bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of hypoxia on the ventilatory and cerebral blood flow (CBF) responses to CO2
Authors: Battisti Anne , Fisher Joseph , Duffin James 
Published: June 2021

ObjectivesThis study examines the proposed approach to a standard measurement regime for characterizing the respiratory chemoreflexes as detailed by Duffin (2007) and develops a similar approach to characterize cerebrovascular responsiveness to hypoxia and CO2. We measured the effect of hypoxia on the isoxic modified rebreathing ventilatory and CBF responses to CO2 in terms of sensitivity, ventilatory recruitment threshold and wakefulness ventilation at 2 levels of isoxia (PO2 = 50 mmHg & 150 mmHg). We also measured the effect of hypercapnia on the isocapnic steady‐state (SS) ventilatory and CBF responses to hypoxia at 3 levels of hypercapnia (PCO2 = 4, 7 & 10 mmHg above resting). Finally we compared the isoxic rebreathing measurements with the SS isocapnic measurements.MethodCustom designed software controlling a specialized gas blending device (RespirAct™; Thornhill Research) was used to implement the steady state and modified rebreathing protocols. Ventilation (VE), PetCO2 and PetO2, middle cerebral artery velocity (MCAv), and blood pressure (BP) were recorded.Results9 subjects completed the tests (6 male).This graph displays the SS response of VE, MCAv and BP to CO2 (PCO2 = 50 mmHg) first in hyperoxia (PO2 = 150 mmHg) and then in hypoxia (PO2 = 50 mmHg). We compared the SS and rebreathing ventilation and CBF responses.Rebreathing analysis (figures above) gives us interesting results. Ventilation shows a higher slope (increase of sensitivity) as well as a lower threshold during the Hypoxic phase as expected. For the MCAv, the interindividual variability is larger than expected. This example shows same slope, as expected. Comparison with SS method is more complex. Some subjects might have limitations of the MCAv increase. Further analysis still need to be done.
Transforming Growth Factor‐beta Expression in Obesity‐Linked kidney Disease
Authors: Maddox David A. , Ingebrigston Dane 
Published: June 2021

ObjectiveTo gain insight into the matrix synthesis cascade in obesity‐linked renal disease.MethodsThe study used obese and lean Zucker rats. Obese rats six weeks of age were fed either ad libitum (Ob‐ ad lib) or restricted (Ob‐Res) in food intake to that consumed by lean Zucker controls, then tested at 6, 12, and 18 weeks for each condition. Tissue mRNA was extracted from kidney cortex (~40 mg) and cDNA was synthesized. Multiplex Real‐Time PCR was performed for transforming growth factors (TGF‐β1, TGF‐ β2 and TGF‐ β3). Housekeeping genes were Rpl19 and Cyclophilin‐A.Summary of ResultsIncreased protein excretion in the Ob ad lib group was evident by 12 weeks of age compared to lean animals and increased further at 18 weeks. Food restriction beginning at 6 weeks of age prevented this from occurring. TGF‐β1 gene expression was elevated at 12 weeks of age in the Ob ad‐lib animals compared to lean or Ob‐Res. TGF‐β3 gene expression was increased at 6 weeks in the Ob ad lib compared to lean and remained elevated at 12 and 18 weeks of age compared to lean or Ob‐Res groups. The TGF‐β2 (not shown) had no elevated expression levels in any group.ConclusionsIncreased gene expression levels of TGF‐β1 and TGF‐ β3 suggest a role for these growth factors early in the development of obesity‐linked kidney disease, a conclusion strengthened by the complete prevention of these changes by food restriction which also prevented proteinuria. Project funded by VA Merit Review award, Avera Research Institute, and Sanford School of Medicine of the University of South Dakota.
Hypertonic saline attenuates cutaneous vasodilation in response to local heating
Authors: DuPont Jennifer J , Farquhar William B , Edwards David G 
Published: June 2021

