Integrating Disease Presentations with Community Engagement in a Human Physiology Class

The Master of Science in Oral Health Sciences (OHS) at Boston University Chobanian & Avedisian School of Medicine is designed for students who wish to improve their academic preparedness for dental school admission. Oral Health Sciences students take some courses, including the first-year Dental Physiology course, alongside dental students at Boston University Henry M. Goldman School of Dental Medicine (GSDM). Since students in the OHS program often struggle in the largely lecture-based Dental Physiology course, we developed a case/problem-based and teamwork-focused Applied Physiology course. This course has run parallel to the Dental Physiology course the past two fall semesters. The primary goal of the Applied Physiology course is to provide additional instruction and academic support and to present course material in a team-based learning mode for the OHS students. We hypothesized that this approach to learning physiology would help to improve student mastery of physiology content critical to their future success. The objective of the current study was to assess the effectiveness of the new Applied Physiology course in enhancing OHS students' motivation and academic performance in the Dental Human Physiology course. We are evaluating the benefits of this course by comparing Dental Physiology final grades and individual exam grades between dental students and OHS students from 2018 to 2023. In addition, we are comparing course performance for OHS students from previous class years (2018 to 2022) who did not take the Applied Physiology course against students from the past two academic years who took the course. When we tested whether the difference in means between dental students and OHS students in 2023 was different than between groups prior to 2023, we found that dental students scored 5% higher on average than OHS students before 2023. In 2023, however, dental students only scored 1% higher than OHS students. We also tested whether the pattern of mean scores over time differed between dental and OHS students. Dental student scores remained relatively stable from 2018-2023, while OHS student scores decreased and increased over time. Analysis and comparisons for individual course exams for the dental and OHS students are ongoing. In addition, analysis of a validated survey containing Likert-style questions to quantify how the new course enhances motivation, engagement, and perceived benefits of student learning is underway. Based on feedback from students who took the course in the first year, faculty have modified the in-class sessions in the second year of the course slightly to include more practice exam questions. Our results indicate that additional team and case/problem-based support can improve academic performance for students hoping to gain admission to Dental School. Graduate Medical Sciences at Boston University Chobanian & Avedisian School of Medicine This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

A typical college-level human physiology course surveys a breadth of physiological topics. Students are expected to demonstrate an understanding of organ system functions from the molecular to the organismal scale as well as an understanding of how interactions between organ systems produce integrated functions. Concept maps are learning tools that help students make connections between seemingly disparate concepts, like physiological processes occurring at different scales and interactions between different organ systems. The purpose of this study was to compare exam scores of students who attended a review session with concept mapping to those who attended a review session without concept mapping, as well as to assess the perceived exam preparedness of students who attended an exam review and those who did not attend an exam review. We hypothesized that the addition of concept mapping during an exam review session would improve average student exam scores and that students who attended a review session would report that they were better prepared for the exam.The concept map intervention was implemented as part of each exam review session for two in-person offerings of a large enrollment intermediate level human physiology course (n=747 students) in 2021–22 at a large public research university. Control exam performance data was collected in the same course without the concept map intervention as part of the exam review sessions for two in-person offerings (n=807 students) during 2017-18. The intervention groups’ exam review sessions consisted of 30 minutes of concept mapping followed by 20 minutes of a student question and answer session. The control groups’ exam review sessions consisted of 50 minutes of a student question and answer session. After each exam, students were asked to report the grade they expected to earn on the exam (A, B, C, D or F) as a measure of their level of exam preparedness. A student’s t-test was used to determine significant differences between exam scores of students in the intervention and control group. Data are presented as mean exam score (%)±SD.Overall exam scores in the control group (80.4±11.7) were significantly higher than the experimental group (78.75±11.8, p=0.007). Of the students who participated in the survey, 2,228 participated in the exam review and 543 did not. Perceived exam preparedness are as follows for groups that attended the exam review (expecting A:25%, B:55%, C:18%, D:2%, F:0%) and those who did not attend (expecting A:20%, B:49%, C:23%, D:4%, F:2%).The overall exam scores from the control group were higher than the experimental group. This suggests that adding concept maps to the review session did not improve exam scores. There may be confounding factors affecting exam scores (ex: transitioning to an in-person setting after the global pandemic). More research needs to be done to understand the impact of including concept map exercises in exam review sessions on student exam performance. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Background: Completing multiple choice questions are a fact of life for undergraduate students. MCQ exams are necessary to evaluate large size classes of 100 or more students. MCQ testing skills are questions is useful information to advise students on how to alter their test taking approaches for greater success. Purpose: This study is a secondary analysis of data collected during the 2015-2016 academic year a two semester Clinical Physiology course series. In this course series, students wrote reflective essays after taking two stage collaborative exams. The purpose of the original study was to determine if reflective writings would improve student exam scores. The purpose of the secondary analysis was to characterize student approaches to individual and collaborative exams consisting of multiple-choice questions. Methods: Students were asked to write essays on three exam questions after taking a two-stage collaborative exam. In a two-stage collaborative exam, student complete an exam individually and then complete the same exam in a group; students discuss each question until they reach consensus on each answer. For their reflection assignment, student chose 3 challenging questions and wrote about how they choice their individual answer, how their group reached the group answer and any insights they learning about testing process. Students’ writings were organized into individual thought processes, group thought processes and any thought processes. The entire corpus of the writing was read as a whole. Then the investigators assigned the following themes to the texts: individual approaches, types of mistakes and group approaches. Results: The most common way students chose their individual answers were 1) recall, 2) process of elimination, 3) gut reactions and 4) reasoning with basic principles. Common types of mistakes include answer based on a misconception, miscomprehension of the question, math or unit errors and conflicts between clinical experience and basic science principles. Students benefited from group discussions because group members were able to reframe a question, supply a missing piece to the solution or explain the mechanism of a physiological process. Students discover their own misconceptions and correct them immediately after an individual exam. As a result, a group of students can score higher on an exam than any individual students. However, groups did not always use mechanistic reasoning or basic principles. Often students resorted to voting on the most popular answer or choosing an answer advocated for by a confident student. Conclusion: Collaborative exams are beneficial to students because they are exposed to different ways of problem solving and reasoning in way that allows students if identify their own misconceptions and engage in deep learning with peers. However, students often use combinations of process of elimination and recall to answer questions. These results suggest an opportunity to encourage students to use basic science principles and mechanistic reasoning on exams for improved testing outcomes. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

G protein-coupled receptors (GPCRs) are the largest class of proteins in the human body and are considered to be excellent targets for drug discovery. However, the vast majority of GPCRs are understudied. Using a large-scale TaqMan array screen on both male and female C57BL6 murine livers, we identified GPR17 as a highly expressed orphan receptor within the liver (ΔCt = 20.23, normalized to GAPDH). Hepatic expression of Gpr17 was confirmed using reverse transcriptase polymerase chain reaction (RT-PCR) and was also identified in murine whole kidneys from both males and females. While GPR17 has known roles in oligodendrocyte maturation and myelination in the central nervous system, its functions within the liver and kidney remain unknown. To investigate its physiological functions in respective tissues, we started by uncovering GPR17’s localization pattern, ligand profile, and signaling mechanism. Using custom RNAScope in-situ hybridization probes, we found Gpr17 mRNA expression within hepatocytes and cortical nephron segments of the kidney. RNAScope colocalization studies using lotus tetragonolobus lectin (LTL) as a proximal tubule marker revealed robust cortical Gpr17 mRNA expression within both LTL+ and LTL- nephron segments. Additionally, ongoing subcellular localization experiments using Alpha mouse liver 12 (AML12) and Madine-Darby canine kidney (MDCK) cell lines will shed light on GPR17 tissue-specific expression within subcellular departments. To screen for potential ligands, we cloned Gpr17 into flag-tagged PME18s and Presto-Tango vectors. Live-cell surface labeling of HEK293T expressing the GPR17 constructs confirmed surface expression facilitating ligand screening. GPR17 