Guidelines for the Evaluation of Prosthetic Valve Function With Cardiovascular Imaging: A Report From the American Society of Echocardiography Developed in Collaboration With the Society for Cardiovascular Magnetic Resonance and the Society of Cardiovascular Computed Tomography.

In patients with significant cardiac valvular disease, intervention with either valve repair or valve replacement may be inevitable. Although valve repair is frequently performed, especially for mitral and tricuspid regurgitation, valve replacement remains common, particularly in adults. Diagnostic methods are often needed to assess the function of the prosthesis.

Novel Humanized Mesothelin-Expressing Genetically Engineered Mouse Models Underscore Challenges in Delivery of Complex Therapeutics to Pancreatic Cancers.

Antibody-based therapies designed for human use frequently fail to cross-react with the murine isoform of their target. Because of this problem, preclinical studies of antibody-based mesothelin (Msl)-targeted therapeutics in immunocompetent systems have been limited by the lack of suitable mouse models. Here, we describe two immunocompetent humanized mesothelin transgenic mouse lines that can act as tolerant hosts for C57Bl/6-syngeneic cell lines expressing the human isoform of mesothelin.

Specific Considerations for Sonographers When Performing Echocardiography during the 2019 Novel Coronavirus Outbreak: Supplement to the American Society of Echocardiography Statement.

Sonographers need to be familiar with and prepared to implement strategies for reducing the risk of exposure to and transmission of the COVID-19 virus. Strategies to employ can be grouped into three broad categories: (1) whom to scan, (2) where to scan, and (3) how to scan. Whom to scan addresses sonographer strategies for determining essential and emergent scan status.

Endemic bot fly larvae infection in Northern New York State.

Tropical botfly infection is well described, though endemic botfly myiasis in humans is rare in temperate regions. Reported is a case of myiasis from botfly larvae in a man from northern New York with no tropical travel. The authors discuss the epidemiology, life-cycle, and diagnosis of non-tropical botfly infection.

Protein Synthesis Inhibition Activity of Mesothelin Targeting Immunotoxin LMB-100 Decreases Concentrations of Oncogenic Signaling Molecules and Secreted Growth Factors.

LMB-100 is a mesothelin-targeted recombinant immunotoxin (iTox) that carries a modified exotoxin A (PE) payload. PE kills cells by inhibiting synthesis of new proteins. We found that treatment of pancreatic cancer cells with LMB-100 for 24⁻48 h did not change total protein level despite inducing protein synthesis inhibition (PSI).

Effects of 5% sodium chloride ophthalmic ointment on thickness and morphology of the normal canine cornea.

Objective: To determine the effect of 5% sodium chloride ophthalmic ointment (5% NaCl) on thickness and morphology of the normal canine cornea using ultrasonic pachymetry (USP), in vivo confocal microscopy (IVCM), and Fourier-domain optical coherence tomography (FD-OCT).

Methods: Five healthy laboratory Beagles received ophthalmic examinations including USP, IVCM, and FD-OCT prior to and at fixed intervals following treatment. The right and left eyes were treated with 5% NaCl and artificial tears ophthalmic ointment (AT), respectively, every 2 hours for 4 treatments/d (days 2-9), and then hourly for 7 treatments/d (day 10).

3D Morphological Changes in LV and RV During LVAD Ramp Studies.

Objectives: The purpose of this study was to investigate the differential impact of the 2 most commonly available left ventricular assist device (LVAD) types on the right ventricle (RV) and left ventricle (LV) using 3-dimensional (3D) echocardiography-based analysis of ventricular morphology.

Background: LVADs have emerged as common therapy for advanced heart failure. Recent data suggest that the heart responds differently to speed settings in the 2 main devices available (HeartMate II [HMII], St Jude Medical, Pleasanton, California, and HVAD, HeartWare International, Framingham, Massachusetts).

Screening for Outflow Cannula Malfunction of Left Ventricular Assist Devices (LVADs) With the Use of Doppler Echocardiography: New LVAD-Specific Reference Values for Contemporary Devices.

