Integration of metabolic flux with hepatic glucagon signaling and gene expression profiles in the conscious dog.

Glucagon rapidly and profoundly stimulates hepatic glucose production (HGP), but for reasons that are unclear, this effect normally wanes after a few hours, despite sustained plasma glucagon levels. This study characterized the time course of glucagon-mediated molecular events and their relevance to metabolic flux in the livers of conscious dogs. Glucagon was either infused into the hepato-portal vein at a sixfold basal rate in the presence of somatostatin and basal insulin, or it was maintained at a basal level in control studies. In one control group, glucose remained at basal, whereas in the other, glucose was infused to match the hyperglycemia that occurred in the hyperglucagonemic group. Elevated glucagon caused a rapid (30 min) and largely sustained increase in hepatic cAMP over 4 h, a continued elevation in glucose-6-phosphate (G6P), and activation and deactivation of glycogen phosphorylase and synthase activities, respectively. Net hepatic glycogenolysis increased rapidly, peaking at 15 min due to activation of the cAMP/PKA pathway, then slowly returned to baseline over the next 3 h in line with allosteric inhibition by glucose and G6P. Glucagon's stimulatory effect on HGP was sustained relative to the hyperglycemic control group due to continued PKA activation. Hepatic gluconeogenic flux did not increase due to the lack of glucagon's effect on substrate supply to the liver. Global gene expression profiling highlighted glucagon-regulated activation of genes involved in cellular respiration, metabolic processes, and signaling, as well as downregulation of genes involved in extracellular matrix assembly and development.NEW & NOTEWORTHY Glucagon rapidly stimulates hepatic glucose production, but these effects are transient. This study links the molecular and metabolic flux changes that occur in the liver over time in response to a rise in glucagon, demonstrating the strength of the dog as a translational model to couple findings in small animals and humans. In addition, this study clarifies why the rapid effects of glucagon on liver glycogen metabolism are not sustained.

Comparing alternative and traditional dissemination metrics in medical education.

CONTEXT: The impact of academic scholarship has traditionally been measured using citation-based metrics. However, citations may not be the only measure of impact. In recent years, other platforms (e.g. Twitter) have provided new tools for promoting scholarship to both academic and non-academic audiences. Alternative metrics (altmetrics) can capture non-traditional dissemination data such as attention generated on social media platforms. OBJECTIVES: The aims of this exploratory study were to characterise the relationships among altmetrics, access counts and citations in an international and pre-eminent medical education journal, and to clarify the roles of these metrics in assessing the impact of medical education academic scholarship. METHODS: A database study was performed (September 2015) for all papers published in Medical Education in 2012 (n = 236) and 2013 (n = 246). Citation, altmetric and access (HTML views and PDF downloads) data were obtained from Scopus, the Altmetric Bookmarklet tool and the journal Medical Education, respectively. Pearson coefficients (r-values) between metrics of interest were then determined. RESULTS: Twitter and Mendeley (an academic bibliography tool) were the only altmetric-tracked platforms frequently (> 50%) utilised in the dissemination of articles. Altmetric scores (composite measures of all online attention) were driven by Twitter mentions. For short and full-length articles in 2012 and 2013, both access counts and citation counts were most strongly correlated with one another, as well as with Mendeley downloads. By comparison, Twitter metrics and altmetric scores demonstrated weak to moderate correlations with both access and citation counts. CONCLUSIONS: Whereas most altmetrics showed limited correlations with readership (access counts) and impact (citations), Mendeley downloads correlated strongly with both readership and impact indices for articles published in the journal Medical Education and may therefore have potential use that is complementary to that of citations in assessment of the impact of medical education scholarship.

A review of teaching skills development programmes for medical students.

