Transcriptomic analysis reveals a critical role for activating Gα mutations in spontaneous feline hyperthyroidism.

Feline hyperthyroidism (FHT) is a debilitating disease affecting > 10% of elderly cats. It is generally characterised by chronic elevation of thyroid hormone in the absence of circulating TSH. Understanding of the molecular pathogenesis of FHT is currently limited.

Hepatic Gene Expression of Angiogenic and Regeneration Markers in Cats with Congenital Portosystemic Shunts (CPSS).

Congenital portosystemic shunts (CPSS) are vascular anomalies resulting in liver hypoplasia and hepatic insufficiency. Cats with CPSS typically show signs of hepatic encephalopathy associated with increased ammonia, inflammatory cytokines, and oxidative stress. Surgical attenuation of the CPSS results in improved liver function, resolution of clinical signs, and increased portal blood flow.

Can ChatGPT pass the MRCP (UK) written examinations? Analysis of performance and errors using a clinical decision-reasoning framework.

Objective: Large language models (LLMs) such as ChatGPT are being developed for use in research, medical education and clinical decision systems. However, as their usage increases, LLMs face ongoing regulatory concerns. This study aims to analyse ChatGPT's performance on a postgraduate examination to identify areas of strength and weakness, which may provide further insight into their role in healthcare.

Pharmacological and Genetic Disruption of C-Type Natriuretic Peptide () Expression in Zebrafish () Causes Stunted Growth during Development.

Human patients with mutations within or genes (encoding C-type natriuretic peptide (CNP) and guanylyl cyclase-B (GC-B), respectively) display clinical signs associated with skeletal abnormalities, such as overgrowth or short stature. Mice with induced models of or deletion display profound achondroplasia, dwarfism and early death. Recent pharmacological therapies to treat short stature are utilizing long-acting CNP analogues, but the effects of manipulating CNP expression during development remain unknown.

Late-onset cluster seizures and intellectual disability associated with a novel truncation variant in .

variants are known to cause Cornelia de Lange Syndrome (CdLS) which encompasses a clinical spectrum of intellectual disability, dysmorphic features (long or thick eyebrows, a hypomorphic philtrum and small nose) and, in some cases, epilepsy. More recently, truncating variants have been described as the cause of a neurodevelopmental disorder with early-childhood onset drug-resistant epilepsy with seizures that occur in clusters, similar to that seen in -related epilepsy, but without the classical features of CdLS. Here, we report the case of a 28-year-old woman with a heterozygous truncating variant in who unusually presented with seizures at the late age of 12 years and had normal development into adulthood.

A review of the clinical spectrum of disorders and case of developmental and epileptic encephalopathy surviving into adulthood.

Pathogenic variants in are associated with a spectrum of clinical syndromes ranging from Lethal Neonatal Rigidity and Multifocal Seizure syndrome (RMFSL) to Neurodevelopmental Disorder with Cerebellar Atrophy and with or without Seizures (NEDCAS). RMFSL is characterized by early-onset multifocal seizures with microcephaly. Death occurs during infancy although a less severe course with later onset seizures and longer survival into childhood has been described.

Sensitivity of the Natriuretic Peptide/cGMP System to Hyperammonaemia in Rat C6 Glioma Cells and GPNT Brain Endothelial Cells.

C-type natriuretic peptide (CNP) is the major natriuretic peptide of the central nervous system and acts via its selective guanylyl cyclase-B (GC-B) receptor to regulate cGMP production in neurons, astrocytes and endothelial cells. CNP is implicated in the regulation of neurogenesis, axonal bifurcation, as well as learning and memory. Several neurological disorders result in toxic concentrations of ammonia (hyperammonaemia), which can adversely affect astrocyte function.

Efficacy of hypophysectomy for the treatment of hypersomatotropism-induced diabetes mellitus in 68 cats.

Background: Hypersomatotropism (HST) is an increasingly recognized endocrinopathy in cats and is mostly described associated with diabetes mellitus (DM).

Objectives: To evaluate the efficacy and safety of transsphenoidal hypophysectomy in treating HST and DM in cats.