Background: Echocardiographic assessment of left ventricular assist devices (LVADs) is used as a screening tool to evaluate the integrity and mechanics of the pump and circuit. We aimed to 1) establish the normal range and upper reference limit of peak velocity of the outflow cannula for the modern era of LVADs and 2) assess the clinical performance of the currently cited and newly proposed reference limits in patients with continuous-flow LVADs as a screening tool for cannula malfunction.

Methods: LVAD outflow peak CW velocities were measured with the use of Doppler transthoracic echocardiography (TTE) in 57 patients with LVADs (44 with Heartmate II (HM2), 13 with Heartware (HW)).

Hemodynamic Ramp Tests in Patients With Left Ventricular Assist Devices.

Objectives: This study tested whether combined invasive hemodynamic and echocardiographic ramp tests can help optimize patient management.

Background: Guidelines for optimizing speed and medications in continuous flow ventricular assist device (cfLVAD) patients are mainly based on expert opinion.

Methods: Thirty-five cfLVAD patients (21 HeartMate II [Thoratec, Pleasanton, California] and 14 HVAD [HeartWare International, Framingham, Massachusetts]) underwent ramp tests with right heart catheterization (including central venous pressure [CVP], pulmonary artery pressure, pulmonary capillary wedge pressure [PCWP], and blood pressure) and echocardiography.

Herbal tonic does not inhibit estrogen receptor negative mammary tumor development in a transgenic mouse model.

Women who are diagnosed with breast cancer often self-administer complementary and alternative medicines to augment their conventional treatments, improve health, or prevent recurrence. Flor-Essence® herbal tonic is a complex mixture of eight herbal extracts used by cancer patients because of anecdotal evidence that it can treat or prevent disease. In this study four experimental groups of female MMTV-Neu mice were left untreated or treated with 3% Flor-Essence® in utero, from birth until 5 weeks of age, or throughout their lifetime.

Impaired exercise tolerance and skeletal muscle myopathy in sulfonylurea receptor-2 mutant mice.

By sensing intracellular energy levels, ATP-sensitive potassium (K(ATP)) channels help regulate vascular tone, glucose metabolism, and cardioprotection. SUR2 mutant mice lack full-length K(ATP) channels in striated and smooth muscle and display a complex phenotype of hypertension and coronary vasospasm. SUR2 mutant mice also display baseline cardioprotection and can withstand acute sympathetic stress better than normal mice.

Semi-automated analysis of dynamic changes in myocardial contrast from real-time three-dimensional echocardiographic images as a basis for volumetric quantification of myocardial perfusion.

Aims: Despite the potential of real-time three-dimensional (3D) echocardiography (RT3DE) to assess myocardial perfusion, there is no quantification method available for perfusion analysis from RT3DE images. Such method would require 3D regions of interest (ROI) to be defined and adjusted frame-by-frame to compensate for cardiac translation and deformation. Our aims were to develop and test a technique for automated identification of 3D myocardial ROI suitable for translation-free quantification of myocardial videointensity over time, MVI(t), from contrast-enhanced RT3DE images.

Evolutionary diversification of SPANX-N sperm protein gene structure and expression.

The sperm protein associated with nucleus in the X chromosome (SPANX) genes cluster at Xq27 in two subfamilies, SPANX-A/D and SPANX-N. SPANX-A/D is specific for hominoids and is fairly well characterized. The SPANX-N gave rise to SPANX-A/D in the hominoid lineage approximately 7 MYA.

Spontaneous and irradiation-induced tumor susceptibility in BRCA2 germline mutant mice and cooperative effects with a p53 germline mutation.

Mutations in both p53 and BRCA2 are commonly seen together in human tumors suggesting that the loss of both genes enhances tumor development. To elucidate this interaction in an animal model, mice lacking the carboxy terminal domain of Brca2 were crossed with p53 heterozygous mice. Females from this intercross were then irradiated with an acute dose of 5 Gy ionizing radiation at 5 weeks of age and compared to nonirradiated controls.

Imaging and quantification of myocardial perfusion using real-time three-dimensional echocardiography.

Objectives: We tested the feasibility of real-time three-dimensional echocardiographic (RT3DE) perfusion imaging and developed and validated an algorithm for volumetric analysis of myocardial contrast inflow. The study included three protocols wherein perfusion was measured: 1) in an ex-vivo model of controlled global coronary flow, 2) in an in-vivo model during regional perfusion variations, and 3) in humans during pharmacologically induced hyperemia.

