Researchers are searching for possible links between unusual clotting and the Oxford-AstraZeneca coronavirus vaccine. Researchers are searching for possible links between unusual clotting and the ...Oxford-AstraZeneca coronavirus vaccine.
Dysfunctional endothelium contributes to more diseases than any other tissue in the body. Small interfering RNAs (siRNAs) can help in the study and treatment of endothelial cells in vivo by durably ...silencing multiple genes simultaneously, but efficient siRNA delivery has so far remained challenging. Here, we show that polymeric nanoparticles made of low-molecular-weight polyamines and lipids can deliver siRNA to endothelial cells with high efficiency, thereby facilitating the simultaneous silencing of multiple endothelial genes in vivo. Unlike lipid or lipid-like nanoparticles, this formulation does not significantly reduce gene expression in hepatocytes or immune cells even at the dosage necessary for endothelial gene silencing. These nanoparticles mediate the most durable non-liver silencing reported so far and facilitate the delivery of siRNAs that modify endothelial function in mouse models of vascular permeability, emphysema, primary tumour growth and metastasis.
Coagulation Dysfunction: A Hallmark in COVID-19 Fei, Yang; Tang, Ning; Liu, Hefei ...
Archives of pathology & laboratory medicine (1976),
10/2020, Letnik:
144, Številka:
10
Journal Article
Recenzirano
Odprti dostop
* Context.--The coronavirus disease 2019 (COVID-19) is a highly contagious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coagulation dysfunction is a ...hallmark in patients with COVID-19. Fulminant thrombotic complications emerge as critical issues in patients with severe COVID-19. Objective.--To present a review of the literature and discuss the mechanisms of COVID-19 underlying coagulation activation and the implications for anticoagulant and thrombolytic treatment in the management of COVID-19. Data Sources.--We performed a systemic review of scientific papers on the topic of COVID-19, available online via the PubMed NCBI, medRxiv, and Preprints as of May 15, 2020. We also shared our experience on the management of thrombotic events in patients with COVID-19. Conclusions.--COVID-19-associated coagulopathy ranges from mild laboratory alterations to disseminated intravascular coagulation (DIC) with a predominant phenotype of thrombotic/multiple organ failure. Characteristically, high D-dimer levels on admission and/or continuously increasing concentrations of D-dimer are associated with disease progression and poor overall survival. SARS-CoV-2 infection triggers the immunehemostatic response. Drastic inflammatory responses including, but not limited to, cytokine storm, vasculopathy, and NETosis may contribute to an overwhelming activation of coagulation. Hypercoagulability and systemic thrombotic complications necessitate anticoagulant and thrombolytic interventions, which provide opportunities to prevent or reduce "excessive" thrombin generation while preserving "adaptive" hemostasis and bring additional benefit via their anti-inflammatory effect in the setting of COVID-19.
The selective biomimetic aptasensor for blood coagulation factor IX protein (FIX) detection was developed using an interdigitated electrode with an Archimedean spiral pattern. In contrast to ...conventional molecularly imprinted polymer (MIP) techniques, aptamer was employed as a macromonomer to accelerate double binding affinity. To preserve the aptamer profile in its protein-binding orientation, FIX protein and thiol-modified RNA aptamers were complexed prior to MIP fabrication. The immobilized aptamer-FIX complex was surrounded by a polymer generated by the electropolymerization of 3-thiophene acetic acid (3TAA). Subsequent to FIX protein removal, leaves imprinted cavities facilitate selective FIX protein detection in conjunction with the affinity of embedded aptamer affinity. The Archimedean IDE surface was functionalized with carbon nanohorn (CNH) and gold nanourchin (GNU) to increase the imprinting ratios and sensor sensitivity. The developed FIX-aptasensor shows a detection limit of 0.06 fM, which is 660-fold higher than aptamer-embedded MIP nanoparticles. Moreover, the sensor exhibited greater selectivity for FIX, discriminating IgG and thrombin. As a preliminary study for clinical use, the sensor was used to analyze human serum without target spiking and detected FIX-protein with a relative standard deviation of 9.18%. It was ascertained that the sensor maintained 85% sustained performance for a duration of five weeks.
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•New generation of MIP-aptasensor developed for the intrinsic Tenase biomarker (FIX).•Embedded carbon nano-horn and gold nano-urchin for a highly sensitive detection.•Binding posture of aptamer was retained in MIP synthesis to assist target rebinding.•MIP-aptasensor gives 0.06 fM limit detection from pure FIX solution with 1.85% RSD.•The sensor detects FIX from human serum albumin without spiking the target.
