bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decoding Stress: The Universal Language of Entropy Production
Authors: Bienerova-Vasku Julie , Zlamal Filip 
Published: May 2024

The accurate quantification of stress remains a formidable challenge in the realm of physiological research, largely owing to the intricate nature of the stress response and its potential overlap with other physiological processes. In this vein, our research introduces a novel metric: the stress entropic load (SEL), grounded in thermodynamic principles. SEL is mathematically construed as a time-dependent function, articulated through various heat and temperature alterations, as well as changes in respiratory gas exchanges. This measure is posited as a predictive tool for stress and metabolic alterations in homeothermic organisms, including humans. Our empirical exploration involved 12 healthy male volunteers, structured in a dual-phase experimental design. The initial phase focused on achieving a resting metabolic rate (RMR), guided by specific criteria encompassing oxygen uptake, carbon dioxide release, and respiratory quotient. In instances where RMR benchmarks were not met within a 40-minute window, the study progressed, presuming RMR attainment. The collected data from this segment were pivotal in calculating the body's entropy production at rest. The subsequent phase entailed participants engaging in tasks via the WinSCAT software, signifying the onset of the stress phase. Here, entropy production was scrutinized to gauge stress levels. Crucially, SEL was ascertained by contrasting entropy production during the RMR phase (serving as a baseline) against that recorded throughout the experiment's entirety. Our findings indicate that SEL, as an indicator of specific entropy production, emerges as a viable marker of stress induced by prolonged mental effort. Notably, extended interaction with WinSCAT software markedly augmented SEL rates. The progression of SEL over time offered insights into when participants commenced stress-inducing tasks, underscoring its viability as a biological marker for mental exertion. Intriguingly, such stress did not manifest in conventional stress indicators like blood pressure or heart rate, though it did affect oxygen and carbon dioxide production. While these results lend credence to the utility of SEL as a stress marker, they are preliminary in nature, illuminating the prospective significance of SEL in the realms of stress measurement and physiological research. The project was funded by MUNI/G/1249/2021 grant by the Masaryk University. This is the full abstract presented at the American Physiology Summit 2024 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.
Hyaluronan Fragments Induce Lung Alveolar Edema by Activating Calcium-Sensing Receptor
Authors: Song Weifeng , Yu Zhihong , Matalon Sadis , Lazrak Ahmed 
Published: May 2024

One of the hallmarks of lung injury is the breakdown of the cell matrix hygroscopic high molecular weight hyaluronan (HMW-HA >106 kD) into smaller fragments of low molecular weight (LMW-HA < 500 kD) which mediate the onset and progression of acute lung injury. We have found that instillation of very low dose (1μg) of LMW-HA to wt. C57/bl6 mice was suffcient to inhibit lung epithelial ions and water transport and cause lung edema assessed by measuring lungs wet/dry ratio. LMW-HA IC50 for the induction of lung edema, the inhibition of alveolar fluid clearance (AFC) and epithelial sodium channels (ENaC) in alveolar epithelial cells, AEC1 and AEC2, in-situ, in freshly cut lung slices, was 120 nM. We found the expression of calcium-sensing receptor (CaSR), a C class G-protein coupled receptor, was activated by LMW-HA. CD44 is known to be the main membrane receptor of hyaluronan expressed by most cells including lung alveolar epithelial cells, however, because it lacks the intrinsic kinase activity necessary for the transduction of extracellular signal carried by LMW-HA, we hypothesized that it cooperated with CaSR to transduce LMW-HA injurious signal and activated intracellular signaling cascades that induced lung edema by inhibiting ENaC and AFC at 24 h. These effects were prevented by NPS2143 (1 μM), a CaSR inhibitor or calcilytic, instilled 6 h post LMW-HA, and were absent in CD44 knockout mouse. The lack of an effect on W/D ratio, AFC, or ENaC in CD44−/− mouse is evidence that LMW-HA does not directly interact with CaSR, but rather activates CD44 which cooperate with CaSR to trigger intracellular signaling cascades that cause the observed effects. Four hours post mouse airway epithelial cells confluent monolayers were incubated with 1 μg LMW-HA, CaSR expression was increased 4-fold, while amiloride sensitive short-circuit current and αβγ-ENaC subunits expression, at the apical membranes, were significantly reduced. These effects were prevented when CaSR, PLC, or PKC were inhibited with 1 μM NPS2143, 10 μM U73122, or 100 μM Rottlerin, applied 4 h prior to cells incubation with 1 μg LMW-HA, respectively. Our data show that the deleterious effect of LMW-HA on ENaC are mediated by intricate interactions between CD44-LMW-HA complex with CaSR in lung alveolar epithelial cells. The use of calcilytics to decouple the molecular complex formed by CD44-LMW-HA and CaSR may prove to be effective in restoring alveolar sodium ion reabsorption required for lung edema clearance. Department of Anesthesiology and Perioperative Medicine. This is the full abstract presented at the American Physiology Summit 2024 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.
