Exploring Visualisation for Embryology Education: A Twenty-First-Century Perspective.

Embryology and congenital malformations play a key role in multiple medical specialties including obstetrics and paediatrics. The process of learning clinical embryology involves two basic principles; firstly, understanding time-sensitive morphological changes that happen in the developing embryo and, secondly, appreciating the clinical implications of congenital conditions when development varies from the norm. Visualising the sequence of dynamic events in embryonic development is likely to be challenging for students, as these processes occur not only in three dimensions but also in the fourth dimensions of time. Consequently, features identified at any one timepoint can subsequently undergo morphological transitions into distinct structures or may degenerate and disappear. When studying embryology, learners face significant challenges in understanding complex, multiple and simultaneous events which are likely to increase student cognitive load. Moreover, the embryology content is very nonlinear. This nonlinear content presentation makes embryology teaching challenging for educators. Embryology is typically taught in large groups, via didactic lecture presentations that incorporate two-dimensional diagrams or foetal ultrasound images. This approach is limited by incomplete or insufficient visualisation and lack of interactivity.It is recommended that the focus of embryology teaching should instill an understanding of embryological processes and emphasise conceptualising the potential congenital conditions that can occur, linking pre-clinical and clinical disciplines together. A variety of teaching methods within case-based and problem-based curricula are commonly used to teach embryology. Additional and supplementary resources including animations and videos are also typically utilised to demonstrate complex embryological processes such as septation, rotation and folding.We propose that there is a need for embryology teaching in the twenty-first century to evolve. This is particularly required in terms of appropriate visualisation resources and teaching methodologies which can ensure embryology learning is relevant to real-world scenarios. Here we explore embryology teaching resources and methodologies and review existing evidence-based studies on their implementation and impact on student learning. In doing so, we aim to inform and support the practice of embryology educators and the learning of their students.

On the importance of integrating comparative anatomy and One Health perspectives in anatomy education.

As a result of many factors, including climate change, unrestricted population growth, widespread deforestation and intensive agriculture, a new pattern of diseases in humans is emerging. With increasing encroachment by human societies into wild domains, the interfaces between human and animal ecosystems are gradually eroding. Such changes have led to zoonoses, vector-borne diseases, infectious diseases and, most importantly, the emergence of antimicrobial-resistant microbial strains as challenges for human health. Now would seem to be an opportune time to revisit old concepts of health and redefine some of these in the light of emerging challenges. The One Health concept addresses some of the demands of modern medical education by providing a holistic approach to explaining diseases that result from a complex set of interactions between humans, environment and animals, rather than just an amalgamation of isolated signs and symptoms. An added advantage is that the scope of One Health concepts has now expanded to include genetic diseases due to advancements in omics technology. Inspired by such ideas, a symposium was organised as part of the 19th International Federation of Associations of Anatomists (IFAA) Congress (August 2019) to investigate the scope of One Health concepts and comparative anatomy in contemporary medical education. Speakers with expertise in both human and veterinary anatomy participated in the symposium and provided examples where these two disciplines, which have so far evolved largely independent of each other, can collaborate for mutual benefit. Finally, the speakers identified some key concepts of One Health that should be prioritised and discussed the diverse opportunities available to integrate these priorities into a broader perspective that would attempt to explain and manage diseases within the scopes of human and veterinary medicine.

Specialist training in medical microbiology across Europe in 2021-an update on the actual training situation based on a survey.

BACKGROUND: The importance of defining and establishing professional standards for Clinical Microbiology (CM) in Europe has long been highlighted, starting with the development of a European curriculum. The first European Curriculum in Medical Microbiology (MM) was adopted by the European Union of Medical Specialists (UEMS) council in 2017. OBJECTIVES: This paper assesses how training programmes in CM in Europe align with the European curriculum, just under 5 years after its introduction, and reviews what methods of assessment are in use to assess the CM trainees' progress during training programmes. SOURCES: Using an internet-based platform, a questionnaire was circulated to the full, associate and observer members of the UEMS MM section. Information collected related to the structure, content and delivery of CM training in the participating countries, as well as methods of assessment used to evaluate training progress. CONTENT: Twenty-one countries responded, from a total of 30 countries invited to participate. All had a structured CM training programme, with a curriculum, dedicated trainers and a record of training activities. Fifteen countries require trainees to pass an exit examination, and over 60% of countries participate in continuous workplace-based assessment. Of the participating countries, 57% meet the European Training Requirements recommendation that duration of specialist training is 60 months. Regarding core competencies, all trainees gain experience in laboratory skills and infection prevention and control, but the emphasis on clinical management and antimicrobial stewardship is more varied across countries. IMPLICATIONS: The UEMS MM curriculum has been largely adopted by 21 countries within less than 5 years of ratification, which speaks optimistically to a future of standardized quality training across Europe. The introduction of a pilot European Examination in Clinical Microbiology in 2021 is the start of a pan-European assessment of the success of the implementation of this curriculum and the first step in quality assurance for CM training in Europe.

