Consistency of aortic distensibility and pulse wave velocity estimates with respect to the Bramwell-Hill theoretical model: a cardiovascular magnetic resonance study

<p>Abstract</p> <p>Background</p> <p>Arterial stiffness is considered as an independent predictor of cardiovascular mortality, and is increasingly used in clinical practice. This study aimed at evaluating the consistency of the automated estimation of regional and local aortic stiffness indices from cardiovascular magnetic resonance (CMR) data.</p> <p>Results</p> <p>Forty-six healthy subjects underwent carotid-femoral pulse wave velocity measurements (<it>CF_PWV</it>) by applanation tonometry and CMR with steady-state free-precession and phase contrast acquisitions at the level of the aortic arch. These data were used for the automated evaluation of the aortic arch pulse wave velocity (<it>Arch_PWV</it>), and the ascending aorta distensibility (<it>AA_Distc, AA_Distb)</it>, which were estimated from ascending aorta strain (<it>AA_Strain</it>) combined with either carotid or brachial pulse pressure. The local ascending aorta pulse wave velocity <it>AA_PWVc </it>and <it>AA_PWVb </it>were estimated respectively from these carotid and brachial derived distensibility indices according to the Bramwell-Hill theoretical model, and were compared with the <it>Arch_PWV</it>. In addition, a reproducibility analysis of <it>AA_PWV </it>measurement and its comparison with the standard <it>CF_PWV </it>was performed. Characterization according to the Bramwell-Hill equation resulted in good correlations between <it>Arch_PWV </it>and both local distensibility indices <it>AA_Distc </it>(r = 0.71, p < 0.001) and <it>AA_Distb </it>(r = 0.60, p < 0.001); and between <it>Arch_PWV </it>and both theoretical local indices <it>AA_PWVc </it>(r = 0.78, p < 0.001) and <it>AA_PWVb </it>(r = 0.78, p < 0.001). Furthermore, the <it>Arch_PWV </it>was well related to <it>CF_PWV </it>(r = 0.69, p < 0.001) and its estimation was highly reproducible (inter-operator variability: 7.1%).</p> <p>Conclusions</p> <p>The present work confirmed the consistency and robustness of the regional index <it>Arch_PWV </it>and the local indices <it>AA_Distc and AA_Distb </it>according to the theoretical model, as well as to the well established measurement of <it>CF_PWV</it>, demonstrating the relevance of the regional and local CMR indices.</p

Mesenchymal Stromal Cells Primed with Paclitaxel Provide a New Approach for Cancer Therapy

BACKGROUND: Mesenchymal stromal cells may represent an ideal candidate to deliver anti-cancer drugs. In a previous study, we demonstrated that exposure of mouse bone marrow derived stromal cells to Doxorubicin led them to acquire anti-proliferative potential towards co-cultured haematopoietic stem cells (HSCs). We thus hypothesized whether freshly isolated human bone marrow Mesenchymal stem cells (hMSCs) and mature murine stromal cells (SR4987 line) primed in vitro with anti-cancer drugs and then localized near cancer cells, could inhibit proliferation. METHODS AND PRINCIPAL FINDINGS: Paclitaxel (PTX) was used to prime culture of hMSCs and SR4987. Incorporation of PTX into hMSCs was studied by using FICT-labelled-PTX and analyzed by FACS and confocal microscopy. Release of PTX in culture medium by PTX primed hMSCs (hMSCsPTX) was investigated by HPLC. Culture of Endothelial cells (ECs) and aorta ring assay were used to test the anti-angiogenic activity of hMSCsPTX and PTX primed SR4987(SR4987PTX), while anti-tumor activity was tested in vitro on the proliferation of different tumor cell lines and in vivo by co-transplanting hMSCsPTX and SR4987PTX with cancer cells in mice. Nevertheless, despite a loss of cells due to chemo-induced apoptosis, both hMSCs and SR4987 were able to rapidly incorporate PTX and could slowly release PTX in the culture medium in a time dependent manner. PTX primed cells acquired a potent anti-tumor and anti-angiogenic activity in vitro that was dose dependent, and demonstrable by using their conditioned medium or by co-culture assay. Finally, hMSCsPTX and SR4987PTX co-injected with human cancer cells (DU145 and U87MG) and mouse melanoma cells (B16) in immunodeficient and in syngenic mice significantly delayed tumor takes and reduced tumor growth. CONCLUSIONS: These data demonstrate, for the first time, that without any genetic manipulation, mesenchymal stromal cells can uptake and subsequently slowly release PTX. This may lead to potential new tools to increase efficacy of cancer therapy

Dynamic metabolic patterns tracking neurodegeneration and gliosis following 26S proteasome dysfunction in mouse forebrain neurons

Metabolite profling is an important tool that may better capture the multiple features of neurodegeneration. With the considerable parallels between mouse and human metabolism, the use of metabolomics in mouse models with neurodegenerative pathology provides mechanistic insight and ready translation into aspects of human disease. Using 400MHz nuclear magnetic resonance spectroscopy we have carried out a temporal region-specifc investigation of the metabolome of neuron-specifc 26S proteasome knockout mice characterised by progressive neurodegeneration and Lewy-like inclusion formation in the forebrain. An early signifcant decrease in N-acetyl aspartate revealed evidence of neuronal dysfunction before cell death that may be associated with changes in brain neuroenergetics, underpinning the use of this metabolite to track neuronal health. Importantly, we show early and extensive activation of astrocytes and microglia in response to targeted neuronal dysfunction in this context, but only late changes in myo-inositol; the best established glial cell marker in magnetic resonance spectroscopy studies, supporting recent evidence that additional early neuroinfammatory markers are needed. Our results extend the limited understanding of metabolite changes associated with gliosis and provide evidence that changes in glutamate homeostasis and lactate may correlate with astrocyte activation and have biomarker potential for tracking neuroinfammation

Search for gravitational waves associated with gamma-ray bursts detected by Fermi and Swift during the LIGO–Virgo run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC–2020 March 27 17:00 UTC). We conduct two independent searches: a generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate