Search Results (26)

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, underscoring the need for continuous innovation in diagnostics and treatment. Mock circulation loops (MCLs) systems have recently emerged as new research platforms capable of replicating the hemodynamics of the human cardiovascular system. This review explores the expanding applications of MCLs to cardiovascular diseases beyond their traditional role in testing ventricular assist devices and heart failure management. We focus on their versatility in simulating various cardiovascular conditions, particularly arterial diseases such as atherosclerosis, stenosis, and aneurysms. This review traces the evolution of MCLs and their integration with computational simulations and real-time data acquisition systems. MCLs provide detailed insights into hemodynamic responses under diverse conditions, enhancing the precision and safety of cardiovascular interventions. This comprehensive review emphasizes the critical role of MCLs in advancing cardiovascular research, refining clinical interventions, and improving patient outcomes. Full article

Fontan circulation is a fragile system in which imperfections at any of multiple levels may compromise the quality of life, produce secondary pathophysiology, and shorten life span. Increased inferior vena caval pressure itself may play a role in “Fontan failure”. This study describes a mock flow loop model (MFL) designed to quantitatively estimate pulmonary flow entrainment induced by continuous and pulsed flow injections. A patient generic 3D-printed phantom model of the total cavopulmonary connection (TCPC) with average dimensions matching those of a 2–4-year-old patient was inserted in an MFL derived from a reduced lumped parameter model (LPM) representing cardiovascular circulation. The LPM comprises four 2-element Windkessel compartments (compliance and resistance), approximating the upper and lower systemic circulations and the right and left pulmonary circulations. The prescribed cardiac output is about 2.3 L/min for a body surface area of $0.675{ \mathrm{m}}^2$. The injections originate from an external pump through a 7–9 fr catheter, following a strict protocol suggested by the clinical team, featuring a variation in injection rate (flow rate), injection volume, and injection modality (continuous or pulsed). The key measurements in this study are the flow rates sampled at the distal pulmonary arteries, as well as at the upper and lower body boundaries. These measurements were then used to calculate effective entrainment as the difference between the measured and expected flow rates, as well as jet relaxation (rise and fall time of injection). The results show that for continuous or pulsed injections, varying the total volume injected has no significant influence on the entrainment rate across all injection rates. On the other hand, for both injection modalities, increasing the injection rate results in a reduction in entrainment that is consistent across all injected volumes. This study demonstrates the effectiveness of a high-speed injection jet entraining a slow co-flow while determining the potential for fluid buildup, which could ultimately cause an increase in caval pressure. To avoid the increase in caval pressure due to mass accumulation, we added a fenestration to our proposed injection jet shunt-assisted Fontan models. It was found that for a set of well-defined parameters, the jet not only can be beneficial to the local flow, but any adverse effect can be obviated by careful tuning. These results were also cross-validated with similar in silico findings. Full article

This research is focused on the laboratory study of salt crystallization inhibitor products as new materials for conservation treatments which can be applied to mortars and painted plasters; as is well known, salt crystallization is one of the most frequent causes of decay processes on decorated architectural surfaces in a wide range of environments. Specifically, the study targets the field of the preventive conservation of mural paintings within rupestrian heritage sites. For the first time, systematic investigations were performed on mock-ups made of plaster painted with two different pigments: yellow ochre and carbon black. Two types of phosphonate inhibitors, PBTC (2-phosphonobutane-1,2,4-tricarboxylic acid) and ATMP (aminotris (methylene phosphonic acid)), were chosen and applied at two different concentrations. Given the limited literature available, and the presence of pigments potentially sensitive to treatment with salt inhibitors, preliminary tests were required. Their effects on the chromatic features of the pigments were evaluated visually and using colorimetry. The changes in the behaviour of water circulation in the mortar resulting from the treatments were evaluated through water vapour permeability and absorption tests. Accelerated crystallization experiments were carried out to assess how inhibitors could influence the growth of salts and the resulting material damage. The latter was carried out by employing sodium sulphate and calcium sulphate solutions, quantifying the damage to the specimens through material loss in weight and the percentage of painted surface loss. Based on the overall results, the product with the best performance was identified was ATMP 0.1% (by volume) in deionized water. The obtained results show that salt inhibitor treatments are promising for in situ application and could represent an innovative approach to promote the sustainable conservation of mural painting, particularly those located in hypogeal contexts, where the salt supply cannot be removed and slowing the growth of salts and/or changing their crystalline habitus may be effective in limiting their damage. Full article

