Mast cell distribution and prevalence in the murine urinary bladder.

BACKGROUND: Mast cells have been implicated in the pathology of various urinary bladder disorders. However, the distribution of mast cells throughout urinary bladder tissue remains uncertain despite mast cell prevalence being relatively well-defined. Using a mouse tissue model, this study aims to characterise the prevalence and distribution of mast cells throughout the urinary bladder. METHODS: Bladder tissues were collected from six C57BL/6J female mice. Mast cell prevalence was quantified by flow cytometry, based on the expression of the following characteristic markers: CD45, CD117 and FcɛRIα. The toluidine blue stain assessed mast cell distribution, size, and proximity to vasculature. A repeated measures one-way ANOVA was used to evaluate the density of mast cells between the discrete layers of the urinary bladder, and an ordinary one-way ANOVA was used to assess potential differences between mast cell size across the urinary bladder wall. RESULTS: It was determined that mast cells compose less than 4% of all live leukocytes in the urinary bladder. They were also found to be more prominent in the lamina propria and detrusor muscle layers, compared to the urothelium and adventitia. In addition, 20.89% of mast cells were located near vasculature, which may be an important factor in consideration of their function and potential to contribute to various bladder pathologies, such as cystitis or overactive bladder. CONCLUSION: These findings provide a baseline understanding of mast cell prevalence and distribution throughout the urinary bladder.

The role of intracellular calcium and Rho kinase pathways in G protein-coupled receptor-mediated contractions of urinary bladder urothelium and lamina propria.

The influence of extracellular and intracellular calcium on smooth muscle contractile activity varies between organs. In response to G protein-coupled receptor (GPCR) stimulation, the urinary bladder detrusor muscle has shown a 70% dependence on extracellular calcium, whereas the urothelium and lamina propria (U&LP) has a 20%-50% dependence. However, as this only accounts for partial contractile activity, the contribution of intracellular calcium and calcium sensitization pathways remains unclear. This study assessed the role of intracellular signaling pathways on GPCR-mediated urinary bladder U&LP contraction. Porcine U&LP responses to activation of the Gq/11-coupled muscarinic, histamine, 5-hydroxytryptamine (serotonin), neurokinin, prostaglandin, and angiotensin II receptors were assessed with three selective inhibitors of store-released intracellular calcium, 2-aminoethyl diphenylborinate (2-APB), cyclopiazonic acid (CPA), and ruthenium red, and three Rho kinase inhibitors, fasudil, Y-27632, and GSK269962. There was no discernible impact on receptor agonist-induced contractions of the U&LP after blocking intracellular calcium pathways, suggesting that this tissue is more sensitive to alterations in the availability of extracellular calcium. However, an alternative mechanism of action for GPCR-mediated contraction was identified to be the activation of Rho kinase, such as when Y-27632 significantly reduced the GPCR-mediated contractile activity of the U&LP by approximately 50% (P < 0.05, n = 8). This suggests that contractile responses of the bladder U&LP do not involve a significant release of calcium from intracellular stores, but that Gq/11-coupled receptor activation causes calcium sensitization via Rho kinase. This study highlights a key role for Rho kinase in the urinary bladder, which may provide a novel target in the future pharmaceutical management of bladder contractile disorders.

Antimuscarinic actions on bladder urothelium and lamina propria contractions are similar to those observed in detrusor smooth muscle preparations.

OBJECTIVES: Antimuscarinic medications are the first-line treatments for overactive bladder, the most common form of bladder dysfunction. Their primary action is thought to block detrusor muscarinic receptors. It is unclear, however, if these therapeutics have actions on other tissues within the lower urinary tract. This study assessed whether clinical antimuscarinics have a functional impact on urothelium with lamina propria (U&LP) tissue. METHODS: Strips of porcine detrusor and U&LP were mounted in carbogen-gassed Krebs-bicarbonate solution at 37°C. The tissues were paired with carbachol-response curves performed in the absence or presence of each antimuscarinic. pEC50 values for each curve were analyzed and estimated affinities calculated. RESULTS: Both detrusor and U&LP tissues contracted with muscarinic receptor stimulation, which was inhibited by commonly used antimuscarinics. In detrusor samples (p < 0.001 for all), right parallel shifts from the control were observed in response to oxybutynin (1 µM), solifenacin (1 µM), tolterodine (1 µM), darifenacin (100 nM), trospium (100 nM) and fesoterodine (100 nM). This shift was consistent in U&LP samples, with no significant differences between the two layers. CONCLUSIONS: The data suggests that clinical antimuscarinics are as effective at inhibiting tonic contractions of the U&LP as they are on detrusor, presenting the U&LP as an alternate target of these medications in the treatment of lower urinary tract symptoms.