Salt may have a direct effect on vascular function by reducing nitric oxide (NO) production.PURPOSEThe purpose of this study was to examine the effects of hypertonic saline on NO‐mediated cutaneous vasodilation in response to local heating.METHODSNine healthy subjects (23 ± 2 years) were studied. We measured cutaneous red blood cell flux via laser Doppler in conjunction with intradermal microdialysis of 1) Ringer's solution (R), 2) 0.9% normal saline (NS), 3) 3% hypertonic saline (HS), and 4) 10 mM NG‐nitro‐L‐arginine methyl ester (L‐NAME) during local heating to 42°C. Microdialysis of 28 mM sodium nitroprusside (SNP) at 43°C was used for assessment of maximum cutaneous vascular conductance (CVCmax) and data was expressed as a percentage of CVCmax (%CVCmax).RESULTSBaseline %CVCmax did not differ between the four microdialysis sites (HS: 9 ± 4, R: 11 ± 6, NS: 7 ± 4, L‐NAME: 7 ± 2%; p = 0.9). Hypertonic saline significantly attenuated the plateau %CVCmax compared to Ringer's and 0.9% normal saline (HS: 74 ± 12, R: 89 ± 4, NS: 89 ± 5%; p< 0.01) and L‐NAME reduced the plateau %CVCmax compared to other three sites (47 ± 7%, p< 0.01).CONCLUSIONHypertonic saline attenuates the cutaneous vasodilation response to local heating suggesting a direct effect of salt on microvascular function. This effect may be mediated through a decreased production and/or availability of NO.Supported by Grant DK080469.
25‐Hydroxyvitamin D deficiency is associated with vascular endothelial dysfunction in middle‐aged and older adults
Authors: Jablonski Kristen L , Pierce Gary L , Walker Ashley E , Chonchol Michel , Seals Douglas R 
Published: June 2021

Aging is associated with impaired endothelium‐dependent dilation (EDD) and increased 25‐hydroxyvitamin D (25(OH)D) deficiency. 25(OH)D deficiency is predictive of incident cardiovascular events and mortality. We hypothesized that healthy middle‐aged and older adults (MA/O) who were 25(OH)D insufficient (20–29 ng/mL) or deficient (<20 ng/mL) would demonstrate greater impairment in EDD compared with their 25(OH)D sufficient (>30 ng/mL) peers. Groups did not differ in cardiovascular risk factors or physical activity/fitness. EDD, measured using brachial artery flow‐mediated dilation (FMD), was 25% and 42% lower in insufficient (63±1 yr, n=24, mean±S.E.) and deficient (64±1 yr, n=14) vs. sufficient (60±2 yr, n=8) subjects (3.0±0.3 vs. 3.9±0.3 vs. 5.2±0.5 %, p<0.01), whereas endothelium‐independent dilation (brachial dilation to sublingual nitroglycerine) did not differ among groups (p=0.30). In the overall sample, 25(OH)D was positively related to FMD (r= 0.50; p<0.01) and inversely related to vascular endothelial cell nitrotryosine, a marker of oxidative damage (n=24; r=−0.63; p<0.01). These results indicate that lower circulating 25(OH)D may contribute to oxidative stress‐associated impairment of EDD among healthy MA/O, and suggest vitamin D supplementation may improve EDD in this group.NIH AG013038, AG022241, AG006537, AG0015897, AG03114, AG033994, RR00051
Food insecurity is prevalent in rural communities of El Salvador, Guatemala, Honduras and Nicaragua
Authors: Bermudez Odilia I. , de Fulladolsa Patricia Palma , Deman Hedi , Melgar‐Quinones Hugo 
Published: June 2021

IntroductionAlthough food insecurity affects groups in Central America, little is known about the magnitud and severity of this situation.ObjectivesTo assess psychometric properties of the 15‐item Food Security (FS) Scale for Latin American (ELCSA) and estimate FS in rural households (HH) of El Salvador (Sal), Guatemala (Gua), Honduras (Hon) and Nicaragua (Nic)MethodsWe assesed reliability and tested a Rasch model of the ELCSA and evaluated levels of FS in 502 families (Sal=180, Gua=120, Hon=64; Nic=138).ResultsCronbach's alpha was 0.90 with inter item correlation of 0 0.37, range=0.09–0.74. From Rasch analysis, we found that the less severe item was question1 about worrying for not having enough food (Measure = −4.6). and the most severe (6.5) was the item on children not eating in a day. Excluding question1, the INFIT values ranged from 0.8 to 1.2. Very low FS was highly prevalent in the studied HH: Nic=50%, Hon=31%, Gua=18% and Sal=14%.ConclusionsThe ELCSA was valid and reliable for measuring FS in Central America. The levels of very low FS were highly prevalent, therefore additional efforts are needed to protect those vulnerable population groups.
Evidence for distributed processing during hypoxic stimulation by the brainstem cardiorespiratory network
Authors: Morris Kendall , Ott Mackenzie M , Nuding Sarah C , Segers Lauren S , O'Connor Russell , Dick Thomas E , Solomon Irene C , Shannon Roger , Lindsey Bruce G 
Published: June 2021

