bluuebunny/crossref_metadata_2025 huggingface dataset:
Promotion of hair growth by Lactobacillus and fermented traditional Korean berry in C57BL/6 mice
Authors: Jang Se Jin , Kim Jae Young , Cheon Se Jin , Kim Sae Hun , Lee Jung Yun
Published: May 2023

Hair loss is the state of losing hair from the scalp or entire body when new hair does not replace the hair that has fallen out. Currently, remedies such as oral finasteride and topical minoxidil are commonly used. However, these drugs may have temporary effects and cause side effects such as depression, irregular heartbeat and weight gain when used long term. Therefore, an alternative hair growth promoting agent is needed. The hair follicle undergoes anagen, catagen, and telogen phase which affect hair growth, and this hair-growth cycle is regulated by growth factors, cytokines, and hormones. Some studies reported that the gut microbiome (GM) regulates the transition between the hair growth cycle by producing hair growth-related factors and nutrients. Also, inflammation by GM affects the cascade of the inflammation in the hair follicle, which may lead to hair growth arrest. Previous studies showed strains of Lactobacillus (LAB) have anti-oxidative and anti-inflammatory effects in an HT-29 human colon epithelial cell model and an HaCaT human keratinocyte cell model. Also, traditional Korean berry has anti-inflammatory effects in an HT-29 model. Thus, LAB and fermented traditional Korean berry by LAB (FB) may promote hair growth by regulating gut microbiome. This study investigated the effect of LAB and FB on hair growth in vivo. Six-week-old male C57BL/6 mice were used for evaluating the hair growth-promoting effects of the LAB and FB. The dorsal hair of mice was depilated, and they were orally treated with LAB at 1010 CFU/kg and FB at 250mg/kg daily for 22 days. As a result, the hair re-growth rate was significantly increased in LAB and FB groups compared with the control group. In the histological analysis of skin, FB increased the number of hair follicle and subcutaneous fat layer thickness. The mRNA expression levels of hair growth-related growth factors such as VEGF and IGF-1 are significantly increased in colon and skin. Moreover, Treatment of LAB and FB changed the composition of the microbiome and short chain fatty acids in mice. Altogether, LAB and FB supplementation may promote hair growth by regulating growth factors and altering gut microbiota compositions. In conclusion, strain of LAB and FB are potential novel approaches for hair growth promotion.

This work was supported by Korea Testing Laboratory

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.
SPP1, a potential diagnostic marker that correlated with immune infiltration in right heart failure
Authors: Yang Xiaomei , Lu Kangping , Li Kai , Liu Zihua , Bai Yu , Yao Youxiu , Zhang Peng
Published: May 2023

Background: Right ventricle failure (RVF) is a clinical syndrome with high mortality that is frequently secondary to cardiovascular and pulmonary vascular diseases. There is growing evidence that the outcome of RVF is closely related to the immune response. This study is to explore SPP1 as a potential diagnostic marker related to the infiltration of immune cells in RVF. Methods: The gene expression profile of GSE161473 was downloaded from Gene Expression Omnibus and analyzed by R. Protein-protein interaction (PPI) networks which were established with STRING. Gene Ontology and KEGG enrichment analysis were performed using R-package “Clusterprofiler.” Differentially expressed immune-related genes (DEIRG) were identified using ImmPort. The infiltration of immune cells in RVF was evaluated using CIBERSORT, and the correlation between key hub genes and immune cells was analyzed by R. Rats model of RVF which was established by monocrotaline (MCT) (60 mg/kg, IP). The immune status and differentially expressed immune-related genes (IRGs) in the right heart tissue of rats with RVF in PAH were verified by immunofluorescence, immunohistochemistry, Real-time PCR, and western blotting. In addition, the serum of right heart-failing patients was used to verify the possibility of SPP1 as a biomarker. Result: A total of 107 differentially expressed genes (DEGs) were screened, from which 20 DEIRGs were screened by ImmPort, PPI, and functional enrichment analysis. 4 Hub genes (ADM, FGF12, AREG and SPP1) were confirmed by RT-PCR. In addition, SPP1 was identified as the most potent biomarker. ImmuCellAI immune infiltration analysis showed that a higher proportion of monocytes, M2 macrophages, memory B cells, resting NK cells, and resting mast cells were elavated in the RVF group. Finally, SPP1 was positively correlated with monocytes and M2 macrophages and negatively correlated with memory B cells and CD8+ T cells. Conclusion: A variety of immune cells such as monocytes, macrophages, T cells, B cells, and mast cells are involved in the development of RVF. Dysregulated immune responses were found in the right cardiac tissue of patients with RVF. SPP1 was considered a key hub gene to discriminate between RVF and normal groups. Parts of IRGs, especially SPP1, may be used as biomarkers to assist in the diagnosis and evaluation of RVF.

