Building a nonclinical pathology laboratory of the future for pharmaceutical research excellence.

We describe a roadmap for a fully digital artificial intelligence (AI)-augmented nonclinical pathology laboratory across three continents. Underpinning the design are Good Laboratory Practice (GLP)-validated laboratory information management systems (LIMS), whole slide-scanners (WSS), image management systems (IMS), and a digital microscope intended for use by the nonclinical pathologist. Digital diagnostics are supported by tools that include AI-based virtual staining and deep learning-based decision support. Implemented during the COVID-19 pandemic, the initial digitized workflow largely mitigated disruption of pivotal nonclinical studies required to support pharmaceutical clinical testing. We believe that this digital transformation of our nonclinical pathology laboratories will promote efficiency and innovation in the future and enhance the quality and speed of drug development decision making.

Does prebiotic feeding affect equine gastric health? A study on the effects of prebiotic-induced gastric butyric acid production on mucosal integrity of the equine stomach.

Fructo-oligosaccharides are commonly administered as prebiotics to horses in order to reduce the risk of disruption of microbial populations in the hindgut. Their microbial degradation to SCFA already begins in the stomach potentially resulting in increased gastric concentrations of SCFA such as butyric acid. The impact of butyric acid on the squamous mucosa is postulated to be detrimental, its effects on the glandular mucosa are yet unknown. Thus, the aim of this study was to determine the effects of butyric acid exposure on the functional integrity and morphology of the equine nonglandular and glandular gastric mucosa using butyric acid concentrations equivalent to the ones found in horses subjected to prebiotic fructo-oligosaccharides feeding. Gastric mucosal samples of healthy horses were exposed to butyric acid using the in vitro Ussing chamber technique. Electrophysiological parameters were continuously monitored, mucosal samples were blinded and histomorphological analysis was performed using a scoring system for assessment of histopathologic changes. Exposure to butyric acid resulted in pathohistomorphological changes in the glandular mucosa and in impairment of functional mucosal integrity in the squamous and the glandular mucosa as documented by significant changes in tissue conductances (Gt). Administration of fructo-oligosaccharides as a preventive prebiotic measure to horses should therefore be carefully considered, particularly in horses known to be at risk of developing EGUS.

Equine atypical myopathy caused by hypoglycin A intoxication associated with ingestion of sycamore maple tree seeds.

REASONS FOR PERFORMING STUDY: Evidence suggest there is a link between equine atypical myopathy (EAM) and ingestion of sycamore maple tree seeds. OBJECTIVES: To further evaluate the hypothesis that the ingestion of hypoglycin A (HGA) containing sycamore maple tree seeds causes acquired multiple acyl-CoA dehydrogenase deficiency and might be associated with the clinical and pathological signs of EAM. STUDY DESIGN: Case report. METHODS: Necropsy and histopathology, using hematoxylin and eosin and Sudan III stains, were performed on a 2.5-year-old mare that died following the development of clinical signs of progressive muscle stiffness and recumbency. Prior to death, the animal ingested sycamore maple tree seeds (Acer pseudoplatanus). Detection of metabolites in blood and urine obtained post mortem was performed by rapid ultra-performance liquid chromatography-tandem mass spectrometry. Data from this case were compared with 3 geldings with no clinical history of myopathy. RESULTS: Macroscopic examination revealed fragments of maple tree seeds in the stomach and severe myopathy of several muscle groups including Mm. intercostales, deltoidei and trapezii. Histologically, the affected muscles showed severe, acute rhabdomyolysis with extensive accumulation of finely dispersed fat droplets in the cytoplasm of degenerated skeletal muscle cells not present in controls. Urine and serum concentrations of several acyl carnitines and acyl glycines were increased, and both contained metabolites of HGA, a toxic amino acid present in sycamore maple tree seeds. CONCLUSIONS: The study supports the hypothesis that ingestion of HGA-containing maple tree seeds may cause EAM due to acquired multiple acyl-CoA dehydrogenase deficiency.