volumetric characterisation and correlation to established classification systems

Objective and sensitive assessment of cartilage repair outcomes lacks suitable methods. This study investigated the feasibility of 3D ultrasound biomicroscopy (UBM) to quantify cartilage repair outcomes volumetrically and their correlation with established classification systems. 32 sheep underwent bilateral treatment of a focal cartilage defect. One or two years post- operatively the repair outcomes were assessed and scored macroscopically (Outerbridge, ICRS-CRA), by magnetic resonance imaging (MRI, MOCART), and histopathology (O'Driscoll, ICRS-I and ICRS-II). The UBM data were acquired after MRI and used to reconstruct the shape of the initial cartilage layer, enabling the estimation of the initial cartilage thickness and defect volume as well as volumetric parameters for defect filling, repair tissue, bone loss and bone overgrowth. The quantification of the repair outcomes revealed high variations in the initial thickness of the cartilage layer, indicating the need for cartilage thickness estimation before creating a defect. Furthermore, highly significant correlations were found for the defect filling estimated from UBM to the established classification systems. 3D visualisation of the repair regions showed highly variable morphology within single samples. This raises the question as to whether macroscopic, MRI and histopathological scoring provide sufficient reliability. The biases of the individual methods will be discussed within this context. UBM was shown to be a feasible tool to evaluate cartilage repair outcomes, whereby the most important objective parameter is the defect filling. Translation of UBM into arthroscopic or transcutaneous ultrasound examinations would allow non-destructive and objective follow-up of individual patients and better comparison between the results of clinical trials

Preclinical good laboratory practice-compliant safety study to evaluate biodistribution and tumorigenicity of a cartilage advanced therapy medicinal product (ATMP)

Background: The clinical development of advanced therapy medicinal products (ATMPs), a new class of drugs, requires initial safety studies that deviate from standard non-clinical safety protocols. The study provides a strategy to address the safety aspects of biodistribution and tumorigenicity of ATMPs under good laboratory practice (GLP) conditions avoiding cell product manipulation. Moreover, the strategy was applied on a human ATMP for cartilage repair

The Treatment In Morning versus Evening (TIME) study:Analysis of recruitment, follow-up and retention rates post-recruitment

Abstract Background The use of information technology (IT) is now the preferred method of capturing and storing clinical research data. The Treatment In Morning versus Evening (TIME) study predominantly uses electronic data capture and IT to compare morning dosing of hypertensive medication against evening dosing. Registration, consent, participant demographics and follow-up data are all captured via the study website. The aim of this article is to assess the success of the TIME methodology compared with similar studies. Methods To assess the TIME study, published literature on similar clinical trials was reviewed and compared against TIME recruitment, follow-up and email interaction data. Results The TIME website registered 31,695 individuals, 21,116 of whom were randomised. Recruitment cost per randomised participant varied by strategy: £17.40 by GP practice, £3.08 by UK Biobank and £58.82 for GoShare. Twelve-month follow-up retention rates were 96%. A total of 1089 participants have withdrawn from their assigned time of dosing, 2% of whom have declined follow-up by record linkage or further contact. When the TIME data are compared with similar study data, study recruitment is very successful. However, TIME suffers difficulties with participant follow-up and withdrawal rates similar to those of conventional studies. Conclusions The TIME study has been successful in recruitment. Follow-up, retention rates and withdrawal rates are all acceptable, but ongoing work is required to ensure participants remain engaged with the study. Various recruitment strategies are necessary, and all viable options should be encouraged to maintain participant engagement throughout the life of studies using IT

A Trigger Enzyme in Mycoplasma pneumoniae: Impact of the Glycerophosphodiesterase GlpQ on Virulence and Gene Expression

