Increased functional potency of multi-edited CAR-T cells manufactured by a non-viral transfection system.

Chimeric antigen receptor (CAR)-T cell therapy represents a breakthrough for the treatment of hematological malignancies. However, to treat solid tumors and certain hematologic cancers, next-generation CAR-T cells require further genetic modifications to overcome some of the current limitations. Improving manufacturing processes to preserve cell health and function of edited T cells is equally critical.

Current practices in equine minimally invasive soft tissue surgery.

Equine minimally invasive surgical techniques are frequently utilized in the treatment of a variety of conditions. Standing sedated endoscopic surgery is commonly selected in horses, requiring specialized facilities, anesthetic protocols, and surgeon and assistant expertise. This review examines current methods and potential strategies in equine soft tissue surgery, in which there is an emphasis on laparoscopic urogenital and gastrointestinal diagnostic and therapeutic procedures.

Emergency Standing Laparoscopic Treatment of Uncontrolled Post-Castration Hemorrhage in Two Geldings.

Background: Persistent hemorrhage of testicular vessels is a potentially life-threatening complication of equine castration. Frequently, general anesthesia is required to retrieve and ligate the bleeding vasculature when standing wound packing and retrieval of the spermatic cord are unsuccessful. We propose standing laparoscopic ligation of the testicular arteries via the paralumbar fossa as a rapid, effective means of halting hemorrhage while avoiding castration site trauma as well as the cardiovascular and recovery risks of general anesthesia.

Cardiac Disease Related to Primary Hyperthyroidism in a 20-Year-Old Mule.

Primary hyperthyroidism is a rarely diagnosed endocrinopathy in equids and there have been no previous reports of structural and functional cardiac changes associated with hyperthyroidism in these species. This case report investigates a 20-year-old mule gelding that presented for a three-month history of thin body condition despite polyphagia, with a heart murmur and elevated free and total thyroid hormone concentrations. On presentation, physical exam revealed a body condition score of two out of nine, persistent tachycardia, pansystolic heart murmur and firm bilateral ventral proximal cervical masses.

Resolution of chronic regurgitation in an 8 month old Babydoll sheep by thoracoscopic treatment of a vascular ring anomaly.

Objective: The objective was to describe the successful thoracoscopic treatment of esophageal entrapment resulting from a vascular ring anomaly (VRA) comprising a persistent right aortic arch (PRAA) and left ligamentum arteriosum (LA) in a Babydoll sheep wether.

Study Design: Case report.

Animal: Eight month old Babydoll sheep wether, 13 kg.

β-glucans from mushroom products drive Trained Immunity.

Introduction: Macrofungi, such as edible mushrooms, have been used as a valuable medical resource for millennia as a result of their antibacterial and immuno-modulatory components. Mushrooms contain dietary fibers known as β-glucans, a class of polysaccharides previously linked to the induction of Trained Immunity. However, little is known about the ability of mushroom-derived β-glucans to induce Trained Immunity.

Recognition of yeast β-glucan particles triggers immunometabolic signaling required for trained immunity.

Fungal β-glucans are major drivers of trained immunity which increases long-term protection against secondary infections. Heterogeneity in β-glucan source, structure, and solubility alters interaction with the phagocytic receptor Dectin-1 and could impact strategies to improve trained immunity in humans. Using a panel of diverse β-glucans, we describe the ability of a specific yeast-derived whole-glucan particle (WGP) to reprogram metabolism and thereby drive trained immunity in human monocyte-derived macrophages and mice bone marrow .

Longitudinal assessment of mitochondrial dysfunction in acute traumatic brain injury using hyperpolarized [1- C]pyruvate.

Purpose: [ C]Bicarbonate formation from hyperpolarized [1- C]pyruvate via pyruvate dehydrogenase, a key regulatory enzyme, represents the cerebral oxidation of pyruvate and the integrity of mitochondrial function. The present study is to characterize the chronology of cerebral mitochondrial metabolism during secondary injury associated with acute traumatic brain injury (TBI) by longitudinally monitoring [ C]bicarbonate production from hyperpolarized [1- C]pyruvate in rodents.

Methods: Male Wistar rats were randomly assigned to undergo a controlled-cortical impact (CCI, n = 31) or sham surgery (n = 22).

Negative Regulation of Innate Immune Signaling by Components of the Button Mushroom Agaricus bisporus.

Scope: Mushrooms are valued as an edible and medical resource for millennia. As macrofungi, they possess conserved molecular components recognized by innate immune cells like macrophages, yet unlike pathogenic fungi, they do not trigger the immune system in the same way. That these well-tolerated foods both avoid immuno-surveillance and have positive health benefits, highlights the dearth of information on the interactions of mushroom-derived products with the immune system.

A Novel Near-Surface Wave-Coherent Instantaneous Profiling System for Atmospheric Measurements.

