Assessment of an online tooth morphology course and 3D examination tool during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic brought major disruptions to dental teaching and has impacted the delivery of tooth morphology courses where students are introduced to the three-dimensional features of the dentition. The aim of this study was to assess the implementation of newly developed online teaching modalities for tooth morphology, evaluate their usefulness and identify elements that are beneficial for learners. MATERIALS AND METHODS: Following the delivery of an online course that included online 3D models, 2D cue cards, live discussion sessions and Socrative™ quizzes, the participants were asked to rate the usability and usefulness of each tool. The participants' knowledge of tooth morphology was assessed through an online examination using 3D-digitised tooth models. RESULTS: The participants identified lecture handouts and online 3D models as their preferred learning tools, while lecture video recordings and 2D cue cards were viewed as less useful. Data analysis from Socrative™ quizzes demonstrated improvement in tooth identification skills throughout the course delivery. Finally, results from the final assessment are in line with previous in-person deliveries of this course. CONCLUSIONS: The study provides valuable information on the usefulness of teaching modalities that were implemented in response to the COVID-19 pandemic and their merit to be retained in future deliveries of the course. The 3D models have been identified as particularly useful in this context, but the participants still value the opportunity to learn with extracted teeth. Furthermore, it remains to be confirmed whether tooth identification skills acquired using 3D models can be transferred to the clinical setting.

Cytology Techniques Can Provide Insight into Human Placental Structure Including Syncytiotrophoblast Nuclear Spatial Organisation.

The aim of this study was to provide the first systematic description of human placental cytology appearances and to investigate syncytiotrophoblast nuclear organisation patterns using cytology techniques. Term placentas from normal pregnancies were sampled using fine-needle aspiration (FNA) and direct scrapes. Standard histological examination was also performed to exclude pathological changes in the placentas being studied. Both Papanicolaou-stained cytospin preparations and air-dried Giemsa slides from FNA provided high-quality material for cytological assessment with good cellularity. Among the key features of the cytology preparations were villous "microbiopsies" that allowed for the three-dimensional appreciation of villous branching patterns. Cytological appearances, including nuclear characteristics of villous cytotrophoblast and syncytiotrophoblast, were also well demonstrated. In microbiopsies and detached villous trophoblast sheets, complex patterns of syncytiotrophoblast nuclear organisation, not previously described cytologically, were observed, including irregular spacing of nuclei, syncytioplasm windows and linear nuclear arrangements. This study showed that placental cytology (a) provides technically excellent material for cytological evaluation, (b) confirms the presence of complex nuclear organisational patterns in the syncytiotrophoblast by eliminating the possibility of tangential sectioning artefact, (c) provides superior nuclear detail over standard histological sections and (d) may be an untapped research resource for the investigation of normal and pathological processes because of its ability to look at the placenta in a novel way and through its potential for both ex vivo and in vivo placental sampling.

Visualizing Anatomy in Dental Morphology Education.

Tooth morphology is a foundation course for all dental healthcare students including dentists, dental hygiene, dental therapy, and dental nursing students. This chapter explores the conventional and innovative teaching methods to deliver tooth morphology educational modules. The teaching tools are explored with a 2D and 3D lens, with a particular focus on visualization, student understanding, and engagement. Traditional methods of teaching tooth morphology must be complemented with innovative pedagogical approaches in order to maintain student's attention and accommodate their diverse learning methods. Teaching 3D anatomy enables students to visualize and spatially comprehend the link between various anatomical components. Online tests and quizzes motivate students and are also beneficial in preparing students for exams. Online self-examinations offering visualization with 3D teeth enable students to evaluate their knowledge and offers immediate feedback, which aids in the long-term retention of information. These tools can be as efficient as other teaching methods, allowing the students to study at their own pace and with repetition. The authors conclude that blended and innovative teaching methods should supplement student learning and not replace, traditional face-to-face educational methods.

Animated teaching improves student learning of human gastrulation and neurulation.