This work was supported by the Shandong Provincial Natural Science Foundation of China (ZR2022MH052), China Postdoctoral Science Foundation (No. 2021M691944) to Xiaomei Yang.

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.
Impact of Deep Reading in Case-Based Learning in Graduate Physiology Students
Authors: Brainard Robert , Britten Jack
Published: May 2023

Introduction: In universities, a traditional lecture style has shown to be less effective in helping students learn compared to a more active approach to teaching and learning. Previous research has stated that passive learning triggers a shift to a more superficial style of learning that is associated with a lower level of cognitive skill. Active learning is defined as activities that students do to construct knowledge and understanding. An active learning concept known as deep reading has been suggested to improve academic performance. In recent studies, deep reading was utilized in graduate science courses and was shown to enhance reading and comprehension skills as well as increasing overall academic ability. Objective: In this study, the aim was to assess how deep reading impacted a student’s self-perception of their understanding of course material in a graduate-level physiology course. Methods: Over a six-week period, 23 graduate physiology students participated in weekly deep reading assignments that correlated with the material taught in class that week. At the end of each week, students filled out an evaluation form indicating how they felt their assigned reading impacted their understanding of the material taught in class. Results: Results indicated that almost 70% of the class agreed that deep reading helped in understanding the course material. Student feedback data showed frequent use of the words “understanding,” “enjoyed,” “relevant,” and “helped.” Students who spent between 0-2 hours per week deep reading gave positive feedback. Individuals who spent more than 2 hours per week indicated negative feedback and perceived that deep reading counteracted their understanding of course material. Conclusion: The data implies that student understanding of material was improved with 0-2 hours of deep reading per week. More than 2 hours of deep reading per week had a countereffect. Excess time spent reading could have caused students to lose sight of the important concepts from the articles and thereby eliciting a negative effect and more confusion. Some, 1-2hrs, seemed to be helpful, however, more had a detrimental effect on learning. Future studies should aim to have more consistency in the difficulty of reading materials between students. Addition of comprehensive reading questions could also be implemented to assess student understanding. Overall, we found in this study that deep reading, when used in moderation, was effective in helping students learn and see real-world application of concepts learned in class

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.
MicroRNA-206 improves alcohol-mediated decreased myoblast differentiation
Authors: Bergeaux Peter , Bourgeois Brianna , Molina Patricia , Simon Liz
Published: May 2023

Background: With recent advances in antiretroviral therapy (ART), people living with HIV (PLWH) have a near-normal life expectancy but have higher risk for aging-related comorbidities, such as metabolic disorders and frailty earlier in life than the general population. At-risk alcohol use is twice as likely in PLWH compared to the general population and alcohol-related myopathy occurs in 40- 60% of people with alcohol use disorder. Previous studies demonstrated that in vivo chronic binge alcohol (CBA) administration in simian immunodeficiency virus (SIV)-infected male rhesus macaques decreased myoblast differentiation and downregulated microRNA-206 (miR-206) expression in skeletal muscle. We hypothesized that increasing miR-206 expression would increase differentiation in CBA-derived primary macaque myoblasts. Methods: Eight SIV-infected female rhesus macaques received either water (VEH) or CBA (13- 14 g/kg/week) for 14.5 months. Three months into either VEH or CBA administration, animals were vaginally infected with SIVmac251, and ART was started 2.5 months later. Animals were sacrificed after 9 months, and primary myoblasts isolated from vastus lateralis muscle 24 hours after the last dose of alcohol (blood alcohol=0 mM). Myoblasts at passage 4 (VEH & CBA) were proliferated for three days. Cells were then transfected with either miR-206 mimic or control (miR scramble). Four experimental groups were studied at day 5 of differentiation: VEH+scramble, CBA+scramble, VEH+miR-206, and CBA+miR-206. Expression of miR-206 was determined by qPCR. Myoblast differentiation was determined by myotube density, calculated as the average number of myotubes per frame, and fusion index calculated as the percentage of myonuclei that fused into myotubes. Results: In non-transfected CBA-derived cells, myotube density and miR-206 expression was lower compared to VEH-derived myotubes (p<0.001 and p<0.05, respectively). miR-206 transfection resulted in over 150-fold higher miR-206 expression compared to VEH-scramble (p<0.05) in CBA- and VEH-derived cells. miR-206 overexpression significantly increased myotube fusion index (p<0.05) compared to myoblasts transfected with miR scramble in CBA-derived cells. Conclusions: Data show significant improvement of alcohol-mediated decreased myoblast differentiation with miR-206 overexpression. These findings suggest that increasing muscle miR-206 can potentially be used as a therapeutic strategy to improve regenerative capacity in response to muscle injury or atrophy.

