bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sympathetic Neurovascular Regulation During Pregnancy: A Longitudinal Case Study
Authors: Steinback Craig , Usselman Charlotte , Davenport Margie 
Published: June 2021

Pregnancy is associated a ~50% increase in blood volume, ~40% increase in cardiac output (Q), offset by a drop in total peripheral resistance (TPR). While limited data indicate a concurrent increase in sympathetic nerve activity (SNA) in normal pregnancy, suggesting reduced transduction of SNA into TPR, longitudinal neurovascular adaptation during gestation remains poorly understood.We conducted a longitudinal assessment of SNA and TPR in a 36 year old woman during her second pregnancy. Measures were made on 2 occasions in the month prior to conception, 4 occasions during pregnancy (9, 24, 30, and 38 wks gestation) and again 10 wks postpartum. Mean arterial pressure (MAP; Finometer) and Q (ModelFlow) were measured and used to calculate TPR. SNA was measured using microneurography (peroneal nerve).There was a gestationally dependent increase in SNA burst frequency (r2=0.970, P<0.01) and incidence (r2=0.977, P<0.01); frequency (24 bpm to 59 bpm) and incidence (34 b/100hb to 65 b/100hb) increased 145% and 89% respectively by 38 wks compared to early follicular values. However, transduction (TPR/SNA Burst Frequency) decreased throughout pregnancy (r2=0.952, P<0.05; 0.80 au to 0.21 au). By 10 wks postpartum, SNA (24 bpm; 28 b/100hb) had returned to pre‐pregnant values whereas transduction (0.44au) remained lower.These longitudinal data highlight the progressive sympoathoexcitation during pregnancy which is offset by a concurrent reduction in neurovascular transduction. Sympathetic hyperactivity reverses early in the post‐partum whereas transduction remains decreased. Funded by WCHRI, NSERC, HPF
The Effect of Dobutamine on Susceptibility to Ischemia‐Induced Ventricular Fibrillation in the Isolated Rat Heart
Authors: Clements‐Jewery Hugh , Haines Jeremiah 
Published: June 2021

Sudden cardiac death due to ventricular fibrillation (VF) continues to be a major cause of mortality, but the triggers of VF in ischemia remain poorly understood. Our hypothesis is that VF is triggered in myocardial ischemia as a result of ATP depletion, which causes ionic imbalance and electrical dysfunction that creates an arrhythmogenic substrate. The purpose of this study was to test this hypothesis by determining the effect of increasing cardiac ATP consumption on susceptibility to VF using a classical inotrope, dobutamine.Isolated rat hearts (n=12 per group) were perfused in the Langendorff mode with modified Krebs containing 3 mM K+. Dobutamine or vehicle was locally infused in a randomized and blinded manner to achieve a concentration of dobutamine of 3µM. After a further 15 min, regional ischemia was induced by coronary artery occlusion and maintained for 30 min. VF was determined from the ECG, and cardiac function was evaluated using an intraventricular balloon.Dobutamine increased heart rate and left ventricular developed pressure compared to controls as expected. The incidence of VF (75% vs 67%; P=NS) and time to onset of VF (892±68s vs 730±80s; P=NS) were similar in control and dobutamine groups respectively. Dobutamine reduced ischemic contracture, with end diastolic pressure 36±6 vs 15±3 mmHg after 25 min ischemia in control and dobutamine groups respectively (P<0.05). Thus, although β1 stimulation by dobutamine increased cardiac work, it did not increase susceptibility to ischemic VF.
Hypocapnic Hypoxia Silences the Retrotrapezoid Nucleus (RTN)
Authors: Basting Tyler , Burke Peter , Stornetta Daniel , Stornetta Ruth , Guyenet Patrice 
Published: June 2021

