Medical professionalism in the formal curriculum:5th year medical students' experiences

BACKGROUND: The standards and outcomes outlined in the General Medical Council’s publication ‘Tomorrow’s Doctors’ include proposals that medical professionalism be included in undergraduate curricula. Learning the values and attitudes necessary to become a ‘doctor as a professional’ has traditionally been left largely to the informal and hidden curricula. There remains no consensus or confirmed evidence upon which to base best practice for teaching in this area. In 2010, as part of a revision of the fifth year curriculum the University of Bristol Medical School introduced tutorials which focused on students’ achievement of the learning objectives in ‘Tomorrow’s Doctors Outcomes 3: the doctor as a professional’. This study sought to explore the students’ experiences of these tutorials in order to develop the evidence base further. METHODS: Sixteen medical students participated in three focus-group interviews exploring their experiences of medical professionalism tutorials. A course evaluation questionnaire to all fifth year students also provided data. Data were analysed using the principles of Interpretative Phenomenological Analysis. RESULTS: Four main themes were identified: students’ aversion to ‘ticking-boxes’, lack of engagement by the students, lack of engagement by the tutors and students’ views on how medical professionalism should be taught. CONCLUSIONS: A curriculum innovation which placed the achievement of medical professionalism in the formal curriculum was not unanimously embraced by students or faculty. Further consideration of the students’ aversion to ‘ticking-boxes’ is warranted. With continued demand for increased accountability and transparency in medical education, detailed check-lists of specific learning objectives will continue to feature as a means by which medical schools and learners demonstrate attainment. Students’ experiences and acceptance of these check-lists deserves attention in order to inform teaching and learning in this area. Learner and faculty ‘buy in’ are imperative to the success of curriculum change and vital if the students are to attain the intended learning objectives. Effective faculty development and student induction programmes could be employed to facilitate engagement by both parties

Broadly Neutralizing Bovine Antibodies: Highly Effective New Tools against Evasive Pathogens?

Potent antibody-mediated neutralization is critical for an organism to combat the vast array of pathogens it will face during its lifetime. Due to the potential genetic diversity of some viruses, such as HIV-1 and influenza, standard neutralizing antibodies are often ineffective or easily evaded as their targets are masked or rapidly mutated. This has thwarted efforts to both prevent and treat HIV-1 infections and means that entirely new formulations are required to vaccinate against influenza each year. However, some rare antibodies isolated from infected individuals confer broad and potent neutralization. A subset of these broadly neutralizing antibodies possesses a long complementarity-determining 3 region of the immunoglobulin heavy chain (CDR H3). This feature generates unique antigen binding site configurations that can engage conserved but otherwise inaccessible epitope targets thus neutralizing many viral variants. Remarkably, ultralong CDR H3s are a common feature of the cow antibody repertoire and are encoded by a single variable, diversity, joining (VDJ) recombination that is extensively diversified prior to antigen exposure. Recently, it was shown that cows rapidly generate a broadly neutralizing response upon exposure to HIV-1 and this is primarily mediated by these novel ultralong antibody types. This review summarises the current knowledge of these unusual CDR H3 structures and discusses their known and potential future uses

Evidence that avian reovirus σNS is an RNA chaperone: implications for genome segment assortment.

Reoviruses are important human, animal and plant pathogens having 10-12 segments of double-stranded genomic RNA. The mechanisms controlling the assortment and packaging of genomic segments in these viruses, remain poorly understood. RNA-protein and RNA-RNA interactions between viral genomic segment precursors have been implicated in the process. While non-structural viral RNA-binding proteins, such as avian reovirus σNS, are essential for virus replication, the mechanism by which they assist packaging is unclear. Here we demonstrate that σNS assembles into stable elongated hexamers in vitro, which bind single-stranded nucleic acids with high affinity, but little sequence specificity. Using ensemble and single molecule fluorescence spectroscopy, we show that σNS also binds to a partially double-stranded RNA, resulting in gradual helix unwinding. The hexamer can bind multiple RNA molecules and exhibits strand-annealing activity, thus mediating conversion of metastable, intramolecular stem-loops into more stable heteroduplexes. We demonstrate that the ARV σNS acts as an RNA chaperone facilitating specific RNA-RNA interactions between genomic precursors during segment assortment and packaging

Temocillin: a new candidate antibiotic for local antimicrobial delivery in orthopaedic surgery?

