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Background and Objective: Urinary tract infections (UTIs) are some of the most encountered infections in clinical practice, exhibiting increasing antimicrobial resistance. Bacterial species identification and antimicrobial resistance testing at point of care (POCT) could improve adequate initial antibiotic therapy and antimicrobial stewardship. In this work, the Vivalytic UTI test, which represents a qualitative PCR-based microarray test, able to detect specific uropathogenic bacteria and associated antimicrobial resistance genes was evaluated at POCT., Methods: In September 2023, we used this point-of-care testing (POCT) to analyse 126 consecutive urine samples of patients with complicated UTI. Samples processed with the Vivalytic UTI POCT were preselected for the presence of bacteriuria by screening with urine flow cytometry (cut-off ≥70 bacteria per microlitre). We performed the POCT before and after sample transport, and compared the results to standard urine culture and antibiotic sensitivity tests according to the European Committee on Antimicrobial Susceptibility Testing., Key Findings and Limitations: Nineteen different bacterial species were detected. Sixteen species reached a diagnostic accuracy of ≥90.27% with negative predictive values of ≥93.67%. The POCT was able to detect bacterial species under the estimated concentration of 10 4 -5 × 10 4  CFU/ml. The concordant (Vivalytic vs. culture) antimicrobial resistance gene detection rate reached a higher accuracy after transport (≥84.15%) compared to POC-testing before transport (≥81.71%), except for Vancomycin. Aerococcus urinae, Enterococcus hirae, Hafnia alvei, and Staphylococcus lugdunensis are not part of the POCT test panel; these were detected by urine culture only in 19% of cases., Conclusions and Clinical Implications: The Vivalytic UTI POCT displayed high sensitivity and specificity in identifying uropathogenic bacteria and antibiotic resistance markers to be further evaluated in clinical practice. However, it would be helpful to expand the resistance to include information about more commonly used antibiotics like aminopenicillins, cephalosporines and fluoroquinolones., Patient Summary: In this study, we tested 126 consecutive urine samples of urological patients with complicated urinary tract infections (UTIs) by using the Vivalytic UTI point-of-care testing before and after sample transport. We found out that the sample transport to some extent influences the pathogen and resistance detection rate of the Vivalytic UTI assay. Compared to standard-of-care diagnostics, pathogen identification was more accurate before sample transport, while the concordant antimicrobial resistance gene detection rate reached higher accuracy after transport., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Flavivirus infection is tightly connected to host lipid metabolism. Here, we performed shotgun lipidomics of cells infected with neurotropic Zika, West Nile, and tick-borne encephalitis virus, as well as dengue and yellow fever virus. Early in infection specific lipids accumulate, e.g., neutral lipids in Zika and some lysophospholipids in all infections. Ceramide levels increase following infection with viruses that cause a cytopathic effect. In addition, fatty acid desaturation as well as glycerophospholipid metabolism are significantly altered. Importantly, depletion of enzymes involved in phosphatidylserine metabolism as well as phosphatidylinositol biosynthesis reduce orthoflavivirus titers and cytopathic effects while inhibition of fatty acid monounsaturation only rescues from virus-induced cell death. Interestingly, interfering with ceramide synthesis has opposing effects on virus replication and cytotoxicity depending on the targeted enzyme. Thus, lipid remodeling by orthoflaviviruses includes distinct changes but also common patterns shared by several viruses that are needed for efficient infection and replication., (© 2024. The Author(s).)

Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen. Its RNA genome consists of two negative-sense segments (L and M) with one gene each, and one ambisense segment (S) with two opposing genes separated by the noncoding "intergenic region" (IGR). These vRNAs and the complementary cRNAs are encapsidated by nucleoprotein (N). Using iCLIP2 (individual-nucleotide resolution UV crosslinking and immunoprecipitation) to map all N-vRNA and N-cRNA interactions, we detect N coverage along the L and M segments. However, the S segment vRNA and cRNA each contain approximately 100 non-encapsidated nucleotides stretching from the IGR into the 5'-adjacent reading frame. These exposed regions are RNase-sensitive and predicted to form stem-loop structures with the mRNA transcription termination motif positioned near the top. Moreover, optimal S segment transcription and replication requires the entire exposed region rather than only the IGR. Thus, the RVFV S segment contains a central, non-encapsidated RNA region with a functional role., (© 2024. The Author(s).)