Rationale and objectivesIn conscious mammals, hypoxia produces respiratory alkalosis which is assumed to silence central respiratory chemoreceptors (CRCs). We tested this theory by examining how hypoxia changes the activity of the RTN, a likely CRC and chemoreflex integrator.MethodsRTN and nearby C1 neurons were bilaterally transduced with archaerhodopsin using a lentiviral vector (PRSx8‐ArchT‐EYFP‐LVV). We first showed that RTN neurons were silenced by green light in anesthetized rats. We then recorded the effect of RTN inhibition (10s) on breathing (fR, VT), BP, EEG and neck EMG in conscious rats exposed to normoxia, hypocapnic hypoxia (12 or 15% O2), isocapnic hypoxia (12% O2 + 3% CO2) or hypoxia in presence of acetazolamide (ACTZ). Arterial PO2, PCO2, pH and HCO3 were measured in each condition.ResultsIn normoxia RTN inhibition reduced breathing equally during non‐REM sleep and quiet wake and BP was unchanged. ΔfR was largest in normoxia, reduced in 15% O2, nul in 12% O2 and back to control (normoxia level) in normocapnic hypoxia.ΔVT followed the same trend. RTN inhibition caused much larger fR and VT reductions in ACTZ‐treated rats. Overall the bradypnea caused by RTN inhibition was linearly correlated with pHa (p < 0.0002). Above pHa 7.5, no fR change was elicited.ConclusionsRTN neurons regulate breathing equally during sleep and wake. RTN neurons are the first putative CRCs demonstrably silenced by hypocapnic hypoxia in conscious mammals. RTN is silent above pHa 7.5 and increasingly active below this value. Under hypocapnic hypoxia carotid body stimulation drives breathing via pathways that bypass RTN. ACTZ increases breathing by activating RTN. Funding: HL074011 (PGG), 5T32HL007284‐38 (TMB).
Sustained Hypoxic Pulmonary Hypertension and Systemic Vascular Dysfunction in High‐Altitude Dwellers Prone to Re‐Entry High Altitude Pulmonary Edema, Improvement by Anti‐Oxidants
Authors: Cerny David , Rexhaj Emrush , Bouillet Elisa , Soria Rodrigo , Meister Théo , Villena Mercedes , Sartori Claudio , Allemann Yves , Scherrer Urs , Rimoldi Stefano 
Published: June 2021

Re‐entry high altitude pulmonary edema (HAPE) is a live‐threatening problem that occurs on return from low altitude in otherwise healthy high‐altitude dwellers. The underlying mechanism is poorly understood. Circumstantial data suggest that pulmonary vascular dysfunction facilitating hypoxic pulmonary vasoconstriction plays a role. There is increasing evidence that at in high altitude dwellers, pulmonary vascular dysfunction is often associated with alterations of the systemic circulation related to altered redox regulation. We speculated that re‐entry HAPE prone subjects display sustained pulmonary and systemic vascular dysfunction related to increased oxidative stress.We therefore measured systolic pulmonary artery pressure (PAP, echocardiography), flow mediated dilation of the brachial artery and carotid intima‐media thickness (IMT) in re‐entry HAPE prone subjects and controls living at 3600 m. The main new findings were 2‐fold: 1) PAP was significantly higher in re‐entry‐HAPE prone than control subjects (38±2 vs. 24±1 mm Hg, p<0.001, X±SE) and this pulmonary vascular dysfunction was associated with systemic vascular alterations, as evidenced by increased IMT (485±21 vs. 404±10µm, p=0.002) and decreased FMD (5.1±0.6 vs. 9.7±0.8%, p<0.001). 2) Vit. C administration normalized FMD (Vit C 3 g i.v., 9.2±1.3% p=NS vs. controls) and decreased PAP (Vit C 1g/d for 30 d, 31 ± 1 vs. 38±2 mm Hg, p=0.04) in re‐entry HAPE prone subjects. Here we show for the first time that re‐entry HAPE prone high‐altitude dwellers display generalized vascular dysfunction that is related to altered redox‐regulation.
Acute Ascorbic Acid Ingestion Does Not Blunt Sympathetically‐Mediated Vasoconstriction During Handgrip Exercise in Older Adults
Authors: Richards Jennifer , Hearon Christopher , Racine Matthew , Luckasen Gary , Larson Dennis , Dinenno Frank 
Published: June 2021

