bluuebunny/crossref_metadata_2025 huggingface dataset:
O‐GlcNAcylation of CaMKII in Cardiac Myocytes can be Pro‐Arrhythmic
Authors: Bers Donald
Published: June 2021

We found that high extracellular [glucose] (Hi‐Gluc) increased the activity level of Ca‐Calmodulin dependent protein kinase II (CaMKII) in adult cardiac myocytes, using both traditional biochemical activity measurements as well as a FRET based activation state reporter, Camui. Hi‐Gluc can induce O‐GlcNAcylation (covalent O‐linked β‐D‐N‐acetylglucosamine, GlcNAc) at Ser/Thr residues, and is a ‐translational modification of proteins (often at or near kinase target sites). GlcNAcylation is dynamic and is catalyzed by O‐GlcNAc transferase (OGT) (which is inhibitable upstream by DON) and GlcNAc is removed by O‐GlcNAase (which can be blocked by Thiamet G). Hi‐Gluc‐induced CaMKII activation was blocked by DON, promoted by Thiamet G and isoproterenol (ISO), and also promoted autonomous CaMKII activation (similar to that induced by autophosphorylation and oxidation). Mutation of CaMKII (S279A), adjacent to the known oxidation site prevented Hi‐Gluc –dependent activation, but did not prevent autonomous activation by autophosphorylation or oxidation. Mass spec confirmed S279 as a site of GlcNAcylation, and CaMKII was more highly GlcNAcylated in diabetic hearts and brains (human and rat). Hi‐Gluc caused activation of cardiac myocyte Ca sparks, action potential alterations and cardiac arrhythmias. These effects were prevented by either CaMKII or GlcNAc inhibition (DON) and in genetic CaMKIIδ‐KO mice. This new pathway may be an important pathophysiological synergy between GlcNAcylation and CaMKII signaling relevant in diabetic hyperglycemia.
Specificity and Promiscuity in Small Molecule Binding to Intrinsically Disordered Protein Regions
Authors: Metallo Steven
Published: June 2021

Intrinsically disordered (ID) proteins lack stable secondary and tertiary structure in substantial regions (or throughout) existing instead as ensembles of rapidly fluctuating structures. In eukaryotes, ID proteins are prevalent and are overrepresented in major disease pathways making them desirable targets for inhibition. Given their lack of a stable structure, however, these proteins were not considered potential drug targets. We have determined that short, linear segments of ID proteins are sufficient for specific binding to small molecules and have demonstrated multiple binding sites in the dimerization region of monomeric, disordered c‐Myc. Using mutagenesis of a small‐molecule binding site on c‐Myc, we find that both hydrophobic and hydrophilic amino‐acids are crucial for binding, likely indicating that both hydrophobic interactions and hydrogen bonding contribute to the binding free‐energy. Over half of the residues in the binding site are important for binding affinity, allowing us to provide a model for how specificity can be achieved without structure. To explain the apparent promiscuity of involved in multiple chemotypes binding to the same short stretch of amino acids we provide a model based on different peptide conformations displaying different constellations of functional groups in order to recognize various chemotypes with chemical specificity. The model implies that while specific binding can and does occur, recognition of promiscuous binders is also likely.
Pharmaceutical Control of the Microbiome
Authors: Redinbo Matthew
Published: June 2021

The intestinal microbiota encode millions of genes that represent unique pharmaceutical targets for human diseases from neurological disorders to drug toxicity. We are focused on the role the intestinal microbiota play in reactivating compounds that have been inactivated through glucuronidation in the liver and tagged for excretion. In particular, the chemotherapy drug CPT‐11 (irinotecan) is inactivated by UGTs in the liver and then reactivated by bacterial glucuronidases in the large intestine resulting in dose‐limiting diarrhea. CPT‐11 is part of the FOLFIRI and FOLFIRINOX regimens essential in the treatment of colon and pancreas cancers, respectively. We characterized the structure and function of three glucuronidase enzymes from different bacteria and showed that a key bacterial loop allows for selective inhibition of these enzymes versus human enzyme orthologue. We developed using chemical biology novel inhibitors that potently and non‐lethally inhibit bacterial glucuronidases and alleviate CPT‐11‐induced GI toxicity in mouse models. We also examined the toxicity caused by the nonsteroidal anti‐inflammatory drugs (NSAIDs) diclofenac, ketoprofen, and indomethacin. These drugs has been hypothesized to be reactivated by bacterial glucuronidases, resulting in the longitudinal small intestinal ulcers that cause 40% of NSAID‐associated hospitalizations. We found our inhibitors are also effective against this type of drug toxicity and alleviated intestinal ulcers in mouse models. Thus, we have established that the microbiome contains targets for non‐lethal pharmacological intervention to address acute problems of human health.
Distinct Roles of the Mucus Layer and Microbiota in Conferring Innate Host Defense and Susceptibility to Disease
Authors: Leon‐Coria Aralia , Moreau France , Surette Michael , Chadee Kris
Published: June 2021

