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Work 1-10 of 1863

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Article

Modulation of choroidal neovascularization by subretinal injection of retinal pigment epithelium and polystyrene microbeads

by Adam Marcus; Hans Grossniklaus; Hua Yang; I Schmack; L Berglin; X Nie; J Wen; SJ Kang; MJ Lynn; JA Kapp

2009

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Abstract:Close

Purpose: The study was conducted to create a rapidly developing and reproducible animal model of subretinal choroidal neovascularization (CNV) that allows a time-dependent evaluation of growth dynamics, histopathologic features, and cytokine expression. Methods: C57BL/6 and chemoattractant leukocyte protein-2 deficient (ΔCcl-2) mice were studied. Mice received single or combined subretinal injections of cultured retinal pigment epithelium (RPE; C57BL/ 6-derived), polystyrene microbeads, or phosphate buffer solution (PBS). Fluorescence angiograms were performed over a period of 3 weeks. Mice were euthanized on post inoculation day 3, 7, 10, 14, or 21, and their eyes were evaluated by light, confocal, and electron microscopy. Results: CNV membranes occurred in all study groups with an overall incidence of 94.3%. They extended in the subretinal space through central breaks in Bruch's membrane. CNV lesions were characterized by dynamic changes such as initiation, active inflammatory, and involution stages. CNV thickness peaked around PI day 7 and was greater in mice that received combined injections of RPE and microbeads or RPE cells alone. Small lesions developed in the control groups (microbeads or PBS only), in ΔCcl-2, and old C57BL/6 mice. Variable expression of cytokines and growth factors was detected within the membranes. Conclusions: Our murine model represents a reliable approach inducing CNV growth by subretinal injection of either RPE cells alone or RPE cells and microbeads. The development of CNV lesions is a dynamic process that relies in part on macrophage trafficking and age. © 2009 Molecular Vision.

Article

Use of troponin assay 99th percentile as the decision level for myocardial infarction diagnosis

by Akshay Bagai; Karen P. Alexander; Jeffrey S. Berger; Roxy Senior; Chakkanalil Sajeev; Radoslaw Pracon; Kreton Mavromatis; Jose Luis Lopez-Sendon; Gilbert Gosselin; Ariel Diaz; Gian Perna; Jarozlaw Drozdz; Dennis Humen; Birute Petrauskiene; Asim N. Cheema; Denis Phaneuf; Subhash Banerjee; Todd D. Miller; Sasko Kedev; Herwig Schuchlenz; Gregg W. Stone; Shaun G. Goodman; Kenneth W. Mahaffey; Allan S. Jaffe; Yves D. Rosenberg; Sripal Bangalore; L. Kristin Newby; David J. Maron; Judith S. Hochman; Bernard R. Chaitman

2017

Subjects
  • Health Sciences, Medicine and Surgery
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Background The Universal Definition of Myocardial Infarction recommends the 99th percentile concentration of cardiac troponin in a normal reference population as part of the decision threshold to diagnose type 1 spontaneous myocardial infarction. Adoption of this recommendation in contemporary worldwide practice is not well known. Methods We performed a cohort study of 276 hospital laboratories in 31 countries participating in the National Heart, Lung, and Blood Institute–sponsored International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial. Each hospital laboratory's troponin assay manufacturer and model, the recommended assay's 99th percentile upper reference limit (URL) from the manufacturer's package insert, and the troponin concentration used locally as the decision level to diagnose myocardial infarction were ascertained. Results Twenty-one unique troponin assays from 9 manufacturers were used by the surveyed hospital laboratories. The ratio of the troponin concentration used locally to diagnose myocardial infarction to the assay manufacturer–determined 99th percentile URL was <1 at 19 (6.6%) laboratories, equal to 1 at 91 (31.6%) laboratories, >1 to ≤5 at 101 (35.1%) laboratories, >5 to ≤10 at 34 (11.8%) laboratories, and >10 at 43 (14.9%) laboratories. The variability in troponin decision level for myocardial infarction relative to the assay 99th percentile URL was present for laboratories in and outside of the United States, as well as for high- and standard-sensitivity assays. Conclusions There is substantial hospital-level variation in the troponin threshold used to diagnose myocardial infarction; only one-third of hospital laboratories currently follow the Universal Definition of Myocardial Infarction consensus recommendation for use of troponin concentration at the 99th percentile of a normal reference population as the decision level to diagnose myocardial infarction. This variability across laboratories has important implications for both the diagnosis of myocardial infarction in clinical practice as well as adjudication of myocardial infarction in clinical trials.