Background: This study was conducted to confirm the reliability of an in vitro mechanically induced hemolysis test (ISO 10993-4:2017), which is essential for ensuring the safety of blood pumps. Methods: For appropriate anticoagulant selection, porcine blood was prepared in anticoagulant citrate dextrose solution A (ACD-A), heparin, and citrate phosphate dextrose adenine (CPDA-1), respectively, according to the ASTM F1830 standard. Anticoagulant-treated porcine and bovine blood were circulated in a mock circulatory loop (MCL) for 6 h to observe the rate of plasma-free hemoglobin (pfHb) and RBCs with morphological integrity. Results: A morphological loss of red blood cells (RBCs) was observed over time. While there were differences in morphological loss depending on the anticoagulant, no consistent trend could be identified. The pfHb concentration was significantly higher in bovine than in porcine blood. Conversely, the number of RBCs with morphological integrity decreased over time in both, but the ratio of RBCs with morphological integrity was similar across all timepoints. Conclusions: The percentage of RBCs with morphological integrity can be used as a reliable indicator for the interpretation of mechanically induced hemolysis results in different blood types. Furthermore, the reliability of the in vitro mechanically induced hemolysis test (ISO 10993-4:2017) was assessed. Full article

The application of tissue-engineered heart valves in the high-pressure circulatory system is still challenging. One possible solution is the development of biohybrid scaffolds with textile reinforcement to achieve improved mechanical properties. In this article, we present a manufacturing process of bio-inspired fiber reinforcement for an aortic valve scaffold. The reinforcement structure consists of polyvinylidene difluoride monofilament fibers that are biomimetically arranged by a novel winding process. The fibers were embedded and fixated into electrospun polycarbonate urethane on a cylindrical collector. The scaffold was characterized by biaxial tensile strength, bending stiffness, burst pressure and hemodynamically in a mock circulation system. The produced fiber-reinforced scaffold showed adequate acute mechanical and hemodynamic properties. The transvalvular pressure gradient was 3.02 ± 0.26 mmHg with an effective orifice area of 2.12 ± 0.22 cm². The valves sustained aortic conditions, fulfilling the ISO-5840 standards. The fiber-reinforced scaffold failed in a circumferential direction at a stress of 461.64 ± 58.87 N/m and a strain of 49.43 ± 7.53%. These values were above the levels of tested native heart valve tissue. Overall, we demonstrated a novel manufacturing approach to develop a fiber-reinforced biomimetic scaffold for aortic heart valve tissue engineering. The characterization showed that this approach is promising for an in situ valve replacement. Full article

The vibration of the heart valves’ closure is an important component of the heart sound and contains important information about the mechanical activity of a heart. Stenosis of the distal pulmonary artery can lead to pulmonary hypertension (PH). Therefore, in this paper, the relationship between the vibration sound of heart valves and the pulmonary artery blood pressure was investigated to contribute to the noninvasive detection of PH. In this paper, a lumped parameter circuit platform of pulmonary circulation was first set to guide the establishment of a mock loop of circulation. By adjusting the distal vascular resistance of the pulmonary artery, six different pulmonary arterial pressure states were achieved. In the experiment, pulmonary artery blood pressure, right ventricular blood pressure, and the vibration sound of the pulmonary valve and tricuspid valve were measured synchronously. Features of the time domain and frequency domain of two valves’ vibration sound were extracted. By conducting a significance analysis of the inter-group features, it was found that the amplitude, energy and frequency features of vibration sounds changed significantly. Finally, the continuously varied pulmonary arterial blood pressure and valves’ vibration sound were obtained by continuously adjusting the resistance of the distal pulmonary artery. A backward propagation neural network and deep learning model were used, respectively, to estimate the features of pulmonary arterial blood pressure, pulmonary artery systolic blood pressure, the maximum rising rate of pulmonary artery blood pressure and the maximum falling rate of pulmonary artery blood pressure by the vibration sound of the pulmonary and tricuspid valves. The results showed that the pulmonary artery pressure parameters can be well estimated by valve vibration sounds. Full article