Objectives - To assess the performance of the Gram-negative-specific antibiotic temocillin in polymethylmethacrylate bone cement pre-loaded with gentamicin, as a strategy for local antibiotic delivery. Methods - Temocillin was added at varying concentrations to commercial gentamicin-loaded bone cement. The elution of the antibiotic from cement samples over a 2 week period was quantified by LC-MS. The eluted temocillin was purified by fast protein liquid chromatography and the MICs for a number of antibiotic-resistant Escherichia coli were determined. The impact strength of antibiotic-loaded samples was determined using a Charpy-type impact testing apparatus. Results - LC-MS data showed temocillin eluted to clinically significant concentrations within 1 h in this laboratory system and the eluted temocillin retained antimicrobial activity against all organisms tested. Impact strength analysis showed no significant difference between cement samples with or without temocillin. Conclusions - Temocillin can be added to bone cement and retains its antimicrobial activity after elution. The addition of up to 10% temocillin did not affect the impact strength of the cement. The results show that temocillin is a promising candidate for use in antibiotic-loaded bone cement.</p

Analysis of linezolid and tigecycline as candidates for local prophylaxis via antibiotic-loaded bone cement

Objectives To assess the Gram-positive-specific antibiotic linezolid and the broad-spectrum antibiotic tigecycline for use in local antibiotic delivery via antibiotic-loaded bone cement. Methods Linezolid and tigecycline were added to Biomet bone cement at varying concentrations. Antibiotic elution over 1 week was quantified by HPLC-MS. The effect of wear on elution over 51 h was determined using a modified TE-66 wear tester. Eluted antibiotics were used to determine the MICs for a panel of clinically relevant bacteria. The impact strength of antibiotic-loaded samples was determined using a Charpy-type impact testing apparatus. Cytotoxicity of eluted antibiotics against MG-63 cells was evaluated using an MTT assay. Results Linezolid and tigecycline eluted from bone cement to clinically relevant levels within 1 h and retained activity over 1 week. Mechanical wear significantly reduced elution of tigecycline, but had little effect on elution of linezolid. Linezolid showed low cytotoxicity towards MG-63 cells with ≤300 mg/mL resulting in >50% cell activity. Cytotoxicity of tigecycline was higher, with an IC50 of 5–10 mg/L. Conclusions Linezolid and tigecycline retain activity after elution from bone cement. The concentration of tigecycline may need to be carefully controlled due to cytotoxicity. The effect of wear on bone cement may need to be considered if tigecycline is to be used for local delivery. Up to 10% linezolid can be added without affecting the impact strength of the bone cement. These results are promising indications for future investigation of these antibiotics for use in local antibiotic delivery strategies

A Master equation approach to modeling an artificial protein motor

Linear bio-molecular motors move unidirectionally along a track by coordinating several different processes, such as fuel (ATP) capture, hydrolysis, conformational changes, binding and unbinding from a track, and center-of-mass diffusion. A better understanding of the interdependencies between these processes, which take place over a wide range of different time scales, would help elucidate the general operational principles of molecular motors. Artificial molecular motors present a unique opportunity for such a study because motor structure and function are a priori known. Here we describe use of a Master equation approach, integrated with input from Langevin and molecular dynamics modeling, to stochastically model a molecular motor across many time scales. We apply this approach to a specific concept for an artificial protein motor, the Tumbleweed.Comment: Submitted to Chemical Physics; 9 pages, 7 figure

Characterization of RNA aptamers that disrupt the RUNX1-CBFbeta/DNA complex.

