Substantial Increases in Healthcare Students' State Empathy Scores Owing to Participation in a Single Improvisation Session.

PURPOSE: To determine whether the 12-item state empathy scale could be modified reliably to measure empathy in healthcare professions students and to detect changes in their empathy owing to a single improvisation (improv) session. METHODS: Three cohorts of students from two healthcare professions programs (total = 165 students) participated in an improv session. During the session, one of the researchers (BS) tasked the students with several improv activities. Participants' self-reported state empathy scores were assessed at three time points (pre-improv, post-improv, and end of semester) using revised, in-class paper versions of the State Empathy Scale. RESULTS: The exploratory factor analysis revealed a single factor solution for the revised scale, justifying the creation of an overall state empathy score from the questionnaire. Cronbach's alpha reliability values averaged 0.87. Students' mean empathy scores were higher directly after the improv session than directly prior to the session (p < 0.0001; effect size = r = 0.67, 0.55, and 0.79 for cohorts 1, 2, and 3, respectively). CONCLUSIONS: These findings show that a single one- or two-hour improv session can foster substantial increases in healthcare professional students' state empathy for one another. Greater healthcare professional empathy and compassion foster better healthcare team cooperation and patient outcomes, so healthcare professionals and their students should engage in such empathy-enhancing activities at regular intervals throughout their training and careers.

Survey of attitudes toward performing and reflecting on required team service-learning (SASL): psychometric data and reliability/validity for healthcare professions students in preclinical courses.

Purpose: Previously we assessed healthcare professional students' feelings about team-based learning, implicit bias, and service to the community using an in-house paper survey. In this study, we determined whether this survey is a reliable and valid measure of prospective medical students' attitudes toward required service-learning in an Immunology course. To our knowledge, no published questionnaire has been shown to be dependable and useful for measuring such attitudes using only eight survey items. Methods: Fifty-eight prospective medical students in Colorado (CO) and 15 in Utah (UT) completed the same Immunology course using remote technology. In addition to the usual course content, students were required to write critical reflections on required team service-learning. On the last day of class, they completed the survey of attitudes toward service-learning (SASL). Results: Data analyses found Cronbach's alpha values of 0.84 and 0.85 for the surveys of UT and CO students, respectively. Factor analysis of CO student data revealed only one Eigenvalue greater than one (3.95) justifying retention of a single factor termed "attitudes toward required service-learning." In addition, CO students' attitudes toward community service were highly positive, while UT students' attitudes were nearer neutral (p < 0.0001). Conclusion: Our factor analysis and good Cronbach's alpha values support the conclusion that the SASL was a reliable measure of prospective medical students' attitudes toward required team service-learning for an Immunology course. Moreover, we used the SASL to distinguish these attitudes in CO versus UT students, and, thus, the SASL appears to be a valid measure of this difference. Calculation of similarly good Cronbach's alpha values - for a predecessor of the SASL among pharmacy, masters, and medical students at another institution - indicates that the SASL may be useful more widely. However, the reliability and validity of the SASL needs to be demonstrated more rigorously for other healthcare students at different universities.

Molecular and Clinical Advances in Understanding Early Embryo Development.

The articles in this Special Issue address a wide variety of topics concerning molecular and clinical advances in understanding early embryo development [...].

Perspective: Might Maternal Dietary Monosodium Glutamate (MSG) Consumption Impact Pre- and Peri-Implantation Embryos and Their Subsequent Development?

MSG alters metabolism, especially in the brain, when administered to experimental animals via gavage or similar means. Such administration is, however, not applicable to humans. More recently, though, MSG was shown to have these effects even when added to the food of mammals. Moreover, the levels of MSG in food needed to cause these metabolic changes are the same as those needed for optimum flavor enhancement. Near physiological concentrations of glutamate also cause mammalian blastocysts to develop with fewer cells, especially in their inner cell masses, when these embryos are cultured with this amino acid. We propose that consumption of MSG in food may overwhelm the otherwise well-regulated glutamate signaling needed for optimal development by pre- and peri-implantation mammalian embryos. In addition to immediate changes in cellular proliferation and differentiation as embryos develop, MSG ingestion during early pregnancy might result in undesirable conditions, including metabolic syndrome, in adults. Since these conditions are often the result of epigenetic changes, they could become transgenerational. In light of these possibilities, we suggest several studies to test the merit of our hypothesis.

Critical reflection on required service to the community propels prospective medical students toward higher empathy, compassion, and bias mitigation but are these gains sustainable?