The normal ability of contracting skeletal muscle to blunt sympathetic vasoconstriction is impaired in older adults, potentially contributing to the age‐associated impairment in skeletal muscle blood flow during exercise. Acute ingestion of 2g of ascorbic acid (AA) improves forearm blood flow (FBF) during moderate intensity handgrip exercise in older adults. We tested the hypothesis that acute AA ingestion improves the ability to blunt a sympathetically‐mediated vasoconstrictor stimulus during handgrip exercise (15% maximal voluntary contraction: MVC) in 10 older (63±2 years) adults. FBF was measured (Doppler ultrasound) and vasoconstriction was calculated (%Δ forearm vascular conductance [FVC]) in response to reflex sympathetic activation achieved via 2 minutes of ‐40mmHg lower body negative pressure (LBNP) at rest and during steady‐state handgrip exercise prior to and 2h post ingestion of AA. Compared to control, AA increased FBF during exercise (185±15 vs. 212±19 ml/min P<0.05) however there was no change in the amount of vasoconstriction to LBNP at rest (ΔFVC = ‐16±2 vs. ‐16±2%) or during exercise (ΔFVC= ‐12±2 vs. ‐11±4 %). We conclude that acute oral AA is capable of improving FBF during handgrip exercise in healthy older adults but does not improve the ability to blunt sympathetically‐mediated vasoconstriction.Supported by HL095573
Cardiovascular Risk Related to Body Fat and Physical Activity in Young Girls
Authors: Bea Jennifer , Lee Vinson , Blew Robert , Funk Janet , Going Scott 
Published: June 2021

Adiposity has been associated with cardiovascular (CVD) risk factors in children, but whether moderate to vigorous physical activity (MVPA) affects the association remains unclear.
PURPOSETo determine if MVPA modifies associations between total body fat (TBF) and CVD risk biomarkers of C‐reactive protein (CRP); total (TC), LDL, and HDL cholesterol; triglycerides (TG), and glucose in girls aged 9‐12 years (N=95).
METHODSFasting serum CRP was measured by high‐sensitivity nephelometric bead‐based immunoassay; glucose and lipids were measured by clinical laboratory. Dual energy X‐ray absorptiometry estimated TBF. MVPA was assessed by the Past Year Physical Activity Questionnaire. Maturity offset was computed using age and anthropometric measures according to the Mirwald equation.
RESULTSMean age and maturity offset were 11.1 ± 1.1yrs and ‐1.83 ± 0.86yrs, respectively. Average TBF was 16.7 kg ± 11.0kg, while %TBF was 33.0 ± 10.6%. Mean MVPA was 45.8 ± 68.2 minutes/day. After controlling for maturity offset in linear regression models, %TBF was positively associated with CRP (β= 0.60, P<0.001), glucose (β=0.24, P=0.02), TC (β=0.29, P<0.01), TG (β=0.31, P<0.01), and LDL (β=0.43, P<0.001). HDL cholesterol was inversely associated with %TBF (β= ‐0.39, P<0.001). When stratified by adequate (蠅60min/d, N=21) versus inadequate MVPA (N=74), %TBF remained significantly associated with all CVD risk biomarkers (P蠄0.05) among those with adequate MVPA, with the exception of glucose.CONCLUSIONPhysical activity may help mediate the effects of body fat on glucose, but it did not attenuate the relationship between body fat and most cardiovascular risk factors among the girls.Supported by NIH HD074565
Effect of Sit‐Stand Workstations on Metabolic Risk in Sedentary Workers: A Randomized Controlled Trial
Authors: Carpenter Katie , Feltes Linda , Vuong Brenna , Kalbes Ashley , Koepp Gabriel , Dutta Nirjhar , Levine James , Pereira Mark 
Published: June 2021