Physician Associate Students' Experience of Anatomy Dissection.

The role of physician assistant/associate (PA) has expanded from its inception in the United States over 50 years ago, to European countries including Ireland. While there is an increasing body of evidence exploring the role and training of PAs in clinical settings, there is a scarcity of research exploring PA students' perspectives in relation to their experience of anatomy dissection, or how these experiences may contribute to the development of their core professional identity. Students in the first two cohorts of PA Program at the Royal College of Surgeons in Ireland program were invited to interviews which solicited them to reflect and report on their own experiences of anatomical dissection during their course. Participants' responses were analyzed using a thematic inductive approach; common themes and patterns were organized into a hierarchical structure, which generated the final framework of themes. Ten participants took part in the study; only one had previous personal experience of dissection, while two further participants had some familiarity with prosected specimens. The first theme concerned the participants' expectation of anatomical dissection, with sub-themes of preconceptions, smell, and emotions. The second theme involves discussion of coping strategies that the participants used, including talking, viewing the cadaver as their first patient, and naming (or not naming) the cadaver. The third theme includes how the participants' talked about respect and compassion in the dissection room, development of team working skills, and awareness of bereavement and organ donation. A number of recommendations were also made for the experience and orientation of future students in such a program.

The anatomical society core embryology syllabus for undergraduate medicine.

A modified Delphi methodology was used to develop a consensus regarding a series of learning outcome statements to act as the foundation of an undergraduate medical core embryology syllabus. A Delphi panel was formed by recruiting stakeholders with experience in leading undergraduate teaching of medical students. The panel (n = 18), including anatomists, embryologists and practising clinicians, were nominated by members of Council and/or the Education Committee of the Anatomical Society. Following development of an a priori set of learning outcome statements (n = 62) by the authors, panel members were asked in the first of a two-stage process to 'accept', 'reject' or 'modify' each learning outcome, to propose additional outcomes if desired. In the second stage, the panel was asked to either accept or reject 16 statements which had either been modified, or had failed to reach consensus, during the first Delphi round. Overall, 61 of 62 learning outcome statements, each linked to examples of clinical conditions to provide context, achieved an 80% level of agreement following the modified Delphi process and were therefore deemed accepted for inclusion within the syllabus. The proposed syllabus allows for flexibility within individual curricula, while still prioritising and focusing on the core level of knowledge of embryological processes by presenting the essential elements to all newly qualified doctors, regardless of their subsequent chosen specialty.

A Systematic Review of the Educational Effectiveness of Simulation Used in Open Surgery.

STATEMENT: The role of simulation to teach and access open surgical skills has become more prevalent in recent years. This systematic review synthesizes the totality of evidence with respect to the educational effectiveness of simulators used in open surgical training. A systematic literature search was conducted in PubMed, Embase, CINAHL, Scopus, and Web of Science. Only randomized controlled trials were included that explored the educational efficacy of theses simulators. Six randomized controlled trials were included from the 9934 studies found. The methodological quality of the included studies was variable. Overall, the use of the simulators was more educationally effective compared with standard teaching of the skill without a simulator (P < 0.05). Two studies showed that the simulator was as good as an animal model of much higher fidelity. Further studies are needed to secure higher evidence for the educational value, validity, and transferability of the skills to the hospital setting for all simulators.

Learning Cardiac Embryology-Which Resources Do Students Use, and Why?