downstream signaling has yet to be studied. Thus, we used the PRESTO-TANGO assay, an exogenous chemical ligand screening assay that relies on a luminescence readout to indicate -arrestin recruitment and receptor activation. A large, non-biased chemical screen of over 500 physiological compounds was tested for activation of GPR17. To date, we identified seven exogenous activators of GPR17. Additionally, literature suggests that synthetic MDL29,951 (MDL) and endogenous oxysterols function as GPR17 ligands. To determine GPR17 signaling mechanisms, we employed Dual Luciferase cAMP-based reporter assays. On their own, GPR17 ligands did not induce a rise in intracellular cAMP. However, when cAMP levels were elevated via forskolin treatment alongside ligand administration, GPR17 activation resulted in a significant reduction of intracellular cAMP, suggesting that GPR17 signaling is coupled to the Gi pathway. Results confirmed MDL and select oxysterol ligand behavior and indicated the utilization of a Gi signaling mechanism by hepatic and renal GPR17. Ongoing bioluminescence resonance energy transfer studies using compact ONE vector G-protein Optical biosensors are aimed at confirming GPR17’s coupling to the Gi pathway. NIH This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

The Master of Science in Medical Physiology program at the Medical College of Georgia, Augusta University was designed to improve the academic readiness and application competitiveness of students seeking admission to medical and dental school programs, ultimately enriching and diversifying the respective applicant pools. The 30-credit, course-based program establishes a strong foundation of knowledge in human physiology, which underpins the field of medicine. More than half of the credits in the program are in medical physiology and pathophysiology, which serves to establish a solid foundation in medical physiology upon which students will build their pre-clinical medical or dental school knowledge upon matriculation. In similar programs at other institutions, students sit in medical school physiology lectures. In contrast, students in the Master of Science in Medical Physiology program receive instruction by medical school faculty delivered in an extended class format, providing additional opportunities for content reinforcement and student engagement. To accomplish the goal of improving academic readiness, the program curriculum utilizes evidence-based best practices for learning. Frequent no- and low-stakes formative assessments provide opportunities for active recall to improve content reinforcement and to prioritize mastery over memorization in preparation for summative assessments. Case-based learning and in-class interactive lab activities using Lt sensors (Lt by ADI Instruments) provide opportunities for scaffolding and integration of content. Self-directed learning using Lt assignments and activities provide opportunities for interleaving and spaced retrieval of content. Currently in its third cohort of students, the Master of Science in Medical Physiology program at the Medical College of Georgia establishes a strong foundation of knowledge in medical physiology while providing students targeted academic support to facilitate their development into stronger, and more confident learners. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Ca2+ signaling in metanephric mesenchymal (MM) cells contributes to key pattern forming events including branching morphogenesis in the embryonic rat kidney (Fontana et al., FASEB J, 2019). We previously reported that basolateral exposure of tubular structures isolated from MM-derived kidney organoids to the PIEZO1 channel agonist Yoda1 elicited a maturation stage-dependent elevation of intracellular Ca2+ concentration, [Ca2+]i (Carrisoza-Gaytán et al., AJP Cell Physiol, 2023). The aim of our current study is to explore whether tubular cells in human iPSC-derived UB and CD organoids exhibit similar developmental increases in PIEZO1 function.To investigate this, tubular structures from UB and CD organoids cultured for 34-35 or 61-65 d (4 tubules/group; n=38-40 cells/group) are loaded with the Ca2+-sensitive fluorophore Fura2-AM to measure [Ca2+]i before and after basolateral exposure to Yoda1 (5 µM). Baseline [Ca2+]i was 108.5±3.6 nM across all tubular cells studied, with no differences detected between UBs and CDs or days in culture. Subsequent exposure to Yoda1 induced an increase in [Ca2+]i and appearance of Ca2+ oscillations. The Yoda1-induced [Ca2+]i signals of individually identified cells are then subject to spectral analysis using the multitaper method along with a harmonic F-test to identify predominant frequencies in the signal. We found that with advancing days in culture from 34-35 to 61-65 d: (i) Yoda1 induced an increase in [Ca2+]i in UBs from 45.3±18.5 to 275.6±43.7 nM (p≤0.001) and in CDs from 61.7±16.1 to 254.3±56.2 nM (p≤0.001), (ii) the proportion of cells exhibiting Ca2+ oscillations increased in UBs from 70 to 83% and in CDs from 75 to 84%, and (iii) the predominant oscillatory frequency fell by 50% in UBs and 30% in CDs from 15 mHz. These observations suggest that kidney organoids undergo a developmental increase in PIEZO1 abundance/activity and maturation of Ca2+ signal transduction pathways, especially those involved in Ca2+ oscillatory activity. Decoding Ca2+ oscillations may unveil molecular mechanisms underlying maturation/differentiation. This work was supported by the NIH Re(Building) a Kidney Consortium (NIH UC2DK126023) and the Welcome LEAP Human Organs, Physiology and Engineering (HOPE) program. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Background: In the United States over 10% of all neonates are born premature (less than 37 weeks gestational age) and many face complications, such as necrotizing enterocolitis (NEC). NEC is the most deadly gastrointestinal disease in preterm neonates with up to 50% mortality. Survivors face life-long complications. NEC is a multifactorial disease caused by 1) intestinal immaturity, including a poorly developed physical barrier between luminal contents and the rest of the body; 2) an exaggerated immune response; and 3) intestinal dysbiosis, which together can result in irreparable damage to the intestine. Since there is no cure for NEC, prevention is the best strategy. Enhancing our understanding of intestinal epithelial cell (IEC) barrier regulation during early development will provide novel therapeutic targets to prevent NEC. Published evidence indicates roles for the RNA-binding protein insulin-like growth factor 2 mRNA binding protein 1 (IMP1) in intestinal development, barrier function, and intestinal repair. Sequencing data from the inflamed tissue of a NEC patient indicates that IMP1 is down-regulated relative to uninflamed tissue. Notably, roles for IMP1 in NEC are not defined. Emerging evidence suggests that mucus complexity, governed by enzymes such as Qsox1, impacts intestinal barrier function and inflammation susceptibility. This study aimed to define the role of IMP1 in NEC pathogenesis using a model of NEC-like intestinal injury in mice with IEC-specific Imp1 overexpression or Imp1 loss. Hypothesis: IMP1 expression is protective in a mouse model of NEC-like intestinal injury. Methods: All studies are OHSU IACUC-approved. This study used: wild-type (WT, control), Imp1 IEC-knockout ( VillinCre;Imp1 fl/fl ; Imp1 Δ IEC ), and Imp1 IEC-overexpression ( VillinCre;lslFLAG-Imp1 OE ; Imp1 IEC-OE ) mice. At post-natal day 4 mice of both sexes were randomly assigned to control or NEC groups. The control mice remained with the dam. NEC was induced with the well-established experimental NEC-like intestinal injury model. Mice were separated from the dam and maintained for 72 hours in an incubator. Pups were gavage-fed NEC formula (mixture of infant formula, puppy replacer, 1:10 dilution of bacteria derived from a premature infant with NEC, and 2.5 ug/g body weight of lipopolysaccharide) every 3 hours from 7am-10pm. Twice daily the pups were exposed to hypoxia (5% oxygen). After 72 hours, tissue was collected for histology, gene, and protein expression analyses. Survival was assessed with Kaplan-Meier curves. Total RNA sequencing was performed using the NovaSeq S4. The mucus and tissue barrier were evaluated by immunofluorescence staining for mucin 2, mucus lectins, occludin, and E-cadherin. Statistical analyses were performed using 2-way ANOVA with Tukey’s test for multiple comparisons and the Mantel-Cox log-rank test for survival analysis. Results: The NEC model induces pneumatosis, histological damage, and a significant up-regulation of inflammatory cytokine gene expression Lcn2 and Il1 b in all three genotypes, p <0.05, n=5-15. Despite damage, Imp1 IEC-OE mice survive 2-times better than WT or Imp1 Δ IEC mice (survival for WT: 27.8%, n=36; Imp1 Δ IEC : 31.6%, n=19; Imp1 IEC-OE : 60%, n=10 mice, p<0.05). RNA-sequencing data indicates that Imp1 IEC-OE mice significantly up-regulate expression of the disulfide catalyst Qsox1 (In NEC: WT: 1077 ± 94.6, Imp1 Δ IEC : 1017 ± 12.75, Imp1 IEC-OE : 1446 ± 45.73, p=0.003 vs WT and p=0.002 vs Imp1 Δ IEC ). Conclusion: Our data suggest that Imp1 expression enhances survival in a mouse model of NEC and promotes expression of a disulfide catalyst Qsox1, which may promote mucus maturation and protect the neonatal small intestine. NIH K01DK129401, R01HD097367, the Gerber Foundation, the OHSU Knight Cancer Institute This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Glomeruli number and glomerular volume are indicators of kidney health and chronic kidney disease (CKD) progression. Low nephron number is predictive of the development of CKD, and increased glomerular volume is associated with hyperfiltration and hypertension. Accurate estimates of glomeruli number are necessary for relating whole body GFR to single nephron GFR (SNGFR) which is an important parameter for mathematical modeling of transport along the nephron. In addition, previous studies had observed larger volumes and greater SNGFR in juxtamedullary glomeruli compared to cortical glomeruli. To enable routine estimation of cortical glomerular density and the size of cortical and juxtamedullary glomeruli, we optimized a cost- and time-effective method for labeling and imaging glomeruli in mouse models. Mice were injected with Alexa fluor 647 conjugated wheat germ agglutinin (WGA-647; 0.5 mg) intracardially. After 4 minutes circulation time, kidneys were perfusion fixed and harvested. Kidneys were sectioned at the midline at 600 µm up to 999 µm and cleared with ethyl cinnamate. Cross sections were imaged on Leica Sp8 with either 10x or 25x objective and 15 µm z-step size. This method enabled visualization of perfused glomerular capillaries and kidney vasculature. The cortical region was identified based on autofluorescence (488 nm laser). Individual glomeruli were identified and