Expanding Genetic Counselor Roles: A Model for Global Research Development.

Purpose: Genetic counselors (GCs) increasingly play key roles in advancing genomic medicine through innovative research. Here, we examine one large cohort of GCs' evolving contributions to the literature, with the goal of facilitating worldwide professional development for GCs through scholarly activities.

Methods: Publications were cataloged by members of the Section of Genetic Counseling (Section), established at the Children's Hospital of Philadelphia and the University of Pennsylvania in 2014, including publication year, journal, impact factor, and author position.

Detection of flap tissue ischemia in a rat model: Real-time monitoring of changes in oxygenation and perfusion through injectable biosensors.

Background: The success of surgical flaps is improved by timely correction of vascular compromise. Current monitoring methods are labor or cost intensive or have limited clinical benefit. We hypothesize that injectable oxygen sensors can identify acute vascular compromise.

Near-Infrared Optical Nanosensors for Continuous Detection of Glucose.

Background: Continuous glucose monitors (CGMs) enable people with diabetes to proactively manage their blood glucose and reduce the risk of hypoglycemia. Commercially available CGMs utilize percutaneous electrodes that, after days to weeks of implantation, are subjected to the foreign body response that severely reduces sensor accuracy. The previous work demonstrated the use of hydrogels containing a glucose-responsive viologen that quenches a nearby fluorophore.

Temporal expression of cytokines and B-cell phenotypes during mechanical circulatory support.

Background: Allosensitization during mechanical circulatory support (MCS) is a well-described phenomenon, although its mechanism remains unknown. Although immune-mediated interactions from devices or blood transfusions have been proposed, the role of inflammation in this development is less clear. This study was undertaken to further investigate the temporal association of cytokines and B-cell phenotypes in the MCS population.

Continuous monitoring of interstitial tissue oxygen using subcutaneous oxygen microsensors: In vivo characterization in healthy volunteers.

Measurements of regional tissue oxygen serve as a proxy to monitor local perfusion and have the potential to guide therapeutic decisions in multiple clinical disciplines. Transcutaneous oximetry (tcpO) is a commercially available noninvasive technique that uses an electrode to warm underlying skin tissue and measure the resulting oxygen tension at the skin surface. A novel approach is to directly measure interstitial tissue oxygen using subcutaneous oxygen microsensors composed of a biocompatible hydrogel carrier platform with embedded oxygen sensing molecules.

Integrated phosphorescence-based photonic biosensor (iPOB) for monitoring oxygen levels in 3D cell culture systems.

Physiological processes, such as respiration, circulation, digestion, and many pathologies alter oxygen concentration in the blood and tissue. When designing culture systems to recapitulate the in vivo oxygen environment, it is important to integrate systems for monitoring and controlling oxygen concentration. Herein, we report the design and engineering of a system to remotely monitor and control oxygen concentration inside a device for 3D cell culture.

Antibiotic-induced changes in the microbiota disrupt redox dynamics in the gut.

How host and microbial factors combine to structure gut microbial communities remains incompletely understood. Redox potential is an important environmental feature affected by both host and microbial actions. We assessed how antibiotics, which can impact host and microbial function, change redox state and how this contributes to post-antibiotic succession.

T cell dysfunction and patient age are associated with poor outcomes after mechanical circulatory support device implantation.

Immunologic impairment may contribute to poor outcomes after implantation of mechanical circulatory support device (MCSD), with infection often as a terminal event. The study of immune dysfunction is of special relevance given the growing numbers of older patients with heart disease. The aim of the study was to define which immunologic characteristics are associated with development of adverse clinical outcomes after MCSD implantation.

Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced motor neurons.

An intronic GGGGCC repeat expansion in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but the pathogenic mechanism of this repeat remains unclear. Using human induced motor neurons (iMNs), we found that repeat-expanded C9ORF72 was haploinsufficient in ALS. We found that C9ORF72 interacted with endosomes and was required for normal vesicle trafficking and lysosomal biogenesis in motor neurons.

Integrative model of leukocyte genomics and organ dysfunction in heart failure patients requiring mechanical circulatory support: a prospective observational study.

Background: The implantation of mechanical circulatory support devices in heart failure patients is associated with a systemic inflammatory response, potentially leading to death from multiple organ dysfunction syndrome. Previous studies point to the involvement of many mechanisms, but an integrative hypothesis does not yet exist. Using time-dependent whole-genome mRNA expression in circulating leukocytes, we constructed a systems-model to improve mechanistic understanding and prediction of adverse outcomes.

