bluuebunny/crossref_metadata_2025_split huggingface dataset:
Examining Vascular Function and Oxidative Stress in Young Individuals with Generalized Anxiety Disorder
Authors: Richardson Jake , Weggen Jennifer , Darling Ashley , Chiu Alex , Decker Kevin , Garten Ryan 
Published: May 2022

Generalized anxiety disorder (GAD) is a disabling psychiatric condition that can result in physiological manifestations linked to a greater risk for cardiovascular disease (CVD). Peripheral vascular dysfunction may be one mechanism augmenting CVD risk as GAD is linked to an overactivation of the sympathetic nervous system, a phenomenon that can result in excessive vasoconstriction and increases in oxidant production in the vasculature and bloodstream. Excessive oxidant production can overpower the body’s endogenous antioxidant defense system resulting in oxidative stress, a known modulator of peripheral vascular function.PurposeThe purpose of this study was to evaluate peripheral vascular function and oxidant production in young individuals with GAD. We hypothesized that young individuals with GAD would exhibit blunted vascular function and greater oxidant production when compared to age‐ and sex‐matched individuals without GAD.MethodsFifteen individuals with GAD (11 females, 4 males; age 22 ± 2 years), and 13 healthy controls (CTRL; 9 females, 4 males, 23 ± 4 years), participated in the study. The 7‐item Generalized Anxiety Disorder (GAD‐7) self‐report scale was utilized to screen for GAD with a GAD‐7 score of ≥ 10 used as the cut‐off point for the GAD group and a score of ≤ 5 used as the cut‐off point for the control group. Arm vascular function was assessed via the reactive hyperemia‐induced flow mediated dilation of the brachial artery (BAFMD) technique and evaluated with Doppler ultrasonography. Brachial artery and arm microvascular function were determined by percent change of diameter from baseline normalized for BA shear rate (BAD/Shear) and blood flow area under the curve (BF AUC), respectively. Whole blood superoxide concentration was assessed via electron paramagnetic resonance (EPR) to determine potential differences in oxidant production.ResultsYoung individuals with GAD had greater GAD‐7 scores (p < 0.001) when compared to controls (GAD: 15 ± 3; range 12 – 21; CTRL: 2 ± 2; range 0 – 5). BAD/Shear (GAD: 0.11 ± 0.06; CTRL: 0.10 ± 0.05 %/sec; p = 0.6), BF AUC (GAD: 21029 ± 11320; CTRL: 21727 ± 14493 milliliters; p = 0.9), and oxidant production (GAD: 52463 ± 72474; CTRL: 83472 ± 185805; p = 0.6) were not significantly different between groups.ConclusionContrary to our hypothesis, young individuals with GAD demonstrated similar macro‐ and microvascular function as well as similar whole blood oxidant production when compared to age‐ and sex‐matched individuals without GAD. This may highlight preserved cardiovascular health in young individuals with GAD.
Evaluating the Association of Sleep & Physical activity with Prolonged Concussion Symptoms
Authors: Neely Linda , Smulligan Katherine L. , Wingerson Mathew J. , Seehusen Corrine , Simon Stacey , Wilson Julie C. , Howell David R. 
Published: May 2022

IntroductionAdolescents with concussion will typically experience symptom resolution within 4‐weeks of injury; however, persistent post‐concussion symptoms (PPCS) may develop in approximately 30% of adolescents. Concussion management guidelines currently recommend a brief (24‐48 hour) rest period followed by sub‐symptom exercise to facilitate recovery. Additionally, poor sleep is associated with longer recovery, and early physical activity (PA) may accelerate symptom resolution. By understanding the individual association of both sleep and PA with symptom recovery, a basis can be provided for future recommendations on concussion intervention. Therefore, the purpose of this study was to determine whether sleep characteristics (duration, timing) and/or PA (steps/day, exercise frequency, duration, exercise intensity) in the first month after concussion are associated with PPCS.MethodsWe performed a prospective study of adolescent athletes who sustained a concussion and were evaluated within 14 days of injury. Participants received a Fitbit Charge 3TM to track PA and sleep parameters during recovery. The Post‐Concussion Symptom Inventory (PCSI) was used to determine symptom severity at the initial visit and the clearance visit. Participants were followed until symptom resolution, and the main outcome interest was development of PPCS (symptom duration ≥ 28 days). We then used a logistic regression model to examine associations between PA and sleep parameters with PPCS.ResultsOf the 49 patients included in the analysis, 47% (n=23, symptom resolution=57±23 days post‐injury) developed PPCS and 53% (n=26, symptom resolution=15±7 days post‐injury) did not. There was a significant difference between the PPCS and no PPCS groups in three different variables: steps/day (7526±2975 vs. 9803±3786; p=0.02), exercise days/week (2.5±2.2 vs. 4.4±2.1; p=0.005), and time in bed awake (1.2±0.3 hours/night vs. 0.8±0.3 hours/night; p=0.03). In our multivariable model, the risk of developing PPCS decreased by 1.6x with each additional exercise session/week (adjusted odds ratio=0.616, 95% confidence interval=0.389, 0.974, p=0.038).ConclusionsThe results suggest that participating in multiple exercise sessions per week during concussion recovery is associated with a lower risk of developing PPCS. Furthermore, taking more steps/day and spending less time awake in bed are associated with a shorter recovery period. Counseling patients on optimizing sleep and PA during concussion recovery may be one method for clinicians to promote recovery for their patients.
Investigating the Effect of Small Extracellular Vesicles at Varying Concentrations on Wound Healing
Authors: Henretta Sara , Kasper Anna , Gaborski Thomas 
Published: May 2022