Brainstem neural networks play an important integrative role in the regulation of respiratory and cardiovascular responses to hypoxia, but their organization remains poorly understood. We addressed the hypothesis that a distributed brainstem network, including rostral medullary neurons (RMNs) in the region of the retrotrapezoid nucleus, dorsolateral pons, raphé, and ventrolateral cardiorespiratory column (VRC), integrate central and peripheral chemoreceptor inputs. Data were obtained from decerebrate adult cats. We used multi‐electrode arrays to record from up to 118 neurons simultaneously. Firing rate responses were measured during hypoxia and stimulation of central chemoreceptors. Spike trains were also analyzed with respiratory and cardiac cycle triggered histograms and cross correlation. Results include: 1. Multiple cardiorespiratory rhythms in neurons responsive to hypoxic stimulation. 2. Co‐expression of distributed eupneic network activity present together with gasp patterns during recovery from severe brain hypoxia. 3. Reciprocal effective RMN‐VRC connectivity of neurons responsive to both hypoxia and hypercapnia. The results suggest a brainstem network architecture with connectivity that shapes the respiratory motor pattern via overlapping circuits that modulate central and peripheral chemoreceptor‐mediated influences on breathing.Supported by NS19814, NS46062
Cyclooxygenase enzyme activation in human skeletal muscle after acute resistance exercise
Authors: Del Mundo Jonathan D , Pierce Nick B , McMullan David R , Ramos Jahir E , Whitt Jamie A , Letham Tanya , Worden Kate , Carroll Chad C 
Published: June 2021

The purpose of this study was to evaluate cyclooxygenase (COX)‐1 and ‐2 activation in response to an acute bout of resistance exercise (RE) in human skeletal muscle. Before, 4, and 24 hours after a bout of unilateral knee extensor RE (3 sets of 10 repetitions at 70% of maximum) muscle biopsies were taken from the vastus lateralis of seven young males (25±0.4 y). Biopsy samples were assayed for COX‐1 and COX‐2 activity (700200, Cayman Chemical). COX‐1 activity was not increased with RE (PRE: 5.0±1.0, 4 hrs: 6.5±1.1, 24 hrs: 7.7±1.9 nmol PGH2·g muscle−1·min−1) while COX‐2 activity was elevated at 24 (p<0.05) but not four hours after exercise (PRE: 4.5±1.1, 4 hrs: 5.8±1.1, 24 hrs: 8.9±1.4 nmol PGH2·g muscle−1·min−1). Prostaglandin (PG) production due to COX‐1 and COX‐2 was similar (COX‐1/COX‐2 ratio: 1.1±0.3) before RE. This ratio (0.8±0.3) decreased at 24 hours indicating a greater proportion of PG production from COX‐2. COX activity has been implicated as a necessary component of a RE‐induced increase in skeletal muscle protein synthesis. Muscle protein synthesis is elevated as early as 1–4 hours after RE. Thus our data suggest that an elevation in COX‐1 or COX‐2 activity may not be necessary for the RE‐induced increase in protein synthesis. Our findings also support the general consensus that COX‐2 is inducible and that COX‐2 enzyme activity is present in resting skeletal muscle.Funding: MWU Start‐Up Funds, and MWU College of Health Sciences
Modulation of postjunctional α‐adrenergic vasoconstriction during exercise and exogenous ATP infusions in aging humans
Authors: Kirby Brett S , Richards Jennifer C , Crecelius Anne R , Voyles Wyatt F , Dinenno Frank A 
Published: June 2021

The ability to modulate α‐adrenergic vasoconstriction in contracting muscle is impaired with age. In young adults, adenosine triphosphate (ATP) has been shown to inhibit vasoconstrictor responsiveness similar to exercise. We tested the hypothesis that modulation of postjunctional α‐adrenergic vasoconstriction to exogenous ATP is impaired in aging humans. We measured forearm blood flow (FBF; Doppler ultrasound) and calculated vascular conductance (FVC) to intra‐arterial infusions of phenylephrine (α1‐agonist) and dexmedetomidine (α2‐agonist) during rhythmic handgrip exercise (15% MVC), a control non‐exercise vasodilator condition (adenosine), and ATP infusion in 7 young (22±1) and 7 older (64±3 yrs) adults. Forearm hyperemia was matched across all conditions. During adenosine, forearm vasoconstrictor responses to direct α1‐stimulation were lower in older adults (ΔFVC= −25±3 vs −41±5%); the responses to α2‐stimulation were not different (−38±5% vs −44±7%). The ability to blunt α1‐ and α2‐vasoconstriction was impaired in older adults during exercise (α1 = 31±9 vs 74±8%; α2 = 28±10 vs 60±10%). In contrast, ATP reduced the vasoconstrictor responses by ~85–90% in both age groups. We conclude that the sympatholytic effect of exogenous ATP is not reduced with age, and thus blunted ATP release during exercise may contribute to the impaired exercise sympatholysis in older adults.Supported by HL‐087952
Laser‐speckle analysis of renal cortical perfusion – regional perfusion dynamics
Authors: Cupples William A , Waring Jennifer , Holstein‐Rathlou Niels‐Henrik , Chon Ki , Braam Branko 
Published: June 2021