counted by automated 3D segmentation in Python. The diameters of individual glomeruli were measured in higher magnification images using Leica LAS X software. Juxtamedullary glomeruli were identified as those within the inner third of the cortex, nearest the medulla. On average, juxtamedullary glomeruli had larger diameters compared to cortical glomeruli. However, the extent of WGA-647 perfusion within individual glomeruli varied along the interlobular vessels. Including heparin (500 U/L) in the WGA-647 injection resulted in better filling or perfusion of glomeruli, especially in the superficial cortex, and as a result the estimated average glomerular diameter increased. In future, this methodology will be applied to compare cortical glomerular density and average glomerular volume in male and female mice and in genetic kidney disease models. National Institutes of Health T32 DK007052, R01 DK125049, U54 DK137329 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Introduction: Skeletal muscle regeneration is an energy-demanding process that relies on mitochondria to generate ATP. While healthy skeletal muscle fibers have organized interfibrillar mitochondrial networks organizing architecture segregated into columns along the Z-line of the myofiber, regenerating fibers exhibits altered mitochondrial networks that span several sarcomeres. Despite links between muscle regeneration and altered mitochondrial dynamics and biogenesis, the role of specific cells in remodeling these networks remains unclear. Because muscle stem cells (MuSCs) play a critical role in muscle regeneration, we explored the relationship between MuSCs and mitochondria in regenerating muscle fibers. Methods: To induce muscle regeneration, we used the hindlimb ischemia mouse model of peripheral artery disease (PAD) and the mdx mouse model of Duchenne’s muscular dystrophy (DMD). Furthermore, transgenic reporter mice such as Pax7-tdTomato, H2B-EGFP, and mitoDendra2 were used to mark MuSCs, track nuclei, and label mitochondria, respectively. Fluorescently labeled MuSCs were also transplanted into BaCl 2 -injured muscle to elucidate their behavior and interactions throughout muscle regeneration. Immunofluorescence, single fiber staining, and biochemical assays from harvested muscles were performed for data analysis. Results: Following injury, a significant increase in the number of endogenous MuSCs was observed 7 days post-injury compared to contralateral control, while a dramatic increase in the fusion of MuSCs into myofibers was noted at days 14 and 28. Interestingly, all fused myofibers at days 14 and 28 displayed central nucleation, a hallmark of regeneration that fusion of the MuSC is critical for myofiber regeneration. Primary MuSCs from H2B-EGFP reporter mice were isolated and transplanted into the injured muscle to determine the origin of the centrally located myonuclei. In myofibers where the transplanted MuSCs had fused, centrally located myonuclei were GFP + , indicating their origin from MuSCs. Surprisingly, regenerating muscle fibers isolated from the mitoDendra2 mouse model exhibited high densities of mitochondrial content near the centrally located myonuclei. To evaluate whether MuSCs contribute to producing these central myonuclei near mitochondria, primary MuSCs isolated from mitoDendra2 reporter mice were transplanted into mdx mice. Fused myofibers indeed exhibited high Dendra2 + mitochondrial density between central nuclei along with a restoration of the mitochondrial network. Finally, we also observed a change in myogenic potential and mitochondrial respiration after transplanting MuSCs that have been preconditioned to enhance mitochondrial biogenesis. SIGNIFICANCE RELEVANCE: Overall, these data indicate that MuSC-derived myonuclei synthesize new mitochondria to generate the bioenergetics for myofiber regeneration after muscle injury. This relationship between MuSCs and myofiber mitochondria provides a basis for MuSC-derived mitochondrial transplantation as a therapeutic approach for muscular diseases associated with mitochondrial dysfunction. Acknowledgements: This work was supported by the NIH R01AR080169, R01AG072309, VA Merit Award I02RX005009 (to YCJ) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

objective: WDR77, a component of 20S PRMT5 containing a methyltransferase complex, can modify certain arginines in several splicosome Sm proteins and histones to dimethylarginine, which may play a role in transcriptional regulation. Studies have shown that the expression level of WDR77 plays a role in many systemic cancers such as non-small cell lung cancer, prostate cancer and ovarian cancer, and is positively correlated with poor prognosis of most cancers. However, WDR77 has not been studied in detail in glioma, and its biological significance in glioma has not been fully clarified. This study focused on glioma and explored the characterization and prognostic value of WDR77 in glioma, aiming to explore the role of WDR77 in glioma and its feasibility as a potential prognostic factor, so as to guide the clinical treatment of glioma in order to improve the prognosis of patients. Methods: In this study, the role of WDR77 in glioma and its feasibility as a potential prognostic factor were studied by bioinformatics analysis. In this study, transcriptome gene expression profiles and clinical data of 1018 glioma patients were collected from the Chinese glioma Genome Atlas Database (CGGA). The target gene