Proteases in Staphylococcal Arthritis

Proteases in Staphylococcal Arthritis Ann-Marie Calander Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborg University, Guldhedsgatan 10A, 413 46 Göteborg, Sweden Staphylococcus aureus (S. aureus) is a ubiquitous bacterium. Due to an increasing prevalence of immunodeficiency states in the world population and the emergence of antibiotic resistant strains, the incidence of S. aureus septicaemia and its complications is increasing worldwide, as is the mortality thereof. S. aureus has an impressive capacity to adjust to the environment since it has developed a multitude of invasive and evasive mechanisms to cope with host defence. Many studies have been performed mapping S. aureus virulence determinants with the aim of improving our ability to combat S. aureus infections. So far, little is known concerning the impact of S. aureus extracellular proteases on virulence. The aim of the first part of this thesis was to investigate the role of bacterial extracellular proteases as potential virulence factors in S. aureus induced septic arthritis. Inherent to this goal was to investigate whether there is a specific immune response to S. aureus extracellular proteases and if so, whether protease specific antibodies have any inhibitory function on the protease activity and thereby modulating the biological properties of the bacteria. The second part of this thesis aimed at shedding light on the impact of a host protease, matrix metalloproteinase 9 (MMP-9) on the development of septic arthritis. S. aureus strain 8325-4 with a known high production of extracellular proteases and its mutants lacking extracellular proteases, Aur-, Ssp- and SspB- were compared concerning their capacity to induce arthritis and to prevail in kidneys and joints. Total serum levels of IgG and IgM were measured, as were antibodies specific for the deleted proteases. Silencing of the ssp, aur, or sspB genes did not affect the clinical nor the histological course of septic arthritis. Polyclonal B-cell activation was illustrated by auto-antibody production and a 10-fold increase in total IgG and a 50% increase in total IgM. Specific antibody response was demonstrated since only mice infected with bacteria expressing SspB and V8 responded with anti-protease specific antibody production. Functional capacity of the specific antibodies was illustrated by the fact that the V8 protease antibodies inhibited the activity of the enzyme in vitro. To study the production of host protease MMP-9 over time, zymographic analyses were performed of spleen homogenates at different time points after bacterial inoculation. At day 9 after inoculation there was a four-fold increase of MMP-9 expression. To further investigate the role of MMP-9 in infectious arthritis, MMP-9 KO mice and their littermates C57Bl/6 wt mice, were inoculated i.v. with S. aureus. MMP-9 deficient mice showed more clinical arthritis and thrived less well. Importantly, the MMP-9 KO mice harboured significantly more bacteria in kidneys and joints than did their congenic controls, indicating MMP-9 as an indispensable molecule in the clearance of the infective agent. Altogether this thesis shows that S. aureus proteases can evoke a specific immune response in the host, but that they are not essential in mediating bacterial arthritis. Furthermore, host MMP-9 contributes to innate immune responses during septic arthritis. Keywords: Staphylococcus aureus, septic arthritis, proteases, matrix metalloproteinases ISBN 978-91-628-7040-

Energy monitoring system for industrial use

Energy meters are essential for monitoring and managing electricity consumption across residential, commercial, and industrial environments. These devices enable consumers and utility providers to optimize energy efficiency, reduce costs, and support environmental sustainability, aligning with the EU’s carbon neutrality goals for 2050. The advancement of smart meters has further transformed energy monitoring by providing real-time data collection, remote accessibility, and seamless integration with the Internet of Things (IoT). This thesis examines the differences users can expect when selecting an energy meter, focusing on metering methods and data logging capabilities. The study is conducted through a combination of literature review and mathematical calculations. The primary objective is to evaluate the performance and accuracy of a selected energy metering system by comparing it to a reference energy meter. The results indicate that a lesser-known measurement device can be a viable option for industrial applications, demonstrating promising measurement accuracy and user-friendly software that enhances the consumer experience. However, a key limitation of the study is the use of a Fluke a3001 FC current measurement device as a reference device, which has known accuracy limitations. Despite this, the findings suggest that the Shelly pro 3em energy meter offers reliable performance and ease of use, making it a competitive choice in the industrial sector.Energimätare är avgörande för att övervaka och hantera elförbrukning inom bostäder, kommersiella fastigheter och industriella miljöer. Dessa enheter gör det möjligt för både konsumenter och elleverantörer att optimera energieffektivitet, minska kostnader och bidra till hållbar utveckling i linje med EU:s mål om koldioxidneutralitet till 2050. Utvecklingen av smarta mätare har ytterligare förbättrat energimonitorering genom realtidsdatainsamling, fjärråtkomst och smidig integration med Internet of Things (IoT). Denna studie undersöker de skillnader som konsumenter kan förvänta sig vid val av energimätare, med fokus på olika mätmetoder och loggningsfunktioner. Studien genomförs för det mesta genom litteraturgranskning, med matematiska beräkningar som stöder undersökningen. Det primära målet är att utvärdera prestandan och noggrannheten hos ett utvalt energimätningssystem genom att jämföra det med en referensmätare. Resultaten visar att en mindre känd mätutrustning kan vara ett konkurrenskraftigt alternativ för industriella tillämpningar. Den uppvisar lovande mätnoggrannhet och ett användarvänligt program som förbättrar användarupplevelsen. En begränsning i studien är dock användningen av en Fluke a3001 FCströmmätare som referensenhet, vilken har noggrannhetsbegränsningar. Trots detta tyder resultaten på att energimätaren Shelly Pro 3EM erbjuder pålitlig prestanda och enkel användning, vilket gör den till ett alternativ inom industrisektorn