Purpose: We observed increased cognitive empathy and reflective capacity scores when prospective medical students wrote critical reflections on mandatory team service-learning in a Medical Humanities course, but these findings did not include a control group. Here we compare these survey results in similar courses with and without required service-learning. Methods: Forty-three prospective medical students completed a Medical Humanities course requiring critical reflection on team service-learning. In comparison, 32 students finished a similar course in which service to the community was not mandatory. Before starting the courses, students completed reliable surveys of their cognitive empathy and reflective capacity, and more than 93% of the students completed the same surveys after finishing the courses. Results: Students' cognitive empathy and reflective capacity scores increased significantly when service-learning was required, but the scores did not increase significantly when service to the community was not required. The effect size for the empathy increase was of crucial practical importance (r = 0.50), whereas it was of moderate practical importance for the increase in reflective capacity (r = 0.34). Conclusions: These and prior findings strongly support the conclusion that students' critical reflection on mandatory team service-learning fosters development of their cognitive empathy and reflective capacity. We present a model program to incorporate critical reflection on service to the community throughout the curricula of all healthcare professions trainees.

Epigenetic Regulation of Development, Cellular Differentiation, and Disease Progression/Protection in Adults.

Epigenetic changes drive early embryonic and later stages of development [...].

Epigenetic Modifications at the Center of the Barker Hypothesis and Their Transgenerational Implications.

Embryo/fetal nutrition and the environment in the reproductive tract influence the subsequent risk of developing adult diseases and disorders, as formulated in the Barker hypothesis. Metabolic syndrome, obesity, heart disease, and hypertension in adulthood have all been linked to unwanted epigenetic programing in embryos and fetuses. Multiple studies support the conclusion that environmental challenges, such as a maternal low-protein diet, can change one-carbon amino acid metabolism and, thus, alter histone and DNA epigenetic modifications. Since histones influence gene expression and the program of embryo development, these epigenetic changes likely contribute to the risk of adult disease onset not just in the directly affected offspring, but for multiple generations to come. In this paper, we hypothesize that the effects of parental nutritional status on fetal epigenetic programming are transgenerational and warrant further investigation. Numerous studies supporting this hypothesis are reviewed, and potential research techniques to study these transgenerational epigenetic effects are offered.

Amino Acid Transport and Metabolism Regulate Early Embryo Development: Species Differences, Clinical Significance, and Evolutionary Implications.

In this review we discuss the beneficial effects of amino acid transport and metabolism on pre- and peri-implantation embryo development, and we consider how disturbances in these processes lead to undesirable health outcomes in adults. Proline, glutamine, glycine, and methionine transport each foster cleavage-stage development, whereas leucine uptake by blastocysts via transport system B0,+ promotes the development of trophoblast motility and the penetration of the uterine epithelium in mammalian species exhibiting invasive implantation. (Amino acid transport systems and transporters, such as B0,+, are often oddly named. The reader is urged to focus on the transporters' functions, not their names.) B0,+ also accumulates leucine and other amino acids in oocytes of species with noninvasive implantation, thus helping them to produce proteins to support later development. This difference in the timing of the expression of system B0,+ is termed heterochrony-a process employed in evolution. Disturbances in leucine uptake via system B0,+ in blastocysts appear to alter the subsequent development of embryos, fetuses, and placentae, with undesirable consequences for offspring. These consequences may include greater adiposity, cardiovascular dysfunction, hypertension, neural abnormalities, and altered bone growth in adults. Similarly, alterations in amino acid transport and metabolism in pluripotent cells in the blastocyst inner cell mass likely lead to epigenetic DNA and histone modifications that produce unwanted transgenerational health outcomes. Such outcomes might be avoided if we learn more about the mechanisms of these effects.

Interkingdom Comparison of Threonine Metabolism for Stem Cell Maintenance in Plants and Animals.

In multicellular organisms, tissue generation, maintenance, and homeostasis depend on stem cells. Cellular metabolic status is an essential component of different differentiated states, from stem to fully differentiated cells. Threonine (Thr) metabolism has emerged as a critical factor required to maintain pluripotent/multipotent stem cells in both plants and animals. Thus, both kingdoms conserved or converged upon this fundamental feature of stem cell function. Here, we examine similarities and differences in Thr metabolism-dependent mechanisms supporting stem cell maintenance in these two kingdoms. We then consider common features of Thr metabolism in stem cell maintenance and predict and speculate that some knowledge about Thr metabolism and its role in stem cell function in one kingdom may apply to the other. Finally, we outline future research directions to explore these hypotheses.

Impact of a Pandemic and Remote Learning on Team Development and Elements of Compassion in Prospective Medical Students Taking a Medical Humanities Course.

