Exploring wellbeing in first year medical students amidst a curriculum change.

BACKGROUND: The support of student wellbeing features highly in all higher education institutional agendas. For medical students good physical and mental health can help prevent burnout, equip students for their future healthcare setting and indirectly improve patient care. At the University of Nottingham (UK), we were keen to explore undergraduate medical students perceived wellbeing before, during, and after an early years' (years 1-3) curriculum change. A restructure of the curriculum enabled personal wellbeing sessions to be embedded and directly linked to the pastoral support system. METHODS: Students' perceived wellbeing was assessed through a questionnaire distributed to three cohorts of first year students at the start and end of the autumn semester. RESULTS: The data showed a clear improvement of perceived physical health at the end of the first semester following the curriculum change, alongside increased mood and ability to relax. A surprising outcome of this study was that students reported increased stress levels at the end of the semester, which we believe may be attributed to the change in assessment within the new curriculum. Our medical students are now facing end of year summative examinations, but are acutely aware of their progress as they undertake frequent formative assessments during the year. We propose that comparison of performance with peers is having a direct impact on perceived stress in these cohorts. CONCLUSIONS: The study has shown that embedding wellbeing in the curriculum can have positive effects even within a changing curriculum. The importance of evolving wellbeing provision and support based on the needs of the student population is essential and probably never more in need than at this moment in time.

Evaluation of a human neural stem cell culture method for prediction of the neurotoxicity of anti-epileptics.

Human neural stem cells have been proposed as an in vitro model to predict neurotoxicity. In this study, the potential of in vitro cultures of human-derived neurospheres to predict the effects of various anti-epileptic drugs (sodium valproate, phenytoin, carbamazepine and phenobarbitone) was evaluated. In general, these drugs had no significant effects on cell viability, total cellular protein, and neuronal process length at low doses, but at high doses these parameters were reduced significantly. Therapeutic doses of sodium valproate and phenytoin had a clear effect on neurosphere size and cell migration, with a significant reduction in both parameters when compared with the control group. The other drugs (carbamazepine and phenobarbitone) reduced neurosphere size and cell migration only at higher doses. The expression levels of glial fibrillary protein and tubulin III, which were used to identify astrocytes and neuronal cells, respectively, were reduced in a dose-dependent manner that became significant at high doses. The levels of glial fibrillary protein did not indicate any occurrence of reactive astrocytosis.

The impact of caffeine on connexin expression in the embryonic chick cardiomyocyte micromass culture system.

Cardiomyocytes are electrically coupled by gap junctions, defined as clusters of low-resistance multisubunit transmembrane channels composed of connexins (Cxs). The expression of Cx40, Cx43 and Cx45, which are present in cardiomyocytes, is known to be developmentally regulated. This study investigates the premise that alterations in gap junction proteins are one of the mechanisms by which teratogens may act. Specifically, those molecules known to be teratogenic in humans could cause their effects via disruption of cell-to-cell communication pathways, resulting in an inability to co-ordinate tissue development. Caffeine significantly inhibited contractile activity at concentrations above and including 1500 µm (P < 0.05), while not affecting cell viability and total protein, in the embryonic chick cardiomyocyte micromass culture system. The effects of caffeine on key cardiac gap junction protein (Cx40, Cx43 and Cx45) expression were analysed using immunocytochemistry and in-cell Western blotting. The results indicated that caffeine altered the expression pattern of Cx40, Cx43 and Cx45 at non-cytotoxic concentrations (≥2000 µm), i.e., at concentrations that did not affect total cell protein and cell viability. In addition the effects of caffeine on cardiomyocyte formation and function (contractile activity score) were correlated with modulation of Cxs (Cx40, Cx43 and Cx45) expression, at above and including 2000 µm caffeine concentrations (P < 0.05). These experiments provide evidence that embryonic chick cardiomyocyte micromass culture may be a useful in vitro method for mechanistic studies of perturbation of embryonic heart development. Copyright © 2015 John Wiley & Sons, Ltd.

Evaluation of bupropion hydrochloride developmental cardiotoxic effects in chick cardiomyocyte micromass culture and stem cell derived cardiomyocyte systems.

