Vector integration and fate in the hemophilia dog liver multiple years after AAV-FVIII gene transfer.

Gene therapy using adeno-associated virus (AAV) vectors is a promising approach for the treatment of monogenic disorders. Long-term multiyear transgene expression has been demonstrated in animal models and clinical studies. Nevertheless, uncertainties remain concerning the nature of AAV vector persistence and whether there is a potential for genotoxicity.

Correction: A vesicular stomatitis virus-based prime-boost vaccination strategy induces potent and protective neutralizing antibodies against SARS-CoV-2.

[This corrects the article DOI: 10.1371/journal.ppat.

The Use of Waterless Alcohol-based Antiseptic for Surgical Skin Preparation in Rhesus Macaques ().

Ensuring asepsis of the surgical site before surgery is an essential component of safe surgical practices to reduce the incidence of surgical site infections in veterinary medicine. The current accepted method of skin preparation is a multistep process that alternates either a povidone-iodine or chlorhexidine soap scrub with a 70% alcohol rinse. After cleansing, the site is left to dry before draping.

Characterization of cerebrospinal fluid biomarkers associated with neurodegenerative diseases in healthy cynomolgus and rhesus macaque monkeys.

Monkeys are becoming important translational models of neurodegenerative disease. To facilitate model development, we measured cerebrospinal fluid (CSF) concentrations of key biomarkers in healthy male and female cynomolgus and rhesus macaques. Amyloid beta (Aβ40, Aβ42), tau (total tau [t-tau], phosphorylated tau [pThr181]), and neurofilament light (NfL) concentrations were measured in CSF of 82 laboratory-housed, experimentally naïve cynomolgus (n = 33) and rhesus (n = 49) macaques.

A vesicular stomatitis virus-based prime-boost vaccination strategy induces potent and protective neutralizing antibodies against SARS-CoV-2.

The development of safe and effective vaccines to prevent SARS-CoV-2 infections remains an urgent priority worldwide. We have used a recombinant vesicular stomatitis virus (rVSV)-based prime-boost immunization strategy to develop an effective COVID-19 vaccine candidate. We have constructed VSV genomes carrying exogenous genes resulting in the production of avirulent rVSV carrying the full-length spike protein (SF), the S1 subunit, or the receptor-binding domain (RBD) plus envelope (E) protein of SARS-CoV-2.

A Meta-Analysis of Rhesus Macaques (), Cynomolgus Macaques (), African green monkeys (), and Ferrets () as Large Animal Models for COVID-19.

Animal models are at the forefront of biomedical research for studies of viral transmission, vaccines, and pathogenesis, yet the need for an ideal large animal model for COVID-19 remains. We used a meta-analysis to evaluate published data relevant to this need. Our literature survey contained 22 studies with data relevant to the incidence of common COVID-19 symptoms in rhesus macaques (), cynomolgus macaques (), African green monkeys (), and ferrets ().

The effect of lumbar puncture on the neurodegeneration biomarker neurofilament light in macaque monkeys.

Introduction: Neurofilament light (NFL) in cerebrospinal fluid (CSF) is elevated in neurodegenerative disease patients, and may track disease progression and treatment. Macaque monkeys are emerging as important translational models of neurodegeneration, and NFL may be a useful biomarker.

Methods: To determine the influence of a previous lumbar puncture (LP) on NFL, we collected CSF at multiple time points in macaque monkeys via LP or cisterna magna puncture.

Poly-Arginine Peptide-18 (R18) Reduces Brain Injury and Improves Functional Outcomes in a Nonhuman Primate Stroke Model.

Poly-arginine peptide-18 (R18) is neuroprotective in different rodent middle cerebral artery occlusion (MCAO) stroke models. In this study, we examined whether R18 treatment could reduce ischemic brain injury and improve functional outcome in a nonhuman primate (NHP) stroke model. A stroke was induced in male cynomolgus macaques by MCAO distal to the orbitofrontal branch of the MCA through a right pterional craniotomy, using a 5-mm titanium aneurysm clip for 90 min.

The diabetes drug liraglutide reverses cognitive impairment in mice and attenuates insulin receptor and synaptic pathology in a non-human primate model of Alzheimer's disease.

Alzheimer's disease (AD) is a devastating neurological disorder that still lacks an effective treatment, and this has stimulated an intense pursuit of disease-modifying therapeutics. Given the increasingly recognized link between AD and defective brain insulin signaling, we investigated the actions of liraglutide, a glucagon-like peptide-1 (GLP-1) analog marketed for treatment of type 2 diabetes, in experimental models of AD. Insulin receptor pathology is an important feature of AD brains that impairs the neuroprotective actions of central insulin signaling.

Low profile halo head fixation in non-human primates.

Background: We present a new halo technique for head fixation of non-human primates during electrophysiological recording experiments. Our aim was to build on previous halo designs in order to create a simple low profile system that provided long-term stability.

New Method: Our design incorporates sharp skull pins that are directly threaded through a low set halo frame and are seated into implanted titanium foot plates on the skull.

Efficacy of Intravenous Mannitol in the Management of Orbital Compartment Syndrome: A Nonhuman Primate Model.

Purpose: To report the efficacy of intravenous mannitol in the treatment of orbital compartment syndrome.

Methods: An experimental study was conducted on 4 nonhuman primates (8 orbits). Orbital compartment syndrome was simulated by injecting autologous blood into both orbits of each nonhuman primate until a pressure of 80 mm Hg was reached (time 0).