WDR77 was selected from the candidate genes after four-layer analysis filtering (including survival analysis filtering, independent prognostic analysis filtering, ROC curve filtering and clinical correlation analysis filtering). Differential expression analysis, survival analysis, independent prognosis analysis, ROC curve analysis and clinical correlation analysis of the target gene WDR77 were performed to explore the feasibility of WDR77 as a potential prognostic factor for glioma. Then, immunoinfiltration analysis, co-expression analysis and GSEA analysis of the target gene WDR77 were performed to explore the role and mechanism of WDR77 in glioma. Results: WDR77 is significantly overexpressed in gliomas, which is associated with poor prognosis in gliomas (including GBM and LGG), and leads to shorter overall survival in LGG patients (HR =2.8, P =8.9 e-08). WDR77 was an independent prognostic factor for glioma (HR=2.110; 95%CI=1.700 – 2.618; P <0.001), WDR77 had good prognostic accuracy (AUC values for 1-year, 3-year, and 5-year overall survival were 0.710, 0.761, and 0.799, respectively). WDR77 was positively correlated with regulatory pathways such as regulatory T cell differentiation and macrophage differentiation, and with immune cell infiltration such as CD4 + T cells (r=0.523, P =8.78e-35) and macrophages (r=0.509, P =1.36e-32). Conclusion: WDR77 is a novel molecular marker that can be used as an independent prognostic factor for human glioma, and the high expression of WDR77 suggests a poor prognosis for glioma. WDR77 may be a potential immunotherapeutic target for human glioma, and WDR77 affects the occurrence and development of glioma through multiple molecular pathways. National Clinical Key Specialty Project Foundation ; Shanxi Scholarship Council of China;Lvliang City high-level scientific and technological talents development project This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

The Special Master’s Program at Georgetown University Medical Center (GUMC SMP) is a one year academic enhancement MS program that prepares students for future success in medical school. Its curriculum covers about half of the material in the first year basic science curriculum of Georgetown’s School of Medicine, supplemented with complementary graduate courses. GUMC SMP students attend the relevant basic science lectures with first year medical students (M1), are assessed by completing the same multiple choice questions used for their M1 counterparts and are graded against the M1 average to determine grades for corresponding SMP medical courses. In 2015, a second campus, the Georgetown Downtown SMP (GTDT), was opened that follows the same curriculum, but with all material delivered in a fully “flipped” manner. The GTDT students' average undergraduate GPA and MCAT scores are not different from the GUMC SMP students, whereas the average GPAs of SMP students are significantly lower than GPAs of their M1 peers (3.2 vs 3.7 in M1 class). The GTDT students review the lecture capture (LC) recordings of medical (or graduate) lectures on their own time and attend 2-4 hrs of class time four days per week during which the GTDT instructor provides active learning sessions to reinforce the material. The current research expands on our earlier findings, by evaluating the GTDT cohort performance in six medical physiology exams and three medical gross anatomy (GA) exams over the past five years compared to GUMC SMP peers and M1 students. Using the Student’s t test with the Bonferroni correction for multiple comparisons, significance level was designated at p<0.05. Our results indicate that the GTDT students continued to outperform their GUMC SMP counterparts in all exams, reaching statistical significance in three out of six medical physiology exams and three out of three medical GA exams. The GTDT students also had higher average scores than their peer M1 students on five out of six medical physiology exams, reaching significance in three out of the six M1 exams. GTDT averages were higher than M1 students on GA exams, but differences did not reach statistical significance. The higher GTDT performance is most likely attributable to the students being actively engaged in flipped learning in all classroom sessions. Additionally, GTDT students’ responses to anonymous polling showed that they felt the active learning exercises were beneficial to their overall learning and their long-term retention of the material. Overall, our results continue to validate the successful use of the active learning environment in medical education, confirm its successful use in the GTDT program, and suggest that the flipped learning modality results in overall better learning outcomes in a rigorous medical curriculum. Georgetown University This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Parasympathetic reactivation is the underlying mechanism for the rapid fall in heart rate (HR) post-exercise. A delayed decrease in the HR during the first minute after graded exercise is a powerful predictor of overall mortality and is linked to unfavorable clinical outcomes. Chronic kidney disease (CKD) is characterized by an altered autonomic function with heightened sympathetic and weakened parasympathetic activity. Given that exercise training has been shown to improve autonomic function and parasympathetic reactivation after exercise, the purpose of the present study was to test two hypotheses: 1) patients with CKD experience