Injectable Phosphorescence-based Oxygen Biosensors Identify Post Ischemic Reactive Hyperoxia.

Novel injectable biosensors were used to measure interstitial oxygenation before, during, and after transient ischemia. It is well known that reactive hyperemia occurs following a period of ischemia. However, increased blood flow does not necessarily mean increased oxygen tension in the tissue.

Tissue-Integrating Oxygen Sensors: Continuous Tracking of Tissue Hypoxia.

We describe a simple method of tracking oxygen in real-time with injectable, tissue-integrating microsensors. The sensors are small (500 μm × 500 μm × 5 mm), soft, flexible, tissue-like, biocompatible hydrogel s that have been shown to overcome the foreign body response for long-term sensing. The sensors are engineered to change luminescence in the presence of oxygen or other analytes and function for months to years in the body.

Relationship of disease-associated gene expression to cardiac phenotype is buffered by genetic diversity and chromatin regulation.

Expression of a cohort of disease-associated genes, some of which are active in fetal myocardium, is considered a hallmark of transcriptional change in cardiac hypertrophy models. How this transcriptome remodeling is affected by the common genetic variation present in populations is unknown. We examined the role of genetics, as well as contributions of chromatin proteins, to regulate cardiac gene expression and heart failure susceptibility.

In vivo detection of SERS-encoded plasmonic nanostars in human skin grafts and live animal models.

Surface-enhanced Raman scattering (SERS)-active plasmonic nanomaterials have become a promising agent for molecular imaging and multiplex detection. Among the wide variety of plasmonics-active nanoparticles, gold nanostars offer unique plasmon properties that efficiently induce strong SERS signals. Furthermore, nanostars, with their small core size and multiple long thin branches, exhibit high absorption cross sections that are tunable in the near-infrared region of the tissue optical window, rendering them efficient for in vivo spectroscopic detection.

Characterization of Lactate Sensors Based on Lactate Oxidase and Palladium Benzoporphyrin Immobilized in Hydrogels.

An optical biosensor for lactate detection is described. By encapsulating enzyme-phosphor sensing molecules within permeable hydrogel materials, lactate-sensitive emission lifetimes were achieved. The relative amount of monomer was varied to compare three homo- and co-polymer materials: poly(2-hydroxyethyl methacrylate) (pHEMA) and two copolymers of pHEMA and poly(acrylamide) (pAam).

Preclinical Evaluation of Poly(HEMA-co-acrylamide) Hydrogels Encapsulating Glucose Oxidase and Palladium Benzoporphyrin as Fully Implantable Glucose Sensors.

Background: Continuous glucose monitors (CGMs) require percutaneous wire probes to monitor glucose. Sensors based on luminescent hydrogels are being explored as fully implantable alternatives to traditional CGMs. Our previous work investigated hydrogel matrices functionalized with enzymes and oxygen-quenched phosphors, demonstrating sensitivity to glucose, range of response, and biofouling strongly depend on the matrix material.

The First-in-Man "Si Se Puede" Study for the use of micro-oxygen sensors (MOXYs) to determine dynamic relative oxygen indices in the feet of patients with limb-threatening ischemia during endovascular therapy.

Objective: Patients with limb-threatening ischemia exhibit uneven patterns of perfusion in the foot, which makes it challenging to determine adequate topographic perfusion by angiography alone. This study assessed the feasibility of reporting dynamic relative oxygen indices and tissue oxygen concentration from multiple locations on the foot during endovascular therapy using a novel micro-oxygen sensor (MOXY; PROFUSA, Inc, South San Francisco, Calif) approach.

Methods: A prospective, 28-day, single-arm, observational study was performed in 10 patients who underwent endovascular therapy for limb-threatening ischemia.

Cancer of the gingiva.

Cancer of the gingiva is a rare disease in the Western World. It most commonly affects elderly population. Because of its rarity, the reporting on the disease is sparse and often grouped with other subsites of oral cancer, which makes conclusions difficult to interpret.

Comparison of whole blood and peripheral blood mononuclear cell gene expression for evaluation of the perioperative inflammatory response in patients with advanced heart failure.

Background: Heart failure (HF) prevalence is increasing in the United States. Mechanical Circulatory Support (MCS) therapy is an option for Advanced HF (AdHF) patients. Perioperatively, multiorgan dysfunction (MOD) is linked to the effects of device implantation, augmented by preexisting HF.