The human intestine has approximately 100 trillion microorganisms, mainly bacteria that form the microbiota. These microorganisms play a key role in digestive health as well as in the development of a balanced immune system. The intestinal mucosa is covered by MUC2 mucus that acts as a protective barrier. Alteration in microbiota composition (dysbiosis) and the mucus barrier is common in several gastrointestinal pathologies. The distinct contribution of the microbiota and the mucus barrier play in the pathogenesis of colitis is not well understood. The aim of this study was to determine whether shifts in microbiota could alter the onset and progression of colitis in Muc2 mucin deficient and sufficient mice. F2 littermates Wt (Muc2+/+) and homozygous (Muc2‐/‐) mice were gavaged with antibiotics, fecal transplanted with their littermate stool and susceptibility to dextran sulphate sodium (DSS) was quantified. Fecal samples pre‐ and post‐antibiotic was analyzed by MiSeq lll lluminar sequencing. Intestinal permeability was assessed using FITC‐dextran. DNA analysis showed clear phyla differences in microbiota composition between the two groups of mice. Muc2+/+ mice that received Muc2‐/‐ microbiota were highly susceptible to DSS‐induced colitis and showed increased mortality as compared to controls. As predicted, these animals had higher histopathological scores as compared to Muc2+/+ receiving their own microbiota. Surprisingly, Muc2‐/‐ mice showed no increase/decrease in disease susceptibility receiving Muc2+/+ microbiota. Our results establish that Muc2‐/‐microbiota is highly colitogenic and is capable of exacerbating DSS‐induced colitis in Wt mice with an intact Muc2 layer.

Grant: Crohn's and Colitis Canada
Inhibition of AMPK by Adenylate Kinase 4 Promotes EMT in Lung Cancer through ROS‐dependent Stabilization of HIF1‐α
Authors: Jan Yi‐Hua , Hsiao Michael
Published: June 2021

The field of cancer metabolism has largely focused on the metabolic reprogramming in supporting cancer proliferation. However, the metabolic alterations that are critical for cancer progression remain largely unknown. In this study, we analyzed lung cancer microarray datasets and found a set of metabolic genes that is positively correlated with mesenchymal signature in lung cancer patients. Upstream kinase analysis of EMT‐associated metabolic gene signature predicted AMP‐activated protein kinase (AMPK) inactivation by adenylate kinase may up‐regulate NADPH oxidase which leads to the production of intracellular reactive oxygen species (ROS). We next show TGF‐β‐induced EMT is accompanied by reduced AMPK activity and concurrent up‐regulation of adenylate kinase 4 (AK4) and NADPH oxidase. Knockdown of AK4 was sufficient to suppress TGF‐β‐induced EMT through AMPK activation. On the other hand, overexpression of AK4 inhibits AMPK activation, leading to NADPH oxidase‐mediated production of ROS, which in turn exaggerates HIF1‐α protein expression and induces EMT. IHC analysis showed an inverse correlation between AK4 and phosphorylated AMPK and a positive correlation between AK4 and nuclear HIF1‐α in lung cancer patients. Moreover, patients with high AK4 and low phosphorylated AMPK showed worse outcome compared to patients with low AK4 and high phosphorylated AMPK. Taken together, we identified overexpression of AK4 is critical for lung cancer cells to avoid AMPK‐mediated metabolic checkpoint and undergo EMT.
Control of Lung Cancer with Aspirin‐Triggered Stimulation of Resolution
Authors: Gilligan Molly , Sulciner Megan , Ramon Sesquile , Colas Romain , Huang Sui , Serhan Charles , Panigrahy Dipak
Published: June 2021

Background

Inflammation in the tumor microenvironment is now recognized as a promoter of tumor growth. While substantial epidemiological evidence suggests that the anti‐inflammatory drug aspirin reduces cancer risk, the underlying mechanism remains unclear and toxicity has limited its clinical use. Aspirin increases resolvins ('aspirin‐triggered' resolvins (AT‐Rvs)) in humans, providing a novel pathway to explain the anti‐cancer activity of aspirin. We hypothesize that AT‐Rvs may partially account for the chemopreventive activity of aspirin in lung cancer via novel anti‐inflammatory and pro‐resolution mechanisms.

Results

Flow cytometry confirmed apoptotic/necrotic lung tumor cell debris by cytotoxic chemotherapeutic agents etoposide, cisplatin or with the targeted therapy erlotinib (Tarceva). Cisplatin‐induced Lewis lung carcinoma (LLC) debris stimulated tumor growth in mice in a dose‐dependent manner. AT‐Rvs enhance macrophage phagocytosis of lung tumor cell debris at nanomolar concentrations. To determine whether resolvins could inhibit spontaneous metastasis, we used a well‐established model in which resection of LLC stimulates spontaneous lung metastasis. Resolvins potently inhibited lung metastases and lung weight compared to vehicle‐treated mice.

Conclusions

Aspirin triggers the human body's production of resolvins. AT‐Rvs may provide a novel pathway and molecular mechanism to explain how aspirin reduces cancer risk so broadly.