Chronic prenatal ethanol exposure alters expression of central and peripheral insulin signaling molecules in adult guinea pig offspring.

Maternal ethanol consumption during pregnancy can produce a range of teratogenic outcomes in offspring. The mechanism of ethanol teratogenicity is multi-faceted, but may involve alterations in insulin and insulin-like growth factor (IGF) signaling pathways. These pathways are not only important for metabolism, but are also critically involved in neuronal survival and plasticity, and they can be altered by chronic prenatal ethanol exposure (CPEE).

Omental implantation of BOECs in hemophilia dogs results in circulating FVIII antigen and a complex immune response.

Ex vivo gene therapy strategies avoid systemic delivery of viruses thereby mitigating the risk of vector-associated immunogenicity. Previously, we delivered autologous factor VIII (FVIII)-expressing blood outgrowth endothelial cells (BOECs) to hemophilia A mice and showed that these cells remained sequestered within the implanted matrix and provided therapeutic levels of FVIII. Prior to translating this strategy into the canine (c) model of hemophilia A, we increased cFVIII transgene expression by at least 100-fold with the use of the elongation factor 1 alpha (EF1α) promoter and a strong endothelial enhancer element.

Implantation of scaffold-free engineered cartilage constructs in a rabbit model for chondral resurfacing.

Joint resurfacing techniques offer an attractive treatment for damaged or diseased cartilage, as this tissue characteristically displays a limited capacity for self-repair. While tissue-engineered cartilage constructs have shown efficacy in repairing focal cartilage defects in animal models, a substantial number of cells are required to generate sufficient quantities of tissue for the repair of larger defects. In a previous study, we developed a novel approach to generate large, scaffold-free cartilaginous constructs from a small number of donor cells (20 000 cells to generate a 3-cm(2) tissue construct).

Hemodynamic and behavioral differences after administration of meloxicam, buprenorphine, or tramadol as analgesics for telemeter implantation in mice.

Cannulation of the common carotid artery for chronic, continuous radiotelemetric recording of aortic hemodynamic properties in mice is a highly invasive recovery surgery. Radiotelemetric recording, by its continuous nature, gives the most accurate measurements of hemodynamic variables in experimental animals, and is widely used in the study of cardiovascular diseases including hypertension. The American Heart Association has recommended data acquisition by radiotelemetric recording but did not provide guidelines regarding postoperative analgesic support.

Development of large engineered cartilage constructs from a small population of cells.

Confronted with articular cartilage's limited capacity for self-repair, joint resurfacing techniques offer an attractive treatment for damaged or diseased tissue. Although tissue engineered cartilage constructs can be created, a substantial number of cells are required to generate sufficient quantities of tissue for the repair of large defects. As routine cell expansion methods tend to elicit negative effects on chondrocyte function, we have developed an approach to generate phenotypically stable, large-sized engineered constructs (≥3 cm(2) ) directly from a small amount of donor tissue or cells (as little as 20,000 cells to generate a 3 cm(2) tissue construct).

Sensitivity of modified Biel-maze task, compared with Y-maze task, to measure spatial learning and memory deficits of ethanol teratogenicity in the guinea pig.

Ethanol consumption during pregnancy can produce a variety of teratogenic effects in offspring, termed Fetal Alcohol Spectrum Disorders (FASD). The most debilitating and permanent consequence of chronic prenatal ethanol exposure (CPEE) is neurobehavioral teratogenicity, which often manifests as cognitive and behavioral impairments, including deficits in spatial learning and memory. This study tested the hypothesis that a modified dry-land version of the multi-choice Biel-maze task is more sensitive than the rewarded-alternation Y-maze task for the determination of spatial learning and memory deficits of ethanol teratogenicity.

Comparison of buprenorphine and meloxicam for postsurgical analgesia in rats: effects on body weight, locomotor activity, and hemodynamic parameters.

Buprenorphine is administered to humans and animals for postoperative pain management, although its use is associated with complications. Alternative analgesics, including the nonsteroidal antiinflammatory meloxicam, are available, but information on their postoperative effects is limited. The objective of the present study was to compare buprenorphine (0.

The efficacy of orally dosed ketamine and ketamine/medetomidine compared with intramuscular ketamine in rhesus macaques (Macaca mulatta) and the effects of dosing route on haematological stress markers.

Background: This study compared the efficacy of two orally-dosed (PO) anaesthetic regimens for chemical immobilization in rhesus macaques (Macaca mulatta), versus the standard protocol of intramuscular (TM) ketamine. In addition, the effects of dosing route on haematological stress markers were evaluated.

Methods: Testing was conducted on 18 chronically housed animals.

Development of a rapid and sensitive LC-ESI/MS/MS assay for the quantification of propofol using a simple off-line dansyl chloride derivatization reaction to enhance signal intensity.

A rapid, selective and sensitive method was developed for the determination of propofol concentration using an off-line dansyl chloride derivatization step to enhance signal intensity. The method consisted of a protein precipitation extraction followed by derivatization with dansyl chloride and analysis by liquid chromatography ionspray tandem mass spectrometry (LC-ESI/MS/MS). The separation was achieved using a 100 mm x 2 mm C8 analytical column combined with an isocratic mobile phase composed of 80:20 acetonitrile: 0.