Scaffolding competence-based learning design in the dental simulation curriculum.

INTRODUCTION: Learning in a clinical domain in dentistry is complex and learners may face uncertain clinical scenarios. A simulation curriculum can be designed to have simple clinical scenarios and learning activities which progress in complexity and employ competence assessments of simulated clinical practice before students can undertake authentic practice on patients. This paper presents how scaffolding of competence can be used for designing learning with simulators (haptics and phantom head) demonstrated in a specific domain in restorative dentistry. METHODS: A collaborative workshop as a research approach was undertaken to inform the iterative analysis, development, and discussion on scaffolding the learning design with respect to competence assessments of learning cavity preparation with simulation-based learning technologies. A workshop was conducted, which was collaborative and involved design negotiations between researchers, technologists, and teachers/practitioners in developing the simulation curriculum. RESULTS: A competence assessment with feedback in a specific domain in preparing interproximal caries was used as a context to describe how the learning activities and outcomes were designed to meet assessment of competence with varied levels of simple to complex learning activities and structured sessions. CONCLUSION: Simulation curriculum can be designed and implemented by scaffolding the level of competence that can be learned using simulation between haptics and phantom-head. This brings impetus to the need in meeting the relevant competence criteria in context to a specific affordance of the simulation-based learning technologies to provide optimal patient-centred holistic care.

Disseminating cells in human oral tumours possess an EMT cancer stem cell marker profile that is predictive of metastasis in image-based machine learning.

Cancer stem cells (CSCs) undergo epithelial-mesenchymal transition (EMT) to drive metastatic dissemination in experimental cancer models. However, tumour cells undergoing EMT have not been observed disseminating into the tissue surrounding human tumour specimens, leaving the relevance to human cancer uncertain. We have previously identified both EpCAM and CD24 as CSC markers that, alongside the mesenchymal marker Vimentin, identify EMT CSCs in human oral cancer cell lines. This afforded the opportunity to investigate whether the combination of these three markers can identify disseminating EMT CSCs in actual human tumours. Examining disseminating tumour cells in over 12,000 imaging fields from 74 human oral tumours, we see a significant enrichment of EpCAM, CD24 and Vimentin co-stained cells disseminating beyond the tumour body in metastatic specimens. Through training an artificial neural network, these predict metastasis with high accuracy (cross-validated accuracy of 87-89%). In this study, we have observed single disseminating EMT CSCs in human oral cancer specimens, and these are highly predictive of metastatic disease.

When oral cancers metastasise ­ that is, when tumour cells invade other parts of the body ­ they typically do so by first colonizing the lymph nodes present in the neck. As this event significantly reduces chances of survival, oral cancer patients often have their neck lymph nodes removed to prevent the spread of the disease. However, this surgery carries risks and leads to longer hospital stays, stressing the need for better ways to predict which oral tumours will metastasise. Evidence from lab-grown cells and mice studies suggest that, in oral cancer, metastasis occurs when some cells in the original tumour go through a process called the epithelial-mesenchymal transition (EMT for short). This transformation allows the cells to detach from the tumour and become invasive. However, it has so far been difficult to observe this process in actual human tumours; this is partly because cells undergoing EMT stop producing the proteins that scientists rely on to distinguish cancer and healthy cells. To address this knowledge gap, Youssef et al. focused on three proteins: two tumour markers, EpCAM and CD24; and Vimentin, which is produced in greater quantities in the invasive mesenchymal state. Previous work had shown that a specific population of oral tumour cells can continue to express all three proteins even when adopting a mesenchymal identity through EMT. Based on this knowledge, Youssef et al. hypothesised that tracking Vimentin, EpCAM and CD24 using fluorescence microscopy would allow them to identify metastasising cells in human samples. An analysis of over 12,000 images from 74 tumours obtained from surgeries revealed that, in the metastatic samples, the cells detaching from primary tumours were more likely to express these three proteins. Finally, Youssef et al. used these images to train a machine learning algorithm. When applied to data from new oral cancer patients, the programme was able to predict whether their tumours were likely to spread with 89% accuracy. If confirmed by further work, and in particular on larger samples, these findings could in the future help clinicians decide which patients with oral cancer would benefit the most from surgery to remove neck lymph nodes.

