bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cessation of Nightly Voluntary Wheel Running Activity Following Exposure to a Mouse Model of Posttraumatic Stress
Authors: Stroh Courtney M. , Kinney Erin M. , Coste Sarah C. 
Published: June 2021

Regular physical activity (PA) is well known to positively impact physical and mental health outcomes. In our work to examine cardiovascular benefits of PA in a mouse model of post‐traumatic stress, we stumbled upon the reciprocal relationship between PA and stress exposure, wherein stress significantly reduced healthy levels of routine PA. The aim of the present studies was to define the parameters of our paradigm as first steps for its future use in examining mechanisms that underlie stress‐induced declines in PA. Five week old, C67BL/6J male mice were divided into four groups (n=8/group); sedentary/control, voluntary running/control, sedentary/stress and voluntary running/stress. Voluntary running groups were given 24 hr unlimited access to a running wheel in the home cage for 9 weeks. Mice ran a nightly average of 4.75 ± 1 km. During the 9th week, stress groups were exposed to a 5 day resident‐intruder social stress that models human post traumatic stress outcomes. Running behavior essentially ceased following stress. Running distance dropped to 0.31 km following the 1st stress day. Some habituation to stress occurred, as running distance increased to 1.12 km by the 5th day of stress but remained significantly lower then pre‐stress running distances and distances recorded in non‐stressed mice. A separate study examined a single exposure to resident‐intruder social stress and found plasma corticosterone significantly increased (16.66 ± 4 ng/ml basal to 496 ± 155 ng/ml immediately post stress) while nightly running dropped significantly from 5.58 ± 1.7 km to 1.22 ± 1.1 km, and returned to near normal levels (4.35 ±1.7 km) by the 3rd night post stress. Food intake was moderately increased in the first 2 nights post stress, but also returned to normal by the 3rd night. These studies show the sensitivity of habitual running behavior to stress exposure and suggest the utility of this mouse model in exploring the means by which stress negatively impacts routine PA.Support or Funding InformationLinfield College Student‐Faculty Collaborative Research GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Biomarker Time Course Recovery Profile in Military Exertional Heat Stroke Populations
Authors: Ward Matthew , King Michelle , Leon Lisa 
Published: June 2021

Current return‐to‐duty and training decisions following Exertional Heat Stroke (EHS) are based on ‘best‐guess' criteria. A time‐resolved progression of biomarker changes following EHS has previously not been determined to describe ‘normal’ recovery. In order to characterize EHS injury severity and recovery progression in military populations and identify objective measures of medical readiness, we performed a retrospective clinical records review focusing on available clinical laboratory values assessed on the day of injury, and all follow‐up visits. This dataset was limited to US active duty service members (ADSM) who had at least one EHS during the years 2008–2014. Incidence was identified using the International Classification of Disease 9th (ICD‐9) Revision code for Heat Stroke (992.0). We collated and analyzed daily clinical laboratory values of circulating biomarkers from de‐identified electronic medical records contained in the Medical Health System Data Repository (MDR). Lacking consensus laboratory reference ranges between treatment facilities, the most prevalent reported reference ranges were used as consensus values to orient the analysis. Over the prescribed period, 2,529 ADSM experienced at least one episode of EHS. A total of 181,918 daily clinical laboratory results for 50 laboratory analytes were used for this analysis including a range of blood counts, and serum/plasma or urine assays from 0–340 days following the initial injury. As expected, the median daily value for 11 analytes (ALT, AST, Cl, CK, hematocrit, creatinine, hemoglobin, LDH, myoglobin, WBC, RBC) exceeded the upper limit of the normal reference range, indicating multi‐organ damage or dysfunction. Notably, creatine kinase (CK; consensus reference range 22–269 unit/L) exhibited the highest deviation 3‐days following the initial injury, the median value topped at 4.65‐fold elevation above the upper reference limit; median = 1,251 units/L (interquartile range, 321.25–5,256.75) units/L. Median CK values persisted above the reference range for 8‐days. Each biomarker showed a distinct pattern of peaks (ranging from 0–3 days). In conclusion, this work exploited population‐based EHS responses to characterize injury severity and recovery progression that has not previously been defined. However, due to the high degree of inter‐individual variability in the magnitude and duration of biomarker fluctuations, it remains difficult to set a generalizable criterion for diagnosis, recovery and medical readiness following EHS. The opinions or assertions contained herein are the private views of the authors and should not be construed as official or reflecting the views of the Army or the Department of Defense.Support or Funding InformationSupported, in part, by Defense Health Program grant, award #W81XWH‐13‐MOMJPC5‐IPPEHA.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Critical Environmental Limits for Prolonged Work in the Heat Using a Simulated Burn Injury Model
Authors: Cramer Matthew N. , Moralez Gilbert , Huang Mu , Crandall Craig G. 
Published: June 2021