Article

Neuropsychological Functioning in Girls with Premature Adrenarche

by A. Tissot; L. D. Dorn; D. Rotenstein; S. R. Rose; L. M. Sontag-Padilla; C. L. Jillard; S. F. Witchel; S.L. Berga; Tammy Loucks; S. R. Beers

2012

Subjects
  • Biology, Neuroscience
  • Health Sciences, Medicine and Surgery
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Contemporary research indicates that brain development occurs during childhood and into early adulthood, particularly in certain regions. A critical question is whether premature or atypical hormone exposures impact brain development (e.g., structure) or function (e.g., neuropsychological functioning). The current study enrolled 40 girls (aged 6-8 years) diagnosed with premature adrenarche (PA) and a comparison group of 36 girls with on-time maturation. It was hypothesized that girls with PA would demonstrate lower IQ and performance on several neuropsychological tasks. The potential for a sexually dimorphic neuropsychological profile in PA was also explored. No significant univariate or multivariate group differences emerged for any neuropsychological instrument. However, effect size confidence intervals contained medium-sized group differences at the subscale level. On-time girls performed better on verbal, working memory, and visuospatial tasks. Girls with PA showed improved attention, but not a sexually dimorphic profile. These results, though preliminary, suggest that premature maturation may influence neuropsychological functioning.

Article

Individual Characteristics of Resilience are Associated With Lower-Than-Expected Neighborhood Rates of Cardiovascular Disease in Blacks: Results From the Morehouse-Emory Cardiovascular(MECA) Center for Health Equity Study

by Matthew L. Topel; Jeong Hwan Kim; Mahasin S. Mujahid; Yi-An Ko; Viola Vaccarino; Mohamed Mubasher; Chang Liu; Sandra Dunbar; Mario Sims; Herman Taylor; Arshed Quyyumi; Peter Baltrus; Tene Lewis

2019

Subjects
  • Health Sciences, Medicine and Surgery
  • Psychology, Behavioral
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Background: Factors promoting cardiovascular health in the face of high risk, ie, resilience, are unknown and may identify novel areas of intervention for reducing racial health disparities. We examined neighborhood perceptions and psychological attributes of blacks living in high and low cardiovascular–risk neighborhoods, as potential characteristics of resilience promoting cardiovascular health. Methods and Results: We identified 1433 blacks residing in census tracts of Atlanta, GA, with higher-than-expected (“high” risk) or lower-than-expected (“low” risk) rates of cardiovascular mortality, hospitalizations, and emergency department visits during 2010–2014. Domains of psychosocial well-being and neighborhood quality were assessed via telephone survey between August 2016 and October 2016. Using multilevel logistic regression, odds of reporting better resilient characteristics were compared between individuals living in low- versus high-risk neighborhoods. Those from low-risk (versus high-risk) neighborhoods reported better neighborhood aesthetic quality (odds ratio [OR], 1.84), healthy food access (OR, 1.69), and absence of violence (OR, 0.67). Individuals from low-risk neighborhoods reported greater optimism (OR, 1.38), purpose in life (OR, 1.42), and fewer depressive symptoms (OR, 0.69). After full adjustment, these associations remained significant for neighborhood factors (aesthetic quality, healthy food access, violence) and psychosocial well-being (purpose in life). We found no evidence of differences in self-reported cardiovascular risk factors or disease history between low- versus high-risk neighborhoods. Conclusions: Positive neighborhood environments and psychological characteristics are associated with low cardiovascular–risk neighborhoods, despite similar prevalence of cardiovascular risk factors, in the census tracts studied. These factors may confer cardiovascular resilience among blacks.

