Evolution of functional antibodies following acute Epstein-Barr virus infection.

While Epstein-Barr virus causes mostly asymptomatic infection, associated malignancies, and autoimmune and lymphoproliferative diseases occur. To dissect the evolution of humoral immune responses over the course of EBV infection and to gain a better understanding of the potential contribution of antibody (Ab) function to viral control, we comprehensively profiled Ab specificities and Fc-functionalities using systems serology and VirScan. Ab functions against latent (EBNA1), early (p47/54) and two late (gp350/220 and VCA-p18) EBV proteins were overall modest and/or short-lived, differing from humoral responses induced during acute infection by other viruses such as HIV.

Optimizing Glutaraldehyde-Fixed Tissue Heart Valves with Chondroitin Sulfate Hydrogel for Endothelialization and Shielding against Deterioration.

Porcine glutaraldehyde-fixed pericardium is widely used to replace human heart valves. Despite the stabilizing effects of glutaraldehyde fixation, the lack of endothelialization and the occurrence of immune reactions contribute to calcification and structural valve deterioration, which is particularly significant in young patients, in whom valve longevity is crucial. This report shows an optimization system with which to enhance endothelialization of fixed pericardium to mimic the biological function of a native heart valve.

Quantification of thrombus formation in malapposed coronary stents deployed in vitro through imaging analysis.

Stent thrombosis is a major complication of coronary stent and scaffold intervention. While often unanticipated and lethal, its incidence is low making mechanistic examination difficult through clinical investigation alone. Thus, throughout the technological advancement of these devices, experimental models have been indispensable in furthering our understanding of device safety and efficacy.

Targeting STUB1-tissue factor axis normalizes hyperthrombotic uremic phenotype without increasing bleeding risk.

Chronic kidney disease (CKD/uremia) remains vexing because it increases the risk of atherothrombosis and is also associated with bleeding complications on standard antithrombotic/antiplatelet therapies. Although the associations of indolic uremic solutes and vascular wall proteins [such as tissue factor (TF) and aryl hydrocarbon receptor (AHR)] are being defined, the specific mechanisms that drive the thrombotic and bleeding risks are not fully understood. We now present an indolic solute-specific animal model, which focuses on solute-protein interactions and shows that indolic solutes mediate the hyperthrombotic phenotype across all CKD stages in an AHR- and TF-dependent manner.

The Systems Biocompatibility of Coronary Stenting.

The coronary stent has propelled our understanding of the term "biocompatibility." Stents are expanded at sites of arterial blockage and mechanically reestablish blood flow. This simplicity belies the complex reactions that occur when a stent contacts living substrates.

Ultra-hydrophilic stent platforms promote early vascular healing and minimise late tissue response: a potential alternative to second-generation drug-eluting stents.

Aims: Simple surface modifications can enhance coronary stent performance. Ultra-hydrophilic surface (UHS) treatment of contemporary bare metal stents (BMS) was assessed in vivo to verify whether such stents can provide long-term efficacy comparable to second-generation drug-eluting stents (DES) while promoting healing comparably to BMS.

Methods And Results: UHS-treated BMS, untreated BMS and corresponding DES were tested for three commercial platforms.

Microbial lysate upregulates host oxytocin.

Neuropeptide hormone oxytocin has roles in social bonding, energy metabolism, and wound healing contributing to good physical, mental and social health. It was previously shown that feeding of a human commensal microbe Lactobacillus reuteri (L. reuteri) is sufficient to up-regulate endogenous oxytocin levels and improve wound healing capacity in mice.

Constraining OCT with Knowledge of Device Design Enables High Accuracy Hemodynamic Assessment of Endovascular Implants.

Background: Stacking cross-sectional intravascular images permits three-dimensional rendering of endovascular implants, yet introduces between-frame uncertainties that limit characterization of device placement and the hemodynamic microenvironment. In a porcine coronary stent model, we demonstrate enhanced OCT reconstruction with preservation of between-frame features through fusion with angiography and a priori knowledge of stent design.

Methods And Results: Strut positions were extracted from sequential OCT frames.

Vascular Response to Experimental Stent Malapposition and Under-Expansion.

Up to 80% of all endovascular stents have malapposed struts, and while some impose catastrophic events others are inconsequential. Thirteen stents were implanted in coronary arteries of seven healthy Yorkshire pigs, using specially-designed cuffed balloons inducing controlled stent malapposition and under-expansion. Optical coherence tomography (OCT) imaging confirmed that 25% of struts were malapposed (strut-wall distance View Article and Find Full Text PDF

Degree of bioresorbable vascular scaffold expansion modulates loss of essential function.

Unlabelled: Drug-eluting bioresorbable vascular scaffolds (BVSs) have the potential to restore lumen patency, enable recovery of the native vascular environment, and circumvent late complications associated with permanent endovascular devices. To ensure therapeutic effects persist for sufficient times prior to scaffold resorption and resultant functional loss, many factors dictating BVS performance must be identified, characterized and optimized. While some factors relate to BVS design and manufacturing, others depend on device deployment and intrinsic vascular properties.

