bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary zinc intake is inversely associated with stunting among adolescent girls in Tanzania
Authors: Chen Shanshan , Ronnenberg Alayne , Cordeiro Lorraine 
Published: June 2021

Stunting is a highly prevalent public health problem in developing countries, particularly among populations exposed to food insecurity and chronic malnutrition. Empirical research has shown that early childhood malnutrition is a strong predictor of stunting. Zinc is essential to growth and development, deficiency in this micronutrient may further contribute to stunting in childhood and adolescence. This cross‐sectional study examined the associations between stunting and dietary intake of zinc among a sample of never‐married adolescent girls (n=296) living in Kilosa District, Tanzania. Dietary, anthropometric, physical activity, morbidity and demographic data were collected. The associations between stunting (determined as height by age less than 3rd percentile of WHO reference) and dietary intake of zinc were tested using logistic regression, adjusting for age, socioeconomic status, BMI, energy intake, physical activity and individual dietary diversity. The prevalence of stunting was 62.2%. Adolescent diets were generally deficient in zinc, with a mean intake of 3.4 mg/day compared to the RDA value of zinc intake as 8–9 mg/day for adolescent girls. Higher intake of zinc was found to be associated with lower risk of stunting (OR, 0.872; 95%CI, 0.763–0.998, p<0.05). These findings suggest that dietary intake of zinc may play a significant role in the chronic nutritional status of adolescent girls. Longitudinal studies examining these associations in developing countries settings are needed.Grant Funding Source : ASN
New Therapeutics Targeting Heart Failure: Development of GRK2 Selective Inhibitors
Authors: Homan Kristoff T , Thal David M , Wu Emily , Chen Jun , Sklar Larry , Tesmer John JG 
Published: June 2021

Heart failure is a leading cause of death in adults throughout the world. One of the defining characteristics of heart failure is dysregulation of G protein‐coupled receptor (GPCR) signaling, namely that mediated by the β‐adrenergic receptors (βARs). Prolonged stimulation of βARs results in receptor desensitization, which is initiated through phosphorylation by G protein‐coupled receptor kinases (GRKs). It has been demonstrated that inhibition of one of these GRKs, GRK2, improves prognosis in heart failure through increased cardiac performance. Given the therapeutic potential of inhibiting GRK2, considerable effort has been devoted towards developing selective inhibitors. In this work, high‐throughput screening methods were used to identify potential GRK2 inhibitors. One set of related compounds has been identified as potent inhibitors of GRK2 for which structure‐activity relationships are being elucidated. Another inhibitor is a previously approved FDA drug which demonstrated high selectivity for GRK2 in vitro and was efficacious in vivo.Support was provided by NIH grants HL086865, HL071818, and MH089378.
Applicability of Cable Theory to Vascular Conducted Responses
Authors: Hald Bjørn Olav , Jensen Lars Jørn , Sørensen Preben Graae , Holstein-Rathlou Niels-Henrik , Jacobsen Jens-Christian Brings 
Published: June 2021

Conduction processes in the vasculature are usually described using cable theory, i.e. locally induced signals decay passively along the arteriolar wall. The steady state length constant, λ, derived from cable theory quantifies the decay. However, cable theory depends on assumptions not necessarily fulfilled in small arteries and arterioles. We employ a recently developed mathematical model by Kapela et. al 2010 of a rat mesenteric arteriole to investigate if the assumptions hold and whether λ adequately describes simulated conduction profiles.We find that although many important cable theory assumptions are violated, a phenomenological use of the length constant derived from cable theory is a good measure of conduction length. Hence, λ should be interpreted as a descriptive measure and not in light of cable theory.Determination of λ using cable theory assumes steady state conditions. In contrast, using the model it is possible to probe how conduction behaves before steady state is achieved. The time‐dependent activation of ion channels leads to changing conduction profiles during this period and may partly explain the different conduction properties of different agonists.
Subendothelial pericytes in the intima of venous bypass grafts catalyze thromboembolic and atherosclerotic processes
Authors: Nees Stephan , Gansera Brigitte , Juchem Gerd 
Published: June 2021