Article

The architecture of the IgG anti-carbohydrate repertoire in primary antibody deficiencies

by Peter Jandus; Kayluz Frias Boligan; David F. Smith; Elisabeth de Graauw; Bodo Grimbacher; Camilla Jandus; Mai M. Abdelhafez; Alain Despont; Nicolai Bovin; Dagmar Simon; Robert Rieben; Hans-Uwe Simon; Richard D. Cummings; Stephan von Gunten

2019

Subjects
  • Health Sciences, Immunology
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Immune system failure in primary antibody deficiencies (PADs) has been linked to recurrent infections, autoimmunity, and cancer, yet clinical judgment is often based on the reactivity to a restricted panel of antigens. Previously, we demonstrated that the human repertoire of carbohydrate-specific immunoglobulin G (IgG) exhibits modular organization related to glycan epitope structure. The current study compares the glycan-specific IgG repertoires between different PAD entities. Distinct repertoire profiles with extensive qualitative glycan-recognition defects were observed, which are characterized by the common loss of Galα and GalNAc reactivity and disease-specific recognition of microbial antigens, self-antigens, and tumor-associated carbohydrate antigens. Antibody repertoire analysis may provide a useful tool to elucidate the degree and the clinical implications of immune system failure in individual patients.

Article

Respiratory Effects on Fontan Circulation During Rest and Exercise Using Real-Time Cardiac Magnetic Resonance Imaging

by Zhenglun Wei; Kevin K. Whitehead; Reza H. Khiabani; Michael Tree; Elaine Tang; Stephen M Paridon; Mark A. Fogel; Ajit Yoganathan

2016

Subjects
  • Health Sciences, Medicine and Surgery
  • Health Sciences, Radiology
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Background It is known that respiration modulates cavopulmonary flows, but little data compare mean flows under breath-holding and free-breathing conditions to isolate the respiratory effects and effects of exercise on the respiratory modulation. Methods Real-time phase-contrast magnetic resonance combined with a novel method to track respiration on the same image acquisition was used to investigate respiratory effects on Fontan caval and aortic flows under breath-holding, free-breathing, and exercise conditions. Respiratory phasicity indices that were based on beat-averaged flow were used to quantify the respiratory effect. Results Flow during inspiration was substantially higher than expiration under the free-breathing and exercise conditions for both inferior vena cava (inspiration/expiration: 1.6 ± 0.5 and 1.8 ± 0.5, respectively) and superior vena cava (inspiration/expiration: 1.9 ± 0.6 and 2.6 ± 2.0, respectively). Changes from rest to exercise in the respiratory phasicity index for these vessels further showed the impact of respiration. Total systemic venous flow showed no significant statistical difference between the breath-holding and free-breathing conditions. In addition, no substantial difference was found between the descending aorta and inferior vena cava mean flows under either resting or exercise conditions. Conclusions This study demonstrated that inferior vena cava and superior vena cava flow time variance is dominated by respiratory effects, which can be detected by the respiratory phasicity index. However, the minimal respiration influence on net flow validates the routine use of breath-holding techniques to measure mean flows in Fontan patients. Moreover, the mean flows in the inferior vena cava and descending aorta are interchangeable.

Article

Impact of simulated MitraClip on forward flow obstruction in the setting of mitral leaflet tethering: An in vitro investigation

by Charles H. Bloodworth; Eric L. Pierce; Keshav Kohli; Nancy J. Deaton; Kaitlin J. Jones; Radhika Duvvuri; Norihiko Kamioka; Vasilis Babaliaros; Ajit Yoganathan