A randomised trial of lung sealant versus medical therapy for advanced emphysema.

Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction using emphysematous lung sealant (ELS) in patients with advanced, upper lobe predominant emphysema. We aimed to evaluate the safety and efficacy of ELS in a randomised controlled setting.Patients were randomised to ELS plus medical treatment or medical treatment alone.

Enhancing physiologic simulations using supervised learning on coarse mesh solutions.

Computational modelling of physical and biochemical processes has emerged as a means of evaluating medical devices, offering new insights that explain current performance, inform future designs and even enable personalized use. Yet resource limitations force one to compromise with reduced order computational models and idealized assumptions that yield either qualitative descriptions or approximate, quantitative solutions to problems of interest. Considering endovascular drug delivery as an exemplary scenario, we used a supervised machine learning framework to process data generated from low fidelity coarse meshes and predict high fidelity solutions on refined mesh configurations.

Non-adherence to cardiovascular medications.

Despite evidence-based interventions, coronary heart disease (CHD) remains a leading cause of global mortality. As therapies advance, patient non-adherence to established treatments is well recognized. Non-adherence is a powerful confounder of evidence-based practice and can affect daily patient management, resulting in inappropriate therapeutic escalation with greater costs and potential for harm.

Extent of flow recirculation governs expression of atherosclerotic and thrombotic biomarkers in arterial bifurcations.

Aims: Atherogenesis, evolution of plaque, and outcomes following endovascular intervention depend heavily on the unique vascular architecture of each individual. Patient-specific, multiscale models able to correlate changes in microscopic cellular responses with relevant macroscopic flow, and structural conditions may help understand the progression of occlusive arterial disease, providing insights into how to mitigate adverse responses in specific settings and individuals.

Methods And Results: Vascular architectures mimicking coronary and carotid bifurcations were derived from clinical imaging and used to generate conjoint computational meshes for in silico analysis and biocompatible scaffolds for in vitro models.

Predicting response to endovascular therapies: dissecting the roles of local lesion complexity, systemic comorbidity, and clinical uncertainty.

Through decades of use and refinement, endovascular stents have become part and parcel of the management of obstructive atherosclerotic lesions. Upon stent placement, a variety of biophysical reactions ensue, governed not only by the mechanical and material properties of the device, but also the impact these properties have on the local vascular biology. Anatomic changes and vascular deformations give rise to solid mechanical and fluid forces that are the proximate, functional drivers of the induced reparative response.

Uremic serum and solutes increase post-vascular interventional thrombotic risk through altered stability of smooth muscle cell tissue factor.

Background: Stent thrombosis (ST), a postinterventional complication with a mortality rate of 50%, has an incidence that rises precipitously in patients at risk. Chronic renal failure and end-stage renal disease have emerged as particularly strong ST risk factors, yet the mechanism remains elusive. Tissue factor (TF) is a crucial mediator of injury-related thrombosis and has been implicated for ST.

Stent thrombogenicity early in high-risk interventional settings is driven by stent design and deployment and protected by polymer-drug coatings.

Background: Stent thrombosis is a lethal complication of endovascular intervention. Concern has been raised about the inherent risk associated with specific stent designs and drug-eluting coatings, yet clinical and animal support is equivocal.

Methods And Results: We examined whether drug-eluting coatings are inherently thrombogenic and if the response to these materials was determined to a greater degree by stent design and deployment with custom-built stents.

Antiplatelet therapy in coronary heart disease prevention.

Platelets are central to the pathogenesis of coronary heart disease (CHD). An ever-growing number of antiplatelet therapies used in different doses and combinations have helped manage atherothrombosis, both acutely and in primary and secondary prevention. Despite modern therapy, nearly 800,000 individuals suffer annually from an initial coronary event in the United States alone; almost 500,000 experience a recurrent event.

Overcoming 'resistance' to antiplatelet therapy: targeting the issue of nonadherence.

A wide range of interindividual variability in the measured and clinical effects of antiplatelet drugs exists. As patients with less platelet inhibition consistently have increased rates of adverse cardiovascular outcomes, a great deal of effort is being focused on understanding and treating this apparent 'resistance.' Pharmacogenomic and pharmacodynamic methods to better delineate responders from nonresponders are being developed, and innovative strategies and novel, potent drugs capable of overcoming nonresponsiveness are in active clinical trials.

Echocardiographic capture of right ventricular wall rupture during inferior wall acute myocardial infarction.

We present the case of a 57-year-old woman with no previous cardiovascular history in whom fatal right ventricular wall rupture was diagnosed by bedside echocardiography early in the management of an inferior wall acute myocardial infarction.

Environmental influences on endovascular stent platelet reactivity: an in vitro comparison of stainless steel and gold surfaces.

Thrombosis is an initiating reaction to vascular injury that follows the placement of vascular devices. Platelets play a crucial role in this response. Their interaction with endovascular devices is not solely a function of device properties, but a multifaceted response dependent on several biological factors that interact in the context of a hemodynamic environment.