scholarly journals Advanced culture systems for ex vivo human vascular tissue conditioning

Author(s):  
Gianfranco Beniamino Fiore ◽  
Simona Seminati ◽  
Lorenzo Pietro Coppadoro ◽  
Elia Pederzani ◽  
Marco Piola ◽  
...  

Our experience shows that using bioengineering approaches facilitates the understanding of vascular physio-pathological mechanisms and, in perspective, will speed up the development of new life-saving treatments. The use of human samples, particularly operating room-derived samples, which would have been otherwise discarded, is a very valuable approach. In line with the 3Rs principles, this methodology is worth the cost of being set up and managed, wherever and whenever possible

2020 ◽  
pp. bjophthalmol-2020-317214
Author(s):  
Hasan Naveed ◽  
Fong May Chew ◽  
Hanbin Lee ◽  
Edward Hughes ◽  
Mayank A Nanavaty

PurposeTo assess whether pars plana vitrectomy (PPV) is an aerosol-generating procedure (AGP) in an ex vivo experimental model.MethodsIn this ex vivo study on 10 porcine eyes, optical particle counter was used to measure particles ≤10 μm using cumulative mode in the six in-built channels: 0.3 μm, 0.5 μm, 1 μm, 2.5 μm, 5 μm and 10 μm aerosols during PPV. Two parts of the study were as follows: (1) to assess the pre-experimental baseline aerosol count in the theatre environment where there are dynamic changes in temperature and humidity and (2) to measure aerosol generation with 23-gauge and 25-gauge set-up. For each porcine eye, five measurements were taken for each consecutive step in the experiment including pre-PPV, during PPV, fluid–air exchange (FAX) and venting using a flute with 23-gauge set-up and a chimney with 25-gauge set-up. Therefore, a total of 200 measurements were recorded.ResultsWith 23-gauge and 25-gauge PPV, there was no significant difference in aerosol generation in all six channels comparing pre-PPV versus PPV or pre-PPV versus FAX. Venting using flute with 23-gauge PPV showed significant reduction of aerosol ≤1 μm. Air venting using chimney with 25-gauge set-up showed no significant difference in aerosol of ≤1 μm. For cumulative aerosol counts of all particles measuring ≤5 μm, compared with pre-PPV, PPV or FAX, flute venting in 23-gauge set-up showed significant reduction unlike the same comparison for chimney venting in 25-gauge set-up.ConclusionPPV and its associate steps do not generate aerosols ≤10 μm with 23-gauge and 25-gauge set-ups.


2021 ◽  
Vol 8 (4) ◽  
pp. 39
Author(s):  
Luciana Da Silveira Cavalcante ◽  
Shannon N. Tessier

Heart transplantation became a reality at the end of the 1960s as a life-saving option for patients with end-stage heart failure. Static cold storage (SCS) at 4–6 °C has remained the standard for heart preservation for decades. However, SCS only allows for short-term storage that precludes optimal matching programs, requires emergency surgeries, and results in the unnecessary discard of organs. Among the alternatives seeking to extend ex vivo lifespan and mitigate the shortage of organs are sub-zero or machine perfusion modalities. Sub-zero approaches aim to prolong cold ischemia tolerance by deepening metabolic stasis, while machine perfusion aims to support metabolism through the continuous delivery of oxygen and nutrients. Each of these approaches hold promise; however, complex barriers must be overcome before their potential can be fully realized. We suggest that one barrier facing all experimental efforts to extend ex vivo lifespan are limited research tools. Mammalian models are usually the first choice due to translational aspects, yet experimentation can be restricted by expertise, time, and resources. Instead, there are instances when smaller vertebrate models, like the zebrafish, could fill critical experimental gaps in the field. Taken together, this review provides a summary of the current gold standard for heart preservation as well as new technologies in ex vivo lifespan extension. Furthermore, we describe how existing tools in zebrafish research, including isolated organ, cell specific and functional assays, as well as molecular tools, could complement and elevate heart preservation research.


