bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac Output in Neonates, Noninvasively
Authors: Weaver Barbara Smith , Rodriquez Misael , Bozeman Andrew , Vogel Robert 
Published: June 2021

Cardiac Output in Neonates, NoninvasivelyBarbara Weaver, R.N.1, Misael Rodriguez, M.D.1, Robert L. Vogel, PhD.2, Andrew P. Bozeman, M.D.2, and Joseph M. Van De Water, M.D.2 Departments of 1Pediatrics and 2Surgery, Mercer University School of Medicine at the Medical Center of Central Georgia, Macon, GA, 31201.Our objective was to assess a new noninvasive monitor for measuring cardiac output (CO) in neonates down to 590 grams. We used a new electrical impedance device, Aesculon® (Cardiotronic, Inc., 7855 Ivanhoe Avenue, Suite 226, La Jolla, CA 92037). The technology, Electrical Cardiometry, measures the differences in impedance presumably originating in red blood cell orientation between systole and diastole in the ascending and descending thoracic aorta in order to derive stroke volume (SV). Measurements on 75 neonates, ranging in weight from 590 to 4010 grams, were evaluated. Intra‐ and inter‐operator reproducibility was assessed from a sample of subjects. The correlation of both CO and SV to body mass (wt), body mass index (BMI) and body surface area (BSA) was computed. There were no problems using single electrode placement along the left side of the body at scalp, base of neck, xyphoid and thigh levels. Babys' tolerance was good and device operation was easy, facilitating parental consent. Reproducibility was good with a variance component for operator of less than 1% and for time of less than ½% of total variability for both CO and SV. Standards for CO in this sample of neonates (n = 75) correlated equally well with wt, BMI and BSA (r = 0.89, p = 0.0001). However, the best correlation was SV vs. wt and BSA (r = 0.93, p = 0.0001). This study suggests that a very useful noninvasive neonatal CO monitor now exists.
Critical Role of Dendritic Cells in Wound healing after Myocardial Infarction in CD11c‐DTR‐GFP Mice
Authors: Pruthi Dafina , De Muinck Ebo , Fu Qiangwei , McGarr Robert , Moodie Karen 
Published: June 2021

Dendritic Cells (DC) are known primarily for their function as antigen presenting cells. Recently it has been shown that DC acquire an endothelial phenotype and contribute significantly to tumor angiogenesis and were named vascular leukocytes (VLC). Our laboratory has shown in mice that VLC appear as early as one day after MI in the healing heart and that they reach their peak at day 7 in infarcted area which coincides with the peak of angiogenesis in this model. We asked if early depletion of DC which are the precursors of VLC, would result in changes in wound healing.MethodsWe investigated cardiac wound healing in CD11c‐DTR‐GFP transgenic mice at day 7 after inducing MI with and without depletion of CD11c DC (transgenic mouse has a transgene encoding simian Diphtheria toxin receptor under control of murine CD11c promoter, allows to specifically deplete CD11c DC by injecting Diphtheria toxin (DT)). Mice were randomized to injection with 8ng/g i.p. of DT just before MI surgery or PBS. We measured functional cardiac recovery (%ejection fraction‐ EF%) with echocardiography; cardiac diastolic and systolic function with pressure volume loops system (PV‐loops); morphometry to assess myocardial necrosis on the TTC stained slices.ResultsEchocardiography: average EF% at day 7 for mice with intact DC and depleted DC is 27% and 49% respectively, n=16, p=0.001. Morphometry: MI% at day 7, 57% and 19.4% respectively, n=16, p=0.001. PV loops: Cardiac Output (uL/min) at day 7, 7826 and 3161, End‐diastolic Pressure (mmHg) at day 7, 9.4 and 17.1ConclusionCD11c+ DCs play a significant and previously unrecognized role in post‐MI wound healing with DC depletion after MI resulting in a significant reduction of myocardial necrosis and a significantly better functional recovery of the heart.
Developing metacognitive skills through the use of blogs in an upper level undergraduate anatomy course
Authors: O'Loughlin Valerie Dean , Griffith Lauren Miller 
Published: June 2021