A prospective observational study on hemodynamic risk in cerebral aneurysm growth
Authors: Fukuda Shunichi , Shimogonya Yuji 
Published: May 2024

Introduction: Hemodynamic factors are thought to play a major role in the development, growth, and rupture of cerebral aneurysms, but the hemodynamics related to enlargement remain unclear. We prospectively enrolled patients with unruptured cerebral aneurysms and performed Computational Fluid Dynamics (CFD) analysis using 3D CT images to investigate differences in hemodynamic environments between aneurysms that grew and those that did not grow over a 3-year period. Methods: This prospective observational study was approved by the National Hospital Organization Central Ethics Review Board. Hemodynamic distributions were examined using ANSYS-CFX software. Patient-specific arterial geometries and inflow velocities were obtained from 3D-CTA and carotid ultrasound Doppler examinations. The distributions of hemodynamic metrics of 17 enlarged and 70 unenlarged aneurysms was compared. In addition, the distributions of hemodynamic metrics of the neck, body, and dome of the aneurysm was also examined in 9 enlarged and 41 non-enlarged cases. A multivariate logistic analysis was performed to investigate the influence of the six hemodynamic metrics, i.e., the time-averaged wall shear stress (TAWSS), time-averaged WSS gradient (TAWSSG), oscillatory shear index (OSI), gradient oscillatory number (GON), transverse WSS (transWSS), and normalized transWSS (NtransWSS) after adjustment forknown risk factors for aneurysm growth, i.e., age, sex, hypertension, smoking history, and aneurysm location, size, and history of subarachnoid hemorrhage. Results: Regarding the distributions of hemodynamic metrics throughout the aneurysm, NtransWSS was significantly higher in the cases with growth than in the cases without growth (odds ratio 2.09, 95% CI 1.02-4.29). the distributions of hemodynamic metrics at each cerebral aneurysm growth site showed that NtransWSS at the dome was significantly higher in the growth cases than in the non-enlargement cases (odds ratio 4.14, 95% CI 1.02-16.80). Conclusion: The data suggest that multidirectional disturbance of wall shear stress is involved in cerebral aneurysm growth, and the disturbance at the dome of the aneurysm may be particularly strongly related. This study was supported by a Grant-in-Aid from the Japanese National Hospital Organization Multi-Center Clinical Research, AMED under grant no. JP15gm0810006h0301 and a JSPS KAKENHI Grant, no. 15K10323. This is the full abstract presented at the American Physiology Summit 2024 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 Association Between Cardiovagal Baroreceptor Sensitivity and Hippocampal Tissue Integrity in Young and Middle-aged Adults
Authors: Horvat Fiona , Kramer Mary , Decker Kevin , Johnson Curtis , Wenner Megan , Martens Christopher 
Published: May 2024

Prior research has investigated the association of cardiovagal baroreceptor sensitivity (BRS) with white matter neuronal integrity and cerebral perfusion using magnetic resonance imaging (MRI) techniques such as diffusion tensor imaging (DTI) and arterial spin labeling (ASL); however, less is known about the association with specific regions of gray matter (i.e, hippocampus) involved in memory formation and recall. MR elastography (MRE) has emerged as a constructive tool for assessing the viscoelastic mechanical properties of the brain which are believed to reflect the microstructural integrity of neuronal tissue. PURPOSE: To investigate the association between cardiovagal BRS and the viscoelastic properties of the brain, with a sub goal of examining how advanced age affects this association. We hypothesized that there would be a positive relation between cardiovagal BRS and hippocampal (HC) viscoelastic properties that strengthens with age, indicating a greater influence of blood pressure control on HC microstructural integrity. Methods: Ten young (Yng, 25 ± 2 years) and ten middle-aged adults (MA, 55 ± 3 years) laid in supine position for 10 minutes while arterial blood pressure (ABP) and heart rate (HR) were measured. R-R intervals and systolic blood pressures were plotted within a linear regression to calculate the spontaneous baroreflex slope. Subjects went in an MRI scanner to measure hippocampal viscoelastic properties using MRE. Results: As expected, we observed a lower cBRS in the middle-aged group compared with young (MA: 12.51±4.41 vs. Yng: 25.21±8.77 ms/mmHg, p≤0.05). There were no significant differences in HC stiffness or damping ratio when comparing between age groups (MA: 3.06±0.32 kPa vs. Yng: 3.02±0.09 kPa, p=0.69; MA: 0.2±0.02 vs. Yng: 0.2±0.03, p=0.56). However, a multiple linear regression with age included as a categorical covariate revealed a trend towards a stronger association between HC stiffness and cBRS in the middle-aged compared to the young group (p=0.07). CONCLUSION: In contrast to our hypothesis, preserved BRS was associated with lower HC stiffness in the middle-aged group; however, the physiological importance of this finding needs to be more completely explored. Our findings indicate that the association between short-term blood pressure regulation via cardiovagal BRS may be more closely linked to HC tissue integrity with advancing age. These mechanisms should be explored in a larger cohort including older individuals. Supported by UD Research Foundation 2020 Pilot Grant and P20GM113125. This is the full abstract presented at the American Physiology Summit 2024 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.
Use of Social Learning Tools Improves Engagement and Performance in Undergraduate Medical Physiology Education
Authors: Jim Catarina , Campusano Jessica , Tadal Stephanie , Niño Diego 
Published: May 2024

Objective: We sought to increase engagement, reduce cognitive load, and foster self-directed learning while potentially improving exam performance by incorporating a social annotation tool (SAT) into a flipped classroom setting in an undergraduate medical education curriculum. Hypothesis: We hypothesized that using the SAT (Perusall) as preparatory material for a flipped classroom would increase engagement and academic performance compared to using a pre-recorded lecture video when teaching cardiovascular physiology. Methods: Within a first-year undergraduate medical physiology course, students (n=125) used the SAT to annotate assigned cardiovascular physiology readings before a flipped classroom session. This strategy was compared to the common practice of providing students with a pre-recorded lecture. Students took an assessment before and after to assess knowledge acquisition and engagement with both formats. Results: The SAT intervention identified an average time spent engaged with the material of 142.1 minutes ( n=125), with a pre- and post-assessment score improvement of approximately 20.25% (61.5% vs 82%; n=81). The pre-recorded one-hour lecture found that students engaged with the material, on average, for 51.45 minutes, corresponding to an average of 91% video completion. Findings from this lecture intervention showed the pre- and post-assessment scores improved by an average of 5% (71% vs. 76%; n=80). A paired sample t-test identified a significant difference between the percent improvement between quizzes for SAT (M=19.71, SD=26.374) and percent