Human embryology is a complex topic that brings together core components of anatomy and physiology to describe the developmental process from fertilisation to birth. Embryonic development is a challenging topic of study that is core to the curricula for health science students. There are challenges ingrained in teaching and learning embryology, due to the three-dimensional dynamic processes that occur as the embryo develops. This study aimed to develop and assess two newly developed animations depicting key processes in embryology, namely gastrulation and neurulation, as supplemental learning aids for students. Indeed, animated teaching tools to enhance the learning of gastrulation and neurulation are not widely available. A multi-disciplinary team of physiologists, biochemists, anatomists, and a computer scientist developed the animation sets. A student cohort of 81 first-year health science students were enrolled in this study over a period of three academic years. Both animations are in line with the course content of the first-year health science students undertaking the Human Health and Disease BSc at Trinity College Dublin, who were the study participants. Participants were randomly assigned to a non-animation control group and an animation group. Each set of animated teaching aids was broken down into individual clips which were given identifiable headings to allow the user to interchange between clips to facilitate a more personal learning experience. The animation group had open access to the animations for a three-week period. Questionnaires were designed to assess participants' attitude to the animations and their knowledge of embryology, both at the start of the study and three weeks later following access to the animations. Data presented herein indicate that students incorporated the animated teaching aids into digital home study and that the use of the animations acted as a supplemental tool that increased student knowledge in key areas of human embryology. From a qualitative point of view, students described the animations as enjoyable and helpful in visualising complex processes. This study indicates that the development of gastrulation and neurulation animated learning tools allow for a more engaging learning experience, facilitating student's engagement with academically challenging concepts in human embryology.

Therapeutic Response Evaluation in Advanced Melanoma Patients Incorporating Plasma cfDNA, LDH, VEGF, PD-L1, and IFN-γ Measurements.

BACKGROUND/AIM: Current treatment strategies for advanced melanoma require serial assessment of disease status in affected patients. In this study, we sought to examine the relationship between radiographic tumour burden and blood borne biomarkers including plasma cfDNA, serum LDH, plasma VEGF, PD-L1 and IFN-γ in advanced melanoma patients receiving immunotherapy. We hypothesized that a combination of these explanatory variables in a suitable regression analysis model may predict changes in tumour burden during patient treatment. MATERIALS AND METHODS: We extracted and quantified circulating cfDNA, LDH, VEGF, PD-L1, and IFN-γ from thirty patients with stage IV melanoma at baseline and at six months. All participating patients were evaluated with paired blood sample collection and CT scan assessments during treatment. RESULTS: Changes in radiographic tumour burden correlated with changes in levels of cfDNA (p≤0.001), LDH (p≤0.001), VEGF (p≤0.001), and PD-L1 (p<0.05) during treatment. Multiple regression analysis consisting of the follow-up to baseline assessment ratios of cfDNA, LDH, VEGF and PD-L1 explained changes in tumour burden (F (4, 23)=32.05, p<0.001); with an R2 of 0.8479 (Y=ß0+ß1*B+ß2*C+ß3*D+ß4*E). CONCLUSION: A quantitative measure of cfDNA, LDH, VEGF and PD-L1 may complement current methods of assessing tumour burden in advanced melanoma patients.

The utility of plasma circulating cell-free messenger RNA as a biomarker of glioma: a pilot study.

BACKGROUND: Research into the potential utility of plasma-derived circulating cell-free nucleic acids as non-invasive adjuncts to radiological imaging have been occasioned by the invasive nature of brain tumour biopsy. The objective of this study was to determine whether significant differences exist in the plasma transcriptomic profile of glioma patients relative to differences in their tumour characteristics, and also whether any observed differences were representative of synchronously obtained glioma samples and TCGA glioma-derived RNA. METHODS: Blood samples were collected from twenty glioma patients prior to tumour resection. Plasma ccfmRNAs and glioma-derived RNA were extracted and profiled. RESULTS: BCL2L1, GZMB, HLA-A, IRF1, MYD88, TLR2, and TP53 genes were significantly over-expressed in glioma patients (p < 0.001, versus control). GZMB and HLA-A genes were significantly over-expressed in high-grade glioma patients (p < 0.001, versus low-grade glioma patients). Moreover, the fold change of the BCL2L1 gene was observed to be higher in patients with high-grade glioma (p = 0.022, versus low-grade glioma patients). There was positive correlation between the magnitude of fold change of differentially expressed genes in plasma- and glioma-derived RNA (Spearman r = 0.6344, n = 14, p = 0.017), and with the mean FPKM in TCGA glioma-derived RNA samples (Spearman r = 0.4614, n = 19, p < 0.05). There was positive correlation between glioma radiographic tumour burden and the magnitude of fold change of the CSF3 gene (r = 0.9813, n = 20, p < 0.001). CONCLUSION: We identified significant differential expression of genes involved in cancer inflammation and immunity crosstalk among patients with different glioma grades, and there was positive correlation between their transcriptomic profile in plasma and tumour samples, and with TCGA glioma-derived RNA.