Tubuloglomerular feedback and a myogenic mechanism act on afferent arterioles to mediate autoregulation of renal blood flow (RBF) and their actions may extend beyond single nephrons. We tested for physiologically significant coupling among neighboring nephrons. Cortical surface perfusion was assessed by laser‐speckle perfusion imaging at 1 Hz. Time series from 5 regions of interest (ROI, ~0.5 × 0.5 mm) were extracted. RBF (Transonic 400) was systematically altered by manipulation of perfusion pressure, by captopril (−/+ ANG II), and by L‐NAME. Perfusion in the ROIs (units) was linear in RBF (slope = 1120 ± 63 units × min/mL, r2 = 0.94 ± 0.03, n=5). Power spectra of the ROI time series contain the same information as RBF spectra and spectra of all ROIs are very similar. Comparing adjacent to remotely located ROIs by spectra of difference series, by linear cross spectra, and by nonlinear cross bi‐spectra showed that coupling decreased with separation between ROIs. The cross bi‐spectral coupling index declined with separation of ROIs: adjacent = 0.269, medium = 0.170, remote = 0 during control (greater index = greater coupling). ANG II infusion increased the spread of coupling: adjacent = 0.133, medium = 0.034, remote = 0.014. Local coupling suggests that autoregulation may involve coordinate action of clusters of nephrons. Coupling may be regulated by ANG II.Funded by Heart & Stroke Fdn of BC & Yukon, & Victoria Fdn
Development of damage to porcine renal arterial vascular anatomy and blood flow after cryoablation: acute to 2 weeks
Authors: Spaan Jos , Lagerveld Brunolf , van Horssen Pepijn , van den Wijngaard Jeroen , de la Rosette Jean , Laguna Pilar , Siebes Maria , Wijkstra Hessel 
Published: June 2021

Aimto better understand the acute and successive events of renal cryoablation.MethodsIn 20 anesthetized pigs renal cryoablation was applied for 20 minutes. Kidneys were divided into five groups with pig survival time after ablation of 20 min, 4 hrs, 2, 7 and 14 days after ablation. Before euthanasia, fluorescently labeled microspheres were intravenously administrated. The kidney was harvested, the main renal artery flushed, filled with a fluorescence dyed elastomere, frozen and processed in an imaging cryomicrotome. 2 stacks of 4000 images of 2000×2000 pixels where obtained. The 1st stack resulted in a 3D image of the arterial structure the 2nd stack in the 3D microsphere distribution matched to arterial structure.ResultsIn the 20 min group, vascular structures with diam >200 μm remained in the ablated area but microspheres passing through were only found in surrounding tissue. No spheres were found within the ablated area. Ablated zone vascular structures disappeared completely after 1 week. In this and later groups, all microspheres in the surrounding tissue arrived by the non‐affected vessels.ConclusionAcute injury induced by cryoablation regards vessels smaller than 200 μm leaving the structure of larger vessels intact allowing blood flow to the surrounding tissue. It takes 1 week for complete destruction of vessels in the ablated area and bock blood flow.
Role of atypical TGF in the response of subtotal nephrectomy to ischemia
Authors: Singh Prabhleen , Kashkouli Ali , Blantz R , Thomson Scott C. 
Published: June 2021