Research Support: RO1 01CA170549
A Comparison of Team‐Based Learning Formats: Can We Minimize Stress While Maximizing Results
Authors: Miller Cynthia , Falcone Jeff , Metz Michael
Published: June 2021

Team‐Based Learning (TBL) is used at the University of Louisville School of Medicine as a collaborative teaching method in which students solve challenging physiology problems. Students take an Individual Readiness Assessment Test (iRAT), Team Readiness Assessment Test (tRAT), and Individual Summative Assessment Test (iSAT). While educational gains of TBL have been shown, some student evaluations negatively assessed the teaching method with complaints regarding question difficulty and stress levels. Thus, during implementation of TBL in the School of Dentistry, two changes were made: (1) TBL questions were cognitively aligned with unit exam questions (2) Scratch‐off, lottery response cards were used to create a fun, game‐like environment. This revised TBL format, compared to the original TBL format, resulted in similar student performance during iRAT and tRAT sessions. However, the revised, low‐stress format had significantly higher scores on the iSAT (n=119‐161, p<.05). Furthermore, on Likert‐scale surveys, students participating in the revised TBL format subjectively reported higher effectiveness of the learning format, higher levels of perceived fairness, and lower stress levels. These results suggest that the qualitative experience of students, when using a new teaching format such as TBL, may be an important consideration that should be carefully evaluated during implementation.
Teaching Pathophysiology to BSN Nursing Students: Useful Strategies
Authors: Igbo Immaculata , Landson Margie , Straker Kathleen
Published: June 2021

Pathophysiology is essential for nursing practice and is offered either as a prerequisite or core course for most baccalaureate nursing programs. Learning pathophysiological concepts can be challenging for students, due to variety of factors: family obligations; inadequate study habits; lack of prerequisite knowledge of the biological sciences. However, studies have shown that using a variety of engaging teaching strategies, improve student outcomes (Igbo, Landson, & Straker, 2014; Salamonson, Andrew, & Everett, 2009; and Van Horn, Hyde, Tesh & Kautz, 2014).

Consistently, students who were strong in the pathophysiology course were successful on the exit exam used to assess student preparation for the NCLEX. This presentation will discuss active learning strategies: case studies, group presentations, use of immediate response module and online discussions. These strategies increased comprehension and application of the course material as evidenced by improved performance in an exit exam.

Igbo, N., Landson, M. and Straker, K. (2014). Nursing Student Retention Strategy: An Integrated Study Skills Elective. Caputi, L. (Ed.). Innovations in Nursing Education: Building the Future of Nursing, Volume 2. Washington, DC: NLN.

Salamonson, Y., Andrew, S. and Everett, B. (2009). Academic engagement and disengagement as predictors of performance in pathophysiology among nursing students. Contemporary Nurse: A Journal for the Australian Nursing Profession 32(1‐2): 123‐132.

Van Horn, E.R., Hyde, Y.M., Tesh, A.S. and Kautz, D.D. (2014). Teaching pathophysiology: strategies to enliven the traditional lecture. Nurse Educ. 39(1): 34‐7.
Proposal to Poster: A Model for Individualized Inquiry Based Research Projects in the Context of an Undergraduate Physiology Laboratory Course
Authors: Poteracki J , Dunbar R , Wehrwein E
Published: June 2021

Inquiry‐driven learning is a focus of the 2011 Vision and Change Report. A research skill set is important in multiple career paths. It is atypical for undergraduate students to be able to research their own hypothesis, even in a funded lab. We developed a classroom research project to provide this individualized inquiry‐based learning opportunity to all students. As part of a multi‐site trial at Michigan State Univ (MSU) and the Univ of Minnesota Rochester (UMR), students in an upper division physiology course participated in a “Proposal to Poster” project, allowing each student to engage at all levels of the research experience. Students worked in small groups (2‐6) for the first half of the semester to become familiar with available AD Instruments equipment and the scientific method. For the last 9 weeks of the semester, students designed and proposed a unique human physiology research project, wrote an NRSA‐style grant (outline, rough draft, and final draft), recruited subjects, collected/analyzed data over 2‐3 weeks, and presented their human physiology results in a public poster session. After the end of each course, an anonymous survey was given to MSU and UMR students (n=89) using a 5‐pt Likert scale (1 as the worst and 5 as the best). Student satisfaction with this exercise was 4.0 for UMR and 4.5 for MSU. Value of going through the entire process from proposal to poster was 4.1 at UMR and 4.5 at MSU. A common perception of inquiry‐based learning is that individualized independent research is not feasible, although it is highly valued by both students and faculty. Our data demonstrates that this experience is attainable with existing resources, highly valued, and successful across multiple institutions.
Implementation of a Integrated Program in Human Biology
Authors: Golden A , Spicer Diane , Achterman Rebecca
Published: June 2021

Bastyr University launched a new undergraduate program in integrated human biology in 2012. The curriculum is a progressive, premedical curriculum that was created in response to initiatives to improve undergraduate life sciences education including Vision and Change in Undergraduate Biology Education, and Scientific Foundations for Future Physicians:Report of the AAMC‐HHMI Committee. The program emphasizes science process through inquiry‐based laboratories, and requires research methods courses including statistics, critical evaluation of scientific literature, and writing research proposals. Students are also encouraged to complete a research project. To be more representative of the interdisciplinary approaches that are critical to solving problems related to human health, the program includes a sequence of integrated human biology courses that introduce students to multiple levels of biological complexity in the context of body systems. Concepts in physiology, anatomy, cell biology, and biochemistry are introduced and applied to each body system and to body system integration. Although students take some discipline specific courses (e.g. physics), concepts from these courses are applied through the integrated course sequence. The curriculum includes a required bioethics course and elective courses that require students to examine the application of science to world problems. Students have responded positively to the integrated organization of the curriculum, and most students have chosen to participate in research. The program has also been rewarding to faculty who work collaboratively to develop syllabi, class/lab exercises and exams. We believe that this program is a successful response to the call for improvement in undergraduate biology education.
Student Perception of Achievement Influences Student Evaluation of Teaching
Authors: Selsby Joshua , Sterle Jodi
Published: June 2021

