The Impact of Antimicrobial Therapy Duration in the Treatment of Prosthetic Joint Infections Depending on Surgical Strategies: A Systematic Review and Meta-analysis

The aim of this systematic review was to address the question if short antibiotic treatment (SAT; at least 4 but <12 weeks) versus long antibiotic treatment (LAT) affects outcomes in prosthetic joint infections (PJIs). Database research (Medline, Embase, Web of Science, Scopus, Cochrane) retrieved 3740 articles, of which 10 studies were included in the analysis. Compared to LAT, 11% lower odds of treatment failure in the SAT group were found, although the difference was not statistically significant (pooled odds ratio, 0.89 [95% confidence interval, .53-1.50]). No difference in treatment failure was found between SAT and LAT once stratified by type of surgery, studies conducted in the United States versus Europe, study design, and follow-up. There is still no conclusive evidence that antibiotic treatment of PJIs for 12 weeks or longer is associated with better outcomes, irrespective of the type of surgical procedure. Most recent, high-quality studies tend to favor longer antibiotic courses, making them preferable in most situations

Development of an artificial synovial fluid useful for studying Staphylococcus epidermidis joint infections

Staphylococcus epidermidis is a major causative agent of prosthetic joint infections (PJI). The ability to form biofilms supports this highly selective pathogenic potential. In vitro studies essentially relying on phenotypic assays and genetic approaches have provided a detailed picture of the molecular events contributing to biofilm assembly. A major limitation in these studies is the use of synthetic growth media, which significantly differs from the environmental conditions S. epidermidis encounters during host invasion. Building on evidence showing that growth in serum substantially affects S. epidermidis gene expression profiles and phenotypes, the major aim of this study was to develop and characterize a growth medium mimicking synovial fluid, thereby facilitating research addressing specific aspects related to PJI. Using fresh human plasma, a protocol was established allowing for the large-scale production of a medium that by biochemical analysis matches key characteristics of synovial fluid and therefore is referred to as artificial synovial fluid (ASF). By analysis of biofilm-positive, polysaccharide intercellular adhesion (PIA)-producing S. epidermidis 1457 and its isogenic, PIA- and biofilm-negative mutant 1457-M10, evidence is provided that the presence of ASF induces cluster formation in S. epidermidis 1457 and mutant 1457-M10. Consistent with the aggregative properties, both strains formed multilayered biofilms when analyzed by confocal laser scanning microscopy. In parallel to the phenotypic findings, expression analysis after growth in ASF found upregulation of genes encoding for intercellular adhesins (icaA, aap, and embp) as well as atlE, encoding for the major cell wall autolysin being responsible for eDNA release. In contrast, growth in ASF was associated with reduced expression of the master regulator agr. Collectively, these results indicate that ASF induces expression profiles that are able to support intercellular adhesion in both PIA-positive and PIA-negative S. epidermidis. Given the observation that ASF overall induced biofilm formation in a collection of S. epidermidis isolates from PJI, the results strongly support the idea of using growth media mimicking host environments. ASF may play an important role in future studies related to the pathogenesis of S. epidermidis PJI

Realizing High Thermoelectric Performance of Bi-Sb-Te-Based Printed Films through Grain Interface Modification by an In Situ-Grown β-Cu2-δSe Phase

It has been a substantial challenge to develop a printed thermoelectric (TE) material with a figure-of-merit ZT > 1. In this work, high ZT p-type Bi0.5Sb1.5Te3-based printable TE materials have been advanced by interface modification of the TE grains with a nonstoichiometric β-Cu2-δSe-based inorganic binder (IB) through a facile printing–sintering process. As a result, a very high TE power factor of ∼17.5 μW cm–1 K–2 for a p-type printed material is attained in the optimized compounds at room temperature (RT). In addition, a high ZT of ∼1.2 at RT and of ∼1.55 at 360 K is realized using thermal conductivity (κ) of a pellet made of the prepared printable material containing 10 wt % of IB. Using the same material for p-type TE legs and silver paste for n-type TE legs, a printed TE generator (print-TEG) of four thermocouples has been fabricated for demonstration. An open-circuit voltage (VOC) of 14 mV and a maximum power output (Pmax) of 1.7 μW are achieved for ΔT = 40 K for the print-TEG

Smart City: Zur Bedeutung des aktuellen Diskurses für die Arbeit am Zentrum Technik und Gesellschaft

