Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part II: platelet-related biologic features

Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this second article, we investigate the platelet-associated features of this biomaterial. During PRF processing by centrifugation, platelets are activated and their massive degranulation implies a very significant cytokine release. Concentrated platelet-rich plasma platelet cytokines have already been quantified in many technologic configurations. To carry out a comparative study, we therefore undertook to quantify PDGF-BB, TGFbeta-1, and IGF-I within PPP (platelet-poor plasma) supernatant and PRF clot exudate serum. These initial analyses revealed that slow fibrin polymerization during PRF processing leads to the intrinsic incorporation of platelet cytokines and glycanic chains in the fibrin meshes. This result would imply that PRF, unlike the other platelet concentrates, would be able to progressively release cytokines during fibrin matrix remodeling; such a mechanism might explain the clinically observed healing properties of PRF.     

High Individual Heterogeneity of Neutralizing Activities against the Original Strain and Nine Different Variants of SARS-CoV-2

Background: Since the beginning of the COVID-19 pandemic, several SARS-CoV-2 variants have sequentially emerged. In France, most cases were due to spike D641G-harbouring viruses that descended initially from the Wuhan strain, then by the variant of B.1.160 lineage we called Marseille-4 since the summer of 2020, which was followed by the Alpha and Beta variants in early 2021, then the Delta variant currently. Methods: We determined the neutralising antibody (nAb) titres in sera from convalescent individuals previously infected by these four major local variants and from vaccine recipients to the original Wuhan strain and nine variants, including two recent circulating Delta isolates. Results: The results show high inter-individual heterogeneity in nAbs, especially according to the variant tested. The major variations among nAbs are based on the genotype responsible for the infection. Patients previously infected with the beta and B.1.160 variants had the lowest nAb titres. We show that this heterogeneity is well explained by spike protein mutants modelling using in silico approaches. The highest titres were observed in individuals vaccinated with the Pfizer/BioNTech COVID-19 vaccine, even against the delta variant. Conclusions: Immunity acquired naturally after infection is highly dependent on the infecting variant, and, unexpectedly, mRNA-based vaccine efficacy was shown to be often better than natural immunity in eliciting neutralising antibodies.     

Production of Aluminum AA6061 Hybrid Nanocomposite from Waste Metal Using Hot Extrusion Process: Strength Performance and Prediction by RSM and Random Forest

To date, various studies have analysed the effects of reinforced ceramic on the properties of AA6061 recycled aluminum alloy chips, such as the tensile strength and fractography. However, a comprehensive analysis of the properties of hybrid composite with the addition of nano-silica oxide and nano-copper oxide reinforcements is still very limited. Therefore, this study aimed to optimise the factors comprising the preheating temperature (PHT), preheating time (PHti), and volume fraction (VF) of reinforcements then determine their impacts on the physical and mechanical properties of the recycled solid-state extruded composite aluminum chips. A total of 45 specimens were fabricated through the hot extrusion technique. The response surface methodology (RSM) was employed to study the optimisation at a PHT range of 450–550 °C with PHti of 1–3 h and VF of 1–3 vol% for both reinforcements (SiO₂ and CuO). Moreover, a random forest (RF) model was developed to optimize the model based on a metaheuristic method to improve the model performance. Based on the experimental results the RF model achieve better results than response surface methodology (RSM). The functional quadratic regression is curvature and the tested variable shows stable close data of the mean 0 and α2. Based on the Pareto analysis, the PHT and VF were key variables that significantly affected the UTS, microhardness, and density of the product. The maximum properties were achieved at an optimum PHT, PHti, and VF of 541 °C, 2.25 h, 1 vol% SiO₂ and 2.13 vol% CuO, respectively. Furthermore, the morphological results of the tensile fractured surface revealed the homogenous distribution of nano-reinforced CuO and SiO₂ particles in the specimens’ structure.     

Inhibition of Orbivirus Replication by Fluvastatin and Identification of the Key Elements of the Mevalonate Pathway Involved

Statin derivatives can inhibit the replication of a range of viruses, including hepatitis C virus (HCV, Hepacivirus), dengue virus (Flavivirus), African swine fever virus (Asfarviridae) and poliovirus (Picornaviridae). We assess the antiviral effect of fluvastatin in cells infected with orbiviruses (bluetongue virus (BTV) and Great Island virus (GIV)). The synthesis of orbivirus outer-capsid protein VP2 (detected by confocal immunofluorescence imaging) was used to assess levels of virus replication, showing a reduction in fluvastatin-treated cells. A reduction in virus titres of ~1.7 log (98%) in fluvastatin-treated cells was detected by a plaque assay. We have previously identified a fourth non-structural protein (NS4) of BTV and GIV, showing that it interacts with lipid droplets in infected cells. Fluvastatin, which inhibits 3-hydroxy 3-methyl glutaryl CoA reductase in the mevalonic acid pathway, disrupts these NS4 interactions. These findings highlight the role of the lipid pathways in orbivirus replication and suggest a greater role for the membrane-enveloped orbivirus particles than previously recognised. Chemical intermediates of the mevalonic acid pathway were used to assess their potential to rescue orbivirus replication. Pre-treatment of IFNAR^(−/−) mice with fluvastatin promoted their survival upon challenge with live BTV, although only limited protection was observed.     

Decision support system for the detection and grading of hard exudates from color fundus photographs

Diabetic retinopathy is a major cause of blindness, and its earliest signs include damage to the blood vessels and the formation of lesions in the retina. Automated detection and grading of hard exudates from the color fundus image is a critical step in the automated screening system for diabetic retinopathy. We propose novel methods for the detection and grading of hard exudates and the main retinal structures. For exudate detection, a novel approach based on coarse-to-fine strategy and a new image-splitting method are proposed with overall sensitivity of 93.2% and positive predictive value of 83.7% at the pixel level. The average sensitivity of the blood vessel detection is 85%, and the success rate of fovea localization is 100%. For exudate grading, a polar fovea coordinate system is adopted in accordance with medical criteria. Because of its competitive performance and ability to deal efficiently with images of variable quality, the proposed technique offers promising and efficient performance as part of an automated screening system for diabetic retinopathy.