bluuebunny/crossref_metadata_2025_split huggingface dataset:
Females Maintain Fluid Balance across Consecutive Workdays in Heat When Fluids are Readily Accessible
Authors: Leblanc Hannah , Rawlings Alexander , Kozlin Michael , Przybysz Johnathan , Cavuoto Lora , Schlader Zachary , Pryor Riana 
Published: May 2024

Workers should aim to fully replace fluid losses during work in the heat to maintain work productivity and minimize risk of heat illnesses, however, fluid balance of females working during consecutive days in the heat is unknown. The purpose of this study was to test the hypothesis that females would maintain fluid balance during work across two consecutive workdays. Eight healthy females (age: 29±5, body mass: 75.3±20.1, body fat: 23±8%) completed two consecutive days (Day 1, Day 2) of heavy intensity work in a hot environment (35.9±1.2°C, 24±6% relative humidity). Work consisted of repeated 45/15 work/rest cycles of treadmill walking or cycling at 398±7 W of metabolic heat production and seated rest for 4 h. Every 20 min, participants were provided 237 mL of a sport drink to consume ad libitum. Urine flow rate (UFR) was measured before work. Urine specific gravity (USG) and nude body mass were measured before and after work. Fluid volume consumed and thirst (9-point Likert scale, 1=not thirsty at all, 9=very, very thirsty) were measured during work. Two-way repeated measures analysis of variance and paired samples t-tests were used to compare differences. Significance was set at p≤0.05. Percent body mass loss was not different between Day 1 (0.69±0.82%) and Day 2 (0.96±2.25%, p=0.935). Similarly, sweat rate was not different between Day 1 (0.57±0.12 L/h) and Day 2 (0.65±0.21 L/h, p=0.312). Participants consumed less fluid on Day 1 (64±21%, 25±10 mL/kg) compared to Day 2 (74±20%, p=0.026; 29±10 mL/kg, p=0.025). Participants consumed 68±19% and 77±20% (p=0.040) of fluid offered during work and 55±27% and 66±22% (p=0.173) of fluid offered during rest on Day 1 and Day 2, respectively. Resting thirst (Day 1: 2.1±1.1, Day 2: 1.6±0.5, p=0.096), change in thirst (Day 1: -0.5±0.9, Day 2: +0.3±1.3, p=0.111) and maximum thirst (Day 1: 3.6±1.1, Day 2: 3.6±1.4, p=1.000) were not different between days. USG was not different (p=0.839) across days before (Day 1: 1.009±0.010, Day 2: 1.009±0.010) or after (Day 1: 1.012±1.010, Day 2: 1.012±0.010) work, respectively. UFR was not different between days (Day 1: 2.2±1.4 mL/min, Day 2: 2.0±1.2 mL/min, p=0.836). Females completing heavy intensity work in heat maintained fluid balance across two consecutive days when fluids were readily accessible. Ad libitum fluid consumption may be suffcient to adequately replace fluid losses in females across consecutive days of work in heat. This project was funded by the National Institute for Occupational Safety and Health (1K01OH012016-01A1). 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 Anorexigenic Peptide, Nesfatin-1, Dampens the B Cell Response to Receptor Mediated Stimulation
Authors: Steffen Tara L. , Stafford Joshua , Samson Willis K. , Yosten Gina L.C. 