INTRODUCTION: We reported previously that when teams of students reflect on readings about communication, unconscious bias, and service-learning, their critical reflection, implicit bias mitigation, empathy, and compassionate behavior all increase. However, would these gains occur when intimate classroom settings, in-person team meetings, and direct interactions with people served were lost owing to the COVID-19 pandemic and remote learning? METHODS: Before an online Medical Humanities course began in August 2020 and following the course in December 2020, 61 prospective medical students (54.1% female) completed reliable surveys of their reflective capacity (RC) and cognitive empathy (compassion). Students also completed surveys about their implicit biases and team community service in December 2020. RESULTS: Both RC and empathy scores increased in students after they reflected on difficulties in communication, unconscious biases, and team service-learning experiences in the course. In written reflections, they reported how their compassionate behavior also grew owing to bias mitigation. Most students concurred that "unconscious bias might affect some of (their) clinical decisions or behaviors as a healthcare professional" and vowed to remain aware of these biases in clinical settings. CONCLUSIONS: Compared to previous years, the pandemic and remote learning had minimal effects on the benefits of our Medical Humanities course.

Lysine Deprivation during Maternal Consumption of Low-Protein Diets Could Adversely Affect Early Embryo Development and Health in Adulthood.

The conversion of lysine to glutamate is needed for signaling in all plants and animals. In mouse embryonic stem (mES) cells, and probably their progenitors, endogenous glutamate production and signaling help maintain cellular pluripotency and proliferation, although the source of glutamate is yet to be determined. If the source of glutamate is lysine, then lysine deprivation caused by maternal low-protein diets could alter early embryo development and, consequently, the health of the offspring in adulthood. For these reasons, we measured three pertinent variables in human embryonic stem (hES) cells as a model for the inner cell masses of human blastocysts. We found that RNA encoding the alpha-aminoadipic semialdehyde synthase enzyme, which regulates glutamate production from lysine, was highly expressed in hES cells. Moreover, the mean amount of lysine consumed by hES cells was 50% greater than the mean amount of glutamate they produced, indicating that lysine is likely converted to glutamate in these cells. Finally, hES cells expressed RNA encoding at least two glutamate receptors. Since this may also be the case for hES progenitor cells in blastocysts, further studies are warranted to verify the presence of this signaling process in hES cells and to determine whether lysine deprivation alters early mammalian embryo development.

Consumption of a Branched-Chain Amino Acid (BCAA) during Days 2-10 of Pregnancy Causes Abnormal Fetal and Placental Growth: Implications for BCAA Supplementation in Humans.

A relatively large branched-chain amino acid (BCAA) supplement, consumed for more than 10 days, appears to be especially effective at alleviating muscle damage and soreness during intense human training. However, perturbations in amino acid and protein consumption could have unwanted transgenerational effects on male and female reproduction. This paper hypothesizes that isoleucine consumption by female mice from days 2 to 10 of pregnancy will alter fetal and placental growth later in gestation. Mice that had received 118 mM isoleucine in their drinking water delivered pups on day 19 of pregnancy that were 9% larger than normal, whereas the reverse was true for pups born on day 20. Moreover, the inverse correlation between birth weight and litter size was lost in mice that previously consumed excess isoleucine. Similarly, the normal correlations between fetal and placental weights were lost by day 18 of pregnancy in mice that had consumed excess isoleucine. Mice that consumed excess isoleucine had placentas smaller than, and fetuses larger than normal on day 18 of pregnancy, but the reverse was true on day 15. Other unintended and unexpected effects of BCAA consumption should be studied more thoroughly due to the increasing use of BCAAs to alleviate muscle damage and soreness in athletes.

Fostering Empathy, Implicit Bias Mitigation, and Compassionate Behavior in a Medical Humanities Course.

Increases in compassionate behavior improve patient outcomes and reduce burnout among healthcare professionals. We predicted that selecting and performing service-learning projects by teams of prospective medical students in a Medical Humanities course would foster students' compassion by raising their reflective capacity, empathy, and unconscious bias mitigation. In class, we discussed difficulties in communication and implicit bias. In this observational study, teams wrote individual and team critical reflections on these class discussions and their service-learning experiences, and we analyzed these reflections for dissonance, self-examination, bias mitigation, dissonance reconciliation, and compassionate behavior. Thirty-two students (53% female) completed the Reflective Practice Questionnaire and the Jefferson Scale of Empathy before the course in August 2019 and after it in December 2019. In December, students were surveyed concerning their attitudes toward team service-learning projects and unconscious bias. The students reported changes in their behavior to mitigate biases and become more compassionate, and their reflective capacity and empathy grew in association with discussions and team service-learning experiences in the course. Virtually all students agreed with the statement "Unconscious bias might affect some of my clinical decisions or behaviors as a healthcare professional," and they worked to control such biases in interactions with the people they were serving.

