bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic unpredictable stress changes left ventricular geometry and activation of the inflammasome
Authors: Churillo Amelia , Freeburg Lisa , Stegmann Kyle , Doster James , Frambes Noelle , Crockett Alexia , Priviero Fernanda , Hollis Fiona , Wood Susan , Webb Clinton , Ryan Michael , Spinale Francis 
Published: May 2023

Background: Psychosocial stress, particularly chronic unpredictable stress (CUS) has been identified as a risk factor for cardiovascular disease, but the effects of CUS on left ventricle (LV) function, geometry and systemic hemodynamics remains unclear. Moreover, whether and to what degree CUS activates intracellular formation of the inflammasome, including the NOD-LRR pyrin containing protein 3 (NLRP3) remains unknown. Accordingly, the central hypothesis of this project was that in a murine model of CUS, shifts in LV geometry and systemic hemodynamics would occur and be associated with the induction of NLRP3. Methods and Results: Mice (C57BL/6, 10wks of age, equal sex, n=16) were subjected to CUS for 4 weeks which entailed daily random stressors including tilted cage, wet bedding, and overnight light. Referent age and sex matched non CUS mice served as controls (n=16). LV function was assessed by high fidelity ultrasound and blood pressure measurements by tail cuff for both referent control and CUS mice. The changes in ambient heart rate (HR), LV end-systolic volume (LVEDV), and systolic blood pressure (SBP) were expressed as a function of referent control. All results are reported as mean ± SEM. While LV ejection fraction was equivalent between CUS and control groups (70 ± 3 vs. 67 ± 3%, respectively, p=0.48), HR trended higher (4.5 ± 3.1%, p=0.08), LVEDV was lower (-11 ± 5%, p=0.03) and SBP was elevated (12.1 ± 4.9%, p=0.04) - all indicative of heightened sympathetic tone. LV myocardial NLRP3 (rtPCR) was increased (1.47 ± 0.22 fold change, p=0.04) with CUS as was IL-1β (1.43 ± 0.20 fold change, p=0.05), a downstream cytokine activated by NLRP3. Conclusion: CUS, in and of itself, shifts LV geometry, causes mild hypertension and induction of the myocardial inflammasome- all of which would exacerbate/contribute to cardiovascular disease. This work was supported in part by National Institutes of Health grant R01HL130972-01A1 (F.G.S.), R01HL5949 (F.G.S.), RO1DK132948 (C.W. & F.P.), R01 MH129798 (SKW) and P20GM109091 (F.H.) as well as a Merit Award from the Veterans Health Administration, BX000168-10A1 (F.G.S.), BX005320 (F.G.S.), BX002604 (M.J.R.), and VISN7 RDA (F.H.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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 5-HT1A agonist 8-OH-DPAT reverses the suppression of breathing but not swallowing caused by opioid administration in female rats
Authors: Frazure Michael , Morimoto In , Greene Clinton , Kimberly Iceman , Pitts Teresa 
Published: May 2023

The objective of our study was to determine the role of 5-HT1A receptors in modulating breathing and swallowing following opioid administration. Our previous experiments in anesthetized male and female Sprague Dawley rats demonstrated that swallow is suppressed by the opioid buprenorphine, and that female rats are more susceptible to buprenorphine-induced respiratory arrest (71% mortality at 0.3 mg/kg) than male rats (100% survival at 0.3 mg/kg). We hypothesized that following buprenorphine administration, intravenous administration of the 5-HT1A agonist 8-OH-DPAT would restore breathing and swallowing. Experiments were performed in spontaneously breathing female Sprague Dawley rats anesthetized with sodium pentobarbital ( n = 7). Bipolar electromyography (EMG) wires were inserted into various muscles to measure breathing and airway protective behaviors. Swallow was stimulated by oral water infusion. Intravenous buprenorphine was administered in doses that yield respiratory arrest in female rats. Sustained apnea occurred in 86% of animals following buprenorphine administration (one animal resisted respiratory depression). 8-OH-DPAT was then administered to effect (100, 300, or 1,000 μg/kg i.v.). 8-OH-DPAT did not restore swallow, but breathing was recovered in 100% of animals (33% at 100 μg/kg, 50% at 300 μg/kg, and 17% at 1,000 μg/kg). This effect of 8-OH-DPAT was reversed by the 5-HT1A antagonist WAY 100635 (1 mg/kg i.v.), which abolished breathing in all animals. These results indicate that 5-HT1A agonists may be utilized to restore breathing following respiratory arrest, and that opioid-induced depression of breathing and swallowing are mediated by potentially separate mechanisms. This work was supported by NIH grants HL 111215, HL 103415 and OT20D001983, the Craig H. Neilsen Foundation Pilot Research Grant 546714, Kentucky Spinal Cord and Head Injury Research Trust, and the Commonwealth of Kentucky Challenge for Excellence. 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.
Implementation and effects of low stakes quiz feedback on exam performance in a health professional program
Authors: Bains Mona , Goei Kathleen , Kaliski Debora 
Published: May 2023