With increasing class sizes, small group activities for learning embryology are present in few institutions. How then do students supplement their lectures in order to ask and answer questions, or delve into concepts in detail? Arguably, animations and videos are ideal for visualizing four-dimensional anatomy, but how do students find and filter these? First-year medical students were surveyed with respect to the cardiac embryology component of their course and asked their opinions regarding the clinical relevance of this content and the resources they used to enhance learning. Students indicated that they considered cardiac embryology to be of relevance to clinical practice and that videos are a useful resource in helping them to learn this material. However, when seeking videos or resources, it emerged that students tended to Google information in preference to accessing online resources (or textbooks) specifically recommended by their instructor, despite students' recognition that "accuracy of information" was paramount when choosing what resource to use. While all students seemed reluctant to contact a staff member with questions, those with less proficiency in English were less likely to approach faculty for assistance. While acknowledging students as adult learners, self-regulated learning skills do not develop automatically and the development of these skills should be viewed as a "shared responsibility" between students and staff. Likewise, students also need to be taught critical appraisal of learning resources, especially in the complex online environment, with design of their bespoke institutional virtual learning environment facilitating easy identification and access of recommended resources.

Undergraduate Medical Students' Usage and Perceptions of Anatomical Case-Based Learning: Comparison of Facilitated Small Group Discussions and eLearning Resources.

While case-based discussions can empower students to apply knowledge to contextual clinical situations, scheduling these activities is a challenge in crowded curricula. Case-based eLearning activities, derived from existing cases discussed within anatomy small group tutorials, were created incorporating principles such as interactivity, reinforcement, and feedback. Over half of the students accessed one or more of these online cases, with 18% accessing all eight online cases provided. Access increased as the semester progressed, particularly just before summative examinations, implying students used these primarily as revision aides. Students rated both formats highly, but favored the online format with regard to enjoyment (P = 0.048), learning (P = 0.101), and feedback (P = 0.086). However, more students discussed these cases in small group tutorials within the anatomy dissecting room than completed them online (122 vs. 67) and themes emerging from free text comments included a desire to have more time dedicated to these cases during small group tutorials, and an appreciation for the opportunity for discussion with staff and learning through doing. Additionally, native English speakers rated the anatomy room discussions significantly higher in all aspects than non-native English speakers, suggesting that non-native speakers may be hesitant or reluctant to fully participate in front of peers. While online case-based learning activities are a useful adjunct to anatomy teaching, particularly for revision, assumptions that "digital natives" have an innate preference for digital resources require critical evaluation, as students still place a high value on opportunities for discussion with staff during their studies.

Evaluation of MCQs from MOOCs for common item writing flaws.

OBJECTIVE: There is a dearth of research into the quality of assessments based on Multiple Choice Question (MCQ) items in Massive Open Online Courses (MOOCs). This dataset was generated to determine whether MCQ item writing flaws existed in a selection of MOOC assessments, and to evaluate their prevalence if so. Hence, researchers reviewed MCQs from a sample of MOOCs, using an evaluation protocol derived from the medical health education literature, which has an extensive evidence-base with regard to writing quality MCQ items. DATA DESCRIPTION: This dataset was collated from MCQ items in 18 MOOCs in the areas of medical health education, life sciences and computer science. Two researchers critically reviewed 204 questions using an evidence-based evaluation protocol. In the data presented, 50% of the MCQs (112) have one or more item writing flaw, while 28% of MCQs (57) contain two or more flaws. Thus, a majority of the MCQs in the dataset violate item-writing guidelines, which mirrors findings of previous research that examined rates of flaws in MCQs in traditional formal educational contexts.

Characterization and structural determination of a new anti-MET function-blocking antibody with binding epitope distinct from the ligand binding domain.

The growth and motility factor Hepatocyte Growth Factor/Scatter Factor (HGF/SF) and its receptor, the product of the MET proto-oncogene, promote invasion and metastasis of tumor cells and have been considered potential targets for cancer therapy. We generated a new Met-blocking antibody which binds outside the ligand-binding site, and determined the crystal structure of the Fab in complex with its target, which identifies the binding site as the Met Ig1 domain. The antibody, 107_A07, inhibited HGF/SF-induced cell migration and proliferation in vitro and inhibited growth of tumor xenografts in vivo. In biochemical assays, 107_A07 competes with both HGF/SF and its truncated splice variant NK1 for MET binding, despite the location of the antibody epitope on a domain (Ig1) not reported to bind NK1 or HGF/SF. Overlay of the Fab-MET crystal structure with the InternalinB-MET crystal structure shows that the 107_A07 Fab comes into close proximity with the HGF/SF-binding SEMA domain when MET is in the "compact", InternalinB-bound conformation, but not when MET is in the "open" conformation. These findings provide further support for the importance of the "compact" conformation of the MET extracellular domain, and the relevance of this conformation to HGF/SF binding and signaling.