The use of antidepressant drug bupropion hydrochloride (BPN) during pregnancy results in increased cardiovascular anomalies. In this study, BPN developmental cardiotoxic effects in in vitro system were evaluated using chick cardiomyocyte micromass (MM) culture system and mouse embryonic stem cell derived cardiomyocyte (ESDC) system. In MM system, the cardiomyocyte contractile activity significantly decreased only at BPN 200 µM, while in ESDC system BPN concentration above 75 µM resulted in decreased contractile activity. The increase in drug concentration also affected the cardiomyocyte viability and total cellular protein content in both systems, but in ESDC system the cell viability failed to attain significant difference. The drug failed to induce reactive oxygen species production in both systems, but has affected the cardiac connexin43 expression especially in MM system. We observed that BPN showed developmental cardiotoxic effects irrespective of the stage of cardiac development in both in vitro systems.

Effects of the Herbal Product Curcumin on Cardiomyocytes in Micromass Culture and the Potential Role It May Play in Pregnancy and Development.

Introduction Herbal medicine (HM) consumption during pregnancy has been on the rise in many parts of the world. Curcumin is a proven antioxidant and anti-inflammatory herb component, having demonstrated efficacy in alleviating various diseases. However, there is conflicting evidence with regards to its effect on pregnancy. We assess the safety profile of the main component of turmeric, curcumin, during pregnancy. Furthermore, to investigate curcumin in combination with known teratogen ethanol to identify any protective effect that curcumin might exert. Method Embryonic chick cardiomyocytes in micromass culture were treated with varying concentrations of curcumin. Three endpoints were used to determine the effect of curcumin on these cells: contractile activity (morphological score), cell viability (resazurin assay), and total protein content (kenacid blue assay). Results Curcumin demonstrated cytotoxicity at the highest tested concentrations (10-20µM) by significantly reducing cell activity and total protein. The results of morphological scoring suggest that repeated investigations would have revealed the teratogenic potential of curcumin. Lower concentrations (50nM) of curcumin were comparable to the control. The combination of a non-toxic concentration of curcumin with ethanol revealed additive toxicity. Conclusion It seems unlikely that curcumin will adversely affect the embryo at low doses due to issues of bioavailability. The findings of cytotoxicity and possible teratogenicity at high concentrations are a concern. Due to the limited information available regarding curcumin metabolism in human embryos, advancements in curcumin delivery systems, and the high likelihood of overconsumption, further in vivo research using animal models is required.

Integrating sport and exercise medicine clinics into the National Health Service: a qualitative study.

OBJECTIVES: To explore the services National Health Service (NHS)-based sport and exercise medicine (SEM) clinics can offer, and the barriers to creating and integrating SEM services into the NHS. METHODS: Semi-structured interviews were undertaken to collect data from identified 'stakeholders'. Stakeholders were identified as individuals who had experience and knowledge of the speciality of SEM and the NHS. An inductive thematic analysis approach was taken to analyse the data. RESULTS: N=15 stakeholder interviews. The management of musculoskeletal (MSK) injuries (both acute and chronic) and concussion were highlighted as the two key services that SEM clinics can offer that would most benefit the NHS. MSK ultrasound was also mentioned by all stakeholders as a critical service that SEM clinics should provide. While exercise medicine is an integral part of SEM, SEM clinics should perhaps not have a heavy exercise medicine focus. The key barriers to setting up SEM clinics were stated to be convincing NHS management, conflict with other specialities and a lack of awareness of the speciality. CONCLUSION: The management of acute MSK injuries and concussion should be the cornerstone of SEM services, ideally with the ability to provide MSK ultrasound. Education of others on the speciality of SEM, confirming consistent 'unique selling points' of SEM clinics and promoting how SEM can add value to the NHS is vital. If the successful integration of SEM into the NHS is not widely achieved, we risk the NHS not receiving all the benefits that SEM can provide to the healthcare system.

Micromass Methods for the Evaluation of Developmental Toxicants.

