Superficial femoral artery stenting: Impact of stent design and overlapping on the local hemodynamics

Background: Superficial femoral arteries (SFAs) treated with self-expanding stents are widely affected by in-stent restenosis (ISR), especially in case of long lesions and multiple overlapping devices. The altered hemodynamics provoked by the stent is considered as a promoting factor of ISR. In this context, this work aims to analyze the impact of stent design and stent overlapping on patient-specific SFA hemodynamics.Methods: Through a morphing technique, single or multiple stents were virtually implanted within two patient specific, post-operative SFA models reconstructed from computed tomography. The stented domains were used to perform computational fluid dynamics simulations, quantifying wall shear stress (WSS) based descriptors including time-averaged WSS (TAWSS), oscillatory shear index (OSI), transverse WSS (transWSS), and WSS ratio (WSSRATIO). Four stent designs (three laser-cut - EverFlex, Zilver and S.M.A.R.T. - and one prototype braided stent), and three typical clinical scenarios accounting for different order of stent implantation and overlapping length were compared.Results: The main hemodynamic differences were found between the two types of stent designs (i.e. laser-cut vs. braided stents). The braided stent presented lower median transWSS and higher median WSS(RATIO )than the laser cut stents (p < 0.0001). The laser-cut stents presented comparable WSS-based descriptor values, except for the Zilver, exhibiting a median TAWSS ~30% higher than the other stents. Stent overlapping provoked an abrupt alteration of the WSS-based descriptors. The overlapping length, rather than the order of stent implantation, highly and negatively impacted the hemodynamics.Conclusion: The proposed computational workflow compared different SFA stent designs and stent overlapping configurations, highlighting those providing the most favorable hemodynamic conditions

ECLAIRE: Effects of Climate Change on Air Pollution Impacts and Response Strategies for European Ecosystems. Project final report

The central goal of ECLAIRE is to assess how climate change will alter the extent to which air pollutants threaten terrestrial ecosystems. Particular attention has been given to nitrogen compounds, especially nitrogen oxides (NOx) and ammonia (NH3), as well as Biogenic Volatile Organic Compounds (BVOCs) in relation to tropospheric ozone (O3) formation, including their interactions with aerosol components. ECLAIRE has combined a broad program of field and laboratory experimentation and modelling of pollution fluxes and ecosystem impacts, advancing both mechanistic understanding and providing support to European policy makers. The central finding of ECLAIRE is that future climate change is expected to worsen the threat of air pollutants on Europe’s ecosystems. Firstly, climate warming is expected to increase the emissions of many trace gases, such as agricultural NH3, the soil component of NOx emissions and key BVOCs. Experimental data and numerical models show how these effects will tend to increase atmospheric N deposition in future. By contrast, the net effect on tropospheric O3 is less clear. This is because parallel increases in atmospheric CO2 concentrations will offset the temperature-driven increase for some BVOCs, such as isoprene. By contrast, there is currently insufficient evidence to be confident that CO2 will offset anticipated climate increases in monoterpene emissions. Secondly, climate warming is found to be likely to increase the vulnerability of ecosystems towards air pollutant exposure or atmospheric deposition. Such effects may occur as a consequence of combined perturbation, as well as through specific interactions, such as between drought, O3, N and aerosol exposure. These combined effects of climate change are expected to offset part of the benefit of current emissions control policies. Unless decisive mitigation actions are taken, it is anticipated that ongoing climate warming will increase agricultural and other biogenic emissions, posing a challenge for national emissions ceilings and air quality objectives related to nitrogen and ozone pollution. The O3 effects will be further worsened if progress is not made to curb increases in methane (CH4) emissions in the northern hemisphere. Other key findings of ECLAIRE are that: 1) N deposition and O3 have adverse synergistic effects. Exposure to ambient O3 concentrations was shown to reduce the Nitrogen Use Efficiency of plants, both decreasing agricultural production and posing an increased risk of other forms of nitrogen pollution, such as nitrate leaching (NO3-) and the greenhouse gas nitrous oxide (N2O); 2) within-canopy dynamics for volatile aerosol can increase dry deposition and shorten atmospheric lifetimes; 3) ambient aerosol levels reduce the ability of plants to conserve water under drought conditions; 4) low-resolution mapping studies tend to underestimate the extent of local critical loads exceedance; 5) new dose-response functions can be used to improve the assessment of costs, including estimation of the value of damage due to air pollution effects on ecosystems, 6) scenarios can be constructed that combine technical mitigation measures with dietary change options (reducing livestock products in food down to recommended levels for health criteria), with the balance between the two strategies being a matter for future societal discussion. ECLAIRE has supported the revision process for the National Emissions Ceilings Directive and will continue to deliver scientific underpinning into the future for the UNECE Convention on Long-range Transboundary Air Pollution

ECLAIRE third periodic report

The ÉCLAIRE project (Effects of Climate Change on Air Pollution Impacts and Response Strategies for European Ecosystems) is a four year (2011-2015) project funded by the EU's Seventh Framework Programme for Research and Technological Development (FP7)

Engineering smart biomimetic nanocarriers for biomedical applications

The experimental results presented in this Doctoral Thesis shed light on the versatility and promising potential of cell-derived nanovesicles as a novel platform for addressing key challenges in modern medicine, ranging from targeted drug delivery to gene therapy. The exploration of cellsomes' biomimetic properties has demonstrated their capacity as innovative nanocarriers for molecules and drugs, as well as advanced biomimetic coating for other types of nanoparticles, capitalizing both on their tissue-specific targeting capabilities and on the possibility to engineer these nanocarriers to enhance the intracellular delivery.2024-11-1

Fusogenic Cell-Derived nanocarriers for cytosolic delivery of cargo inside living cells

A surface-engineered cell-derived nanocarrier was developed for efficient cytosolic delivery of encapsulated biologically active molecules inside living cells. Thus, a combination of aromatic-labeled and cationic lipids, instrumental in providing fusogenic properties, was intercalated into the biomimetic shell of self-assembled nanocarriers formed from cell membrane extracts. The nanocarriers were loaded, as a proof of concept, with either bisbenzimide molecules, a fluorescently labeled dextran polymer, the bicyclic heptapeptide phalloidin, fluorescently labeled polystyrene nanoparticles or a ribonucleoprotein complex (Cas9/sgRNA). The demonstrated nanocarrieŕs fusogenic behavior relies on the fusogen-like properties imparted by the intercalated exogenous lipids, which allows for circumventing lysosomal storage, thereby leading to efficient delivery into the cytosolic milieu where cargo regains functionThe authors thank the financial support of the European Research Council (starting grant #950421), the European Union (INTERREG V-A Spain–Portugal #0624_2IQBIONEURO_6_E, NextGenerationEU/PRTR and ERDF), the MCIN/AEI (PID2020-119206RB-I00, PID2020-119479RA-I00, PID2019-111218RB-I00, RYC-2017-23457 and RYC-2019-028238-I), and the Xunta de Galicia (ED431F 2021/02, 2021-CP090, ED431C 2022/018, and Centro Singular De Investigación de Galicia Accreditation 2019–2022 #ED431G 2019/03). This project was also supported by the ISCIII, under the framework of EuroNanoMed III_2020 (AC20/00041, PLATMED). We would also like to thank our colleagues Dr. M. Collado and Dr. M.A. Moreno-Mateos for their valuable insights and suggestions. We thank Dr. M. Collado (IDIS, Spain) for a gift of 293-T-HEK-dEGFP cellsS