Remote Robotic Coronary Interventions and the Impact of Network Jitter: An Ex Vivo Preclinical Study

Abstract Swine dysentery (SD) induced by Brachyspira hyodysentariae (Bhyo) causes colitis and mucohemorrhagic diarrhea in grow-finish pigs, however little is known about the physiological changes that occur to the gastrointestinal tract during Bhyo infection. Thus, the objective of this study was to evaluate the impact of a Bhyo challenge on intestinal function and integrity of pigs fed two divergent diets. A total of 36 Bhyo negative gilts (24.3 ± 3.6 kg BW) were selected and assigned to one of three treatment groups (n=12 pigs/trt): 1) Bhyo negative, 20% DDGS diet (CON), 2) Bhyo challenged, 20% DDGS diet (DDGS), and 3) Bhyo challenged, 10% DDGS, 5% beet pulp and 5% resistant potato starch diet (RS). Pigs were fed diets 21 days prior to challenge and on days post inoculation (dpi) 0 and 1, pigs were inoculated with Bhyo or sham. Fecal samples were collected for ATTD and pigs were euthanized for colon collection within 72 hours of initial observation of clinical SD, or at the end of the study (dpi 10-16). Tissues were assessed for ex vivo measures of intestinal integrity and mitochondrial function. The challenge resulted in high morbidity, with 88% of DDGS and RS pigs developing clinical SD. Colon transepithelial resistance was increased in DDGS pigs compared with CON and RS pigs (P=0.005), and colon macromolecule permeability was reduced in both DDGS and RS pigs compared with CON pigs (P=0.006), likely due to mucoid discharge. Colonic mitochondrial oxygen consumption was not impacted by treatment (P >0.10). Further, ATTD of DM, OM, N, and GE were reduced in DDGS pigs compared with CON pigs (P< 0.001), whilst nutrient digestibility was not reduced in RS pigs. Taken together, these data show Bhyo does not appear to reduce ex vivo colonic integrity. Further, the RS diet may reduce severity of a Bhyo challenge.

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Histological, Biomechanical, and Biological Properties of Genipin-Crosslinked Decellularized Peripheral Nerves

International Journal of Molecular Sciences ◽

10.3390/ijms22020674 ◽

2021 ◽

Vol 22 (2) ◽

pp. 674

Author(s):

Óscar Darío García-García ◽

Marwa El Soury ◽

David González-Quevedo ◽

David Sánchez-Porras ◽

Jesús Chato-Astrain ◽

...

Keyword(s):

Ex Vivo ◽

Nerve Repair ◽

Wistar Rat ◽

Biomechanical Properties ◽

Biological Properties ◽

Suitable Alternative ◽

Promising Alternative ◽

Histological Pattern ◽

The Impact

Acellular nerve allografts (ANGs) represent a promising alternative in nerve repair. Our aim is to improve the structural and biomechanical properties of biocompatible Sondell (SD) and Roosens (RS) based ANGs using genipin (GP) as a crosslinker agent ex vivo. The impact of two concentrations of GP (0.10% and 0.25%) on Wistar rat sciatic nerve-derived ANGs was assessed at the histological, biomechanical, and biocompatibility levels. Histology confirmed the differences between SD and RS procedures, but not remarkable changes were induced by GP, which helped to preserve the nerve histological pattern. Tensile test revealed that GP enhanced the biomechanical properties of SD and RS ANGs, being the crosslinked RS ANGs more comparable to the native nerves used as control. The evaluation of the ANGs biocompatibility conducted with adipose-derived mesenchymal stem cells cultured within the ANGs confirmed a high degree of biocompatibility in all ANGs, especially in RS and RS-GP 0.10% ANGs. Finally, this study demonstrates that the use of GP could be an efficient alternative to improve the biomechanical properties of ANGs with a slight impact on the biocompatibility and histological pattern. For these reasons, we hypothesize that our novel crosslinked ANGs could be a suitable alternative for future in vivo preclinical studies.

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64Cu-ATSM/64Cu-Cl2 and their relationship to hypoxia in glioblastoma: a preclinical study

EJNMMI Research ◽

10.1186/s13550-019-0586-6 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Elodie A. Pérès ◽

Jérôme Toutain ◽

Louis-Paul Paty ◽

Didier Divoux ◽

Méziane Ibazizène ◽

...

Keyword(s):

Ex Vivo ◽

In Vitro Study ◽

Tumor Location ◽

Preclinical Study ◽

Significant Rise ◽

Lower Oxygen ◽

Cu Complexes ◽

Ex Vivo Study

Abstract Background Diacetyl-bis(N4-methylthiosemicarbazone), labeled with 64Cu (64Cu-ATSM) has been suggested as a promising tracer for imaging hypoxia. However, various controversial studies highlighted potential pitfalls that may disable its use as a selective hypoxic marker. They also highlighted that the results may be tumor location dependent. Here, we first analyzed uptake of Cu-ATSM and its less lipophilic counterpart Cu-Cl2 in the tumor over time in an orthotopic glioblastoma model. An in vitro study was also conducted to investigate the hypoxia-dependent copper uptake in tumor cells. We then further performed a comprehensive ex vivo study to compare 64Cu uptake to hypoxic markers, specific cellular reactions, and also transporter expression. Methods μPET was performed 14 days (18F-FMISO), 15 days (64Cu-ATSM and 64Cu-Cl2), and 16 days (64Cu-ATSM and 64Cu-Cl2) after C6 cell inoculation. Thereafter, the brains were withdrawn for further autoradiography and immunohistochemistry. C6 cells were also grown in hypoxic workstation to analyze cellular uptake of Cu complexes in different oxygen levels. Results In vivo results showed that Cu-ASTM and Cu-Cl2 accumulated in hypoxic areas of the tumors. Cu-ATSM also stained, to a lesser extent, non-hypoxic regions, such as regions of astrogliosis, with high expression of copper transporters and in particular DMT-1 and CTR1, and also characterized by the expression of elevated astrogliosis. In vitro results show that 64Cu-ATSM showed an increase in the uptake only in severe hypoxia at 0.5 and 0.2% of oxygen while for 64Cu-Cl2, the cell retention was significantly increased at 5% and 1% of oxygen with no significant rise at lower oxygen percentages. Conclusion In the present study, we show that Cu-complexes undoubtedly accumulate in hypoxic areas of the tumors. This uptake may be the reflection of a direct dependency to a redox metabolism and also a reflection of hypoxic-induced overexpression of transporters. We also show that Cu-ATSM also stained non-hypoxic regions such as astrogliosis.

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Immediate versus staged revascularisation in multivessel coronary disease: an updated meta-analysis

European Heart Journal ◽

10.1093/ehjci/ehaa946.1487 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

F Von Renteln ◽

S Hassan ◽

K Szummer ◽

R Edfors ◽

D Venetsanos ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Coronary Disease ◽