Embedding planetary health concepts in a pre-medical physiology subject.

PURPOSE: There are increasing calls for planetary health (which includes sustainable healthcare) to be included in tertiary health professions education. With already busy curricula, particularly in medicine, educators need to find innovative ways of integrating these important concepts without adding to learners' workload. This study investigated whether planetary health concepts could be integrated into a Physiology subject as a stop-gap approach while longitudinal planning for longitudinal curriculum integration was underway. MATERIALS AND METHODS: Each week, a planetary health fact (Did you know?) with a corresponding link were embedded at the bottom of a relevant PowerPoint lecture slide to match the topic of the week in a health science and medicine Physiology subject. The embedded facts were a mix of effects on health and the environmental impacts of healthcare activities, such as medical imaging. No other formal planetary health teaching was conducted in the subject. At the end of the semester, 44% of 100 students completed a survey regarding their perceptions of the planetary health inclusions. RESULTS: Participants reported an appreciation of the facts, found them helpful for their overall learning, and were interested in learning about healthcare's large environmental footprint. Seventy-one percent were able to provide a reasonable definition of planetary health. Half of the participants reported their actions, behaviours, and thoughts had changed as a result of the planetary health inclusions. CONCLUSIONS: This study provides a relatively simple approach for individual educators to include planetary health concepts into existing health professions subjects until more longitudinal curriculum revisions can be undertaken. Based on our findings, we would, however, recommend providing students with a brief introduction in terms of why planetary health has been included either at the start of the first lecture or as a 10-min video.

Medical students as advocates for a healthy planet and healthy people: Designing an assessment that prepares learners to take action on the United Nations Sustainable Development Goals.

PURPOSE: Health professionals are being called on to be advocates for the planet to ensure health and well-being for current and future generations. Clean air, flourishing ecosystems, a stable climate, and nutritious food are required for health and well-being. Considering the deteriorating state of our natural environment, today's health professionals need to be advocates for a healthy planet. This places an onus on tertiary institutions to prepare graduates to 'take action' for the planet and all of its inhabitants. MATERIALS AND METHODS: This report outlines the development of a team-based Planetary Health Assignment that equips learners to use at least two of the 2030 United Nations Sustainable Development Goals (SDGs). It was identified at the design stage that an effective planetary health educational intervention should not only encourage learners to take action, but also embed creativity, with the best products available for public scrutiny. Several pedagogical principles were used in the design (authentic assessment, learner-centredness, creativity, scholarship). RESULTS: During the first five years of implementation, minor refinements were made based on learner and academic feedback. The assignment criteria sheet was improved to the point that it encouraged thoughtful and reflective submissions, and tasked learners to provide achievable and realistic solutions to pressing environmental issues. The marking rubric was also developed to provide quality feedback and insights for students. CONCLUSIONS: The design of this assessment, framed by the SDGs, allows learners flexibility in their choices while still meeting the required learning outcomes. With the assignment underpinned by a robust design, it provides students with both knowledge and experiences about how they might take action on the SDGs and become advocates for a healthy planet.

Don't forget the veggies! Identifying and addressing a lack of vegetable education in physiology.

Ninety-five percent of Westerners do not consume the recommended daily vegetable intake, exacerbating the incidence of obesity, malnutrition, and nutritional deficiencies such as fiber. This article reviews the literature from PubMed, ERIC, and Web of Science, as well as Internet sites and government resources, to identify what should be considered important inclusions relating to dietary vegetable (including legumes and pulses) intake content in university physiology subjects. The primary aim is to advance the competency relating to good nutrition knowledge for future health professionals to enable them to guide and counsel patients and clients toward better health. A review of the literature provides scant nutritional content relating to vegetable intake, particularly across physiology subjects and health professional programs in general. A review of country dietary guidelines yielded discrepancies and ambiguity around recommended daily vegetable intake, including what constitutes essential vegetables. Educators responsible for embedding nutritional information in the curriculum would therefore be challenged to find reliable, evidence-based resources. Adding quality curriculum content on the importance of vegetable intake also promotes some of the Sustainable Development Goals (SDGs), including SDG 2 (Zero Hunger), thereby contributing to SDG 3 (Good Health and Well-Being). This article offers recommendations on how to embed content relating to the importance of dietary vegetables for good health and guidance for educators of health professions programs wanting to improve their curriculum content relating to adequate nutrition.NEW & NOTEWORTHY Is nutritional literacy an important concept in physiology? This article identifies a paucity of content and addresses the need for vegetable intake education.

