Targeted Ganglionated Plexi Ablation With Nanoformulated Calcium Suppresses Postoperative AF Via Vagosympatholytic and Anti-Inflammatory Effects.

Background: The mechanisms underlying postoperative atrial fibrillation (POAF) remain unclear.

Objectives: The aim of this study was to test the hypothesis that targeted chemical ganglionated plexi (GP) modulation of all major left atrial-pulmonary vein GP using novel nanoformulated calcium chloride (nCaCl) can reverse postoperative neuroelectrical remodeling by suppressing vagosympathetic nerve activity and the localized inflammatory process, both critical substrates of POAF.

Methods: In a novel canine model of POAF with serial thoracopericardiotomies, sympathetic nerve activity (SNA), vagal nerve activity (VNA) and GP nerve activity (GPNA) were recorded; spontaneous and in vivo AF vulnerability were assessed; and atrial and circulating inflammatory markers and norepinephrine (NE) were measured to determine the neuroelectrical remodeling that promotes POAF and its subsequent modulation with nCaCl GP treatment (n = 6) vs saline sham controls (n = 6).

The role of hemodynamic shear stress in healing chronic wounds.

Wounds continue to pose significant challenges to clinicians. Data based on randomized controlled trials from the US Wound Registry showed that less than 50% of wounds heal in an unpredictable period of time. Chronic wounds are difficult to heal, with multiple barriers to healing that include inadequate nutrient flow, an inflammatory-coagulation vicious cycle, redox imbalance, and anatomical, physiological, and biochemical dysfunction in the endothelium.

The role of endothelial shear stress on haemodynamics, inflammation, coagulation and glycocalyx during sepsis.

Sepsis is a multifactorial syndrome primarily determined by the host response to an invading pathogen. It is common, with over 48 million cases worldwide in 2017, and often lethal. The sequence of events in sepsis begins with the damage of endothelium within the microvasculature, as a consequence of the inflammatory and coagulopathic responses to the pathogen that can progress to multiple organ failure and death.

Orientation of the round window membrane: A normative study of inner ear anatomical orientation using 2D projections of 3D volumes.

Introduction: Orientation of the Round Window Membrane (RWM) is an important metric to establish if utilized as a potential access for targeted delivery of magnetically guided nanomedicines to the inner ear. Orientation with respect to an internal reference frame (such as the planes defined by the semicircular-canals [SCC]) may provide an internally consistent basis if the basis is orthogonal and consistent (from patient to patient).

Materials And Methods: Utilizing a micro computed tomography (CT), 20 temporal bones are scanned for anatomical information.

Epicardial injection of nanoformulated calcium into cardiac ganglionic plexi suppresses autonomic nerve activity and postoperative atrial fibrillation.

Background: Imbalanced activation of the cardiac autonomic nervous system triggers postoperative atrial fibrillation (POAF). Neuronal calcium overload induces apoptosis. We hypothesize that epicardial injection of timed-release nanoformulated CaCl (nCaCl) into left atrial ganglionic plexi (GP) modulates autonomic function and suppresses POAF.

Targeted Ganglionated Plexi Denervation Using Magnetic Nanoparticles Carrying Calcium Chloride Payload.

Objectives: This study sought to develop a novel targeted delivery therapy to ablate the major atrial ganglionated plexi (GP) using magnetic nanoparticles carrying a CaCl payload.

Background: Prior studies indicated the role of hyperactivity of the cardiac autonomic nervous system in the genesis of atrial fibrillation.

Methods: Twenty-eight male mongrel dogs underwent a bilateral thoracotomy.

TrueAllele casework on Virginia DNA mixture evidence: computer and manual interpretation in 72 reported criminal cases.

Mixtures are a commonly encountered form of biological evidence that contain DNA from two or more contributors. Laboratory analysis of mixtures produces data signals that usually cannot be separated into distinct contributor genotypes. Computer modeling can resolve the genotypes up to probability, reflecting the uncertainty inherent in the data.

Magnetic targeted delivery of dexamethasone acetate across the round window membrane in guinea pigs.

Hypothesis: Magnetically susceptible PLGA nanoparticles will effectively target the round window membrane (RWM) for delivery of dexamethasone-acetate (Dex-Ac) to the scala tympani.