Following a deep burn injury, excision of devitalized skin and subsequent grafting impair sweat production within grafted sites. Since the capacity for whole‐body evaporative heat dissipation is dependent on sweat production and the total non‐injured skin area available for heat dissipation, burn injuries likely reduce the capacity for whole‐body heat dissipation in proportion to the size of the burn injury during heat stress. To test this possibility, four healthy subjects (1 female; 28 ± 7 years, 71.1 ± 9.0 kg, 1.87 ± 0.12 m2) visited the laboratory on separate days to complete an incremental humidity protocol while cycling at a fixed metabolic heat production (5 W/kg, equivalent to ~35% maximum oxygen uptake) in 40°C with and without simulated burn injuries of 20%, 40%, or 60% of total body surface area. During each trial, exercise was performed at an initial relative humidity (RH) of 25% for 30 min to achieve thermal equilibrium, after which exercise continued as RH was increased by 3% every 5 min up to 90 min. A ‘critical’ RH was identified as the RH value above which a steady‐state esophageal temperature could no longer be maintained, thus providing an indication of maximum evaporative heat dissipation. Burn injuries were simulated by covering skin on the torso, arms, and legs with highly absorbent, vapor‐impermeable material that prevents sweat evaporation. The results show that the average critical RH declined with the size of the simulated burn injury up to 40% (0%: 44.1 ± 2.4%; 20%: 41.8 ± 2.3%; 40%: 31.4 ± 5.1%), with significant reductions in the critical RH at 40% vs. 0% and 20% simulated burn injuries (P=0.009). However, a critical RH value could not be discerned in one subject with a 40% simulated burn injury or in any subject with a 60% simulated burn injury, indicating physiologically uncompensable conditions throughout the experimental protocol. These preliminary data suggest that under the current environmental conditions, burn survivors with injuries of ≥40% have a substantially attenuated capacity for heat dissipation, placing them at greater risk of heat‐related illness during prolonged work and heat stress. Such information may be incorporated into exposure guidelines for burn survivors working under severe occupational heat stress such as military personnel.Support or Funding InformationFunding: Department of Defense – US Army, W81XWH‐15‐1‐0647This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Does electrodermal activity track capacitance hygrometry derived sweat rate during steady‐state and transient cholinergic‐induced sweating?
Authors: Jordan Alys S. , Narra Seetharam C. , White Briana N. , Wilson Thad E. 
Published: June 2021

The classification of hyperhidrosis and hypohidrosis requires a precise quantification of sweat secretion. Recent studies have asserted a non‐invasive electrical conductance could be used to quantify precursor sweat formation. Precursor sweat is the isotonic fluid formed in the bulbous coil and the cell type most likely responsible for sweat gland pathology, rather than the modified fluid that reaches the skin surface. This study was designed to compare electrodermal activity (EDA), capacitance hygrometry, and skin blood flow (SkBF) during steady‐state and dose‐response sweating induced by cholinergic agonists to determine measurement congruence. 3 intradermal microdialysis fibers were placed in the dorsal forearm skin of 4 women and 3 men (age 22±2 years, BMI 25±6 k/m2) to perfuse pilocarpine nitrate (1.66 mg/ml for 60 min), 5 doses of acetylcholine (1•10−5 to 1M via 1•10−1 increments per dose for 5 min each), or the vehicle (lactated Ringer's). Perfusate flow rates were standardized at 5 μL/min. Forearm SkBF (laser‐Doppler flowmetry), EDA (constant voltage of 0.5 V and gain of 5 μS/V), and sweat rate (capacitance hygrometry) were measured directly over the microdialysis membrane. Cholinergic dose‐response relations increased sweat rate (0.0 to 0.56 mg/ml/min), SkBF (16 to 279 units), and EDA (0.61 to 0.91 μS). ACh dose dependent increases in sweat rate and SkBF were similarly correlated to EDA (r = 0.52 and 0.48), although SkBF increased from the first dose and sweat rate and EDA increased from the 3rd dose of ACh. EDA was correlated to SkBF (r = 0.52) but not sweat rate (r = −0.17) during the initial climb to steady‐state sweating, while during state‐steady sweating induced by pilocarpine EDA correlated to sweat rate (r = 0.59) but less so to SkBF (r = 0.21). The lactated Ringer's site did not induce changes in sweat rate, SkBF, or EDA; suggesting that the intradermal microdialysis technique does not affect EDA values. Combined, these data indicate EDA does not track capacitance hygrometry derived sweat rate or laser‐Doppler indexed SkBF consistently in either steady state or transient cholinergic‐induced sweating conditions.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of decreasing peripheral skin blood flow via local axon reflexes, decreases in perfusion pressure, and ischemia during systemic thermal‐induced eccrine sweating in humans
Authors: Wilson Thad E. , Daggett James W. , Alibegovic Kenan , Fang Milie M. , Metzler‐Wilson Kristen 
Published: June 2021