Chick embryonic heart has recently been utilized as a model to create a micromass (MM) culturing system. The aim was to overcome the ethical barriers arising from testing the embryotoxicity of chemicals using human embryonic cells. The system represents a valuable tool to study the ability of chemicals to interfere with various embryonic developmental processes such as cellular communication, differentiation, cellular activity, and proliferation, where the disturbance any of them could result in maldevelopment. The system can also be utilized to investigate ROS production and expression of several transmembrane proteins to study their roles in chemical-induced teratogenicity or embryotoxicity.

Musculoskeletal Radiology Teaching at a UK Medical School: Do We Need to Improve?

The United Kingdom is currently facing crisis due to a shortage of radiology consultants despite ever-increasing demand for medical imaging. The specifics of how best to teach radiology has generated increasing interest. This study aims to determine whether musculoskeletal (MSK) radiology teaching at the University of Nottingham (UoN) Medical School is perceived to be satisfactory by medical students, Foundation-Year doctors, and senior medical professionals in preparing students for the demands working as Foundation-Year doctors. Questionnaires were distributed to all medical students and Foundation-Year doctors that graduated from UoN (n = 307). Semi-structured interviews were conducted with consultants and teaching staff (n = 13). Forty-nine percent of preclinical medical students, 43% of clinical students and 27% of Foundation-Year doctors thought MSK radiology teaching was not sufficient in preparing them for the radiology challenges Foundation-Year doctors' face. This difference was statistically significant (P < 0.001). The consensus from senior medical professionals was that MSK Radiology teaching is currently adequate and producing competent students. Interestingly, only 5% of students were considering a career in radiology compared to 34% of Foundation-Year doctors. Overall, there seems to be concern among students regarding MSK radiology teaching and students have a lack of confidence with MSK radiology. Foundation-Year doctors and senior medical professionals do not share this view. This may be due to medical students' lack of clarity on what is required of them. Formal documentation of set learning objectives for MSK radiology throughout the curriculum may address this.

Chick Embryonic Cardiomyocyte Micromass System for Assessing Developmental Cardiotoxicity of Drugs.

Heart is the first mesodermal organ to develop and is sensitive to life-threatening toxic effects of drugs during development. A number of methods have been devised to study developmental cardiotoxic effects of drugs including micromass system. The micromass system involves the culture of primary embryonic cells and reestablishment of tissue system in vitro. In chick embryonic cardiomyocyte micromass system the chick heart cells are cultured in a small volume at a very high cell density. These cells form synchronized contracting foci. Addition of drugs to this system allows us to study the developmental cardiotoxic effects at molecular level. Using appropriate end points and molecular marker or adopting high-throughput screening, this method can further help to identify and avoid the use of cardiotoxic compounds during development.

An evaluation of a novel chick cardiomyocyte micromass culture assay with two teratogens/embryotoxins associated with heart defects.

This study was aimed at determining whether the chick cardiomyocyte micromass (MM) system could be employed to predict the teratogenicity/embryotoxicity of exogenous chemicals. Two documented teratogens/embryotoxins, sodium valproate (the sodium salt of valproic acid; VPA) and all-trans retinoic acid (tRA), were used in the initial phase of the study. White Leghorn 5-day-old embryo hearts were dissociated to produce a cardiomyocyte suspension in Dulbecco's Modified Eagle's Medium. Cultures were incubated at 37 degrees C in 5% CO(2) in air, and observations were made every 24 hours over 5 days, for the detection of beating. Culture viability was assessed by using the resazurin reduction assay for determining culture activity and the kenacid blue assay for determining cell number. It was found that tRA significantly reduced cell activity and beating, whilst not affecting total cell number. VPA up to 500 microM induced no cytotoxicity in the MM cardiomyocyte cultures, whilst all the VPA concentrations tested reduced beating. The results demonstrate the potential of the chick cardiomyocyte MM culture assay to identify teratogens/embryotoxins that alter functionality, which may result in a teratogenic outcome, whilst not causing cytotoxicity (direct embryotoxicity). This could form part of a screen for developmental toxicity related to cardiac function, whilst limb cultures and brain cultures based on the same system could be relevant to teratogenic effects on those tissues.

Diabetes-induced effects on cardiomyocytes in chick embryonic heart micromass and mouse embryonic D3 differentiated stem cells.

