induce cardiac fibroblasts (CF) pathological responses is far from being elucidated, partly due to the lack of approaches involving complex and simultaneous environmental stimulation. Here, we provide a first analysis of human primary CF behavior by means of a multi-stimulus microdevice for combined application of cyclic mechanical strain and controlled oxygen tension. Our findings elucidate differential human CFs responses to different combinations of the above stimuli. Individual stimuli cause proliferative effects (PHH3
mitotic cells, YAP translocation, PDGF secretion) or increase collagen presence. Interestingly, only the combination of hypoxia and a simulated loss of contractility (2% strain) is able to additionally induce increased CF release of inflammatory and pro-fibrotic cytokines and matrix metalloproteinases.
Saphenous vein graft disease is a timely problem in coronary artery bypass grafting. Indeed, after exposure of the vein to arterial blood flow, a progressive modification in the wall begins, due to ...proliferation of smooth muscle cells in the intima. As a consequence, the graft progressively occludes and this leads to recurrent ischemia. In the present study we employed a novel ex vivo culture system to assess the biological effects of arterial-like pressure on the human saphenous vein structure and physiology, and to compare the results to those achieved in the presence of a constant low pressure and flow mimicking the physiologic vein perfusion. While under both conditions we found an activation of Matrix Metallo-Proteases 2/9 and of microRNAs-21/146a/221, a specific effect of the arterial-like pressure was observed. This consisted in a marked geometrical remodeling, in the suppression of Tissue Inhibitor of Metallo-Protease-1, in the enhanced expression of TGF-β1 and BMP-2 mRNAs and, finally, in the upregulation of microRNAs-138/200b/200c. In addition, the veins exposed to arterial-like pressure showed an increase in the density of the adventitial vasa vasorum and of cells co-expressing NG2, CD44 and SM22α markers in the adventitia. Cells with nuclear expression of Sox-10, a transcription factor characterizing multipotent vascular stem cells, were finally found in adventitial vessels. Our findings suggest, for the first time, a role of arterial-like wall strain in the activation of pro-pathologic pathways resulting in adventitial vessels growth, activation of vasa vasorum cells, and upregulation of specific gene products associated to vascular remodeling and inflammation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Aortic valve replacement has evolved recently with the development of the sutureless bioprosthesis. One such valve is the Perceval bioprosthesis, which is built by mounting leaflets of ...bovine pericardium to a thin stent; this approach has the potential to provide an excellent fluid dynamic performance. We undertook an in vitro study to compare the hydrodynamic performance of the sutureless bioprosthesis with two standard pericardial stented bioprostheses (Crown and Magna). Methods Tests were conducted using a mock loop, testing on two sizes of the three prostheses. The prosthesis sizes were chosen to house the valves in porcine aortic roots with a native annulus diameter of 19 mm (n = 6) or 21 mm (n = 6). The stroke volume ranged from 25 mL to 105 mL at a simulated heart rate of 70 beats per minute. Results Mean pressure drop and energy loss rose with increasing stroke volume in all of the valves tested ( p < 0.001), with the sutureless valve showing the lowest values for both variables ( p < 0.001). Effective orifice area values were stable across the stroke volume intervals and were larger in the sutureless valves ( p < 0.001). Conclusions All of the valves tested provided good fluid dynamic performances. The sutureless bioprosthesis provided the best performance with the least hindrance to flow behavior. From the hydrodynamic perspective, the sutureless prosthesis may present an advance in the evolution of bioprostheses, ensuring low gradients and potential for low incidence of patient-prosthesis mismatch even in small annuli.
Electrical stimulation (ES) of cells has been shown to induce a variety of responses, such as cytoskeleton rearrangements, migration, proliferation, and differentiation. In this study, we have ...investigated whether monophasic and biphasic pulsed ES could exert any effect on the proliferation and differentiation of human cardiac progenitor cells (hCPCs) isolated from human heart fragments. Cells were cultured under continuous exposure to monophasic or biphasic ES with fixed cycles for 1 or 3 days. Results indicate that neither stimulation protocol affected cell viability, while the cell shape became more elongated and reoriented more perpendicular to the electric field direction. Moreover, the biphasic ES clearly induced the upregulation of early cardiac transcription factors, MEF2D, GATA-4, and Nkx2.5, as well as the de novo expression of the late cardiac sarcomeric proteins, troponin T, cardiac alpha actinin, and SERCA 2a. Both treatments increased the expression of connexin 43 and its relocation to the cell membrane, but biphasic ES was faster and more effective. Finally, when hCPCs were exposed to both monophasic and biphasic ES, they expressed de novo the mRNA of the voltage-dependent calcium channel Cav 3.1(α1G) subunit, which is peculiar of the developing heart. Taken together, these results show that ES alone is able to set the conditions for early differentiation of adult hCPCs toward a cardiac phenotype.