improvement for recorded lecture (M=6.57, SD=26.369); [t(69)=3.450, p=0.001]. The use of SAT enhanced academic performance in midterm and final exams. The average performance in questions that mapped back to the flipped classroom utilizing SAT text was 91% (n=6) , as compared to an average performance of 73% to those questions that mapped back to the online pre-recorded lecture (n=11 ). Conclusions: Incorporating SATs into a flipped classroom model increased engagement and academic performance versus passive lectures when teaching medical physiology. Our study provides support to the use of social learning tools to enhance active learning in undergraduate medical education. none. This is the full abstract presented at the American Physiology Summit 2024 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 Heat Exposure on Inflammation and Platelet Activity in Adults with Heart Disease
Authors: Sardar Soha , Barry Hadiatou , Welman Mélanie , Mornas Adèle , Lordkipanidzé Marie , Gagnon Daniel 
Published: May 2024

INTRODUCTION: Extreme heat events are associated with a greater risk of cardiovascular mortality, especially in adults with pre-existing heart disease. The pathophysiological mechanisms mediating these relationships remain unknown. One proposed mechanism, supported by pre-clinical studies employing heat stroke models of severe body hyperthermia, is that heat exposure causes an inflammatory response leading to platelet activation and clot formation. It remains unknown if milder body hyperthermia, such as the one experienced during exposure to a hot environment, elicits an inflammatory response and/or increases platelet activity in adults living with heart disease.OBJECTIVES & HYPTOHESES: To assess whether exposure to a hot and humid environment (1) increases circulating concentrations of inflammatory cytokines and (2) induces platelet activation in adults with heart disease.METHODOLOGY: Adults living with coronary artery disease (67±8 years; 13M/2F) sat within a climate chamber maintained at 38°C and 50% humidity for 3h. Core (rectal) and skin temperatures were measured continuously. Blood samples were drawn before and 2.5h into heat exposure. The blood samples were analyzed for IL-6, IL-8, IL-18, TNFα and IL-1β (multiplexed bead-based immunoassay). Platelet aggregation was measured by impedance (Multiplate assay) induced with ADP (6.5 μM), TRAP (15 μM) and collagen (1.5 μg/ml). The total-thrombus analysis system (T-TAS, PL-CHIP) was used to measure thrombus onset time and total thrombogenicity.RESULTS: Core and skin temperatures increased by 0.35 ± 0.24°C and 4.85 ± 0.84°C, respectively (p<0.05). There were no changes (Δpost-pre) in IL-6 (0.31 ± 1.91 pg/ml, p=0.60), IL-18 (-10.29 ± 21.01 pg/ml, p=0.16), IL-8 (1.10 ± 2.39 pg/ml, p=0.18), TNFα (-1.12 ± 4.10 pg/ml, p =0.39), or IL-1β (0.53 ± 2.36 pg/ml, p=0.48) during heat exposure. Moreover, heat exposure did not increase platelet activation in response to ADP (-8.31 ± 33.70 U, p=0.34), TRAP (16.19 ± 36.54 U, p=0.10), or collagen (-9.19 ± 30.31 U, p=0.24). Lastly, there was no change in thrombus onset time (2.18 ± 37.31 s, p=0.850) or total thrombogenicity (2.8 ± 168.7 PL-AUC, p=0.90).CONCLUSION: These results suggest that inflammation predisposing to thrombus formation may not contribute to the greater cardiac risk associated with short-term exposure to humid heat. Canadian Institutes for Health Research. This is the full abstract presented at the American Physiology Summit 2024 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.
TRPV4-driven Regulation of miR-146a Expression in Macrophages and in a Mouse Model of Atherosclerosis
Authors: Dutta Bidisha , Mahanty Manisha , Rahaman Shaik O. 