Diabetes mellitus during pregnancy is a considerable medical challenge, since it is related to augmented morbidity and mortality concerns for both the fetus and the pregnant woman. Records show that the etiology of diabetic embryopathy is complicated, as many teratological factors might be involved in the mechanisms of diabetes mellitus-induced congenital malformation. In this study, the potential cardiotoxic effect of hyperglycemia with hyperketonemia was investigated by using two in vitro models; primary chick embryonic cardiomyocytes and stem cell derived cardiomyocytes, where adverse effects were recorded in both systems. The cells were evaluated by changes in beating activity, cell activity, protein content, ROS production, DNA damage and differentiating stem cell migration. The diabetic formulae used produced an increase in DNA damage and a decline in cell migration in mouse embryonic stem cells. These results provide an additional insight into adverse effects during gestational diabetes mellitus and a recommendation for expectant mothers and maternity staff to monitor glycaemic levels months ahead of conception. This study also supports the recommendation of using antioxidants during pregnancy to prevent DNA damage by the production of ROS, which might result in heart defects as well as other developmental anomalies.

Antioxidant activity of rosmarinic acid and its principal metabolites in chemical and cellular systems: Importance of physico-chemical characteristics.

Persistent accumulation of reactive oxygen species causes cellular oxidative stress which contributes strongly towards the induction and progression of various diseases. Therapeutic focus has therefore shifted towards the use of antioxidants, with recent interest in those of plant origin. In the current study, rosmarinic acid (RA) and its key metabolites were evaluated in non-cellular and cellular antioxidant assays, using quercetin (Q) as a positive control. The non-cellular assay was performed as scavenging of DPPH radical, whilst the cellular assay was performed as protection from an oxidant stress. Radical-scavenging activity of RA and two of its primary metabolites, CA and DHPLA, were comparable to that of Q, whilst FA was of lower potency and m-CoA was inactive. In the cellular assay, RA and CA were markedly less potent than Q, with DHPLA, FA and m-CoA being inactive, this being true in short-term (5-h) or long-term (20-h) exposure conditions. However, antioxidant potency of Q and methyl rosmarinate, a non-ionisable ester of RA, was similar in the non-cellular and short-term cellular assays. It is proposed that marked ionisation of organic acids such as RA and its metabolites at physiological pH greatly limits their intracellular accumulation, and so attenuates intrinsic antioxidant ability demonstrated in the non-cellular assay. This study demonstrates some of the factors that prevent well-known phytochemicals from progressing further along the drug discovery chain.

Evaluation of embryotoxicity for major components of herbal extracts using the chick embryonic heart micromass and mouse D3 embryonic stem cell systems.

Herbal remedies are often used during the early stages of pregnancy, being considered 'harmless' and 'natural'. There are insufficient data regarding their potential embryotoxicity. The main components of selected herbs, including 6-gingerol from ginger, Ginkgolide A and Ginkgolide B from gingko biloba and Ginsenoside Rg1 from ginseng, have been investigated using chick embryonic heart micromass and Mouse D3 embryonic stem cells. The potential effects were evaluated via alteration in contractility, cell viability, and cell protein content. The myocytes in both systems were also demonstrated by immunocytochemistry using a specific cardiomyocyte marker (α-actinin). For 6-gingerol, Ginkgolide A, Ginkgolide B and Ginsenoside Rg1 in both methods, at moderate to high concentrations, there were alterations in the values for the endpoints. These data indicate that herbal remedies used in the first trimester of pregnancy might not be safe for fetal development.

What anatomy is clinically useful and when should we be teaching it?

Anatomy teaching, once thought of as being the cornerstone of medical education, has undergone much change in the recent years. There is now growing concern for falling standards in medical graduates' anatomical knowledge, coupled with a reduction in teaching time and appropriately qualified teaching staff. With limited contact hours available to teach this important discipline, it is essential to consider what anatomy is taught within the medical curriculum to ensure it is fit for clinical practice. The views of medical students, junior doctors, and consultants were obtained from the University of Nottingham and the Trent Deanery in Nottingham, United Kingdom, to establish what core anatomical knowledge they feel medical students should study and assimilate during preclinical training. All participants felt strongly that medical students should be adept at interpreting modern diagnostic images before entering their clinical placement or specialty. Respondents proposed more teaching emphasis should be placed on specific anatomical areas (including lymphatic drainage and dermatome innervation) and illustrated other areas where less detailed teaching was appropriate. Recommendations from our study highlight a need for greater clinical emphasis in anatomy teaching during preclinical years. To successfully achieve this, it is essential that clinicians become integrally involved in the design and delivery of future medical undergraduate anatomy courses. Anat Sci Educ 9: 468-475. © 2016 American Association of Anatomists.