Unpacking and validating the "integration" core concept of physiology by an Australian team.

Consensus was reached on seven core concepts of physiology using the Delphi method, including "integration," outlined by the descriptor "cells, tissues, organs, and organ systems interact to create and sustain life." This core concept was unpacked by a team of 3 Australian physiology educators into hierarchical levels, identifying 5 themes and 10 subthemes, up to 1 level deep. The unpacked core concept was then circulated among 23 experienced physiology educators for comments and to rate both level of importance and level of difficulty for each theme and subtheme. Data were analyzed using a one-way ANOVA to compare between and within themes. The main theme (theme 1: the body is organized within a hierarchy of structures, from atoms to molecules, cells, tissues, organs, and organ systems) was almost universally rated as Essential. Interestingly, the main theme was also rated between Slightly Difficult to Not Difficult, which was significantly different from all other subthemes. There were two separate subsets of themes in relation to importance, with three themes rating between Essential and Important and the two other themes rating as Important. Two subsets in the difficulty of the main themes were also identified. While many core concepts can be taught concurrently, Integration requires the application of prior knowledge, with the expectation that learners should be able to apply concepts from "cell-cell communication," "homeostasis," and "structure and function," before understanding the overall Integration core concept. As such, themes from the Integration core concept should be taught within the endmost semesters of a Physiology program.NEW & NOTEWORTHY This article proposes the inclusion of a core concept regarding "integration" into physiology-based curricula, with the descriptor "cells, tissues, organs, and organ systems interact to create and sustain life." This concept expands prior knowledge and applies physiological understanding to real-world scenarios and introduces contexts such as medications, diseases, and aging to the student learning experience. To comprehend the topics within the Integration core concept, students will need to apply learned material from earlier semesters.

Establishing consensus for the core concepts of physiology in the Australian higher education context using the Delphi method.

A set of core concepts ("big ideas") integral to the discipline of physiology are important for students to understand and demonstrate their capacity to apply. We found poor alignment of learning outcomes in programs with physiology majors (or equivalent) from 17 Australian universities and the 15 core concepts developed by a team in the United States. The objective of this project was to reach Australia-wide consensus on a set of core concepts for physiology, which can be embedded in curricula across Australian universities. A four-phase Delphi method was employed, starting with the assembling of a Task Force of physiology educators with extensive teaching and curriculum development expertise from 25 Australian universities. After two online meetings and a survey, the Task Force reached agreement on seven core concepts of physiology and their descriptors, which were then sent out to the physiology educator community across Australia for agreement. The seven core concepts and their associated descriptions were endorsed through this process (n = 138). In addition, embedding the core concepts across the curriculum was supported by both Task Force members (85.7%) and educators (82.1%). The seven adopted core concepts of human physiology were Cell Membrane, Cell-Cell Communication, Movement of Substances, Structure and Function, Homeostasis, Integration, and Physiological Adaptation. The core concepts were subsequently unpacked into themes and subthemes. If adopted, these core concepts will result in consistency across curricula in undergraduate physiology programs and allow for future benchmarking.NEW & NOTEWORTHY This is the first time Australia-wide agreement has been reached on the core concepts of physiology with the Delphi method. Embedding of the core concepts will result in consistency in physiology curricula, improvements to teaching and learning, and benchmarking across Australian universities.

The effectiveness of parasympathomimetics for treating underactive bladder: A systematic review and meta-analysis.

AIMS: Biological rationale suggests that parasympathomimetics (cholinergic receptor stimulating agents) could be beneficial for patients with underactive bladder. However, no systematic review with meta-analysis addressing potential benefits or adverse effects exists. The aim of this review was to assess the effectiveness, both benefits and harms, of using parasympathomimetics for the treatment of underactive bladder. METHODS: The protocol was registered in PROSPERO, and searches undertaken in PubMed, Embase, and CENTRAL, including randomized and non-randomized controlled trials of patients with underactive bladder, comparing parasympathomimetic to placebo, no treatment, or other pharmaceuticals. Risk ratios, odds ratios, and mean differences were calculated. RESULTS: Twelve trials with 3024 participants were included. There was a significant difference between parasympathomimetics and comparators (favoring parasympathomimetics) in the number of patients with urinary retention (risk ratio 0.55, 95% confidence interval [CI] 0.3-0.98, p = 0.04, low quality of evidence). There was no difference in mean postvoid volume overall (MD -41.4 ml, 95% CI -92.0 to 9.1, p = 0.11, low quality of evidence). There was a significant difference at up to 1 week post-intervention, favoring parasympathomimetics (MD -77.5 ml, 95% CI -90.9 to -64.1, p < 0.001, low quality of evidence), but no difference at 1 month post-intervention. There was no difference in adverse events (odds ratio 1.19, 95% CI 0.62-2.28, p = 0.6, moderate quality of evidence). CONCLUSIONS: The evidence supporting the use of parasympathomimetics is of low quality, with relatively short follow-up durations. Overall, it is not possible to draw clear evidence-based conclusions from the current literature, presenting the use of parasympathomimetics for treating underactive bladder as a key area that requires future well-controlled clinical trials.