Vascular disease is the leading cause of morbidity and mortality and a major cause of disability for Americans, and arterial stenosis is its most common form in systemic arteries. Hemodynamic characterization in a stenosed arterial system plays a crucial role in the diagnosis of its lesion severity and the decision-making process for revascularization, but it is not readily available in the current clinical measurements. The newly emerged image-based computational hemodynamics (ICHD) technique provides great potential to characterize the hemodynamics with fine temporospatial resolutions in realistic human vessels, but medical data is rather limited for validation requirements. We present an image-based experimental hemodynamics (IEHD) technique through a mock circulation loop (MCL) to bridge this critical gap. The MCL mimics blood circulation in human stenosed systemic arterial systems that can be either 3D-printed silicone, artificial, or cadaver arteries and thus enables in vitro measurement of hemodynamics. In this work, we focus on the development and validation of the MCL for the in vitro measurement of blood pressure in stenosed silicone arteries anatomically extracted from medical imaging data. Five renal and six iliac patient cases are studied. The pressure data from IEHD were compared with those from ICHD and medical measurement. The good agreements demonstrate the reliability of IEHD. We also conducted two parametric studies to demonstrate the medical applicability of IEHD. One was the cardiovascular response to MCL parameters. We found that blood pressure has a linear correlation with stroke volume and heart rate. Another was the effect of arterial stenosis, characterized by the volumetric reduction (VR) of the arterial lumen, on the trans-stenotic pressure gradient (TSPG). We parametrically varied the stenosis degree and measured the corresponding TSPG. The TSPG-VR curve provides a critical VR that can be used to assess the true hemodynamic severity of the stenosis. Meanwhile, the TSPG at VR = 0 can predict the potential pressure improvement after revascularization. Unlike the majority of existing MCLs that are mainly used to test medical devices involving heart function, this MCL is unique in its specific focus on pressure measurement in stenosed human systemic arteries. Meanwhile, rigorous hemodynamic characterization through concurrent IEHD and ICHD will significantly enhance our current understanding of the pathophysiology of stenosis and contribute to advancements in the medical treatment of arterial stenosis. Full article

Pashkevilim, printed wall notices posted around Jewish ultra-Orthodox neighborhoods, serve as one of the religious community’s popular communication channels. The Pashkevilim mostly deal with controversial intra-community issues and feature a unique style, extremist rhetoric, and vocabulary derived from the religious literature. Humorous imitations of the genre arose over the years, which circulated in the community and outside of it, posing a challenge to the rabbinic hegemony. Although humorous Pashkevilim have likely been present for as long as Pashkevilim themselves, there is currently a lack of research investigating them. By adopting a critical discourse analysis approach, the current study aims to address this gap by identifying the predominant types of humorous Pashkevilim and analyzing the discursive practices they employ. The findings indicate three main discursive practices that characterize humorous Pashkevilim: parody, satire, and irony. While parody exaggerates the formal characteristics of the genre and mocks them, satire and irony criticize the content and topics discussed in traditional Pashkevilim, especially on the subject of Jewish law and religious stringency. These practices express an oppositional reading of the genre, which challenges its function as well as its socio-cultural, political, and religious significance. Full article

In this work, a soft-elastic pulsation pump (SEPP) has been made and investigated. Here, 3D printing was used to make casting molds and a melt-removal method using wax was employed. The SEPP was made of silicone rubber and driven by an external squeezing mechanism. A silicone one-way valve was also made which prevented backflow after the fluid was squeezed out of the pump chamber. The material characteristics of the SEPP including durability were examined. The pump operating parameters were confirmed to differential pressure of 100 mm Hg in a close flow loop. The average flow rate was 2 L/min, while yielding a peak flow of 8 L/min, and a stroke volume of 70 mL. A preliminary trial using fresh animal blood had shown that the SEPP has good protection on the blood. Therefore, within the resources available, an interesting idea for an effective SEPP has been proposed and realized in the laboratory. The technical details of the SEPP described, and the experimental results reported here form a good basis for making higher capacity SEPPs. This effort may help make its way to an effective ventricular assist device. Full article

