The Pharmacokinetics of Δ-Tetrahydrocannabinol in Sheep.

The pharmacokinetics of Δ-tetrahydrocannabinol (Δ-THC) has not been established in ruminants. Pharmacokinetic knowledge is important given feeding industrial hemp biomass has been shown to result in tissue residues post feeding in sheep. Due to a lack of testing and available data, a 'maximum' concentration of Δ-THC has not been currently set for foods of animal origin.

Nuclear-penetrating scleroderma autoantibody inhibits topoisomerase 1 cleavage complex formation.

The contributions of anti-Topoisomerase 1 (Top1) autoantibodies to the pathophysiology of diffuse cutaneous systemic sclerosis (dcSSc), the most aggressive scleroderma subtype, are unknown. Top1 catalyzes DNA relaxation and unwinding in cell nuclei, a site previously considered inaccessible to antibodies. The discovery of autoantibodies in systemic lupus erythematosus that penetrate nuclei and inhibit DNA repair raised the possibility that nuclear-penetrating autoantibodies contribute to mechanisms of autoimmunity.

Soft fundamental measure theory functional for the Weeks-Chandler-Andersen repulsive potential.

We introduce a soft fundamental measure theory functional for the purely repulsive Weeks-Chandler-Andersen (WCA) fluid. This classical density functional could serve as a reference fluid for functionals created using thermodynamic perturbation theory instead of the hard-sphere fluid. Our functional incorporates temperature-dependent parameters describing the length scale and effective softness of the particle interaction, and which reproduce the second virial coefficient of the WCA fluid.

Selective B cell depletion upon intravenous infusion of replication-incompetent anti-CD19 CAR lentivirus.

Anti-CD19 chimeric antigen receptor (CAR)-T therapy for B cell malignancies has shown clinical success, but a major limitation is the logistical complexity and high cost of manufacturing autologous cell products. If engineered for improved safety, direct infusion of viral gene transfer vectors to initiate CAR-T transduction, expansion, and anti-tumor activity could provide an alternative, universal approach. To explore this approach we administered approximately 20 million replication-incompetent vesicular stomatitis virus G protein (VSV-G) lentiviral particles carrying an anti-CD19CAR-2A-GFP transgene comprising either an FMC63 (human) or 1D3 (murine) anti-CD19 binding domain, or a GFP-only control transgene, to wild-type C57BL/6 mice by tail vein infusion.

Intake, nutrient digestibility, rumen parameters, growth rate, carcase characteristics and cannabinoid residues of sheep fed pelleted rations containing hemp ( L.) stubble.

The feeding value and impact of hemp stubble in the diet of ruminants is unknown. Fifteen Merino castrated male sheep were maintained in individual pens and fed one of three pelletized experimental inclusion diets, as a 0% (Control), 28% (Hemp 1), and 56% (Hemp 2) pellet that delivered a diet meeting the nutrient requirements of the animals. Inclusion of hemp stubble had no effect ( 0.

Defective Early B Cell Tolerance Checkpoints in Patients With Systemic Sclerosis Allow the Production of Self Antigen-Specific Clones.

Objective: Early selection steps preventing autoreactive naive B cell production are often impaired in patients with autoimmune diseases, but central and peripheral B cell tolerance checkpoints have not been assessed in patients with systemic sclerosis (SSc). This study was undertaken to characterize early B cell tolerance checkpoints in patients with SSc.

Methods: Using an in vitro polymerase chain reaction-based approach that allows the expression of recombinant antibodies cloned from single B cells, we tested the reactivity of antibodies expressed by 212 CD19+CD21 CD10+IgM CD27- new emigrant/transitional B cells and 190 CD19+CD21+CD10-IgM+CD27- mature naive B cells from 10 patients with SSc.

A Combined Immunofluorescence and Fluorescent Viability Cocktail Staining Procedure for Rapid Microscopic Detection and Enumeration of Live Legionella pneumophila.

This report describes a combined immunofluorescence and fluorescence viability stain applied as one staining solution for rapid detection of live Legionella pneumophila in mixed bacterial populations. Instead of sequential viability staining with the Invitrogen BacLight LIVE/DEAD staining kit followed by antibody-Alexa Fluor (AF) 647 conjugate staining to identify live L. pneumophila, a combined single cocktail solution staining protocol was developed to simplify and accelerate the time to detection of viable L.

ENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody.

The blood-brain barrier (BBB) prevents antibodies from penetrating the CNS and limits conventional antibody-based approaches to brain tumors. We now show that ENT2, a transporter that regulates nucleoside flux at the BBB, may offer an unexpected path to circumventing this barrier to allow targeting of brain tumors with an anti-DNA autoantibody. Deoxymab-1 (DX1) is a DNA-damaging autoantibody that localizes to tumors and is synthetically lethal to cancer cells with defects in the DNA damage response.

Framework to Classify Reverse Cardiac Remodeling With Mechanical Circulatory Support: The Utah-Inova Stages.

Background: Variable definitions and an incomplete understanding of the gradient of reverse cardiac remodeling following continuous flow left ventricular assist device (LVAD) implantation has limited the field of myocardial plasticity. We evaluated the continuum of LV remodeling by serial echocardiographic imaging to define 3 stages of reverse cardiac remodeling following LVAD.

Methods: The study enrolled consecutive LVAD patients across 4 study sites.

Delayed Closure of Open Abdomen in Septic Patients Treated With Negative Pressure Vacuum Therapy and Dynamic Sutures: A 10-Years Follow-Up on Long-Term Complications.

Patients with open abdomen after surgical interventions associated with the complication of secondary peritonitis are successfully treated with negative pressure wound therapy. The use of dynamic fascial sutures reduces fascial lateralization and increases successful delayed fascial closure after open abdomen treatment. In 2017 we published the follow-up results of 38 survivors out of 87 open abdomen patients treated with negative pressure wound therapy and dynamic fascial sutures between 2007 and 2012.

Investigations into the source attribution of party sparklers using trace elemental analysis and chemometrics.

In Australia, party sparklers are commonly used to initiate or prepare inorganic based homemade explosives (HMEs) as they are the most easily accessible and inexpensive pyrotechnic available on the market. As sparkler residue would be encountered in cases involving these types of devices, the characterisation and source determination of the residue would be beneficial within a forensic investigation. The aim of this study is to demonstrate the potential of using trace elemental profiling coupled with chemometric and other statistical techniques to link a variety of different sparklers to their origin.

Differential incorporation of SUN-domain proteins into LINC complexes is coupled to gene expression.

LInkers of Nucleoskeleton and Cytoskeleton (LINC) complexes, composed of SUN and KASH-domain proteins, span the nuclear envelope and physically connect the nuclear interior to cytoskeletal elements. Most human cells contain two SUN proteins, Sun1 and Sun2, and several KASH-proteins suggesting that multiple functionally distinct LINC complexes co-exist in the nuclear envelope. We show here, however, that while Sun1 and Sun2 in HeLa cells are each able to bind KASH-domains, Sun1 is more efficiently incorporated into LINC complexes under normal growth conditions.

A knock-in mouse strain facilitates dynamic tracking and enrichment of MEIS1.

Myeloid ecotropic viral integration site 1 (MEIS1), a HOX transcription cofactor, is a critical regulator of normal hematopoiesis, and its overexpression is implicated in a wide range of leukemias. Using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 (Cas9) gene-editing system, we generated a knock-in transgenic mouse line in which a green fluorescent protein (GFP) reporter and a hemagglutinin (HA) epitope tag are inserted near the translational start site of endogenous . This novel reporter strain readily enables tracking of MEIS1 expression at single-cell-level resolution via the fluorescence reporter GFP, and facilitates MEIS1 detection and purification via the HA epitope tag.

Unrecognized Left Heart Failure in LVAD Recipients: The Role of Routine Invasive Hemodynamic Testing.

The role of routine right heart catheterizations (RHCs) in left ventricular assist device (LVAD) patients is undefined. We analyzed 105 continuous-flow LVAD recipients who underwent an RHC approximately 3 months after implant. In 38 patients, LVAD speed was ramped with the goal of optimizing hemodynamics.

Opposing Effects of Valproic Acid Treatment Mediated by Histone Deacetylase Inhibitor Activity in Four Transgenic Models of Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is an inherited retinal degeneration (RD) that leads to blindness for which no treatment is available. RP is frequently caused by mutations in ; in some animal models, RD is exacerbated by light. Valproic acid (VPA) is a proposed treatment for RP and other neurodegenerative disorders, with a phase II trial for RP under way.