eNEUROANAT-CF: a Conceptual Instructional Design Framework for Neuroanatomy e-Learning Tools.

In an era which is witnessing a significant rise in incidence of neurological diseases, there is also a rise in neurophobia: the diminished confidence of clinical practitioners and students to manage patients with neurological conditions. In this context, the perceived nexus between neuroanatomy-phobia (the challenges and fear associated with learning neuroanatomy) and neurophobia highlighted the need to revisit the neuroanatomy pedagogies and their instructional designs. e-Learning can be effectively employed to enhance students' learning of neuroanatomy. This perspective describes a conceptual framework for online neuroanatomy learning (e-neuroanatomy learning conceptual framework (eNEUROANAT-CF)), which provides a theoretical grounding to newly developed neuroanatomy e-learning resources, by offering a set of instructional design principles. The framework is rooted in the theories of adult learning, cognitive load, and Mayer's theory of multimedia learning. eNEUROANAT-CF was validated by imparting user opinion regarding the best perceived instructional design features for learning neuroanatomy. Furthermore, it was effectively employed to inform the pedagogical construct of an e-tool to help students learn the spinal pathways. The perspective highlights the theoretical underpinnings of the eNEUROANAT-CF under seven categories, namely "avoidance of cognitive overload," "learning style preferences," "contextualization," "motivation," "social learning," "feedback/reflection," and "active learning." In addition, elaborative examples are provided, which explains how eNEUROANAT-CF informed the instructional design features of the abovementioned e-tool. The authors propose that any novel, interactive neuroanatomy e-learning resource rooted in the instructional design principles outlined by the eNEUROANAT-CF will improve users' learning and understanding of neuroanatomy. The research shows promise to help break the perceived nexus between neuroanatomy-phobia and neurophobia.

Neuroanatomy of the spinal pathways: Evaluation of an interactive multimedia e-learning resource.

This article was migrated. The article was marked as recommended. Introduction: A diminished number of young doctors opt for specialty neurology training and show reduced confidence in managing neurology patients and interlink difficulties in managing neurology patients with impaired understanding of neuroanatomy and associated clinical correlates. Aim: To evaluate an interactive e-resource for the neuroanatomy of the spinal pathways based on cognitive theories of multimedia learning in aiding medical students learn neuroanatomy. Methods: Using a single-blinded controlled experimental design, knowledge of the spinal pathways was assessed prior and after usage of the novel e-resource compared to control web resource. The perceived usefulness of the tool used was gauged using Likert-scale questionnaires. Results: Performance in the second assessment improved for all users but the learning gain of participants in the experimental groups was higher compared to participants who did not use e-resources. Likert-scale ratings revealed a significantly higher appreciation for the novel tool compared to the control tool when learning clinical correlates. Conclusions: Stronger correlations between the students' perception of the tool used and their second assessment scores suggest that students favored the instructional design of the novel e-tool which shows promising results in bridging the gap between neuroanatomy knowledge and its clinical application.

Evaluation of Neuroanatomy Web Resources for Undergraduate Education: Educators' and Students' Perspectives.