CONTEXT: The CanMEDS role of Scholar requires that medical trainees develop their skills as medical educators. The development of teaching skills in undergraduate medical students is therefore desirable, especially in view of the teaching obligations in residency programmes. OBJECTIVES: The goal of this review was to identify the characteristics and outcomes of programmes designed to develop the teaching skills of undergraduate medical students. METHODS: The authors searched medical literature databases using combinations of the search terms 'medical student', 'teacher', 'teaching skills', 'peer teaching', 'near-peer teaching' and 'student as teacher'. Twenty papers fit the predetermined search criteria, which included original characterisations of specific programmes involving undergraduate medical students. RESULTS: Three types of initiative were identified in the reviewed articles: peer teaching programmes; teaching workshops, and community outreach programmes. The majority of study participants were students in Years 3 and 4. Subjective self-evaluation by participants using Likert scale-based surveys was by far the most commonly used method of measuring project outcomes. Objective, quantitative teaching-related outcomes were rarely noted in the reports reviewed. Self-perceived improvements in teaching skills were noted by participants in most of the reports. Other perceived benefits included increases in organisational skills, knowledge and confidence in giving feedback. CONCLUSIONS: Although several types of programmes have been shown to subjectively improve the teaching skills of undergraduate medical students, characterisation of the objective outcomes of these initiatives is lacking and requires further study.

An Innovative Master in Anatomy: Combining Anatomy With Educational Scholarship.

The purpose of this article is to describe the design of a unique, bilingual (English and French) Master of Applied Sciences (M.Sc.) in Anatomical Sciences Education (ASE) program at a Canadian postsecondary institution. Anatomy is a core foundational discipline that is essential to many undergraduate, graduate, and professional programs in the health sciences. However, the number of new individuals with the necessary knowledge base and the pedagogical training to teach cadaveric anatomy are in short supply and cannot satisfy the number of openings for trained educators in the field. The M.Sc. in ASE was created to meet the increasingly critical need for instructors trained in human anatomy. The program is designed to prepare students for a career teaching human anatomy to students in the health sciences, emphasizing hands-on cadaveric dissection. Moreover, this program aims to develop educational scholarship skills in trainees by leveraging faculty expertise in medical education research, particularly in the field of anatomy education research. This focus on scholarships will make graduates more competitive for future faculty positions. During their first year of the program, learners will develop clinically relevant anatomy knowledge, teaching skills, and anatomy education scholarship. In the second year, students will benefit from an immediate, hands-on application of this acquired knowledge. In the same year, students will serve as anatomy teachers in the faculty's Medical Program and conduct their education scholarship projects, culminating in a formal research paper. Although similar programs have been developed in recent years, this article provides the first description of the creation of a graduate program in anatomy education. It includes needs assessment, program development, challenges faced, and lessons learned during the approval process. The article serves as a valuable resource for other institutions aspiring to develop similar initiatives.

Integration of metabolic flux with hepatic glucagon signaling and gene expression profiles in the conscious dog.

Glucagon rapidly and profoundly simulates hepatic glucose production (HGP), but for reasons which are unclear, this effect normally wanes after a few hours, despite sustained plasma glucagon levels. This study characterized the time course and relevance (to metabolic flux) of glucagon mediated molecular events in the livers of conscious dogs. Glucagon was either infused into the hepato-portal vein at a 6-fold basal rate in the presence of somatostatin and basal insulin, or it was maintained at a basal level in control studies. In one control group glucose remained at basal while in the other glucose was infused to match the hyperglycemia that occurred in the hyperglucagonemic group. Elevated glucagon caused a rapid (30 min) but only partially sustained increase in hepatic cAMP over 4h, a continued elevation in G6P, and activation and deactivation of glycogen phosphorylase and synthase activities, respectively. Net hepatic glycogenolysis and HGP increased rapidly, peaking at 30 min, then returned to baseline over the next 3h (although glucagons stimulatory effect on HGP was sustained relative to the hyperglycemic control group). Hepatic gluconeogenic flux did not increase due to lack of glucagon effect on substrate supply to the liver. Global gene expression profiling highlighted glucagon-regulated activation of genes involved in cellular respiration, metabolic processes, and signaling, and downregulation of genes involved in extracellular matrix assembly and development.

Racism, structural racism, and the American Association for Anatomy: Initial report from a task force.