Incorporating metacognitive approaches into classroom instruction helps students to monitor and adjust their learning strategies throughout the semester. Metacognitive tasks like journaling serve the dual functions of being reflection pieces for students and assessment instruments for instructors.This research examined how the use of “blogs” (online journals) in an upper level human anatomy course (a) facilitated the development of metacognitive skills in the students and (b) provided the researchers insight about the ways students think about their own progression in understanding human anatomy. Specifically, did students become more self‐aware and cognizant of their strengths and weaknesses in mastering anatomy as the semester progressed? Twenty students reviewed 10 radiology online cases each throughout the semester and then reflected about their understanding of the anatomy, pathology and medical imaging interpretation in an online blog. Researchers utilized a grounded theory approach to develop a codebook that scored each line of each blog. Codes were mutually exclusive and Cohen's Kappa was used to test the inter‐rater reliability of the codebook.Students became more confident and assessed their skill in identifying anatomy and pathology more positively as the semester progressed. Students started the semester with more anxiety and frustration comments in their blogs and primarily used guessing to evaluate cases. By the end of the semester, blogs had evidence of self‐confidence and positive, accurate reflections about their understanding of the anatomy. Furthermore, the students described and used a more methodical deductive approach to evaluate each case. The use of blogs made the development of students' metacognitive skills visible and allowed the researchers to methodically assess this development using a grounded theory approach.
DEP‐Induced Changes Observed in Early‐stage Volume Overload Heart Failure Cardiomyocytes
Authors: McAllister Mary Catherine , Wold Loren E , Lucchesi Pamela A 
Published: June 2021

Increases in fatal cardiopulmonary dysfunction in cities with high levels of air pollution may be caused by the exacerbation of underlying heart conditions. The effect of Diesel Exhaust Particulates (DEP) in vitro on cardiomyocyte function was observed to determine if increased susceptibility occurs in heart failure animals. Aortocaval fistula (ACF) surgery was performed on rats to induce volume overload heart failure after 21 weeks. Myocytes were isolated 4 weeks post‐surgery, treated one hour with 1 μg/ml DEP, stimulated at 1 Hz, and analyzed based on sarcomere length and cytosolic calcium levels. No significant changes were observed during the cell contractile phase. DEP exposed ACF myocytes released significantly more calcium from the sarcoplasmic reticulum (SR) during contraction than Sham cells. Thus, Ryanodine receptors in strained ACF cells may be more sensitive to hyper‐phosphorylation. Calcium reuptake by the SR was also significantly faster in myoctyes from Sham versus ACF animals when treated with DEP. This indicates a possible decrease in SERCA2a function or expression. Unexpectedly, alterations in calcium transients did not correspond with changes in overall contractility. Future studies will be performed to investigate a compensatory mechanism involving the affinity of Troponin C for cytosolic calcium during contraction.Funding was provided by the American Physiological Society.
Wnt3a/beta‐catenin increases proliferation in valve interstitial cells
Authors: Xu Songyi , Gotlieb Avrum 
Published: June 2021

BackgroundValve interstitial cells (VICs) mediate valve function in health and disease. It is suggested that valve repair processes are regulated by developmental pathways. We hypothesize that Wnt3a increases the amount of stabilized β‐catenin present in VICs, which then results in its nuclear translocation and subsequent increase in proliferation.MethodsPorcine VIC cultures were maintained in standard media in 10% fetal bovine serum. Cultures were plated, grown to 4–6% confluence, then incubated with 100 ng/ml of exogenous Wnt3a for 3 days, and counted to measure proliferation. VICs were stained with antibody against β‐catenin. Whole cell, cytoplasmic and nuclear levels of β‐catenin were determined using Western blot.ResultsVICs treated with Wnt3a show increased cell number compared to control and vehicle‐treated cultures. Immunofluorescent images of Wnt3a‐treated VICs show slightly increased β‐catenin staining compare to control and vehicle‐treated cultures. Whole cell, cytoplasmic, and nuclear lysates of Wnt3a‐treated VICs show increased levels of β‐catenin compared to control and vehicle‐treated cultures.ConclusionWnt3a may increase VIC proliferation through an increase in β‐catenin.Supported by the Heart and Stroke Foundation of Ontario (grant NA6204) and Canadian Institute of Health Research (grant 84228).
HIV Encephalitis: Atypical Biopsy for a Typical Presentation
Authors: Chapman Sherita Nicole , Kurukumbi Mohankumar , Adams Alice , Jayam‐Trouth Annapurni 
Published: June 2021