Extracellular vesicles (EVs) are nanoscale lipid bilayer particles that are secreted by cells into their surrounding environment. EVs in the extracellular space taken up by nearby cells can influence the recipient cells’ phenotype. For this reason, EVs are believed by some to influence cell‐cell communication, specifically cell motility. While previous literature has claimed EVs have a significant effect of wound healing and cell recovery, we believe these results are due to cells being dosed in super supraphysiological levels of EVs. We hypothesize that cells dosed with EVs at physiological levels will have a less significant effect on wound healing properties than what has previously been seen. This study investigates the effect of adipose derived stem cell (ADSC) derived EVs on human dermal fibroblast (hDFb) migration and wound healing speeds using time lapse imaging and cell migration analysis code.Cell number recovery (CNR) is the ratio of the number of cells which have entered the wound region to the initial number of cells in the wound region prior to scratching. Initial number of cells in the wound region was estimated from the starting density of unscratched cells outside the wound region. A CNR of 1 indicates the wound has fully recovered and reached its initial density. We compared CNR in media control (complete media) and baseline control (serum free media) to cell recovery in EV dosed media with a concentration of 5*108 EVs/mL. EV doses were calculated such that they corresponded to EVs produced by ADSCs within 24 hours at a ratio ranging from 1:1 (5*109 EVs/mL) to 1:10 (5*108 EVs/mL) ADSCs to hDFbs. These ratios were chosen as they likely mimic the upper limits of physiological ratios during wound healing. Previous studies often used very high levels of EVs that may be relevant for therapeutic approaches. A vascular endothelial growth factor (VEGF) ELISA was performed to confirm growth factors did not co‐precipitate during isolation and did not influence the scratch wound assay results. EV Depleted media, collected from the supernatant of the final ultracentrifugation spin, confirmed the presence of VEGF. Conversely, both serum free and small EVs measured below the limit of detection for VEGF. These results confirm the slight increase in CNR is not due to growth factors that co‐isolated with EVs. In conclusion, EVs may provide a therapeutic effect for wound healing when dosed at supraphysiological levels, however, at more physiological levels, only a minor difference in wound healing is seen between the EV dosed cells and baseline controls.
The Effect of Meditation on Heart Rate Variability
Authors: Gonzales Rhianna , Hartman Sarah R. , Luckenbill Courtney , Logan Hannah , Cassel Spencer , Kieffer H. S. 
Published: May 2022