Published: May 2024

Obesity is an inflammatory condition marked by an increase in the accumulation of dysregulated B cells in adipose tissue (AT). These dysregulated B cells secrete pro-inflammatory mediators, cytokines and antibodies, that interfere with the normal function of the AT and contribute to the development of insulin resistance. Furthermore, depletion of the B cell compartment in a murine model has been shown to attenuate the metabolic aberrations associated with obesity. These data emphasize a clear role for B cell contribution to the comorbidities associated with obesity; however, the mechanism(s) regulating their accumulation and function are unknown. Therefore, discovery of targets that normalize the interaction between B cells and adipocytes has the potential to significantly reduce the burden of the inflammatory comorbidities of obesity that lead to metabolic disorders. Nesfatin-1 is a peptide hormone that is cleaved from the nucleobindin 2 (NUCB2) precursor along with two other peptides, nesfatin-2,3. Nesfatin-1 was originally described based on its anorexigenic effects in vivo, however recent reports have documented its anti-inflammatory activity. When NUCB2 is genetically deleted, there is a resultant increase in the presence of pro-inflammatory mediators in subcutaneous white AT (WAT). This is intriguing because humans with obesity have reduced serum nesfatin-1 in addition to low-grade chronic inflammation in WAT. However, the underlying mechanisms of how nesfatin-1 exerts its effects and its sites of action within the immune system have not been fully elucidated. In this study, we sought to determine a mechanism by which this peptide might directly interact with the immune system starting with a human B cell line, Raji. Here, we show that nesfatin-1 directly inhibits lipopolysaccharide (LPS) and B cell receptor (BCR) stimulated B cell proliferation while also protecting from inflammatory cell death. Furthermore, nesfatin-1 prevented stimulation induced secretion of pro-inflammatory mediators IgM and TNFa. Finally, we show that this effect is likely mediated via nesfatin-1’s ability to inhibit inflammatory pathway activation in this B cell line. Taken together, this work highlights a novel action of nesfatin-1 to directly bind to and inhibit B cell responses. These fundamental studies will serve as a springboard for the future development of nesfatin-1-based therapeutics for the treatment of obesity-associated inflammation, thus enabling potential new preventative strategies for forestalling the development of inflammation associated diseases, such as T2D. Saint Louis 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.
Circulating Extracellular Vesicle-Mediated Immune Activation After Resuscitation From Cardiac Arrest in Swine
Authors: Zahra Sumbule , Rolland Tyler J , Cucinotta Daniel , Hudson Emily R , Young Rebeccah , Weil Brian 
Published: May 2024

Objective: Systemic inflammation is a well-established contributor to morbidity and mortality in patients that are initially resuscitated from sudden cardiac arrest (SCA). However, our mechanistic understanding of immune activation in this context remains limited, impeding the development of targeted anti-inflammatory treatments. To address this knowledge gap, we tested the hypothesis that post-resuscitation immune cell activation is mediated, at least in part, by circulating extracellular vesicles (EVs). Methods: Swine (n=3) were subjected to 10 minutes of electrically-induced SCA followed by CPR with defibrillation and epinephrine (0.015 mg/kg iv) to achieve return of spontaneous circulation (ROSC). Blood samples were collected before SCA and 4-hours post-ROSC for isolation of plasma EVs from clarified plasma using 100kD filters, which were subsequently quantified by Nano-particle Tracking Analysis (ZetaView). Naïve PBMCs from healthy swine were cultured with basal media (negative control), lipopolysaccharide (LPS; positive control), or EVs isolated from pre-SCA or post ROSC plasma that were stained with lipophilic dye (DiD) to facilitate assessment of EV uptake (n=3 per group). After 24 hours in culture, PBMC activation was assessed via surface marker expression (flow cytometry) and inflammatory cytokine release (ELISA). Results: Compared with exposure to pre-SCA EVs and basal media, PBMCs exposed to post-ROSC EVs exhibited a significant shift toward an inflammatory phenotype, with enrichment of inflammatory dendritic cells (CD172+CD16+), inflammatory granulocytes (CD172+CD163-), and inflammatory macrophages (CD14+CD163+) in both DiD+ and DiD- cell populations (all p<0.05 vs. pre-SCA EVs). Although TNF-α, IFN-α, and IFN-γ were not detected after EV co-culture, a near-significant increase in IL-1β release was observed in PBMCs exposed to post-ROSC EVs vs. pre-SCA EVs (5.72±2.4 vs. 2.21±0.7 pg/mL; p=0.068). Conclusion: Our findings suggest that circulating plasma EVs may contribute to immune cell activation following systemic ischemia/reperfusion injury associated with resuscitation from SCA. Further studies to delineate mechanisms underlying EV-mediated pro-inflammatory shifts in immune cell phenotype and potentiation of IL-1β release may reveal novel therapeutic targets to mitigate post-resuscitation inflammation and improve patient outcomes following SCA. Supported by funding from the NIH and US Department of Veteran's Affairs. 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.