Description of a European memory clinic cohort undergoing amyloid-PET: The AMYPAD Diagnostic and Patient Management Study.

INTRODUCTION: AMYPAD Diagnostic and Patient Management Study (DPMS) aims to investigate the clinical utility and cost-effectiveness of amyloid-PET in Europe. Here we present participants' baseline features and discuss the representativeness of the cohort. METHODS: Participants with subjective cognitive decline plus (SCD+), mild cognitive impairment (MCI), or dementia were recruited in eight European memory clinics from April 16, 2018, to October 30, 2020, and randomized into three arms: ARM1, early amyloid-PET; ARM2, late amyloid-PET; and ARM3, free-choice. RESULTS: A total of 840 participants (244 SCD+, 341 MCI, and 255 dementia) were enrolled. Sociodemographic/clinical features did not differ significantly among recruiting memory clinics or with previously reported cohorts. The randomization assigned 35% of participants to ARM1, 32% to ARM2, and 33% to ARM3; cognitive stages were distributed equally across the arms. DISCUSSION: The features of AMYPAD-DPMS participants are as expected for a memory clinic population. This ensures the generalizability of future study results.

Teaching with Disruptive Technology: The Use of Augmented, Virtual, and Mixed Reality (HoloLens) for Disease Education.

Modern technologies are often utilised in schools or universities with a variety of educational goals in mind. Of particular interest is the enhanced interactivity and engagement offered by mixed reality devices such as the HoloLens, as well as the ability to explore anatomical models of disease using augmented and virtual realities. As the students are required to learn an ever-increasing number of diseases within a university health science or medical degree, it is crucial to consider which technologies provide value to educators and students. This chapter explores the opportunities for using modern disruptive technologies to teach a curriculum surrounding disease. For relevant examples, a focus will be placed on asthma as a respiratory disease which is increasing in prevalence, and stroke as a neurological and cardiovascular disease. The complexities of creating effective educational curricula around these diseases will be explored, along with the benefits of using augmented reality and mixed reality as viable teaching technologies in a range of use cases.

The five primary prostaglandins stimulate contractions and phasic activity of the urinary bladder urothelium, lamina propria and detrusor.

BACKGROUND: Inflammation is often associated with several bladder dysfunctions, including overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/PBS). As such, inflammation of the bladder and the actions of inflammatory mediators may contribute to the development of urinary symptoms. This study assessed the actions of PGE2, PGF2, PGD2, TXA2, and PGI2 on urinary bladder urothelium with lamina propria (U&LP), and detrusor smooth muscle. METHODS: Studies were carried out using isolated tissue baths, where strips of porcine bladder U&LP or detrusor were exposed to varying concentrations of prostaglandin agonists (1 µM and 10 µM). RESULTS: All assessed prostaglandin agonists contracted both the U&LP and detrusor smooth muscle, with the rank order of contractile response effectiveness as: PGE2 > PGF2α > TXA2 > PGD2 > PGI2. In U&LP, treatment with PGE2 (10 µM) increased tonic contractions by 1.36 ± 0.09 g (n = 42, p < 0.001) and phasic contractions by 40.4 ± 9.6% (n = 42, p < 0.001). In response to PGF2α (10 µM), U&LP tonic contractions increased by 0.79 ± 0.06 g (n = 14, p < 0.001) and phasic activity by 13.3% ± 5.3% (n = 15, p < 0.05). In detrusor preparations, PGE2 (10 µM) increased tonic contractions by 1.32 ± 0.13 g (n = 38, p < 0.001) and PGF2α (10 µM) by 0.97 ± 0.14 g (n = 12, p < 0.001). Only 34% (n = 48) of all detrusor preparations exhibited spontaneous activity prior to the addition of any agonist at a frequency of 2.03 ± 0.12 cpm. In preparations that did not exhibit initial phasic activity, all of the prostaglandin agonists were capable of commencing phasic activity. CONCLUSIONS: The urinary bladder U&LP and detrusor respond to a variety of prostaglandin agonists, with their activation resulting in direct contractions, as well as increases to spontaneous contractile activity. This study presents the prostaglandin receptor system as a potential therapeutic target for lower urinary tract dysfunction.