Heart rate variability (HRV) has been utilized in both medicine and sports sciences as an important marker for managing stress, indicating diseased states, and monitoring training/recovery. HRV reflects the autonomic balance of the sympathetic (SNS) and parasympathetic (PNS) nervous systems. High PNS activity is correlated to high HRV. The frequency and time domains of an ECG may be analyzed to determine the influence of PNS activity. HRV has been shown to be influenced by exercise training; however, meditation and guiding breathing techniques may also influence HRV.PURPOSETo evaluate the effect of a short, guided meditation session on the measures of heart rate variability of inexperienced meditators.METHODS39 participants (18‐21 years) volunteered and gave informed consent. During the experimental session, a Polar H10 heart rate monitor was fitted around the subject to record a 15‐minute ECG. The breathing protocol consisted of sitting in a comfortable position and continuous 5‐minute stages of spontaneous breathing (SP1), controlled breathing (CB), and returning to spontaneous breathing (SP2). During CB, a 6 breath/min guided protocol was followed using a commercially available App. A one‐way ANOVA with repeated measures was conducted for each variable using SPSS, p > 0.05.RESULTSCB produced a significant increase in heart rate from 70.6+11.9 bpm to 72.9+10.4 bpm (p<0.005) during CB, and then decreased to 71.7+10.3 bpm (p<0.05). Measures of the frequency domain included high frequency (HF) and low frequency (LF) power. HF significantly decreased from 49.2+21.1 nu during SP1, to 16.6+9.9 nu (p<0.005), and returned to 34.6+18.3 nu (p<0.005). For LF, SP1 was 50.9+21.0 nu, significancy increased to 83.4+9.9 nu (p<0.005), and returned to 65.4+18.3 nu (p<0.005). The measures of the time domain included rMSSD and SDNN. rMSSD at SP1 was 60.9+33.8, significantly increased to 74.2+36.6 (p<0.005), and returned to 56.0+33.1 (p<0.005). The SP1 for SDNN was 62.7+31.4, significantly increased to 110.4+39.6 (p<0.005), and returned to 66.1+29.7 (p<0.005). CONCLUSION: The direction and magnitude of change in frequency domain (HR, HF and LF) may initially suggest a dampening of the PNS. However, CB has been shown to initiate SNS activity which is represented in the frequency measures. In short‐term HRV measures, rMSSD and SDNN are the more appropriate measures to consider for the PNS activity. Thus, the results of this study indicate that a short session of CB may stimulate a PNS response.
Can Finnish Sauna Bathing Induce Heat Acclimation in Adults with Stable Coronary Artery Disease?
Authors: Bartlett Audrey‐Ann , Garceau Laurence , Gravel Hugo , Debray Amélie , Nigam Anil , Gagnon Daniel 
Published: May 2022

IntroductionExtreme heat is associated with a greater risk of mortality that particularly affects older adults with cardiovascular disease (CVD). Regular heat exposure induces an adaptation of thermoregulatory mechanisms (acclimation) that may alleviate thermal and/or cardiac strain during subsequent heat exposure. However, limited research has examined practical heat acclimation protocols that could be recommended to vulnerable populations, such as adults with CVD. The objective of this study was to test the hypothesis that 8 weeks of Finnish sauna bathing reduces core temperature and heart rate and increases sweating during heat exposure.Method14 participants (11 men/3 women, 63 ± 5 years, 28.7 ± 3.8 kg/m2) with stable coronary artery disease participated in an 8‐week Finnish sauna intervention (4 sessions/week, 20 to 30 min/session, at ~80°C, 20% humidity). Core temperature (ingestible telemetric pill), heart rate (Polar watch), and sweat rate (change in nude body weight) were measured during the first and last sauna sessions.ResultsResting core temperature prior to the first sauna session was 37.4 ± 0.4°C, compared to 37.1 ± 0.3°C prior to the last session (p= 0.04). Core temperature at the end of sauna bathing did not differ between the first (37.77 ±0.34°C) and the last (37.59 ± 0.31°C, p=0.20) sessions. Heart rate at the end of sauna bathing was greater during the last (90 ± 17 bpm) compared to first (85 ± 16 bpm, p=0.13) sessions. Sweat rate was greater during the last sauna session (first session: 8.6 ± 5.9 mL/min vs. last session: 5.1 ± 3.0 mL/min, p<0.01).ConclusionEight weeks of Finnish sauna bathing reduces resting core temperature and increases sweat rate during heat exposure in adults with stable coronary artery disease. However, these adaptations did not translate into reduced thermal and cardiac strain during heat exposure.
Contribution of ASICs to Cardiac Remodeling and Dysautonomia Associated with Heart Failure
Authors: Monaghan Karley , El‐Geneidy Maram , Sabharwal Rasna , Yang Liping , Gibbons David , Harding Anne M. S. , Ward Chad , Benson Chris 
Published: May 2022