Mycoplasma pneumoniae is a causative agent of atypical pneumonia. The formation of hydrogen peroxide, a product of glycerol metabolism, is essential for host cell cytotoxicity. Phosphatidylcholine is the major carbon source available on lung epithelia, and its utilization requires the cleavage of deacylated phospholipids to glycerol-3-phosphate and choline. M. pneumoniae possesses two potential glycerophosphodiesterases, MPN420 (GlpQ) and MPN566. In this work, the function of these proteins was analyzed by biochemical, genetic, and physiological studies. The results indicate that only GlpQ is an active glycerophosphodiesterase. MPN566 has no enzymatic activity as glycerophosphodiesterase and the inactivation of the gene did not result in any detectable phenotype. Inactivation of the glpQ gene resulted in reduced growth in medium with glucose as the carbon source, in loss of hydrogen peroxide production when phosphatidylcholine was present, and in a complete loss of cytotoxicity towards HeLa cells. All these phenotypes were reverted upon complementation of the mutant. Moreover, the glpQ mutant strain exhibited a reduced gliding velocity. A comparison of the proteomes of the wild type strain and the glpQ mutant revealed that this enzyme is also implicated in the control of gene expression. Several proteins were present in higher or lower amounts in the mutant. This apparent regulation by GlpQ is exerted at the level of transcription as determined by mRNA slot blot analyses. All genes subject to GlpQ-dependent control have a conserved potential cis-acting element upstream of the coding region. This element overlaps the promoter in the case of the genes that are repressed in a GlpQ-dependent manner and it is located upstream of the promoter for GlpQ-activated genes. We may suggest that GlpQ acts as a trigger enzyme that measures the availability of its product glycerol-3-phosphate and uses this information to differentially control gene expression

Methionine Sulfoxide Reductase A (MsrA) Deficient Mycoplasma genitalium Shows Decreased Interactions with Host Cells

Mycoplasma genitalium is an important sexually transmitted pathogen that affects both men and women. In genital-mucosal tissues, it initiates colonization of epithelial cells by attaching itself to host cells via several identified bacterial ligands and host cell surface receptors. We have previously shown that a mutant form of M. genitalium lacking methionine sulfoxide reductase A (MsrA), an antioxidant enzyme which converts oxidized methionine (Met(O)) into methionine (Met), shows decreased viability in infected animals. To gain more insights into the mechanisms by which MsrA controls M. genitalium virulence, we compared the wild-type M. genitalium strain (G37) with an msrA mutant (MS5) strain for their ability to interact with target cervical epithelial cell lines (HeLa and C33A) and THP-1 monocytic cells. Infection of epithelial cell lines with both strains revealed that MS5 was less cytotoxic to HeLa and C33A cell lines than the G37 strain. Also, the MS5 strain was more susceptible to phagocytosis by THP-1 cells than wild type strain (G37). Further, MS5 was less able to induce aggregation and differentiation in THP-1 cells than the wild type strain, as determined by carboxyfluorescein diacetate succinimidyl ester (CFSE) labeling of the cells, followed by counting of cells attached to the culture dish using image analysis. Finally, MS5 was observed to induce less proinflammatory cytokine TNF-α by THP-1 cells than wild type G37 strain. These results indicate that MsrA affects the virulence properties of M. genitalium by modulating its interaction with host cells

Using video-reflexive ethnography and simulation-based education to explore patient management and error recognition by pre-registration physiotherapists