Background The in vivo hemodynamic performance of a bioprosthesis implanted in an aortic position is affected by the characteristics of the prosthesis and the sizing strategy adopted. Recently, it ...has been hypothesized that the type of suture used to implant the prosthesis might influence hemodynamics. Methods Bioprostheses with labeled sizes of 19 mm and 21 mm were implanted in 2 groups of 5 porcine aortic roots, with native annuli of 19 mm and 21 mm, by means of 2 different suture techniques: simple interrupted and noneverting mattress with pledgets. The aortic roots were tested in an in vitro mock loop. The stroke volume imposed by the mock loop was set at 40 mL, and was increased by steps of 15 mL until a stroke volume of 100 mL was attained. Main fluid-dynamic parameters were analyzed. Results At each level of stroke volume, ie, 40 mL, 55 mL, 70 mL, 85 mL, and 100 mL, the mean and peak pressure drops were significantly greater with the noneverting mattress suture with pledgets than with the simple interrupted suture. The effective orifice area behaved accordingly, being significantly smaller in the former case. Conclusions Our data show that the type of suture technique can influence bioprosthesis performance and that it is reasonable to assume that this is especially true in small annuli (≤21 mm). Thus, to optimize prosthesis performance and reduce the incidence of patient-prosthesis mismatch, the role of the suture technique should not be disregarded.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Malaria remains the most important mosquito‐borne infectious disease worldwide, with 229 million new cases and 409.000 deaths in 2019. The infection is caused by a protozoan parasite which attacks ...red blood cells by feeding on hemoglobin and transforming it into hemozoin. Despite the WHO recommendation of prompt malaria diagnosis, the quality of microscopy‐based diagnosis is frequently inadequate while rapid diagnostic tests based on antigens are not quantitative and still affected by non‐negligible false negative/positive results. PCR‐based methods are highly performant but still not widely used in endemic areas. Here, a diagnostic tool (TMek), based on the paramagnetic properties of hemozoin nanocrystals in infected red blood cells (i‐RBCs), is reported on. Exploiting the competition between gravity and magnetic forces, i‐RBCs in a whole blood specimen are sorted and electrically detected in a microchip. The amplitude and time evolution of the electrical signal allow for the quantification of i‐RBCs (in the range 10–105 i‐RBC µL−1) and the distinction of the infection stage. A preliminary validation study on 75 patients with clinical suspect of malaria shows on‐field operability, without false negative and a few false positive results. These findings indicate the potential of TMek as a quantitative, stage‐selective, rapid test for malaria.
Malaria is caused by the Plasmodium parasite which feeds on hemoglobin and produces paramagnetic hemozoin crystals within red blood cells (RBCs). A quantitative and stage‐selective pan‐malaria diagnostic test is disclosed, based on a simple concept implemented on a microchip: the sorting and electrical detection of infected RBCs, thanks to the competition between magnetic and gravity forces.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Hydrodynamic performance of stented bioprostheses is far below that of the native valve. One of the reasons is that the internal diameter of the prosthesis is usually smaller than that of the native ...valve. However, other valve characteristics are also important in generating the pressure drop. We aimed to assess, in an ex vivo pulsatile mock loop, the hydrodynamic behavior of two bioprostheses, Trifecta and Mitroflow, to ascertain which geometric terms are limiting factors in hydrodynamic performance. At stroke volumes between 30 and 60 ml, Trifecta showed lower pressure drop, energy dissipation and valve resistance, and greater effective orifice area. This trend was overturned at higher stroke volumes, with Mitroflow slightly outperforming Trifecta. The geometric determinants were consistent with these results. Trifecta achieved its maximum opening area already at the lowest stroke volumes, featuring a divergent shape at the systolic peak. Mitroflow showed a complex opening pattern, featuring a convergent shape at the systolic peak for lower stroke volumes, while reaching its maximum opening area at higher stroke volumes, with a divergent shape. The two bioprostheses, although similar in design, displayed different biomechanical behaviors. The internal diameter of each bioprosthesis did not show to be strictly correlated with its hydrodynamic characteristics.
The formation of thrombi on the streamlined surface of the bileaflet mechanical heart valves is one of the main disadvantages of such valves. Thrombi block the valve leaflets and disrupt the ...cardiovascular system. Diagnosis of thrombosis of the bileaflet mechanical heart valves is relevant and requires the creation of effective diagnostic tools. Hydroacoustic registration of the heart noise is one of the methods for diagnosing the operation of a mechanical heart valve. The purpose of the research is to determine the statistical characteristics of the vortex and jet flow through the open and semi-closed bileaflet mechanical heart valve, to identify hydroacoustic differences and diagnostic signs to determine the operating conditions of the valve. Experimental studies were conducted in laboratory conditions on a model of the left atrium and left ventricle of the heart between which there was the bileaflet mechanical heart valve. Hydrodynamic noise was recorded by miniature pressure sensors, which were located downstream of the valve. The vortex and jet flow behind the prosthetic heart valve were non-linear, random processes and were analyzed using the methods of mathematical statistics and probability theory. The integral and spectral characteristics of the pressure field were obtained and the differences in the noise levels and their spectral components near the central and side jets for the open and semi-closed mitral valve were established. It was shown that hydroacoustic measurements could be an effective basis for developing diagnostic equipment for monitoring the bileaflet mechanical heart valve operation. Doi: 10.28991/SciMedJ-2020-0204-1 Full Text: PDF
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