Search

Currently, no approved vaccines for Listeria monocytogenes are available. Here, the authors use immunopeptidomics to map bacterial peptides presented on infected cells and identify antigens that, as mRNA vaccine, provide protection in mice.

For all their concern with the nature of medical authority, historians of medicine have paid remarkably little attention to the history of the medical script, the main medium in and through which the doctor’s authority is enacted. This essay analyzes the medical prescription as an instance of a written performative. While focusing on the changing uses of one particular documentary genre in turn-of-the-twentieth-century France, it seeks to outline a broader theory of graphic performativity, or of the conditions under which the symbolic power of the oral performance is transferred and transformed as it is transcribed on paper.

The large number of rural Roman settlements known from the Low Countries is generally characterised by a poor preservation of ecological proxies due to the absence of waterlogged contexts. The riverside site of Wijmeers (Wichelen, Belgium), a small rural settlement located in the Lower Scheldt basin, represents a rare exception to this pattern. Due to the presence of a waterlogged sequence with Roman (late 1st–3rd centuries AD) waste layers, located only a few metres from a main building structure, and the covering of the site with alluvial sediments shortly after its abandonment, the preservation condition of charred and uncharred organic materials was exceptional. The combined study of these proxies (pollen, seeds, charcoal, mollusc shells and animal bones) presents unique insights into the subsistence economy of a Roman rural household in the Lower Scheldt valley in general, and especially its exploitation of the valley and river environments. Besides this cultural–economical perspective, the site provides key information for understanding the chronology of fluvial and alluvial processes in the Lower Scheldt Basin for a large part of the Subatlantic period (Iron Age to Early Middle Ages, ca 800 BC–900 AD). [ABSTRACT FROM AUTHOR]

Abstract mRNA therapeutics have become the focus of molecular medicine research. Various mRNA applications have reached major milestones at high speed in the immuno-oncology field. This can be attributed to the knowledge that mRNA is one of nature’s core building blocks carrying important information and can be considered as a powerful vector for delivery of therapeutic proteins to the patient. For a long time, the major focus in the use of in vitro transcribed mRNA was on development of cancer vaccines, using mRNA encoding tumor antigens to modify dendritic cells ex vivo. However, the versatility of mRNA and its many advantages have paved the path beyond this application. In addition, due to smart design of both the structural properties of the mRNA molecule as well as pharmaceutical formulations that improve its in vivo stability and selective targeting, the therapeutic potential of mRNA can be considered as endless. As a consequence, many novel immunotherapeutic strategies focus on the use of mRNA beyond its use as the source of tumor antigens. This review aims to summarize the state-of-the-art on these applications and to provide a rationale for their clinical application.

To date, mRNA-based biologics have mainly been developed for prophylactic and therapeutic vaccination to combat infectious diseases or cancer. In the past years, optimization of the characteristics of in vitro transcribed mRNA has led to significant reduction of the inflammatory responses. Thanks to this, mRNA therapeutics have entered the field of passive immunization. Here, we established an mRNA treatment that is based on mRNA that codes for a bispecific single-domain antibody construct that can selectively recruit innate immune cells to cells infected with influenza A virus. The constructs consist of a single-domain antibody that binds to the ectodomain of the conserved influenza A matrix protein 2, while the other single-domain antibody binds to the activating mouse Fcγ receptor IV. Formulating the mRNA into DOTAP (1,2-dioleoyl-3-trimethylammonium-propane)/cholesterol nanoparticles and delivering these intratracheally to mice allowed the production of the bispecific single-domain antibody in the lungs, and administration of these mRNA-particles prior to influenza A virus infection was associated with a significant reduction in viral titers and a reduced morbidity in mice. Overall, our data provide evidence that the local delivery of mRNA encoding a bispecific single-domain antibody format in the lungs could be a promising pulmonary antiviral prophylactic treatment.

Summary: The fungus Aspergillus fumigatus is ubiquitous in nature and the most common cause of invasive pulmonary aspergillosis (IPA) in patients with a compromised immune system. The development of IPA in patients under immunosuppressive treatment or in patients with primary immunodeficiency demonstrates the importance of the host immune response in controlling aspergillosis. However, study of the host-microbe interaction has been hampered by the lack of tools for their non-invasive assessment. We developed a methodology to study the response of the host's immune system against IPA longitudinally in vivo by using fluorine-19 magnetic resonance imaging (19F MRI). We showed the advantage of a perfluorocarbon-based contrast agent for the in vivo labeling of macrophages and dendritic cells, permitting quantification of pulmonary inflammation in different murine IPA models. Our findings reveal the potential of 19F MRI for the assessment of rapid kinetics of innate immune response against IPA and the permissive niche generated through immunosuppression. : Infection Control in Health Technology; Medical Imaging; Mycology Subject Areas: Infection Control in Health Technology, Medical Imaging, Mycology

Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe inflammation of the synovial tissue. Here, we assess the feasibility of liposome-loaded microbubbles as theranostic agents in a murine arthritis model. First, contrast-enhanced ultrasound (CEUS) was used to quantify neovascularization in this model since CEUS is well-established for RA diagnosis in humans. Next, the potential of liposome-loaded microbubbles and ultrasound (US) to selectively enhance liposome delivery to the synovium was evaluated with in vivo fluorescence imaging. This procedure is made very challenging by the presence of hard joints and by the limited lifetime of the microbubbles. The inflamed knee joints were exposed to therapeutic US after intravenous injection of liposome-loaded microbubbles. Loaded microbubbles were found to be quickly captured by the liver. This resulted in fast clearance of attached liposomes while free and long-circulating liposomes were able to accumulate over time in the inflamed joints. Our observations show that murine arthritis models are not well-suited for evaluating the potential of microbubble-mediated drug delivery in joints given: (i) restricted microbubble passage in murine synovial vasculature and (ii) limited control over the exact ultrasound conditions in situ given the much shorter length scale of the murine joints as compared to the therapeutic wavelength.

U.S. law imposes strict recording and reporting requirements on all entities that manufacture and distribute controlled substances. As a result, the prescription opioid crisis has unfolded in a data-saturated environment. This article asks why the systematic documentation of opioid transactions failed to prevent or mitigate the crisis. Drawing on a recently disclosed trove of 1.4 million internal records from Mallinckrodt Pharmaceuticals, a leading manufacturer of prescription opioids, we highlight a phenomenon we propose to call data diversion, whereby data ostensibly generated or collected for the purpose of regulating the distribution of controlled substances were repurposed by the industry for the opposite aim of increasing sales at all costs. Systematic data diversion, we argue, contributed substantially to the scale of drug diversion seen with opioids and should become a focus of policy intervention. [ABSTRACT FROM AUTHOR]