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      Self-propelled particles that transport cargo through flowing blood and halt hemorrhage

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          Abstract

          Simple, water-reactive particles can carry enzymes upstream through aqueous solutions and into wounds to halt severe bleeding.

          Abstract

          Delivering therapeutics deep into damaged tissue during bleeding is challenging because of the outward flow of blood. When coagulants cannot reach and clot blood at its source, uncontrolled bleeding can occur and increase surgical complications and fatalities. Self-propelling particles have been proposed as a strategy for transporting agents upstream through blood. Many nanoparticle and microparticle systems exhibiting autonomous or collective movement have been developed, but propulsion has not been used successfully in blood or used in vivo to transport therapeutics. We show that simple gas-generating microparticles consisting of carbonate and tranexamic acid traveled through aqueous solutions at velocities of up to 1.5 cm/s and delivered therapeutics millimeters into the vasculature of wounds. The particles transported themselves through a combination of lateral propulsion, buoyant rise, and convection. When loaded with active thrombin, these particles worked effectively as a hemostatic agent and halted severe hemorrhage in multiple animal models of intraoperative and traumatic bleeding. Many medical applications have been suggested for self-propelling particles, and the findings of this study show that the active self-fueled transport of particles can function in vivo to enhance drug delivery.

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          Microscopic artificial swimmers.

          Microorganisms such as bacteria and many eukaryotic cells propel themselves with hair-like structures known as flagella, which can exhibit a variety of structures and movement patterns. For example, bacterial flagella are helically shaped and driven at their bases by a reversible rotary engine, which rotates the attached flagellum to give a motion similar to that of a corkscrew. In contrast, eukaryotic cells use flagella that resemble elastic rods and exhibit a beating motion: internally generated stresses give rise to a series of bends that propagate towards the tip. In contrast to this variety of swimming strategies encountered in nature, a controlled swimming motion of artificial micrometre-sized structures has not yet been realized. Here we show that a linear chain of colloidal magnetic particles linked by DNA and attached to a red blood cell can act as a flexible artificial flagellum. The filament aligns with an external uniform magnetic field and is readily actuated by oscillating a transverse field. We find that the actuation induces a beating pattern that propels the structure, and that the external fields can be adjusted to control the velocity and the direction of motion.
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            Epidemiology of trauma deaths: a reassessment.

            Recognizing the impact of the 1977 San Francisco study of trauma deaths in trauma care, our purpose was to reassess those findings in a contemporary trauma system. Cross-sectional. All trauma deaths occurring in Denver City and County during 1992 were reviewed; data were obtained by cross-referencing four databases: paramedic trip reports, trauma registries, coroner autopsy reports and police reports. There were 289 postinjury fatalities; mean age was 36.8 +/- 1.2 years and mean Injury Severity Score (ISS) was 35.7 +/- 1.2. Predominant injury mechanisms were gunshot wounds in 121 (42%), motorvehicle accidents in 75 (38%) and falls in 23 (8%) cases. Seven (2%) individuals sustained lethal burns. Ninety eight (34%) deaths occurred in the pre-hospital setting. The remaining 191 (66%) patients were transported to the hospital. Of these, 154 (81%) died in the first 48 hours (acute), 11 (6%) within three to seven days (early) and 26 (14%) after seven days (late). Central nervous system injuries were the most frequent cause of death (42%), followed by exsanguination (39%) and organ failure (7%). While acute and early deaths were mostly due to the first two causes, organ failure was the most common cause of late death (61%). In comparison with the previous report, we observed similar injury mechanisms, demographics and causes of death. However, in our experience, there was an improved access to the medical system, greater proportion of late deaths due to brain injury and lack of the classic trimodal distribution.
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              Autonomous movement of platinum-loaded stomatocytes.

              Polymer stomatocytes are bowl-shaped structures of nanosize dimensions formed by the controlled deformation of polymer vesicles. The stable nanocavity and strict control of the opening are ideal for the physical entrapment of nanoparticles which, when catalytically active, can turn the stomatocyte morphology into a nanoreactor. Herein we report an approach to generate autonomous movement of the polymer stomatocytes by selectively entrapping catalytically active platinum nanoparticles within their nanocavities and subsequently using catalysis as a driving force for movement. Hydrogen peroxide is free to access the inner stomatocyte cavity, where it is decomposed by the active catalyst (the entrapped platinum nanoparticles) into oxygen and water. This generates a rapid discharge, which induces thrust and directional movement. The design of the platinum-loaded stomatocytes resembles a miniature monopropellant rocket engine, in which the controlled opening of the stomatocytes directs the expulsion of the decomposition products away from the reaction chamber (inner stomatocyte cavity).
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                Author and article information

                Journal
                Sci Adv
                Sci Adv
                SciAdv
                advances
                Science Advances
                American Association for the Advancement of Science
                2375-2548
                October 2015
                02 October 2015
                : 1
                : 9
                : e1500379
                Affiliations
                [1 ]Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
                [2 ]Biomedical Engineering Program, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
                [3 ]Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
                [4 ]Department of Radiology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
                [5 ]Division of Emergency Medicine, University of Washington, Seattle, WA 98195, USA.
                [6 ]Department of Chemical and Biological Engineering, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
                [7 ]Division of Global Health and Human Rights, Department of Emergency Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
                Author notes
                [* ]Corresponding author. E-mail: ckastrup@ 123456msl.ubc.ca
                Article
                1500379
                10.1126/sciadv.1500379
                4646796
                26601282
                ae334fa5-7f68-45ef-bdc0-f06bb24b97a8
                Copyright © 2015, The Authors

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

                History
                : 16 April 2015
                : 24 June 2015
                Funding
                Funded by: Canadian Institutes of Health Research;
                Award ID: ID0EAEAI1755
                Award ID: MOP-119426
                Award Recipient :
                Funded by: Canadian Institutes of Health Research;
                Award ID: ID0E3MAI1756
                Award ID: MSH-130116
                Award Recipient :
                Funded by: Natural Sciences and Engineering Research Council of Canada;
                Award ID: ID0EYVAI1757
                Award ID: 418652-2012
                Award Recipient :
                Funded by: Canada Foundation for Innovation;
                Award ID: ID0EU5AI1758
                Award ID: 31928
                Award Recipient :
                Funded by: National Center for Advancing Translational Sciences;
                Award ID: ID0EQHBI1759
                Award ID: KL2-TR000421
                Award Recipient :
                Categories
                Research Article
                Research Articles
                SciAdv r-articles
                Biomaterials
                Custom metadata
                Meann Ramirez

                calcium carbonate,self-propelling particles,hemostasis,drug delivery,micromotors,coagulation,foaming,bubble propulsion,antifibrinolytic,surgery

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