In 2021, the American Association for Anatomy (AAA) Board of Directors appointed a Task Force on Structural Racism to understand how the laws, rules, and practices in which the Association formed, developed and continues to exist affect membership and participation. This commentary is the first public report from the Task Force. We focus on African Americans with some comments on Jews and women, noting that all marginalized groups deserve study. Through much of its 130 year history, some members were an essential part of perpetuating racist ideas, the Association largely ignored racism and had some practices that prevented participation. The Task Force concluded that individual and structural racism within the AAA, combined with the broader social context in which the Association developed, contributed to the current underrepresentation of African Americans who constitute 4.1% of the membership even though 13.4% of the U.S. population is Black. Intentional efforts within the AAA to reckon with racism and other forms of bias have only begun in the last 10-20 years. These actions have led to more diverse leadership within the Association, and it is hoped that these changes will positively affect the recruitment and retention of marginalized people to science in general and anatomy in particular. The Task Force recommends that the AAA Board issue a statement of responsibility to acknowledge its history. Furthermore, the Task Force advocates that the Board commit to (a) sustaining ongoing projects to improve diversity, equity, and inclusion and (b) dedicating additional resources to facilitate novel initiatives.

An analysis of anatomy education before and during Covid-19: August-December 2020.

Coronavirus disease-2019 (Covid-19) disrupted the in-person teaching format of anatomy. To study changes in gross anatomy education that occurred during August-December, 2020 compared to before the pandemic, an online survey was distributed to anatomy educators. The 191 responses received were analyzed in total and by academic program, geographic region, and institution type. Cadaver use decreased overall (before: 74.1 ± 34.1%, during: 50.3 ± 43.0%, P < 0.0001), as well as across allopathic and osteopathic medicine, therapy, undergraduate, and veterinary programs (P < 0.05), but remained unchanged for other programs (P > 0.05). Cadaver use decreased internationally and in the US (P < 0.0001), at public and private (P < 0.0001) institutions, and among allopathic medical programs in Northeastern, Central, and Southern (P < 0.05), but not Western, US geographical regions. Laboratories during Covid-19 were delivered through synchronous (59%), asynchronous (4%), or mixed (37%) formats (P < 0.0001) and utilized digital resources (47%), dissection (32%), and/or prosection (21%) (P < 0.0001). The practical laboratory examination persisted during Covid-19 (P = 0.419); however, the setting and materials shifted to computer-based (P < 0.0001) and image-based (P < 0.0001), respectively. In-person lecture decreased during Covid-19 (before: 88%, during: 24%, P = 0.003). When anatomy digital resources were categorized, dissection media, interactive software, and open-access content increased (P ≤ 0.008), with specific increases in BlueLink, Acland's Videos, and Complete Anatomy (P < 0.05). This study provided evidence of how gross anatomy educators continued to adapt their courses past the early stages of the pandemic.

An Analysis of Anatomy Education Before and During Covid-19: May-August 2020.

Coronavirus disease 2019 (Covid-19) created unparalleled challenges to anatomy education. Gross anatomy education has been particularly impacted given the traditional in-person format of didactic instruction and/or laboratory component(s). To assess the changes in gross anatomy lecture and laboratory instruction, assessment, and teaching resources utilized as a result of Covid-19, a survey was distributed to gross anatomy educators through professional associations and listservs. Of the 67 survey responses received for the May-August 2020 academic period, 84% were from United States (US) institutions, while 16% were internationally based. Respondents indicated that in-person lecture decreased during Covid-19 (before: 76%, during: 8%, P < 0.001) and use of cadaver materials declined (before: 76 ± 33%, during: 34 ± 43%, P < 0.001). The use of cadaver materials in laboratories decreased during Covid-19 across academic programs, stand-alone and integrated anatomy courses, and private and public institutions (P ≤ 0.004). Before Covid-19, cadaveric materials used in laboratories were greater among professional health programs relative to medical and undergraduate programs (P ≤ 0.03) and among stand-alone relative to integrated anatomy courses (P ≤ 0.03). Furthermore, computer-based assessment increased (P < 0.001) and assessment materials changed from cadaveric material to images (P < 0.03) during Covid-19, even though assessment structure was not different (P > 0.05). The use of digital teaching resources increased during Covid-19 (P < 0.001), with reports of increased use of in-house created content, BlueLink, and Complete Anatomy software (P < 0.05). While primarily representing US institutions, this study provided evidence of how anatomy educators adapted their courses, largely through virtual mediums, and modified laboratory protocols during the initial emergence of the Covid-19 pandemic.

