Accumulation of alkyl-lysophosphatidylcholines in Niemann-Pick disease type C1.

Lysosomal function is impaired in Niemann-Pick disease type C1 (NPC1), a rare and inherited neurodegenerative disorder, resulting in late endosomal/lysosomal accumulation of unesterified cholesterol. The precise pathogenic mechanism of NPC1 remains incompletely understood. In this study, we employed metabolomics to uncover secondary accumulated substances in NPC1.

Loss of Lymphatic IKKα Disrupts Lung Immune Homeostasis, Drives BALT Formation, and Protects against Influenza.

IκB kinase (IKK)α controls noncanonical NF-κB signaling required for lymphoid organ development. We showed previously that lymph node formation is ablated in IkkαLyve-1 mice constitutively lacking IKKα in lymphatic endothelial cells (LECs). We now reveal that loss of IKKα in LECs leads to the formation of BALT in the lung.

Sodium glucose transporter 2 inhibitors: Will these drugs benefit non-diabetic veterinary patients with cardiac and kidney diseases?

Sodium glucose transporter type 2 (SGLT2) inhibitors have been introduced into human medicine where their beneficial effects go beyond the expected improvement in blood glucose control. These drugs appear to prevent progression of both cardiovascular and kidney diseases, not only in diabetic but also in non-diabetic human patients. As these drugs have received conditional approval for use in diabetic cats and are being used in other veterinary species, the intriguing question as to whether they will have similar cardioprotective and nephroprotective effects in dogs and cats is being asked.

α- or β-Adrenergic blockade does not affect transplanted islet cell responses to hypoglycemia in type 1 diabetes.

Type 1 diabetes recipients of intrahepatic islet transplantation exhibit glucose-dependent suppression of insulin and activation of glucagon secretion in response to insulin-induced hypoglycemia associated with clinical protection from hypoglycemia. Whether sympathetic activation of adrenergic receptors on transplanted islets is required for these responses in defense against hypoglycemia is not known. To evaluate the adrenergic contribution to posttransplant glucose counterregulation, we performed a randomized, double-blind crossover study of responses during a hyperinsulinemic euglycemic-hypoglycemic clamp under phentolamine (α-adrenergic blockage), propranolol (β-adrenergic blockage), or placebo infusion.

Human red blood cells express the RNA sensor TLR7.

Red blood cells (RBCs) express the nucleic acid-binding toll-like receptor 9 (TLR9) and bind CpG-containing DNA. However, whether human RBCs express other nucleic acid-binding TLRs is unknown. Here we show that human RBCs express the RNA sensor TLR7.

Prolonged administration of oral phenylbutazone and firocoxib in horses has no impact on selected cytokine and growth factor concentrations in platelet-rich plasma and autologous protein solution.

Objective: To determine the effects of prolonged administration of the oral NSAIDs phenylbutazone and firocoxib on concentrations of cytokines and growth factors in platelet-rich plasma (PRP) and autologous protein solution (APS).

Animals: 6 adult University owned horses.

Methods: Horses were randomized to receive phenylbutazone (1 g, orally, q 12 h) or firocoxib (57 mg, orally, q 24 h) for 6 days.

Opioid-related xylazine toxicity manifesting as myonecrosis, rhabdomyolysis, multifocal ischemic cerebral infarcts, and cerebral edema.

This article provides a report of a case of organ dysfunction, myonecrosis, rhabdomyolysis, multifocal ischemic cerebral infarcts, and cerebral edema after a patient's use of xylazine and fentanyl. Within the US opioid epidemic, xylazine is emerging as a troubling national sub-story. The prevalence of xylazine within illicitly manufactured opioids and the proportion of opioid-involved overdose deaths with detected xylazine are rising dramatically, the latter increasing 276% between 2019 and 2022.

Saturated fatty acid concentrations are predictive of insulin sensitivity and beta cell compensation in dogs.

Chronic feeding of a high fat diet (HFD) in preclinical species induces broad metabolic dysfunction characterized by body weight gain, hyperinsulinemia, dyslipidemia and impaired insulin sensitivity. The plasma lipidome is not well characterized in dogs with HFD-induced metabolic dysfunction. We therefore aimed to describe the alterations that occur in the plasma lipid composition of dogs that are fed a HFD and examine the association of these changes with the clinical signs of metabolic dysfunction.

Approach to Immune-mediated Ocular Diseases.

Immune-mediated ocular inflammation is a common clinical diagnosis reached for horses with keratitis and uveitis. This diagnosis is made as a diagnosis of exclusion following a thorough effort to rule out an underlying cause for the inflammation, most importantly infectious and neoplastic disease. Practically, response to ophthalmic and systemic anti-inflammatory or immunomodulatory medications is used to support a diagnosis of immune-mediated ocular inflammation; however, such medications are often contraindicated in the face of infection or neoplasia.

Estimation of glucose absorption, insulin sensitivity, and glucose effectiveness from the oral glucose tolerance test.