Assessment of developmental cardiotoxic effects of some commonly used phytochemicals in mouse embryonic D3 stem cell differentiation and chick embryonic cardiomyocyte micromass culture models.

Pregnant women often use herbal medicines to alleviate symptoms of pregnancy. The active phytochemicals eugenol (from holy basil) and α-bisabolol (from chamomile) are recommended to promote calmness and reduce stress. There is evidence that both eugenol and α-bisabolol possess pro-apoptotic and anti-proliferative effects and induce reactive oxygen species. The potential effect was examined by monitoring cardiomyocyte contractile activity (differentiation), cell activity, protein content and ROS production for mouse D3 embryonic stem cell and chick embryonic micromass culture. The results showed that eugenol (0.01-80µM) demonstrated effects on cell activity (both systems) and ROS production (stem cell system only), as well as decreasing the contractile activity and protein content at high concentrations in both systems. Additionally, α-bisabolol (0.01-80µM) at high concentrations decreased the contractile activity and cell activity and in the stem cell system induced ROS production and decreased protein content. The results suggest only low concentrations should be ingested in pregnancy. .

Separating chemotherapy-related developmental neurotoxicity from cytotoxicity in monolayer and neurosphere cultures of human fetal brain cells.

Chemotherapy-induced neurotoxicity can reduce the quality of life of patients by affecting their intelligence, senses and mobility. Ten percent of safety-related late-stage clinical failures are due to neurological side effects. Animal models are poor in predicting human neurotoxicity due to interspecies differences and most in vitro assays cannot distinguish neurotoxicity from general cytotoxicity for chemotherapeutics. We developed in vitro assays capable of quantifying the paediatric neurotoxic potential for cytotoxic drugs. Mixed cultures of human fetal brain cells were differentiated in monolayers and as 3D-neurospheres in the presence of non-neurotoxic chemotherapeutics (etoposide, teniposide) or neurotoxicants (methylmercury). The cytotoxic potency towards dividing progenitors versus differentiated neurons and astrocytes was compared using: (1) immunohistochemistry staining and cell counts in monolayers; (2) through quantitative Western blots in neurospheres; and (3) neurosphere migration assays. Etoposide and teniposide, were 5-10 times less toxic to differentiated neurons compared to the mix of all cells in monolayer cultures. In contrast, the neurotoxicant methylmercury did not exhibit selectivity and killed all cells with the same potency. In 3D neurospheres, etoposide and teniposide were 24 to 10 times less active against neurons compared to all cells. These assays can be used prioritise drugs for local drug delivery to brain tumours.

Potential teratogenic effects of benomyl in rat embryos cultured in vitro.

A possible association between environmental exposure to benomyl and anophthalmia has been suggested. The aim of the present study was to investigate potential teratogenic effects of benomyl using the 9.5 day rat embryo culture method using rat and human serum. Explanted rat embryos were cultured in rat serum (n=121) or human serum (n=90) with differing concentrations of benomyl [170 nM to 13.6 microM], dissolved in ethanol (0.136%), at least five embryos per concentration being cultured. In addition, 18 embryos were cultured in both human and rat serum with the equivalent concentration of ethanol to act as a vehicle control. The cultured embryos were then measured and scored for growth and differentiation by two blinded observers. Embryotoxic effects were considered to be demonstrated by a decrease in parameters of growth such as crown rump length, yolk sac diameter and protein content, whereas embryopathic effects were considered to be those causing a decease in parameters of differentiation such as morphological score, somite number and optic development. Benomyl [> or =5 microM] produced a significant concentration dependent deterioration in morphological score, somite number and optic development. Gross toxic effects were noticed at concentrations of >12 microM in rat serum and >10microM in human serum as indicated by a significant effect on parameters measuring size (crown rump length; yolk sac diameter and protein content). This study provides evidence that benomyl is a potential developmental toxicant, affecting many parameters of differentiation, including optic development at levels below those that could be considered embryotoxic.

