Modulation of expression and cellular distribution of p21 by macrophage migration inhibitory factor

<p>Abstract</p> <p>Background</p> <p>The pleiotropic protein MIF, (macrophage migration inhibitory factor), has been demonstrated to modulate several key proteins governing cell cycle control and is considered to contribute to cell growth and differentiation. In this study we investigated the effect of MIF on the expression and cellular distribution of the CDK inhibitor p21.</p> <p>Methods</p> <p>The effect of endogenous MIF on p21 expression and distribution was examined by comparing murine dermal fibroblasts derived from <it>wt </it>and MIF -/- mice. The effect of MIF on cell growth and apoptotic rates was compared using ³H-Thymidine incorporation assays and annexin V/PI assays respectively. Total p21 protein levels were compared using flow cytometry and western blotting. p21 mRNA was assessed by RT-PCR. Intracellular p21 staining was performed to assess cellular distribution of total protein. To further confirm observations siRNA was used to knockdown MIF protein in <it>wt </it>cells. Cell cycle analysis was performed using PI incorporation assays.</p> <p>Results</p> <p>MIF-/- murine dermal fibroblasts exhibited reduced proliferative responses and were more susceptible to apoptosis. This was associated with reduced p21 expression and nuclear distribution. Treatment with recombinant MIF protein was demonstrated to reduce both basal and induced apoptosis and increase nuclear p21 expression. Reduced nuclear p21 expression was also observed in MIF siRNA treated <it>wt </it>cells.</p> <p>Conclusion</p> <p>The results demonstrate that in the absence of MIF p21 expression and nuclear distribution is reduced which is associated with a reduction in cell growth and increased apoptosis. MIF may therefore play a role in maintaining homeostatic control of p21.</p

How Do Students Enact Group Reasoning Within Online Interprofessional Education?

Background: The capability of an interprofessional healthcare team to reach a shared understanding through group reasoning is critical to good healthcare delivery. Models for clinical reasoning have proved useful but remain focused on individual cognitive processes. Whilst interprofessional education has steadily gained real-world traction, it is unclear how interprofessional student groups practice group reasoning when performing online tasks. Method: We analyzed the group reasoning processes with two teams of health professional students in an online interprofessional education task (n = 13). Two simulated interprofessional team meetings about a palliative case were audio recorded, transcribed, and deductively analyzed to determine the mechanisms of team deliberation using a previously published study of group reasoning.Results: The reasoning mechanisms outlined in a previous study (informationaccumulating, sense-making, and decision-making) were evident in an analysis of student group reasoning. In particular, students focused on sharing and agreeing on information, and to a lesser extent, recording information. Conclusion: Attention to the mechanisms of action may be useful to facilitate teaching interprofessional reasoning. Group reasoning may benefit from focusing student attention on these stages: 1) prioritizing and sequencing of options, methods for exposing agreement about shared information, shared understanding of the situation, and options; 2) techniques for critically evaluating information so that opportunities arise to identify when information may disrupt existing understandings; and 3) development of documentation tools to assist recording of the process

Kindness and competition: Are we striking the right balance in medical education?

Many parents could be excused for no longer hoping that their children pursue careers in medicine. Junior medical staff must cope with unforgiving rosters that often include rigorous on-call commitments and night shifts. Coupled with this, they face the emotional challenges of caring for very sick patients and their families. In addition, recent reports of bullying and harassment from the specialty colleges indicate that hospitals continue to be imperfect workplaces

A systematic literature review of definitions and classification systems for radiotherapy innovation: A first step towards building a value-based assessment tool for radiation oncology.

