Abdominal aortic aneurysm clinical practice guidelines: a methodological assessment using the AGREE II instrument.

OBJECTIVES: Abdominal aortic aneurysm (AAA) clinical practice guidelines (CPGs) provide evidence-based information on patient management; however, methodological differences exist in the development of CPGs. This study examines the methodological quality of AAA CPGs using a validated assessment tool. METHODS: Medline, EMBASE and online CPG databases were searched from 1946 to 31 October 2021. Full-text, English language, evidence-based AAA CPGs were included. Consensus-based CPGs, summaries of CPGs or CPGs which were only available on purchase were excluded. Five reviewers assessed their quality using the Appraisal of Guidelines for Research and Evaluation II instrument. An overall guideline assessment scaled score of ≥80% was considered as the threshold to recommend CPG use in clinical practice. RESULTS: Seven CPGs were identified. Scores showed good inter-reviewer reliability (intraclass correlation coefficient 0.943, 95% CI 0.915 to 0.964). On average, CPGs performed adequately with mean scaled scores of over 50% in all domains. However, between CPGs, significant methodological heterogeneity was observed in all domains. Four CPGs scored ≥80% (European Society of Cardiology, the Society of Vascular Surgery, the European Society of Vascular Surgery and the National Institute of Health and Care Excellence), supporting their use in clinical practice. CONCLUSIONS: Four CPGs were considered of adequate methodological quality to recommend their use in clinical practice; nonetheless, these still showed areas for improvement, potentially through performing economic analysis and trial application of recommendations. A structured approach employing validated CPG creation tools should be used to improve rigour of AAA CPGs. Future work should also evaluate recommendation accuracy using validated appraisal tools

Advanced therapeutic dressings for effective wound healing

Advanced therapeutic dressings that take active part in wound healing to achieve rapid and complete healing of chronic wounds is of current research interest. There is a desire for novel strategies to achieve expeditious wound healing due to the enormous financial burden worldwide. This paper reviews the current state of wound healing and wound management products, with emphasis on the demand for more advanced forms of wound therapy and some of the current challenges and driving forces behind this demand. The paper reviews information mainly from peer reviewed literature and other publicly available sources such as the FDA. A major focus is the treatment of chronic wounds including amputations, diabetic and leg ulcers, pressure sores, surgical and traumatic wounds (e.g. accidents and burns) where patient immunity is low and the risk of infections and complications are high. The main dressings include medicated moist dressings, tissue engineered substitutes, biomaterials based biological dressings, biological and naturally derived dressings, medicated sutures and various combinations of the above classes. Finally, the review briefly discusses possible prospects of advanced wound healing including some of the emerging approaches such as hyperbaric oxygen, negative pressure wound therapy and laser wound healing, in routine clinical care

Computational study of dually phosphorylated peptides binding to the SRC SHZ domain

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Isolation of Leptospira from blood culture bottles

International audienceWith the increasing use of real time PCR techniques, Leptospira isolation has mostly been abandoned for the diagnosis of human leptospirosis. However, there is a great value of collecting Leptospira isolates to better understand the epidemiology of this complex zoonosis and to provide the researchers with different isolates. In this study, we have successfully isolated different Leptospira strains from BacT/Alert aerobic blood culture bottles and suggest that this privileged biological material offers an opportunity to isolate leptospires

Continuous Excretion of Leptospira borgpetersenii Ballum in Mice Assessed by Viability Quantitative Polymerase Chain Reaction.

International audienceRodents are the main reservoir animals of leptospirosis. In this study, we characterized and quantified the urinary excretion dynamics of Leptospira by Mus musculus infected with 2 × 108 virulent Leptospira borgpetersenii serogroup Ballum. Each micturition was collected separately in metabolic cages, at 12 time points from 7 to 117 days post-infection (dpi). We detected Leptospira in all urine samples collected (up to 8 per time point per mouse) proving that Leptospira excretion is continuous with ca. 90% live L. borgpetersenii Ballum, revealed by viability quantitative polymerase chain reaction. Microscopic visualization by Live/Dead fluorescence confirmed this high proportion of live bacteria and demonstrated that L. borgpetersenii Ballum are excreted, at least partly, as bacterial aggregates. We observed two distinct phases in the excretion dynamics, first an increase in Leptospira concentration shed in the urine between 7 and 63 dpi followed by a plateau phase from 63 dpi onward, with up to 3 × 107Leptospira per mL of urine. These two phases seem to correspond to progressive colonization of renal tubules first, then to stable cell survival and maintenance in kidneys. Therefore, chronically infected adult mice are able to contaminate the environment via urine at each micturition event throughout their lifetime. Because Leptospira excretion reached its maximum 2 months after infection, older rodents have a greater risk of contaminating their surrounding environment

Abdominal aortic aneurysm clinical practice guidelines: a methodological assessment using the AGREE II instrument