2021 ◽  
Author(s):  
Spencer Shirk ◽  
Danielle Kerr ◽  
Crystal Saraceni ◽  
Garret Hand ◽  
Michael Terrenzi ◽  
...  

ABSTRACT Upon the U.S. FDA approval in early November for a monoclonal antibody proven to potentially mitigate adverse outcomes from coronavirus disease 2019 (COVID-19) infections, our small overseas community hospital U.S. Naval Hospital Rota, Spain (USNH Rota) requested and received a limited number of doses. Concurrently, our host nation, which previously had reported the highest number of daily deaths from COVID-19, was deep within a second wave of infections, increasing hospital admissions, near intensive care unit capacity, and deaths. As USNH Rota was not normally equipped for the complex infusion center required to effectively deliver the monoclonal antibody, we coordinated a multi-directorate and multidisciplinary effort in order to set up an infusion room that could be dedicated to help with our fight against COVID. Identifying a physician team lead, with subject matter experts from nursing, pharmacy, facilities, and enlisted corpsmen, our team carefully ensured that all requisite steps were set up in advance in order to be able to identify the appropriate patients proactively and treat them safely with the infusion that has been clinically proven to decrease hospital admissions and mortality. Additional benefits included the establishment of an additional negative pressure room near our emergency room for both COVID-19 patients and, when needed, the monoclonal antibody infusion. In mid-January, a COVID-19-positive patient meeting the clinical criteria for monoclonal antibody infusion was safely administered this potentially life-saving medication, a first for small overseas hospitals. Here, we describe the preparation, challenges, obstacles, lessons learned, and successful outcomes toward effectively using the monoclonal antibody overseas.


Materials ◽  
2021 ◽  
Vol 14 (13) ◽  
pp. 3678
Author(s):  
Vera Chernonosova ◽  
Alexandr Gostev ◽  
Ivan Murashov ◽  
Boris Chelobanov ◽  
Andrey Karpenko ◽  
...  

We examined the physicochemical properties and the biocompatibility and hemocompatibility of electrospun 3D matrices produced using polyurethane Pellethane 2363-80A (Pel-80A) blends Pel-80A with gelatin or/and bivalirudin. Two layers of vascular grafts of 1.8 mm in diameter were manufactured and studied for hemocompatibility ex vivo and functioning in the infrarenal position of Wistar rat abdominal aorta in vivo (n = 18). Expanded polytetrafluoroethylene (ePTFE) vascular grafts of similar diameter were implanted as a control (n = 18). Scaffolds produced from Pel-80A with Gel showed high stiffness with a long proportional limit and limited influence of wetting on mechanical characteristics. The electrospun matrices with gelatin have moderate capacity to support cell adhesion and proliferation (~30–47%), whereas vascular grafts with bivalirudin in the inner layer have good hemocompatibility ex vivo. The introduction of bivalirudin into grafts inhibited platelet adhesion and does not lead to a change hemolysis and D-dimers concentration. Study in vivo indicates the advantages of Pel-80A grafts over ePTFE in terms of graft occlusion, calcification level, and blood velocity after 6 months of implantation. The thickness of neointima in Pel-80A–based grafts stabilizes after three months (41.84 ± 20.21 µm) and does not increase until six months, demonstrating potential for long-term functioning without stenosis and as a suitable candidate for subsequent preclinical studies in large animals.


2021 ◽  
Vol 6 (1) ◽  
pp. e004318
Author(s):  
Aduragbemi Banke-Thomas ◽  
Kerry L M Wong ◽  
Francis Ifeanyi Ayomoh ◽  
Rokibat Olabisi Giwa-Ayedun ◽  
Lenka Benova

