Stand-alone transarterial flow diversion for treatment of carotid cavernous fistulas.

Objective: Carotid-cavernous fistulas (CCFs) are rare arteriovenous communications allowing blood to flow from the carotid artery into the cavernous sinus. Although currently coil and/or liquid embolization remain the preferred treatment methods for CCFs, flow diverters (FD) stents represent a viable alternative to traditional embolization techniques. This study explores both the technical aspects and rationale behind using FD stents as a stand-alone treatment approach for CCFs.

Safety and Effectiveness of Expandable Intravertebral Implant Use for Thoracolumbar Burst Fractures.

Purpose: To determine the safety and effectiveness of an expandable intravertebral implant (Spinejack; Stryker, Kalamazoo, Michigan) as a treatment option for patients with thoracolumbar spine burst fractures without fracture-related neurologic deficit.

Materials And Methods: Imaging studies before and after expandable intravertebral implantation and medical records of 33 patients, 11 (33.3%) men and 22 (66.

Altered Electrical, Biomolecular, and Immunologic Phenotypes in a Novel Patient-Derived Stem Cell Model of Desmoglein-2 Mutant ARVC.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive heart condition which causes fibro-fatty myocardial scarring, ventricular arrhythmias, and sudden cardiac death. Most cases of ARVC can be linked to pathogenic mutations in the cardiac desmosome, but the pathophysiology is not well understood, particularly in early phases when arrhythmias can develop prior to structural changes. Here, we created a novel human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) model of ARVC from a patient with a c.

Early Vascular Cells Improve Microvascularization Within 3D Cardiac Spheroids.

A key obstacle in the creation of engineered cardiac tissues of clinically relevant sizes is limited diffusion of oxygen and nutrients. Thus, there is a need for organized vascularization within a three-dimensional (3D) tissue environment. Human induced pluripotent stem cell (hiPSC)-derived early vascular cells (EVCs) have shown to improve organization of vascular networks within hydrogels.

Therapeutic Modulation of the Immune Response in Arrhythmogenic Cardiomyopathy.

Background: Inflammation is a prominent feature of arrhythmogenic cardiomyopathy (ACM), but whether it contributes to the disease phenotype is not known.

Methods: To define the role of inflammation in the pathogenesis of ACM, we characterized nuclear factor-κB signaling in ACM models in vitro and in vivo and in cardiac myocytes from patient induced pluripotent stem cells.

Results: Activation of nuclear factor-κB signaling, indicated by increased expression and nuclear accumulation of phospho-RelA/p65, occurred in both an in vitro model of ACM (expression of in neonatal rat ventricular myocytes) and a robust murine model of ACM (homozygous knock-in of mutant desmoglein-2 []) that recapitulates the cardiac manifestations seen in patients with ACM.

Functional Properties of Engineered Heart Slices Incorporating Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for cardiac studies, but their structural and functional immaturity precludes their use as faithful models of adult myocardium. Here we describe engineered heart slices (EHS), preparations of decellularized porcine myocardium repopulated with hiPSC-CMs that exhibit structural and functional improvements over standard culture. EHS exhibited multicellular, aligned bundles of elongated CMs with organized sarcomeres, positive inotropic responses to isoproterenol, anisotropic conduction of action potentials, and electrophysiological functionality for more than 200 days.

Engineered Heart Slice Model of Arrhythmogenic Cardiomyopathy Using Plakophilin-2 Mutant Myocytes.

Genetic heart diseases such as arrhythmogenic cardiomyopathy (AC), a common genetic cause of sudden cardiac death, can be modeled using patient-specific induced pluripotent stem cell-derived cardiac myocytes (CMs). However, it is important to culture these cells in a multicellular syncytium with exposure to surrounding matrix cues to create more accurate and robust models of the disease due to the importance of cell-cell and cell-matrix interactions. The engineered heart slice, constructed by seeding CMs on intact decellularized matrix slices, allows molecular and functional studies on an aligned multilayered syncytium of CMs.

Emergency Department Utilization Among the Uninsured During Insurance Expansion in Maryland.

Study Objective: We analyzed the effect of insurance expansion on emergency department (ED) utilization among the uninsured in Maryland, which expanded Medicaid eligibility and created health insurance exchanges in 2014.

Methods: This was a retrospective analysis of statewide administrative claims for July 2012 to December 2015. We used coarsened exact matching to pair uninsured and insured (Medicaid, Medicare, commercial, and other) adult Maryland residents who visited an ED or were hospitalized at baseline (July 2012 to December 2013).

Predictors of Survival after Yttrium-90 Radioembolization for Colorectal Cancer Liver Metastases.

Purpose: To identify clinical parameters that are prognostic for improved overall survival (OS) after yttrium-90 radioembolization (RE) in patients with liver metastases from colorectal cancer (CRC).

Materials And Methods: A total of 131 patients who underwent RE for liver metastases from CRC, treated at 2 academic centers, were reviewed. Twenty-one baseline pretreatment clinical factors were analyzed in relation to OS by the Kaplan-Meier method along with log-rank tests and univariate and multivariate Cox regression analyses.

Strategies to enable the adoption of animal biotechnology to sustainably improve global food safety and security.

The ability to generate transgenic animals has existed for over 30 years, and from those early days many predicted that the technology would have beneficial applications in agriculture. Numerous transgenic agricultural animals now exist, however to date only one product from a transgenic animal has been approved for the food chain, due in part to cumbersome regulations. Recently, new techniques such as precision breeding have emerged, which enables the introduction of desired traits without the use of transgenes.