Cancer Stem Cells Regulate Cancer-Associated Fibroblasts via Activation of Hedgehog Signaling in Mammary Gland Tumors.

Many tumors display intracellular heterogeneity with subsets of cancer stem cells (CSC) that sustain tumor growth, recurrence, and therapy resistance. Cancer-associated fibroblasts (CAF) have been shown to support and regulate CSC function. Here, we investigate the interactions between CSCs and CAFs in mammary gland tumors driven by combined activation of Wnt/ß-catenin and Hgf/Met signaling in mouse mammary epithelial cells. In this setting, CSCs secrete the Hedgehog ligand SHH, which regulate CAFs via paracrine activation of Hedgehog signaling. CAFs subsequently secrete factors that promote expansion and self-renewal of CSCs. In vivo treatment of tumors with the Hedgehog inhibitor vismodegib reduce CAF and CSC expansion, resulting in an overall delay of tumor formation. Our results identify a novel intracellular signaling module that synergistically regulates CAFs and CSCs. Targeting CAFs with Hedgehog inhibitors may offer a novel therapeutic strategy against breast cancer. Cancer Res; 77(8); 2134-47. ©2017 AACR.

Out of sight, out of mind: Do repeating students overlook online course components?

E-Learning is becoming an integral part of undergraduate medicine, with many curricula incorporating a number of online activities and resources, in addition to more traditional teaching methods. This study examines physical attendance, online activity, and examination outcomes in a first-year undergraduate medical program. All 358 students who completed the Alimentary System module within the first semester of the program were included, 30 of whom were repeating the year, and thus the module. This systems-based, multidisciplinary module incorporated didactic lectures, cadaveric small group tutorials and additional e-Learning resources such as online histology tutorials. Significant differences were demonstrated in physical attendance and utilization of online resources between repeating students and those participating in the module for the first time. Subsequent analyses confirmed that physical attendance, access of online lecture resources, and utilization of online histology tutorials were all significantly correlated. In addition, both physical attendance and utilization of online resources significantly correlated with summative examination performance. While nonattendance may be due to a variety of factors, our data confirm that significant differences exist in both physical attendance and online activity between new entrants and repeating students, such that all students repeating a module or academic year should be routinely interviewed and offered appropriate supports to ensure that they continue to engage with the program. While the development of complex algorithmic models may be resource intensive, using readily available indices from virtual learning environments is a straightforward, albeit less powerful, means to identify struggling students prior to summative examinations. Anat Sci Educ 9: 555-564. © 2016 American Association of Anatomists.

New Wnt/ß-catenin target genes promote experimental metastasis and migration of colorectal cancer cells through different signals.

OBJECTIVES: We have previously identified a 115-gene signature that characterises the metastatic potential of human primary colon cancers. The signature included the canonical Wnt target gene BAMBI, which promoted experimental metastasis in mice. Here, we identified three new direct Wnt target genes from the signature, and studied their functions in epithelial-mesenchymal transition (EMT), cell migration and experimental metastasis. DESIGN: We examined experimental liver metastases following injection of selected tumour cells into spleens of NOD/SCID mice. Molecular and cellular techniques were used to identify direct transcription target genes of Wnt/ß-catenin signals. Microarray analyses and experiments that interfered with cell migration through inhibitors were performed to characterise downstream signalling systems. RESULTS: Three new genes from the colorectal cancer (CRC) metastasis signature, BOP1, CKS2 and NFIL3, were identified as direct transcription targets of ß-catenin/TCF4. Overexpression and knocking down of these genes in CRC cells promoted and inhibited, respectively, experimental metastasis in mice, EMT and cell motility in culture. Cell migration was repressed by interfering with distinct signalling systems through inhibitors of PI3K, JNK, p38 mitogen-activated protein kinase and/or mTOR. Gene expression profiling identified a series of migration-promoting genes, which were induced by BOP1, CKS2 and NFIL3, and could be repressed by inhibitors that are specific to these pathways. CONCLUSIONS: We identified new direct Wnt/ß-catenin target genes, BOP1, CKS2 and NFIL3, which induced EMT, cell migration and experimental metastasis of CRC cells. These genes crosstalk with different downstream signalling systems, and activate migration-promoting genes. These pathways and downstream genes may serve as therapeutic targets in the treatment of CRC metastasis.