BackgroundTravel time to comprehensive emergency obstetric care (CEmOC) facilities in low-resource settings is commonly estimated using modelling approaches. Our objective was to derive and compare estimates of travel time to reach CEmOC in an African megacity using models and web-based platforms against actual replication of travel.MethodsWe extracted data from patient files of all 732 pregnant women who presented in emergency in the four publicly owned tertiary CEmOC facilities in Lagos, Nigeria, between August 2018 and August 2019. For a systematically selected subsample of 385, we estimated travel time from their homes to the facility using the cost-friction surface approach, Open Source Routing Machine (OSRM) and Google Maps, and compared them to travel time by two independent drivers replicating women’s journeys. We estimated the percentage of women who reached the facilities within 60 and 120 min.ResultsThe median travel time for 385 women from the cost-friction surface approach, OSRM and Google Maps was 5, 11 and 40 min, respectively. The median actual drive time was 50–52 min. The mean errors were >45 min for the cost-friction surface approach and OSRM, and 14 min for Google Maps. The smallest differences between replicated and estimated travel times were seen for night-time journeys at weekends; largest errors were found for night-time journeys at weekdays and journeys above 120 min. Modelled estimates indicated that all participants were within 60 min of the destination CEmOC facility, yet journey replication showed that only 57% were, and 92% were within 120 min.ConclusionsExisting modelling methods underestimate actual travel time in low-resource megacities. Significant gaps in geographical access to life-saving health services like CEmOC must be urgently addressed, including in urban areas. Leveraging tools that generate ‘closer-to-reality’ estimates will be vital for service planning if universal health coverage targets are to be realised by 2030.


Author(s):  
Lina Y Alkaissi ◽  
Martin E Winberg ◽  
Stéphanie DS Heil ◽  
Staffan Haapaniemi ◽  
Pär Myrelid ◽  
...  

Abstract Background The first visible signs of Crohn’s disease (CD) are microscopic erosions over the follicle-associated epithelium (FAE). The aim of the study was to investigate the effects of human α-defensin 5 (HD5) on adherent-invasive Escherichia coli LF82 translocation and HD5 secretion after LF82 exposure in an in vitro model of human FAE and in human FAE ex vivo. Methods An in vitro FAE-model was set up by the coculture of Raji B cells and Caco-2-cl1 cells. Ileal FAE from patients with CD and controls were mounted in Ussing chambers. The effect of HD5 on LF82 translocation was studied by LF82 exposure to the cells or tissues with or without incubation with HD5. The HD5 secretion was measured in human FAE exposed to LF82 or Salmonella typhimurium. The HD5 levels were evaluated by immunofluorescence, immunoblotting, and ELISA. Results There was an increased LF82 translocation across the FAE-model compared with Caco-2-cl1 (P < 0.05). Incubation of cell/tissues with HD5 before LF82 exposure reduced bacterial passage in both models. Human FAE showed increased LF82 translocation in CD compared with controls and attenuated passage after incubation with sublethal HD5 in both CD and controls (P < 0.05). LF82 exposure resulted in a lower HD5 secretion in CD FAE compared with controls (P < 0.05), whereas Salmonella exposure caused equal secretion on CD and controls. There were significantly lower HD5 levels in CD tissues compared with controls. Conclusions Sublethal HD5 reduces the ability of LF82 to translocate through FAE. The HD5 is secreted less in CD in response to LF82, despite a normal response to Salmonella. This further implicates the integrated role of antimicrobial factors and barrier function in CD pathogenesis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
D. Kuetting ◽  
J. Luetkens ◽  
A. Faron ◽  
A. Isaak ◽  
U. Attenberger ◽  
...  

AbstractOur aim was to investigate the diagnostic yield of rapid T1-mapping for the differentiation of malignant and non-malignant effusions in an ex-vivo set up. T1-mapping was performed with a fast modified Look-Locker inversion-recovery (MOLLI) acquisition and a combined turbo spin-echo and inversion-recovery sequence (TMIX) as reference. A total of 13 titrated albumin-solutions as well as 48 samples (29 ascites/pleural effusions from patients with malignancy; 19 from patients without malignancy) were examined. Samples were classified as malignant-positive histology, malignant-negative histology and non-malignant negative histology. In phantom analysis both mapping techniques correlated with albumin-content (MOLLI: r = − 0.97, TMIX: r = − 0.98). MOLLI T1 relaxation times were shorter in malignancy-positive histology fluids (2237 ± 137 ms) than in malignancy-negative histology fluids (2423 ± 357 ms) as well as than in non-malignant-negative histology fluids (2651 ± 139 ms); post hoc test for all intergroup comparisons: < 0.05. ROC analysis for differentiation between malignant and non-malignant effusions (malignant positive histology vs. all other) showed an (AUC) of 0.89 (95% CI 0.77–0.96). T1 mapping allows for non-invasive differentiation of malignant and non-malignant effusions in an ex-vivo set up.