Perspective: One-Cell and Cleavage-Stage Mouse Embryos Thrive in Hyperosmotic Oviductal Fluid Through Expression of a Glycine Neurotransmitter Transporter and a Glycine-Gated Chloride Channel: Clinical and Transgenerational Implications.

The osmolality of mouse oviductal fluid ranges from about 300 mOsmol/kg in the ampulla 0-3 h post coitus (h p.c.) to more than 350 mOsmol/kg in the isthmus 34-36 h p.c. Thus, it has been surprising to find that development of one-cell and cleavage-stage mouse embryos arrests in vitro in media exceeding 300 mOsmol/kg, and they develop best in unphysiological, hypotonic media. The glycine concentration in oviductal fluid can, however, rescue development in hypertonic media, so physiological conditions in vivo and in vitro likely work together to foster embryo well-being. Glycine acts on one-cell and cleavage-stage mouse embryos through the glycine-gated chloride channel, GLRA4, and uptake via the glycine neurotransmitter transporter, GLYT1. Since these processes lead to further signaling in neurons, the presence and function of such signaling in preimplantation embryos also should be investigated. The more we know about the interactions of physiological processes and conditions in vivo, the better we would be able to reproduce them in vitro. Such improvements in assisted reproductive technology (ART) could improve patient outcomes for IVF and potentially help prevent unwanted developmental abnormalities in early embryos, which might include undesirable epigenetic DNA and histone modifications. These epigenetic modifications may lead to transgenerational adult disorders such as metabolic syndrome and related conditions.

One-Carbon Metabolism Regulates Embryonic Stem Cell Fate Through Epigenetic DNA and Histone Modifications: Implications for Transgenerational Metabolic Disorders in Adults.

Human (h) and mouse (m) embryonic stem (ES) cells need specific amino acids to proliferate. mES cells require threonine (Thr) metabolism for epigenetic histone modifications. Thr is converted to glycine and acetyl CoA, and the glycine is metabolized specifically to regulate trimethylation of lysine (Lys) residue 4 in histone H3 (H3K4me3). DNA methylation and methylation of other H3 Lys residues remain unimpaired by Thr deprivation in mES cell culture medium. Similarly, hES cells require methionine (Met) to maintain the Met-SAM (S-adenosyl methionine) cycle of 1-carbon metabolism also for H3K4me3 formation. H3K4me3 is needed specifically to regulate and maintain both mES and hES cell proliferation and their pluripotent states. Better understanding of this regulation is essential since treatment of human diseases and disorders will increasingly involve hES cells. Furthermore, since ES cells are derived from their progenitor cells in preimplantation blastocysts, they serve as models of 1-carbon metabolism in these precursors of all mammalian tissues and organs. One-carbon metabolism challenges, such as a maternal low protein diet (LPD) during preimplantation blastocyst development, contribute to development of metabolic syndrome and related abnormalities in adults. These 1-carbon metabolism challenges result in altered epigenetic DNA and histone modifications in ES progenitor cells and the tissues and organs to which they develop. Moreover, the modified histones could have extracellular as well as intracellular effects, since histones are secreted in uterine fluid and influence early embryo development. Hence, the mechanisms and transgenerational implications of these altered epigenetic DNA and histone modifications warrant concerted further study.

Selecting and Performing Service-Learning in a Team-Based Learning Format Fosters Dissonance, Reflective Capacity, Self-Examination, Bias Mitigation, and Compassionate Behavior in Prospective Medical Students.

More compassionate behavior should make both patients and their providers happier and healthier. Consequently, work to increase this behavior ought to be a major component of premedical and medical education. Interactions between doctors and patients are often less than fully compassionate owing to implicit biases against patients. Such biases adversely affect treatment, adherence, and health outcomes. For these reasons, we studied whether selecting and performing service-learning projects by teams of prospective medical students prompts them to write reflections exhibiting dissonance, self-examination, bias mitigation, dissonance reconciliation, and compassionate behavior. Not only did these students report changes in their behavior to become more compassionate, but their reflective capacity also grew in association with selecting and performing team service-learning projects. Components of reflective capacity, such as reflection-on-action and self-appraisal, correlated strongly with cognitive empathy (a component of compassion) in these students. Our results are, however, difficult to generalize to other universities and other preprofessional and professional healthcare programs. Hence, we encourage others to test further our hypothesis that provocative experiences foster frequent self-examination and more compassionate behavior by preprofessional and professional healthcare students, especially when teams of students are free to make their own meaning of, and build trust and psychological safety in, shared experiences.