Background: Upon graduation, physiotherapists are required to manage clinical caseloads involving deteriorating patients with complex conditions. In particular, emergency on-call physiotherapists are required to provide respiratory/ cardio-respiratory/cardiothoracic physiotherapy, out of normal working hours, without senior physiotherapist support. To optimise patient safety, physiotherapists are required to function within complex clinical environments, drawing on their knowledge and skills (technical and non-technical), maintaining situational awareness and filtering unwanted stimuli from the environment. Prior to this study, the extent to which final-year physiotherapy students were able to manage an acutely deteriorating patient in a simulation context and recognise errors in their own practice was unknown. Methods: A focused video-reflexive ethnography study was undertaken to explore behaviours, error recognition abilities and personal experiences of 21 final-year (pre-registration) physiotherapy students from one higher education institution. Social constructivism and complexity theoretical perspectives informed the methodological design of the study. Video and thematic analysis of 12 simulation scenarios and video-reflexive interviews were undertaken. Results: Participants worked within the professional standards of physiotherapy practice expected of entry-level physiotherapists. Students reflected appropriate responses to their own and others’ actions in the midst of uncertainty of the situation and physiological disturbances that unfolded during the scenario. However, they demonstrated a limited independent ability to recognise errors. Latent errors, active failures, error-producing factors and a series of effective defences to mitigate errors were identified through video analysis. Perceived influential factors affecting student performance within the scenario were attributed to aspects of academic and placement learning and the completion of a voluntary acute illness management course. The perceived value of the simulation scenario was enhanced by the opportunity to review their own simulation video with realism afforded by the scenario design. Conclusions: This study presents a unique insight into the experiences, skills, attitudes, behaviours and error recognition abilities of pre-registration physiotherapy students managing an acutely deteriorating patient in a simulation context. Findings of this research provide valuable insights to inform future research regarding physiotherapy practice, integration of educational methods to augment patient safety awareness and participant-led innovations in safe healthcare practice. Keywords: Error recognition, Deterioration, Physiotherapy, Simulation-based education, Video-reflexive ethnograph

Women in academic surgery over the last four decades.

ObjectiveAs the number of female medical students and surgical residents increases, the increasing number of female academic surgeons has been disproportionate. The purpose of this brief report is to evaluate the AAMC data from 1969 to 2018 to compare the level of female academic faculty representation for surgical specialties over the past four decades.DesignThe number of women as a percentage of the total surgeons per year were recorded for each year from 1969-2018, the most recent year available. Descriptive statistics were performed. Poisson regression examined the percentage of women in each field as the outcome of interest with the year and specialty (using general surgery as a reference) as two predictor variables.SettingData from the American Association of Medical Colleges (AAMC).ParticipantsAll full-time academic faculty physicians in the specialties of obstetrics and gynecology (OB/GYN), general surgery, ophthalmology, otolaryngology (ENT), plastic surgery, plastic surgery, urology, neurosurgery, orthopaedic surgery and cardiothoracic surgery as per AAMC records.ResultsThe percentage of women in surgery for all specialties evaluated increased from 1969 to 2018 (OR 1.04, pConclusionsRepresentation of women in academic surgery is increasing overall but is increasing more slowly in orthopaedic surgery, neurosurgery, cardiothoracic surgery and urology compared with that in general surgery. These data may be used to inform and further the discussion of how mentorship and sponsorship of female students and trainees interested in surgical careers may improve gender equity in the future

Quality of internet-based decision aids for shoulder arthritis: what are patients reading?

Abstract Background The objective of this study was to assess the source, quality, accuracy, and completeness of Internet-based information for shoulder arthritis. Methods A web search was performed using three common Internet search engines and the top 50 sites from each search were analyzed. Information sources were categorized into academic, commercial, non-profit, and physician sites. Information quality was measured using the Health On the Net (HON) Foundation principles, content accuracy by counting factual errors and completeness using a custom template. Results After removal of duplicates and sites that did not provide an overview of shoulder arthritis, 49 websites remained for analysis. The majority of sites were from commercial (n = 16, 33%) and physician (n = 16, 33%) sources. An additional 12 sites (24%) were from an academic institution and five sites (10%) were from a non-profit organization. Commercial sites had the highest number of errors, with a five-fold likelihood of containing an error compared to an academic site. Non-profit sites had the highest HON scores, with an average of 9.6 points on a 16-point scale. The completeness score was highest for academic sites, with an average score of 19.2 ± 6.7 (maximum score of 49 points); other information sources had lower scores (commercial, 15.2 ± 2.9; non-profit, 18.7 ± 6.8; physician, 16.6 ± 6.3). Conclusions Patient information on the Internet regarding shoulder arthritis is of mixed accuracy, quality, and completeness. Surgeons should actively direct patients to higher-quality Internet sources