delayed HR recovery (HRR) compared to controls at the cessation of exercise due to attenuated cardiac vagal reactivation; 2) 12 weeks of aerobic exercise training would improve cardiac vagal reactivation in patients with CKD. Twenty-seven patients with CKD stages III and IV [eGFR between 15-59 mL/min/1.73m2] and eighteen age-matched controls were enrolled. All participants underwent cardiopulmonary exercise testing (CPET) in accordance with the modified Balke protocol. Participants were instrumented with a 12-lead ECG for HR assessment, and ventilation and pulmonary gas exchange were recorded breath-by-breath throughout the exercise tests using a metabolic analyzer. Post-exercise cardiac vagal reactivation was indexed via HRR [absolute HR decay (HRR60s)] and HR variability (HRV) metrics [root mean square of successive differences (RMSSD)] during 60 seconds of recovery following the test. To assess HRR kinetics over the entire recovery period, individual data were modeled with a monoexponential fit and the time constant (τ, time to reach ~63.2% of the total HRR, in seconds) was calculated. Comparisons between patients with CKD and controls were made based on the percentage of predicted HRmax obtained during the CPET using the following equation: HRmax= 208−0.7xage. Patients with CKD were then randomly assigned to exercise (n=17) or non-aerobic stretching (n=11) interventions consisting of three sessions per week for 12 weeks. Training sessions began at 20 minutes and increased by five minutes weekly to a maximum of 45 minutes. Intensity started at 50% of heart rate reserve and rose 5% each week to a target of 75%. CPET was repeated at the end of the 12 weeks. The percentage of predicted HRmax obtained at CPET was similar between patients and controls (CKD: 87±9 vs. CON: 86±5 %HRmax; P =0.448). The HRR60s was blunted in patients with CKD compared to controls (∆HRR60s; CKD: -11±4 vs. CON: -17±5 bpm; P =0.001), and τ was significantly longer in patients with CKD (τ; CKD: 144±31 vs. CON: 116±21 s; P = 0.002). Additionally, RMSSD increased at the cessation of exercise in both groups, but to a lesser extent in CKD patients compared to controls (ΔRMSSD; CKD: 0.5±4 vs. CON: 1.3±3 ms; P = 0.032). There was no significant difference in the maximum HR obtained during the CPET before and after 12 weeks of exercise training (pre: 142±10 vs. post: 136±20 bpm, P =0.178) or stretching (pre: 148±20 vs. post: 142±20 bpm, P =0.107). Twelve weeks of exercise training did not improve HRR60s (ΔHRR60s; pre: -11±4 vs. post: -11±8 bpm, P =0.692) nor vagal activity as measured by HRV. These findings support the hypothesis that patients with CKD exhibit impaired vagal reactivation, which may contribute to the increased cardiovascular risk associated with CKD. However, contrary to our hypothesis, 12 weeks of cycling exercise training may not be sufficient to enhance cardiac vagal reactivation. Future studies should explore different exercise modalities and manipulate training variables such as intensity, volume, and frequency to assess their potential impact on cardiac vagal reactivation in patients with CKD. This project was funded by the National Institutes of Health (NIH R01HL135183; NIH R61AT10457; NIH R33AT010457-03). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Women with a history of preeclampsia (hxPE) are at a higher risk of developing cardiovascular disease and related mortality later in life. This association between preeclampsia and chronic cardiovascular risk may be mediated by persistent endothelial dysfunction following preeclampsia. Low-dose aspirin (LDA; 75-150mg/day) is commonly recommended during high-risk pregnancy to reduce preeclampsia incidence and severity and may also help stabilize endothelial function. We hypothesized that LDA use during pregnancy preserves macrovascular and microvascular endothelial function in postpartum women with hxPE. We included three groups: women with hxPE treated with prenatal LDA (hxPE+LDA; n=6; 34±3 years), women with hxPE not treated with prenatal LDA (hxPE-LDA; n=10; 34±2 years), and women with a history of uncomplicated pregnancy (HC; n=10; 35±2 years). Conduit artery endothelial function was assessed via brachial artery flow-mediated dilation (FMD). Microvascular endothelial function was assessed via cutaneous vascular conductance (CVC, %max) response to graded infusions of acetylcholine (10 -10 -10 -1 M) via microdialysis. Relative and absolute FMD in hxPE-LDA were lower compared to HC (relative: 6.0±0.5% vs. 7.7±0.4%, P =0.04; absolute: 0.19±0.01mm vs. 0.24±0.01mm, P =0.01), while hxPE+LDA did not show a difference from HC (relative: 6.3±0.5% vs. 7.7±0.4%, P =0.16; absolute: 0.21±0.01mm vs. 0.24±0.01mm; P =0.27). hxPE-LDA exhibited reduced microvascular endothelium-dependent dilation compared to HC at acetylcholine doses ≥10 -3 M ( P <0.03). hxPE+LDA also showed reduced endothelium-dependent dilation compared to HC, but only at 10 -3 M ( P <0.01). Peak CVC response to acetylcholine in hxPE-LDA was lower than HC (79±5%max vs. 94±4%max, P =0.04), but no significant difference was observed between hxPE+LDA and HC (93±4%max vs. 94±4%max, P =0.99). These findings suggest that prenatal LDA therapy may reduce persistent vascular endothelial dysfunction after pregnancy in women with hxPE. American Heart Association CDA 937990 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Introduction: The determinants of aortic pulse pressure (aPP) are assessed via 