Controlled Trial ◽

Interventional Treatment ◽

Index Hospitalisation ◽

Coronary Syndrome ◽

Coronary Interventions ◽

Baseline Characteristics ◽

Meta Regression ◽

The Impact

Abstract Background Percutaneous coronary interventions (PCIs) are often aimed at the culprit vessel in acute coronary syndromes (ACSs) followed by revascularisation of other stenoses later in the index hospitalisation or shortly after discharge. PCI delay of non-culprit coronary vessels stenoses is supported by lower contrast fluid use and thrombocyte aggregation. Distinct coronary interventions increase the risk of both non- and coronary artery complications, e.g. acute abdominal and periphery artery bleeding, suggesting undertaking all PCIs at the same time. Purpose To assess the effect on mortality and re-myocardial infarction (MI) of immediate versus staged revascularisation in multivessel coronary disease, with the latter constrained to initial PCI of the culprit coronary vessel. Methods The syntax of “randomised controlled trial (RCT) & acute coronary syndrome & complete revascularisation” was undertaken in PubMed. Clinical characteristics were gathered at the index hospitalisation. The intervention scenario was acute coronary syndrome or not. Meta-analyses calculated relative risk (RR) reductions on outcomes of 1) mortality and 2) re-MI. Meta-regression assessed linear difference between interventional treatment benefits and baseline characteristics. Results A total of 148 studies was found. Of those, 8 was found eligible for further analyses and their baseline characteristics are shown in Table 1. Comparison of immediate versus staged revascularisation on mortality was nonsignificant (RR, 1.19; 95% CI: 0.78–1.81, p=0.43) (Figure 1). The impact of Immediate vs staged revascularisation on re-MI was also nonsignificant (RR, 0.83; 95% CI: 0.44–1.55, p=0.56). Meta-regression found no associations between the outcomes and study characteristics (not shown). Conclusion The intervention of immediate compared to staged revascularisation assessed on outcomes of all-cause mortality and re-MI were nonsignificant. Figure 1 Funding Acknowledgement Type of funding source: None

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Gut-Ex-Vivo system as a model to study gluten response in celiac disease

Cell Death Discovery ◽

10.1038/s41420-021-00430-2 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Mara Gagliardi ◽

Nausicaa Clemente ◽

Romina Monzani ◽

Luca Fusaro ◽

Eleonora Ferrari ◽

...

Keyword(s):

Celiac Disease ◽

Intestinal Epithelium ◽

Complex Disease ◽

Ex Vivo ◽

Dynamic Condition ◽

Model Systems ◽

In Vivo Models ◽

Effective Manner ◽

Junction Protein ◽

The Impact

AbstractCeliac disease (CD) is a complex immune-mediated chronic disease characterized by a consistent inflammation of the gastrointestinal tract induced by gluten intake in genetically predisposed individuals. Although initiated by the interaction between digestion-derived gliadin, a gluten component, peptides, and the intestinal epithelium, the disorder is highly complex and involving other components of the intestine, such as the immune system. Therefore, conventional model systems, mainly based on two- or three-dimension cell cultures and co-cultures, cannot fully recapitulate such a complex disease. The development of mouse models has facilitated the study of different interacting cell types involved in the disorder, together with the impact of environmental factors. However, such in vivo models are often expensive and time consuming. Here we propose an organ ex vivo culture (gut-ex-vivo system) based on small intestines from gluten-sensitive mice cultivated in a dynamic condition, able to fully recapitulate the biochemical and morphological features of the mouse model exposed to gliadin (4 weeks), in 16 h. Indeed, upon gliadin exposure, we observed: i) a down-regulation of cystic fibrosis transmembrane regulator (CFTR) and an up-regulation of transglutaminase 2 (TG2) at both mRNA and protein levels; ii) increased intestinal permeability associated with deregulated tight junction protein expression; iii) induction and production of pro-inflammatory cytokines such as interleukin (IL)-15, IL-17 and interferon gamma (IFNγ); and iv) consistent alteration of intestinal epithelium/villi morphology. Altogether, these data indicate that the proposed model can be efficiently used to study the pathogenesis of CD, test new or repurposed molecules to accelerate the search for new treatments, and to study the impact of the microbiome and derived metabolites, in a time- and cost- effective manner.

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Cell–cell coupling and DNA methylation abnormal phenotypes in the after-hours mice

Epigenetics & Chromatin ◽

10.1186/s13072-020-00373-5 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Federico Tinarelli ◽

Elena Ivanova ◽

Ilaria Colombi ◽

Erica Barini ◽

Edoardo Balzani ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Neuronal Networks ◽