Working whilst studying: a survey of medically-qualified dental students.

Medically-qualified junior trainees who are interested in oral and maxillofacial surgery (OMFS) are faced with the challenging decision to undertake the minimum three years required to obtain a Bachelor of Dental Surgery (BDS) with its associated expenses and loss of income from full-time employment, or to follow a different career path. Trainees have reported duration of training and financial factors, such as cost of attaining additional qualifications and loss of income, as common reasons for loss of interest in OMFS. This survey of students enrolled on King's College London's three-year BDS dentistry entry programme for medical graduates (DPMG)shows that most studentsundertake paid part-time work in various settings and specialties alongside their studies. The average number of hours worked by students whilst studying is reported to be 27.0/week. Students report a wide range of incomes from various sources including secondary-care shifts in the NHS and private sector, as well as non-secondary-care activities such as non-surgical facial aesthetics. Direct correlation is noted between the number of hours worked and earnings, with comparable potential income in OMFS and non-OMFS specialties. Participants working in OMFS report greater educational and training value compared with non-OMFS work.

The 'Clinical Humanities & Wellbeing programme'- sustainable healthcare education for an era of uncertainty.

This article presents a case study where integration of arts and humanities into a clinical programme is being implemented at scale, as core mandatory learning for all students within a UK dental, undergraduate context. The cross-disciplinary programme described, that integrates the Humanities with Clinical Sciences, is a longitudinal professional identity formation curriculum for sustainable oral healthcare which aligns with the UK dental regulator's proposals for a 'safe practitioner' framework for new graduates. The Clinical Humanities & Wellbeing modules embrace the emotional and attitudinal aspects of learning and educate clinical students for the practical wisdom (phronesis) required to deliver 21st century oral healthcare in an era of uncertainty. The overarching aim of the curriculum and its accompanying assessment is to promote critical reflection, student insight and development of integrity, reflexivity, and responsibility. Enabling the subjectification of professional identity formation in this cross-disciplinary way aims to develop students as 'safe practitioners', with increased professional autonomy, responsible for their own actions, and who are better equipped for the uncertainties and phronesis of clinical practice. At present, the programme is being evaluated, employing illuminative evaluation methodology and we present some tentative initial findings. The authors believe that this unique approach and signature pedagogy is, with careful curation, transferrable to other health professions' contexts.

Experiential learning spaces and student wellbeing: a mixed-methods study of students at three research intensive UK universities.

There is clear evidence that university students are experiencing significant mental health difficulties, further exacerbated by the temporary closure of university campuses during the height of the COVID-19 pandemic. Against this backdrop, our study - Student Wellbeing and Experiential Learning Spaces (SWELS) - explored the role of experiential learning spaces in supporting student wellbeing. We adopted a mixed-methods approach, consisting of an online survey and interviews with students from three research intensive UK Universities. The survey results revealed that compared to the national average of 16-25-year-olds from the UK Office for National Statistics' (ONS) wellbeing questionnaire, the sampled students exhibited significantly lower levels of life satisfaction, happiness, perceived worthwhileness and higher levels of anxiety. The qualitative results further confirmed that students perceived their wellbeing to be affected by their university experience and the COVID pandemic. However, the results also suggest that experiential learning spaces (such as museums, collections, libraries, and gardens) hold strong potential to support student mental health. Accordingly, the study indicates that diversifying module content and conscientiously considering both physical and digital learning spaces can positively impact students. In short, curricula that are cognisant of the physical learning environment and embed a focus on wellbeing into their content might help to bolster student wellbeing.

Pineal and leptomeningeal metastases from a parotid carcinoma ex pleomorphic adenoma.

