Public health trends in neurologically relevant infections: a global perspective

Neuroinfectious diseases represent a growing threat to public health globally. Infections of the central nervous system remain challenging to diagnose and treat, partially driven by the fact that a high proportion of emerging pathogens are capable of causing neurological disease. Many of the trends driving the emergence of novel pathogens, including climate change, ecological degradation, urbanization, and global travel, have accelerated in recent years. These circumstances raise concern for the potential emergence of additional pathogens of pandemic potential in the coming years, necessitating a stronger understanding of the forces that give rise to the emergence and spread of neuroinvasive pathogens and a commitment to public health infrastructure to identify and treat these diseases. In this review, we discuss the clinical and epidemiological features of three types of emerging neuroinvasive pathogens of significant public health consequences that are emblematic of key ongoing trends in global health. We first discuss dengue viruses in the context of climate change, considering the environmental factors that allow for the expansion of the geographic range and seasonal population of the viruses’ vector. We then review the rising prevalence of fungal meningitis secondary to medical tourism, a trend representative of the highly globalized nature of modern healthcare. Lastly, we discuss the increasing prevalence of antibiotic-resistant neurological infections driven by the intersection of antibiotic overuse in medical and agricultural settings. Taken together, the rising prevalence of these conditions necessitates a recommitment to investment in public health infrastructure focused on local and global infectious disease surveillance coupled with ongoing development of novel therapeutics and vaccines for emerging pathogens. Such emerging threats also obviate the need to address the root causes driving the emergence of novel infectious diseases, including a sustained effort to address anthropogenic climate change and environmental degradation

Both activating and inhibitory Fc gamma receptors mediate rituximab-induced trogocytosis of CD20 in mice.

Item does not contain fulltextAntigenic modulation by trogocytosis during anti-CD20 mAb treatment with rituximab (RTX) leads to loss of CD20 and therefore can compromise therapy. During trogocytosis, effector cells, such as macrophages, remove CD20 from the surface of antibody-coated cells in an Fc receptor-dependent manner. Importantly, Fcgamma receptors (FcgammaRs) are also crucial in the anti-tumor effects of RTX by inducing antibody dependent cell-mediated cytotoxicity (ADCC). Here we studied the role of FcgammaR during RTX-induced trogocytosis of CD20 in an intraperitoneal tumor model with EL4-CD20 cells. We found marked RTX-induced trogocytosis of CD20 in FcgammaRI- or FcgammaRIII-deficient mice, similar to wild type mice, demonstrating a redundancy for activating FcgammaR in trogocytosis. Interestingly, in FcRgamma-chain-deficient mice, trogocytosis was still apparent, indicating that the inhibitory receptor FcgammaRIIB alone can also mediate trogocytosis. These data were confirmed by in vitro analysis with blocking antibodies. Decreasing the amount of RTX in vivo resulted in less trogocytosis of CD20, supporting clinical studies with lower RTX dose. Importantly, we show that cells which undergo in vivo trogocytosis can still be killed ex vivo by ADCC but not by complement-mediated cytotoxicity (CDC), underscoring the clinical relevance of trogocytosis. Taken together, our study provides more insights into the mechanism and consequences of RTX-induced trogocytosis of CD20

Adult-onset central nervous system hemophagocytic lymphohistiocytosis: A case report

© 2015 Pastula et al.Background: Hemophagocytic lymphohistiocytosis (HLH) is a clinical syndrome with both genetic and acquired causes characterized by elevated cytokine levels, hyperinflammation, and overactivation of lymphocytes and macrophages. It is t

Advances in Design of Solid Oxide Fuel Cell Hybrid Power Systems for Underwater Applications

A hybrid propulsion system for torpedo propulsion applications was developed. The hybrid system utilizes a solid oxide fuel cell (SOFC) to provide low power propulsion and hotel loads supplemented by a high power turbine for high speed pursuit, with both systems using common fuel and oxidant sources. A solid LiClO4 oxidant source was investigated. Individual subsystems including the SOFC stack and LiClO4 oxidant source were physically tested. Trade studies were performed comparing various fuel, oxidant, low power, and high power sources, based on testing performance of the subsystems. The SOFC low power system was demonstrated to provide the longest low power range while maintaining the necessary high power reserve for target pursuit.</jats:p