Animals: Sixty-eight client-owned cats with HST and DM treated by transsphenoidal hypophysectomy.

Pituitary Neoplasm Nomenclature Workshop: Does Adenoma Stand the Test of Time?

The designates pituitary neoplasms as adenomas. A proposed nomenclature change to pituitary neuroendocrine tumors (PitNETs) has been met with concern by some stakeholder groups. The Pituitary Society coordinated the Pituitary Neoplasm Nomenclature (PANOMEN) workshop to address the topic.

Natriuretic Peptide Expression and Function in GH3 Somatolactotropes and Feline Somatotrope Pituitary Tumours.

Patients harbouring mutations in genes encoding C-type natriuretic peptide (CNP; ) or its receptor guanylyl cyclase B (GC-B, ) suffer from severe growth phenotypes; loss-of-function mutations cause achondroplasia, whereas gain-of-function mutations cause skeletal overgrowth. Although most of the effects of CNP/GC-B on growth are mediated directly on bone, evidence suggests the natriuretic peptides may also affect anterior pituitary control of growth. Our previous studies described the expression of and in a range of human pituitary tumours, normal human pituitary, and normal fetal human pituitary.

Long-term effect of neutering on plasma luteinising hormone concentration in cats.

Objectives: The objectives of this study were to validate a commercially available luteinising hormone (LH) cat ELISA, to determine whether the increases in plasma LH concentration that occur after neutering are maintained throughout cats' lives and if other factors such as calendar seasons in both intact and neutered cats, and neutering age in neutered cats, influence plasma LH concentrations.

Methods: Stored plasma samples from client-owned cats were used for the measurement of LH concentrations. Clinical data, including age, sex, age at neutering and medical history, were reviewed.

Infectious Causation of Abnormal Host Behavior: and Its Potential Association With Dopey Fox Syndrome.

The apicomplexan parasite , the causative agent of toxoplasmosis, can infect all warm-blooded animals. can subtly alter host behaviors-either through manipulation to enhance transmission to the feline definitive host or as a side-effect, or "constraint," of infection. In humans, infection, either alone or in association with other co-infecting neurotropic agents, has been reliably associated with both subtle behavioral changes and, in some cases, severe neuropsychiatric disorders, including schizophrenia.

Incidence and risk factors for neurological signs after attenuation of a single congenital portosystemic shunt in 50 cats.

Objective: To determine the incidence, outcome, and risk factors for postattenuation neurological signs (PANS) in cats treated for single congenital portosystemic shunts (CPSS).

Study Design: Retrospective cohort study.

Animals: Cats (n = 50) with a single CPSS.

Pilot study assessing the use of cabergoline for the treatment of cats with hypersomatotropism and diabetes mellitus.

Objectives: An affordable and effective treatment is needed to manage feline hypersomatotropism. The aim of this study was to assess whether treatment with oral cabergoline for 90 days in cats with hypersomatotropism and diabetes mellitus improved diabetic and insulin-like growth factor 1 (IGF-1) control.

Methods: This was a prospective cohort non-blinded pilot study enrolling client-owned cats with spontaneously occurring diabetes mellitus and hypersomatotropism.

Minimally Invasive Markers of Stress and Production Parameters in Dairy Cows before and after the Installation of a Voluntary Milking System.

Automatic milking systems (AMS) are a low-labour alternative to conventional parlours, with previous studies demonstrating that cows vary in their ability to cope with the change to AMS. Cortisol expression can be combined with other measures to assess stress: saliva and hair have the advantage of requiring minimally invasive sampling. No work has investigated the long-term impact of introduction of AMS.

Osteoarthritis-related nociceptive behaviour following mechanical joint loading correlates with cartilage damage.

Objective: In osteoarthritis (OA), the pain-structure relationship remains complex and poorly understood. Here, we used the mechanical joint loading (MJL) model of OA to investigate both knee pathology and nociceptive behaviour.

Design: MJL was used to induce OA in the right knees of 12-week-old male C57BL/6 mice (40 cycles, 9N, 3x/week for 2 weeks).

Hormonal Regulation of Glucocorticoid Inactivation and Reactivation in αT3-1 and LβT2 Gonadotroph Cells.