BackgroundHuman Immunodeficiency Virus is neurotropic; approximately two‐thirds of patients with HIV infection will develop central nervous involvement during the course of their disease. Biopsy is still considered the gold standard in diagnosing cranial lesions in HIV patients.Case Presentation36 year old male, with a history of HIV infection and recent CD4 count of 65, presented with complaints of weakness and numbness over left face and difficulty speaking for the four days. Clinical examination was normal except for mild flattening of the left nasolabial fold and decreased perception of pain and touch on left side of the face. Imaging revealed a right lateral frontal homogeneous enhancing lesion with surrounding edema. A craniotomy with biopsy was performed. Histopathology revealed acute and chronic vasculitis with focal tissue vacuolization, reactive gliosis and astrocytosis, consistent with HIV encephalitis. Special stains for fungi and Toxoplasma gondii were negative and there was no evidence of neoplasm.ConclusionThis case report emphasizes the persisting challenge in evaluating cranial lesions in patients with HIV infection, including the gold standard brain biopsy.
Endothelial CaMKIIs and their alteration in mesenteric arteries from hypertensive mice
Authors: Charbel Chimène , Toussaint Fanny , Blanchette Alexandre , Villeneuve Louis Robert , Ledoux Jonathan 
Published: June 2021

Modulation of local calcium levels appears to be an important regulatory mechanism for endothelial function. Localized spontaneous endothelial calcium oscillations have recently been described within the myoendothelial projection. Interestingly, calmodulin‐dependent protein kinase II (CaMKII) is involved in endothelial function and is characterized by its ability to decode oscillatory calcium signals into specific outcomes. The aim of this study was then to determine the activation of CaMKII by calcium pulsars in endothelial cells from mesenteric arteries and their alteration in hypertension. qPCR experiments suggest that all four CaMKII isoforms (α, β, δ and γ) are expressed in mesenteric arteries but their expression was significantly decreased (27–57%) in hypertensive animals. Immunohistochemistry confirmed that all isoforms are expressed in mesenteric endothelium and were homogeneously distributed in normotensive animals. However, hypertension is correlated with a distribution of endothelial CaMKII in clusters. Ca2+ pulsars agonists appear to stimulate clustering of CaMKII as evidenced by immunohistochemistry. This data suggest that endothelial CaMKII is activated by Ca2+ pulsars and that this mechanism is altered in hypertension.Supported by CIHR, FRSQ, CFI and HSFC
The vasodilatory peptide maxadilan increases plasma leakage in postcapillary venules due to activation of leukocytes via CXCL2‐release
Authors: Svensjö Erik , Saraiva Elvira M , Barja‐Fidalgo Christina , Bozza Marcelo T , Lerner Ethan A. , Teixeira Mauro M , Scharfstein Julio 
Published: June 2021

