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The urgency for action on climate change is regarded as the defining issue of our time. Planetary health education prepares future healthcare professionals to promote the health of the planet, including sustainable healthcare. This has potential benefits for the healthcare system, patients, community, and the environment. However, many educators are not confident in explaining and inspiring students and many deans and educational staff report challenges when integrating planetary health into education. The roadmap presented in this paper uses evidence from medical education literature to support medical schools with implementing this type of education. The roadmap can be used as a guide for educators, university leadership, and policy-makers in the design of planetary health education. [ABSTRACT FROM AUTHOR]

Context: Applicant perceptions of selection methods can affect motivation, performance and withdrawal and may therefore be of relevance in the context of widening access. However, it is unknown how applicant subgroups perceive different selection methods. Objectives: Using organisational justice theory, the present multi‐site study examined applicant perceptions of various selection methods, rationales behind perceptions and subgroup differences. Methods: Applicants to five Dutch undergraduate health professions programmes (N = 704) completed an online survey including demographics and a questionnaire on applicant perceptions applied to 11 commonly used selection methods. Applicants rated general favourability and justice dimensions (7‐point Likert scale) and could add comments for each method. Results: Descriptive statistics revealed a preference for selection methods on which applicants feel more 'in control': General favourability ratings were highest for curriculum‐sampling tests (mean [M] = 5.32) and skills tests (M = 5.13), while weighted lottery (M = 3.05) and unweighted lottery (M = 2.97) were perceived least favourable. Additionally, applicants preferred to distinguish themselves on methods that assess attributes beyond cognitive abilities. Qualitative content analysis of comments revealed several conflicting preferences, including a desire for multiple selection methods versus concerns of experiencing too much stress. Results from a linear mixed model of general favourability indicated some small subgroup differences in perceptions (based on gender, migration background, prior education and parental education), but practical meaning of these differences was negligible. Nevertheless, concerns were expressed that certain selection methods can hinder equitable admission due to inequal access to resources. Conclusions: Our findings illustrate that applicants desire to demonstrate a variety of attributes on a combination of selection tools, but also observe that this can result in multiple drawbacks. The present study can help programmes in deciding which selection methods to include, which more negatively perceived methods should be better justified to applicants, and how to adapt methods to meet applicants' needs. The authors report that applicants to undergraduate health professions education prefer selection methods that provide a sense of control and allow the demonstration of more than just academic ability. [ABSTRACT FROM AUTHOR]

Studies to show that transcriptional repressor, Tbx3 controls the sinoartrial node gene by delineating the region, hence imposing a distinct pacemaker function on the atria cells are conducted. The mice models employed reveal that ectopic expression of Tbx3 helps in repression of atrial phenotype imposing the pacemaker phenotype and causing a partial loss of sinoatrial node-specific gene expression as well.

We investigated the contribution of the intracellular calcium (Ca) transient to acetylcholine (ACh)-mediated reduction of pacemaker frequency and cAMP content in rabbit sinoatrial nodal (SAN) cells. Action potentials (whole cell perforated patch clamp) and Ca transients (Indo-1 fluorescence) were recorded from single isolated rabbit SAN cells, whereas intracellular cAMP content was measured in SAN cell suspensions using a cAMP assay (LANCE®). Our data show that the Ca transient, like the hyperpolarization-activated “funny current” ( If) and the ACh-sensitive potassium current ( IK,ACh), is an important determinant of ACh-mediated pacemaker slowing. When If and IK,ACh were both inhibited, by cesium (2 mM) and tertiapin (100 nM), respectively, 1 μM ACh was still able to reduce pacemaker frequency by 72%. In these If and IK,ACh-inhibited SAN cells, good correlations were found between the ACh-mediated change in interbeat interval and the ACh-mediated change in Ca transient decay ( r2 = 0.98) and slow diastolic Ca rise ( r2 = 0.73). Inhibition of the Ca transient by ryanodine (3 μM) or BAPTA-AM (5 μM) facilitated ACh-mediated pacemaker slowing. Furthermore, ACh depressed the Ca transient and reduced the sarcoplasmic reticulum (SR) Ca2+ content, all in a concentration-dependent fashion. At 1 μM ACh, the spontaneous activity and Ca transient were abolished, but completely recovered when cAMP production was stimulated by forskolin (10 μM) and IK,ACh was inhibited by tertiapin (100 nM). Also, inhibition of the Ca transient by ryanodine (3 μM) or BAPTA-AM (25 μM) exaggerated the ACh-mediated inhibition of cAMP content, indicating that Ca affects cAMP production in SAN cells. In conclusion, muscarinic receptor stimulation inhibits the Ca transient via a cAMP-dependent signaling pathway. Inhibition of the Ca transient contributes to pacemaker slowing and inhibits Ca-stimulated cAMP production. Thus, we provide functional evidence for the contribution of the Ca transient to ACh-induced inhibition of pacemaker activity and cAMP content in rabbit SAN cells. [ABSTRACT FROM AUTHOR]

