Consensus-based antimicrobial resistance and stewardship competencies for UK undergraduate medical students.

BACKGROUND: In the UK there is limited coverage of antimicrobial stewardship across postgraduate curricula and evidence that final year medical students have insufficient and inconsistent antimicrobial stewardship teaching. A national undergraduate curriculum for antimicrobial resistance and stewardship is required to standardize an adequate level of understanding for all future doctors. OBJECTIVES: To provide a UK national consensus on competencies for antimicrobial resistance and stewardship for undergraduate medical education. METHODS: Using the modified Delphi method over two online survey rounds, an expert panel comprising leads for infection teaching from 25 UK medical schools reviewed competency descriptors for antimicrobial resistance and stewardship education. RESULTS: There was a response rate of 100% with all 28 experts who agreed to take part completing both survey rounds. Following the first-round survey, of the initial 55 descriptors, 43 reached consensus (78%). The second-round survey included the 12 descriptors from the first round in which agreement had not been reached, four amended descriptors and 12 new descriptors following qualitative feedback from the panel members. Following the second-round survey, a total of 58 consensus-based competency descriptors within six overarching domains were identified. CONCLUSIONS: The consensus-based competency descriptors defined here can be used to inform standards, design curricula, develop assessment tools and direct UK undergraduate medical education

Automatic quantification of microvessel density in urinary bladder carcinoma

Seventy-three TUR-T biopsies from bladder carcinoma were evaluated regarding microvessel density, defined as microvessel number (nMVD) and cross-section endothelial cell area (aMVD). A semi-automatic and a newly developed, automatic image analysis technique were applied in immunostainings, performed according to an optimized staining protocol. In 12 cases a comparison of biopsy material and the corresponding cystectomy specimen were tested, showing a good correlation in 11 of 12 cases (92%). The techniques proved reproducible for both nMVD and aMVD quantifications related to total tumour area. However, the automatic method was dependent on high immunostaining quality. Simultaneous, semi-automatic quantification of microvessels, stroma and epithelial fraction resulted in a decreased reproducibility. Quantification in ten images, selected in a descending order of MVD by subjective visual judgement, showed a poor observer capacity to estimate and rank MVD. Based on our results we propose quantification of MVD related to one tissue compartment. When staining quality is of high standard, automatic quantification is applicable, which facilitates quantification of multiple areas and thus, should minimize selection variability. © 1999 Cancer Research Campaig

Characterisation of genes involved in biosynthesis of coronafacic acid, the polyketide component of the phytotoxin coronatine

Coronafacic acid (CFA) is the polyketide component of coronatine (COR), a phytotoxin produced by the plant pathogen, Pseudomonas syringae. In the present study we have determined the nucleotide sequence of a 3.92-kb DNA fragment involved in CFA biosynthesis. Analysis of the sequence revealed four complete open reading frames (ORFs) designated cfal to cfa4 and one incomplete ORF (cfa5), all transcribed in the same direction. The predicted translation products of cfal, cfa2 and cfa3 showed relatedness to acyl carrier proteins, fatty acid dehydrases and ß-ketoacylsynthases, respectively, which are required for polyketide synthesis. cfal was subcloned, its sequence was confirmed, and it was overexpressed in E. coli to yield a peptide with an apparent molecular mass of 6 kDa

The structure of TolB, an essential component of the tol-dependent translocation system, and its protein-protein interaction with the translocation domain of colicin E9.

AbstractBackground: E colicin proteins have three functional domains, each of which is implicated in one of the stages of killing Escherichia coli cells: receptor binding, translocation and cytotoxicity. The central (R) domain is responsible for receptor-binding activity whereas the N-terminal (T) domain mediates translocation, the process by which the C-terminal cytotoxic domain is transported from the receptor to the site of its cytotoxicity. The translocation of enzymatic E colicins like colicin E9 is dependent upon TolB but the details of the process are not known.Results: We have demonstrated a protein–protein interaction between the T domain of colicin E9 and TolB, an essential component of the tol-dependent translocation system in E. coli, using the yeast two-hybrid system. The crystal structure of TolB, a procaryotic tryptophan–aspartate (WD) repeat protein, reveals an N-terminal α+β domain based on a five-stranded mixed β sheet and a C-terminal six-bladed β-propeller domain.Conclusions: The results suggest that the TolB-box residues of the T domain of colicin E9 interact with the β-propeller domain of TolB. The protein–protein interactions of other β-propeller-containing proteins, the yeast yPrp4 protein and G proteins, are mediated by the loops or outer sheets of the propeller blades. The determination of the three-dimensional structure of the T domain–TolB complex and the isolation of mutations in TolB that abolish the interaction with the T domain will reveal fine details of the protein–protein interaction of TolB and the T domain of E colicins