Background: A systemic and dysregulated immune response to infection contributes to morbidity and mortality associated with sepsis. Peripheral blood-derived mesenchymal stromal cells (PB-MSC) mitigate inflammation in animal models of sepsis. Allogeneic PB-MSC administered IV to horses is well-tolerated but therapeutic benefits are unknown. Hypothesis: After IV lipopolysaccharide (LPS) infusion, horses treated with PB-MSC would have less severe clinical signs, clinicopathological abnormalities, inflammatory cytokine gene expression, and oxidative stress compared to controls administered a placebo. Animals: Sixteen horses were included in this study. Methods: A randomized placebo-controlled experimental trial was performed. Sixteen healthy horses were assigned to 1 of 2 treatment groups (1 × 109 PB-MSC or saline placebo). Treatments were administered 30 minutes after completion of LPS infusion of approximately 30 ng/kg. Clinical signs, clinicopathological variables, inflammatory cytokine gene expression, and oxidative stress markers were assessed at various time points over a 24-hour period. Results: A predictable response to IV LPS infusion was observed in all horses. At the dose administered, there was no significant effect of PB-MSC on clinical signs, clinicopathological variables, or inflammatory cytokine gene expression at any time point. Antioxidant potential was not different between treatment groups, but intracellular ROS increased over time in the placebo group. Other variables that changed over time were likely due to effects of IV LPS infusion. Conclusions and Clinical Importance: Administration of allogeneic PB-MSC did not cause clinically detectable adverse effects in healthy horses. The dose of PB-MSC used here is unlikely to exert a beneficial effect in endotoxemic horses.

Stress is a complex but poorly understood topic, especially in commercial poultry species. However, hypothalamic-pituitary-adrenal axis (HPA) activation through either exogenous glucocorticoid or adrenocorticotropic hormone (ACTH) administration in birds generally results in increased circulating glucocorticoid levels, often associated with stress. HPA activation responses are complicated by physiological changes while the birds mature and enter production. The objective of this study was to evaluate changes in HPA activation in relation to physiological age of the bird. Ten each of Lohmann LSL-Lite hens received either a saline-mannitol or synthetic ACTH (ACTH1-24) injection at 6, 17, and 26 weeks of age (WOA). Blood was collected prior to ACTH injections, and one-, and two-hours post-injection. From these blood samples, white blood cell (WBC) differential counts, heterophil:lymphocyte (H:L) ratios (N = 10/treatment), and corticosterone and cortisol levels were measured using a high-performance liquid chromatography (HPLC) system coupled to a mass spectrometer (MS/MS) (N = 5/treatment). At 26 weeks of age, egg albumen samples were collected and corticosterone and cortisol measured using an HPLC system coupled to a mass spectrometer (MS/MS) (N = 5/treatment). In this study, plasma cortisol was unaffected by treatment and egg albumen corticosterone and cortisol were below detectable limits at all time points for both treatments. Plasma corticosterone increased 1 h after injection in the ACTH group at all ages; this was significant at 17 WOA (P < 0.0001). The H:L ratio was not affected by treatment but heterophils increased and lymphocytes decreased in the ACTH group compared to the control group, this difference was observed at 26 WOA (P < 0.0004). The results of this study suggest that the H:L ratio is not an accurate measure of acute HPA activation during the pullet phase and that plasma cortisol and albumen corticosterone and cortisol are not an accurate measure of acute HPA activation during the pullet or adult phases. Corticosterone may have some utility in capturing a physiological stress response in pullets and adult hens but requires further investigation.

Management choices during the pullet phase can affect behavior, welfare, and health later in life, but few studies have evaluated the pullet phase, particularly in extensive housing systems. This study was a 2 × 2 factorial randomized complete block design (RCBD) with two strains and two stocking densities. The Lohmann LB-Lite and Lohmann LSL-Lite were housed on the floor at high-stocking density (619–670 cm²/bird) and low-stocking density (1249–1352 cm²/bird), which changed with age from 2 to 16 weeks of age (WOA). Bird-based measures of appearance, blood parameters, organ measurements, and production values were evaluated. Stocking density alone affected (p < 0.05) only relative bursal weight (% of body weight)—3.32% in the low-density versus 3.08% in the high-density group. High-stocking density was correlated with decreased uniformity (high—89.33 ± 0.24%; low—90.41 ± 0.24; p < 0.02) and worse feather coverage in the brown strain. High-stocking density was correlated with greater uniformity (High—90.39 ± 0.24%; Low—88.47 ± 0.24%; p < 0.001) and better feather coverage in the white strain. This study’s feed conversion ratio (FCR) was improved by 0.07 in the low-stocking density for both strains. The remaining parameters were affected by strain and age only. Thus, while stocking density effects vary slightly depending on the strain used, cage-free pullets had limited negative effects at both the high and low-stocking densities tested in this study; there were few to no changes in the numerous bird-based welfare parameters tested.

Background: Folate, an essential vitamin B9, is crucial for diverse biological processes, including neurogenesis. Folic acid (FA) supplementation during pregnancy is a standard practice for preventing neural tube defects (NTDs). However, concerns are growing over the potential risks of excessive maternal FA intake. Objectives/Methods: Here, we employed a mouse model and spatial transcriptomic and single-nucleus multi-omics approaches to investigate the impact of high maternal FA supplementation during the periconceptional period on offspring brain development. Results: Maternal high FA supplementation affected gene pathways linked to neurogenesis and neuronal axon myelination across multiple brain regions, as well as gene expression alterations related to learning and memory in thalamic and ventricular regions. Single-nucleus multi-omics analysis revealed that maturing excitatory neurons in the dentate gyrus (DG) are particularly vulnerable to high maternal FA intake, leading to aberrant gene expressions and chromatin accessibility in pathways governing ribosomal biogenesis critical for synaptic formation. Conclusions: Our findings provide new insights into specific brain regions, cell types, gene expressions and pathways that can be affected by maternal high FA supplementation.