INTRODUCTIONThe American Heart Association projects that by 2030 more than 8 million American adults will have heart failure (HF). HF is a condition in which the heart muscle is unable to sufficiently pump blood to meet the needs of the body. A characteristic of HF, and a major driver of the disease process, is an imbalance in the autonomic nervous system. Our lab and others have shown that the Acid Sensing Ion Channel subunit 3 (ASIC3) is highly expressed in the sensory nerves innervating the heart. Recent studies showed that chemically ablating these nerves attenuates cardiac remodeling after myocardial infarction (MI).METHODSWild type (WT) and ASIC3‐/‐ mice underwent either left anterior descending coronary artery ligation or a sham surgery. Echocardiograms were done before surgery as well as two days and three weeks after surgery to evaluate the size and function of the heart. Radio telemeters were implanted one week after surgery to record hemodynamic changes to autonomic nervous system altering drugs. In a separate cohort a catheter was inserted into the left ventricle and isoproterenol was administered to evaluate left ventricular (LV) contractile reserve. Finally, histological staining was done on heart slices to quantify the level of fibrosis in each of the groups.RESULTSWe have demonstrated that knocking out ASIC3 prevents disadvantageous remodeling after MI in mice. Two days after MI surgery both WT and ASIC3‐/‐ mice have a decrease in their LV ejection fraction (LVEF), a measure for how well the left ventricle is able to pump blood to the rest of the body. However, three weeks after MI the ASIC3‐/‐ mice have a significant increase in their LVEF compared to their WT counterparts. However, preliminary autonomic studies found no differences between WT and ASIC3‐/‐. Also, there wasn’t a difference between WT Sham and WT MI, indicating that mice don’t undergo the same changes in autonomic tone that we see in other animals such as humans or rats. Although not statistically significant, isoproterenol infusion shows a trend towards a higher contractile reserve in ASIC3‐/‐ MI mice compared to WT MI mice.CONCLUSIONOur echo data shows that ASIC3 contributes to the remodeling that occurs after MI. Along with that, our data from the isoproterenol study indicates that knocking out ASIC3 in mice after MI may help to conserve cardiac contractile reserve. The preliminary work done for our autonomic studies indicate that the dysregulation of the autonomic nervous system in mice is different than what is expected from studies done in humans and rats.
High‐Fat Diet and Environmentally Relevant Secondhand Smoke Co‐exposure and Cardiovascular Regulation in Mice
Authors: Pan Shiyue , Karey Emma , Pinkerton Kent E. , Chen Chao‐Yin 
Published: May 2022

BACKGROUNDOver the past few decades, cardiovascular disease incidence significantly decreased by 27%. Paradoxically, the number of deaths from cardiovascular diseases increased by 42% over the same period, owing to population growth and longevity. Consequently, cardiovascular diseases remain the leading cause of global death. Cardiovascular diseases are complex, multifactorial diseases that cannot be ascribed to a single factor. High‐fat diet (HFD) and secondhand smoke (SHS) are two preventable risk factors for the development of cardiovascular diseases. Studies have shown that SHS exposure is associated with poor dietary habits, suggesting the importance of potential confounding diet effects on health effects of SHS exposure. We previously showed that, in mice, environmentally relevant SHS exposure resulted in 10% decrease in baroreflex sensitivity (BRS) and 13% decrease in measures of heart rate variability (HRV). Here, we sought to characterize how HFD interplay with SHS in inducing cardiovascular dysfunction.METHODSMale C57BL/6J mice (11 wk) implanted with BP/ECG telemetry devices were fed with either normal diet (ND, 13.6 kcal% fat) or HFD (60 kcal% fat) and exposed to either filtered air (FA) or SHS (3 mg/m3, 6 hr/d, 5 d/wk) for 11 weeks. 36‐hr continuous BP/ECG recordings were performed. Data were divided into three 12‐hour periods: the first dark cycle (dark 1) immediately after the last day of exposure, and the following light and dark (dark 2) cycles. Spontaneous baroreflex sensitivity (BRS) was determined with the sequence method. Standard time domain heart rate variability (HRV) parameters were obtained from normal‐to‐normal R‐R intervals.RESULTSHFD‐fed mice had significantly greater weight gain than ND‐fed group (+15.3 g and +2.8 g over 11 weeks, HFD and ND, respectively). SHS exposure had no effect on body weight. Compared to ND mice, HFD mice had significantly higher BP (~6.5 mmHg), HR (~98 bpm), and lower BRS (~15% decrease) in the light cycle. Furthermore, HFD significantly reduced overall and short‐term HRV (36% and 47% reduction for SDNN and rMSSD, respectively, p < 0.05) across all three light cycles. The reduction in HRV is unlikely due to a higher HR in HFD mice because normalizing the HRV measures to baseline R‐R intervals did not change the results. SHS exposure did not pose additional effects on these HFD‐induced changes. While HFD alone did not affect BP variability, co‐exposure of SHS and HFD significantly increased BP variability during the first dark cycle (16.8%, 15.6%, and 17.3% higher than HFD+FA group, for systolic, diastolic, and mean BP variability, respectively, p < 0.05), suggesting a co‐exposure‐induced BP dysregulation.CONCLUSIONSThis study emphasizes the importance of accounting for differences in diet when studying the cardiovascular effects of SHS.
6‐O‐sulfation of endothelial glycocalyx heparan sulfates regulates systemic coagulation
Authors: Oshima Kaori , Davizon‐Castillo Pavel , Hernandez Giovanny , Baird Christine , Manco‐Johnson Marilyn , Schmidt Eric 
Published: May 2022