(Supported by: T35AA021097, F30AA029358, P60AA009803, K01AA024494)

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.
Metabolism-insulin secretion coupling in pancreatic beta-cells: the protective role of urolithin B towards IAPP aggregation, insulin release and mitochondrial respiration
Authors: Monteiro Rodrigues Luis , Ferreira Sofia , Raimundo Ana , Pobre Vania , Garcez Marcia , da Silva Mafalda , Brito Jose , dos Santos Daniel , Saraiva Nuno , Homem Catarina , dos Santos Claudia , Echaniz Regina
Published: May 2023

Intracellular aggregation and pancreatic deposition of Islet Amyloid Polypeptide (IAPP, or amylin) is an important trigger of β-cell dysfunction in type 2 diabetes and prevention of this process represents an attractive strategy to improve β-cell functionality. (Poly)phenols, particularly small molecule polyphenol metabolites (SMPMs) resulting from the metabolism by the colonic microbiota, have emerged as promising lead molecules.This study aimed to identify SMPMs inhibiting IAPP aggregation and to elucidate their activity towards the improvement of β-cell function. Docking analyzes revealed urolithin B (UroB) as the SMPM with the highest potential to interact with IAPP. In cell-free assays, UroB modulated the aggregation kinetics of IAPP fibril formation probably due to its accommodation in the hydrophobic pocket of IAPP monomer. The cytoprotective effects of UroB were then investigated in INS-1 832/3 pancreatic β-cells challenged with in vitro pre-formed IAPP aggregates. The pre-treatment of cells with 50 μM urolithin B for 12 h ameliorated IAPP-impaired cell viability and improved redox homeostasis and membrane integrity. Transcriptomic analysis pointed out Ca2+-signaling, and insulin secretion as top molecular pathways enriched in IAPP-exposed cells treated with UroB compared to the untreated control. Corroborating this, UroB protected against Ca2+ imbalance and mitochondrial dysregulation, resulting in improved glucose stimulated insulin secretion. Monitoring of oxygen consumption rate showed that UroB restored the mitochondrial respiration function in cells damaged by IAPP aggregates. Particularly, UroB re-established the energetic demand of the cells under baseline conditions, restored the ATP levels produced by the mitochondria, and rescued the spare respiratory capacity of cells subjected to IAPP insult. These effects translate into an increased capacity of cells to respond to energetic demands and, consequently, an improved cell fitness.Overall, our data revealed that UroB inhibits IAPP aggregation and modulates diverse cellular mechanisms assisting β-cells to deal with IAPP damage. This study discloses a novel set of molecules, the SMPMs, with the potential to prevent IAPP proteotoxicity and to promote metabolic homeostasis.

This research is funded by Fundação Ciência Tecnologia (FCT) by grant UIDB/04567/2020. R. Menezes is supported by the Science Employment Stimulus program from FCT.

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.
The worsening of cardiac function by the repeated micro-embolization attenuates the very short-term blood pressure lability index in dogs
Authors: Yoshida Yuki , Kakuuchi Midori , Uemura Kazunori , Yokota Shohei , Matsushita Hiroki , Kawada Toru , Saku Keita
Published: May 2023

Background: Recently, we developed a novel method for the assessment of very short-term blood pressure lability (BLI). BLI is calculated from the integrated area of blood pressure (BP) power spectral density from 0.01 Hz to 0.1 Hz. Given that low cardiac function suppresses blood pressure (BP) variation, we investigated how the worsening of cardiac function can be reflected in BLI by using a dog model of heart failure with reduced ejection fraction (HFrEF). Methods: In 6 dogs, chronic heart failure was induced through the use of multiple sequential microembolization via bolus injection of polyester microspheres (90μm) into the left descending or circumflex coronary arteries. We repeated coronary microembolization every two weeks and checked the arterial pressure, left ventricular pressure, and echocardiogram under general anesthesia in every session. BLI was calculated from the continuous BP recording by the catheter placed at ascending aorta before micro-embolization. We examined the changes of cardiac function and BLI, and compared them among the sessions of microembolization. Results: In every dog, the repeated microembolization significantly reduced left ventricular ejection fraction　(Baseline: 66±4 vs. HF: 38±6, %, P<0.01) and increased left ventricular end diastolic volume (Baseline: 23±4 vs. HF: 36±4, ml, P<0.01), indicating the worsening of cardiac function and remodeling. Although the mean BP did not change significantly, the BLI were significantly lower in heart failure condition (6±2 times microembolization) compared to baseline (Baseline: 0.7±0.2 vs. HF: 0.4±0.1, mmHg, P<0.05). Conclusions: Our findings demonstrate that the BLI in a HFrEF model dog was lower than that in baseline condition with normal hemodynamics. The BLI showed the potential for the assessment of the cardiac function and hemodynamic severity in HFrEF.