Carcinoma ex pleomorphic adenoma (CEPA) is an uncommon complication of an untreated pleomorphic adenoma (PA), but one that has a life-threatening significance. This case report documents the clinical, radiological and histopathological features of an extremely rare case of biopsy-proven pineal metastasis, with cerebellopontine and leptomeningeal spread, from CEPA of the parotid gland in spite of the patient having undergone parotidectomy, ipsilateral neck dissection and adjuvant radiotherapy. In spite of the current surgical and oncological treatment of CEPA, the rates of recurrence and distant metastases are high, with a subsequently poor prognostic outcome in most patients. Distant spread is usually to the bones and the lungs; however, more unusual locations have been documented. Our finding of pineal metastasis from CEPA has not previously been reported in the literature. Although this is a rare complication of an unusual condition, the aggressive behaviour of these malignancies warrants close clinical follow-up, with a low threshold for re-imaging and investigation if indicated.

Erratum to "Rare benign mixed tumour of the upper lip: A case report" [Ann. Med. Surg. 4 (2015) 380-383].

[This corrects the article DOI: 10.1016/j.amsu.2015.10.001.].

Rare benign mixed tumour of the upper lip: A case report.

BACKGROUND: Chondroid syringomas (CS) are rare benign mixed tumours. Clinical differentiation can be misleading due to the silent presentation, with only histopathological findings confirming the diagnosis. CASE REPORT: A 23-year-old Caucasian gentleman presented with an eighteen month history of increasing size of his exophytic upper lip mass. The initial clinical impression was thought to be related to the skin. Following a punch biopsy, histopathology confirmed appearance in keeping with part of a chondroid syringoma with subsequent excision of the lesion. DISCUSSION: CS present as a slow-growing, asymptomatic, non-tender, nonulcerated, smooth, firm subcutaneous, or intradermal nodule and can range from 0.5 to 3.0 cm, predominantly occurring in the head and neck region in patients aged above 35 years with a male predication. The most effective diagnostic method is microscopic examination. The gold standard treatment modality is by complete excision with a margin of normal tissue in order to examine the histopathologic features and prevent recurrence. CONCLUSION: CS should be included as a differential diagnosis of facial subcutaneous skin lesions in middle aged male patients. Careful evaluation, with a view of total excision and adequate surgical margin will enable diagnostic confirmation, whilst maintaining the aesthetic and functional unit.

Staging and treatment of oropharyngeal cancer in the human papillomavirus era.

BACKGROUND: Oropharyngeal squamous cell carcinoma (SCC) is staged using the TNM system. Human papillomavirus (HPV)-positive tumors have improved prognosis, despite presenting at advanced stage. Optimal treatment and stratification of HPV-positive patients are not clearly defined. METHODS: We retrospectively analyzed 266 patients with oropharyngeal SCC for mortality and feeding tube dependency related to TNM stage, HPV status, and treatment. RESULTS: TNM staging was prognostic in HPV-negative patients (stage III/IV hazard ratio [HR], 2.00; p = .05; N(+) HR, 2.19; p = .02). Only T classification was prognostic in HPV-positive tumors (T3/T4 HR 3.31; p = .006). HPV-positive tumors showed improved survival regardless of treatment. Patients receiving chemotherapy had a significantly increased risk of feeding tube dependency (odds ratio [OR], 1.72; p = .03). CONCLUSION: These data suggest that the current TNM system has little prognostic value in HPV-positive oropharyngeal SCC. Patients with HPV-positive tumors show improved survival independent of treatment. The addition of chemotherapy increases the risk of feeding tube dependency and could potentially be avoided in T1/T2 HPV-positive tumors without compromising survival.

Implication of Epstein-Barr virus infection in disease-specific autoreactive B cell activation in ectopic lymphoid structures of Sjögren's syndrome.