ObjectiveThe endothelial glycocalyx is a glycosaminoglycan‐rich layer that lines the surface of all vessels and is critical for vascular homeostasis, including the maintenance of an anticoagulant vascular surface. Heparan sulfate (HS), a linear polysaccharide composed of repeating disaccharide units of glucosamine and iduronic acid, is the major glycosaminoglycan comprising the endothelial glycocalyx. The mechanism by which glycocalyx HS regulates coagulation is unknown. As the biological function of HS derives from its unique pattern of sulfation (2‐O‐, 6‐O‐, and/or N‐sulfation) within constituent disaccharides, we hypothesized that the degree of heparan sulfate sulfation critically regulates systemic hemostasis.MethodsWe performed thromboelastography on whole blood collected from tamoxifen‐treated VE‐Cadherin‐Cre‐ERT2‐Sulf1/2 knockout mice, which have loss of endothelial sulf‐1 (a 6‐O specific HS sulfatase) and thus increased heparan sulfate 6‐O‐sulfation at the endothelial surface. Tamoxifen‐treated floxed mice (no Cre recombinase) served as controls. To determine the effects of HS in clot initiation and propagation, separate from platelet contributions, we treated platelet‐poor plasma from healthy donors (pooled and deidentified) with highly‐sulfated HS (HS09) and lower‐sulfated HS (HS01) and measured endogenous thrombin potential with calibrated automated thrombography. To explore the potential mechanism by which HS functions as anticoagulant, we repeated calibrated automated thrombography with antithrombin‐III‐, heparin cofactor‐II depleted plasma.ResultsMice lacking endothelial sulf‐1 demonstrated increased R‐time, decreased angle, and increased K‐time compared to tamoxifen‐treated controls, suggesting that increased endothelial‐surface 6‐O HS sulfation decreases coagulation. In platelet poor plasma, highly‐sulfated HS09 attenuated thrombin generation in dose‐dependent manner while such effect was not observed with the same dose of less‐sulfated HS01. Repeated analysis using platelet poor plasma depleted of antithrombin‐III and of heparin cofactor‐II showed dose‐dependent decrease of thrombin generation with HS09, suggesting that HS exerts this anticoagulant effect independently of heparin‐like activation of antithrombin‐III.ConclusionThe anticoagulant effect of endothelial‐surface HS is dependent on 6‐O sulfation of its constituent disaccharides, and this effect is mediated by the mechanisms distinct from well‐known heparin anticoagulation mechanisms.
Characterizing the Real‐Time Endogenous Methane Release in a Rat for 26‐days: Effect of Diets, Fasting, and Ethanol Consumption Across Different Time Scales
Authors: McKenna Kenneth Z. , Lighton John R. , McCue Marshall D. 
Published: May 2022

IntroductionMethane is a byproduct of methanogenic archaea that oxidize H2 gas produced by other microflora in the gut. This methane gas is readily absorbed into the into systemic circulation and excreted in the breath down its concentration gradient (similar to CO2) or may be acutely expelled as flatus. While ruminant animals can generate over 100 liters of methane per day, technological limitations have precluded detailed measurements of methane production and release in humans and other non‐ruminants.MethodsWe paired a Promethion metabolic measurement system with a high‐precision (<1ppb) methane analyzer capable of real‐time methane measurements in an individual mouse or rat. We then subjected a rat to multiple diet switches, 48h of fasting, and ethanol treatments and continuously measured food/water intake, metabolic rate, and methane release over 26 days.ResultsVCO2 responses were unaffected by diet changes and only decreased slightly during the fasting treatment. Methane release was diminished by some diet treatments and could be restored by others. Ethanol had no observable effects. We discovered that methane production generally followed a circadian cycle whereby total rates were ~50% higher and large flatus events were more frequent during the scotophase. Methane release during flatus varied by >1,000‐fold ranging from as little as 0.1 up to 60μl/min. Integrating the continuous data stream (at 1 Hz) we confirmed that the vast majority of methane release occurred in the breath and not in the flatus as is often repeated in the literature. Finally, we provide evidence that the constitutive rate of methane release in the breath is positively correlated with rates of CO2 release, the latter of which is indicative of overall activity levels of the rat.ConclusionGiven the growing number of molecular‐based studies investigating how gut microbiota can alter physiological function at higher levels of biological organization the approach of using real‐time methane measurements promises to provide a powerful new tool to establish causal linkages between microbiome dynamics and whole‐animal responses.