28 research outputs found
Recommended from our members
Imaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers.
Occult bacterial infections represent a worldwide health problem. Differentiating active bacterial infection from sterile inflammation can be difficult using current imaging tools. Present clinically viable methodologies either detect morphologic changes (CT/ MR), recruitment of immune cells (111In-WBC SPECT), or enhanced glycolytic flux seen in inflammatory cells (18F-FDG PET). However, these strategies are often inadequate to detect bacterial infection and are not specific for living bacteria. Recent approaches have taken advantage of key metabolic differences between prokaryotic and eukaryotic organisms, allowing easier distinction between bacteria and their host. In this report, we exploited one key difference, bacterial cell wall biosynthesis, to detect living bacteria using a positron-labeled D-amino acid. After screening several 14C D-amino acids for their incorporation into E. coli in culture, we identified D-methionine as a probe with outstanding radiopharmaceutical potential. Based on an analogous procedure to that used for L-[methyl-11C]methionine ([11C] L-Met), we developed an enhanced asymmetric synthesis of D-[methyl-11C]methionine ([11C] D-Met), and showed that it can rapidly and selectively differentiate both E. coli and S. aureus infections from sterile inflammation in vivo. We believe that the ease of [11C] D-Met radiosynthesis, coupled with its rapid and specific in vivo bacterial accumulation, make it an attractive radiotracer for infection imaging in clinical practice
Impact of investigational microbiota therapeutic RBX2660 on the gut microbiome and resistome revealed by a placebo-controlled clinical trial
BACKGROUND: Intestinal microbiota restoration can be achieved by complementing a subject\u27s perturbed microbiota with that of a healthy donor. Recurrent Clostridioides difficile infection (rCDI) is one key application of such treatment. Another emerging application of interest is reducing antibiotic-resistant genes (ARGs) and organisms (AROs). In this study, we investigated fecal specimens from a multicenter, randomized, double-blind, placebo-controlled phase 2b study of microbiota-based investigational drug RBX2660. Patients were administered either placebo, 1 dose of RBX2660 and 1 placebo, or 2 doses of RBX2660 via enema and longitudinally tracked for changes in their microbiome and antibiotic resistome.
RESULTS: All patients exhibited significant recovery of gut microbiome diversity and a decrease of ARG relative abundance during the first 7 days post-treatment. However, the microbiome and resistome shifts toward average configurations from unperturbed individuals were more significant and longer-lasting in RBX2660 recipients compared to placebo. We quantified microbiome and resistome modification by RBX2660 using a novel transplantation index metric. We identified taxonomic and metabolic features distinguishing the baseline microbiome of non-transplanted patients and taxa specifically enriched during the process of transplantation. We elucidated the correlation between resistome and taxonomic transplantations and post-treatment dynamics of patient-specific and RBX2660-specific ARGs. Whole genome sequencing of AROs cultured from RBX2660 product and patient samples indicate ARO eradication in patients via RBX2660 administration, but also, to a lesser extent, introduction of RBX2660-derived AROs.
CONCLUSIONS: Through shotgun metagenomic sequencing, we elucidated the effects of RBX2660 in the microbiome and resistome. Antibiotic discontinuation alone resulted in significant recovery of gut microbial diversity and reduced ARG relative abundance, but RBX2660 administration more rapidly and completely changed the composition of patients\u27 microbiome, resistome, and ARO colonization by transplanting RBX2660 microbiota into the recipients. Although ARGs and AROs were transmitted through RBX2660, the resistome post-RBX2660 more closely resembled that of the administered product-a proxy for the donor-than an antibiotic perturbed state.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT02299570 . Registered 19 November 2014 Video Abstract
Cassette Notes
https://orc.library.atu.edu/atu_cass065/1013/thumbnail.jp
Computational chemistry for graphene-based energy applications: progress and challenges
YesResearch in graphene-based energy materials is a rapidly growing area. Many graphene-based energy applications involve interfacial processes. To enable advances in the design of these energy materials, such that their operation, economy, efficiency and durability is at least comparable with fossil-fuel based alternatives, connections between the molecular-scale structure and function of these interfaces are needed. While it is experimentally challenging to resolve this interfacial structure, molecular simulation and computational chemistry can help bridge these gaps. In this Review, we summarise recent progress in the application of computational chemistry to graphene-based materials for fuel cells, batteries, photovoltaics and supercapacitors. We also outline both the bright prospects and emerging challenges these techniques face for application to graphene-based energy materials in future.vesk
Recommended from our members
Evaluation of D-Amino Acids as Probes for Molecular Imaging of Bacterial Infections
Purpose: The goal of this study was to investigate a panel of D-amino acids and select potential probe candidates for imaging bacterial infections in vivo.Methods: Uptake of radiolabeled D-amino acids was tested in E. coli. Selection of candidates was based on the following criteria: (1) high uptake in E. coli and (2) ease of 18F labeled analog synthesis. Selected D-amino acid candidates were then tested for uptake and specificity in E. coli at several time points and with coadministration of non-radioactive D-amino acid blocking dose. 18F D-Phenylalanine was synthesized to test uptake in E. coli over time. 18F-FDG was tested for uptake and specificity in E. coli at several time points and with coadministration of non-radioactive Cytochalasin B blocking dose.Results: D-Methionine showed the highest uptake in E. coli. D-Methionine uptake increased over time in E. coli and showed specific uptake. D-Phenylalanine uptake increased over time in E. coli and showed specific uptake. 18F D-Phenylalanine showed higher uptake in E. coli and showed more bacteria specific uptake than 18F-FDG.Conclusion: D-Methionine and D-Phenylalanine were selected as potential probe candidates for imaging bacterial infections in vivo
Recommended from our members
Imaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers
Recommended from our members
Imaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers.
Occult bacterial infections represent a worldwide health problem. Differentiating active bacterial infection from sterile inflammation can be difficult using current imaging tools. Present clinically viable methodologies either detect morphologic changes (CT/ MR), recruitment of immune cells (111In-WBC SPECT), or enhanced glycolytic flux seen in inflammatory cells (18F-FDG PET). However, these strategies are often inadequate to detect bacterial infection and are not specific for living bacteria. Recent approaches have taken advantage of key metabolic differences between prokaryotic and eukaryotic organisms, allowing easier distinction between bacteria and their host. In this report, we exploited one key difference, bacterial cell wall biosynthesis, to detect living bacteria using a positron-labeled D-amino acid. After screening several 14C D-amino acids for their incorporation into E. coli in culture, we identified D-methionine as a probe with outstanding radiopharmaceutical potential. Based on an analogous procedure to that used for L-[methyl-11C]methionine ([11C] L-Met), we developed an enhanced asymmetric synthesis of D-[methyl-11C]methionine ([11C] D-Met), and showed that it can rapidly and selectively differentiate both E. coli and S. aureus infections from sterile inflammation in vivo. We believe that the ease of [11C] D-Met radiosynthesis, coupled with its rapid and specific in vivo bacterial accumulation, make it an attractive radiotracer for infection imaging in clinical practice