Effect of 11 beta-hydroxysteroid dehydrogenase-1 inhibition on hepatic glucose metabolism in the conscious dog.

Inactive cortisone is converted to active cortisol within the liver by 11 beta-hydroxysteroid dehydrogenase-1 (11 beta-HSD1), and impaired regulation of this process may be related to increased hepatic glucose production (HGP) in individuals with type 2 diabetes. The primary aim of this study was to investigate the effect of acute 11 beta-HSD1 inhibition on HGP and fat metabolism during insulin deficiency. Sixteen conscious, 42-h-fasted, lean, healthy dogs were studied. Somatostatin was infused to create insulin deficiency, and the animals were treated with a specific 11 beta-HSD1 inhibitor (compound 531) or placebo for 5 h. 11 beta-HSD1 inhibition completely suppressed hepatic cortisol production, and this attenuated the increase in HGP that occurred during insulin deficiency. PEPCK and glucose-6-phosphatase expression were decreased when 11 beta-HSD1 was inhibited, but gluconeogenic flux was unchanged, implying an effect on glycogenolysis. Since inhibition of hepatic cortisol production reduces HGP during insulin deficiency, 11 beta-HSD1 is a potential therapeutic target for the treatment of excess glucose production that occurs in diabetes.

The regulation of AMPK signaling in a natural state of profound metabolic rate depression.

In response to energy stress (and elevated AMP), the AMP-activated protein kinase (AMPK) coordinates the restoration of energy homeostasis. We determined that AMPK is activated in a model system (desert snail Otala lactea) during a physiological state of profound metabolic rate depression (estivation) in the absence of a rise in AMP. Kinetic characterization indicated a strong increase in AMPK activity and phosphorylation in estivation, consistent with an increase in P-Ser428 LKB, an established regulator of AMPK. Accordingly, approximately 2-fold increases in AMPKalpha1 protein and activity were observed with LKB1 immunoprecipitates from estivating snails. In vitro studies determined that AMPK in crude extracts was activated in the presence of cGMP and deactivated in conditions that permitted protein phosphatase type-2A (PP2A) activity. Furthermore, AMPKalpha1 protein and activity increased in PKG immunoprecipitates from estivating tissues, suggesting a novel role for PKG in the regulation of AMPK in vivo. We evaluated several downstream targets of AMPK. Acetyl-CoA carboxylase (ACC) activity was strongly inhibited in estivation, consistent with increased P-Ser79 content, and in vitro stimulation of AMPK negated citrate's ability to stimulate ACC aggregation. Analysis of other targets revealed a strong decrease in PPARgamma-coactivator 1alpha expression in both tissues, which was related to decreased gluconeogenic protein expression in hepatic tissue, but no changes in mitochondrial biogenesis markers in muscle. We concluded that AMPK activation in O. lactea aids in facilitating the suppression of anabolic pathways, without necessarily activating ATP-generating catabolism.

A physiological increase in the hepatic glycogen level does not affect the response of net hepatic glucose uptake to insulin.