Assessing the correlation between resting cerebral blood flow and three different cerebrovascular reactivity stressors
Authors: Khademi Motlagh Hedyeh , Haley Travis , Didier Kaylin , Muer Jessica , Wannebo Brett , Wieben Oliver , Al-Subu Awni 
Published: May 2024

Background: Understanding the regulation of resting cerebral blood flow (CBF) is crucial in the realm of brain health as previous studies indicate reduced CBF is associated with an increased risk of several neurological and cerebrovascular conditions. Concurrently, cerebrovascular reactivity (CVR), which assesses the ability of blood vessels to respond to stimuli, is a valuable indicator of cerebrovascular health, as reduced CVR to increased CO2 is associated with increased stroke, cognitive decline, and mortality risk. Thus, evaluating CVR may serve as a useful tool to understand pathologic brain conditions. In this study, we sought to address these intricacies by examining how the brain responds to different physiological stressors, such as hypercapnia, hyperoxia, and hypoxia. We tested the hypothesis that a) lower resting CBF is associated with reduced CVR-CO2, b) lower resting CBF is associated with reduced CVR-hyperoxia c) lower resting CBF is associated with reduced CVR-hypoxia. Methods: 51 young, healthy adults (19F) were included (23±4 yr). Females were not taking hormonal birth control and studied on days 1-7 of the menstrual cycle. Participants completed a magnetic resonance imaging (MRI) scan and CBF was quantified using arterial spin labeling (ASL). CVR was evaluated using a resting normoxia compared to: hypercapnia (5% CO2; 32M/19F), isocapnic-hyperoxia (100% O2; 8M/7F) and isocapnic hypoxia (80-85±1% oxygen saturation (SpO2); 12M/2F). Relative CVR was calculated by the ratio of %ΔCBF/ΔEnd tidal CO2 (ETCO2) for hypercapnia, %ΔCBF/ΔSpO2 for hypoxia, and hyperoxic reactivity was analyzed as relative CBF change (%Δ). Data were analyzed using correlation with significance set at p<0.05 and are displayed as mean ± SD. Results: ETCO2 increased from 35±3 to 42±3 mmHg during hypercapnia (p<0.05), but did not change significantly during hyperoxia or hypoxia conditions (p>0.05 for both). SpO2 decreased from 98±1% to 84±2 % during hypoxia (p<0.05). There was no significant correlation between resting CBF and CVR-CO2 (r2=0.02, p=0.23), as well as CVR-hyperoxia (r2=0.07, p=0.3). However, lower CVR-hypoxia was significantly correlated with lower resting CBF (r2=0.27; p=0.05). Conclusion: These findings suggest there is an association between resting CBF and hypoxic reactivity, but not hypercapnic or hyperoxic reactivity indicating a single measure of vascular health may not be suffcient to understand cerebrovascular function in health. Further studies with larger and more diverse populations may provide deeper insights into these intricate interactions. Funding NIH R01 HL 150361. 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.