Background and Objective: Urinary tract infections (UTIs) are common infections affecting the urinary system, predominantly caused by bacterial pathogens, with Escherichia coli being the most frequent pathogen. Infections of the kidney (eg, pyelonephritis) are severe and challenging to treat, due to the specific tissue microenvironment. In this study, the influence of different parameters mimicking the kidney environment on the effectiveness of antibiotics prescribed for pyelonephritis on the growth of uropathogenic strains was analyzed., Methods: To investigate the influence of different factors mimicking the kidney environment, we tested the effect of different kidney-representative concentrations of sodium chloride and urea, and different pH values on the efficacy of ertapenem, levofloxacin, and ceftriaxone. The effectiveness was assessed by determining the minimal inhibitory concentrations (MICs) against various E. coli strains., Key Findings and Limitations: The study revealed that pH significantly influences the MIC values of levofloxacin. Acidification of the pH led to an increase of the MIC values, while an alkaline pH had the opposite effect. The influence of sodium chloride and urea concentrations was strain and antibiotic specific. Since three different antibiotics were tested in this study, further research with additional antibiotics is warranted., Conclusions and Clinical Implications: These results suggest that the physicochemical conditions within the kidney can substantially influence the success of antibiotic therapy for pyelonephritis. Therefore, it is crucial for clinicians to consider these factors when selecting and dosing antibiotics. Further research is needed to evaluate a broader range of antibiotics and additional environmental parameters, to develop a more comprehensive understanding of how the kidney environment affects antimicrobial activity. This knowledge will be vital in optimizing treatment strategies for pyelonephritis, ultimately improving patient outcomes., Patient Summary: The physicochemical conditions within the kidney influence the success of antibiotic therapy for pyelonephritis. Our findings are vital in optimizing treatment strategies and will ultimately improve patient outcomes., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) represents a serious health condition, impacting the lives of many patients worldwide. The condition challenges clinical care due to its complex etiology and limited therapeutic options. A thorough understanding of the pathophysiological and patient-related factors that promote disease development is essential. Recently, the oral microbiome has been implicated as a potential driver and modulating factor of BRONJ by several studies. Modern genomic sequencing methods have provided a wealth of data on the microbial composition of BRONJ lesions; however, the role of individual species in the process of disease development remains elusive. A comprehensive PubMed search was conducted to identify relevant studies on the microbiome of BRONJ patients using the terms "microbiome", "osteonecrosis of the jaws", and "bisphosphonates". Studies focusing on symptoms, epidemiology, pathophysiology, risk factors, and treatment options were included. The principal risk factors for BRONJ are tooth extraction, surgical procedures, and the administration of high doses of bisphosphonates. Importantly, the oral microbiome plays a significant role in the progression of the disease. Several studies have identified alterations of microbial composition in BRONJ lesions. However, there is no consensus regarding bacterial species that are associated with BRONJ across studies. The bacterial genera typically found include Actinomyces , Fusobacterium , and Streptococcus . It is postulated that these microbes contribute to the pathogenesis of BRONJ by promoting inflammation and disrupting normal bone remodeling processes. Current therapeutic approaches are disease-stage-specific and the necessity for more effective treatment strategies remains. This review examines the potential causes of and therapeutic approaches to BRONJ, highlighting the link between microbial colonization and BRONJ development. Future research should seek to more thoroughly investigate the interactions between bisphosphonates, the oral microbiome, and the immune system in order to develop targeted therapies.

Selective demolition of building components and recycling construction demolition waste is a growing tendency as we move towards a circular construction. This study investigates the feasibility of using demolition waste from calcium silicate brick masonry as an aggregate in concrete and mortar. The purpose is to assess its impact on concrete and mortar properties, including compressive strength, durability, and workability. Silicate bricks from two demolished buildings were processed into aggregate, and laboratory experiments were conducted to evaluate concrete and mortar made with varying proportions of recycled aggregate. Results indicate that replacing natural aggregate (limestone rubble and sand) with recycled silicate brick aggregate up to 50% does not significantly compromise concrete performance, with no significant decrease in compressive strength observed. Frost resistance of the concrete made with recycled aggregate even surpasses that of reference concrete, possibly due to the lower density and higher (closed) porosity of the recycled aggregate. However, challenges such as increased water demand and loss of workability over time are noted with higher proportions of recycled aggregate. Further research is recommended to explore strategies for mitigating these challenges and to assess the effects of chemical admixtures on concrete properties. Overall, the findings suggest that recycled calcium silicate brick holds promise as a sustainable alternative for aggregate in concrete production.

Introduction: Protein kinases are indispensable reversible molecular switches that adapt and control protein functions during cellular processes requiring rapid responses to internal and external events. Bacterial infections can affect kinase-mediated phosphorylation events, with consequences for both innate and adaptive immunity, through regulation of antigen presentation, pathogen recognition, cell invasiveness and phagocytosis. Streptococcus pneumoniae ( Spn ), a human respiratory tract pathogen and a major cause of community-acquired pneumoniae, affects phosphorylation-based signalling of several kinases, but the pneumococcal mediator(s) involved in this process remain elusive. In this study, we investigated the influence of pneumococcal H 2 O 2 on the protein kinase activity of the human lung epithelial H441 cell line, a generally accepted model of alveolar epithelial cells., Methods: We performed kinome analysis using PamGene microarray chips and protein analysis in Western blotting in H441 lung cells infected with Spn wild type ( SpnWT ) or with SpnΔlctOΔspxB -a deletion mutant strongly attenuated in H 2 O 2 production- to assess the impact of pneumococcal hydrogen peroxide (H 2 O 2 ) on global protein kinase activity profiles., Results: Our kinome analysis provides direct evidence that kinase activity profiles in infected H441 cells significantly vary according to the levels of pneumococcal H 2 O 2 . A large number of kinases in H441 cells infected with SpnWT are significantly downregulated, whereas this no longer occurs in cells infected with the mutant SpnΔlctOΔspxB strain, which lacks H 2 O 2. In particular, we describe for the first time H 2 O 2 -mediated downregulation of Protein kinase B (Akt1) and activation of lymphocyte-specific tyrosine protein kinase (Lck) via H 2 O 2 -mediated phosphorylation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Bazant, Weiss, Baldauf, Schermuly, Hain, Lucas and Mraheil.)