Background: The RT3DE technology offers an opportunity for myocardial perfusion imaging without multi-slice reconstruction and repeated contrast maneuvers.

Interrupted infusion of echocardiographic contrast as a basis for accurate measurement of myocardial perfusion: ex vivo validation and analysis procedures.

Background: Echocardiographic quantification of myocardial perfusion is based on analysis of contrast replenishment after destructive high-energy ultrasound impulses (flash-echo). This technique is limited by nonuniform microbubble destruction and the dependency on exponential fitting of a small number of noisy time points. We hypothesized that brief interruptions of contrast infusion (ICI) would result in uniform contrast clearance followed by slow replenishment and, thus, would allow analysis from multiple data points without exponential fitting.

Quantitative echocardiographic evaluation of myocardial perfusion using interrupted contrast infusion technique: in vivo validation studies and feasibility in human beings.

Background: We recently developed a new approach for contrast echocardiographic quantification of myocardial perfusion, based on brief interruptions of contrast infusion, which was designed to overcome the limitations of existing techniques. In this study, our technique was initially validated in a series of animal experiments designed to detect regional perfusion variations in vivo. Subsequently, clinical feasibility of perfusion measurements was tested.

The microcephaly ASPM gene is expressed in proliferating tissues and encodes for a mitotic spindle protein.

The most common cause of primary autosomal recessive microcephaly (MCPH) appears to be mutations in the ASPM gene which is involved in the regulation of neurogenesis. The predicted gene product contains two putative N-terminal calponin-homology (CH) domains and a block of putative calmodulin-binding IQ domains common in actin binding cytoskeletal and signaling proteins. Previous studies in mouse suggest that ASPM is preferentially expressed in the developing brain.

The role of still-frame parametric imaging in magnetic resonance assessment of left ventricular wall motion by non-cardiologists.

Background: Cardiac magnetic resonance (MR) images are often reviewed by non-cardiologists who are not trained in the interpretation of regional left ventricular (LV) function. We hypothesized that the use of still-frame parametric MR images of wall motion could aid in the assessment of regional LV function.

Methods: Dynamic, electrocardiogram-gated, steady-state free precession (FIESTA) short-axis images were obtained in 6 to 10 slices in 18 consecutive patients.

Automated quantitative assessment of wall motion in patients with poor acoustic windows.

Background: No technique exists for objective evaluation of left ventricular wall motion in contrast-enhanced images. We tested a new technique for quantification of regional fractional area change using contrast-enhanced power modulation imaging with color kinesis.

Methods: The feasibility of this technique for detecting acute ischemia was first tested in 11 pigs.

Secondary coronary artery vasospasm promotes cardiomyopathy progression.

Genetic defects in the plasma membrane-associated sarcoglycan complex produce cardiomyopathy characterized by focal degeneration. The infarct-like pattern of cardiac degeneration has led to the hypothesis that coronary artery vasospasm underlies cardiomyopathy in this disorder. We evaluated the coronary vasculature of gamma-sarcoglycan mutant mice and found microvascular filling defects consistent with arterial vasospasm.

The SPANX gene family of cancer/testis-specific antigens: rapid evolution and amplification in African great apes and hominids.

Human sperm protein associated with the nucleus on the X chromosome (SPANX) genes comprise a gene family with five known members (SPANX-A1, -A2, -B, -C, and -D), encoding cancer/testis-specific antigens that are potential targets for cancer immunotherapy. These highly similar paralogous genes cluster on the X chromosome at Xq27. We isolated and sequenced primate genomic clones homologous to human SPANX.

Harmonic imaging for endocardial visualization and myocardial contrast echocardiography during transesophageal echocardiography.

Background: Although harmonic imaging (HI) improves endocardial visualization and is necessary for myocardial perfusion imaging, it has yet to be implemented in transesophageal echocardiography. Our goal was to determine whether HI implemented in a prototype transesophageal echocardiography probe improved endocardial visualization and allowed perfusion imaging.

Methods: In 23 patients, fundamental and harmonic images were obtained in the transgastric short-axis (TSAX) and midesophageal 4-chamber views, and reviewed for endocardial visualization by 3 readers blinded to imaging mode.