Seit 2013 befasst sich eine interdisziplinäre Arbeitsgruppe am Zentrum Technik und Gesellschaft (ZTG) mit dem Thema Smart City. In diesem discussion paper werden die Ergebnisse dieser Arbeit zusammengefasst und diskutiert, um die ZTG-interne Diskussion und Meinungsbildung zum Thema zu unterstützen und unsere Perspektiven interessierten Dritten zugänglich zu machen. Kapitel 2 bietet ein Überblick über den Forschungs- und Diskussionsstand zum Thema Smart Cities sowie zu den vielfältigen Definitionen und Begriffsverständnissen. Die Smart City Strategien einiger Städte werden exemplarisch analysiert sowie eine Abgrenzung zu ähnlichen Konzepten vorgenommen. Des Weiteren werden kritische Aspekte des Smart City Konzepts dargestellt. In Kapitel 3 wird der Arbeitskreisinterne Diskussionsstand zusammenfasst (3.1) und berichten einzelne Forschungsbereiche des ZTG über ihre bisherigen Erfahrungen und die für diese relevanten Aspekte von Smart Cities (3.2). Im abschließenden 4. Kapitel wird der wissenschaftliche Diskussionsstand mit den ZTG-internen Perspektiven zusammengeführt und die Bedeutung für die zukünftige Arbeit am ZTG und darüber hinaus reflektiert. Eine wesentliche Erkenntnis lautet, dass Smart City Konzepte keine neuartigen Entwicklungsperspektiven repräsentieren, sondern existierende Leitvorstellungen ergänzen. Weiter sind Technologien dann smart, wenn sie den Interessen und Bedürfnissen der Menschen dienen und wenn sie soziale und politische Teilhabe und Inklusion sowie gerechte und demokratische Gesellschaftsstrukturen fördern. So können Smart Cities entstehen, die sich durch ihre hohe Lebensqualität auszeichnen.Since 2013, an interdisciplinary working group at the Center for Technology and Society (CTS) is dealing with the topic smart city. This discussion paper summarizes and discusses results of its activities. Thus, the CTS-internal discussion and opinion building on the topic shall be supported and the findings be made accessible to third parties. Chapter 2 of the paper looks at the state of research and discussion on smart cities and gives an overview of the diverse definitions and understandings of the term. Smart City strategies of selected examples are analysed. Furthermore, similarities and differences with related concepts are worked out and critical aspects of the smart city concept are outlined. Chapter 3 summarizes the working group's internal state of discussion (3.1) and CTS research areas describe their experiences and relevant aspects regarding smart city (3.2). The final chapter 4 merges the scientific discussion with the CTS-internal perspectives and reflects them towards their implications for the future work at the CTS and beyond. Major findings show that smart city concepts do not represent new development perspectives but complement existing conceptions. Furthermore they say that technology is smart when it serves the interests and needs of people, promotes social and political participation and inclusion as well as just and democratic social structures. In this way, cities characterized by a high quality of life will develop

Integration of Golgi trafficking and growth factor signaling by the lipid phosphatase SAC1

When a growing cell expands, lipids and proteins must be delivered to its periphery. Although this phenomenon has been observed for decades, it remains unknown how the secretory pathway responds to growth signaling. We demonstrate that control of Golgi phosphatidylinositol-4-phosphate (PI(4)P) is required for growth-dependent secretion. The phosphoinositide phosphatase SAC1 accumulates at the Golgi in quiescent cells and down-regulates anterograde trafficking by depleting Golgi PI(4)P. Golgi localization requires oligomerization of SAC1 and recruitment of the coat protein (COP) II complex. When quiescent cells are stimulated by mitogens, SAC1 rapidly shuttles back to the endoplasmic reticulum (ER), thus releasing the brake on Golgi secretion. The p38 mitogen-activated kinase (MAPK) pathway induces dissociation of SAC1 oligomers after mitogen stimulation, which triggers COP-I–mediated retrieval of SAC1 to the ER. Inhibition of p38 MAPK abolishes growth factor–induced Golgi-to-ER shuttling of SAC1 and slows secretion. These results suggest direct roles for p38 MAPK and SAC1 in transmitting growth signals to the secretory machinery

Staphylococcal Biofilm Exopolysaccharide Protects against Caenorhabditis elegans Immune Defenses

Staphylococcus epidermidis and Staphylococcus aureus are leading causes of hospital-acquired infections that have become increasingly difficult to treat due to the prevalence of antibiotic resistance in these organisms. The ability of staphylococci to produce biofilm is an important virulence mechanism that allows bacteria both to adhere to living and artificial surfaces and to resist host immune factors and antibiotics. Here, we show that the icaADBC locus, which synthesizes the biofilm-associated polysaccharide intercellular adhesin (PIA) in staphylococci, is required for the formation of a lethal S. epidermidis infection in the intestine of the model nematode Caenorhabditis elegans. Susceptibility to S. epidermidis infection is influenced by mutation of the C. elegans PMK-1 p38 mitogen-activated protein (MAP) kinase or DAF-2 insulin-signaling pathways. Loss of PIA production abrogates nematocidal activity and leads to reduced bacterial accumulation in the C. elegans intestine, while overexpression of the icaADBC locus in S. aureus augments virulence towards nematodes. PIA-producing S. epidermidis has a significant survival advantage over ica-deficient S. epidermidis within the intestinal tract of wild-type C. elegans, but not in immunocompromised nematodes harboring a loss-of-function mutation in the p38 MAP kinase pathway gene sek-1. Moreover, sek-1 and pmk-1 mutants are equally sensitive to wild-type and icaADBC-deficient S. epidermidis. These results suggest that biofilm exopolysaccharide enhances virulence by playing an immunoprotective role during colonization of the C. elegans intestine. These studies demonstrate that C. elegans can serve as a simple animal model for studying host–pathogen interactions involving staphylococcal biofilm exopolysaccharide and suggest that the protective activity of biofilm matrix represents an ancient conserved function for resisting predation