OBJECTIVE: To examine whether the B cell tropic γ-herpesvirus Epstein-Barr virus (EBV) is aberrantly expressed in its latent and lytic forms within ectopic lymphoid structures (ELS) in the salivary glands of patients with Sjögren's syndrome (SS), and to investigate the relationship between EBV dysregulation, B cell activation, in situ differentiation of autoreactive plasma cells, disease-specific autoantibody production, and cytotoxicity. METHODS: Latent and lytic EBV infection in the salivary glands of 28 patients with SS and 38 patients with nonspecific chronic sialadenitis (NSCS), characterized for the presence or absence of ELS, was investigated by reverse transcription-polymerase chain reaction, in situ hybridization, and immunohistochemical/immunofluorescence staining. Glandular versus synovial production of anti-Ro 52, anti-citrullinated protein antibodies (ACPAs), and anti-EBV peptide antibodies was analyzed in situ or in vivo in human SS/SCID and human rheumatoid arthritis/SCID mouse chimeras. RESULTS: EBV dysregulation within inflammatory infiltrates was observed exclusively in ELS+ SS salivary gland tissue, as revealed by latent EBV infection and lytic EBV infection in B cells and plasma cells, respectively. Conversely, epithelial latent membrane protein 2A expression was observed in both patients with SS and patients with NSCS. Importantly, perifollicular plasma cells displaying Ro 52 immunoreactivity were frequently infected by EBV. Furthermore, ELS-containing SS salivary gland tissue that was transplanted into SCID mice supported the production of anti-Ro 52/anti-La 48 and anti-EBV antibodies but not ACPAs. Analysis of CD4+ and CD8+ T cell localization and granzyme B expression demonstrated that the persistence of EBV in ELS-containing SS salivary glands was associated with follicular exclusion of CD8+ T cells and impaired CD8-mediated cytotoxicity. CONCLUSION: Active EBV infection is selectively associated with ELS in the salivary glands of patients with SS and appears to contribute to local growth and differentiation of disease-specific autoreactive B cells.

Preparation of mineralized tissue for light microscopy.

Production of stained tissue sections for examination by light microscopy is a step-wise process which begins with preservation of tissue (fixation), then dehydration and clearing of the tissue, and finally impregnation with wax (processing). Mineralized tissues such as bone and teeth are subject to a further step (decalcification). Thin sections are then attached to a glass slide for staining and light microscopy.In the UK, it is usual for a preliminary diagnosis to be made using hematoxylin and eosin (H&E) staining. A definitive diagnosis may need further investigation with immunocytochemistry. All of these procedures must allow morphology and tissue structure to remain in tact, as any pathology present must not be compromised.

Bone pathology.

This chapter is an approach to bone pathology for a scientist rather than a histopathologist. It deals with the approach to cutting the bone biopsy, the relative merits of one method over another. The chapter also discusses the importance of correlation with both known clinical information, radiological appearances, and the final histology in reaching a diagnosis. A discussion of selected more common pathologies is covered, this is however not an exhaustive chapter on all bone pathologies.

Non-junctional human desmoglein 3 acts as an upstream regulator of Src in E-cadherin adhesion, a pathway possibly involved in the pathogenesis of pemphigus vulgaris.

E-cadherin, a classical cadherin, is an adhesion receptor in adherens junctions and has important functions in cell-cell adhesion and cell signalling. Recently we reported that a desmosomal cadherin, desmoglein 3 (Dsg3), an autoantigen in pemphigus vulgaris (PV), associates with E-cadherin and activates Src, which results in tyrosine phosphorylation of adherens junction proteins. However, the nature of such an interaction and its role in cell-cell adhesion remain unclear. In this report, we provide direct evidence that it is the detergent-soluble, non-desmosomal Dsg3 that regulates the activity of Src and its association with E-cadherin in adherens junction formation. Modulation of Dsg3 levels, either by Dsg3 silencing or over-expression, alters Src activity and its association with E-cadherin. Dsg3 silencing caused retardation of calcium-induced E-cadherin junction assembly and a reduction of desmosomal protein expression. Furthermore, we provide evidence that this signalling pathway is involved, at least in part, in the pathophysiology of pemphigus. Along with the reduced expression of Dsg3, loss and disruption of E-cadherin and a concomitant decreased pSrc signalling was identified in the basal keratinocytes surrounding the blisters in PV. These findings suggest a novel function for Dsg3 in the control of E-cadherin-Src signalling and cell-cell adhesion.