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.
Shear stress facilitates Akt activation in human pulmonary microvascular endothelial cells
Authors: Yan Simin , Philip Nicolas , Quintara Celia , Damarla Mahendra , Suresh Karthik , Shimoda Larissa , Kolb Todd
Published: May 2023

Introduction: Pulmonary arterial obstruction due to acute thromboembolism causes local reduction or cessation of blood flow. Under normal conditions, pulmonary blood flow exerts shear stress on endothelial cells, known to play an important role in maintaining vascular homeostasis. We hypothesized that pulmonary microvascular endothelial cells exposed to abrupt reductions in shear stress would demonstrate attenuated phosphatidylinositol 3-kinase (PI3K)-dependent signaling and phosphorylation of downstream effectors Akt and endothelial nitric oxide synthase (eNOS). Methods: We tested our hypothesis in primary cultures of human lung microvascular endothelial cells (hLMVECs). We cultured early passage (p≤8) hLMVECs from 5 unique donor lots in standard 6-well culture plates and exposed cells to shear stress using an orbital shaker. Using a fixed depth (volume) and viscosity of tissue culture media, we adjusted the magnitude of shear stress exerted on hLMVECs by changing the angular velocity of orbital rotation. We acclimatized hLMVECs to physiologically-relevant shear stress (~12 dyn/cm2) for 24 hours, then exposed cells to low shear stress (~3 dyn/cm2) or no shear stress (0 dyn/cm2) for 30 minutes. Control cells were maintained at 12 dyn/cm2 of shear stress. In some experiments, PI3K activity was inhibited throughout the acclimatization and shear stress manipulation period by including LY294002 (10 μM) or vehicle (DMSO, 0.1% v/v) in culture media. We prepared whole cell lysates and used western blot to evaluate the expression and phosphorylation of Akt (ser473) and eNOS (ser1177). Results: We found that phosphorylation of Akt, but not Akt expression, decreased significantly (p<0.05) when shear stress was acutely reduced (~3 dyn/cm2) or removed (0 dyn/cm2). Inhibition of PI3K activity with LY294002 further diminished shear-mediated changes in Akt phosphorylation in all 3 groups. Conversely, eNOS phosphorylation was not modified by acute reductions in shear stress, but eNOS expression was markedly attenuated by PI3K inhibition under all conditions. Conclusions: Our results indicate that phosphorylation of Akt, but not its downstream target eNOS, is rapidly attenuated by abrupt reductions in shear stress in hLMVECs. However, shear stress appears to regulate eNOS expression in a PI3K-dependent manner. Taken together, these findings suggest that acute disruption of flow, as seen in pulmonary embolism, may disrupt human lung microvascular endothelial cell homeostasis and nitric oxide bioavailability via multiple PI3K-dependent signaling pathways.

This work is supported by HL126514 and HL159906.

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.
Effect of Acute Diathermy on Leg Blood Flow and Vascular Function
Authors: Richard Kimberly , Wallace Taysom , Gifford Jayson , Nelson W
Published: May 2023

Endothelial dysfunction is a common predecessor of many cardiovascular diseases. Heat therapy has been shown to improve cardiovascular health by stimulating changes within the endothelium. The purpose of this study was to examine the effect of acute diathermy, a heating modality, on leg blood flow and endothelial function. We hypothesized that diathermy treatment would increase leg blood flow compared to baseline, as well as increase endothelial function, as measured by peak increase in blood flow during passive leg movement. Nine healthy, young subjects (4 males, 5 females; mean (± SD) age = 23 ± 3.2 years, height = 174.8 ± 9.6 cm, mass = 74 ± 11.5 kg, body mass index = 24.1 ± 1.2) with no history of cardiovascular disease volunteered for this study. Subjects underwent 100 minutes of diathermy treatment on the vastus lateralis of a single, randomly assigned leg. Blood flow was measured at the common femoral artery using a Doppler ultrasound before, immediately after, and 30 minutes after heating. Passive leg movement was performed on the subjects before heating, and 30 minutes post-heating and peak blood flow was measured using Doppler ultrasound. Blood flow was found to significantly increase 20.4% from baseline to immediately post-heating (baseline, 355.3 ± 145.7 mL·min-1, immediately post, 428 ± 111.1 mL·min-1, p=0.045), and returned to baseline 30 minutes post-heating (30 min post, 361 ± 101.3 mL·min-1, p=0.853). Additionally, peak leg blood flow during passive leg movement significantly increased by 19.8% from baseline to 30 minutes post-heating (baseline, 1046.4 ± 379 mL·min-1, 30 min post, 1253.4 ± 430.2 mL·min-1, p=0.029). In conclusion, both leg blood flow and endothelial function, assessed by peak leg blood flow, significantly increased from baseline following 100 minutes of diathermy treatment. These data provide evidence for the benefits of acute diathermy treatment in improving leg vascular function via enhancements to endothelial function.