Student evaluation of teaching (SET) continues to be commonly used as the sole evaluation tool of teaching effectiveness during departmental evaluations and promotion and tenure packages. The validity of these measures, however, is unclear and alternative factors that influence SET continue to be identified. We tested the hypothesis that the difference between anticipated achievement at the beginning and end of a physiology course impacted SET. To test this hypothesis students were given a survey toward the end of the course that included standard SET questions and questions regarding perceived achievement. For all instances a grade of A was assigned a value of 1 through a value of 5 for an F; SET was evaluated on a scale of 1‐5 where 5 was the best. For statistical tests students giving SET scores of 1‐3 were combined into a single group due to the low number of students giving SET scores in each of those groups. At the beginning of the semester all groups were similar and anticipated earning a B (~2/5). Mid‐semester, the 1‐3 group anticipated earning 3.77±0.29/5.0, which was significantly worse than the 4 and 5 groups, which anticipated earning 2.92±0.13 and 2.58±0.11/5.0, respectively. At the end of the semester all groups were different from each other as students in the 1‐3, 4, and 5 groups anticipated earning 3.23±0.3, 2.35±0.09, and 1.95±0.0.8/5.0, respectively. When evaluating the difference between anticipated performance and perceived final performance the 1‐3 group (‐1.31±0.85) was significantly less than the 4 and 5 groups (‐0.27±0.11 and ‐0.17±0.08, respectively). In total, these data indicate that student perception of performance and perceived differences between expectations at the onset and conclusion of a course have a significant impact on SET. Supported by the Harman Endowment.
Steps for Building a Learning Community in a Medical Physiology Course
Authors: Modell Harold
Published: June 2021

Among the first principles for promoting meaningful learning is creating a safe learning environment (Modell, H.I. FASEB J. 22:767.5, 2008). Building a learning community not only provides a safe environment in which students are willing to take intellectual risks to test their mental models, it provides an environment in which instructors and students work together to maximize learning for the whole community. Community building is a process that begins on the first day of the course and continues throughout the duration of the course. Steps to accomplishing this goal include: 1) Community members becoming acquainted with each other; 2) Setting community learning goals for the course; 3) Establishing behavioral guidelines for the community; 4) Reinforcing the premise that all members of the community contribute to community learning; 5) Providing positive reinforcement for the learning process throughout the course. Examples of activities designed to engage the community in these steps will be presented.
The Profile of Mononuclear Phagocyte Subsets in the Murine Ileum and Mesenteric Lymph Nodes During Intestinal Schistosomiasis Points to a Central Role of CD11c+CX3CR1+F4/80‐ Dendritic Cells
Authors: Alpaerts Katrien , Buckinx Roeland , Cools Nathalie , Nullens Sara , Berneman Zwi , De Winter Benedicte , Van Nassauw Luc , Timmermans Jean‐Pierre
Published: June 2021

Intestinal dendritic cells (DCs) are key regulators of intestinal immune homeostasis. We studied the mononuclear phagocyte (MNP) subsets of the murine ileum and mesenteric lymph nodes in a mouse model of Schistosoma mansoni‐induced inflammation. Intraperitoneally injected, fluorescently labeled S. mansoni‐related antigens, i.e. soluble worm proteins as well as soluble egg antigens, were preferentially taken up by CX3CR1+ and F4/80+ MNPs and not readily observed in other MNP populations. Using a combination of immunohistochemistry and multiparametric flow cytometry, we demonstrated a significant increase in CD11c+CX3CR1+F4/80‐ DCs in the ileal lamina propria and the mesenteric lymph nodes during schistosomiasis. Our results point to an important role of CD11c+CX3CR1+F4/80‐ DCs in the immune response to trematode infection, lending support to the presumed role of these cells as specialized sentinel cells of the intestinal lamina propria.
Protective Effects of Camel Milk on Carbon Tetrachloride induced Hepatoxicity in Wistar Rats
Authors: IHENTUGE CHURCHILL , UGOCHUKWU Chioma , ANIBEZE Chike
Published: June 2021