Introduction: The inclusion of interactive learning approaches in graduate education including mobile polling, game-based learning, physiology apps, eLearning activities and tablet use to supplement course content is an established means to improve student engagement. Strategies that continue to support learning asynchronously with the purpose of driving deeper critical thinking and reasoning has the potential to further advance course outcomes. The purpose of this investigation was to assess whether the incorporation of detailed asynchronous feedback to low stakes quizzes as an additional learning tool translates into improved exam performance in the Foundational Sciences. Methods: ExamSoft assessment data was collected across 2 semesters from 101 Doctor of Physical Therapy students enrolled in a Foundational Sciences course series encompassing cardiopulmonary, pediatrics and neuro blocked content. Exam performance was compared between 2 cohorts (non-feedback, n=53 and feedback group, n=48) following the implementation of detailed question feedback on low stakes semester quizzes with the second cohort. Exam performance on specific subject areas was also reviewed for select exam questions that directly aligned with quiz questions. Results: Independent samples t-test analyses indicated that learners in the feedback group demonstrated consistently improved exam performance for midterm (p < 0.001 for summer midterm and p < 0.01 for fall midterm) and final exams (p < 0.01 for both summer and fall final exams) across the 2 semesters when compared to the non-feedback group. Similar results were observed when specific exam questions were reviewed across physiology content areas. Vestibular physiology exam performance was significantly (p = 0.05) improved in the feedback group, while basal ganglia physiology showed a trend but was not significant. Pharmacology exam performance was significantly improved for the fall final exam (p < 0.001), but not for the fall midterm. Conclusions: Instructor tailored quiz question feedback, which requires student review to view the correct answer choice is an additional learning opportunity that results in improved course outcomes. This approach to providing feedback to low stakes assessments focuses the in-class time on new material because the quiz feedback can be reviewed asynchronously as needed by the learner. Using the learning management system quiz feedback feature provides a valuable strategy to further support learning outside of the classroom and provides an opportunity for students to synthesize and apply content at a deeper level. 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 Mechanical Stretch on Sex-Dependent Gene Expression by RNA Sequencing in Mouse Renal Endothelial Cells
Authors: Colvert C , Hawkins Kennedy , Oates Jim , DeLeon-Pennell Kristine , Van Beusecum Justin 
Published: May 2023

Increased mechanical endothelial cell stretch contributes to the development of numerous cardiovascular and renal pathologies by orchestration of immune cell activation. While endothelial cells are not recognized as professional antigen presenting cells, they can express both major histocompatibility complexes (MHC) I and II. MHCs are essential to form part of the immunological synapse during antigen presentation to adaptive immune cells. The mechanisms by which increased endothelial cell stretch regulates renal endothelial antigen processing and presentation is unknown. We hypothesized that increased mechanical endothelial stretch promotes upregulation of key antigen processing and presentation genes in mouse renal endothelial cells (MRECs) in a sex-dependent manner. MRECs derived from both sexes underwent 5%, 10%, and 15% (1 Hz) uniaxial cyclical stretch for 48 hours. After stretch, RNA sequencing was performed and bioinformatic and pathway analysis was executed to determine potential inflammatory mechanisms of action. We found that 10% stretch induced downregulation in MHC and costimulatory genes ( H2-Da, H2-K1, H2-T23, H2-T24) and upregulation of antigen processing associated genes ( tap1, psmb2, psmb4, and psmb8) in male MRECs. Females undergoing 10% stretch exhibited inverse gene expression profiles with upregulation of MHC genes and downregulation of antigen processing and presentation genes. At 15% stretch, the sex-specific gene expression tendencies were inverse from 10% stretch. To understand the function of differential gene expression we performed gene ontology enrichment pathway analysis. Male MRECs undergoing 10% stretch exhibited an enrichment for renal and cardiovascular development processes and inflammatory processes including chemokine-mediated signaling and cytokine-mediated signaling. When we compared female MRECs at 10% stretch, we found enrichment for renal and cardiovascular development processes including endothelial cell migration, angiogenesis and glomerular vascular, kidney, and artery development. Interestingly, 10% mechanical stretch enriched pro-inflammatory processes including positive regulation of cell migration and leukocyte migration. These data provide novel insight into how mechanical stretch regulates key antigen processing and presentation pathways in renal endothelial cells in a stretch and sex-dependent manner. This work was funded by MUSC Core Centers for Clinical Research Project Award to JPVB and Biomedical Laboratory Research and Development Service of the VA office of Research and Development Awards IK2BX003922 to KYDP and IK2BX005605 to JPVB. 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.
Cerebrovascular reactivity to carbon dioxide is not altered in otherwise healthy individuals six months post-concussion
Authors: Young Benjamin , Skow Rachel , Nandadeva Damsara , Garza Nicole , Stephens Brandi , Smith Scott , Lockette Warren , Fadel Paul 
Published: May 2023