The objective of this paper was to analyze the effect of yellow-safety-line designs on the behavior of passengers at the platform edge in metro stations. To achieve this, an experimental approach, based on observation, was used in existing metro stations in Santiago and Valparaiso, Chile. The experiments were carried out for different widths of the yellow safety line: 5 cm, 10 cm, 24 cm, and 40 cm. In addition, the material was also changed to include yellow adhesive tape, PVC material with yellow pods, and carbon- and fiberglass-reinforced material with yellow pods. The experiments considered a mock-up to represent the hall entrance of the train and its adjacent platform, in which 25 participants were recruited, some of whom had reduced mobility. The results obtained from the experiments showed that the greater the width of the yellow safety line at the edge of the platform, the greater the level of compliance that was achieved. In addition, surveys were carried out with the passengers who participated in the experiment; the majority felt more comfortable and safer for a width of 24 cm. Some participants highlighted the phenomenon of “safety offers comfort”. In conclusion, the results of this research will allow the generation of new design and safety standards for the train–platform interface, which can then be tested in existing stations. Future research is expected to study the space occupied by different types of passengers and to study accessibility in other circulation spaces of metro stations. Full article

Current influenza vaccines demonstrate low vaccine efficacy, especially when the predominantly circulating strain and vaccine are mismatched. The novel influenza vaccine platform M2- or BM2-deficient single replication (M2SR and BM2SR) has been shown to safely induce strong systemic and mucosal antibody responses and provide protection against significantly drifted influenza strains. In this study, we demonstrate that both monovalent and quadrivalent (Quad) formulations of M2SR are non-pathogenic in mouse and ferret models, eliciting robust neutralizing and non-neutralizing serum antibody responses to all strains within the formulation. Following challenge with wildtype influenza strains, vaccinated mice and ferrets demonstrated reduced weight loss, decreased viral replication in the upper and lower airways, and enhanced survival as compared to mock control groups. Mice vaccinated with H1N1 M2SR were completely protected from heterosubtypic H3N2 challenge, and BM2SR vaccines provided sterilizing immunity to mice challenged with a cross-lineage influenza B virus. Heterosubtypic cross-protection was also seen in the ferret model, with M2SR vaccinated animals exhibiting decreased viral titers in nasal washes and lungs following the challenge. BM2SR-vaccinated ferrets elicited robust neutralizing antibodies toward significantly drifted past and future influenza B strains. Mice and ferrets that received quadrivalent M2SR were able to mount immune responses equivalent to those seen with each of the four monovalent vaccines, demonstrating the absence of strain interference in the commercially relevant quadrivalent formulation. Full article

This study characterized the susceptibility and dynamic of porcine deltacoronavirus infection in grower pigs under experimental conditions using a combination of syndromic and laboratory assessments. Seven-week-old conventional pigs (n = 24) were randomly distributed into PDCoV- (n = 12) and mock-inoculated (n = 12) groups. Serum was collected at −7, 0, 3, 7, 10, 14, 17, 21, 28, 35, and 42 days post-inoculation (DPI) to evaluate viremia (RT-qPCR) and antibody response (S1-based ELISA). Viral shedding and potential infectivity were determined using pen-based oral fluids and feces collected every other day between DPI 0 and 42. Pigs showed no clinical signs or viremia throughout the study. Active virus shedding was detected in feces (6-22 DPI) and oral fluids (2-30 DPI), peaking at DPI 10. IgG was first detected at DPI 10, being statistically significant after DPI 14 and increasing thereafter, coinciding with the progressive resolution of the infection. Likewise, a significant increase in proinflammatory IL-12 was detected between DPI 10 and 21 in PDCoV-inoculated pigs, which could enhance innate resistance to PDCoV infection. This study demonstrated that active surveillance based on systematic sampling and laboratory testing combining molecular and serological tools is critical for the accurate detection of subclinical circulation of PDCoV in pigs after weaning. Full article