In humans, skin blood flow (SkBF) and sweating are tightly coupled, suggesting common neural control and regulation and possible interactive effects of extracellular fluid delivery and sweat secretion. This study was designed to separate these two sympathetic nervous system end‐organ responses via SkBF‐decreasing mechanical perturbations in the presence of a strong sudomotor drive. Two women and 4 men (age 26±1 yrs and BMI 24±4 kg/m2) were tested in normothermia and heat stress conditions, by pumping neutral (34°C) and hot (46–50°C) water through a high‐density tube‐lined suit to either maintain internal temperature (pill telemetry) or increase it by ~1.0°C. Arm and leg SkBF (laser‐Doppler flowmetry) was decreased for 3 min by engaging the venoarteriolar response (limb lowered ~30 cm from heart level; CVAR), venoarteriolar response plus a decrease in perfusion pressure (venous occlusion by proximal cuff inflation; CVAR with ΔPP), and ischemia (arterial occlusion by proximal cuff inflation). Decreased SkBF was observed with CVAR (30±7 and 60±15%), CVAR with ΔPP (44±12 and 86±11%), and ischemia (96±1 and 99±1% for the arm and leg, respectively) during normothermia. Despite these significant decreases in SkBF, there were no significant effects on transepidermal water loss (TEWL). Heat stress increased intestinal temperature from 37.1±0.1 to 38.0±0.1°C, heart rate (ECG) from 65±5 to 93±4 bpm, arm cutaneous vascular conductance (SkBF/mean arterial pressure*100) from 52±12 to 473±85 units, and forearm sweat rate (capacitance hygrometry) from 0.0 to 0.6±0.1 mg/ml/min. During heat stress, decreased SkBF was also observed during CVAR (20±7 and 17±6%), CVAR with ΔPP (39±9 and 52±13%), and ischemia (99±1 and 100±1% for the arm and leg, respectively). Despite these significant decreases in SkBF, eccrine sweat rate was not significantly affected. These data indicate that a wide range of acute changes in SkBF do not appear to affect TEWL or eccrine sweating in peripheral skin.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Exertional Heat Stroke: Discovering Specific and Sensitive Diagnostic Criteria
Authors: King Michelle , Ward Matthew , Plamper Mark , Leon Lisa 
Published: June 2021