A Lentiviral Fluorescent Genetic Barcoding System for Flow Cytometry-Based Multiplex Tracking.

Retroviral integration site analysis and barcoding have been instrumental for multiplex clonal fate mapping, although their use imposes an inherent delay between sample acquisition and data analysis. Monitoring of multiple cell populations in real time would be advantageous, but multiplex assays compatible with flow cytometric tracking of competitive growth behavior are currently limited. We here describe the development and initial validation of three generations of lentiviral fluorescent genetic barcoding (FGB) systems that allow the creation of 26, 14, or 6 unique labels.

Designing coastal conservation to deliver ecosystem and human well-being benefits.

Conservation scientists increasingly recognize that incorporating human values into conservation planning increases the chances for success by garnering broader project acceptance. However, methods for defining quantitative targets for the spatial representation of human well-being priorities are less developed. In this study we employ an approach for identifying regionally important human values and establishing specific spatial targets for their representation based on stakeholder outreach.

Opposing roles for distinct LINC complexes in regulation of the small GTPase RhoA.

Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes span the nuclear envelope and transduce force from dynamic cytoskeletal networks to the nuclear lamina. Here we show that LINC complexes also signal from the nuclear envelope to critical regulators of the actin cytoskeleton. Specifically, we find that LINC complexes that contain the inner nuclear membrane protein Sun2 promote focal adhesion assembly by activating the small GTPase RhoA.

A prototype piecewise-linear dynamic attenuator.

The piecewise-linear dynamic attenuator has been proposed as a mechanism in CT scanning for personalizing the x-ray illumination on a patient- and application-specific basis. Previous simulations have shown benefits in image quality, scatter, and dose objectives. We report on the first prototype implementation.

Open and Laparo-Endoscopic Repair of Incarcerated Abdominal Wall Hernias by the Use of Biological and Biosynthetic Meshes.

Introduction: Although recently published guidelines recommend against the use of synthetic non-absorbable materials in cases of potentially contaminated or contaminated surgical fields due to the increased risk of infection (1, 2), the use of bio-prosthetic meshes for abdominal wall or ventral hernia repair is still controversially discussed in such cases. Bio-prosthetic meshes have been recommended due to less susceptibility for infection and the decreased risk of subsequent mesh explantation. The purpose of this review is to elucidate if there are any indications for the use of biological and biosynthetic meshes in incarcerated abdominal wall hernias based on the recently published literature.

Prevention of a Parastomal Hernia by Biological Mesh Reinforcement.

Introduction: In the field of hernia prevention, the prophylactic mesh-reinforcement of stoma-sites is one of the most controversially discussed issues. The incidence of parastomal hernias in the literature reported to be up to 48.1% after end colostomy and up to 30.

Understanding the Groundwater Hydrology of a Geographically-Isolated Prairie Fen: Implications for Conservation.

The sources of water and corresponding delivery mechanisms to groundwater-fed fens are not well understood due to the multi-scale geo-morphologic variability of the glacial landscape in which they occur. This lack of understanding limits the ability to effectively conserve these systems and the ecosystem services they provide, including biodiversity and water provisioning. While fens tend to occur in clusters around regional groundwater mounds, Ives Road Fen in southern Michigan is an example of a geographically-isolated fen.

Assessment of Pain and Quality of Life in Lichtenstein Hernia Repair Using a New Monofilament PTFE Mesh: Comparison of Suture vs. Fibrin-Sealant Mesh Fixation.

Background: Inguinal hernia repair is one of the most common operations in general surgery. The Lichtenstein tension-free operation has become the gold standard in open inguinal hernia repair. Despite the low recurrence rates, pain and discomfort remain a problem for a large number of patients.

Groundwater nitrogen processing in Northern Gulf of Mexico restored marshes.

Groundwater nitrogen processing was examined in a restored black needlerush (Juncus roemerianus) marsh to assess its potential for removing land-derived nitrogen pollution. Two restoration designs, one initially planted at 50% cover (half density plots) and the other one at 100% cover (full density plots), were compared with non-vegetated controls. The introduction via groundwater of a NO3(-) solution with a conservative tracer (Br(-)) and labeled isotopically ((15)N) allowed calculation of nitrogen removal in the plots following two methods.