To determine the effect of an acute increase in hepatic glycogen on net hepatic glucose uptake (NHGU) and disposition in response to insulin in vivo, studies were performed on two groups of dogs fasted 18 h. During the first 4 h of the study, somatostatin was infused peripherally, while insulin and glucagon were replaced intraportally in basal amounts. Hyperglycemia was brought about by glucose infusion, and either saline (n = 7) or fructose (n = 7; to stimulate NHGU and glycogen deposition) was infused intraportally. A 2-h control period then followed, during which the portal fructose and saline infusions were stopped, allowing NHGU and glycogen deposition in the fructose-infused animals to return to rates similar to those of the animals that received the saline infusion. This was followed by a 2-h experimental period, during which hyperglycemia was continued but insulin infusion was increased fourfold in both groups. During the initial 4-h glycogen loading period, NHGU averaged 1.18 +/- 0.27 and 5.55 +/- 0.53 mg x kg(-1) x min(-1) and glycogen synthesis averaged 0.72 +/- 0.24 and 3.98 +/- 0.57 mg x kg(-1) x min(-1) in the saline and fructose groups, respectively (P < 0.05). During the 2-h hyperinsulinemic period, NHGU rose from 1.5 +/- 0.4 and 0.9 +/- 0.2 to 3.1 +/- 0.6 and 2.5 +/- 0.5 mg x kg(-1) x min(-1) in the saline and fructose groups, respectively, a change of 1.6 mg x kg(-1) x min(-1) in both groups despite a significantly greater liver glycogen level in the fructose-infused group. Likewise, the metabolic fate of the extracted glucose (glycogen, lactate, or carbon dioxide) was not different between groups. These data indicate that an acute physiological increase in the hepatic glycogen content does not alter liver glucose uptake and storage under hyperglycemic/hyperinsulinemic conditions in the dog.

Regulation of global protein translation and protein degradation in aerobic dormancy.

We hypothesized that protein turnover would be substantially suppressed during estivation in the land snail, Otala lactea, as part of a wholesale move to conserve ATP in the hypometabolic state, and that decreased rates of protein synthesis and degradation would be mediated by altering the phosphorylation state of key proteins. Rates of protein translation, measured in vitro, decreased by approximately 80% in extracts of foot muscle and hepatopancreas after 2 days of estivation, and this reduction was associated with strong increases in the phosphorylation of ribosomal factors, eIF2 alpha and eEF2, as well as decreased phosphorylation of 4E-BP1. Reductions in levels of markers of ribosomal biogenesis and a tissue-specific reduction in the phosphorylation state of eIF4E and eIF4GI were also evident after 14 days of estivation. Activity of the 20S proteasome decreased by 60-80% after 2 days of estivation and this decrease was mediated by protein kinase G in vitro, whereas protein phosphatase 2A activated the proteasome. Levels of protein carbonyls did not change in snail tissues during estivation whereas the expression heat shock proteins increased, suggesting that protein resistance to damage is enhanced in estivation. In conclusion, protein synthesis and degradation rates were coordinately suppressed during estivation in O. lactea and this is associated with the phosphorylation of ribosomal initiation and elongation factors and the 20S proteasome.

Benefits of extracurricular participation in dissection in a prosection-based medical anatomy program.

The purpose of this study was to evaluate the extracurricular cadaveric dissection program available to medical students at an institution with a modern (time-compressed, student-centered, and prosection-based) approach to medical anatomy education. Quantitative (Likert-style questions) and qualitative data (thematic analysis of open-ended commentary) were collated from a survey of three medical student cohorts who had completed preclerkship. Perceived benefits of dissection included the hands-on learning style and the development of anatomy expertise, while the main barrier that limited participation was the time-intensive nature of dissection. Despite perceived benefits, students preferred that dissection remain optional. Analysis of assessments for the MD2016 cohort revealed that dissection participation was associated with enhanced performance on anatomy items in each systems-based unit examination, with the largest benefits observed on discriminating items that assessed knowledge application. In conclusion, this study revealed that there are academic and perceived benefits of extracurricular participation in dissection. While millennial medical students recognized these benefits, these students also indicated strong preference for having flexibility and choice in their anatomy education, including the choice to participate in cadaveric dissection. Anat Sci Educ 11: 294-302. © 2017 American Association of Anatomists.

Akt and its downstream targets play key roles in mediating dormancy in land snails.