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.
Developing a mathematical model for early detection of viral hepatitis induced liver dysfunction
Authors: Agrawal Deepak Kumar
Published: May 2023

Acute liver failure (ALF) is characterized by a sudden loss of hepatic function within a few weeks without pre-existing cirrhosis or prior history of liver disease. ALF can be difficult to identify using non-invasive methods such as coagulation abnormality and encephalopathy alone as alternative causes may confound the ALF diagnostic. This often results in delayed treatment at the onset of the disease, and a liver transplant might be the only option for ALF patients with a limited success rate. Due to these variables, ALF treatment is highly subjective to the clinicians' expertise, with a very high morbidity and mortality rate. Therefore, a prognostic model can help identify patients who can be managed with medical treatments and those who need liver transplants, along with an optimum intervention time window. Currently, only statistical models are available to identify ALF, such as King's College Hospital criteria, Clichy criteria, and End-Stage Liver Disease score. While these models provide much-needed critical support to clinicians, these models have limited specificity and sensitivity toward the cause of ALF and liver disease progression. For example, among all the common causes, the viral hepatitis-induced liver disease remains a major cause of ALF in developing countries such as in India and Bangladesh. Therefore, a dynamic patient-specific model is needed to improve patient care by correlating liver dysfunction with various healthcare variables and interventions. In this work, a new physiological linked data-driven model is formulated that can track the progression of liver disease and failure due to viral hepatitis. The approach relies on integrating the dynamics of healthy hepatocytes with immune system response, which is a vital component in tracking the time-sensitive infectious disease progression. The model uses the patient-specific measured values of alanine transaminase and aspartate transaminase enzymes and the clinically calculated international normalized ratio value to estimate the sensitive model parameter. This patient-specific model is then used to determine the disease progression by predicting the number of damaged hepatocytes and correlating it with the indication criteria for liver transplantation. The model can reproduce the essential dynamics seen in the ALF patient data and can be adapted to incorporate the effect of different therapeutic interventions. Thus, providing a vital bridge between understanding and treating viral hepatitis-induced liver dysfunction.

No conflicts of interest, financial or otherwise, are declared by the author.

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.
Disruption of the surfactant protein A receptor isoform SP-R210L in alveolar macrophages alters airway, vascular, and immune homeostasis in the lung
Authors: Chroneos Zissis , Umstead Todd
Published: May 2023

Surfactant protein A modulates alveolar macrophage activation and pathogen clearance through the receptor SP-R210, which consists of a homeostatic SP-R210L and an inflammatory SP-R210S isoform in alveolar macrophages (AMs). Both isoforms are encoded from alternatively spliced mRNAs of the Myo18α/MYO18Aα gene in mice and humans. The objective of this study is to elucidate the functions of SP-R210 isoforms in AM function in vivo. We hypothesized that disruption of SP-R210L in AMs would alter the local microenvironment. To address this hypothesis in vivo, we generated conditional transgenic mice by targeting exon 1 encoding the unique amino-terminal KE/PDZ domain of SP-R210L. This strategy enabled selective deletion of SP-R210L in AMs via ITGAXCre-mediated inversion recombination. The impact of AM selective deletion of SP-R210L was studied by histological, biochemical, flow cytometric, and respiratory mechanics measurements in young and aged mice. Airway hyperresponsiveness was measured during exposure to escalating doses of methacholine. These studies show that conditional disruption of SP-R210L results in pulmonary disease consisting of hemosiderin deposition in AMs, decline in long-term maintenance of AMs and lung immune cells, obstructive-restrictive pulmonary mechanics, increased airway hyper-responsiveness, alteration in small solute permeability, arterial smooth muscle hyperplasia and inflammation. Our findings support the novel idea that SP-R210L modulates paracrine functions of AMs in maintenance of alveolar- and airway-capillary homeostasis in the lung. SP-R210L dysfunction may increase the risk for development of pulmonary hypertension.

Department of Pediatrics, Penn State College of Medicine, The Children's Miracle Network, NIH HL128746

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.
Gamification, reasoning, application and situated learning approach in Physiology - GRASP the concepts
Authors: Taranikanti Madhuri , John Nitin Ashok , M Kalpana , Kamble Prafull , Singhal Anish , Ganji Vidya , U Madhusudhan , Gaur T Archana , Ansari Afna
Published: May 2023