Objectivedeeper insight into the mechanisms of thrombotic and proliferative occlusion of coronary bypass grafts of venous origin and remedy. Common preparation and intraoperative storage of grafts in usual preservation solutions (such as saline) cause vast endothelial denudation (>50%) and exposure of newly detected subendothelial pericytes (P) of the intima. P express a high tissue factor concentration and form the prothrombinase complex (31±4 nmol Xa bzw. 5.7nmol ± 1.08 Prothrombin •min−1•10−6cells), thus catalysing rapid formation of fibrin thrombi. Following exposure to locally formed serum, P proliferate more rapidly (doubling time <18h). Attached platelets and leukocytes accelerate the procoagulatory and proliferative processes further, and endothelium‐dependent anticoagulatory activities are significantly abolished. In contrast, sealing venous grafts using a custom‐built injector system to prevent pressure artifacts during sealing and storage in a plasma derivative preserve graft endothelialization (>90%) with retention of typical anti‐thrombogenic endothelial activities. Given their general presence in the vascular intima, P may play a hitherto unrecognized role in many thrombotic and sclerotic illnesses. The optimized intraoperative handling techniques described can improve graft prognosis considerably. Supported by a grant of the Friedrich‐Baur‐Stiftung, Munich.
[Nle3, D‐Phe6]‐gamma melanocyte stimulating hormone (NDP γMSH), increases glomerular filtration rate (GFR) in high salt fed rats
Authors: Healy Vincent , Flanagan Evelyn T , Cope Georgina , Johns Edward J 
Published: June 2021

This study examined the cardiovascular and renal actions of the natriuretic peptide γMSH with those of a synthetic analogue, NDP‐γMSH.Both γMSH and NDP‐γMSH were infused systemically (3–1000 nmol/kg) and intrarenally (500 fmol/min) into innervated and renally denervated normal and high salt fed rats. The effect of the infusion of these peptides on mean arterial pressure (MAP), urinary sodium excretion, urinary output, GFR and fractional sodium excretion was measured.Both renal and systemic infusion of γMSH increased MAP by 23±2% and 54±4% respectively but no pressor effects were observed upon renal or systemic infusion of NDP‐γMSH. The analogue increased urine flow and sodium excretion by 2–3 fold in fed a normal salt (0.4% Na+) diet and by 6–7 fold in rats fed a high salt (4% Na+) diet and induced a 3.5‐fold increase in GFR in high salt fed rats compared to normal salt fed controls. These renal effects of NDP‐γMSH were not abolished by prior renal denervation.NDP‐γMSH possessed the natriuretic but not the cardiovascular properties of γMSH. These natriuretic effects occur independently of renal innervation suggesting a direct effect of NDP‐γMSH on the kidney.
Peripheral Chemoreceptors Contribute Significantly to Hypertension in Spontaneously Hypertensive Rats (SHR)
Authors: Whiteis Carol A. , Post Collin E. , Morgan Donald A. , Rahmouni Kamal , Chapleau Mark W. , Abboud Francois M. 
Published: June 2021

In carotid body glomus cells of young pre hypertensive SHR the overexpression of acid sensing ion channels increases their pH sensitivity and is associated with increased sympathetic nerve activity (Tan et al., Circ. Res. 2010). Here we tested the hypothesis that early resection of the carotid bodies might reduce hypertension in SHR. Under anesthesia both carotid bodies were resected (CBX) in young (<5 weeks) SHR and in their normotensive control WKY. Arterial blood pressure (BP) recorded using a tail cuff twice a week over a 5 month period was lower in SHR with CBX than in sham‐operated SHR (p<0.05 ANOVA). The 24 hour intra‐arterial BP recordings in awake rats at 23 weeks of age are below.

Systolic BP (mmHg)
Mean BP (mmHg)

Sham
CBX
Sham
CBX

WKY
149±5 (n=5)
146±6 (n=6)
120±5
119±7

SHR
239±6* (n=10)
202±8*† (n=9)
185±3*
159±6*†

p<0.05 (SHR vs. WKY)
p<0.05 (CBX vs. Sham)

Compared to WKY, the mean BP was 65±3 mmHg higher in SHR‐Sham and only 40±6 mmHg higher in SHR‐CBX. Under anesthesia ventilatory and renal nerve activity responses to chemoreceptor stimulation were measured. The left ventricular (LV) weight of SHR‐Sham (1.04±0.03 gm) was significantly greater (p<0.002) than that of SHR‐CBX (0.92±0.01) and WKY (0.91±0.01).ConclusionThe contribution of the hypersensitive peripheral chemoreceptors to the increase in mean BP in SHR is estimated to be 38% and may account for most of the LV hypertrophy. (NIH/HL14388)
Non‐peptide Agonist of the Receptor MAS, AVE 0991, Increases PPARα Expression in Muscle of Rats Fed Fructose‐ Rich Diet
Authors: Mario Érica Guilhen , Santos Robson , Botion Leida Maria 
Published: June 2021