The COVID-19 pandemic emerged in 2020 and has caused an unprecedented burden to all countries in the world. SARS-CoV-2 continues to circulate and antigenically evolve, enabling multiple reinfections. To address the issue of the virus antigenic variability, T cell-based vaccines are being developed, which are directed to more conserved viral epitopes. We used live attenuated influenza vaccine (LAIV) virus vector to generate recombinant influenza viruses expressing various T-cell epitopes of SARS-CoV-2 from either neuraminidase (NA) or non-structural (NS1) genes, via the P2A self-cleavage site. Intranasal immunization of human leukocyte antigen-A*0201 (HLA-A2.1) transgenic mice with these recombinant viruses did not result in significant SARS-CoV-2-specific T-cell responses, due to the immunodominance of NP₃₆₆ influenza T-cell epitope. However, side-by-side stimulation of peripheral blood mononuclear cells (PBMCs) of COVID-19 convalescents with recombinant viruses and LAIV vector demonstrated activation of memory T cells in samples stimulated with LAIV/SARS-CoV-2, but not LAIV alone. Hamsters immunized with a selected LAIV/SARS-CoV-2 prototype were protected against challenge with influenza virus and a high dose of SARS-CoV-2 of Wuhan and Delta lineages, which was confirmed by reduced weight loss, milder clinical symptoms and less pronounced histopathological signs of SARS-CoV-2 infection in the lungs, compared to LAIV- and mock-immunized animals. Overall, LAIV is a promising platform for the development of a bivalent vaccine against influenza and SARS-CoV-2. Full article

Extracorporeal membrane oxygenation (ECMO) has become an important therapeutic approach in the COVID-19 pandemic. The development and research in this field strongly relies on animal models; however, efforts are being made to find alternatives. In this work, we present a new mock circuit for ECMO that allows measurements of the oxygen transfer rate of a membrane lung at full ECMO blood flow. The mock utilizes a large reservoir of heparinized porcine blood to measure the oxygen transfer rate of the membrane lung in a single passage. The oxygen transfer rate is calculated from blood flow, hemoglobin value, venous saturation, and post-membrane arterial oxygen pressure. Before the next measuring sequence, the blood is regenerated to a venous condition with a sweep gas of nitrogen and carbon dioxide. The presented mock was applied to investigate the effect of a recirculation loop on the oxygen transfer rate of an ECMO setup. The recirculation loop caused a significant increase in post-membrane arterial oxygen pressure (paO₂). The effect was strongest for the highest recirculation flow. This was attributed to a smaller boundary layer on gas fibers due to the increased blood velocity. However, the increase in paO₂ did not translate to significant increases in the oxygen transfer rate because of the minor significance of physically dissolved oxygen for gas transfer. In conclusion, our results regarding a new ECMO mock setup demonstrate that recirculation loops can improve ECMO performance, but not enough to be clinically relevant. Full article

To provide an alternative treatment option for patients with end-stage lung disease, we aim for biohybrid lung development (BHL) based on hollow fiber membrane (HFM) technology used in extracorporeal membrane oxygenators. For long-term BHL application, complete hemocompatibility of all blood-contacting surfaces is indispensable and can be achieved by their endothelialization. Indeed, albumin/heparin (AH) coated HFM enables initial endothelialization, but as inexplicable cell loss under flow conditions was seen, we assessed an alternative HFM coating using fibronectin (FN). Therefore, endothelial cell (EC) adherence and viability on both coated HFM were analyzed by fluorescence-based staining. Functional leukocyte and thrombocyte adhesion assays were performed to evaluate hemocompatibility, also in comparison to blood plasma coated HFM as a clinically relevant control. To assess monolayer resistance and EC behavior under clinically relevant flow conditions, a mock circulation setup was established, which also facilitates imitation of lung-disease specific blood gas settings. Besides quantification of flow-associated cell loss, endothelial responses towards external stimuli, like flow exposure or TNFα stimulation, were analyzed by qRT-PCR, focusing on inflammation, thrombus formation and extracellular matrix production. Under static conditions, both coated HFM enabled the generation of a viable, confluent, non-inflammatory and anti-thrombogenic monolayer. However, by means of homogenous FN coating, cell retention and physiologic gene regulation towards an improved hemocompatible-and extracellular matrix producing phenotype, was significantly superior compared to the inhomogeneous AH coating. In summary, our adaptable in-house FN coating secures the endothelial requirements for long-term BHL application and may promote monolayer establishment on all other blood contacting surfaces of the BHL (e.g., cannulae). Full article