Background: Deep learning happens through comprehension of various mechanisms particularly in concept oriented disciplines like Physiology. Hypothesis: Students when exposed to real life situations especially in a collaborative learning environment become more active and immersed in learning. Gamification models can sustain the attention of learners for longer periods and instill interest and motivate them to explore the concepts further. These models can enhance knowledge retention and make learning more enjoyable transforming them into self directed learners. Objectives: To design multifaceted gamification models using situated learning approaches to enhance learning, knowledge retention, application and performance in Physiology. Methodology: Students of first year medical course of both sexes were divided into teams and exposed to the gamification models. Individual and team based performances were assessed. Nine stations with time bound team based gaming activities were designed through focused group discussions. A total of 100 marks were allotted for all activities together. Activities had elements to understand the significance of team work, critical thinking, situated learning using gaming modules. Faculty moderators at each station scored the team performance based on correctness of the activity. Performance as a team was also given scores by observing various attributes and extent of involvement of each team member in the activity. Students, as a team, were given an opportunity to instantly rate each gaming activity. Pretest to assess initial knowledge followed by activities by rotation through stations and post test to assess individual performance were given. Results / Observations: Pretest, Post test scores, faculty assessment of activity, performance as a team and feedback rating by students were tabulated and analyzed. The class average score was 70% (out of total 100 marks) which is considered good. The post test score was significantly higher than the pre test mean scores (p<0.0001) using the situated learning approach model with gamification. There was a significant improvement in the performance in the Formative Assessment (p<0.05) conducted after the GRASP activity. Conclusion: Situated learning approach using near real life situations is an effective learning strategy and can be a useful formative assessment tool. Multifaceted gaming modules enabled actual visualization and critical thinking rather than mere imagination. Team based performance helped exchange of thoughts for higher order thinking and projected significance of teamwork in healthcare setup.

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.
Reduced venous oxygen depletion in response to at-sea acoustic disturbance in diving northern elephant seals
Authors: Williams Cassondra , McDonald Birgitte , Horning Markus , Klinck Holger , Ponganis Paul , Costa Daniel , Hindle Allyson
Published: May 2023

Marine mammals face increased human activities in the ocean, including shipping, recreation, and seismic exploration. Such disturbances may alter short-term behavior and long-term life history patterns; however, many of the mechanistic details of responses remain unknown. Because marine mammals survival depends on their diving abilities, physiological specializations to diving will likely define the scope of underwater responses to a disturbance. Prior research in aquatic animals has demonstrated an increased bradycardia in response to underwater stressors. We examined cardiovascular physiological responses to disturbances at sea in freely diving juvenile northern elephant seals ( Mirounga angustirostris). We predicted that, after an acoustic disturbance at sea, seals would intensify the dive response, resulting in reduced whole-body oxygen (O2) consumption and slower venous O2 depletion. To test this hypothesis, we recorded venous PO2 and diving behavior in translocated juvenile northern elephant seals that were exposed to experimental acoustic disturbances while freely diving at sea. Venous PO2 was measured in the extradural vein using a Clark polarographic electrode attached to a biologger. After being exposed to an acoustic noise during the ascent phase of deep dives, seals typically exhibited an immediate inversion of the dive, descending to deeper depths. Dives with acoustic disturbances were significantly longer than dives prior to the acoustic disturbance (24.8 ± 6.2 mins vs 19.1 ± 2.9 mins). Although the magnitude of PO2 depletion was not significantly different between pre-disturbance dives and disturbed dives (52.6 ± 21.6 mmHg vs 53.5 ± 20.8 mmHg, n= 27 paired dives), the depletion rate was slower in disturbed dives. In dives prior to the disturbance, PO2 depletion was 3.2 ± 1.5 mmHg min-1, but in dives with a disturbance, PO2 depletion was 2.5 ± 1.3 mmHg min-1. This reduction in venous PO2 depletion rate suggests O2 consumption during disturbed dives may be similar to the amount consumed during non-disturbed dives. This reduction may be a result of altered perfusion, including reduced muscle blood flow. In particular, reduced perfusion to working muscle would likely reduce O2 extraction, and may be a key factor in fine-tuning the dive response after a disturbance to conserve O2 for the brain and heart.

National Science Foundation

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.
The role of CXCR4 in vascular endothelial cells in ischemic heart diseases
Authors: Wang Yang , Gadd James , Enrick Molly , Ogunmiluyi Blessing , Dong SARAH , Zhang Lily , Zhang Laura , Yin Liya
Published: May 2023

CXCR4 and CXCL12 signaling pathways are essential in cardiovascular development, ischemia heart diseases, and cardiovascular regeneration. Coronary collaterals are nature bypass of ischemic heart diseases. Recently reports showed that CXCR4 and CXCL12 signaling is involved in coronary collateral growth (CCG) in a mouse model of myocardial infarction. Our study showed that endothelial cell (EC) sprouting is essential to coronary collateral formation in a mouse model of CCG induced by repetitive ischemia (RI). It is unknown the role of CXCR4 in EC in CCG. In this study, we used genetically modified mice (CXCR4 EC-specific knockout) to study the role of CXCR4 in ECs in myocardial ischemia. First, we generated EC-specific CXCR4 knockout (CXCR4 flox/flox-tie-2-cre). Surprisingly we found spontaneous aortic stenosis in these EC-specific CXCR4 knockout mice. To exclude the effect of CXCR4 in ECs during embryonic development, we generated an inducible CXCR4 EC-specific knockout (CXCR4 flox/flox-VE-cadherin-cre). Our preliminary data showed no aortic stenosis in these mice after being induced by tamoxifen at six weeks old, suggesting that CXCR4 signaling in EC affects cardiovascular development. We compared the phenotypes of two mouse lines of CXCR4 endothelial knockouts by echocardiography and histology. Furthermore, these CXCR4 EC-specific knockout mice and their littermate controls underwent myocardial infarction (MI) and RI surgery. We measured the cardiac function, vessel density, and coronary blood flow in the mice with RI. We measured the cardiac function, vessel density and infarction size, and fibrosis in the mice with MI. Our preliminary data showed that the CXCR4 and CXCL12 signaling in vascular EC is essential to cardiovascular regeneration during myocardial ischemia, suggesting that CXCR4/CXCL12 signaling pathway could be a potential target for treating ischemic heart diseases and preventing heart attack.