Published: May 2024

MicroRNAs (miRs) are small, non-coding RNAs that have emerged as powerful regulators of gene expression. Emerging evidence suggests that miR-146a orchestrates anti-inflammatory/fibrotic processes in numerous cell types. Trpv4 (Transient Receptor Potential subfamily V member 4), a mechanosensitive, calcium-permeant channel/receptor, is expressed in numerous cell types including macrophages. Published work by our group and others show that Trpv4 is activated by a range of soluble and physical stimuli including matrix stiffness and cytokines. In mice, Trpv4 deficiency is associated with altered pressure responses, foreign body response, fibrosis, and inflammation. Previous work by our group and others suggest a pro-inflammatory/atherogenic role for Trpv4. Herein, we tested the hypothesis that Trpv4 regulates the expression of microRNA-146a in macrophages and in a mouse model of atherosclerosis. Our research found a 38% drop in miR-146a expression in macrophages treated with lipopolysaccharide (LPS) on a stiffer polyacrylamide hydrogel compared to a softer one as determined by RNAseq analysis, signifying miR-146a's sensitivity to mechanical factors. Trpv4's presence suppresses the LPS-induced increase of miR-146a in macrophages based on time and dosage. Trpv4 also plays a role in the suppression of miR-146a due to matrix stiffness. Notably, in mice, Trpv4 reduces the increase of macrophage miR-146a caused by a high-fat diet in aortic root regions. Given that matrix stiffening is common in atherosclerosis, this indicates a link between stiffness, Trpv4, and miR-146a. On the mechanism side, Trpv4 affects miR-146a expression not through its promoter methylation or activation of MAPKs, Stat1, AKT, and NFκB. Trpv4 residues 100 to 130 are required for suppression of LPS-induced upregulation of miR-146a. To sum up, Trpv4 appears to inhibit macrophage miR-146a expression through pathways that are distinct from those involving MAKPs/Stat1/AKT or NFκB. Understanding this mechanism could pave the way for new treatments targeting miR-146a to counter inflammatory diseases. Source of research support: NIH (R01 AI172086) grant to Shaik O. Rahaman. This is the full abstract presented at the American Physiology Summit 2024 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.
Mir-146a is required for foreign body response and giant cell formation
Authors: Mahanty Manisha , Dutta Bidisha , Rahaman Shaik O. 
Published: May 2024

The implantation of biomaterials or medical devices often leads to the development of a foreign body response (FBR), an inflammatory condition that can lead to implant failure, which may cause harm to or death of the patient. Hallmarks of the FBR include accumulation of macrophages and destructive foreign body giant cells (FBGCs), and development of fibrous scar tissue encompassing the implant. There are no effective medical treatments for FBR, although improved fundamental understanding of the molecular mechanisms underlying the development of FBR may lead to novel strategies for the amelioration of FBR. MicroRNAs (miRs) are endogenous, small, non-coding RNAs that have emerged as powerful regulators of gene expression in numerous cellular processes including macrophage activation, inflammation, and fibrosis. In this research, we tested the hypothesis that specific miRs play a crucial role in regulating the FBR to biomaterials. In our subcutaneous implantation mouse model, we found that: 1) miR-146a expression levels decreased in the implant-adhered tissues, and the decrease correlated with increased macrophage accumulation, FBGC formation, and collagen accumulation; and 2) miR-146a deletion in mice exacerbated in vivo macrophage accumulation, FBGC formation, and collagen accumulation. In our in vitro model, we found that deficiency of miR-146a function exacerbated key macrophage functions including adhesion on stiff matrix, and FBGC formation in primary mouse macrophages. In essence, our findings suggest that miR-146a might act as a suppressor of FBR. We expect that the results of this study may provide invaluable information and insight regarding the molecular mechanisms mediating the FBR to biomaterials, which may lead to the development of a novel microRNA-based therapeutic strategy for the amelioration of the poorly understood FBR to biomaterials. NIH (R01 AI172086) grant to Shaik O. Rahaman. This is the full abstract presented at the American Physiology Summit 2024 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.