Quantitative analysis of optical coherence tomography and histopathology images of normal and dysplastic oral mucosal tissues.

Selecting the most representative site for biopsy is crucial in establishing a definitive diagnosis of oral epithelial dysplasia. The current process involves clinical examination that can be subjective and prone to sampling errors. The aim of this study was therefore to investigate the use of optical coherence tomography (OCT) for differentiation of normal and dysplastic oral epithelial samples, with a view to developing an objective and reproducible approach for biopsy site selection. Biopsy samples from patients with fibro-epithelial polyps (n = 13), mild dysplasia (n = 2), and moderate/severe dysplasia (n = 4) were scanned at 5-µm intervals using an OCT microscope and subsequently processed and stained with hematoxylin and eosin (H&E). Epithelial differentiation was measured from the rate of change (gradient) of the backscattered light intensity in the OCT signal as a function of depth. This parameter is directly related to the density of optical scattering from the cell nuclei. OCT images of normal oral epithelium showed a clear delineation of the mucosal layers observed in the matching histology. However, OCT images of oral dysplasia did not clearly identify the individual mucosal layers because of the increased density of abnormal cell nuclei, which impeded light penetration. Quantitative analysis on 2D-OCT and histology images differentiated dysplasia from normal control samples. Similar analysis on 3D-OCT datasets resulted in the reclassification of biopsy samples into the normal/mild and moderate/severe groups. Quantitative differentiation of normal and dysplastic lesions using OCT offers a non-invasive objective approach for localizing the most representative site to biopsy, particularly in oral lesions with similar clinical features.

Langerhans cell histiocytosis: a diagnostic dilemma.

UNLABELLED: Langerhans cell histiocytosis (LCH) is a rare clonal neoplastic disorder of unknown aetiology which can present with a diverse range of clinical presentations. It encompasses a diverse number of idiopathic conditions which can involve multiple body systems and is characterized by bone marrow-derived Langerhans cell proliferation. The disease can affect multiple body systems and lesions can be solitary or widespread. We present a case of a multifocal eosinophilic granuloma (LCH) in a young adult female with clinical signs and symptoms similar to aggressive periodontitis. CLINICAL RELEVANCE: Langerhans cell histiocytosis is a rare disease which can have a similar clinical presentation to aggressive periodontitis.

Stromal features are predictive of disease mortality in oral cancer patients.

Worldwide, approximately 405 000 cases of oral cancer (OSCC) are diagnosed each year, with a rising incidence in many countries. Despite advances in surgery and radiotherapy, which remain the standard treatment options, the mortality rate has remained largely unchanged for decades, with a 5-year survival rate of around 50%. OSCC is a heterogeneous disease, staged currently using the TNM classification, supplemented with pathological information from the primary tumour and loco-regional lymph nodes. Although patients with advanced disease show reduced survival, there is no single pathological or molecular feature that identifies aggressive, early-stage tumours. We retrospectively analysed 282 OSCC patients for disease mortality, related to clinical, pathological, and molecular features based on our previous functional studies [EGFR, αvß6 integrin, smooth muscle actin (SMA), p53, p16, EP4]. We found that the strongest independent risk factor of early OSCC death was a feature of stroma rather than tumour cells. After adjusting for all factors, high stromal SMA expression, indicating myofibroblast transdifferentiation, produced the highest hazard ratio (3.06, 95% CI 1.65-5.66) and likelihood ratio (3.6; detection rate: false positive rate) of any feature examined, and was strongly associated with mortality, regardless of disease stage. Functional assays showed that OSCC cells can modulate myofibroblast transdifferentiation through αvß6-dependent TGF-ß1 activation and that myofibroblasts promote OSCC invasion. Finally, we developed a prognostic model using Cox regression with backward elimination; only SMA expression, metastasis, cohesion, and age were significant. This model was independently validated on a patient subset (detection rate 70%; false positive rate 20%; ROC analysis 77%, p < 0.001). Our study highlights the limited prognostic value of TNM staging and suggests that an SMA-positive, myofibroblastic stroma is the strongest predictor of OSCC mortality. Whether used independently or as part of a prognostic model, SMA identifies a significant group of patients with aggressive tumours, regardless of disease stage.