Large knowledge gaps concerning the effect of ocean surface waves on near-surface vertical distributions of temperature and humidity exist due to practical limitations and sensor fidelity challenges of direct measurements. Measurements of temperature and humidity are classically made using rocket- or radiosondes and fixed weather stations and can utilize a tethered profiling system. However, these measurement systems have limitations when obtaining wave-coherent measurements near the sea surface.

Stress response as a contributing factor in horses with laminitis.

Background: Laminitis is a complex and debilitating disease of horses. Numerous predisposing factors contribute to laminitis development, however the exact pathogenesis remains undetermined. Serum T4, cortisol, and histamine are components of the innate stress response and could play a causative or contributory role.

Shariant platform: Enabling evidence sharing across Australian clinical genetic-testing laboratories to support variant interpretation.

Sharing genomic variant interpretations across laboratories promotes consistency in variant assertions. A landscape analysis of Australian clinical genetic-testing laboratories in 2017 identified that, despite the national-accreditation-body recommendations encouraging laboratories to submit genotypic data to clinical databases, fewer than 300 variants had been shared to the ClinVar public database. Consultations with Australian laboratories identified resource constraints limiting routine application of manual processes, consent issues, and differences in interpretation systems as barriers to sharing.

von Willebrand factor links primary hemostasis to innate immunity.

The plasma multimeric glycoprotein von Willebrand factor (VWF) plays a critical role in primary hemostasis by tethering platelets to exposed collagen at sites of vascular injury. Recent studies have identified additional biological roles for VWF, and in particular suggest that VWF may play an important role in regulating inflammatory responses. However, the molecular mechanisms through which VWF exerts its immuno-modulatory effects remain poorly understood.

Serial venous lactate measurement following gastrointestinal surgery in horses.

Background: Prospective clinical study of blood lactate concentration in horses undergoing colic surgery is needed to determine utility in outcome prediction.

Objectives: To evaluate venous lactate measurements in horses following colic surgery, including immediately after anesthetic recovery and daily throughout hospitalization, as well as to determine if lactate concentrations were significantly higher in horses that developed postoperative complications or did not survive to hospital discharge.

Methods: Horses > 1 year of age undergoing surgery for colic and recovered from general anesthesia were sampled.

Profiling Carbohydrate Metabolism in Liver and Hepatocellular Carcinoma with [C]-Glycerate Probes.

The interplay between glycolysis and gluconeogenesis is central to carbohydrate metabolism. Here, we describe novel methods to assess carbohydrate metabolism using [C]-probes derived from glycerate, a molecule whose metabolic fate in mammals remains underexplored. Isotope-based studies were conducted via NMR and mass spectrometry analyses of freeze-clamped liver tissue extracts after [2,3-C]glycerate infusion.

C-Labeled Diethyl Ketoglutarate Derivatives as Hyperpolarized Probes of 2-Ketoglutarate Dehydrogenase Activity.

The TCA cycle is a central metabolic pathway for energy production and biosynthesis. A major control point of metabolic flux through the cycle is the decarboxylation of 2-ketoglutarate by the TCA cycle enzyme 2-ketoglutarate dehydrogenase (2-KGDH). In this project, we developed C labeled 2-ketoglutarate derivatives to monitor 2-KGDH activity in vivo.

Patient-reported outcomes and neurotoxicity markers in patients treated with bispecific LV20.19 CAR T cell therapy.

Background: With the rising number of chimeric antigen receptor (CAR) T cell treated patients, it is increasingly important to understand the treatment's impact on patient-reported outcomes (PROs) and, ideally, identify biomarkers of central nervous system (CNS) adverse effects.

Methods: The purpose of this exploratory study was to assess short-term PROs and serum kynurenine metabolites for associated neurotoxicity among patients treated in an anti-CD20, anti-CD19 (LV20.19) CAR T cell phase I clinical trial (NCT03019055).

Clinical outcome of horses with guttural pouch infection following transpharyngeal fenestration.

Objective: To report the clinical outcomes of horses with chronic guttural pouch infection characterized by accumulation of mucopurulent material following transpharyngeal diode laser fenestration.

Animals: 13 client-owned horses.

Procedures: Horses undergoing diode laser fenestration for chronic guttural pouch infection were identified by medical record search.

Complications and Comorbidities in Foals Undergoing Surgical Repair for Uroperitoneum.

Surgical repair is frequently effective at resolving uroperitoneum in foals, though complications occur. Despite their occurrence, management strategies used to address these complications, and their impact on survival are not clearly defined. To better describe the complications following surgical correction of uroperitoneum and to document treatment strategies and outcomes after intervention, a multi-center retrospective case series was performed.

A qualitative exploration of motivations and barriers for community leisure organisations' engagement with the Jooay™ mobile app.

Purpose: Participation in leisure activities is key to the physical and mental health of children and adolescents with disabilities. The Jooay™ mobile app aims to link children and adolescents with disability to participation opportunities in their community. This study explored the perspectives of community leisure organisations and their motivations and perceived barriers to be listed as a leisure service on Jooay™.