Is a picture worth a thousand words: an analysis of the difficulty and discrimination parameters of illustrated vs. text-alone vignettes in histology multiple choice questions.

BACKGROUND: Advances in cognitive load theory have led to greater understanding of how we process verbal and visual material during learning, but the evidence base with regard to the use of images within written assessments is still sparse. This study examines whether the inclusion of images within the stimulus format of multiple choice questions (MCQs) has a predictable or consistent influence on psychometric item properties, such as difficulty or discrimination. METHODS: Item analysis data from three consecutive years of histology multiple choice examinations were included in this study. All items were reviewed and categorised according to whether their stem, or stimulus format, was purely textual or included an associated image. RESULTS: A total of 195 MCQs were identified for inclusion and analysed using classical test theory; 95 used text alone and 100 included an image within the question stem. The number of students per examination ranged from 277 to 347, with a total of 60,850 student-question interactions. We initially examined whether the inclusion of an image within the item stem altered the item difficulty using Mann-Whitney U. The median item difficulty for images with purely textual stems was 0.77, while that for items incorporating an appropriate image was 0.80; this difference was not significant (0.77 vs. 0.80; p = 0.862, Mann-Whitney-U = 4818.5). Mean values showed that the Item Discrimination Index appeared unaffected by the inclusion of an image within the stem, and Item point biserial correlation also showed no difference in means between these two groups (Independent samples t-test; 2-tailed). CONCLUSION: We demonstrate that the addition of illustrations within undergraduate histology Multiple Choice Question stems has no overall influence on item difficulty, or measures of item discrimination. We conclude that the use of images in this context is statistically uncritical, and suggest that their inclusion within item stems should be based upon the principles of constructive alignment. However, further research with respect to the effect of images within item stems on cognitive processing, particularly with regard to image complexity or type, would enable the development of more informed guidelines for their use.

Shp2 signaling suppresses senescence in PyMT-induced mammary gland cancer in mice.

In this study, we have used techniques from cell biology, biochemistry, and genetics to investigate the role of the tyrosine phosphatase Shp2 in tumor cells of MMTV-PyMT mouse mammary glands. Genetic ablation or pharmacological inhibition of Shp2 induces senescence, as determined by the activation of senescence-associated ß-gal (SA-ß-gal), cyclin-dependent kinase inhibitor 1B (p27), p53, and histone 3 trimethylated lysine 9 (H3K9me3). Senescence induction leads to the inhibition of self-renewal of tumor cells and blockage of tumor formation and growth. A signaling cascade was identified that acts downstream of Shp2 to counter senescence: Src, focal adhesion kinase, and Map kinase inhibit senescence by activating the expression of S-phase kinase-associated protein 2 (Skp2), Aurora kinase A (Aurka), and the Notch ligand Delta-like 1 (Dll1), which block p27 and p53. Remarkably, the expression of Shp2 and of selected target genes predicts human breast cancer outcome. We conclude that therapies, which rely on senescence induction by inhibiting Shp2 or controlling its target gene products, may be useful in blocking breast cancer.

Heregulin-HER3-HER2 signaling promotes matrix metalloproteinase-dependent blood-brain-barrier transendothelial migration of human breast cancer cell lines.