Scattering attenuation microscopy of oral epithelial dysplasia.

We present a new method for quantitative visualization of premalignant oral epithelium called scattering attenuation microscopy (SAM). Using low-coherence interferometry, SAM projects measurements of epithelial optical attenuation onto an image of the tissue surface as a color map. The measured attenuation is dominated by optical scattering that provides a metric of the severity of oral epithelial dysplasia (OED). Scattering is sensitive to the changes in size and distribution of nuclear material that are characteristic of OED, a condition recognized by the occurrence of basal-cell-like features throughout the epithelial depth. SAM measures the axial intensity change of light backscattered from epithelial tissue. Scattering measurements are obtained from sequential axial scans of a 3-D tissue volume and displayed as a 2-D SAM image. A novel segmentation method is used to confine scattering measurement to epithelial tissue. This is applied to oral biopsy samples obtained from 19 patients. Our results show that imaging of tissue scattering can be used to discriminate between different dysplastic severities and furthermore presents a powerful tool for identifying the most representative tissue site for biopsy.

Wegener's granulomatosis presenting as an abdominal aortic aneurysm: a case report.

INTRODUCTION: Aortic aneurysm is not common in young patient. When a young patient presents with abdominal aortic aneurysm, there may be an underlying cause. CASE PRESENTATION: Here, we describe a case of a 33-year-old gentleman who presented with flu like illness, chest and abdominal pains following a tooth extraction. A chest X-ray and subsequent computerised tomogram of the chest and abdomen demonstrated lung nodules and an abdominal aortic aneurysm. The aneurysm was repaired and his serology was positive for Wegener's granulomatosis. A nasal mucosal biopsy confirmed WG. He was treated with oral steroids and cyclophosphamide. His graft leaked and had to be replaced with a synthetic graft. Two months after his re-operation, he remains well. CONCLUSION: Whenever a young patient presents with an abdominal aortic aneurysm, an underlying connective disease should be excluded because early steroid/immunosuppressive treatment may prevent the development of further aneurysms.

Synovial sarcoma presenting as a parotid mass: case report and review of literature.

BACKGROUND: Synovial sarcoma is an unusual neoplasm of mesenchymal derivation, which is uncommon in the head and neck sites. In the parotid gland, it is most likely to be misdiagnosed as a myoepithelial, primary mesenchymal, or metastatic neoplasm. METHODS: We report a case of synovial sarcoma in a young woman who was seen with temporomandibular joint symptoms with a 10-year history. A review of the literature was undertaken to highlight the radiologic and histologic features that help in diagnosis as well as the suggested therapeutic protocols most likely to ensure better survival. RESULTS: Radiologic and histologic studies of the parotid mass led to a diagnosis of synovial sarcoma. A total parotidectomy was performed, and the individual remains tumor free at 36 months. CONCLUSIONS: Review of the literature suggests an aggressive long-term outcome for synovial sarcoma and advocates early diagnosis and radical surgical excision for a favorable prognosis.

Low-grade myofibroblastic sarcoma of the tongue.

Low-grade myofibroblastic sarcoma is a neoplasm of atypical myofibroblasts with fibromatoseslike features and a predilection for head and neck sites, including the oral cavity. These lesions have only been characterized in the last 2 decades, and controversies in the concept of neoplastic myofibroblasts still exist. Lack of obvious cytological atypia may result in their being mistaken for reactive fascitislike lesions or fibromatosis and architectural similarities to fibrosarcoma or leiomyosarcoma may complicate the diagnostic process. This paper describes a spindle cell neoplasm in a 40-year-old man that was diagnosed 9 years ago as an unclassifiable myofibroblastic proliferation. The recurrent tumor, which presented 6 years following excision of the original tumor, was subsequently classified as a low-grade myofibroblastic sarcoma. The morphological, immunohistochemical, and electron microscopic features of this unusual sarcoma and the most likely differential diagnoses are discussed.