Objectives: Abdominal aortic aneurysm (AAA) clinical practice guidelines (CPGs) provide evidence-based information on patient management; however, methodological differences exist in the development of CPGs. This study examines the methodological quality of AAA CPGs using a validated assessment tool. Design: Medline, EMBASE and online CPG databases were searched from 1946 to 31st October 2021. Full-text, English language, evidence-based AAA CPGs were included. Consensus-based CPGs, summaries of CPGs or CPGs which were only available upon purchase were excluded. Five reviewers assessed their quality using the Appraisal of Guidelines for Research and Evaluation II instrument. An overall guideline assessment scaled score of ≥80% was considered as the threshold to recommend CPG use in clinical practice. Results: Seven CPGs were identified. Scores showed good inter-reviewer reliability (ICC 0.943, 95% CI 0.915-0.964). On average, CPGs performed adequately with mean scaled scores of over 50% in all domains. However, between CPGs, significant methodological heterogeneity was observed in all domains. Four CPGs scored ≥80% (European Society of Cardiology, the Society of Vascular Surgery, the European Society of Vascular Surgery, and the National Institute of Health and Care Excellence), supporting their use in clinical practice. Conclusions: Four CPGs were considered of adequate methodological quality to recommend their use in clinical practice; nonetheless, these still showed areas for improvement, potentially through performing economic analysis and trial application of recommendations. A structured approach employing validated CPG creation tools should be used to improve rigour of AAA CPGs. Future work should also evaluate recommendation accuracy using validated appraisal tools

Insights from the energetics binding at the domain-ligand of the Src SH2 domain of water interface

SH2 domains play important roles in signal transduction by binding phosphorylated tyrosine residues on cell surface receptors. In an effort to understand the mechanism of ligand binding and more specifically the role of water, we have designed a general computational protocol based on the potential of mean force to compute the thermodynamics of water molecules at the protein-ligand interface for two SH2 domain complexes of the Src kinase, those bound to the two peptides Ac-PQpYEpYI-NH2 and Ac-PQpYIpYV-NH2 where pY indicates a phosphotyrosine. These two peptides were chosen because they have similar binding affinities but very different entropic/enthalpic thermodynamic binding signatures, indicating different interactions with solvent. We find that the isoleucine to valine mutation at position +3 (the third amino acid C-terminal to pY) in the ligand has only limited impact on the water structure. By contrast, the glutamic acid to isoleucine mutation at position +1 has a significant impact by not only abrogating a local hydrophilic binding site but, more importantly and surprisingly, inducing a favorable nonlocal entropic contribution from the water molecules around the phophorylated tyrosine at the +2 position. Our study demonstrates the validity of the method reported here for exploring the thermodynamic solvation landscape of protein-protein interactions. Proteins 2008. © 2008 Wiley-Liss, Inc

Seeking the environmental source of Leptospirosis reveals durable bacterial viability in river soils.

International audienceBACKGROUND:Leptospirosis is an important re-emerging infectious disease that affects humans worldwide. Infection occurs from indirect environment-mediated exposure to pathogenic leptospires through contaminated watered environments. The ability of pathogenic leptospires to persist in the aqueous environment is a key factor in transmission to new hosts. Hence, an effort was made to detect pathogenic leptospires in complex environmental samples, to genotype positive samples and to assess leptospiral viability over time.METHODOLOGY/PRINCIPAL FINDINGS:We focused our study on human leptospirosis cases infected with the New Caledonian Leptospira interrogans serovar Pyrogenes. Epidemiologically related to freshwater contaminations, this strain is responsible for ca. 25% of human cases in New Caledonia. We screened soil and water samples retrieved from suspected environmental infection sites for the pathogen-specific leptospiral gene lipL-32. Soil samples from all suspected infection sites tested showed detectable levels of pathogenic leptospiral DNA. More importantly, we demonstrated by viability qPCR that those pathogenic leptospires were viable and persisted in infection sites for several weeks after the index contamination event. Further, molecular phylogenetic analyses of the leptospiral lfb-1 gene successfully linked the identity of environmental Leptospira to the corresponding human-infecting strain.CONCLUSIONS/SIGNIFICANCE:Altogether, this study illustrates the potential of quantitative viability-PCR assay for the rapid detection of viable leptospires in environmental samples, which might open avenues to strategies aimed at assessing environmental risk

Cytokine, iNOS and chemokine gene expression in the kidneys depending on infected animals during <i>Leptospira</i> carrier state.

<p>Mice (open squares) and hamsters (filled squares) were infected with a sublethal dose of <i>L</i>. <i>borgpetersenii</i> serogroup Ballum isolate B3-13S. Total mRNA was extracted from kidneys at 14 and between 21 and 28 days postinfection and RT-qPCR assays were processed as described in Materials and Methods. Results are expressed as expression ratio relative to non-infected animal controls (time 0). Values are means (horizontal line) and individual ratio (dots). Significant difference in the gene expression levels were evaluated between animals and compared to control individual using an unpaired <i>t</i>-test. *<i>P</i><0.05, **<i>P</i><0.005, ***<i>P</i><0.0005, <i>ns</i>: not significant.</p