Protection against murine listeriosis by an attenuated recombinant Salmonella typhimurium vaccine strain that secretes the naturally somatic antigen superoxide dismutase.

A recombinant (r)-Salmonella typhimurium aroA vaccine strain was constructed which secretes the naturally somatic protein of Listeria monocytogenes, superoxide dismutase (SOD), by the HlyB/HlyD/TolC export machinery. Vaccine efficacy of the SOD-bearing carrier strain was compared with that of the p60-secreting construct, S. typhimurium p60s (J. Hess, I. Gentschev, D. Miko, M. Welzel, C. Ladel, W. Goebel, and S. H. E. Kaufmann, Proc. Natl. Acad. Sci. USA 93:1458-1463, 1996). Vaccination of mice with both constructs induced protection against a lethal challenge with the intracellular pathogen, L. monocytogenes. While the somatic listerial antigen, SOD, is immunologically uncharacterized, the naturally secreted protein of L. monocytogenes, p60, is known to be highly immunogenic. Our data emphasize the high vaccine potential of r-Salmonella constructs secreting antigens of somatic or secreted origin. Moreover, they suggest that the HlyB/HlyD/TolC-based antigen delivery system with attenuated Salmonella spp. as the carrier is capable of potentiating the immune response against foreign proteins independent from their immunogenicity in and display by the natural host.     

Anti-SARS-CoV-2 activity of targeted kinase inhibitors: Repurposing clinically available drugs for COVID-19 therapy

Coronavirus disease 2019 (COVID-19) remains a major public health concern, and vaccine unavailability, hesitancy, or failure underscore the need for discovery of efficacious antiviral drug therapies. Numerous approved drugs target protein kinases associated with viral life cycle and symptoms of infection. Repurposing of kinase inhibitors is appealing as they have been vetted for safety and are more accessible for COVID-19 treatment. However, an understanding of drug mechanism is needed to improve our understanding of the factors involved in pathogenesis. We tested the in vitro activity of three kinase inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including inhibitors of AXL kinase, a host cell factor that contributes to successful SARS-CoV-2 infection. Using multiple cell-based assays and approaches, gilteritinib, nintedanib, and imatinib were thoroughly evaluated for activity against SARS-CoV-2 variants. Each drug exhibited antiviral activity, but with stark differences in potency, suggesting differences in host dependency for kinase targets. Importantly, for gilteritinib, the amount of compound needed to achieve 90% infection inhibition, at least in part involving blockade of spike protein-mediated viral entry and at concentrations not inducing phospholipidosis (PLD), approached a clinically achievable concentration. Knockout of AXL, a target of gilteritinib and nintedanib, impaired SARS-CoV-2 variant infectivity, supporting a role for AXL in SARS-CoV-2 infection and supporting further investigation of drug-mediated AXL inhibition as a COVID-19 treatment. This study supports further evaluation of AXL-targeting kinase inhibitors as potential antiviral agents and treatments for COVID-19. Additional mechanistic studies are needed to determine underlying differences in virus response.     

Ethical considerations in the use of brain-computer interfaces

Nervous system disorders are among the most severe disorders. Significant breakthroughs in contemporary clinical practice may provide brain-computer interfaces (BCIs) and neuroprostheses (NPs). The aim of this article is to investigate the extent to which the ethical considerations in the clinical application of brain-computer interfaces and associated threats are being identified. Ethical considerations and implications may significantly influence further development of BCIs and NPs. Moreover, there is significant public interest in supervising this development. Awareness of BCIs’ and NPs’ threats and limitations allow for wise planning and management in further clinical practice, especially in the area of long-term neurorehabilitation and care.     

First successful use of leukocyte apheresis as maintenance therapy for Crohn's disease in the United Kingdom

We describe the case of a 24 year old male with severe fistulating Crohn's disease who failed mutliple modalities of medical and surgical therapy. We present objective and subjective evidence of disease remission after induction and maintenance treatment with leukocyte apheresis. This is the first described case of successful maintenance treatment of severe Crohn's disease with leukocyte apheresis in the United Kingdom. J. Clin. Apheresis 29:181–182, 2014. © 2013 Wiley Periodicals, Inc.     

Dermatosis bullosa in patient with chronic renal failure under hemodialysis treatment--case report

A case of 45-year-old patient with chronic renal failure treated by hemodialysis associated with skin changes typical for porphyria cutanea tarda is reported. The diagnosis was based on clinical manifestations and on histopathologic examination of the skin segment. The skin was low sensitive for UVA rays, serum levels of aluminium and lead were significantly elevated. We did not find porphyrins in the urine (24-hour collection 100 ml) as well as in the dialysis fluid.