Chronic Unpredictable Stress Induces Mitochondrial Dysfunction in Hypothalamic Pituitary Adrenal Axis Regions
Authors: Hollis Fiona , Frambes Noelle , Churillo Amelia , Mullaly Alaina , Doster James , Stegmann Kyle , Priviero Fernanda 
Published: May 2024

Background: Stress elicits physiological and behavioral responses via adaptive responses like the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) activation. Under chronic stress, however, these responses become dysfunctional leading to pathological changes in behavior and health. Mitochondria are dynamic organelles that provide cellular energy, activate immune responses, and synthesize glucocorticoids in the adrenal glands in response to stress. Thus, the mitochondrion is a key candidate linking the effects of chronic stress and health, however, the effects of chronic stress on mitochondrial function in the HPA axis, particularly with respect to sex differences, are largely unexplored. Hypothesis: Chronic unpredictable stress (CUS) decreases mitochondrial function and dynamics in key regions within the HPA axis. Methods: Adult male and female C57Bl6/J mice were exposed to 28 consecutive days of CUS or handling (non-CUS) with weekly weighing. Mice were euthanized 24h after the last stress exposure and the brain and adrenal glands dissected and weighed. Mitochondrial function was assessed using high resolution respirometry in hypothalamus and adrenal tissues. Protein expression was assessed by immunoblot. Results: CUS decreased mitochondrial respiration within key stress centers, with stressed males exhibiting decreased respiration in the amygdala (20%, p=0.05), and stressed females exhibiting decreased respiration in the hypothalamus (20%, p=0.004) and adrenal glands (17%, p=0.06). CUS increased mitochondrial complex protein in male adrenal gland (47%, p=0.01) and mitochondrial mass in hypothalamus (p=0.007). Finally, cleaved Gasdermin D expression was increased nearly 2-fold in male hypothalamus (p=0.03). Conclusions: Our data show sex- and region-dependent decreases in HPA axis mitochondrial function concurrent with upregulated protein expression and pore formation. These observations point to sex-specific effects of CUS to induce mitochondrial dysfunction. This work was supported by P20GM109091 (F.H.), R01HL130972-01A1, R01HL5949, BX000168-10A1, BX005320 (F.G.S.), R01DK132948 (C.W. & F.P.) R01 MH129798 (SKW); VA VISN7 RDA (F.H.), 1U54HL169191-01 & BX002604 (M.J.R.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the abstract. 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.
Carbon Dioxide as a Novel Blood Pressure Therapy for Neurogenic Orthostatic Hypotension
Authors: Baker Jacquie , Ranada Shaun , Incognito Anthony , Sheldon Robert , Wilson Richard , Phillips Aaron , Raj Satish 
Published: May 2024

BACKGROUND: On standing, people with neurogenic orthostatic hypotension (nOH) experience plummeting blood pressure (>20/10mmHg), crippling symptoms, and syncope. Current blood pressure therapies lack effcacy and have serious side effects. In healthy people, increased inspired CO2 increases blood pressure. This raises the tantalizing possibility that increased inspired CO2 may effectively treat nOH patients. OBJECTIVE: We aimed to understand if increased inspired CO2 can increase standing blood pressure in nOH. METHODS: Seventeen patients with nOH (F=5; 71±8 years) completed three randomized sit-to-stand tests with inspired CO2 maintained 0mmHg (0CO2), +5mmHg (+5CO2) or +10mmHg (+10CO2) relative to baseline. Respiratory and hemodynamics (blood pressure, heart rate, stroke volume, cardiac output, systemic vascular resistance) were continuously measured. Data are reported as mean ± SD. The change (stand-sit) in respiratory and hemodynamics between 0mmHg, +5mmHg and +10mmHg were compared using a repeated measures ANOVA with a Bonferroni correction. RESULTS: Inspired CO2 caused a dose-dependent increase in standing blood pressure (0CO2:-43±25mmHg; +5CO2:-22±26mmHg; +10CO2:-4±30mmHg; p<0.001). Blood pressure changes were predominantly facilitated by increased stroke volume (0CO2:-10±10mL; +5CO2:-5±10mL; +10CO2:0.1±10mL;p<0.001) and cardiac output (0CO2:-0.2±0.6L/min; +5CO2:0.2±0.5L/min; +10CO2:0.7±0.5L/min; p<0.001) as neither the changes in heart rate (p=0.2) nor systemic vascular resistance (p=0.6) were different across CO2 conditions. Breathing CO2 decreased the percentage of time that standing systolic blood pressure dropped ≥20mmHg (0CO2:75±35%; +5CO2:48±38%; +10CO2:32±37%; p<0.001) and fewer patients met the blood pressure