Context: Glucose tolerance during an oral glucose tolerance test (OGTT) is affected by variations in glucose effectiveness (GE) and glucose absorption and thus affects minimal model calculations of insulin sensitivity (SI). The widely used OGTT SI by Dalla Man et al. does not account for variances in GE and glucose absorption.

Transvaginal aspiration, oocyte maturation and production of blastocysts and a pregnancy via ICSI in an endangered breed: Baudet du Poitou donkey.

Two Poitou donkey jennies were presented for clinical oocyte recovery and embryo production via intracytoplasmic sperm injection (ICSI). Both jennies underwent transvaginal ultrasound-guided follicle aspiration on two occasions. Recovered oocytes were held overnight then placed into maturation culture, using standard methods for mare oocytes.

Gilts prefer an open pen to a stall.

Stalls or crates are a very common type of housing used on pig farms that restrict an animal's movement. How this confinement impacts the animal's affective states is seldom investigated. We conducted a preference test over 7 days where trios of gilts (n = 10 trios, 27.

Modulation of recovery from neonatal hyperoxic lung injury by sex as a biological variable.

Recovery from lung injury during the neonatal period requires the orchestration of many biological pathways. The modulation of such pathways can drive the developing lung towards proper repair or persistent maldevelopment that can lead to a disease phenotype. Sex as a biological variable can regulate these pathways differently in the male and female lung exposed to neonatal hyperoxia.

Comparison of four in vitro test methods to assess nucleus pulposus replacement device expulsion risk.

Background: Nucleus replacement devices (NRDs) are not routinely used in clinic, predominantly due to the risk of device expulsion. Rigorous in vitro testing may enable failure mechanisms to be identified prior to clinical trials; however, current testing standards do not specify a particular expulsion test. Multiple methods have therefore been developed, complicating comparisons between NRD designs.

Perception of vocoded speech in domestic dogs.

Humans have an impressive ability to comprehend signal-degraded speech; however, the extent to which comprehension of degraded speech relies on human-specific features of speech perception vs. more general cognitive processes is unknown. Since dogs live alongside humans and regularly hear speech, they can be used as a model to differentiate between these possibilities.

Applications and Opportunities for Immune Cell CAR Engineering in Comparative Oncology.

Chimeric antigen receptor (CAR) T-adoptive cell therapy has transformed the treatment of human hematologic malignancies. However, its application for the treatment of solid tumors remains challenging. An exciting avenue for advancing this field lies in the use of pet dogs, in which cancers that recapitulate the biology, immunological features, and clinical course of human malignancies arise spontaneously.

Iterative oxidation by TET1 is required for reprogramming of imprinting control regions and patterning of mouse sperm hypomethylated regions.

Ten-eleven translocation (TET) enzymes iteratively oxidize 5-methylcytosine (5mC) to generate 5-hydroxymethylcytosine (5hmC), 5-formylcytosine, and 5-carboxylcytosine to facilitate active genome demethylation. Whether these bases are required to promote replication-coupled dilution or activate base excision repair during mammalian germline reprogramming remains unresolved due to the inability to decouple TET activities. Here, we generated two mouse lines expressing catalytically inactive TET1 (Tet1-HxD) and TET1 that stalls oxidation at 5hmC (Tet1-V).

Biomaterial-mediated intracellular control of macrophages for cell therapy in pro-inflammatory and pro-fibrotic conditions.

Macrophages are key modulators of all inflammatory diseases and essential for their resolution, making macrophage cell therapy a promising strategy for regenerative medicine. However, since macrophages change rapidly in response to microenvironmental cues, their phenotype must be controlled post-administration. We present a tunable biomaterial-based strategy to control macrophages intracellularly via small molecule-releasing microparticles.

Equine mesenchymal stem cell-derived extracellular vesicle productivity but not overall yield is improved via 3-D culture with chemically defined media.

Objective: Mesenchymal stem cell (MSC) extracellular vesicles (EVs) have emerged as a biotherapeutic for osteoarthritis; however, manufacturing large quantities is not practical using traditional monolayer (2-D) culture. We aimed to examine the effects of 3-D and 2-D culture 2 types of media: Dulbecco modified Eagle medium and a commercially available medium (CM) on EV yield.

Animals: Banked bone marrow-derived MSCs (BM-MSCs) from 6 healthy, young horses were used.

Computed tomographic diagnosis of a common bile duct abscess and secondary extrahepatic biliary duct obstruction in a potbelly pig.

A potbelly pig was evaluated for anorexia and icterus. Clinicopathologic abnormalities suggested an active inflammatory hepatobiliary process. Ultrasound and CT of the abdomen revealed an extrahepatic biliary obstruction of the common bile duct (CBD).

National Institute on Drug Abuse Clinical Trials Network Meeting Report: Managing Patients Exposed to Xylazine-Adulterated Opioids in Emergency, Hospital and Addiction Care Settings.

Used as a veterinary sedative and not approved for human use, xylazine has been increasingly linked with opioid overdose deaths in the United States. A growing number of people have been exposed to xylazine in the illicit opioid supply (especially fentanyl) or in other drugs, particularly in some areas of the Northeast. Xylazine is an α-2 adrenergic agonist that decreases sympathetic nervous system activity.