Molecular Mechanisms ◽

Ex Vivo ◽

Neuronal Cultures ◽

Functional Impairments ◽

After Hours ◽

The Impact

Abstract Background DNA methylation has emerged as an important epigenetic regulator of brain processes, including circadian rhythms. However, how DNA methylation intervenes between environmental signals, such as light entrainment, and the transcriptional and translational molecular mechanisms of the cellular clock is currently unknown. Here, we studied the after-hours mice, which have a point mutation in the Fbxl3 gene and a lengthened circadian period. Methods In this study, we used a combination of in vivo, ex vivo and in vitro approaches. We measured retinal responses in Afh animals and we have run reduced representation bisulphite sequencing (RRBS), pyrosequencing and gene expression analysis in a variety of brain tissues ex vivo. In vitro, we used primary neuronal cultures combined to micro electrode array (MEA) technology and gene expression. Results We observed functional impairments in mutant neuronal networks, and a reduction in the retinal responses to light-dependent stimuli. We detected abnormalities in the expression of photoreceptive melanopsin (OPN4). Furthermore, we identified alterations in the DNA methylation pathways throughout the retinohypothalamic tract terminals and links between the transcription factor Rev-Erbα and Fbxl3. Conclusions The results of this study, primarily represent a contribution towards an understanding of electrophysiological and molecular phenotypic responses to external stimuli in the Afh model. Moreover, as DNA methylation has recently emerged as a new regulator of neuronal networks with important consequences for circadian behaviour, we discuss the impact of the Afh mutation on the epigenetic landscape of circadian biology.

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The impact of skin massage frequency on the intrafollicular transport of silica nanoparticles: Validation of the ratchet effect on an ex vivo porcine skin model

European Journal of Pharmaceutics and Biopharmaceutics ◽

10.1016/j.ejpb.2020.11.018 ◽

2021 ◽

Vol 158 ◽

pp. 266-272

Author(s):

Loris Busch ◽

Yasemin Keziban ◽

Lars Dähne ◽

Cornelia M. Keck ◽

Martina C. Meinke ◽

...

Keyword(s):

Silica Nanoparticles ◽

Ex Vivo ◽

Skin Model ◽

Porcine Skin ◽

Ratchet Effect ◽

The Impact

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Towards Transabdominal Functional Photoacoustic Imaging of the Placenta: Improvement in Imaging Depth Through Optimization of Light Delivery

Annals of Biomedical Engineering ◽

10.1007/s10439-021-02777-0 ◽

2021 ◽

Author(s):

Kristie Huda ◽

Kenneth F. Swan ◽

Cecilia T. Gambala ◽

Gabriella C. Pridjian ◽

Carolyn L. Bayer

Keyword(s):

Delivery System ◽

Light Propagation ◽

Ex Vivo ◽

Photoacoustic Imaging ◽

Incidence Angle ◽

Incident Angle ◽

Placental Tissue ◽

Light Delivery ◽

Imaging Depth ◽

The Impact

AbstractFunctional photoacoustic imaging of the placenta could provide an innovative tool to diagnose preeclampsia, monitor fetal growth restriction, and determine the developmental impacts of gestational diabetes. However, transabdominal photoacoustic imaging is limited in imaging depth due to the tissue’s scattering and absorption of light. The aim of this paper was to investigate the impact of geometry and wavelength on transabdominal light delivery. Our methods included the development of a multilayer model of the abdominal tissue and simulation of the light propagation using Monte Carlo methods. A bifurcated light source with varying incident angle of light, distance between light beams, and beam area was simulated to analyze the effect of light delivery geometry on the fluence distribution at depth. The impact of wavelength and the effects of variable thicknesses of adipose tissue and muscle were also studied. Our results showed that the beam area plays a major role in improving the delivery of light to deep tissue, in comparison to light incidence angle or distance between the bifurcated fibers. Longer wavelengths, with incident fluence at the maximum permissible exposure limit, also increases fluence within deeper tissue. We validated our simulations using a commercially available light delivery system and ex vivo human placental tissue. Additionally, we compared our optimized light delivery to a commercially available light delivery system, and conclude that our optimized geometry could improve imaging depth more than 1.6×, bringing the imaging depth to within the needed range for transabdominal imaging of the human placenta.

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