Involvement of the Iron-Regulated Loci hts and fhuC in Biofilm Formation and Survival of Staphylococcus epidermidis within the Host

Staphylococcus epidermidis is a major nosocomial pathogen with a remarkable ability to persist on indwelling medical devices through biofilm formation. Nevertheless, it remains intriguing how this process is efficiently achieved under the host’s harsh conditions, where the availability of nutrients, such as essential metals, is scarce. Following our previous identification of two iron-regulated loci putatively involved in iron transport, hts and fhuC, we assessed here their individual contribution to both bacterial physiology and interaction with host immune cells. Single deletions of the hts and fhuC loci led to marked changes in the cell iron content, which were partly detrimental for planktonic growth and strongly affected biofilm formation under iron-restricted conditions. Deletion of each of these two loci did not lead to major changes in S. epidermidis survival within human macrophages or in an ex vivo human blood model of bloodstream infection. However, the lack of either hts or fhuC loci significantly impaired bacterial survival in vivo in a murine model of bacteremia. Collectively, this study establishes, for the first time, the pivotal role of the iron-regulated loci hts and fhuC in S. epidermidis biofilm formation and survival within the host, providing relevant information for the development of new targeted therapeutics against this pathogenWe acknowledge the assistance of Nurse Filomena and thank all the blood donors. N.C. and M.V. acknowledge the support by the Portuguese Foundation for Science and Technology (FCT) through the funded project PTDC/BIAMOL/29553/2017, under the scope of COMPETE2020 (POCI-01-0145-FEDER-029553). N.C. acknowledges the strategic funding of UID/BIO/04469/2019 unit by FCT. M.V. acknowledge the support of the i3S Scientific Platform HEMS, member of the Portuguese Platform of BioImaging (PPBI) (PPBIPOCI-01-0145-FEDER-022122), funded by FCT. H.R. acknowledges support from the German Research Council (DFG Ro 2413/4-1), the Damp Foundation (2013-19), and the Joachim Herz Foundation. F.O. was supported by an individual Ph.D. scholarship (SFRH/BD/101399/2014). F.O., M.V., H.R., and N.C. designed research; F.O., T.L., A.M.S., and C.S. performed research; S.M. contributed new reagents/analytic tools; F.O., T.L., A.C., C.S., S.M., and S.W. analyzed data; M.V., H.R., and N.C. supervised research; and F.O., M.V., H.R., and N.C. wrote the paper. All authors read and approved the final version of the manuscriptinfo:eu-repo/semantics/publishedVersio

Usability of rectal swabs for microbiome sampling in a cohort study of hematological and oncological patients

Objectives Large-scale clinical studies investigating associations between intestinal microbiota signatures and human diseases usually rely on stool samples. However, the timing of repeated stool sample collection cannot be predefined in longitudinal settings. Rectal swabs, being straightforward to obtain, have the potential to overcome this drawback. Therefore, we assessed the usability of rectal swabs for microbiome sampling in a cohort of hematological and oncological patients. Study design We used a pipeline for intestinal microbiota analysis from deep rectal swabs which was established and validated with test samples and negative controls. Consecutively, a cohort of patients from hematology and oncology wards was established and weekly deep rectal swabs taken during their admissions and re-admissions. Results Validation of our newly developed pipeline for intestinal microbiota analysis from rectal swabs revealed consistent and reproducible results. Over a period of nine months, 418 rectal swabs were collected longitudinally from 41 patients. Adherence to the intended sampling protocol was 97%. After DNA extraction, sequencing, read pre-processing and filtering of chimeric sequences, 405 of 418 samples (96.9%) were eligible for further analyses. Follow-up samples and those taken under current antibiotic exposure showed a significant decrease in alpha diversity as compared to baseline samples. Microbial domination occurred most frequently by Enterococcaceae (99 samples, 24.4%) on family level and Enterococcus (90 samples, 22.2%) on genus level. Furthermore, we noticed a high abundance of potential skin commensals in 99 samples (24.4%). Summary Deep rectal swabs were shown to be reliable for microbiome sampling and analysis, with practical advantages related to high sampling adherence, easy timing, transport and storage. The relatively high abundance of putative skin commensals in this patient cohort may be of potential interest and should be further investigated. Generally, previous findings on alpha diversity dynamics obtained from stool samples were confirmed