Camel milk has been deeply studied for its special properties of insulin like, antibacterial and anticancer activities. Twenty adult wistar rats weighing between 150g and 200g were used in the study to determine the protective effective of camel milk on carbon tetrachloride (CCl4) induced hepatoxicity in rats. The rats were divided into 5 groups (A, B, C, D and E) of 4 animals each and were fed with rat feed and water for 30days. Control groups (A and B) were injected intraperitoneally (i/p) with 1ml/kgbw of paraffin oil on the 1st and 2nd days, and in addition group B was fed with camel milk for the remaining days. Groups C and D were injected i/p with CCl4 (1ml/kgbw) for 2 consecutive days and group D fed with camel milk for the remaining period. Group E were fed with camel milk and were injected i/p with CCl4 on the last two days. Results showed a 5.76% decrease in mean body weight of group C significant at p<0.05% while A and B; D and E showed increase in mean body weight of 7.69%, 12.60%, 4.40% and 9.21% respectively. The weight and relative weight of liver of Group C was significantly higher (p<0.05) compared with group A and other groups. The levels of Aspartate aminotransferase(AST), Alanine aminotransferase(ALT) and Alkaline Phosphatase( ALP) of 218.75±18.20, 158.00±33.22 and 429.75±73.01 in group C were significantly higher (p<0.05) compared with control group (88.25±3.64, 63.50±9.22 and 253.25±71.97) while that of groups B, D and E were normal. Histologically the liver showed fatty changes and necrosis in group C while groups A, B, D and E appear normal. This showed that camel milk is capable of preventing and restoring the distortion of liver structure caused by CCl4 and could be used for treatment of hepatic diseases.
Histological Changes in the Pancreas of Streptozotocin induced Diabetic Rats fed with Rind of Citrullus lanatus
Authors: Okechukwu Hope , IHENTUGE CHURCHILL , Ugochukwu Chioma , Anibeze Chike
Published: June 2021

Citrullus lanatus has been used widely in the treatment of disease conditions such as kidney disorders, high blood pressure and impotence. Twenty four Wister rats weighing between 180g and 220grams were used in this research work to determine the histological changes in the pancreas of streptozotocin induced diabetic rats fed with rind of C. lanatus. They were divided into three groups; A, B and C of eight rats each. Diabetes was induced in Group B and C using a single intraperitoneal injection of 65mg/kg of streptozotocin after an overnight fast. Group A served as the normal control while Group B served as the diabetic control. Group C were fed with extract of rind of C lanatus mixed with guinea feed in a ratio of 3:1. All the other animals were given normal guinea feed and water freely. The experiment lasted for 28 days and the animals reweighed. The results showed a 16.21% and 3.80% increase in mean body weight of groups A and C while in group B there was a 13.95% decrease in mean body weight which is significant at p<0.05. Also there was a significant decrease in mean glucose level of group C animals from 350.00±45.64mg/dl to 96.75±1.65mg/dl when compared with group B which was high throughout the experimental period (450.00±23.80 to 288.25±39.44). Histology showed regenerative changes of pancreatic islet cell in group C animals while there was a loss of definite capsule, cell death and atrophy of islets of langerhans in Group B. This showed that the rind of Citrullus lanatus possess some antidiabetic properties considering its hypoglycemic activities and regenerative properties of the islets of langerhans of pancreas
Genistein Treatment Increases Bone Mass in Obese Diabetic Mice
Authors: Michelin Richard , Al‐Nakkash Layla , Broderick Tom , Plochocki Jeffrey
Published: June 2021

Genistein, a phytoestrogen that demonstrates bone‐protective properties, is currently being investigated as a treatment for a number of conditions that affect skeletal health, including type 2 diabetes. Type 2 diabetics have an elevated risk of developing fractures, particularly in bones of the lower limb. Type 2 diabetics also tend to be obese ‐ as many as 85% according to the World Health Organization. This study investigates the effects of genistein treatment on the properties of lower limb bones in obese, diabetic mice. Twenty mice of the ob/ob strain aged 6 weeks were randomly divided into two groups. One group received 600 mg/kg of genistein in their chow for 4 weeks. Comparisons of tibial midshafts show mice treated with genistein have significantly greater diameters and ratios of cortical bone to total tissue area (B.ar/Tt.Ar) than controls (P < 0.05). Evaluation of the proximal tibial growth plate reveals significantly decreased growth plate thickness in genistein‐treated mice, suggesting genistein affects endochondral ossification. Although these initial findings are promising, further study is needed to assess the effects of genistein on fracture risk in type 2 diabetics.
Digital microscopy: a new method for histology teaching
Authors: Romana‐Souza Bruna , Porto Luís Cristóvão , Monte‐Alto‐Costa Andréa
Published: June 2021

The use of digital microscopy combined with Internet facilities has increased in the Histology and Pathology teaching. The aim of this study was evaluated the use of digital microscopy on Histology teaching in the Rio de Janeiro State University. For this, tissue and organ slides were digitalized with Pannoramic Midi (3DHistech, Budapeste). Subsequently, histological structures were identified in the images using Pannoramic viewer (3DHistech). A script was prepared to facilitate the visualization of the image set of each histologic topic by the students. At the end of classes, students answered a questionnaire comparing microscopic based learning lessons to digital microscopy lessons. The digital microscopy was evaluated by 60 dental and 97 medical students from 2013 to 2014. The majority of students (83 percent) found the digital microscopy easy to use, and 89 percent reported that digital microscopy facilitated the identification of the specific structures. A total of 48 percent of students said they learned with digital microscopy more than with microscopic based study. In addition, only 34 percent of students reported that they preferred the microscopic lessons. In conclusion, digital microscopy was found to be evaluated very positively by dental and medical students and may improve learning and productivity in the histology classes

Financial support: Coordination for the Improvement of Higher Education Personnel (CAPES) – Edital Pró‐Ensino em Saúde.
Soft Embalming of Cadaveric Components for Training Purposes
Authors: Sochor Mark , Heltzel Sara , Sikon Dana , Sikon Richard
Published: June 2021