The aim of the present study was to evaluate the role of AVE 0991, agonist non‐peptide of Angiotensin‐(1–7), in lipidic profile of Sprague‐Dawley male rats. Animals were randomly distributed into fed commercial diet plus 10% fructose in drinking water during 3 weeks, after animals were treated with (FA) or without (F) 1 mg/Kg AVE0991 during 2 weeks. To evaluate the effects of AVE, it was analyzed: serum biochemical parameters, activity of lipoprotein lipase (LPL) in muscle and gene expression of PPARγ, SREBP‐1c and PPARα by real time PCR. Treatment with AVE0991 promoted reduction in serum levels of free fatty acids (F 0.707±0.02mmol/L vs. FA 0.558±0.06mmol/L) and triacylglycerol (F 163.9±18.18mg/dL vs. FA 108.7±11.65mg/dL) without altering the levels of total cholesterol in animals fed with fructose. The activity of LPL in muscle was increased (F 0.014±0.005mU vs. FA 0.04±0.01mU) without changing gene expression of PPARγ and SREBP‐1c. However, there was an increase in gene expression of PPARα (F1.1±0.14 unit arbitrary vs. FA 5.4±1.8 unit arbitrary). These data suggest that treatment with AVE0991 increased the consumption of lipids by muscle, and this can contribute to the reduction of free fatty acids and triacylglycerol found in serum of rats fed a fructose‐rich diet.Financial support: CNPq, CAPES, FAPEMIG.
Perceptions of second year medical students to interactive tools, games, and audience response systems incorporated to teach pharmacology
Authors: Gorman A. Laurel , Berry Andrea 
Published: June 2021

Second year medical students were surveyed to determine perceptions of the effectiveness of innovative, interactive methods employed to teach pharmacology in clinically integrated, systems‐based modules.METHODSInteractive techniques included clicker audience‐response questions, game‐based competitions, and interactive automated slides completed with audience participation. An anonymous survey was distributed to students assessing perceptions of the techniques in encouraging engagement, knowledge acquisition, and critical thinking. Observations of student participation were made comparing traditional sessions with more interactive sessions.RESULTSStudents had very positive perceptions of interactive techniques, consistently agreeing or strongly agreeing that they promoted classroom engagement, encouraged critical thinking/group discussion, and increased interest in learning pharmacology. Observations included an increase in the number of student‐generated questions as well as a wider distribution of students participating in the interactive sessions.CONCLUSIONSSecond year medical students perceived that incorporation of interactive exercises and clicker‐style games into pharmacology sessions were effective learning tools that promoted engagement, interest, and critical thinking about pharmacology concepts.
Sex and Racial Population Differences in the Arthro‐kinematics of the Carrying Angle: Potential Clinical Implications
Authors: Baral Sumit , Elnekaveh Brandon M. , Adar Tony , Pagano Anthony S. , Marquez Samuel 
Published: June 2021

The carrying angle (CA) of the elbow is defined as the angle between the long axis of the extended forearm as it lies lateral to the long axis of the arm. It develops in response to pronation of the forearm and keeps the swinging upper extremity away from the side of the pelvis during locomotive gait. Larger CA's may be a risk factor leading to elbow instability and pain. This study compares the CA between males and females and between Euro‐Americans (EA) and African Americans (AA). 10 male (5 EA, 5 AA) and 10 female (5 EA, 5 AA) volunteers drawn from an urban population with no past history of elbow pathology had their CA's measured via goniometer. Results showed that males had an average CA of 12.32 degrees compared to an average 15.08 degrees in females. EA and AA had less discrepant angles of 13.68 degrees and 13.72 degrees, respectively. Student's t‐test revealed that the angles of females were significantly (p<0.05) larger than those of males, while no significant variation was shown in the angles between EA and AA. The cultural role of females in rearing children typically involve the carrying of their young, which generates a significant amount of stress on the proximal muscle attachments of the medial and lateral epicondyles of the elbow. Our results suggest that CA may be a predisposing factor of the female predilection to epicondylitis particularly in eccentric contraction during routine activities.Grant Funding Source: SUNY Downstate College of Medicine Alumni Association
THE SURGICAL IMPORTANCE OF THE BLOOD SUPPLY OF THE TIBIA
Authors: Shaibah Hassan S , Altaf Faris Altaf M 
Published: June 2021