Background: Targeted delivery of therapeutics to specific tissues can be accomplished using different targeting mechanisms. One technology includes iron oxide nanoparticles, susceptible to external magnetic fields.

A Two-Magnet System to Push Therapeutic Nanoparticles.

Magnetic fields can be used to direct magnetically susceptible nanoparticles to disease locations: to infections, blood clots, or tumors. Any single magnet always attracts (pulls) ferro- or para-magnetic particles towards it. External magnets have been used to pull therapeutics into tumors near the skin in animals and human clinical trials.

Autonomic denervation with magnetic nanoparticles.

Background: prior studies indicated that ablation of the 4 major atrial ganglionated plexi (GP) suppressed atrial fibrillation.

Methods And Results: superparamagnetic nanoparticles (MNPs) made of Fe(3)O(4) (core), thermoresponsive polymeric hydrogel (shell), and neurotoxic agent (N-isopropylacrylamide monomer [NIPA-M]) were synthesized. In 23 dogs, a right thoracotomy exposed the anterior right GP (ARGP) and inferior right GP (IRGP).

Autonomic denervation using magnetic nanoparticles.

Nanoparticles with their unique physical and biochemical properties, such as modifiable surface functionalization and versatility for carrying various therapeutic payloads, are excellent vehicles for targeted drug delivery. The diffuse nature of cardiovascular diseases presents a great challenge to nanotechnology-based drug delivery therapy. Cardiac arrhythmias, frequently caused by heterogeneity of conduction, repolarization, and cell-cell communication, are particularly sensitive to any therapy that targets the presumed arrhythmogenic myocardium but inadvertently introduces further heterogeneity into the heart.

Distribution of PLGA nanoparticles in chinchilla cochleae.

Objectives: To study the distribution of polylactic/glycolic acid-encapsulated iron oxide nanoparticles (PLGA-NPs) in chinchilla cochleae after application on the round window membrane (RWM).

Study Design And Setting: Six chinchillas (12 ears) were equally divided into controls (no treatments) and experimentals (PLGA-NP with or without magnetic exposure). After 40 minutes of PLGA-NP placement on the RWM, perilymph was withdrawn from the scala tympani.

Magnetic characterization of superparamagnetic nanoparticles pulled through model membranes.

Background: To quantitatively compare in-vitro and in vivo membrane transport studies of targeted delivery, one needs characterization of the magnetically-induced mobility of superparamagnetic iron oxide nanoparticles (SPION). Flux densities, gradients, and nanoparticle properties were measured in order to quantify the magnetic force on the SPION in both an artificial cochlear round window membrane (RWM) model and the guinea pig RWM.

Methods: Three-dimensional maps were created for flux density and magnetic gradient produced by a 24-well casing of 4.

Magnetic resonance imaging compatibility and safety of the SOUNDTEC Direct System.

Objective/hypothesis: The purpose of this study was to evaluate magnetic resonance imaging (MRI) compatibility and safety of an electromagnetic implanted hearing device (the SOUNDTEC Direct System; SOUNDTEC, Inc., Oklahoma City, OK) implant during a 0.3-Tesla open MRI imaging examination of the head and neck and to develop an MRI protocol that maximizes patient safety while minimizing the need for implant removal.

The permeability of SPION over an artificial three-layer membrane is enhanced by external magnetic field.

Background: Sensorineural hearing loss, a subset of all clinical hearing loss, may be correctable through the use of gene therapy. We are testing a delivery system of therapeutics through a 3 cell-layer round window membrane model (RWM model) that may provide an entry of drugs or genes to the inner ear. We designed an in vitro RWM model similar to the RWM (will be referred to throughout the paper as RWM model) to determine the feasibility of using superparamagnetic iron oxide (Fe3O4) nanoparticles (SPION) for targeted delivery of therapeutics to the inner ear.

Magnetic nanoparticles: inner ear targeted molecule delivery and middle ear implant.