BackgroundSedentary time has been shown to have deleterious effects on health. Today's workforce spends most of the day sitting. The objective of this study was to evaluate the effect of workplace interventions to decrease sedentary time on cardiometabolic risk factors.MethodsSedentary office workers (n=127; ages 22‐64; BMI=28.5±6.1 kg/m2) were recruited from three Minnesota employers and randomized to one of four intervention groups for 6 months: 1) Control, 2) Move (蠅30 min of light activity during the workday), 3) Stand (standing 蠅50% of the workday using a sit‐stand workstation), or 4) Stand+Move (combined Stand and Move). A 'metabolic risk score' (MRS) was calculated at baseline and 6 months using the following cardiometabolic risk factors: blood pressure, fasting blood glucose, log of fasting triglycerides, and HDL‐cholesterol. A z‐score was computed for each risk factor for each subject [(subject value – sample mean)/sample SD]. The MRS was derived by summing the z‐scores (HDL‐z subtracted).ResultsThere was a significant intervention effect on MRS (p<.01). A seasonal time trend was observed, with MRS increasing significantly in Control and Move groups (p<.001), but not for the Stand and Stand+Move. Results (mean±se) are shown in Figure 1.ConclusionsSit‐stand workstations combined with an intervention to increase light physical activity at work may be an effective tool to improve cardiometabolic risk.image
Leptin Regulates Synaptic Activity of Brown Adipose Tissue‐Related Pre‐Sympathetic Neurons in the Paraventricular Nucleus of the Mice
Authors: Jiang Yanyan , Munzberg Heike , Derbenev Andrei , Zsombok Andrea 
Published: June 2021

Brown adipose tissue (BAT) thermogenesis is critical for maintaining body temperature and thus energy expenditure and it is regulated by the sympathetic nervous system. Recent evidence demonstrated the involvement of leptin in the regulation of the sympathetic outflow to the BAT; however, the underlying cellular mechanisms are poorly understood. In this study, we identified BAT‐related neurons in the paraventricular nucleus of hypothalamus (PVN) of mice (BAT‐PVN) by inoculating BAT with pseudorabies virus 152. Whole‐cell patch‐clamp recordings were performed to test the hypothesis that leptin regulates the synaptic activity of pre‐sympathetic BAT‐PVN neurons. The majority of BAT‐PVN neurons responded to leptin application. Leptin (300 nM) caused an increase of spontaneous excitatory post‐synaptic current (sEPSC) frequency in a subset (40%) of BAT‐PVN neurons, whereas sEPSC frequency was decreased in other subset of BAT‐PVN neurons (30%). This effect was observed without alteration of the amplitude. On the other hand, the frequency of spontaneous inhibitory post‐synaptic currents (sIPSC) was decreased in 50% of BAT‐PVN neurons, while a subset of BAT‐PVN neurons (20%) responded with an increase of sIPSC frequency following leptin application. Leptin did not change the resting membrane potential or input resistance of the recorded BAT‐PVN neurons. These data suggest that leptin contributes to the regulation of sympathetic outflow to the BAT via modulating the synaptic activity of PVN neurons.Supported: NIDDK R01‐DK092587 (HM) and R01‐DK099598 (AZs).
Glycan Targeted Vaccines for The Induction of Immunity
Authors: van Kooyk Yvette , Fehres Cynthia , Horrevorts Sophie , Bruijns Sven , Kalay Hakan , Ambrosini Martino , Garcia Vallejo Juan , Unger Wendy 
Published: June 2021

