An international collaborative approach to learning histology using a virtual microscope.

Histology is often taught in higher education settings using online virtual microscopes (VM). This study aimed to develop and evaluate the use of VM in teaching on a BSc degree at the University of Nottingham by surveying students and staff. A key development was the use of an e-workbook so that students were actively engaged in creating their own bespoke revision material. Subsequently, this approach was used in a second study evaluating the use of VM in teaching the histology and pathology of the gastrointestinal (GI) tract via group work with students from two BSc courses at the University of Nottingham; one based at Derby (RDHC) and the other in Malaysia (UNMC). Students worked together in groups to complete an e-workbook, develop a presentation, and decide how to collaborate and communicate. An evaluation of these activities revealed advantages in developing transferrable skills, and good engagement with both the histology topic and group work. Analysis of assessment of the module at UNMC showed that student performance improved in the histology-based module after the intervention (p < 0.01) and that this improvement was not evident in other modules taken by the cohort. Furthermore, when interrogating the questions from the examination paper that asked students to identify features from histological images, fewer questions were seen as 'difficult' (p < 0.001) and more were seen as 'average' (p < 0.01). This study demonstrates that the use of VM in histology combined with active learning in creating a revision resource enhances engagement and depth of learning. When further combined with collaborative active group work, students developed a range of histology knowledge and transferrable skills, with notable improvement in examination performance relative to other contemporaneous modules.

Schwarzinicine A inhibits transient receptor potential canonical channels and exhibits overt vasorelaxation effects.

This study investigated the vasorelaxant effects of schwarzinicine A, an alkaloid recently reported from Ficus schwarzii Koord. Regulation of calcium homeostasis in vascular smooth muscle cells (VSMC) is viewed as one of the main mechanisms for controlling blood pressure. L-type voltage-gated calcium channel (VGCC) blockers are commonly used for controlling hypertension. Recently, the transient receptor potential canonical (TRPC) channels were found in blood vessels of different animal species with evidence of their roles in the regulation of vascular contractility. In this study, we studied the mechanism of actions of schwarzinicine A focusing on its regulation of L-type VGCC and TRPC channels. Schwarzinicine A exhibited the highest vasorelaxant effect (123.1%) compared to other calcium channel blockers. It also overtly attenuated calcium-induced contractions of the rat isolated aortae in a calcium-free environment showing its mechanism to inhibit calcium influx. Fluorometric intracellular calcium recordings confirmed its inhibition of hTRPC3-, hTRPC4-, hTRPC5- and hTRPC6-mediated calcium influx into HEK cells with IC50 values of 3, 17, 19 and 7 µM, respectively. The evidence gathered in this study suggests that schwarzinicine A blocks multiple TRPC channels and L-type VGCC to exert a significant vascular relaxation response.

Diversifying the medical curriculum as part of the wider decolonising effort: A proposed framework and self-assessment resource toolbox.

The narrative of decolonisation has recently amassed momentum, with the student and public voice providing the greatest advocacy, resulting in medical schools and universities embarking on a broader range of initiatives in response to the wider decolonisation agenda. Part of this wider effort is the diversification of the curriculum to create a more culturally responsive and equity focussed experience and training. Diversifying the curriculum poses considerable challenges due to limited expertise and/or relevant resources. It is from identification of this deficit, as well as our own experience in a UK medical school of diversifying our medical curriculum in the context of our decolonising efforts and the nature of the work required, that we developed a framework and created a toolbox of reflective questions, examples and resources to aid this work. As authors, we acknowledge that this process will be ongoing as we educate ourselves and reframe perceptions of the world, learn from lived experiences and incorporate advice from experts. The aspiration of this toolbox is to support those involved in efforts and initiatives to undo the effects of colonialism in medical education and research, and more specifically those who seek to diversify their curriculum within this context. This will ultimately benefit the education of our students, with the objective of equipping them with the knowledge, understanding and skills to provide equitable care to their patients.

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.

Data on the Lignosus rhinocerotis water soluble sclerotial extract affecting intracellular calcium level in rat dorsal root ganglion cells.

The data in this article contain supporting evidence for the research manuscript entitled "Bronchodilator effects of Lignosus rhinocerotis extract on rat isolated airways is linked to the blockage of calcium entry" by Lee et al. (2018) [1]. The data were obtained by calcium imaging technique with fluorescent calcium indicator dyes, Fura 2-AM, to visualize calcium ion movement in the rat dorsal ganglion (DRG) cells. The effects of L. rhinocerotis cold water extract (CWE1) on intracellular calcium levels in the DRG cells were presented.

Bronchodilator effects of Lignosus rhinocerotis extract on rat isolated airways is linked to the blockage of calcium entry.