Superparamagnetic iron oxide nanoparticles (SNP) composed of magnetite (Fe(3)O(4)) were studied preliminarily as vehicles for therapeutic molecule delivery to the inner ear and as a middle ear implant capable of producing biomechanically relevant forces for auditory function. Magnetite SNP were synthesized, then encapsulated in either silica or poly (D,L,-Lactide-co-glycolide) or obtained commercially with coatings of oleic acid or dextran. Permanent magnetic fields generated forces sufficient to pull them across tissue in several round window membrane models (in vitrocell culture, in vivo rat and guinea pig, and human temporal bone) or to embed them in middle ear epithelia.

Epithelial internalization of superparamagnetic nanoparticles and response to external magnetic field.

Superparamagnetic magnetite nanoparticles (MNP) coated with silica were synthesized and chronically implanted into the middle ear epithelial tissues of a guinea pig model (n=16) for the generation of force by an external magnetic field. In vivo limitations of biocompatibility include particle morphology, size distribution, composition and mode of internalization. Synthesis of MNP was performed using a modified precipitation technique and they were characterized by transmission electron microscopy, X-ray diffractometry and energy dispersive spectroscopy, which verified size distribution, composition and silica encapsulation.

Human middle ear transfer function measured by double laser interferometry system.

Hypothesis: Simultaneous measurements of vibrations on the stapes footplate, incudostapedial (IS) joint, and tympanic membrane (TM) can be made in both normal and drained cochleae, and the stapes displacement transfer function (S-DTF) and TM displacement transfer function (TM-DTF) are derived.

Background: A single laser Doppler interferometer previously has been used for measuring movement of the stapes or TM in temporal bones. However, there may be a limitation to optimally describing acoustic-mechanical transmission when the interferometer and temporal bone are moved frequently during experimental recordings.

Computer-integrated finite element modeling of human middle ear.

The objective of this study was to produce an improved finite element (FE) model of the human middle ear and to compare the model with human data. We began with a systematic and accurate geometric modeling technique for reconstructing the middle ear from serial sections of a freshly frozen temporal bone. A geometric model of a human middle ear was constructed in a computer-aided design (CAD) environment with particular attention to geometry and microanatomy.

Biomechanical influences of magnetic resonance imaging on the SOUNDTEC Direct System implant.

Objective: The purpose of this study was to measure the forces experienced by the SOUNDTEC Direct System magnetic implant during 0.3-T MRI.

Study Design: Torsional and linear forces imposed on 8 implants were measured by using calibrated neurologic Von Frey hairs and were compared with finite-element analysis predictions and the forces required to separate the incudostapedial joints of unpreserved temporal bones.

An advanced computer-aided geometric modeling and fabrication method for human middle ear.

This paper presents a practical and systematic method for reconstructing accurate computer and physical models of the entire human middle ear. The proposed method starts with the histological section preparation of human temporal bone. Through tracing outlines of the middle ear components on the sections, a set of discrete points is obtained and employed to construct B-spline curves that represent the exterior contours of the components using a curve-fitting technique.

Three-dimensional modeling of middle ear biomechanics and its applications.

Hypothesis: This study investigated whether combined technologies of finite element (FE) analysis and three-dimensional reconstruction of human temporal bones could be used to construct a computational model, useful in describing normal and pathologic middle ear sound conduction.

Background: FE models for biologic systems have been used in ear biomechanics. Three-dimensional reconstructions have also been made, but not in combination with FE modeling and laser interferometry measuring of human temporal bones.

Biomaterials for implantable middle ear hearing devices.

The use of biomaterials to ameliorate the effects of diseases dates back centuries to the ancient Greeks and Chinese. In the twentieth century, the use of synthetic and natural materials rapidly increased as clinicians developed problem-solving strategies. From replacement prostheses, to structural polymers, to the controlled release of engineered proteins into the body, to the present-day tissue engineering, biomaterials have transformed medicine.

Mass loading on the ossicles and middle ear function.

The middle ear as a levered vibrating system for sound transmission from the external to the inner ear is affected by changes in ossicular chain mass. Mass loading of the ossicles may impair ossicular dynamics and sound transmission to the inner ear. It is incumbent on otologic surgeons and researchers of middle ear mechanics to consider the mass loading effect on middle ear function in clinical and physiological applications.