1) Wave separation analysis to quantify forward (Pf) and backward pressure (Pb) and 2) Reservoir-wave analysis to quantify excess (XSP) and reservoir pressure (RP). Patients with heart failure with preserved ejection fraction (HFpEF) have high arterial stiffness and present with central and peripheral arterial hypertension and a variable stroke volume (SV) response to exercise. The aim of our analysis was to acutely lower ventricular afterload (aPP and its components [RP, Pb]) during exercise with sublingual nitroglycerin (NTG) to determine whether high exercise afterload contributes to the low SV reserve during exercise in adults with HFpEF. Methods: In 34 adults with HFpEF (75% female, age: 69±6 years; BMI: 39±7 kg/m 2 ), we acquired continuous pulmonary (right-heart catheter) and arterial pressures (radial catheter) and simultaneously derived ascending aortic pressure waveforms (via SphygmoCor generalized inverse transfer function) at rest and during 6-minutes of submaximal cycling exercise (20 Watts). Participants were studied in the seated upright position during either a NTG (q15 mins, 400 μg) or placebo (PL) spray condition. We calculated stroke volume (SV) from heart rate (HR; EKG) and cardiac output ([Formula: see text]c; Direct Fick). Data were compared using two-way (condition*stage) ANOVA. Results: Aortic systolic pressure (PL: 135±23 vs NTG: 123±23 mmHg) and aPP (PL: 60±18 vs NTG: 50±18, mmHg) were lower with NTG during exercise (Condition: both, P <0.011), but the changes from rest to exercise were not different (both, Condition*Stage: P >0.290). Pf (PL: 18±6 vs NTG: 14±6 mmHg, condition: P =0.019), Pb (PL: 6±3 vs NTG: 4±2 mmHg, P <0.001) and RP (PL: 50±17 vs NTG: 39±18 mmHg, P =0.003) were lower with NTG at rest and during exercise; whereas, XSP was not different with NTG (PL: 21±7 vs NTG: 22±7 mmHg, P =0.298). The change in pulmonary artery wedge pressure (PAWP) with exercise was lower with NTG (PL: ∆13±7 vs NTG: ∆9±6 mmHg, condition*stage: P =0.024), with lower PAWP at 20 Watts only (PL: 20±9 vs NTG: 15±8 mmHg P =0.004), but the changes in HR, SV, and [Formula: see text]c were not different (all, condition*stage: P >0.566). Conclusion: NTG lowered left ventricular afterload (Pf, Pb, and RP) at rest and during exercise but there was no effect on exercise cardiac reserve in adults with HFpEF. However, the effects of NTG were not limited to changes in afterload as preload was also lower which potentially negated effects on cardiac reserve. NIH - 1P01HL137630 (BDL); AHA - 23POST1022536 (DJW). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Bardet-Biedl Syndrome (BBS) is a genetic condition that is characterized by multiple features including obesity and type 2 diabetes. Recently, our group showed that disruption of the BBSome, a protein complex of eight BBS proteins, is associated with mitochondrial defects due to a decrease in the activity of key mitochondrial fission protein, dynamin-related protein 1 (DRP1). Prior reports have demonstrated that caffeine promotes mitochondrial fission, resulting in shortening of the mitochondria and a subsequent improvement in mitochondria quality. Interestingly, this was associated with improvement in obesity and insulin resistance. Similarly, Elamipretide (SS-31) is a synthetic peptide that has been primarily used to target a variety of mitochondrial disorders. Because of their shown involvement in maintaining healthy mitochondria quality, we hypothesized that caffeine and SS-31 treatments will lead to improved mitochondrial function in BBS cells by increasing the activity of DRP1. Subsequently, we postulated that caffeine and SS-31 treatment will improve body weight and glucose homeostasis in BBS mice. To test our hypothesis, mouse hypothalamic N39 cells lacking the Bbs1 gene (Bbs1KO) were treated with 50 μM caffeine, 50 nM SS-31, or vehicle. Cell morphology was assessed via transmission electron microscopy. We found that treatment of Bbs1KO cells with both caffeine and SS-31 improved mitochondria dynamics as indicated by the decrease in mitochondria length, area, and form factor (length untreated: 1.31±0.07 vs caffeine: 1.13±0.04 and SS-31: 0.95±0.04 μm, p<0.05). Furthermore, proteins from these cells were extracted and processed via Western blot to assess levels of DRP1 phosphorylation. Mitochondrial reactive oxygen species in Bbs1KO cells were also quantified using Mito-SOX fluorescence indicator. Bbs1KO cells treated with caffeine and SS-31 showed heightened levels of phosphorylated DRP1 (untreated: 1±0.16 vs caffeine: 1.65±0.22 and SS-31: 2.54±0.34 AU, p<0.05) and reduced reactive oxygen species (untreated: 9845±770 vs caffeine: 4841±292 and SS-31: 6242±400 CTCF, p<0.05) compared to untreated cells. Next, mice lacking the Bbs1 gene were treated with 50 mg/kg caffeine BID for 6 weeks beginning at 8 weeks of age. Body weight, weekly food intake, glucose handling (measured via glucose tolerance test, GTT) and insulin sensitivity (measured via insulin tolerance test, ITT) were compared to wildtype littermate controls. Preliminary data show that caffeine treatment trended to attenuate weight gain and improve glucose handling in BBS1 global knockout mice. Additional studies are underway to complete these results. Ultimately, these findings suggest caffeine and SS-31 as potential effective therapies to mitigate the obesity and diabetes associated with BBS. NIH NHLBI T35HL166206 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.