Peptides for Surface Modification Applicate of Vascular Polymer

Polymeric biomaterials used for applications such as coronary and vascular bypass grafting have demonstrated poor patency due to their surface thrombogenicity, initiation of chronic inflammation and unfavourable host tissue responses. The aim of this thesis has been to develop a peptide which would demonstrate an inhibitory effect on blood coagulation and/or improved endothelial cell adhesion. Employing the RGD (Arginine-Glycine-Aspartate) peptide as a base, GRGD, GRGDS and GRGD(AhxGRGD)3 were produced. In order to allow incorporation of the peptide into the polymer matrix the corresponding lauric acid (LA) conjugated peptides were synthesised. In vitro determination of blood clotting time and tissue factor activity was utilised to determine the optimum peptide concentration for an anti-thrombogenic effect. Cytotoxicity and cell adhesion were assessed on endothelial cells. The results obtained suggest that LA-GRGD offered the best anti-thrombogenic effect whilst LA-GRGDS had the most improved cell adhesive effect. These two peptides were then used to investigate the surface modification of poly(carbonate-urea)urethane (PCU). The PCU surface was modified by passive peptide coating or peptide incorporation into the polymer matrix. Cell adhesion and activity studies showed that the incorporated LA-GRGDS peptide produced a significant (P<0.05) improvement. Biocompatibility studies demonstrated no adverse effects with respect to either platelet adhesion or haemolysis. The inhibition of platelet factor 4 obtained with coated GRGD, GRGDS and incorporated LA-GRGD was comparable to that obtained with heparin coating. An in vitro flow study showed that significantly (P<0.005) more incorporated peptide (42.6%) was retained on the surface of the polymer after 8 hours flow compared to coated (20%). In conclusion the direct incorporation of an LA conjugated peptide into the matrix of the polymer was successful with the peptide retaining its activity. This process of incorporation by solvent casting is attractive from a commercial viewpoint and shows the potential for future development and use in a clinical situation to produce a surface modified PCU polymer

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century