Despite the development of novel teaching strategies and the abundance of adjunct teaching web resources, students and early career physicians have continuously reported difficulties in learning and clinically applying neuroanatomy. Differences in instructional design of these resources, the lack of assessment of their capacity to meet intended educational goals, and a poor understanding of the user's perspective may have hindered their success in increasing understanding and retention of neuroanatomical knowledge. To decipher the limitations of existing web resources, an online search for neuroanatomy web resources was performed and distilled through a strict filtration rubric. A selection of resources were analyzed by a panel of educators and rated using Likert scales, focusing on the identification of features influencing their usefulness in learning the anatomy of the spinal pathways. The top three ranked web resources were subsequently evaluated by a panel of medical and neuroscience students to assess how specific features aided in their learning of the subject. This detailed analysis has identified features of neuroanatomy web resources that are valued by both educators and users with regard to instructional design. One resource was rated highest by end users and educators on a series of Likert scale questions in terms of clarity of explanation, step-wise teaching design, summarization of information, control of instructional-pace, integration with neurophysiology, neuroradiology and clinical correlates, deployment of a wide array of pedagogical tools, and factors for visualizing neuroanatomical inter-relationships. These results have provided a novel user perspective on the influence of specific elements of neuroanatomy web resources to improve instructional design and enhance learner performance.

Development and Assessment of a Three-Dimensional Tooth Morphology Quiz for Dental Students.

Tooth morphology has a pivotal role in the dental curriculum and provides one of the important foundations of clinical practice. To supplement tooth morphology teaching a three-dimensional (3D) quiz application (app) was developed. The 3D resource enables students to study tooth morphology actively by selecting teeth from an interactive quiz, modify their viewpoint and level of zoom. Additionally, students are able to rotate the tooth to obtain a 3D spatial understanding of the different surfaces of the tooth. A cross-over study was designed to allow comparison of students' results after studying with the new application or traditionally with extracted/model teeth. Data show that the app provides an efficient learning tool and that students' scores improve with usage (18% increase over three weeks, P < 0.001). Data also show that student assessment scores were correlated with scores obtained while using the app but were not influenced by the teaching modality initially accessed (r2  = 0.175, P < 0.01). Comparison of the 2016 and 2017 class performance shows that the class that had access to the app performed significantly better on their final tooth morphology assessment (68.0% ±15.0 vs. 75.3% ±13.4, P < 0.01). Furthermore, students reported that the 3D application was intuitive, provided useful feedback, presented the key features of the teeth, and assisted in learning tooth morphology. The 3D tooth morphology app thus provides students with a useful adjunct teaching tool for learning dental anatomy. Anat Sci Educ 00: 000-000. © 2018 American Association of Anatomists.

Fossilized skin reveals coevolution with feathers and metabolism in feathered dinosaurs and early birds.

Feathers are remarkable evolutionary innovations that are associated with complex adaptations of the skin in modern birds. Fossilised feathers in non-avian dinosaurs and basal birds provide insights into feather evolution, but how associated integumentary adaptations evolved is unclear. Here we report the discovery of fossil skin, preserved with remarkable nanoscale fidelity, in three non-avian maniraptoran dinosaurs and a basal bird from the Cretaceous Jehol biota (China). The skin comprises patches of desquamating epidermal corneocytes that preserve a cytoskeletal array of helically coiled α-keratin tonofibrils. This structure confirms that basal birds and non-avian dinosaurs shed small epidermal flakes as in modern mammals and birds, but structural differences imply that these Cretaceous taxa had lower body heat production than modern birds. Feathered epidermis acquired many, but not all, anatomically modern attributes close to the base of the Maniraptora by the Middle Jurassic.

Understanding neurophobia: Reasons behind impaired understanding and learning of neuroanatomy in cross-disciplinary healthcare students.

Recent studies have highlighted a fear or difficulty with the study and understanding of neuroanatomy among medical and healthcare students. This has been linked with a diminished confidence of clinical practitioners and students to manage patients with neurological conditions. The underlying reasons for this difficulty have been queried among a broad cohort of medical, dental, occupational therapy, and speech and language sciences students. Direct evidence of the students' perception regarding specific difficulties associated with learning neuroanatomy has been provided and some of the measures required to address these issues have been identified. Neuroanatomy is perceived as a more difficult subject compared to other anatomy topics (e.g., reproductive/pelvic anatomy) and not all components of the neuroanatomy curriculum are viewed as equally challenging. The difficulty in understanding neuroanatomical concepts is linked to intrinsic factors such as the inherent complex nature of the topic rather than outside influences (e.g., lecture duration). Participants reporting high levels of interest in the subject reported higher levels of knowledge, suggesting that teaching tools aimed at increasing interest, such as case-based scenarios, could facilitate acquisition of knowledge. Newer pedagogies, including web-resources and computer assisted learning (CAL) are considered important tools to improve neuroanatomy learning, whereas traditional tools such as lecture slides and notes were considered less important. In conclusion, it is suggested that understanding of neuroanatomy could be enhanced and neurophobia be decreased by purposefully designed CAL resources. This data could help curricular designers to refocus attention and guide educators to develop improved neuroanatomy web-resources in future. Anat Sci Educ 11: 81-93. © 2017 American Association of Anatomists.