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.
Cardioprotection from Acute Myocardial Infarction with RRx-001, an NLRP3 Inflammasome Inhibitor, in Phase 3 for the Treatment of Cancer
Authors: Cabrales Pedro , Reid Tony , Caroen Scott , Oronsky Bryan
Published: May 2023

Acute myocardial infarction (MI) is a major cause of morbidity and mortality. Massive cell death leads to inflammation, a necessary evil for wound healing, but also “evil” or harmful due to infarct expansion and adverse remodeling. Also, studies in experimental models have demonstrated the potential cytoprotective effects of nitric oxide (NO) supplemented at the time of reperfusion. In these experiments, we investigated whether RRx-001, a NO donor only under hypoxia and an NLRP3 inflammasome inhibitor, in a Phase 3 trial (REPLATINUM; NCT03699956) for the treatment of cancer was protective after MI. Methods: Male Sprague-Dawley rats (n=8/group) subjected to coronary ligation and reperfusion were randomized to receive either no treatment (sham), vehicle control, or 5mg/kg intravenous RRx-001 at 1-hour post-infarction. We assessed structural and functional cardiac remodeling, infarct expansion, fibrosis, cardiomyocyte hypertrophy, and the expression of inflammatory genes. Results: Treatment with RRx-001 after reperfused MI decreased infarct expansion and scarring, increased left ventricular systolic function to levels approaching normal values, and reduced myocardial hypertrophy. No hypotensive effects were observed. Postinfarction was associated with the activation of NF-κB and NLRP3 inflammasome components and increased the protein and expression of IL-1β. Compared with vehicle, infarcted rats treated with RRx-001 significantly attenuated myocardial messenger RNA and protein levels of NF-κB, NLRP3 inflammasome, mature caspase-1, and IL-1β. Significance: This is the first report that RRx-001 reduces infarct size. It provides proof of principle for administering RRx-001 against ischemia/reperfusion injury. RRx-001 increases local NO levels under hypoxia without requiring the continuous intravenous infusion of NO donors and without altering systemic hemodynamics. It can potentially improve wound healing responses and pathological remodeling, thereby attenuating the development of ischemic heart failure.

Commercial and private foundation grants.

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.
Importance of learning the connection between form and function together - redesigning anatomy and physiology for improved student learning outcomes
Authors: Bates Holly , West Sarah
Published: May 2023

First-year undergraduate level human anatomy and physiology courses are required for numerous degrees and programs, including nursing, kinesiology, and biomedical sciences. These courses create an important foundation for students to build their continued learning. However, identifying the best way to offer these courses is still not fully clear. Some post-secondary institutions and/or programs offer integrated anatomy and physiology courses, while others, separate anatomy from physiology. As well, with the increased requirement and desire for online formats, additional consideration into course delivery is needed. Previously, we evaluated and reported student human physiology content retention 3-months following course completion at our institution that offers separate anatomy and physiology courses. We found that overall content retention was poor and exacerbated in the online format of course delivery. Given this, we identified that there may be a disconnect in the way these courses are delivered that is problematic to learning. Currently, the physiology course follows in the semester after the anatomy course. In both courses, a new body system is discussed each week in rapid succession. Out of necessity, the anatomy course includes some basic physiology to improve understanding and a review of anatomy occurs in the physiology course to fully understand function. Thus, there is significant overlap that takes away from time that can be spent reinforcing complex physiological topics. We hypothesize that redesign of these courses using a systems-based approach to combine the anatomy and physiology within one course will improve student retention of core physiological concepts, since students would learn both the form (anatomy) and function (physiology) together. We will discuss the considerations that we have evaluated with respect to the redesign of these courses and welcome discussion with respect to the strengths and weaknesses of separate versus combined anatomy and physiology curriculum delivery.