Introduction: Concussion, a form of mild traumatic brain injury (TBI), has an estimated annual incidence of 1-4 million cases in the US alone. Studies have documented impairments in cerebral vascular function following concussion which often coincide with other neurocognitive symptoms but, in some cases, persist despite symptom resolution. However, the majority of these studies were performed 3 months or less post-concussion. Therefore, we tested the hypothesis that cerebral vasodilator function is impaired in adults who had a concussion 6 months prior and are asymptomatic relative to healthy age- and sex- matched controls with no known history of concussion. Methods: Six adults (3 Male/3 Female, 26 ± 5 years) with a history of diagnosed concussion ~6 months prior to the study visit (average, 6 ± 1 months) and six controls (3 Male/3 Female, 28 ± 5 years) without a known history of concussion were recruited. Beat-to-beat blood pressure (finger photoplethysomography), middle cerebral artery blood velocity (MCAv; transcranial Doppler ultrasound) and partial pressure of end-tidal carbon dioxide (PETCO2; capnography) were measured continuously during two-minutes of quiet supine rest and throughout a rebreathing protocol designed to increase PETCO2 up to +15mmHg. Cerebral vascular conductance index (CVCi) was calculated as mean MCAv divided by mean arterial pressure (MAP) on a beat-to-beat basis. Cerebrovascular reactivity was assessed as the percent change in MCAv or CVCi at increasing levels of PETCO2 (Δ3,6,9,12,15 mmHg PETCO2) and the gain of the relationship between MCAv or CVCi and PETCO2. Results: Resting MAP (P=0.33), MCAv (control: 76 ± 6 cm/sec; TBI: 74 ± 8 cm/sec, P=0.82), and CVCi (control: 0.91 ± 0.08 cm/sec/mmHg; TBI: 0.86 ± 0.11 cm/sec/mmHg, P=0.72) were not different between groups. The CO2 rebreathing protocol increased MCAv and CVCi in both groups (main effect of time; P<0.001 for both). However, the percent change in MCAv and CVCi did not differ between control and TBI participants throughout the rebreathing protocol (Interaction, P=0.13 and P=0.26, respectively). Likewise, the MCAv (control: 3.5 ± 0.4 cm/sec/mmHg; TBI: 4.0 ± 0.6 cm/sec/mmHg, P=0.51) and CVCi (P=0.72) gains were not different between groups. Conclusion: These preliminary findings suggest that individuals six-months post-concussion who are asymptomatic do not exhibit impaired cerebral vasodilator function. This project was supported by the Henry M Jackson Foundation HU0001-18-2-0016. 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 influence of early menopause on the hemodynamic responses to isometric exercise
Authors: Anselmo Miguel , Panigrahy Nisha , Teshome Soliana , Tahsin Chowdhury Tasnova , Stokes William , Lee Emma , Glazos Aline , Vanden Noven Marnie , Carter Jason , Keller-Ross Manda 
Published: May 2023

Introduction: Menopause is linked to a heightened risk of hypertension and cardiovascular disease and early menopause (EM; age<46yrs) increases this risk. Exaggerated hemodynamic responses to exercise are associated with a greater risk of developing hypertension. Postmenopausal females demonstrate elevated blood pressure (BP) reactivity to isometric exercise compared with premenopausal females. It remains unknown whether these differences are attributable to menopause or age, and how EM influences reactivity. We hypothesized that females who experienced EM would have greater BP and heart rate (HR) reactivity to an isometric handgrip exercise (IHG) compared with typical-age-menopausal females (TAM; age 46-55yrs). Methods: Twenty-two postmenopausal females completed two study visits. Participants were divided into two age-matched groups: EM (n=11) and TAM (n=11). Visit 1 consisted of consent and health questionnaires. Visit 2 consisted of three maximal voluntary contractions of the left hand, three minutes of baseline rest, and IHG at 30% of maximal strength to failure; continuous measurements of HR and BP were collected. Results: Groups were similar in age (EM:60±3; TAM:60±3yrs; p=0.89), BMI (EM:26±1; TAM:24±1kg/m2; p=0.14), maximal voluntary contraction (EM:154±10; TAM:155±8N), but different in menopause duration (EM:20±2: TAM:12±2yrs; p=0.01). There were no differences in resting systolic BP (EM:125±6; TAM:124±4mmHg; p=0.97), diastolic BP (EM:79±3; TAM:75±3mmHg; p=0.45), mean BP (EM:94±3; TAM:92±3mmHg; p=0.79), and HR (EM:61±3; TAM:59±1bpm; p=0.46). During IHG, BP and HR increased similarly in both groups (p>0.05 for all). Conclusion: We have observed that neither duration of menopause nor age of menopause influence BP and HR reactivity during IHG. Although the sample size is low, these data suggest that greater hemodynamic reactivity to isometric exercise does not contribute to cardiovascular disease risk in EM females. This study was supported by a NIH 1 K01 AG064038-01A1 (MLKR), UMN Grant-in-Aid (MLKR), F32HL160012 (EL), and NIH National Center for Advancing Translational Sciences grant UL1TR002494. 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.
Mixed Matrix Thermoset Casting with Thermoplastic Fused Filament Fabrication 3D Printing
Authors: Khanjar Saleh , Tyagi Prisha , Ajjarapu Kameswara Pavan Kuma , Kate Kunal 
Published: May 2023