The objectives wereto study the blood supply to the tibia to show its possible use as vascularized bone allograft.Materials and Methods20 lower limbs of both sexes and both sides. The femoral artery of each cadaver was injected with red latex in lead oxide. The tibia was dissected to show its blood vessels.ResultsThe tibia was supplied by vascular circles made essentially by the periosteal branches of the anterior tibial artery which was supported by periosteal branches from the inferior genicular arteries at the upper fourth of the tibia. In the following fourth, the periosteal branches of the posterior tibial artery and the nutrient artery support the anterior tibial artery. At the next fourth (distal diaphysis), these circles were made only by the periosteal branches of the anterior tibial artery while at the distal fourth, the vascular circles were made by periosteal branches of the anterior and posterior tibial arteries and the peroneal artery. The nutrient artery of the tibia originated from the posterior tibial artery.ConclusionTibia has a rich blood supply with sizable feeding vessels; the anterior and posterior tibial and the nutrient arteries. It can be used as free vascularized bone allograft. Its richly supplied periosteum can be used as vascularized periosteal allograft to treat nonunion fractures.Grant Funding Source: N/A
Epicardial HIF1 regulates vascular precursor cell invasion into the myocardium through the VEGF signaling pathway
Authors: tao jiayi , Doughman Yongqiu , Yang Ke , Ramirez-Bergeron Diana , Watanabe Michiko 
Published: June 2021

During cardiogenesis, a subset of epicardial cells undergoes epithelial‐mesenchymal‐transition (EMT) and the resulting epicardial derived cells (EPDC) migrate into the sub‐epicardium and myocardium and differentiate into several cell types of the coronary vasculature. Our previous data suggested a link between HIF and epicardial EMT and further coronary vasculogenesis. To better understand the autocrine role of HIF in the epicardium, we used an adenoviral system to constitutively express active HIF1a in the embryonic quail epicardium. We observed that over‐expression of HIF1a in the epicardium prevented EPDC from proper migration into the myocardium. In vitro collagen gel assays confirmed that infection with AdcaHIF1a impaired the invasiveness of epicardial cells. Results from immunostaining and real‐time PCR revealed that epicardial EMT and differentiation of EPDC into endothelial cells and smooth muscle cells were not disrupted. Further investigation suggests that the increase in VEGFR1 expression caused the inhibition of EPDC invasion. In conclusion, our studies support the hypothesis that epicardial HIF is required for regulating epicardially derived mesenchyme invasion into the myocardium, a critical step in the vascularization of the myocardium. This role of HIF suggests that the differentially hypoxic microenvironment may inform epicardial cells when to stop or start migration.Grant Funding Source: American Recovery and Reinvestment Act (ARRA) R01HL091171
NMD‐deficient Upf3b‐null mice display behavioral and neuropathological defects
Authors: Huang Lulu , Shum Eleen Y. , Karam Rachid , Nguyen Lam Son , Gecz Jozef , Wilkinson Miles F 
Published: June 2021

To address the physiological role of nonsense‐mediated RNA decay (NMD), we generated mice with a null mutation in the Upf3b NMD gene. While these Upf3b‐null mice are viable, fertile, and grossly normal, a battery of behavioral tests revealed they exhibit a specific defect in sensorimotor gating. This defect is commonly displayed in Schizophrenia patients, a subset of whom have recently been shown by several groups to have mutations in the human UPF3B gene. Neuropathological examination of the frontal cortex, the site responsible for sensorimotor gating, revealed decreased dendritic spine density and mature dendritic spines in pyramidal cells. Intriguingly, such defects are also observed in schizophrenic and autistic patients. To understand the underlying mechanisms by which UPF3B acts in this circuit, we performed exon‐array analysis of the frontal cortex of Upf3b‐null mice. This revealed dysregulation of several mRNAs transcribed from genes mutated in intellectual disability patients, most of which encode proteins that function in sensory perception and cognition. NMD is likely to have a direct role in regulating many of these transcripts, as most have “NMD‐inducing features.” We propose that Upf3b‐null mice are a useful model system to understand the underlying mechanism of sensorimotor gating and how it is disrupted in Schizophrenia patients.This study was supported by the NIH.
Salt‐inducible kinase 1 links p300 phosphorylation to CREB regulated gluconeogenesis post burn
Authors: Brooks Natasha C , Smith Alexandra H , Hiyama Yaeko , Finnerty Celeste C , Herndon David N , Boehning Darren , Jeschke Marc G 
Published: June 2021