Overview of the CSIRO Australian Animal Health Laboratory.

Emerging infectious diseases arising from livestock and wildlife pose serious threats to global human health, as shown by a series of continuous outbreaks involving highly pathogenic influenza, SARS, Ebola and MERS. The risk of pandemics and bioterrorism threats is ever present and growing, but our ability to combat them is limited by the lack of available vaccines, therapeutics and rapid diagnostics. The use of high bio-containment facilities, such as the CSIRO Australian Animal Health Laboratory, plays a key role studying these dangerous pathogens and facilitates the development of countermeasures.

Genome-wide siRNA Screening at Biosafety Level 4 Reveals a Crucial Role for Fibrillarin in Henipavirus Infection.

Hendra and Nipah viruses (genus Henipavirus, family Paramyxoviridae) are highly pathogenic bat-borne viruses. The need for high biocontainment when studying henipaviruses has hindered the development of therapeutics and knowledge of the viral infection cycle. We have performed a genome-wide siRNA screen at biosafety level 4 that identified 585 human proteins required for henipavirus infection.

Stem cell-derived vasculature: A potent and multidimensional technology for basic research, disease modeling, and tissue engineering.

Proper blood vessel networks are necessary for constructing and re-constructing tissues, promoting wound healing, and delivering metabolic necessities throughout the body. Conversely, an understanding of vascular dysfunction has provided insight into the pathogenesis and progression of diseases both common and rare. Recent advances in stem cell-based regenerative medicine - including advances in stem cell technologies and related progress in bioscaffold design and complex tissue engineering - have allowed rapid advances in the field of vascular biology, leading in turn to more advanced modeling of vascular pathophysiology and improved engineering of vascularized tissue constructs.

Ethics and policy issues for stem cell research and pulmonary medicine.

Stem cell research and related initiatives in regenerative medicine, cell-based therapy, and tissue engineering have generated considerable scientific and public interest. Researchers are applying stem cell technologies to chest medicine in a variety of ways: using stem cells as models for drug discovery, testing stem cell-based therapies for conditions as diverse as COPD and cystic fibrosis, and producing functional lung and tracheal tissue for physiologic modeling and potential transplantation. Although significant scientific obstacles remain, it is likely that stem cell-based regenerative medicine will have a significant clinical impact in chest medicine.

An in silico analysis of nanoparticle/cell diffusive transfer: application to nano-artificial antigen-presenting cell:T-cell interaction.

Unlabelled: Polymeric nanoparticles (nano-paAPCs) modified with T-cell antigens and encapsulating immunostimulatory or immunoinhibitory factors may act as artificial antigen-presenting cells to circulating immune cells, improving the selective delivery of encapsulated drug or cytokine to antigen-specific T-cells. Paracrine delivery of encapsulated agents from these nanoparticles to adjacent cells facilitate sustained delivery lowering the overall administered dose, thus enhancing the overall drug efficacy while reducing toxicity of pleiotropic factors. Little is known mathematically regarding the local concentration of released agent that accumulates around a nanoparticle that is near or embeds in a cell.

Studying immunity to zoonotic diseases in the natural host - keeping it real.

Zoonotic viruses that emerge from wildlife and domesticated animals pose a serious threat to human and animal health. In many instances, mouse models have improved our understanding of the human immune response to infection; however, when dealing with emerging zoonotic diseases, they may be of limited use. This is particularly the case when the model fails to reproduce the disease status that is seen in the natural reservoir, transmission species or human host.

The DISCUSS Project: induced pluripotent stem cell lines from previously collected research biospecimens and informed consent: points to consider.

Human somatic cell reprogramming is a leading technology for accelerating disease modeling and drug discovery. Research organizations are sponsoring initiatives to create libraries of induced pluripotent stem cell (iPSC) lines for broad distribution and application. Donor informed consent plays a critical role in supporting the ethical conduct of iPSC research.

A new method for producing transgenic birds via direct in vivo transfection of primordial germ cells.

Traditional methods of avian transgenesis involve complex manipulations involving either retroviral infection of blastoderms or the ex vivo manipulation of primordial germ cells (PGCs) followed by injection of the cells back into a recipient embryo. Unlike in mammalian systems, avian embryonic PGCs undergo a migration through the vasculature on their path to the gonad where they become the sperm or ova producing cells. In a development which simplifies the procedure of creating transgenic chickens we have shown that PGCs are directly transfectable in vivo using commonly available transfection reagents.

Chicken interferons, their receptors and interferon-stimulated genes.

The prevalence of pathogenic viruses is a serious issue as they pose a constant threat to both the poultry industry and to human health. To prevent these viral infections an understanding of the host-virus response is critical, especially for the development of novel therapeutics. One approach in the control of viral infections would be to boost the immune response through administration of cytokines, such as interferons.

The chicken TH1 response: potential therapeutic applications of ChIFN-γ.

The outcomes of viral infections are costly in terms of human and animal health and welfare worldwide. The observed increase in the virulence of some viruses and failure of many vaccines to stop these infections has lead to the apparent need to develop new anti-viral strategies. One approach to dealing with viral infection may be to employ the therapeutic administration of recombinant cytokines to act as 'immune boosters' to assist in augmenting the host response to virus.

Promotion of Hendra virus replication by microRNA 146a.

Hendra virus is a highly pathogenic zoonotic paramyxovirus in the genus Henipavirus. Thirty-nine outbreaks of Hendra virus have been reported since its initial identification in Queensland, Australia, resulting in seven human infections and four fatalities. Little is known about cellular host factors impacting Hendra virus replication.