Assessment of Thiel-Embalmed Cadavers as a Teaching Tool for Oral Anatomy and Local Anesthesia.

The aim of this study was to determine whether Thiel-embalmed cadavers would provide a useful anatomy teaching tool for topics that cannot be approached using formalin-fixed cadavers such as oral cavity examination and maxillary anesthesia. The suitability of Thiel-embalmed bodies for performing oral examinations was assessed by asking first-year dental and dental hygiene students at a dental school in Ireland to identify oral structures on a classmate and on a Thiel-embalmed body. The study was conducted in 2016. The ease of location was compared in the two settings, and their quality was assessed on the cadavers. The suitability of Thiel-embalmed cadavers to teach maxillary anesthesia was assessed by students' performing mock injections at five adjacent sites daily for five consecutive days, followed by inspection of the gingival surface by experienced anatomists and dentists. Data were obtained from 57 students, but only the 54 forms that were fully completed were analyzed, for an overall response rate of 85.7%. The results showed that most oral structures were more difficult to locate on cadavers. The texture and appearance of features in the cadavers were rated at a midpoint between realistic and unrealistic. The relative inexperience of the participants, the accumulation of fixative in the oral cavity, and discoloration were mentioned as potential confounding factors. Visual analysis of images obtained following repeated injections revealed no deterioration of the tissue. Importantly, the puncture marks appeared to reduce over time, suggesting that the gingival tissue maintains some elasticity following Thiel fixation. These findings suggest that Thiel-embalmed cadavers may be a useful tool to provide students more time to localize and study aspects of the oral cavity. Likewise, the recoiling capacity of gingival tissue suggests that Thiel-embalmed cadavers may provide an ideal tool for teaching injection technique of local anesthetics.

RNAi therapeutics for brain cancer: current advancements in RNAi delivery strategies.

Malignant primary brain tumors are aggressive cancerous cells that invade the surrounding tissues of the central nervous system. The current treatment options for malignant brain tumors are limited due to the inability to cross the blood-brain barrier. The advancements in current research has identified and characterized certain molecular markers that are essential for tumor survival, progression, metastasis and angiogenesis. These molecular markers have served as therapeutic targets for the RNAi based therapies, which enable site-specific silencing of the gene responsible for tumor proliferation. However, to bring about therapeutic success, an efficient delivery carrier that can cross the blood-brain barrier and reach the targeted site is essential. The current review focuses on the potential of targeted, non-viral and viral particles containing RNAi therapeutic molecules as delivery strategies specifically for brain tumors.

Mitogen-Activated Protein Kinase Phosphatase (MKP)-1 in Nervous System Development and Disease.

Mitogen-activated protein kinase phosphatase (MKP)-1 provides a negative feedback mechanism for regulating mitogen-activated protein kinase (MAPK) activity and thus a variety of cellular processes such as proliferation, differentiation, growth and apoptosis. MKP-1 is established as a central regulator of a variety of functions in the immune, metabolic and cardiovascular systems, and it is now increasingly acknowledged as having a role to play in the nervous system. It has been implicated in regulating processes of neuronal cell development and death as well as in glial cell function. Reduced MKP-1 levels have been observed in models of neurological conditions including Huntington's disease, multiple sclerosis, ischemia and cerebral hypoxia. It has also been suggested to have a role to play in psychiatric disorders such as major depressive disorder. Here, we discuss the role of MKP-1 in nervous system development and disease and examine current evidence providing insight into MKP-1 as a potential therapeutic target for various diseases of the central nervous system.

Expression of endogenous Mkp1 in 6-OHDA rat models of Parkinson's disease.