Severe burn injury results in sustained catecholamine release and increased cyclic AMP (cAMP) levels. cAMP‐induced inhibition of salt‐inducible kinase 1 (SIK1) has been shown to promote recruitment of the transcriptional co‐activator p300 to cAMP response element binding protein (CREB), resulting in gluconeogenesis. Gluconeogenesis is increased and maintained post‐burn injury yet the molecular mechanism is unknown. We hypothesize that catecholamine‐induced inhibition of SIK1 resulting in increased p300 transcriptional activity sustains gluconeogenesis. The 60% total body surface area burn model on rats was employed as a model system. The catecholamine surge during burn injury led to the inhibition of SIK1, increased blood glucose levels, and increased p300 mediated transcription of CREB‐regulated gluconeogenic genes. Restoration of SIK1 activity by administration of propranolol, a non‐selective β1/2 adrenergic receptor antagonist, resulted in inhibition of p300‐ mediated transcription and decreased blood glucose levels. We conclude that catecholamine release after severe burn injury leads to inhibition of SIK1, resulting in sustained gluconeogenesis.This work was supported by grants from Shriners Hospitals for Children and (SHG 8660 and 6840) the National Institute of Health (RO1‐ GM087285‐0182)
Modulation of H2O2 production in vitro by low level magnetic fields
Authors: Martino Carlos F , Castello Pablo 
Published: June 2021

BackgroundIn this paper, we present data on the influence of low level magnetic fields (0.5 μT‐2 μT) on the modulation of hydrogen peroxide (H2O2) biogenesis in human fibrosarcoma cancer cell line HT1080, and bovine pulmonary artery endothelial cells (PAEC) compared to cells exposed to geomagnetic field (control; 45 μT‐60 μT).MethodsThe extracellular quantification of the production of H2O2 may be a direct measure of the production and decomposition of superoxide radical. H2O2 can freely pass through cell membranes and can be detected outside the cell. For the quantification of H2O2 we used a method that has been successfully applied before. This method involves the oxidation of Amplex Red by H2O2 in the presence of horseradish peroxidase (HRP). Tri‐axial Helmholtz coils established the control static magnetic field. Low level fields were implemented by a μ–metal cylinder. The background time‐varying magnetic field was measured by induction with a sensor comprised of a set of square perpendicular coils.ResultsReduction of the Earth's magnetic field suppressed H2O2 production in cancer cells and PAEC. The addition of catalase and superoxide dismutase (SOD) mimetic MnTBAP inhibited the magnetic field effect on H2O2 production.ConclusionBecause most cancer cells undergo increased oxidative stress and ROS production due to excessive metabolic requirements to support an increased rate of cell division, it is reasonable to consider investigating a therapeutic that might target cancer cells through a free radical mechanism. Whether radio frequency exposure can influence growth rates and H2O2 production remains open and we propose to investigate it in the future. Modulating ROS production by magnetic fields may open new venues of biomedical research and therapeutic strategies.
CD45 is a Major Receptor Involved in Galectin‐8 Signaling of Preaparesis in HL‐60 cells
Authors: Gourdine Jean-Philippe Francois , Stowell Sean R , Cummings Richard D 
Published: June 2021

The mechanisms of leukocyte turnover during an inflammatory response and its resolution are poorly understood. We recently showed that upon interactions with Galectin‐8 (Gal‐8), a 34 kilodalton heterodimeric tandem‐repeat galectin expressed by endothelial and epithelial cells, activated leukocytes express phosphatidylserine (PS) on their surface in the absence of apoptosis or DNA fragmentation. This can lead to phagocytosis of the cells in a process termed preaparesis, which fundamentally differs from that induced by factors signaling apoptosis. To identify the surface receptors involved in Gal‐8 signaling we took a proteomic approach to identify Gal‐8‐binding glycoproteins from human HL‐60 cells, a promyelocytic leukemic cell line with many signaling pathways in common to human neutrophils. Our previous studies showed that glycans containing poly‐N‐acetyllactosamine (poly‐N‐LacNAc) on HL‐60 cells were important for signaling. One major glycoprotein identified as a Gal‐8‐binding receptor on HL‐60 cells is CD45, a membrane glycoprotein that bears poly‐N‐LacNAc. We further characterized CD45/Gal‐8 interaction, by Western‐Blot, flow cytometry and confocal microscopy. Inhibition of CD45 cytoplasmic phosphatase activity reduced Gal‐8 induced PS exposure indicating a possible role of CD45 in Gal‐8 signaling preaparesis in human leukocytes.This work was supported by National Institutes of Health Grant HL085607 to R.D.C.