Dendritic cells (DC) are specialized in the recognition of antigen and play a pivotal role in the control of immunity and tolerance. For antigen recognition DC express several C‐type lectins, that function as innate receptors that facilitate antigen uptake and presentation. Many of these receptors also modify responses through signalling interference with TLR. We and others have shown that the C‐type lectins DC‐SIGN, MGL and Siglecs recognize specific glycan structures on pathogen related antigens but also on tumours. We have identified glycan structures that can either contribute to the tumour suppressive programming of the immune system, or oppositely activate the immune system.By modifying antigens with specific glycans we can favour directional targeting of tumour antigens to human DC and Langerhans Cells (LC) in situ, in the skin, facilitating the induction of tumour specific CD4+ and CD8+ T cell responses and Th1 differentiation. Therapeutic vaccination of mice with glycan modified antigen show long term anti‐tumour immunity when tumour induced T regulatory cells are temporarily reduced. All together our work sheds new light on the contribution of glycans to control tumour immunity by either contributing to the induction of anti‐cancer immunity or tumour induced immune suppression.
Constant rules to guide nutrition guidelines
Authors: Thomas Diana , Heymsfield Steven 
Published: June 2021

PurposeBecause of their simplicity, constant rules like the 3500 kcal rule, the 5% weight loss rule, and the three‐quarter fat free mass‐fat mass rule are being applied to offer nation‐wide weight loss advice, guide treatment, and inform experimental design. Despite their wide‐spread application, the accuracy of constant rules are rarely tested.MethodsWe tested the capacity of three different constant rules currently being applied to predict weight loss, determine effectiveness of weight loss treatment, and designate appropriate safe degree of fat‐free mass loss during weight loss against experimental data. The results were then compared to new models personalized to individual patient characteristics.ResultsComparison of the 3500 kcal Rule to experimental data yielded inaccuracies of higher than 30 kg at three months even when subjects were placed on reasonable energy deficits. Similarly, prediction of long‐term weight loss success relying on only percent weight loss was not better at identifying true positives than random chance. Finally, we can show that loss of fat free mass during energy restriction is a non‐constant function of aging and gender. On the other hand, emerging dynamic and statistical models which incorporate continuous changes in physiology and consider covariates of age, height, gender, and baseline parameters, yield a substantially higher predictive accuracy on all fronts.ConclusionsConstant rules have been historically applied in patient care because of their simplicity. However, inaccurate predictions can have severe implications contributing to reduced patient motivation or poor experimental design. We suggest the field move toward more physiologically sound and clinically tested models delivered through web‐based software.
Moderately High Protein Diets During Resistance/Aerobic Exercise Training Improve Body Composition Via Positive Changes in Adiposity But Not Lean Mass Accretion
Authors: Gordon Susannah , Kim Jung Eun , Weinheimer‐Haus Eileen , Campbell Wayne 
Published: June 2021

Middle‐aged overweight/obese adults are faced with an environment of food abundance. This food excess challenges their ability to adjust eating behaviors and maintain body weight. We conducted a 36‐week diet supplementation and exercise training study where 35‐65 year‐old overweight and obese adults were exposed to a “controlled source” of potentially excess energy via 200 kcal supplements with varying amounts of maltodextrin and whey protein. The supplements were consumed 2x daily with breakfast and lunch along with their otherwise unrestricted, self‐chosen diets. Training included resistance (2 d/wk) and aerobic (1 d/wk) exercises. This retrospective data analysis assessed the effect of total protein intake (TPro) on changes in body weight and composition. 85 subjects were classified into 3 groups based on TPro: < 1.0 (low TPro, LP, n=29), 蠄 1.0 to < 1.2 (medium TPro, MP, n=24), and 蠅 1.2g•kg‐1•d‐1 (high TPro, HP, n=32). Weight was measured bi‐weekly and body composition (plethysmography) every 9 weeks. Over time, LP progressively gained weight and fat mass, while MP and HP maintained weight and lost fat mass. All three groups gained lean body mass (mainly during the first 9 weeks). These findings support that moderately high protein intake improves weight control and adiposity, but does not augment lean mass accretion among exercising overweight/obese adults who are challenged by potential excess energy intake. High protein intakes do not enhance these responses.Support: US Whey Protein Res Consort; NIH T32AG025671; NIH UL1TR001108; Purdue Ingest Behav Res Ctr
Sex‐specific Effects of Prenatal and Post‐weaning High Fat Diet on Adult Mouse Offspring Skeletal Muscle Contraction
Authors: Jones Lisa , Markiewicz Filip , James Rob , Cagampang Felino , Rustighi Emiliano , Poore Kirsten , Newland Philip , Green Lucy 
Published: June 2021