VA State Anatomical Program (VSAP) has developed soft embalming method (modified Thiel) for research & medical training. VSAP soft embalming technique(VSAP SE) accomplishes realistic tissue feel w/out rapid biological breakdown. Cadavers increasing in expense leading to need for extended retention times. Thus there is increased demand for cadaveric components which fulfill educational needs.
Can VSAP soft embalming method be used to embalm cadaveric components (head, arms and legs) from fresh frozen tissue donors.
Frozen cadavers sectioned utilizing reciprocating saw which creates clean tissue plane for identifying the blood vessels for injection of VSAP SE fluid. Cadaveric components allowed to thaw over 2 day period to room temperature. Larger arterial vessels identified in each component and smaller collaterals, etc. were clamped off. VSAP SE fluid introduced into the vessels and component was hand massaged for increased fluid penetration.
VSAP SE components had excellent results of tissue penetration & soft fixation. Head inspected by ENT surgeons & deemed realistic tissue feel. Arms utilized by orthopedic hand surgeons & legs were utilized for private sports industry anatomical dissection & teaching.
Soft embalmed component tissue possible & tissue in this pilot study well received by educators. Multiple educational sessions can be given utilizing same tissue specimen & performance of surgical techniques in step‐wise fashion over several weeks utilizing same component.
Research supported by University of VA Center for Applied Biomechanics internal grant & VSAP SE provided by VSAP
Pilot Study Evaluating Three Light‐embalming Solutions for Preparation of Cadavers for Short‐term Medical Training Courses
Authors: Schmalz Naomi , Challyandra Lucky , Siems Travis , Stark Elena
Published: June 2021

A need for cadaveric tissue that is pliable and more realistic than traditionally embalmed material for teaching and practicing surgical and emergency medical techniques necessitates an embalming technique that elicits life‐like physical characteristics and temporary prevention of tissue decomposition. This pilot study seeks to identify a short‐term “light” embalming technique to produce cadaveric tissue comparable to fresh tissue for usage during week‐long surgical courses. In our pilot study, embalmed cadavers are prepared with one of three different solutions containing varying concentrations of primary embalming agents (Dodge Plasdopake, Aardbalm, and Wessels) and accessory chemicals. Range of motion, rate of decomposition, and resemblance to fresh tissue in surgical practice are being measured blindly on these specimens and un‐embalmed cadavers. Preliminary results suggest that while cadavers embalmed with Aardbalm are rated highest among clinicians in resemblance to fresh tissue, the rate of decomposition is rapid. A solution of both Dodge and Wessels fluids initially shows promise in producing cadaveric tissue that is comparable to fresh tissue in range of motion, tissue consistency, and neurovascular architecture while resisting rapid decomposition. Data collection is ongoing and preliminary findings will be presented in full at the current meeting.
Benefits of Extracurricular Participation in Dissection in a Prosection‐Based Medical Anatomy Program
Authors: Whelan Alexander , Leddy John , Ramnanan Christopher
Published: June 2021

The benefits of cadaveric dissection vs. prosection in medical anatomy education have been extensively debated. The University of Ottawa offers compressed (46.5 lab hours), prosection‐based curricular anatomy education with extracurricular regional dissection electives. This study aimed to characterize benefits related to elective cadaveric dissection. Undergraduate medical students were surveyed in May 2014 regarding motivations and perceived benefits of participation in dissection. The response rate for the survey was 47% (225/478 students). The survey included both Likert‐style items and open‐ended items, which were qualitatively analyzed for emerging themes. We then characterized dissector (DIS) and non‐dissector (NON) student academic performance. The majority of students (70%) participated in at least one dissection elective. The primary motivation for, and benefit derived from, this elective was related to perceived enhancement of clinically relevant anatomical knowledge. Relative to NON group, performance of the DIS group was significantly greater (P<0.001) on practical examinations (+5%), anatomy‐related items (+7%) and discriminating anatomy items (+9%) that typically assessed knowledge application. Finally, performance along these assessment metrics generally was enhanced when students participated in multiple electives. Our results show that dissection electives were valued by the majority of medical students and were perceived to address curricular deficits in clinical anatomy knowledge. Dissection participation had a significant impact on student examination performance, with the largest impact observed on discriminating items related to anatomical knowledge application.
Subject Specific Cross Word Puzzles Were Effective Active Learning Tools
Authors: Svoboda Kathy , Ruest L‐Bruno , Spears Robert , Roeche Darren , Opperman Lynne
Published: June 2021

The purpose was to use lecture specific cross word puzzles to increase active learning activities. The puzzles were used in General Histology, Oral Histology, Mechanisms of Development, Dental, Medical, and Applied Pharmacology. All puzzles were developed by faculty members with Discovery Education Puzzle Maker. Course directors used the puzzles in different ways. A survey was developed and approved by the IRB (#2014‐0630‐BCD EXM) to assess the student's opinions. Survey Monkey surveys were sent to 517 individuals and 32% responded in the first week. All responses were confidential and anonymous. The dental classes had the highest response rate (36 D1, 40 D2, 30 D3, 27 D4, 12 Graduate Students, and 16 Residents). The students agreed or strongly agreed with the following survey questions: I initially thought the puzzles were a good idea >60%; The crossword puzzles helped me learn/study the material associated with each puzzle >80%; I used crossword puzzles as a resource for studying for exams >85%; The puzzles helped me focus on the topic >80%. The students were either favorable or neutral on the statement: I learned more in class because of the crossword puzzle and they strongly disagreed that the puzzles were too difficult. More of the D1 students wanted the puzzles to be mandatory and graded than the upperclassmen. The residents and graduate students were in favor of the puzzles being voluntary and not graded. In conclusion, we found that the students thought that the crossword puzzles were a good way to help learning, but most didn't want them to be mandatory and graded. Future studies could compare the puzzles to other active learning tools or determine if the students that completed the puzzles had a deeper or better understanding of the material.
Contextualizing Basic Science, Preclinical, and Clinical Concepts via Adaptive Multimedia Networks: 'BlueLink,' a Novel Approach to Interdisciplinary Education
Authors: Fox Glenn , Alsup Kathleen
Published: June 2021