Thermoplastic materials are known for their toughness and elasticity, Thermosets are known for their stiffness and hardness. Multiple additive manufacturing processes can 3D Print thermoplastic or thermoset, but no current additive manufacturing technique can handle 3D printing both materials (thermoplastic & epoxy thermoset resins) simultaneously. Additionally, not enough studies highlight how materials would perform when a mixture of thermoset and thermoplastic are manufactured together. To address this issue in this work we are combining thermoplastics with the casting of thermoset. We printed tensile bars and 3-point bending bars with PLA with different infill percentages, Then infilled them with epoxy. The percentage increase on the toughness and elongation of the part by combining thermosets and thermoplastic was compared. Additive manufacturing of polymer composites infilled with epoxy thermosets has enormous potential for 3D printed construction structures. The application of Mixed Matrix Thermoset Casting within Thermoplastic Fused Filament Fabrication 3D Printing revealed promising results, addressing component efficiency and sustainability. Especially when virgin thermoplastic is replaced with recycled thermoplastic material and petroleum-based epoxies are replaced with bio-based epoxy. This work focused on engineering toughness and stiffness of mixed matrix composite material to match industrial requirements of construction materials. self funded 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 contribution of intermediate conductance calcium-dependent potassium channels to hypothalamic vasopressin neuronal excitability
Authors: Shook Erin , Kirchner Matthew , Campos-Lira Elba , Stern Javier 
Published: May 2023

Vasopressin (VP) magnocellular neurosecretory neurons of the supraoptic nucleus (SON) in the hypothalamus are critical regulators of renal water retention and vascular tone. VP neurons undergo detrimental plastic changes in cardiovascular diseases such as heart failure (HF), resulting in hyperexcitability and thus altered fluid/electrolyte balance. Hyperexcitability is caused in part by changes in intrinsic excitability mechanisms, including the slow afterhyperpolarization (sAHP), a phenomenon underlain by a calcium-dependent K+ current ( I sAHP). The sAHP is activated by Ca2+ and results in an efflux of K+ from the cell, hyperpolarizing it, and throttling firing. Importantly, we found that the sAHP is greatly inhibited in VP neurons from HF rats, contributing to increased neuronal excitability in this condition. While the features of the sAHP are well characterized, the identification of the channel underlying the I sAHP is unknown. Combining patch clamp electrophysiology and pharmacology in Wistar rats, we investigated Intermediate conductance Ca2+-dependent K+ (IK) channels as a potential candidate responsible for carrying the I sAHP. We generated and measured I sAHPs in voltage clamp via fixed steps of twenty spikes at twenty Hz and measured the the I sAHP as the resulting tail current at the end of the pulse. To account for rundown of the current over the recording period and for the pharmacological blocker’s slow mechanism of action, we measured I sAHPs every 60 seconds for at least 15 minutes. Bath application of TRAM-34 (2 μM) at 7 minutes, a specific IK channel blocker, failed to inhibit I sAHP peak amplitude or area (p > 0.05; n=36 SON neurons). We used biocytin-filled pipettes to identify neurons post hoc and run immunohistochemistry for oxytocin (OT) and VP to identify cell type within the SON. We found no significant difference in I sAHP amplitude or area between VP and OT cells under either control or TRAM-34 application. Taken together, our studies indicate that IK channels do not contribute to the I sAHP in SON neurosecretory neurons, despite robust IK expression in this region. Future studies will aim at identifying the role that IK channels play in SON, as well as targeting other potential K+ channel candidates for this NHLBI F32 HL158172 (MKK) NHLBI HL090948 (JES) NINDS NS094640 (JES) 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.