We have previously demonstrated that mitogen-activated protein kinase phosphatase 1, Mkp1, is expressed in the developing and rat adult substantia nigra and striatum, where it promotes the growth of nigral dopaminergic neurons. Mkp1 may therefore have therapeutic potential for Parkinson's disease. In the present study, we have assessed the expression of Mkp1 and TH in the substantia nigra and striatum of parkinsonian rat models. Expression was measured at 4 and 10 days post-lesion in the 6-hydroxydopamine (6-OHDA) medial forebrain bundle lesion model and after 4, 10 and 28 days in the 6-OHDA striatal lesion model. Our results show that Mkp1 expression was transiently up-regulated in the substantia nigra at 4 days post-6-OHDA administration in the two models while TH expression was decreased at the later time-points examined. These data suggest that Mkp1 may play a role in counteracting the neurotoxic effects of 6-OHDA in nigral dopaminergic neurons.

Therapeutic concentrations of valproate but not amitriptyline increase neuropeptide Y (NPY) expression in the human SH-SY5Y neuroblastoma cell line.

Neuropeptide Y (NPY) is a peptide found in the brain and autonomic nervous system, which is associated with anxiety, depression, epilepsy, learning and memory, sleep, obesity and circadian rhythms. NPY has recently gained much attention as an endogenous antiepileptic and antidepressant agent, as drugs with antiepileptic and/or mood-stabilizing properties may exert their action by increasing NPY concentrations, which in turn can reduce anxiety and depression levels, dampen seizures or increase seizure threshold. We have used human neuroblastoma SH-SY5Y cells to investigate the effect of valproate (VPA) and amitriptyline (AMI) on NPY expression at therapeutic plasma concentrations of 0.6mM and 630nM, respectively. In addition, 12-O-tetradecanoylphorbol-13-acetate (TPA) known to differentiate SH-SY5Y cells into a neuronal phenotype and to increase NPY expression through activation of protein kinase C (PKC) was applied as a positive control (16nM). Cell viability after drug treatment was tested with a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. NPY expression was measured using immunofluorescence and quantitative RT-PCR (qRT-PCR). Results from immunocytochemistry have shown NPY levels to be significantly increased following a 72h but not 24h VPA treatment. A further increase in expression was observed with simultaneous VPA and TPA treatment, suggesting that the two agents may increase NPY expression through different mechanisms. The increase in NPY mRNA by VPA and TPA was confirmed with qRT-PCR after 72h. In contrast, AMI had no effect on NPY expression in SH-SY5Y cells. Together, the data point to an elevation of human NPY mRNA and peptide levels by therapeutic concentrations of VPA following chronic treatment. Thus, upregulation of NPY may have an impact in anti-cancer treatment of neuroblastomas with VPA, and antagonizing hypothalamic NPY effects may help to ameliorate VPA-induced weight gain and obesity without interfering with the desired central effects of VPA.

Mitogen-activated protein kinase phosphatase (MKP)-1 as a neuroprotective agent: promotion of the morphological development of midbrain dopaminergic neurons.

A greater understanding of the mechanisms that promote the survival and growth of dopaminergic neurons is essential for the advancement of cell replacement therapies for Parkinson's disease (PD). Evidence supports a role for the mitogen-activated protein kinase p38 in the demise of dopaminergic neurons, while mitogen-activated protein kinase phosphatase-1 (MKP-1), which negatively regulates p38 activity, has not yet been investigated in this context. Here, we show that MKP-1 is expressed in dopaminergic neurons cultured from E14 rat ventral mesencephalon (VM). When dopaminergic neurons were transfected to overexpress MKP-1, they displayed a more complex morphology than their control counterparts in vitro. Specifically, MKP-1-transfection induced significant increases in neurite length and branching with a maximum increase observed in primary branches. We demonstrate that inhibition of dopaminergic neurite growth induced by treatment of rat VM neurons with the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) in vitro is mediated by p38 and is concomitant with a significant and selective decrease in MKP-1 expression in these neurons. We further show that overexpression of MKP-1 in dopaminergic neurons contributes to neuroprotection against the effects of 6-OHDA. Collectively, we report that MKP-1 can promote the growth and elaboration of dopaminergic neuronal processes and can help protect them from the neurotoxic effects of 6-OHDA. Thus, we propose that strategies aimed at augmenting MKP-1 expression or activity may be beneficial in protecting dopaminergic neurons and may provide potential therapeutic approaches for PD.