Subtotal nephrectomy (STN) leads to atypical and highly variable tubuloglomerular feedback (TGF) behavior in the residual nephrons in which the mean TGF response is zero (Singh P. AJP, 2009). Since TGF is a major hemodynamic mechanism causing fall in GFR after ischemia reperfusion (IR) injury, we examined the response of STN to IR.STN and unilateral nephrectomy (UN) rats underwent IR 1 week after surgery. GFR (inulin clearance) was measured at 24 hours post IR. GFR fell by 75% in UN after IR and only 28% in STN, p=0.0001. Losartan, which paradoxically normalizes TGF in STN (Singh P, 2009) made STN susceptible to IR (p=0.001). Micropuncture experiments examined the magnitude and heterogeneity of individual nephron responses to IR. Mean SNGFR dropped from 52 to 40 nl/min in UN post IR, but did not change in STN (60 to 66 nl/min). The variance in SNGFR differed among groups (p=0.000), with STN+IR being most variable (Fig. 2). The Fmax test for raw variances in SNGFR was significant between UN+IR and STN+IR groups (172 vs. 1107), p<0.01.Early STN kidneys are largely resistant to IR and we propose that the atypical TGF in STN contributes to this resistance. The effect of IR on SNGFR in STN parallels the effect of STN on TGF (fixed mean with high variability). Whether the high variance in SNGFR in STN+IR reflects the heterogeneous TGF responses prior to ischemia or the variable tubular injury after IR will need to be determined.imageimage
Visualizing multiscale models of the nephron
Authors: Terkildsen Jonna , Nickerson David , Hamilton Kirk , Hunter Peter 
Published: June 2021

We present the development of a tool which provides users with the ability to visualize and interact with multiscale models of the nephron – from the scale of models of membrane bound proteins, to that of an individual nephron.A 1‐D finite element model of the nephron has been created and is used for both visualization and modeling of the tubule transport. Mathematical models of nephron segments (for example, Weinstein et al., Am. J. Physiol. 292:F1164‐F1181, 2007 for the proximal tubule) are embedded in the finite element model. At the cellular level these segment models utilize models encoded in CellML (www.cellml.org) to describe cellular transport kinetics.A user interface has been developed which allows the visualization and interaction with the multiscale nephron models and simulation results. The zinc extension to Firefox (http://www.cmiss.org/cmgui/zinc/) is used to provide an interactive 3‐D view of the model(s). This model viewer is embedded in a web page which dynamically presents content based on user input. For example, when viewing the whole nephron model the user might be presented with information on the various embedded segment models as they select them in the 3‐D model view. Similarly, the user might choose to focus the model viewer on a cellular model in a particular segment in order to view the various membrane transport proteins. Selecting a specific protein might present the user with a full reference description of the mathematical model governing the behavior of that protein (Nickerson et al., Bioinformatics 24:1112‐1114, 2008).
Towards a global sensitivity analysis of the Guyton model of blood pressure regulation.
Authors: Bazin Jérôme , Grosse Thibault , Thomas S. Randall 
Published: June 2021

We present a partial sensitivity analysis of the Guyton model of blood pressure regulation. Starting from a steady state, 190 selected model parameters were systematically perturbed one at a time, and the effect on the 286 selected model variables was evaluated at 1 minute, 5 minutes, 1 hour, 1 day, and 1 week after the perturbation.Resultsparameters of a given sub‐module did not preferentially affect variables from the same sub‐module. Rather, most variables are relatively insensitive to small parameter changes, in confirmation of the system's robustness. However, those variables that are sensitive show sensitivity to many parameters. Details will be given in the presentation.ConclusionsThis one‐at‐a‐time parameter study is a useful start towards a comprehensive study, but it will be more physiologically interesting to study sequential changes of several parameters. This will require a sensible strategy to avoid combinatorial explosion of CPU time.
Stereo photogrammetric characterization of wishboning strain in the colobine mandibular symphysis
Authors: Daegling David John , Bucinell Ronald , McGraw William Scott , Rapoff Andrew Jordan 
Published: June 2021

The masticatory loading regime of lateral transverse bending (wishboning) is hypothesized to be instrumental in the evolution of symphyseal form among primates. The biomechanics of wishboning have largely been inferred by assuming that the mandible behaves as a curved beam under this load; however, the characterization of stress and strain in the anthropoid symphysis has been interpretively challenging. This is due, in part, to both limitations of sampling strain in an in vivo context and the incongruence of beam theory assumptions on the one hand and the anatomical complexity of mandibular morphology on the other.Utilizing stereo photogrammetry, we employ an in vitro approach to characterize the strain field in a sample of colobine mandibles under simulated wishboning loads in order to assess the utility of idealized curved beam models for characterizing strain gradients in symphyseal bone. This full‐field method also provides an opportunity to evaluate the effects of morphological variation on the distribution of wishboning strains.Conventional theory of curved beams suggest that colobine mandibles should exhibit reduced disparity of labial and lingual stresses relative to papionin primates given differences in overall mandibular architecture. This prediction is borne out by our analysis: whereas macaques experience lingual:labial strain disparities of 3.5:1, the colobine mandibles exhibit ratios on the order of 2‐3:1. Despite the fact that wishboning loads represent a case of asymmetric bending, details of the wishboning strain field do not conform to expected stress distribution under this model.