HER2-positive breast tumors are associated with a high risk of brain relapse. HER3 is thought to be an indispensible signaling substrate for HER2 (encoded by ERBB2) and is induced in breast cancer-brain metastases, though the molecular mechanisms by which this oncogenic dimer promotes the development of brain metastases are still elusive. We studied the effects of the HER3-HER2 ligand, heregulin (neuregulin-1, broadly expressed in the brain), on luminal breast cancer cell lines in vitro. Treatment of SKBr3 (ERBB2-amplified), MDA-MB-361 (ERBB2-amplified, metastatic brain tumor-derived) and MCF7 (HER2-positive, not ERBB2-amplified) cells with exogenous heregulin increased proliferation and adhesive potential, concomitant with induction of cyclin D1 and ICAM-1, and suppression of p27. All three cell lines invaded through matrigel toward a heregulin chemotactic signal in transwell experiments, associated with activation of extracellular cathepsin B and matrix metalloproteinase-9 (MMP-9). Moreover, heregulin induced breast cancer cell transmigration across a tight barrier of primary human brain microvascular endothelia. This was dependent on the activity of HER2, HER3 and MMPs, and was completely abrogated by combination HER2-HER3 blockade using Herceptin® and the humanized HER3 monoclonal antibody, EV20. Collectively these data suggest mechanisms by which the HER3-HER2 dimer promotes development of metastatic tumors in the heregulin-rich brain microenvironment.

Combined Wnt/ß-catenin, Met, and CXCL12/CXCR4 signals characterize basal breast cancer and predict disease outcome.

Prognosis for patients with estrogen-receptor (ER)-negative basal breast cancer is poor, and chemotherapy is currently the best therapeutic option. We have generated a compound-mutant mouse model combining the activation of ß-catenin and HGF (Wnt-Met signaling), which produced rapidly growing basal mammary gland tumors. We identified the chemokine system CXCL12/CXCR4 as a crucial driver of Wnt-Met tumors, given that compound-mutant mice also deficient in the CXCR4 gene were tumor resistant. Wnt-Met activation rapidly expanded a population of cancer-propagating cells, in which the two signaling systems control different functions, self-renewal and differentiation. Molecular therapy targeting Wnt, Met, and CXCR4 in mice significantly delayed tumor development. The expression of a Wnt-Met 322 gene signature was found to be predictive of poor survival of human patients with ER-negative breast cancers. Thus, targeting CXCR4 and its upstream activators, Wnt and Met, might provide an efficient strategy for breast cancer treatment.

Wnt/ß-catenin signalling induces MLL to create epigenetic changes in salivary gland tumours.

We show that activation of Wnt/ß-catenin and attenuation of Bmp signals, by combined gain- and loss-of-function mutations of ß-catenin and Bmpr1a, respectively, results in rapidly growing, aggressive squamous cell carcinomas (SCC) in the salivary glands of mice. Tumours contain transplantable and hyperproliferative tumour propagating cells, which can be enriched by fluorescence activated cell sorting (FACS). Single mutations stimulate stem cells, but tumours are not formed. We show that ß-catenin, CBP and Mll promote self-renewal and H3K4 tri-methylation in tumour propagating cells. Blocking ß-catenin-CBP interaction with the small molecule ICG-001 and small-interfering RNAs against ß-catenin, CBP or Mll abrogate hyperproliferation and H3K4 tri-methylation, and induce differentiation of cultured tumour propagating cells into acini-like structures. ICG-001 decreases H3K4me3 at promoters of stem cell-associated genes in vitro and reduces tumour growth in vivo. Remarkably, high Wnt/ß-catenin and low Bmp signalling also characterize human salivary gland SCC and head and neck SCC in general. Our work defines mechanisms by which ß-catenin signals remodel chromatin and control induction and maintenance of tumour propagating cells. Further, it supports new strategies for the therapy of solid tumours.

Wnt signaling in stem and cancer stem cells.

The functional versatility of Wnt/ß-catenin signaling can be seen by its ability to act in stem cells of the embryo and of the adult as well as in cancer stem cells. During embryogenesis, stem cells demonstrate a requirement for ß-catenin in mediating the response to Wnt signaling for their maintenance and transition from a pluripotent state. In adult stem cells, Wnt signaling functions at various hierarchical levels to contribute to specification of different tissues. This has raised the possibility that the tightly regulated self-renewal mediated by Wnt signaling in stem and progenitor cells is subverted in cancer cells to allow malignant progression. Intensive work is currently being performed to resolve how intrinsic and extrinsic factors that regulate Wnt/ß-catenin signaling coordinate the stem and cancer stem cell states.