Exertional heat stroke (EHS) is currently defined as presenting with arectal core temperature (Tc) of ≥104°F accompanied by central nervous system (CNS)dysfunction. This definition often lacks in specificity and sensitivity for diagnostic purposes and does not distinguish EHS from exercise‐induced hyperthermia or less severe conditions of exertional heat illness. The purpose of this study was to analyze 179EHS clinical records from the U.S. Marine Corps Base Quantico, VA (2012–2015)to: 1) determine the specificity and sensitivity of the current EHS definition and, 2) identify a more sensitive and specific definition that accurately diagnoses EHS cases with a distinguishable biomarker profile. Specificity and sensitivity was determined through Receiver Operating Characteristic (ROC) curve analysis. The sensitivity of the traditional EHS clinical definition was 64.7% (95% CI 55.9%–72.8%) and specificity was 30.4% (95% CI 17.7%–45.8%). Positive predictive value (PPV) was 72.9% (95% CI 68.1%–77.2%), the negative predictive value (NPV) was 23.0%, (95% CI 15.4%–32.8%), and overall disease prevalence was 74.3% (95% CI 67.3%–80.5%) with an accuracy of 55.9% (95% CI48.3%–63.3%). Using this diagnostic criteria, blood biomarker profiles of EHS and non‐EHS cases were similar. In a secondary analysis, we re‐defined EHS as Tc ≥106°F with at least one form of CNS dysfunction. Sensitivity was lower(30.1%; 95%CI 22.4%–38.6%) whereas these criteria proved more specific (73.3%;95% CI 58.1%–85.4%). PPV and NPV were higher (76.9%; 95%CI 65.8%–85.4%, and 26.2%; 95% CI 22.4%–30.4% respectively)with this classification, while disease prevalence (74.7%; 95% CI 67.6%–80.9%)was indistinguishable and accuracy of diagnosis suffered (41.0%; 95%CI 33.71%–48.62%). Interestingly with this revised EHS definition, blood biomarker profiles (iStat hand held clinical analyzer)separated the most severe cases of EHS (Tc ≥106°F with CNS dysfunction vs. any case with Tc <106). Specifically, chloride (103.1 ± 0.7 vs. 105.2 ± 0.3 (mEq/L); p=0.0089), total carbon dioxide (13.4 ± 1 vs. 16.06 ±0.6 (mEq/L); p=0.0414), glucose (184.1 ± 13.7 vs. 148.2 ± 6.5 (mg/dL); p= 0.021), creatinine (6.5 ± 4.9 vs 1.5 ± 0 (mg/dL); p=0.0285), anion gap (27.8 ± 1.1 vs. 23.7 ± 0.6 (mEq/L); p=0.0016), hematocrit (44.3 ± 1.1 vs. 39.7 ± 0.6 (%); p=0.0377), and hemoglobin (15.0 ± 0.4 vs. 13.5 ± 0.2 (g/dL); p= 0.0390) were significantly different in EHS vs non‐EHS cases, respectively. These results demonstrate that a revised clinical definition of Tc of ≥106° F with CNS dysfunction does not improve sensitivity or accuracy of EHS diagnosis, but it does stratify EHS severity via blood biomarkers. Author view not official USARMY or DoD policy.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
NOVEL ROLE OF GLYCINE IN CONTROL OF SYMPATHETIC OUTFLOW
Authors: Hong Gao , Korim Willian S. , Yao Song T. , Heesch Cheryl M. , Derbenev Andrei V. 
Published: June 2021

The arterial baroreflex is one of the essential negative‐feedback mechanisms that compensates rapid changes in blood pressure (BP) through inhibition of presympathetic neurons in the rostral ventrolateral medulla (RVLM). There is general consensus that GABAergic projections originating from the caudal VLM (CVLM) provide the primary inhibitory input that controls the excitability of presympathetic RVLM neurons and sympathetic output. However, glycine, another inhibitory neurotransmitter, is also present in the RVLM. In anesthetized rats, we found that RVLM glycine played a critical role in arterial baroreflex function by controlling the time course of baroreflex mediated inhibition of renal sympathetic nerve activity. Blockade of glycine receptors in the RVLM, following an increase in BP, increased recovery of renal sympathetic nerve activity to baseline levels (5.1 ± 1.0 vs 11.7 ± 1.3 min, N=6, P<0.01) in comparison to control. In addition, tonic glycinergic inhibition of the RVLM was unmasked following blockade of output from the nucleus tractus solitaries and/or during disinhibition of the CVLM. Our whole‐cell, patch‐clamp recordings were obtained from brainstem slices containing presympathetic neurons in the RVLM labeled with PRV‐152. We confirmed that in steady state conditions GABAergic inhibition of RVLM neurons predominated and glycine contributed less than 25% of overall inhibition. In contrast, activation of the network produced saturation of GABAergic inhibition and glycinergic inhibition became prominent. Our findings demonstrated that blockade of glycine receptors in the RVLM decreased duration of baroreflex sympathoinhibition; increase of BP and activation of the network unmasked glycinergic inhibition of the RVLM; and release of glycine in the RVLM depended on the activity of presynaptic inhibitory inputs.Support or Funding InformationNational Institutes of Health R01 HL98602 (Cheryl M. Heesch) and HL122829 (Andrei V. Derbenev). Australian Research Council Future Fellowship FT170100363 and the National Health and Medical Research Council of Australia GNT 1079680 (Song T. Yao). High Blood Pressure Research Council of Australia, the Rebecca L Cooper Medical Foundation, and the Victorian Government through the Operational Infrastructure Scheme (Willian S. Korim).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Baroreflex Sensitivity and Mortality in Septic dysfunction
Authors: dos Santos Fernando , Nogueira Antonio Carlos , Biselli Paolo , Hoshino Wagner , Mostarda Cristiano Teixeira , De Angelis Katia , Soriano Francisco Garcia , Irigoyen Maria Claudia 
Published: June 2021