Teaching Fellows Program, Trent University

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.
IGSF3 (immunoglobulin superfamily 3) and glycosphingolipids associated with lung cell proliferation during recovery from respiratory SARS-CoV-2 infection
Authors: Schweitzer Kelly , Egersdorf Nicholas , Rivera Tanner , DuBois Betty , Cornell Christina , Borowiec Alexander , Poczobutt Joanna , Matsuda Jennifer , Berdyshev Evgeny , Bowen Richard , Petrache Irina
Published: May 2023

RATIONALE: IGSF3, a transmembrane tetraspanin interacting protein, is required for lung epithelial scratch wound repair and migration via inhibition of glucosyl ceramide synthase. However, as a result, a decrease in glycosphingolipids such as lactosylceramide may decrease cell proliferation and impair lung recovery from infections such as SARS-CoV-2 (CoV2). We hypothesized that recovery from CoV2 is associated with downregulation of lung IGSF3, increased glycosphingolipid synthesis, and enhanced lung cell proliferation. METHODS: Lung IGSF3, sphingolipid levels, and cell proliferation were measured in Golden Syrian hamsters harvested during the early recovery (at 7 days) following a single intranasal exposure to CoV2 (strain WA01; 10E4 pfu). Lung cell proliferation was measured in mice with constitutive deletion of IGSF3 (KO). Immunofluorescence (IF) was performed for cell-specific markers CD11b and CD11c, as well as CD31. Lipids were quantified using LC-MS/MS. RESULTS: CoV2 infection was associated with decreased Igsf3 [log2FC (fold change) -0.914; p<0.01] expression and immunostaining in the lung tissue and increased glucosylceramide (FC 11, p<0.001), lactosylceramide (FC 5, p<0.01), and lysophosphatidic acid (FC 6, p<0.001) in the BALF. Lung cell proliferation was increased, with high Proliferation Marker Protein Ki-67 expression (Ki-67; log2FC 2.17; p<0.0001). In mice, compared to control, IGSF3 KO mice exhibited increased lung Proliferating Cell Nuclear Antigen (PCNA; FC 2.44; p=0.03) and Ki-67 (FC 1.71; p=0.03) IF and enhanced EdU incorporation (in female mice only, FC 1.9; p=0.007), predominantly in the lung epithelium. Of the Ki-67+ cells in the IGSF3 KO lung parenchyma, the populations of cells that had higher proliferation rates than in control mice were alveolar epithelial (>70% of all proliferating cells) followed by recruited monocytes/macrophages, and vascular cells. CONCLUSIONS: Inhibition of IGSF3 may accelerate lung epithelial cell proliferation and lung repair during recovery from respiratory viral infections such as with CoV2 by a mechanism that may involve enhanced glycosphingolipid production.

DOD W81XWH-21-PRMRP-IIRA, ALA ETRA736704

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.
Effect of adipose biopsy technique on adipocyte size and integrity
Authors: Brandt Anna , Lynch Colleen , Boyd Gerard , Vincenty Caroline , Skiles Chad , Robbins Ethan , Gouw Aaron , Kuszmaul Dillon , Naruse Masatoshi , Chambers Toby , Minchev Kiril , Belangee Alicia , Douglass Matthew , Trappe Todd , Trappe Scott
Published: May 2023

Objectives: The purpose of this study was to compare adipocyte size and integrity in adipose tissue between Mercedes and Bergström biopsy techniques in healthy, recreationally active adults. Hypothesis: There would be no difference in adipocyte size between the Mercedes and Bergström techniques. Mercedes biopsy samples would have a smaller area of intact adipocytes compared to Bergström biopsy samples. Methods: Baseline abdominal subcutaneous adipose tissue was obtained from 10 (7M, 3F; 28±4 y; 87±9 kg; Body Fat 30±8%; VO2max 3.4±0.8 L/min) healthy, recreationally active adults (i.e., regular aerobic and/or resistance exercise 3-5 days/wk) on contralateral sides via the Mercedes and Bergström biopsy techniques. Samples were cryopreserved until downstream processing and analysis. Adipocyte quality [i.e. intact cells and cross-sectional area (CSA)] was analyzed and compared between biopsy techniques. Results: Average tissue yield for the Mercedes biopsy was greater than the Bergström biopsy (1171±545 mg vs. 318±58 mg, respectively; P<0.05). The Mercedes and Bergström techniques had a range of yields (393-1940 mg vs. 215-380 mg, respectively) with the Mercedes technique obtaining more than 3.5x the amount of adipose tissue compared to the Bergström biopsy. Mean CSA did not differ between Mercedes and Bergström biopsy techniques (6517±952 μm2 vs. 6116±1652 μm2, respectively; P>0.05). The percent distribution for CSA clustering followed the same trend for both techniques. Intact area was similar between Mercedes (61±16%) and Bergström (63±11%) (P>0.05) techniques. Conclusions: Adipocyte size and integrity did not differ between Mercedes and Bergström biopsies suggesting that the two sampling techniques provide comparable quality of tissue for analysis. However, research questions may impact the technique chosen as the Mercedes biopsy obtains larger tissue yields whereas the Bergström technique may allow for an increased number of biopsies due to the abdominal area utilized.

This research was supported by the Human Bioenergetics program at Ball State University.

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.