Maxadilan (MAX) isolated from the sand fly Lutzomyia longipalpis induce plasma leakage in postcapillary venules of the hamster cheek pouch (HCP) via PAC‐1‐receptor stimulation. Arteriolar dilation, plasma leakage (FITC‐dextran 150) and accumulation of rhodamine‐labeled leukocytes in the HCP was measured after topical applications of MAX 134 nM alone or combined with 8 μM M‐65, a PAC1‐receptor antagonist or after dextranSO4 (500 kDa, 2–4 mg/kg i.v.) or after repertaxin (CXCR2‐antagonist, 30–60 mg/kg i.v.) in order to study role of leukocyte activation by MAX. Measurements were made in images of a digital camera. Five groups of hamsters were studied, saline control, MAX 134 nM, MAX + M‐65, MAX + DxSO4 and MAX + repertaxin. Topical applications of MAX and M‐65 were made on the HCPs in 250 μl of saline and images were recorded for 60 minutes. There was no plasma leakage increase in the saline control group and a slight increase in leukocyte accumulation but there was a lasting increase in plasma leakage (180%, P < 0.05) and leukocyte accumulation (150%, P < 0.05) in the MAX‐group with peak responses at 40 min and 60 min, respectively, that was inhibited by M‐65, DxSO4, and repertaxin. Arteriolar dilation was inhibited by M‐65 and repertaxin but not by dextranSO4.ConclusionsPAC1 receptor activation by maxadilan caused plasma leakage and leukocyte accumulation via chemokine (CXCL2) release independent of its vasodilatory effect.
Glucagon‐like peptide‐1 (GLP‐1) improves coronary microvascular endothelial function after cardiac arrest and resuscitation and prevents anoxia‐induced coronary microvascular endothelial cell death
Authors: Dokken Betsy B , Piermarini Charles V , Asghar Mostafa Aeen , Teachey Mary K , Gura Michael , Dameff Christian J , Heller Brian D , Hilwig Ronald W , Kern Karl B 
Published: June 2021

Cardiac arrest and resuscitation cause dysfunction of the coronary microcirculation. The aims of this study were to determine: 1) effects of GLP‐1 on coronary endothelial microvascular function after cardiac arrest and resuscitation, and 2) effects of GLP‐1 on coronary endothelial cell viability after anoxia and reoxygenation in vitro. Ventricular fibrillation (VF) was induced electrically in 20 anesthetized domestic swine (30–35 Kg). Following 8 min of untreated VF, animals were resuscitated and randomized to receive either GLP‐1 (10 pM/Kg/min) or saline as placebo (PBO) for 4 hr. Coronary flow reserve (CFR) was measured before and after intracoronary administration of Substance‐P (0.2 nG/2 min) pre‐arrest, 1 and 4 hr post‐resuscitation. In addition, human microvascular coronary endothelial cells (HCMVECs) were subjected to 1 hr of anoxia after pre‐incubation with GLP‐1 (0.3 nM) followed by reoxygenation for 72 hr.ResultsCFR was increased in those treated with GLP‐1 (1 Hr: PBO group 0.8 ± 0.1, GLP‐1 group 1.3 ± 0.1; 4 Hr: PBO group 0.8 ± 0.1, GLP‐1 group 1.1 ± 0.1, p< 0.05). Viability of ECs decreased by 77% in untreated cells; GLP‐1 prevented anoxia‐induced cell death (untreated group 23% viable/total, GLP‐1 group 94% viable/total, p< 0.01).ConclusionsGLP‐1 attenuates post‐resuscitation coronary microvascular endothelial dysfunction in vivo, and prevents anoxia‐induced HCMVEC cell death in vitro.
Challenging O2 delivery: metabolism coupling in small muscle mass exercise
Authors: Bentley Robert Francis , Hong Terence , Poitras Veronica , Kellawan Jeremy Mikhail , Pak Melissa , Jazuli Farah , Chung Beryl , Tschakovsky Michael E 
Published: June 2021