2018

Subjects
  • Health Sciences, Medicine and Surgery
  • Engineering, Biomedical
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Objectives: We aimed to evaluate diastolic leaflet tethering as a factor that may cause mitral stenosis (MS) after simulated MitraClip implantation, using an in vitro left heart simulator. Background: Leaflet tethering commonly seen in functional mitral regurgitation may be a significant factor affecting the severity of MS after MitraClip implantation. Methods: A left heart simulator with excised ovine mitral valves (N = 6), and custom edge-to-edge clip devices (GTclip) was used to mimic implantation of MitraClip in a variety of positions. Anterior mitral leaflet (AML) tethering severity was varied for each case (leaflet excursion of 75°, 60°, and 45°, consistent with mild, moderate and severe tethering), and the baseline mitral annular area (MAA) was varied across samples (3.6–4.8 cm2). The resulting mitral valve area (MVA), and peak/mean mitral valve gradient (MVG) were measured in each case. Results: AML tethering severity was a highly significant factor increasing MVG and decreasing MVA (P < 0.001). When GTclip placement was simulated with severe AML tethering, mean MVG >5 mmHg resulted more frequently than with GTclip placement alone (46% vs. 4%, respectively). However, severe AML tethering alone significantly reduced baseline MVA to 3.6 ± 0.2 cm2, and increased baseline MVG to 3.0 ± 0.4 mmHg. At MAA above 4.7 cm2, severe AML tethering did not cause moderate MS, even with placement of two GTclips (95% confidence). Conclusions: Our results show that diastolic AML tethering may predispose to MS after clip placement, however, MS was not observed when baseline MVA was above 4.0 cm2. Severity of AML tethering may be an important criterion in selecting patients for edge-to-edge repair.

Article

Therapies on the horizon for cholesterol reduction

by W. Virgil Brown

2001

Subjects
  • Health Sciences, Medicine and Surgery
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Statins are powerful agents for the reduction of low-density lipoprotein cholesterol (LDL-C) and reduction of cardiovascular risk. Newly developed statins with increased potency, such as rosuvastatin (Crestor™) and NK-104 (in earlier clinical development), are capable of achieving marked LDL-C reductions. Cholesterol-lowering agents with mechanisms of action distinct from those of the statins are in active development. These include bile transport inhibitors, such as improved bile acid-absorbing resins and specific inhibitors of the ileal Na+/bile acid cotransporter. There are also specific inhibitors of cholesterol absorption, such as ezetimibe, which may provide cholesterol lowering that is additive to that achieved with statin treatment. Another approach is to reduce cardiovascular risk by modifying atherosclerotic processes within the arterial wall, as represented by the acyl CoA:cholesterol acyltransferase (ACAT) inhibitor avasimibe; ibe; ACAT inhibitors may reduce atherosclerotic lesions by inhibiting macrophage cholesterol storage.

Article

Is Depression an Inflammatory Disorder?

by Charles L Raison; Andrew H Miller

2011

Subjects
  • Psychology, Behavioral
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Studies consistently report that groups of individuals with major depressive disorder (MDD) demonstrate increased levels of a variety of peripheral inflammatory biomarkers when compared with groups of nondepressed individuals. These findings are often interpreted as meaning that MDD, even in medically healthy individuals, may be an inflammatory condition. In this article, we examine evidence for and against this idea by looking more closely into what the actual patterns of inflammatory findings indicate in terms of the relationship between MDD and the immune system. Data are presented in support of the idea that inflammation only contributes to depression in a subset of patients versus the possibility that the depressogenic effect of inflammatory activation is more widespread and varies depending on the degree of vulnerability any given individual evinces in interconnected physiologic systems known to be implicated in the etiology of MDD. Finally, the treatment implications of these various possibilities are discussed.

Article

The vesicular monoamine transporter 2: An underexplored pharmacological target

by Alison I. Bernstein; Kristen A. Stout; Gary Miller

2014

Subjects
  • Biology, Neuroscience
  • Health Sciences, Pharmacology
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Active transport of neurotransmitters into synaptic vesicles is required for their subsequent exocytotic release. In the monoamine system, this process is carried out by the vesicular monoamine transporters (VMAT1 and VMAT2). These proteins are responsible for vesicular packaging of dopamine, norepinephrine, serotonin, and histamine. These proteins are essential for proper neuronal function; however, compared to their plasma membrane counterparts, there are few drugs available that target these vesicular proteins. This is partly due to the added complexity of crossing the plasma membrane, but also to the technical difficulty of assaying for vesicular uptake in high throughput. Until recently, reagents to enable high throughput screening for function of these vesicular neurotransmitter transporters have not been available. Fortunately, novel compounds and methods are now making such screening possible; thus, a renewed focus on these transporters as potential targets is timely and necessary.
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