criteria for orthostatic hypotension (p=0.02). CONCLUSION: Our data indicates increased inspired CO2 can increase standing blood pressure in nOH patients by increasing stroke volume and cardiac output. CO2 may offer a novel pressor therapy for patients with nOH. This work was supported by a University of Calgary Seed Funding (S.R.R). J.R.B is supported by a Canadian Institutes of Health Research (CIHR) Fellowship, a Libin Cardiovascular Institute Post-Doctoral Fellowship in Women’s Cardiovascular Health, the Natural Sciences and Engineering Research Council of Canada (NSERC) Brain CREATE Program, and a Canadian Cardiovascular Society Fellowship. S.I.R. is supported by the NSERC Brain CREATE Program, an Alberta Graduate Excellence Scholarship, and an Alberta Strategy for Patient Oriented SUPPORT Unit scholarship. A.V.I is supported by a CIHR Fellowship and an Achievers in Medical Science Postdoctoral Fellowship. 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 Cross-Correlation Between Spikes and Local Field Potentials at Different Running Speeds During Entorhinal Cortex Inactivation
Authors: Zhao Ben , Qin Yu , Lovett Sarah , Besosa Cristina , Kennedy Jack , Burke Sara , Maurer Andrew 
Published: May 2024

Understanding neural spike dynamics and their interaction with local field potentials is crucial for deciphering neural connectivity. This study utilizes data generously shared by Zutshi et al. in 2022 (PMID: 34890566) to investigate spike characteristics and their cross-correlation with local field potentials. Our findings reveal significant shifts in the interspike interval (ISI) distributions during the medial entorhinal cortex (mEC) inactivation, with the instantaneous burst frequency exhibiting an overall decrease and preference for lower frequencies. These differences in the spike distributions were observed in individual cells, accompanied by changes in mean firing rates. Further exploration of the cross-correlation between spike multiunit activity (MUA) and the theta rhythm uncovers distinct coupling patterns. In the control cases, spikes closely align with theta peaks, whereas this alignment is disrupted during the mEC inactivation. Notably, we find that the strength of this cross-correlation is amplified at higher running speeds. This research enhances our understanding of neural dynamics, shedding light on the intricate relationship between spikes, local field potentials, and running speed, with potential implications for neural connectivity studies. R01MH126236 1R01MH109548-01A1. 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.
Impact of lymphangiogenesis on renal phosphate handling following kidney injury
Authors: Phan Thien , Creed Heidi , Weiss Dawson , Vu Myles , van der Weiden Christiaan , Reyna Andrea , Rutkowski Joseph 
Published: May 2024

Overconsumption of inorganic phosphate (Pi) causes tubular cell damage and kidney dysfunction, and hyperphosphatemia can lead to Ca2+ retention, vascular calcification, and cardiovascular disease. Conversely, kidney injury and chronic kidney disease (CKD) cause hyperphosphatemia and Pi retention. We hypothesized that the damage caused by chronic Pi consumption likely induces kidney lymphangiogenesis and that changes to renal lymphatic density may alter kidney mineral handling. We identified significant lymphangiogenesis and increased expression of the lymphatic growth factors VEGF-C/D in kidneys of mice fed a 2% Pi diet for 2 months and as early as three weeks of diet. We then utilized “KidVD” mice, a mouse model of kidney-specific inducible expression of VEGF-D, to expand renal lymphatic density and test Pi handling. Mineral handling was largely normal in male and female KidVD mice compared to littermates on Pi diet. In a Pi-driven CKD model mice were injured with 10 mg/kg cisplatin dose, allowed to recover for 2 weeks, then challenged with chow or 2% Pi diet for 3 weeks with VEGF-D induction. This resulted in Pi retention in all mice. Pi handling in both male and female KidVD mice were normal to controls. Female KidVD, however, demonstrated significantly increased Ca2+ excretion compared to controls. Circulating FGF23 levels were significantly elevated in male and female with VEGF-D overexpression. Gene expression of Fgfr1 was also significantly increased in male and female KidVD mice. Renal lymphangiogenesis thus appears to specifically impact Ca2+ retention through the FGF23-Fgfr1 axis. National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R01 DK119497). 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.