PURPOSETo understand how O2del: metabolism matching is defended in the face of increased duration of contraction‐induced mechanical impedance to exercising muscle blood flow.METHODS7 healthy young males, (21.8 ±1.8 yrs) performed a handgrip ramp exercise protocol (increase contraction force 2.5 kg every 3 min) under Control (CON; 2 s isometric contraction + forearm compression cuff inflation: 4 s relaxation duty cycle) and Impedance (IMP; 2 s contraction + forearm compression + extra 2 s of forearm compression: 2 s relaxation duty cycle). Forearm blood flow ((FBF (ml/min); brachial artery Doppler and Echo ultrasound), mean arterial blood pressure (MAP (mmHg); finger photoplethysmography) were measured. Forearm vascular conductance during relaxation (FVCrelax ml/min/100 mmHg)) was calculated (FBFrelax/MAP x 100).RESULTSData are mean ± SD. Up to 7.5 kg workload, FBF (therefore O2del) was not different between conditions due to compensatory vasodilation in IMP (eg. 7.5 kg FVCrelax IMP 596 ±140 vs. CON 396 ±60, P<0.05). Above 7.5 kg workload a small pressor response in IMP was added (MAP IMP 103.5 ±7.8 vs. CON 98.8 ±8.6, P<0.05), but O2del: metabolism matching was not achieved.CONCLUSIONSCompensatory vasodilation successfully maintains O2del: metabolism matching at lower workloads. When it fails, a pressor response is evoked, but cannot maintain O2del: metabolism matching at higher workloads. NSERC.
Inter‐individual differences in coupling oxygen delivery to demand during a progressive exercise test
Authors: Bravo Michael , Kellawan Jeremy Mikhail , Moynes Jaclyn , Bentley Robert , Shantz Rebecca , Tschakovsky Michael E 
Published: June 2021

Oxygen delivery (O2del) to exercising muscle is thought to be tightly coupled to metabolic demand, as evidenced by proportional increases in O2del with increasing exercise intensity. Little consideration has been given to investigation of inter‐individual differences in this coupling.PURPOSETo characterize inter‐individual differences in O2del:metabolism coupling during progressive increases in exercise intensity.METHODS8 healthy males (24.4 ±6.4 yrs) performed rhythmic isometric handgrip contractions (1 s:2 s contraction:relaxation duty cycle, contraction force increased by 2.5 kg every 3 min. until failure). Forearm O2del was calculated as arterial oxygen content (O2 saturation via pulse oximeter; [hemoglobin] via venous blood sample) x brachial artery blood flow (BABF; Doppler and Echo ultrasound).RESULTSData are mean ±SD. From rest to end of the 17.5 kg stage the 1) total blood delivered to the forearm was 3565.282 ±1013.584 mL, coefficient of variation (CV) 28%, range 2321.132 to 5384.500 mL and 2) total O2 delivered to the forearm was 533.306 ±153.192 mL, CV 29%, range 312.520 to 786.140 mL. Mean blood flow at 17.5 kg was 345.510 ±89.782 mL.CONCLUSIONSInter‐individual differences in blood flow and O2del:metabolism coupling during small muscle mass ramp exercise protocol can be substantial. Implications for understanding O2del:metabolism coupling need to be considered.
PARP‐1 inhibition improves coronary arteriole function in type 2 diabetic mice
Authors: Choi Soo‐Kyoung , Kassan Modar , Galan Maria , Partyka Megan , Matrougui Khalid 
Published: June 2021

ObjectiveType 2 diabetes is associated with microvascular dysfunction. We hypothesized that increased Poly‐(ADP‐ribose) polymerase 1 (PARP‐1) activity contributes to coronary arteriolar dysfunction.Methods and ResultsType 2 diabetic db−/db− (diabetic) and non‐diabetic db−/db+ (control) mice were treated with PARP‐1 inhibitors (INO‐1001, 5mg/Kg/day and ABT‐888, 15mg/Kg/day) for two weeks. Isolated coronary arterioles were mounted in an arteriograph. Pressure‐induced myogenic tone (MT) was significantly potentiated, while endothelium‐dependent relaxation was significantly attenuated in diabetic mice compared to control. These results are associated with increased PARP‐1 activity in coronary arterioles from diabetic mice compared to control. Interestingly, diabetic mice treated by PARP‐1 inhibitors significantly reduced the potentiation of myogenic tone and improved the endothelium‐dependent relaxation. Down regulation of PARP‐1 in coronary arterioles using lentivirus‐shRNA‐PARP‐1 significantly improved coronary arteriole function in diabetic mice compared to control. The inhibition of nitric oxide synthesis by L‐NAME significantly reduced the endothelium‐dependent relaxation in coronary arterioles from sham and diabetic mice treated with PARP‐1 inhibitors and lentivirus‐shRNA‐PARP‐1.ConclusionsWe provide evidence of a link between the increased PARP‐1 activity and coronary arteriole dysfunction in type 2 diabetic mice. Thus, PARP‐1 may be a potential target for overcoming diabetic microvessels complications.
cAMP mediated Ca2+‐desensitization of mouse tail arteries involves disinhibition of myosin light chain phosphatase (MLCP) in a PKA‐dependent and independent manner
Authors: Pfitzer Gabriele , Lubomirov Lubomir Todorov , Drinhaus Hendrik , Neulen Axel 
Published: June 2021