The regulation of reproductive function by glucocorticoids occurs at all levels of the hypothalamo-pituitary-gonadal axis. Within the pituitary, glucocorticoids have been shown to directly alter gene expression in gonadotrophs, indicating that these cell types are sensitive to regulation by the glucocorticoid receptor. Whilst the major glucocorticoid metabolising enzymes, 11β-hydroxysteroid dehydrogenase (11βHSD; HSD11B1 and HSD11B2), have been described in human pituitary adenomas, the activity of these enzymes within different pituitary cell types has not been reported.

Regulation and Function of C-Type Natriuretic Peptide (CNP) in Gonadotrope-Derived Cell Lines.

C-type natriuretic peptide (CNP) is the most conserved member of the mammalian natriuretic peptide family, and is implicated in the endocrine regulation of growth, metabolism and reproduction. CNP is expressed throughout the body, but is particularly abundant in the central nervous system and anterior pituitary gland. Pituitary gonadotropes are regulated by pulsatile release of gonadotropin releasing hormone (GnRH) from the hypothalamus, to control reproductive function.

What can we learn from the hair of the dog? Complex effects of endogenous and exogenous stressors on canine hair cortisol.

Hair is an emerging biological matrix in which to measure chronic HPA axis activity, offering a longer term view into an animal's life. We explored effects of exogenous (e.g.

Pituitary Pathology and Gene Expression in Acromegalic Cats.

The prevalence of GH-secreting pituitary tumors in domestic cats () is 10-fold greater than in humans. The predominant inhibitory receptors of GH-secreting pituitary tumors are somatostatin receptors (SSTRs) and D dopamine receptor (DRD2). The expression of these receptors is associated with the response to somatostatin analog and dopamine agonist treatment in human patients with acromegaly.

Dynamic changes in gene expression and signalling during trophoblast development in the horse.

Equine chorionic girdle trophoblast cells play important endocrine and immune functions critical in supporting pregnancy. Very little is known about the genes and pathways that regulate chorionic girdle trophoblast development. Our aim was to identify genes and signalling pathways active in vivo in equine chorionic girdle trophoblast within a critical 7-days window.

C-Type Natriuretic Peptide (CNP) Inhibition of Interferon-γ-Mediated Gene Expression in Human Endothelial Cells In Vitro.

Cardiovascular diseases, including atherosclerosis, now account for more deaths in the Western world than from any other cause. Atherosclerosis has a chronic inflammatory component involving Th1 pro-inflammatory cytokines such as IFN-γ, which is known to induce endothelial cell inflammatory responses. On the other hand CNP, which acts via its receptors to elevate intracellular cGMP, is produced by endothelium and endocardium and is upregulated in atherosclerosis.

Incidence and risk factors for neurological signs after attenuation of single congenital portosystemic shunts in 253 dogs.

Objective: To determine the incidence, outcome, and risk factors for postattenuation neurological signs (PANS) and seizures after attenuation of single congenital portosystemic shunts (CPSS) in dogs.

Study Design: Retrospective cohort study.

Sample Population: Dogs (N = 253) with single CPSS.

Glial Cells Missing 1 Regulates Equine Chorionic Gonadotrophin Beta Subunit Binding to the Proximal Promoter.

Equine chorionic gonadotrophin (eCG) is a placental glycoprotein critical for early equine pregnancy and used therapeutically in a number of species to support reproductive activity. The factors in trophoblast that transcriptionally regulate eCGβ-subunit (), the gene which confers the hormones specificity for the receptor, are not known. The aim of this study was to determine if glial cells missing 1 regulates promoter activity.

Perturbation of the T cell receptor repertoire occurs with increasing age in dogs.

Immunosenescence is the gradual deterioration in immune system function associated with ageing. This decline is partly due to involution of the thymus, which leads to a reduction in the output of naive T cells into the circulating lymphocyte pool. Expansion of existing naive and memory T cell populations, to compensate for the reduction in thymic output, can lead to reduced diversity in the T cell repertoire with increasing age, resulting in impairment of immune responses to novel antigenic challenges, such as during infection and vaccination.