Structure and function of gap junction proteins: role of gap junction proteins in embryonic heart development.

Intercellular (cell-to-cell) communication is a crucial and complex mechanism during embryonic heart development. In the cardiovascular system, the beating of the heart is a dynamic and key regulatory process, which is functionally regulated by the coordinated spread of electrical activity through heart muscle cells. Heart tissues are composed of individual cells, each bearing specialized cell surface membrane structures called gap junctions that permit the intercellular exchange of ions and low molecular weight molecules. Gap junction channels are essential in normal heart function and they assist in the mediated spread of electrical impulses that stimulate synchronized contraction (via an electrical syncytium) of cardiac tissues. This present review describes the current knowledge of gap junction biology. In the first part, we summarise some relevant biochemical and physiological properties of gap junction proteins, including their structure and function. In the second part, we review the current evidence demonstrating the role of gap junction proteins in embryonic development with particular reference to those involved in embryonic heart development. Genetics and transgenic animal studies of gap junction protein function in embryonic heart development are considered and the alteration/disruption of gap junction intercellular communication which may lead to abnormal heart development is also discussed.

Developmental cardiotoxicity effects of four commonly used antiepileptic drugs in embryonic chick heart micromass culture and embryonic stem cell culture systems.

Antiepileptic drugs (AEDs) are commonly used drugs in pregnant women with epilepsy. Prenatal exposure to AEDs increases the risk of major or minor congenital malformation during embryonic development. The precise mode of action and intracellular mechanisms of these AEDs during embryonic development remains unclear. To determine relative teratogenic risk of AEDs, four AED drugs including valproic acid (VPA), phenytoin (PHT), phenobarbital (PB), and trimethadione (TMD) were tested using two in vitro systems (the embryonic chick heart micromass (MM) culture and the in vitro differentiating mouse embryonic stem cells into cardiomyocytes culture systems). Cardiomyocyte cultures (the heart MM and ES cell-derived cardiomyocytes) were treated with or without different concentrations of PHT, PB, TMD (10-100 µM), and VPA (100-2000 µM). 5-Fluorouracil (5-FU) (1-10 µM) and l-ascorbic acid (10-1000 µM) were used as positive and negative controls. It was found that these four commonly used AEDs and 5-FU tested have the potential to inhibit embryonic heart cell differentiation (p<0.05) without inducing any cytotoxicity. VPA at higher concentrations (≥800 µM), and 5-FU at all doses proved to be cytotoxic in the differentiating ES cell culture system. The results demonstrated in this study suggest that the use of these four commonly prescribed AEDs during pregnancy may have an effect on embryonic heart development, and may be associated with congenital cardiovascular defects.

Group in-course assessment promotes cooperative learning and increases performance.

The authors describe and evaluate a method to motivate medical students to maximize the effectiveness of dissection opportunities by using In-Course-Assessments (ICAs) to encourage teamwork. A student's final mark was derived by combining the group dissection mark, group mark for questions, and their individual question mark. An analysis of the impact of the ICA was performed by comparing end of module practical summative marks in student cohorts who had, or had not, participated in the ICAs. Summative marks were compared by two-way ANOVA followed by Dunnets test, or by repeated measures ANOVA, as appropriate. A cohort of medical students was selected that had experienced both practical classes without (year one) and with the new ICA structure (year two). Comparison of summative year one and year two marks illustrated an increased improvement in year two performance in this cohort. A significant increase was also noted when comparing this cohort with five preceding year two cohorts who had not experienced the ICAs (P <0.0001). To ensure that variation in the practical summative examination was not impacting on the data, a comparison was made between three cohorts who had performed the same summative examination. Results show that students who had undertook weekly ICAs showed significantly improved summative marks, compared with those who did not (P <0.0001). This approach to ICA promotes engagement with learning resources in an active, team-based, cooperative learning environment.