BACKGROUND: Lignosus rhinocerotis (Cooke) Ryvarden is a popular medicinal mushroom used for centuries in Southeast Asia to treat asthma and chronic cough. The present study aimed to investigate the effect of this mushroom on airways patency. MATERIALS AND METHODS: The composition of L. rhinocerotis TM02 cultivar was analyzed. Organ bath experiment was employed to study the bronchodilator effect of Lignosus rhinocerotis cold water extract (CWE) on rat isolated airways. Trachea and bronchus were removed from male Sprague-Dawley rats, cut into rings of 2 mm, pre-contracted with carbachol before adding CWE into the bath in increasing concentrations. To investigate the influence of incubation time, tissues were exposed to intervals of 5, 15 and 30 min between CWE concentrations after pre-contraction with carbachol in subsequent protocol. Next, tissues were pre-incubated with CWE before the addition of different contractile agents, carbachol and 5-hydroxytrptamine (5-HT). The bronchodilator effect of CWE was compared with salmeterol and ipratropium. In order to uncover the mechanism of action of CWE, the role of beta-adrenoceptor, potassium and calcium channels was investigated. RESULTS: Composition analysis of TM02 cultivar revealed the presence of ß-glucans and derivatives of adenosine. The extract fully relaxed the trachea at 3.75 mg/ml (p < 0.0001) and bronchus at 2.5 mg/ml (p < 0.0001). It was observed that lower concentrations of CWE were able to fully relax both trachea and bronchus but at a longer incubation interval between concentrations. CWE pre-incubation significantly reduced the maximum responses of carbachol-induced contractions (in both trachea, p = 0.0012 and bronchus, p = 0.001), and 5-HT-induced contractions (in trachea, p = 0.0048 and bronchus, p = 0.0014). Ipratropium has demonstrated a significant relaxation effect in both trachea (p = 0.0004) and bronchus (p = 0.0031), whereas salmeterol has only affected the bronchus (p = 0.0104). The involvement of ß2-adrenoceptor and potassium channel in CWE-mediated airway relaxation is ruled out, but the bronchodilator effect was unequivocally affected by influx of calcium. CONCLUSIONS: The bronchodilator effect of L. rhinocerotis on airways is mediated by calcium signalling pathway downstream of Gαq-coupled protein receptors. The airway relaxation effect is both concentration- and incubation time-dependent. Our findings provide unequivocal evidence to support its traditional use to relieve asthma and cough.

Effects of cannabinoid receptor activation by CP55,940 on normal bladder function and irritation-induced bladder overactivity in non-awake anaesthetised rats.

INTRODUCTION AND HYPOTHESIS: This study was designed to evaluate the effects of CP55,940 on normal bladder function in vivo and examine whether it suppresses urinary frequency induced by nociceptive stimuli in the bladder. Cannabinoid receptor (CBR) activity may be involved in the regulation of bladder function. However, the role of CBR subtypes in micturition has yet to be established. CP55,940 is a synthetic analogue of tetrahydrocannabidiol, which is a psychoactive ingredient of the Cannabis plant. METHODS: Cystometry under urethane anaesthesia was performed to evaluate the effect of intravesical delivery of CP55,940 with or without administration of CB1 antagonist AM251 or CB2 antagonist AM630 on bladder function in female rats. The effects of CP55,940 were also examined in rats with urinary irritation induced by intravesical infusion of acetic acid. RESULTS: Infusion of CP55,940 significantly (p < 0.05) increased micturition interval (MI) and bladder capacity (BC) by 52 % and decreased maximal voiding pressure (MP) by 25 %. Pretreatment with AM251 or AM630 before CP55,940 administration prevented CP55,940-induced increases in MI, BC and reduced MP. Acetic acid induced urinary frequency as evidenced by a reduction in MI and was suppressed by CP55,940. CONCLUSIONS: CP55,940 decreases bladder activity and urinary frequency induced by nociceptive stimuli, probably by suppression of bladder afferent activity. Effects of CP55,940 were abolished by both CBR antagonists. This data implicates a role for the endocannabinoid system in bladder mechanoafferent function in rats. In addition, our results show that CP55,940 reverses urinary frequency exemplified in an overactive bladder model, suggesting it could be an effective treatment for patients with lower urinary tract symptoms.

5-HT 2A receptor activation of the external urethral sphincter and 5-HT 2C receptor inhibition of micturition: a study based on pharmacokinetics in the anaesthetized female rat.

Central and peripheral 5-hydroxytryptamine (5-HT) receptors play a critical role in the regulation of micturition. Bolus doses of 5-HT(2A/2C) receptor agonists have been shown to activate the external urethral sphincter (EUS) and to inhibit micturition. This study was designed to determine the contribution of these two 5-HT receptor subtypes to activation of the EUS and inhibition of micturition utilising pharmacokinetic knowledge to better control drug exposure. Recordings of urethral and bladder pressure, EUS-Electromyogram (EMG), the micturition reflex induced by bladder filling, blood pressure and heart rate were made in anaesthetized female rats. The effects of intravenous (i.v.) infusions of the 5-HT(2) receptor agonist (2S)-1-(6-chloro-5-fluoroindol-1-yl)propan-2-amine fumarate (Ro 60-0175) in the absence or presence of the selective 5-HT(2C) receptor antagonist 6-chloro-5-methyl-N-[6-(2-methylpyridin-3-yl)oxypyridin-3-yl]-2,3-dihydroindole-1-carboxamide dihydrochloride (SB 242084) or 5-HT(2A) receptor antagonist (R)-(2,3-dimethoxyphenyl)-[1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl]methanol (MDL-100,907) were studied on these variables. Continuous infusion of increasing concentrations of Ro 60-0175 only evoked EUS-EMG activity at the highest concentration, which was blocked by co-infusion of MDL-100,907 but not SB 242084. Urethral pressure was unaffected by any drug infusion. Ro 60-0175 at the lowest concentration inhibited the micturition reflex but as the concentration increased this was reversed to facilitation. SB 242084 blocked the inhibition while MDL-100,907 blocked the excitation. Activation of 5-HT(2A) not 5-HT(2C) receptors evoked EUS-EMG activity. In conclusion, 5-HT(2A) receptor activation facilitated the micturition reflex and evoked EUS-EMG while 5-HT(2C) receptor activation only inhibited the micturition reflex.