Two issues affecting the efficacy of higher education are: (a) a dearth of genuine context to help students relate information as it is acquired and assimilated, and (b) relatively low levels of student participation in reading print texts. While these issues are related, a solution for one may not necessarily ameliorate the other. To help solve these issues we are developing BlueLink, a portal that dynamically networks and tailors multimedia (images, videos, screencasts, assessment modules, etc.) to the individual learner. The navigator is not live, but a wealth of materials are developed. We are testing these materials with a M1 audience at the University of Michigan and assessing their effectiveness. Results indicative a strong positive correlation between BlueLink material usage and student success.
Facilitating OT and PT Graduate Student Laboratory Participation, Preparedness, and Professionalism in a Compressed, Intensive Gross Anatomy Dissection Course Series
Authors: Theiss Renee
Published: June 2021

Adjusting to the rigors and pace of a graduate health professional program can be a challenge for both new graduate students and their instructors. At our university, students in the Masters in Occupational Therapy (MOT) and Doctorate in Physical Therapy (DPT) programs take a Human Gross Anatomy Lecture and Dissection Laboratory course series in two six‐week sessions in the first semester of their first year. For many students, this course series is their first introduction to graduate level education. Each week, students attend 9‐hours of lecture and 8‐hours of cadaver dissection lab. For lab dissections, students of both programs are together in groups of 4‐6 students per cadaver. The fast pace of this course necessitates that students prepare and participate in each day's dissection and act collegially toward their inter‐professional lab partners. To achieve these goals, I devised a method to facilitate student's active participation in their learning by guiding their pre‐lab study and outlining lab group interactions. This method involves defining and scripting five areas of participation/collegiality, promoting equal participation by rotating dissection lab roles, and assigning a pre‐lab “homework” assignment. At the end of each course in the series, students may evaluate their group‐mates in these five areas. The instructors also evaluated each student. Overall, having scripted and expressly written expectations of active participation as well as collegial and professional interactions through guided preparation enhanced students' experiences, learning, and professional interactions in the Human Anatomy Dissection Laboratory.
A salamander model for atrial septal defects and cardiopulmonary evolution
Authors: Lewis Zachary , Hanken James
Published: June 2021

Congenital atrial septal defects (ASDs) rank among the three most common birth defects in humans. However, the proportion of ASDs with a known genetic basis is small. New methods, models and systems for studying ASD are needed to further our understanding of its etiology and to develop possible treatments. We demonstrate that salamanders offer an effective model for studying ASD. Surprisingly, most salamander species have no lungs. By making 3‐D reconstructions of a broad sample of salamander species, both lunged and lungless, we resolve the morphology of the atrial septum in lungless salamanders. These lungless salamanders naturally display heart morphology that resembles ASDs in humans. Transcriptome sequencing provides evidence that pleiotropic genes control both lung development and atrial septum formation in the same species. Alterations in expression of these genes may result in lung loss as well as morphological changes in the atrial septum. Lungless salamanders provide a useful model of ASD and offer insight into the evolution and development of the cardiopulmonary system.
Differential Lectin Binding in Giant Danio, Goldfish, and Zebrafish hearts
Authors: Lafontant Pascal , May Adam
Published: June 2021

Lectins are carbohydrate‐binding proteins commonly used in the study of mammalian cells and tissues. However lectins have received little use in fish models. Here, we determine the binding patterns of three commonly used lectins: wheat germ agglutinin (WGA), Ulex europaeus agglutinin (UEA lectin), Bandeiraea simplicifolia lectin (BS lectin), in giant danio (GD), zebrafish (ZF), and goldfish (GF) hearts. Our results show that WGA stained cardiac myocyte borders of all three fish in patterns similar to that seen in mammalian hearts, with staining markedly stronger in the fish compact hearts. By contrast, UEA lectin, an endothelial cell marker in mammalian vascular beds, showed little to no binding to the coronary vasculature of these fish. Interestingly, BS lectin reacted poorly to the zebrafish coronary vasculature similar to our previously reported study in the goldfish. However BS lectin strongly stained coronary vessels of the Giant danio. Importantly, BS lectin biding was particularly strong in the vascular endothelium compared to endocardium of the Giant danio. This differential regional staining allowed for coronary angiography of the Giant danio heart and 3D reconstruction by confocal and light sheet fluorescence microscopy. In addition we were able to quantify coronary revascularization following cautery injury and during repair and regeneration of the Giant danio heart. Our results demonstrate that lectins differentially bind to coronary vasculature of fish and can be used as simple but powerful tools for the study of adult and regenerating fish hearts.
Age‐related Changes in Endothelial Ca2+ Signaling Revealed by Imaging from Inside Arteries at Normal Physiological Pressures
Authors: Wilson Calum , Saunter Christopher , Girkin John , McCarron John
Published: June 2021