Estivation, a state of aerobic dormancy, facilitates survival during adverse environmental conditions and is characterized at the molecular level by regulatory protein phosphorylation. The Akt (protein kinase B) signaling pathway regulates diverse responses in cells and the present study analyzes its role in the estivating desert snail Otala lactea. Kinetic analysis (maximal velocity, substrate affinities) determined that Akt was activated in tissues of estivating snails and Western blotting and in vitro incubations promoting changes to Akt phosphorylation state both confirmed that higher amounts of active (phosphorylated Ser473) Akt were present during estivation. Akt protein stability was also enhanced during estivation as assessed from urea denaturation studies. Multiple downstream targets of Akt were differentially regulated during estivation. Estivating animals showed elevated levels of phosphorylated FOXO3a (Ser253) and BAD (Ser136), no change in mTOR (Ser2481 and Ser2448), and reduced amounts of phosphorylated glycogen synthase kinase-3 (GSK-3) beta subunit (Ser9). Kinetic analysis of GSK-3 showed 1.5-1.7 fold higher activities in estivating snails coupled with increased GSK-3 substrate affinities in hepatopancreas. The data suggest an active role for Akt signaling during estivation emphasizing anti-apoptotic actions but uncoupling growth/proliferation actions to help achieve life extension on a limited energy budget.

Advances in medical education and practice: student perceptions of the flipped classroom.

The flipped classroom (FC) approach to teaching has been increasingly employed in undergraduate medical education in recent years. In FC applications, students are first exposed to content via online resources. Subsequent face-to-face class time can then be devoted to student-centered activities that promote active learning. Although the FC has been well received by students in other contexts, the perceptions of medical students regarding this innovation are unclear. This review serves as an early exploration into medical student perceptions of benefits and limitations of the FC. Medical students have generally expressed strong appreciation for the pre-class preparation activities (especially when facilitated by concise, readily accessed online tools) as well as for interactive, engaging small group classroom activities. Some students have expressed concerns with the FC and noted that suboptimal student preparation and insufficient direction and structure during active learning sessions may limit the student-centered benefits. Although students generally perceive that FC approaches can improve their learning and knowledge, this has not been conclusively shown via performances on assessment tools, which may be related to caveats with the assessment tools used. In any case, lifelong self-directed learning skills are perceived by medical students to be enhanced by the FC. In conclusion, medical students have generally expressed strong satisfaction with early applications of the FC to undergraduate medical education, and generally prefer this method to lecture-based instruction.

MedTalks: developing teaching abilities and experience in undergraduate medical students.

OBJECTIVES: According to the CanMEDS' Scholar competency, physicians are expected to facilitate the learning of colleagues, patients and other health professionals. However, most medical students are not provided with formal opportunities to gain teaching experience with objective feedback. METHODS: To address this, the University's Medical Education Interest Group (MEIG) created a pilot teaching program in January 2015 entitled 'MedTalks'. Four 3-hour sessions were held at the University Faculty of Medicine, where first and second year medical students taught clinically oriented topics to undergraduate university students. Each extracurricular session included three 30-minute content lectures, and a 90-minute small group session on physical examination skills. Each medical student-teacher received formal feedback from undergraduate students and from faculty educators regarding teaching style, communication abilities, and professionalism. In addition, medical student-teachers self-evaluated their own teaching experience. RESULTS: Over 50 medical students from the University participated as medical student-teachers. Based on quantitative and qualitative evaluation surveys, 100% of medical students agreed that MedTalks was a useful way to develop teaching skills and 92% gained a greater confidence in individual teaching capabilities, based largely on the opportunity to gain experience (with feedback) in teaching roles. CONCLUSIONS: A program designed to give medical students multi-source teaching experience (lecture- and small group-based) and feedback on their teaching (from learners and Faculty observers, in addition to their own self-reflection) can improve medical student confidence and enthusiasm towards teaching. Future studies will clarify if medical student self-perceived enhancements in teaching ability can be corroborated by independent (Faculty, learner) observations of future teaching activity.