Enhancing Teaching in Biomedical, Health and Exercise Science with Real-Time Physiological Visualisations.

Muscle physiology constitutes a core curriculum for students and researchers within biomedical, health and exercise science disciplines. The variations between skeletal and smooth muscle, mechanisms underlying excitation-contraction coupling, as well as the relationships between muscle anatomy and physiology are commonly taught from illustrations, static models or textbooks. However, this does not necessarily provide students with the required comprehension surrounding the dynamic nature of muscle contractions or neuromuscular activities. This chapter will explore alternative methods of visualising skeletal and smooth muscle physiology in real-time. Various recording hardware, isolated tissues bath experiments, neurophysiological applications and computer-based software will be discussed to provide an overview of the evidence-based successes and case studies for using these techniques when assisting students with their understanding of the complex mechanisms underlying muscle contractions.

Utilising Anatomical and Physiological Visualisations to Enhance the Face-to-Face Student Learning Experience in Biomedical Sciences and Medicine.

The introduction of online learning and interactive technology into tertiary education has enabled biomedical science and medical faculties to provide students with quality resources for off-campus study. This encompasses online self-directed learning, interactive blogs, quizzes, recordings of lectures and other resources. In addition, textbooks are now supplemented with interactive online learning tools, meaning that the student now has more accessibility than ever to engage with content. However, in biomedical sciences and medicine, technology has also enhanced the in-classroom experience. Anatomical and physiological visualisations in virtual, augmented and mixed reality provide students with an unprecedented ability to explore virtual content in-class, while learning remains structured by the facilitator and teaching team. This chapter will provide insights into the past use of technology to enhance off-campus learning, and then focus on the range of visualisations utilised within the laboratory or classroom in order to facilitate learning in biomedical sciences and medicine, including: augmented reality, virtual reality; mixed reality and Holograms; 3D printing; simulated dissections and anatomy simulation tables; and "Smart" tablets and touchscreen devices.

Multimodal Learning in Health Sciences and Medicine: Merging Technologies to Enhance Student Learning and Communication.

Advances in consumer-level educational technologies show great promise for enhancing the learning experiences of students in health and medicine. There are particular benefits to using a combination of various devices and technologies when teaching challenging concepts. These include augmented reality-enabled devices enriched with accompanying 3D printed models, or virtual reality sessions coupled with online quizzes or revision activities. Tablet applications can also be integrated while students engage concurrently in desktop-based online learning. This mixing and merging of different technologies can allow educators to focus on the strengths of each device, while mitigating limitations arising from a single mode's stand-alone use. This chapter describes a series of options to integrate multiple digital modes when educating health science and medical students using technology. It also presents the opportunity for health professional program graduates to be trained in teaching using technology, as their future careers can be enhanced by an ability to educate effectively, or from the skills developed when incorporating innovations such as serious games into a health curriculum. With the dynamic and ever-changing nature of health and medical education, educators can find great benefits when introducing multimodal digital learning into their respective courses.

Enhancing capillary blood collection: The influence of nicotinic acid and nonivamide.

BACKGROUND: Nicotinic acid and nonivamide are often applied topically during capillary blood collection to induce vasodilation. These molecules may have an influence on immune effector cell activity in nearby tissues. This study investigates whether the induction of flushing by nicotinic acid and nonivamide causes an inflammatory response that influences the composition of immune cells present in a capillary blood sample. METHODS: Females aged between 18 and 30 years old provided capillary blood samples. Experimental samples were taken from an earlobe treated with nicotinic acid and nonivamide with controls obtained from the untreated earlobe. Immunophenotypic analyses were conducted using polychromatic flow cytometry to determine whether any changes occurred in leucocyte subpopulations (CD3, CD4, CD8, CD19, CD56, and CD14) and granulocytic functional-related surface antigen markers (CD11b, CD18, CD16b, and CD66b). RESULTS: No significant differences were observed between experimental and control samples in the mean percent of parent for the lymphocyte, monocyte, or granulocyte subpopulations, or in the median fluorescence intensity of particular surface markers expressed on these leucocytes. CONCLUSION: The topical application of nicotinic acid and nonivamide is a possible method to improve capillary blood collection for immunological assessments. The use of these agents may increase the safety and compliance of patients who suffer from needle phobia or are unable to provide venous blood samples.