The transcription factor RUNX1 (AML1) is an important regulator of haematopoiesis, and an important fusion partner in leukaemic translocations. High-affinity DNA binding by RUNX1 requires the interaction of the RUNX1 Runt-Homology-Domain (RHD) with the core-binding factor beta protein (CBFbeta). To generate novel reagents for in vitro and in vivo studies of RUNX1 function, we have selected high-affinity RNA aptamers against a recombinant RHD-CBFbeta complex. Selection yielded two sequence families, each dominated by a single consensus sequence. Aptamers from each family disrupt DNA binding by the RUNX1 protein in vitro and compete with sequence-specific dsDNA binding. Minimal, high-affinity ( approximately 100-160 nM) active aptamer fragments 28 and 30 nts in length, consisting of simple short stem-loop structures, were then identified. These bind to the RHD subunit and disrupt its interaction with CBFbeta, which is consistent with reduced DNA affinity in the presence of aptamer. These aptamers represent new reagents that target a novel surface on the RHD required to stabilize the recombinant RHD-CBFbeta complex and thus will further aid exploring the functions of this key transcription factor

Using rhythm for rehabilitation: evaluation of a novel haptic device

This project explored how new and novel approaches to stroke rehabilitation could improve physical function and the confidence of stroke survivors to remain active and engaged in the community. The innovation trialed was a ‘Haptic bracelet/cueing device’, developed at The Open University. An overview of the Haptic device, its development and role in stroke rehabilitation can be viewed at: https://www.youtube.com/watch?v=S4ZxN6H6XGk The Haptic bracelets provide a physical (embodied) beat that someone can walk to as an alternative to existing audio cuing ways of working. The haptic device provides a non-invasive, relatively cheap way of facilitating people after stroke to continue to maintain or even improve their mobility after intensive rehabilitation has finished. This research explored the impact of the haptic device to gains in mobility. The project had two key aims: 1. To develop a usable and practical prototype of a haptic device to restore gait symmetry after stroke. 2. To investigate the feasibility and acceptability of the prototype in stroke patients. Summary of findings and recommendations When introduced to the Haptic Bracelets participants hoped the product would provide them with: • More confidence and make them feel safer when walking. • Greater ability to take bigger strides rather than little steps. • A way to combat the silly mistakes participants reported making due to tiredness. • Reduced pain (knees, hips) The physiotherapists saw potential for the Haptic devices as part of post stroke rehabilitation, but expressed concern about their lack of access to mobile technologies when out in community practice settings. There were also concerns about use with some stroke survivors because of issues of cognition; and the sensation from the Haptic beat. In the Haptic gait testing • All the participants demonstrated good mobility performance prior to the study (high score on the Rivermead mobility scale) • 4/7* (57.1%) participants who were the most asymmetrical at baseline improved their gait symmetry whilst wearing the haptic device • 3/7* (42%) participant’s gait symmetry continued to improve in the post off condition. • All the participants walked quicker in post-op condition. However, gait speed varied between participants when they were wearing the haptic bracelets. • Participants were had had their strokes between 3-10 years ago, but there was still an indication that the Haptic bracelets were having some impact on mobility. • Syncing of the Haptic device and more mobile Inertial Measurement Unit (IMU) to the fixed gait laboratory (gold standard) system has improved the potential for more community based rehabilitation and commercialisation of the Haptic bracelets. • Post Haptic interviews identified that there were mixed participant feelings about the bracelets. However, some did express positive experiences from testing the Haptic bracelets, including a carry over effect after the devices were removed. Recommendations As this was a pilot study more work is now required to explore the: • use of the Haptic bracelets in community rehabilitation settings • feasibility of the using Haptic bracelets in community settings, particularly looking at staff access to new technologies • potential for the Haptic bracelets to be used in the home as part of ongoing rehabilitation • benefits of Haptic bracelets in the context of longer term stroke rehabilitation • future design needs to improve the look, size and ease of application • cost benefits of using Haptic bracelets as part of an overall program of stroke rehabilitation

Genomic RNA folding mediates assembly of human parechovirus

Assembly of the major viral pathogens of the Picornaviridae family is poorly understood. Human parechovirus 1 is an example of such viruses that contains 60 short regions of ordered RNA density making identical contacts with the protein shell. We show here via a combination of RNA-based systematic evolution of ligands by exponential enrichment, bioinformatics analysis and reverse genetics that these RNA segments are bound to the coat proteins in a sequence-specific manner. Disruption of either the RNA coat protein recognition motif or its contact amino acid residues is deleterious for viral assembly. The data are consistent with RNA packaging signals playing essential roles in virion assembly. Their binding sites on the coat proteins are evolutionarily conserved across the Parechovirus genus, suggesting that they represent potential broad-spectrum anti-viral targets.Peer reviewe