Leishmania infantum infection after visiting southern Spain in patients on biological treatment; an observational, longitudinal, cohort study

Background: Reports of leishmaniasis in immunosuppressed patients after visiting the Mediterranean Basin are becoming increasingly common. Still, awareness of the risk of infection and its clinical manifestations may be insufficient among healthcare professionals in the travellers' home countries. Methods: This observational, longitudinal study included 47 patients from Sweden with rheumatic disease and ongoing immunomodulatory treatment, who visited a rehabilitation centre in southern Spain where leishmaniasis is endemic. Patients were evaluated for clinical signs of leishmaniasis at baseline and after three years. Patients with leishmaniasis were followed for 4-5 years. The treatment outcome was assessed by clinical evaluation and determination of the cell-mediated immunological response to Leishmania by a whole blood cytokine release assay. Results: Seven patients (15%) were diagnosed with leishmaniasis. The median time from exposure to the onset of symptoms was 3 [1-17] months. The median delay between the onset of symptoms and treatment start was 9 [1-12] months. All patients with leishmaniasis responded well to treatment. Only one patient had a relapse, which occurred within the first year. Conclusion: Healthcare professionals need to be aware of the increased risk of leishmaniasis for travellers who are immunosuppressed. Knowledge of the symptoms is crucial for a timely diagnosis and early treatment.S

Nanoscale plasmonic resonators with high Purcell factor: Spontaneous and stimulated emission

Plasmonic nanoparticles with silver cores and silica shells containing Eu fluorophores near the surface have been produced by wet chemistry method and their spontaneous emission properties characterized. Fluorescence amplification and decreased lifetime is interpreted within the Purcell framework which highlights the role of surface plasmon polariton modes of the nanoparticle. These behave as energy-storing resonators, with values of the Q factor between 50 and 170 at the fluorophore wavelength of 615 nm, and very small mode volumes, in the order of 104 nm3, producing high Purcell factors of over 4000. Comparison of experiment with theoretical calculations by using the Mie theory shows that the values of cavity Q factors are moderated by the nonradiative rate of fluorophore molecules close to metal. The criteria for laser action in such composite nanoparticles are also presented, including lasing frequencies and threshold gain. © 2011 SPIE

Left-handed metamaterial coatings for subwavelength-resolution imaging

We report on a procedure to improve the resolution of far-field imaging by using a neighboring high-index medium that is coated with a left-handed metamaterial. The resulting plot can also exhibit an enhanced transmission by considering proper conditions to retract backscattering. Based on negative refraction, geometrical aberrations are considered in detail since they may cause a great impact in this sort of diffraction-unlimited imaging by reducing its resolution power. We employ a standard aberration analysis to refine the asymmetric configuration of metamaterial superlenses. We demonstrate that low-order centrosymmetric aberrations can be fully corrected for a given object plane. For subwavelength-resolution imaging, however, high-order aberrations become of relevance, which may be balanced with defocus. Not only the point spread function but also numerical simulations based on the finite-element method support our theoretical analysis, and subwavelength resolution is verified in the image plane.This research was funded by the Spanish Ministry of Economy and Competitiveness under the project TEC2009-11635