Background: In contrast to fine particles, less is known of the inflammatory and coagulation impacts of coarse particulate matter (PM.sub.10-2.5, particulate matter with aerodynamic diameter less ...than or equal to10 microm and >2.5 microm). Toxicological research suggests that these pathways might be important processes by which PM.sub.10-2.5 impacts health, but there are relatively few epidemiological studies due to a lack of a national PM.sub.10-2.5 monitoring network. Objectives: We used new spatiotemporal exposure models to examine associations of both 1-y and 1-month average PM.sub.10-2.5 concentrations with markers of inflammation and coagulation. Methods: We leveraged data from 7,071 Multi-Ethnic Study of Atherosclerosis and ancillary study participants 45-84 y of age who had repeated plasma measures of inflammatory and coagulation biomarkers. We estimated PM.sub.10-2.5 at participant addresses 1 y and 1 month before each of up to four exams (2000-2012) using spatiotemporal models that incorporated satellite, regulatory monitoring, and local geographic data and accounted for spatial correlation. We used random effects models to estimate associations with interleukin-6 (IL-6), C- reactive protein (CRP), fibrinogen, and D-dimer, controlling for potential confounders. Results: Increases in PM.sub.10-2.5 were not associated with greater levels of inflammation or coagulation. A 10-microg/m.sup.3 increase in annual average PM.sub.10-2.5 was associated with a 2.5% decrease in CRP 95% confidence interval (CI): -5.5, 0.6. We saw no association between annual average PM.sub.10-2.5 and the other markers (IL-6: -0.7%, 95% CI: -2.6, 1.2; fibrinogen: -0.3%, 95% CI: -0.9, 0.3; D- dimer: -0.2%, 95% CI: -2.6, 2.4). Associations consistently showed that a 10-microg/m.sup.3 increase in 1- month average PM.sub.10-2.5 was associated with reduced inflammation and coagulation, though none were distinguishable from no association (IL-6: -1.2%, 95% CI: -3.0, 0.5; CRP: -2.5%, 95% CI: -5.3, 0.4; fibrinogen: -0.4%, 95% CI: -1.0, 0.1; D-dimer: -2.0%, 95% CI: -4.3, 0.3). Discussion: We found no evidence that PM.sub.10-2.5 is associated with higher inflammation or coagulation levels. More research is needed to determine whether the inflammation and coagulation pathways are as important in explaining observed PM.sub.10-2.5 health impacts in humans as they have been shown to be in toxicology studies or whether PM.sub.10-2.5 might impact human health through alternative biological mechanisms.
Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient. When these recommendations are implemented patient outcomes may be improved.
The ...multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document represents an updated version of the guideline published by the group in 2007 and updated in 2010. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature.
Key changes encompassed in this version of the guideline include new recommendations on the appropriate use of vasopressors and inotropic agents, and reflect an awareness of the growing number of patients in the population at large treated with antiplatelet agents and/or oral anticoagulants. The current guideline also includes recommendations and a discussion of thromboprophylactic strategies for all patients following traumatic injury. The most significant addition is a new section that discusses the need for every institution to develop, implement and adhere to an evidence-based clinical protocol to manage traumatically injured patients. The remaining recommendations have been re-evaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies.
A comprehensive, multidisciplinary approach to trauma care and mechanisms with which to ensure that established protocols are consistently implemented will ensure a uniform and high standard of care across Europe and beyond.
Medical cotton dressing is cheap and widely used in diversified fields, but in the application of promoting wound healing, the continuous research of multifunctional medical cotton dressing is still ...of great significance. Here, we developed a fresh type of antibacterial cotton dressing through a succinct strategy based on chemically anchoring polyhexamethylene biguanide (PHMB). Intriguingly, after PHMB modification, the cotton dressing exhibited outstanding antibacterial performance which could maintain >99.99% antibacterial rate after several treatments, including washing 50 times, repeated use 10 times, UV irradiation for 7 days, cationic dyes dying, and conditioned under 90 °C water bath for 2 h. In addition, the water contact angle of cotton dressing increased dramatically from 0° to 111°, which could facilitate bacterial adhesion, thus further enhance the antibacterial efficiency, and easily remove the bacterial debris. Apart from that, the developed cotton dressing showed good cytocompatibility, promoted blood clotting and expression of platelets, and promoted the wound healing process in the infection intervened skin wound model. Taken together, this antibacterial cotton dressing with desirable blood clotting, sustained protection against bacterial infection and bacterial removal features shows the potential to be a candidate for infected skin wound healing.
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Rurioctocog alfa (recombinant factor VIII: Advate
®
) is available for the control of bleeding among patients with hemophilia A in Japan. To evaluate the perioperative safety and hemostatic efficacy ...of Advate
®
, a postmarketing surveillance was conducted in Japanese patients undergoing surgery in a real-world setting. A total of 74 surgical procedures performed in 58 subjects aged 0–75 years, including three females, were studied. A hemostatic efficacy rating of “excellent” or “good” was reported in 73/74 surgical procedures (98.6%). Perioperative bleeding was successfully controlled by Advate
®
in five subjects with positive FVIII inhibitors (2.4-9.1 BU/mL). Advate
®
was administered at higher initial bolus doses (114-385 IU/kg) and at higher rates by subsequent initial continuous infusion (8.3-15 IU/kg/hour) in the five subjects with inhibitor than in the subjects without inhibitor (
n
= 47; mean initial bolus dose: 53.4 IU/kg; subsequent mean initial continuous infusion: 3.8 IU/kg/h). Adverse drug reactions were reported in 7/74 (9.5%) procedures, two of which were the development of de novo FVIII inhibitors. Overall, the perioperative use of Advate
®
in a real-world setting was found to be safe and effective among Japanese patients with hemophilia A.
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