2014 ◽  
Vol 665 ◽  
pp. 643-646
Author(s):  
Ying Liu ◽  
Yan Ye ◽  
Chun Guang Li

Metalearning algorithm learns the base learning algorithm, targeted for improving the performance of the learning system. The incremental delta-bar-delta (IDBD) algorithm is such a metalearning algorithm. On the other hand, sparse algorithms are gaining popularity due to their good performance and wide applications. In this paper, we propose a sparse IDBD algorithm by taking the sparsity of the systems into account. Thenorm penalty is contained in the cost function of the standard IDBD, which is equivalent to adding a zero attractor in the iterations, thus can speed up convergence if the system of interest is indeed sparse. Simulations demonstrate that the proposed algorithm is superior to the competing algorithms in sparse system identification.


Hand ◽  
2018 ◽  
Vol 15 (2) ◽  
pp. 208-214 ◽  
Author(s):  
Joseph A. Gil ◽  
Avi D. Goodman ◽  
Andrew P. Harris ◽  
Neill Y. Li ◽  
Arnold-Peter C. Weiss

Background: The objective of this study was to determine the comparative cost-effectiveness of performing initial revision finger amputation in the emergency department (ED) versus in the operating room (OR) accounting for need for unplanned secondary revision in the OR. Methods: We retrospectively examined patients presenting to the ED with traumatic finger and thumb amputations from January 2010 to December 2015. Only those treated with primarily revision amputation were included. Following initial management, the need for unplanned reoperation was assessed and associated with setting of initial management. A sensitivity analysis was used to determine the cost-effectiveness threshold for initial management in the ED versus the OR. Results: Five hundred thirty-seven patients had 677 fingertip amputations, of whom 91 digits were initially primarily revised in the OR, and 586 digits were primarily revised in the ED. Following initial revision, 91 digits required unplanned secondary revision. The unplanned secondary revision rates were similar between settings: 13.7% digits from the ED and 12.1% of digits from the OR ( P = .57). When accounting for direct costs, an incidence of unplanned revision above 77.0% after initial revision fingertip amputation in the ED would make initial revision fingertip amputation in the OR cost-effective. Therefore, based on the unplanned secondary revision rate, initial management in the ED is more cost-effective than in the OR. Conclusions: There is no significant difference in the incidence of unplanned/secondary revision of fingertip amputation rate after the initial procedure was performed in the ED versus the OR.


2002 ◽  
Vol 13 (2) ◽  
pp. 263-279 ◽  
Author(s):  
Dominique Finon

Nuclear phase-out policies and the European obligation to liberalise electricity markets could put the French nuclear option dramatically at risk by influencing social preferences or by constraining power producers' investment choices in the future. So far, the particular institutional set-up which has allowed the efficient build-up and operation of several series of standardised reactors preserves the stability of the main elements of the option. However, important adaptations to the evolving industrial and political environment occur and contribute to changing the option. Some institutional changes (such as local public inquiry, creation of a Parliamentary committee, independence of safety authorities) and divergence between industrial interests already allow debates on internal options such as reprocessing, type of waste management deposits, ordering of an advanced PWR. These changes improve the cost transparency, even if internalisation of nuclear externalities (cost of insurance, provisions for waste management) is still incomplete. However, when effective, this internalisation would not affect definitively the competitive position of the nuclear production because of the parallel internalisation of CO2 externalities from fossil fuel power generation in the official rationale. Consequently the real issue for the future of the nuclear option in France remains the preservation of social acceptability in the perception of nuclear risks.


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