Extracellular acidification by osteoclasts is essential to bone resorption. During proton pumping, intracellular pH (pHi) is thought to be kept at a near-neutral level by chloride/bicarbonate exchange. Here we show that the Na+-independent chloride/bicarbonate anion exchanger 2 (Ae2) is relevant for this process in the osteoclasts from the long bones of Ae2a,b-/- mice (deficient in the main isoforms Ae2a, Ae2b1, and Ae2b2). Although the long bones of these mice had normal numbers of multinucleated osteoclasts, these cells lacked a ruffled border and displayed impaired bone resorption activity, resulting in an osteopetrotic pheno-type of long bones. Moreover, in vitro osteoclastogenesis assays using long-bone marrow cells from Ae2a,b-/- mice suggested a role for Ae2 in osteoclast formation, as fusion of preosteoclasts for the generation of active multinucleated osteoclasts was found to be slightly delayed. In contrast to the abnormalities observed in the long bones, the skull of Ae2a,b-/- mice showed no alterations, indicating that calvaria osteoclasts may display normal resorptive activity. Microfluorimetric analysis of osteoclasts from normal mice showed that, in addition to Ae2 activity, calvaria osteoclasts---but not long-bone osteoclasts--possess a sodium-dependent bicarbonate transporting activity. Possibly, this might compensate for the absence of Ae2 in calvaria osteoclasts of Ae2a,b-/- mice. [ABSTRACT FROM AUTHOR]

Background: Computerized adaptive testing tailors test items to students' abilities by adapting difficulty level. This more efficient, and reliable assessment form may provide advantages over a conventional medical progress test (PT). Prior to our study, a direct comparison of students' performance on a computer adaptive progress test (CA-PT) and a conventional PT, which is crucial for nationwide implementation of the CA-PT, was missing. Therefore, we assessed the correlation between CA-PT and conventional PT test performance and explored the feasibility and student experiences of CA-PT in a large medical cohort., Methods: In this cross-over study medical students (n = 1432) of three Dutch medical schools participated in both a conventional PT and CA-PT. They were stratified to start with either a conventional PT or CA-PT to determine test performance. Student motivation, engagement and experiences were assessed by questionnaires in students from seven Dutch medical schools. Parallel-forms reliability was assessed using the Pearson correlation coefficient., Results: A strong correlation was found (0.834) between conventional PT and CA-PT test performance. The CA-PT was administered without system performance issues and was completed in a median time of 83 minutes (67-102 minutes). Questionnaire response rate was 31.7% (526/1658). Despite a higher experienced difficulty, most students reported persistence, adequate task management and good focus during the CA-PT., Conclusions: CA-PT provides a reliable estimation of students' ability level in less time than a conventional non-adaptive PT and is feasible in students throughout the entire medical curriculum. Despite the strong correlation between PT scores, students found the CA-PT more challenging., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Studying the pre-clinical foundations of the medical profession sharpens the mind, improves critical thinking skills, builds academic stamina, and stimulates scientific curiosity. However, incorporation of the ever-growing clinical knowledge body into medical curricula jeopardizes the time undergraduate medical students are exposed to covering the basic sciences. In addition, clinical practice guidelines and clinical protocols lessen the importance of fostering critical thinking skills in our students. Inasmuch as mastering basic sciences demands a substantial time consuming intellectual effort, medical students prefer memorization and reproduction tasks to analysing challenging basic science questions. These three factors increase the risk of training (future) generations of doctors less well equipped to manage complex patients and lacking the essential knowledge and academic inquisitiveness to advance health care and medicine.