INTRODUCTION: Timely access to radiotherapy innovations remains suboptimal, partly because there is no commonly agreed appraisal system suitable for the broad range of radiotherapy interventions. The Health Economics in Radiation Oncology (HERO) programme of ESTRO therefore engaged in building a radiotherapy-specific value-based framework. We report on a first step towards that aim, documenting the available definitions and classification systems for radiotherapy interventions. METHODS: A systematic literature search was carried out in Pubmed and Embase, following PRISMA methodology and using search terms on 'innovation', 'radiotherapy', 'definition' and 'classification'. Data were extracted from articles that met prespecified inclusion criteria. RESULTS: Out of 13,353 articles, 25 met the inclusion criteria, resulting in the identification of 7 definitions of innovation and 15 classification systems applicable to radiation oncology. Iterative appraisal divided the classification systems into two groups. A first group of 11 systems categorized innovations according to the perceived magnitude of innovation, typically 'minor' versus 'major'. The remaining 4 systems categorised innovations according to radiotherapy-specific characteristics, such as the type of radiation equipment or radiobiological properties. Here, commonly used terms as 'technique' or 'treatment' were found to be used in different meanings. DISCUSSION: There is no widely accepted definition or classification system for radiotherapy innovations. The data however suggest that unique properties of radiotherapy interventions can be used to categorise innovations in radiation oncology. Still, there remains a need for clear terminology denoting radiotherapy-specific characteristics. CONCLUSION: Building on this review, the ESTRO-HERO project will define what is required for a radiotherapy-specific value-based assessment tool

Understanding students' and clinicians' experiences of informal interprofessional workplace learning : an Australian qualitative study

OBJECTIVES: While postgraduate studies have begun to shed light on informal interprofessional workplace learning, studies with preregistration learners have typically focused on formal and structured work-based learning. The current study investigated preregistration students' informal interprofessional workplace learning by exploring students' and clinicians' experiences of interprofessional student-clinician (IPSC) interactions. DESIGN: A qualitative interview study using narrative techniques was conducted. SETTING: Student placements across multiple clinical sites in Victoria, Australia. PARTICIPANTS: Through maximum variation sampling, 61 participants (38 students and 23 clinicians) were recruited from six professions (medicine, midwifery, nursing, occupational therapy, paramedicine and physiotherapy). METHODS: We conducted 12 group and 10 individual semistructured interviews. Themes were identified through framework analysis, and the similarities and differences in subthemes by participant group were interrogated. RESULTS: Six themes relating to four research questions were identified: (1) conceptualisations of IPSC interactions; (2) context for interaction experiences; (3) the nature of interaction experiences; (4) factors contributing to positive or negative interactions; (5) positive or negative consequences of interactions and (6) suggested improvements for IPSC interactions. Seven noteworthy differences in subthemes between students and clinicians and across the professions were identified. CONCLUSIONS: Despite the results largely supporting previous postgraduate research, the findings illustrate greater breadth and depth of understandings, experiences and suggestions for preregistration education. Educators and students are encouraged to seek opportunities for informal interprofessional learning afforded by the workplace

Direct aperture optimization as a means of reducing the complexity of intensity modulated radiation therapy plans

Intensity Modulated Radiation Therapy (IMRT) is a means of delivering radiation therapy where the intensity of the beam is varied within the treatment field. This is done by dividing a large beam into many small beamlets. Dose constraints are assigned to both the target and sensitive structures and computerised inverse optimization is performed to find the individual weights of this large number of beamlets. The computer adjusts the intensities of these beamlets according to the required planning dose objectives. The optimized intensity patterns are then decomposed into a series of deliverable multi leaf collimator (MLC) shapes in the sequencing step

A Review of the Tools Used for Marine Monitoring in the UK: Combining Historic and Contemporary Methods with Modeling and Socioeconomics to Fulfill Legislative Needs and Scientific Ambitions

Marine environmental monitoring is undertaken to provide evidence that environmental management targets are being met. Moreover, monitoring also provides context to marine science and over the last century has allowed development of a critical scientific understanding of the marine environment and the impacts that humans are having on it. The seas around the UK are currently monitored by targeted, impact-driven, programmes (e.g., fishery or pollution based monitoring) often using traditional techniques, many of which have not changed significantly since the early 1900s. The advent of a new wave of automated technology, in combination with changing political and economic circumstances, means that there is currently a strong drive to move toward a more refined, efficient, and effective way of monitoring. We describe the policy and scientific rationale for monitoring our seas, alongside a comprehensive description of the types of equipment and methodology currently used and the technologies that are likely to be used in the future. We contextualize the way new technologies and methodologies may impact monitoring and discuss how whole ecosystems models can give an integrated, comprehensive approach to impact assessment. Furthermore, we discuss how an understanding of the value of each data point is crucial to assess the true costs and benefits to society of a marine monitoring programme