Nicht-Cholera-Vibrionen – derzeit noch seltene, aber wachsende Infektionsgefahr in Nord- und Ostsee

Hintergrund: Nicht-Cholera-Vibrionen nehmen im Rahmen des Klimawandels eine zunehmende Bedeutung als humane Pathogene ein, da die Prävalenz dieser Erreger im Meereswasser entscheidend von der Wassertemperatur abhängt. In den letzten Jahren konnten während der Sommermonate wiederholt größere Infektionsausbrüche in gemäßigten Klimazonen beobachtet werden. Ziel der Arbeit: Information einer breiten ärztlichen Leserschaft über potenziell lebensbedrohliche Krankheitsbilder, die durch Infektionen mit Nicht-Cholera-Vibrionen ausgelöst werden. Material und Methoden: Übersicht über aktuelle Literatur zu Infektionen mit Nicht-Cholera-Vibrionen im Allgemeinen und zur epidemiologischen Situation in Deutschland im Speziellen. Ergebnisse: Nicht-Cholera-Vibrionen verursachen vorwiegend Wund- und Ohrinfektionen nach Kontakt mit kontaminiertem Meereswasser sowie Gastroenteritiden nach dem Konsum nicht ausreichend gegarter Meerestiere. Da bis März 2020 keine Meldepflicht für diese Erreger in Deutschland bestand, muss von einer hohen Dunkelziffer ausgegangen werden. Immunsupprimierte sowie chronisch erkrankte Menschen haben ein deutlich erhöhtes Risiko für schwere Krankheitsverläufe. Schon bei klinischem Verdacht sollte eine kalkulierte antiinfektive Therapie erfolgen und bei Wundinfektionen eine chirurgische Sanierung erwogen werden. Diskussion: Aufgrund des fortschreitenden Klimawandels muss in den kommenden Jahren mit dem vermehrten Auftreten von Infektionen mit Nicht-Cholera-Vibrionen gerechnet werden. Ärzte sollten über diese potenziell lebensbedrohlichen Erkrankungen informiert sein, um Patienten einer entsprechenden Diagnostik und Behandlung zuzuführen.Background: The abundance of non-cholera Vibrio spp. in the aquatic environment shows a positive correlation with water temperatures. Therefore, climate change has an important impact on the epidemiology of human infections with these pathogens. In recent years large outbreaks have been repeatedly observed during the summer months in temperate climate zones. Objective: To inform medical professionals about the potentially life-threatening diseases caused by non-cholera Vibrio spp. Material and methods: Review of the current literature on infections with non-cholera Vibrio spp. in general and on the epidemiological situation in Germany in particular. Results: Non-cholera Vibrio spp. predominantly cause wound and ear infections after contact with contaminated seawater and gastroenteritis after consumption of undercooked seafood. As there have not been mandatory notification systems for these pathogens in Germany up to March 2020, a high number of unreported cases must be assumed. Immunosuppressed and chronically ill patients have a much higher risk for severe courses of diseases. If an infection with non-cholera Vibrio spp. is suspected anti-infective treatment should be promptly initiated and surgical cleansing is often necessary for wound and soft tissue infections. Conclusion: Due to the ongoing global warming an increased incidence of human infections with non-cholera Vibrio spp. must be expected in the future. Medical professionals should be aware of these bacterial pathogens and the potentially life-threatening infections in order to enable timely diagnostics and treatment.Peer Reviewe

The Impact of Antimicrobial Therapy Duration in the Treatment of Prosthetic Joint Infections Depending on Surgical Strategies: A Systematic Review and Meta-analysis

The aim of this systematic review was to address the question if short antibiotic treatment (SAT; at least 4 but <12 weeks) versus long antibiotic treatment (LAT) affects outcomes in prosthetic joint infections (PJIs). Database research (Medline, Embase, Web of Science, Scopus, Cochrane) retrieved 3740 articles, of which 10 studies were included in the analysis. Compared to LAT, 11% lower odds of treatment failure in the SAT group were found, although the difference was not statistically significant (pooled odds ratio, 0.89 [95% confidence interval, .53-1.50]). No difference in treatment failure was found between SAT and LAT once stratified by type of surgery, studies conducted in the United States versus Europe, study design, and follow-up. There is still no conclusive evidence that antibiotic treatment of PJIs for 12 weeks or longer is associated with better outcomes, irrespective of the type of surgical procedure. Most recent, high-quality studies tend to favor longer antibiotic courses, making them preferable in most situations