Mortality in experimental septic shock has been attributed to systemic hypotension, hyporeactiveness to vasocostrictors, metabolic acidosis and organ damage but there is no clear information about the involvement of the baroreflex sensitivity (BRS) or autonomic dysfunction in the survival of these animals. In patients with multiple organ dysfunction syndrome autonomic function is impaired and this impairment seems to have prognostic implications. In this study we aimed to observe the role of the baroreflex sensitivity (BRS) in mortality of the patients who were admitted in the intensive care unit from the University of São Paulo Hospital (Univesitary Hospital) with sepsis or septic shock diagnosis (follow up of 28 days). The protocol was approved by Ethics Committee of Hospital and the written informed consent had been obtained from the closest family member. Thirty patients were included in this observational and prospective study in which the patients were analyzed in two groups: survivors and nonsurvivors.. The patients were instrumentalized with direct blood pressure and heart rate recordings, obtained in the first 24 hs in the Instensive Care Unit. The measurements of C reactive protein (Surv: 206.8±25.7, NonS: 204.4±43.6) and gravity APACHE score (Surv: 24.7±0.9, NonS: 24.8±1.0) were similar in the two groups. However, the nonsurvivor group presented reduced glycaemia (NonS: 133.7±10.7 vs Surv: 185.5±16.2 mg/dl) and elevated plasma levels of citokines, IL‐6 (NonS: 1654.1±420.4 vs Surv: 390.1±123.5) and IL‐10 (NonS: 532.3±180.3 vs Surv: 76.0±35.4) and of troponin I (NonS: 1.56±0.4 vs Surv: 0.63±0.2), indicating a myocardial agression. Heart rate variability and the relationship between Heart rate and Blood pressure variation (LF index of BRS) were reduced in septic patients and additionaly reduced in nonsurvivor group. BRS < or =6.5 ms/mmHg were found to be related to mortality in nonsurvivors group by The Kaplan Meyer analysis, suggesting that autonomic dysfunction could be indicative of mortality risk in these patients.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Re‐expression of REST Promotes Ventricular Arrhythmogenesis via Repressing N‐type Calcium Channel in Ventricular Vagal Neurons in Chronic Heart Failure
Authors: Zhang Dongze , Tu Huiyin , Wadman Michael C. , Li Yu‐Long 
Published: June 2021

Ventricular arrhythmia is a common complication in chronic heart failure (CHF) and accounts for nearly 50–60% of mortality in patients with CHF. Decrease in cardiac vagal activity is considered to be an important trigger for ventricular arrhythmogenesis in CHF. Our previous study has demonstrated that expression of N‐type calcium channel α‐subunits (Cav2.2‐α) and N‐type Ca2+ currents were reduced in atrioventricular ganglion (AVG) neurons in CHF rats. We have also demonstrated that reduced expression of Cav2.2‐α in AVG neurons contributes to ventricular arrhythmogenesis. The repressor element 1‐silencing transcription factor (REST) is a key to block Cav2.2‐α expression. Normally REST is not expressed in neuronal cells. Here, we test the hypothesis that re‐expression of REST inhibits N‐type Ca2+ channel function in AVG neurons and further trigger ventricular arrhythmogenesis in coronary arterial ligation‐induced CHF rat. Using reverse‐phase protein array, we found that there was no expression of REST in the AVG from sham rats, while REST expression was significantly increased in the AVG from CHF rats. In vivo transfection of lentiviral REST shRNA (2 μl, 1×107 TU/ml) into the AVG markedly reduced REST expression in the AVG from CHF rats. REST shRNA also increased Cav2.2‐α expression in AVG neurons from CHF rats. The results from whole‐cell patch clamp recording showed that REST shRNA increased N‐type Ca2+ currents in AVG neurons from CHF rats (19.47±1.13 pA/pF in REST shRNA transfected CHF rats vs. 11.37±1.65 pA/pF in non‐transfected CHF rats). The data obtained from radiotelemetry ECG recording in conscious rat demonstrated that transfection of REST shRNA into AVG neurons reduced the cumulative duration of ventricular tachycardia/fibrillation in CHF rats (2.64 ±2.05 sec/hour in REST shRNA transfected CHF rats vs. 10.03±3.43 sec/hour in non‐transfected CHF rats). We conclude that re‐expression of REST decreases Cav2.2‐α expression and N‐type Ca2+ currents in AVG neurons and subsequently triggers ventricular arrhythmogenesis in the CHF state.Support or Funding InformationThis study was supported by AHA Grant‐in‐Aid (15GRANT24970002)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.