Maternal obesity is linked to altered offspring skeletal muscle structure and function. We tested the idea that prenatal (PRE) high fat (HF) diet would alter the deleterious effect of post‐weaning (POST) HF diet on offspring skeletal muscle contraction.C57 mice were fed a control (C, 7% kcal) or HF (45% kcal) diet in PRE and/or POST periods (C/C, C/HF, HF/C, HF/HF). Male and female 30 wk offspring (n=7‐8/group) soleus and extensor digitorum longus (EDL) muscle peak force (PF) of isometric contraction was measured in response to several electrical stimulation frequencies.In soleus and EDL, PF was greater in females than males. In female soleus (not EDL), POST HF alone markedly reduced PF (C/HF vs. C/C, P<0.01). In female soleus and EDL there was only a trend for a reduction in PF in HF/C and HF/HF groups (P=0.1). In male soleus and EDL, combined PRE and POST HF tended to reduce PF (HF/HF vs. C/C, P=0.1). In male soleus (not EDL), POST HF tended to reduce PF in PRE HF animals (HF/HF vs. HF/C, P=0.1), and PRE HF tended to reduce PF in POST HF animals (HFHF vs. C/HF, P=0.1).Thus reduced adult skeletal muscle isometric contraction force by POST HF diet is modified by a prior PRE HF diet in a sex‐ and muscle bed‐specific manner. This could reflect developmental differences in myofibre type composition or lipid deposition, and has potential implications for muscle health in adult/ageing obese individuals.Supported by The Gerald Kerkut Charitable Trust and Diabetes UK.
Evaluating the Discrimination of Sugar Content Thresholds in the Canadian Nutrient File Classification System
Authors: Bernstein Jodi , L'Abbe Mary 
Published: June 2021

The objective of this study was to evaluate the discrimination of sugar thresholds in the Canadian Nutrient File Classification System (CNFCS). The CNFCS was developed and validated to evaluate the consistency of food and beverages with dietary guidance such as 'limit food and beverages high in sugar'. The CNFCS classifies products into one of four tiers separated by upper and lower thresholds for sugar, sodium, fat, and saturated fat content. Most choices should come from tiers 1&2, few from tier 3, and limited from tier 4. Unlike the other nutrients, sugar has no intake recommendations to base the CNFCS thresholds on. Assessing the discrimination of nutrient classification systems is integral as they categorize the overall healthiness of a food. Using the University of Toronto 2013 food database, the proportion of breakfast cereals (n=250) and yogurts (n=240) that met and/or exceeded the thresholds for sugar content was assessed and compared to the proportion categorized within each CNFCS tier. The majority of cereals (77%) and yogurts (85%) exceeded the lower threshold for sugar, but few (1% and 2%, repsectively) exceeded the upper thresholds. Despite surpassing the lower threshold for sugar, 64% of cereals and 55% of yogurts were classified into tier 1&2, based on other nutrient contents. In total, 86% and 65% fell into tier 1&2 and 3% and 8% into tier 4 for cereal and yogurt, respectively. These results demonstrate products with up to 19g of sugar for most food categories, or 28g for flavoured yogurt, could be categorized in the healthiest tiers. Few items fell in tier 4 or exceeded the upper sugar threshold, indicating CNFCS sugar criteria may be too lenient and hence provide little incentive for reformulation.Funding: McHenry Chair (ML); CIHR PICDP & PHP (JB).