Background: Sphingosine-1-phosphate plays vital roles in cardiomyocyte physiology, myocardial ischemia-reperfusion injury, and ischemic preconditioning. The function of the cardiomyocyte sphingosine-1-phosphate receptor 1 (S1P1) in vivo is unknown., Methods and Results: Cardiomyocyte-restricted deletion of S1P1 in mice (S1P1 (α) (MHCC) (re)) resulted in progressive cardiomyopathy, compromised response to dobutamine, and premature death. Isolated cardiomyocytes from S1P1 (α) (MHCC) (re) mice revealed reduced diastolic and systolic Ca(2+) concentrations that were secondary to reduced intracellular Na(+) and caused by suppressed activity of the sarcolemmal Na(+)/H(+) exchanger NHE-1 in the absence of S1P1. This scenario was successfully reproduced in wild-type cardiomyocytes by pharmacological inhibition of S1P1 or sphingosine kinases. Furthermore, Sarcomere shortening of S1P1 (α) (MHCC) (re) cardiomyocytes was intact, but sarcomere relaxation was attenuated and Ca(2+) sensitivity increased, respectively. This went along with reduced phosphorylation of regulatory myofilament proteins such as myosin light chain 2, myosin-binding protein C, and troponin I. In addition, S1P1 mediated the inhibitory effect of exogenous sphingosine-1-phosphate on β-adrenergic-induced cardiomyocyte contractility by inhibiting the adenylate cyclase. Furthermore, ischemic precondtioning was abolished in S1P1 (α) (MHCC) (re) mice and was accompanied by defective Akt activation during preconditioning., Conclusions: Tonic S1P1 signaling by endogenous sphingosine-1-phosphate contributes to intracellular Ca(2+) homeostasis by maintaining basal NHE-1 activity and controls simultaneously myofibril Ca(2+) sensitivity through its inhibitory effect on adenylate cyclase. Cardioprotection by ischemic precondtioning depends on intact S1P1 signaling. These key findings on S1P1 functions in cardiac physiology may offer novel therapeutic approaches to cardiac diseases., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Extracellular acidification by osteoclasts is essential to bone resorption. During proton pumping, intracellular pH (pH(i)) is thought to be kept at a near-neutral level by chloride/bicarbonate exchange. Here we show that the Na(+)-independent chloride/bicarbonate anion exchanger 2 (Ae2) is relevant for this process in the osteoclasts from the long bones of Ae2(a,b)(-/-) mice (deficient in the main isoforms Ae2a, Ae2b(1), and Ae2b(2)). Although the long bones of these mice had normal numbers of multinucleated osteoclasts, these cells lacked a ruffled border and displayed impaired bone resorption activity, resulting in an osteopetrotic phenotype of long bones. Moreover, in vitro osteoclastogenesis assays using long-bone marrow cells from Ae2(a,b)(-/-) mice suggested a role for Ae2 in osteoclast formation, as fusion of preosteoclasts for the generation of active multinucleated osteoclasts was found to be slightly delayed. In contrast to the abnormalities observed in the long bones, the skull of Ae2(a,b)(-/-) mice showed no alterations, indicating that calvaria osteoclasts may display normal resorptive activity. Microfluorimetric analysis of osteoclasts from normal mice showed that, in addition to Ae2 activity, calvaria osteoclasts--but not long-bone osteoclasts--possess a sodium-dependent bicarbonate transporting activity. Possibly, this might compensate for the absence of Ae2 in calvaria osteoclasts of Ae2(a,b)(-/-) mice.