Tensile and Compressive Mechanical Behaviour of Human Blood Clot Analogues

Endovascular thrombectomy procedures are significantly influenced by the mechanical response of thrombi to the multi-axial loading imposed during retrieval. Compression tests are commonly used to determine compressive ex vivo thrombus and clot analogue stiffness. However, there is a shortage of data in tension. This study compares the tensile and compressive response of clot analogues made from the blood of healthy human donors in a range of compositions. Citrated whole blood was collected from six healthy human donors. Contracted and non-contracted fibrin clots, whole blood clots and clots reconstructed with a range of red blood cell (RBC) volumetric concentrations (5–80%) were prepared under static conditions. Both uniaxial tension and unconfined compression tests were performed using custom-built setups. Approximately linear nominal stress–strain profiles were found under tension, while strong strain-stiffening profiles were observed under compression. Low- and high-strain stiffness values were acquired by applying a linear fit to the initial and final 10% of the nominal stress–strain curves. Tensile stiffness values were approximately 15 times higher than low-strain compressive stiffness and 40 times lower than high-strain compressive stiffness values. Tensile stiffness decreased with an increasing RBC volume in the blood mixture. In contrast, high-strain compressive stiffness values increased from 0 to 10%, followed by a decrease from 20 to 80% RBC volumes. Furthermore, inter-donor differences were observed with up to 50% variation in the stiffness of whole blood clot analogues prepared in the same manner between healthy human donors

Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Funding: F Carvalho and E Fernandes acknowledge support from Fundação para a Ciência e a Tecnologia, I.P. (FCT), in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy i4HB; FCT/MCTES through the project UIDB/50006/2020. J Conde acknowledges the European Research Council Starting Grant (ERC-StG-2019-848325). V M Costa acknowledges the grant SFRH/BHD/110001/2015, received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006.proofepub_ahead_of_prin

Development of a patient-specific cerebral vasculature fluid-structure-interaction model

Development of in-silico models of patient-specific cerebral artery networks presents several significant technical challenges: (i) The resolution and smoothness of medical CT images are much lower than the required element/cell length for FEA/CFD/FSI models; (ii) contact between vessels, and indeed self contact of high tortuosity vessel segments are not clearly identifiable from medical CT images. Commercial model construction software does not provide customised solutions for such technical challenges, with the result that accurate, efficient and automated development of patient-specific models of the cerebral vessels is not facilitated. This paper presents the development of a customised and highly automated platform for the generation of high resolution patient-specific FEA/CFD/FSI models from clinical images. This platform is used to perform the first fluid-structure-interaction patient-specific analysis of blood flow and artery deformation of an occluded cerebral vessel. Results demonstrate that in addition to flow disruption, clot occlusion significantly alters the geometry and strain distribution in the vessel network, with the blocked M2 segment undergoing axial elongation. The new computational approach presented in this study can be further developed as a clinical diagnostic tool and as a platform for thrombectomy device design

Applicability assessment of a stent-retriever thrombectomy finite-element model

An acute ischaemic stroke appears when a blood clot blocks the blood flow in a cerebral artery. Intra-arterial thrombectomy, a mini-invasive procedure based on stent technology, is a mechanical available treatment to extract the clot and restore the blood circulation. After stent deployment, the clot, trapped in the stent struts, is pulled along with the stent towards a receiving catheter. Recent clinical trials have confirmed the effectiveness and safety of mechanical thrombectomy. However, the procedure requires further investigation. The aim of this study is the development of a numerical finiteelement- based model of the thrombectomy procedure. In vitro thrombectomy tests are performed in different vessel geometries and one simulation for each test is carried out to verify the accuracy and reliability of the proposed numerical model. The results of the simulations confirm the efficacy of the model to replicate all the experimental setups. Clot stress and strain fields from the numerical analysis, which vary depending on the geometric features of the vessel, could be used to evaluate the possible fragmentation of the clot during the procedure. The proposed in vitro/in silico comparison aims at assessing the applicability of the numerical model and at providing validation evidence for the specific in vivo thrombectomy outcomes prediction

Cycloplatinated(II) Complexes Bearing 1,1′-Bis(diphenylphosphino)ferrocene Ligand: Biological Evaluation and Molecular Docking Studies

In this study, the cytotoxic activities of structurally related cycloplatinated(II) complexes containing chelating and bridging 1,1′-bis(diphenylphosphino)ferrocene (dppf) ligand derived from a wide range of C^N cyclometalating ligands (vpy = deprotonated 2-vinylpyridine, bzq = deprotonated benzo[h]quinoline, bpy = deprotonated 2,2′-bipyridine, bpyO = deprotonated 2,2′-bipyridine N-oxide, and ppy = deprotonated 2-phenylpyridine), were evaluated against human lung (A549), ovarian (SKOV3) and breast (MCF-7) cancer cell lines. The most cytotoxic compounds, 2a, 2c and 2d, effectively produced cell death by inducing apoptosis in the A549, SKOV3 and MCF-7 cancer cell lines. In addition, the molecular docking simulation was performed to determine the specific binding mode and the orientation of binding to DNA. According to the results of biological evaluation, the dppf-containing cycloplatinated(II) complexes exhibited strong interactions with DNA as well as high cytotoxicity and apoptosis-inducing activities to human cancer cell line. The present study suggests that precise rational design of new platinum-based complexes would result in the preparation of potential anticancer drugs, which can induce facile apoptosis

Metal–Organic Frameworks and Covalent Organic Frameworks as Platforms for Photodynamic Therapy

We describe the newest approach to photodynamic therapy (PDT) using metal-organic frameworks (MOFs) and covalent organic frameworks (COFs). PDT’s characteristic method of treating cancer as noninvasive and selective has garnered much attention. PDT has entered the realm of nanotechnology to overcome various challenges that are hindering its effectiveness. Porous materials, which are more functional than small molecules, are being explored as platforms for PDT. MOFs are at the forefront of these investigations, and the anti-tumor ability of well-designed nano-MOFs (nMOFs) has recently been reported. We also discuss the possibility of using COFs for future-use PDT

(Benzyl isocyanide)gold(I) pyrimidine‐2‐thiolate complex: Synthesis and biological activity

The reaction of [(Me2S)AuCl] with an equimolar amount of benzyl isocyanide (PhCH2NC) ligand led to the formation of complex [(PhCH2NC)AuCl] (1). The solid‐state structure of 1 was determined using the X‐ray diffraction method. Through a salt metathesis reaction, the chloride ligand in 1 was replaced by pyrimidine‐2‐thiolate (SpyN−) to afford the complex [(PhCH2NC)Au(η1‐S‐Spy)] (2), which was characterized spectroscopically. The cytotoxic activities of 1 and 2 were evaluated against three human cancer cell lines: ovarian carcinoma (SKOV3), lung carcinoma (A549) and breast carcinoma (MCF‐7). Complex 2 showed higher cytotoxicity than cisplatin against SKOV3 and MCF‐7 cancer cell lines. It showed a strong anti‐proliferative activity with IC50 of 7.80, 6.26 and 6.14 μM, compared with that measured for cisplatin which was 7.62, 12.36 and 11.47 μM, against A549, SKOV3 and MCF‐7 cell lines, respectively. The induction of cellular apoptosis by 2 was also studied on MCF‐7 cell line. Our results indicated that 2 could induce apoptosis in cancerous cells in a dose‐dependent manner