Here, we investigated whether the non‐canonical cAMP sensor, Epac decreases Ca2+‐sensitivity by activating MLCP. Submaximally contracted (pCa 6.1) α‐toxin permeabilized arteries were relaxed by the specific activator of PKA, 6‐Bnz‐cAMP (Bnz) or Epacs, 8‐pCPT‐O‐Me‐cAMP (pCPT). Phosphorylation of MLC20, the regulatory subunit of MLCP, MYPT1, and VASP was determined by Western blots using phosphospecific antibodies.ResultsBoth cAMP analogues relaxed the vessels at constant pCa=6.1 but with different potencies (pIC50 4.6 for 8‐pCPT‐cAMP; 6.6 for Bnz). At equipotent concentrations both compounds increased the rate of dephosphorylation of MLC20 while phosphorylation of MYPT1‐T696/T853 decreased by a similar extent suggesting activation of MLCP. Bnz but not pCPT increased phosphorylation of the PKA sites on VASP (S157) and MYPT1 (S695) the latter being known to prevent subsequent phosphorylation of MYPT1‐T696. The effect of Bnz on MYPT1 phosphorylation was inhibited by the PKA inhibitor, H‐89. Ca2+‐desensitization by pCPT but not by Bnz was partially blocked by NSC 23766, a Rac1 inhibitor. In conclusion, MLCP is activated by PKA and Epac. Both pathways converge at the level of MYPT1 and decrease phosphorylation of T696 and T853, but the upstream mechanisms only partially overlap.Supported by the German Research Foundation.
Angiotensin Converting Enzyme Exerts System Control Over Fuel Handling In Skeletal Muscle
Authors: Flueck Martin , Vaughan David , Allwood William , Hoppeler Hans , Huber‐Abel Felicitas , Rittweger Joern , Dunn Warwick , O'Hagen Steven , Goodacre Royston 
Published: June 2021

Using a genetical metabolomics approach we assessed whether altered energy supply in locomoter muscle underlies the elevated aerobic performance of human genotypes containing a silencer region (I‐allele) of the major regulatory enzyme of vasoconstriction, angiotensin converting enzyme (ACE).Extensor muscle, m. vastus lateralis, of ACE‐II/ID genotypes holding the I‐allele demonstrated a trend for elevated capillarity compared to ACE‐DD counterparts lacking the I‐allele (311.0 vs. 279.7 mm‐2, n=20, p=0.10). In untrained subjects, maximal oxygen uptake during bicycle exercise was lower in ACE‐DD genotypes (44.9 vs. 47.8 ml O2/min/kg). Exhaustive aerobic exercise selectively reduced low density lipoproteins in serum of ACE‐II/ID genotypes (−14%) but was spared in ACE‐DD (+6%, p=0.25). By contrast, non‐polar metabolites in exercised muscle, comprising tentatively identified LDL‐derived glycerophosphocholine species, were depleted in ACE‐DD genotypes (q=2.8%; statistical analysis of microarrays). The interaction effect of exercise and genotype on lipidic muscle metabolites was maintained in trained subjects (p=0.03, ANOVA). The observations indicate that elevated import of serum lipids into exercised muscle underlies the enhanced aerobic exercise performance of I‐allelic genotypes for this major checkpoint of vascular perfusion.