Aging is the summation of many, mostly invisible, but deleterious changes associated with altered structure and function of the cardiovascular system. Age‐induced impairment of endothelial function contributes to and reinforces the changes that occur in vascular disease. Normally, the endothelium transduces multiple chemical and mechanical signals into changes in cytoplasmic calcium (Ca2+) concentration that control vascular function. Thus, understanding age‐related functional changes in the endothelium requires an appreciation of Ca2+ control. We developed a wide‐field, gradient‐index (GRIN) fluorescence imaging system to visualize the endothelium from within the lumen of intact, pressurized arteries. The GRIN system enables rapid imaging of a 500 μm diameter area of the curved endothelial surface (~200 endothelial cells; ECs) with subcellular resolution. We also developed a semi‐automated data extraction procedure to quantify signal dynamics in the individual ECs loaded with fluorescent Ca2+ indicators. In the carotid artery of young rats (3 months), acetylcholine (ACh) evoked endothelial Ca2+ signals that were suppressed as intraluminal pressure increased. In aged rats (18 months) the pressure‐dependent suppression of ACh‐evoked Ca2+ signaling and the frequency of ACh‐evoked intracellular Ca2+ oscillations were reduced, whilst the temporal propagation of Ca2+ signals increased. Significantly, dose response measurements revealed that aging increased EC sensitivity to ACh, yet had no effect on the magnitude of the Ca2+ response in each cell. We propose that such alterations in EC Ca2+ signaling may manifest as a loss of functionality, and explain endothelial dysfunction in aging.
Loss of axin2 in murine aortic valves leads to myxomatous disease
Authors: Hulin Alexia , Alfieri Christina , Yutzey Katherine
Published: June 2021

In the older population, calcific and myxomatous valve diseases are the two main heart valve diseases. Mechanisms involved in aortic valve calcification are similar to bone formation while myxomatous valves display cartilaginous features with proteoglycan accumulation and increased chondrogenic markers; Sox9, Hapln1 and aggrecan. Similarly, increased Wnt/β‐catenin signaling is measured in calcific aortic valve while loss of Wnt/β‐catenin signaling promotes chondrogenic differentiation in aortic valves. This indicates a major role of Wnt/β‐catenin signaling in heart valve homeostasis although underlying mechanisms are still poorly understood. To further investigate the role of Wnt/β‐catenin signaling, we analyzed heart valves from mice deficient in axin2, a negative regulator of β‐catenin. X‐gal staining performed on Axin2‐lacZ knockout mice (KO) indicates that axin2 is expressed in endothelial and interstitial cells in adult heart valves. At 2 months, KO mice demonstrate thickened proteoglycan‐rich aortic valves with increased Sox9 and Hapln1 expression while focal aggrecan‐rich areas are observed in 4 months old KO mice. Surprisingly thickened aortic valves do not calcify as indicated by lack of alizarin red staining in 1 year old KO mice. These markers are consistent with increased chondrogenic features observed in human myxomatous mitral valves. Interestingly, melanocyte accumulation also is observed in thickened aortic valve, suggesting that axin2 regulates neural crest cells contribution to heart valves. Altogether these data indicate a role for axin2 in heart valve homeostasis and in myxomatous disease. Ongoing in vivo and in vitro studies are investigating the specific functions of axin2 in valve diseases mechanisms.
Scleraxis: A Novel Transcriptional Regulator of Cardiac Fibroblast Function and Phenotype
Authors: Bagchi Rushita , Roche Patricia , Schweitzer Ronen , Czubryt Michael
Published: June 2021

The cardiac extracellular matrix (ECM) plays a crucial role in maintenance of mechanical integrity, initiation of biochemical signaling and facilitation of intercellular communication in the myocardium. Increased ECM production due to chronic stress impairs cardiac function leading to heart failure. Our laboratory has previously reported that the transcription factor scleraxis (Scx) directly regulates collagen 1α2 gene expression in primary cardiac fibroblasts, and is up‐regulated in response to TGF‐β signaling and in post‐infarct scar tissue. Here we examined the regulatory role of Scx in basal ECM synthesis in vivo. Scx null hearts exhibited a significant reduction in fibrillar collagens, proteoglycans and matrix metalloproteinases. Exogenous Scx gene delivery was sufficient to rescue these down‐regulated target genes in cardiac myofibroblasts derived from Scx null mice. Gain and loss‐of‐function studies in cardiac proto‐myofibroblasts resulted in a significant upregulation or downregulation of fibroblast phenoconversion markers. Scx caused a direct transactivation of the α‐smooth muscle actin (αSMA) gene promoter, increasing synthesis of αSMA+ stress fibers and contractility. Interestingly, the ECM‐producing DDR2+ fibroblasts were significantly reduced in null hearts due to altered fibroblast development as demonstrated by decreased mesenchymal and increased epithelial marker gene expression. These findings collectively support Scx's novel role as a required regulator of cardiac fibroblast function and phenotype thus providing a rationale for development of anti‐fibrotic drugs targeting scleraxis.