Project description:The aim of this first study was to reveal the new potential biomarkers by a metabolomics approach in severe septic calves. Sepsis is a common cause of morbidity and mortality in newborn dairy calves. The main challenges with the use of biomarkers of sepsis in domestic animals are their availability, cost, and time required to obtain a result. Metabolomics may offer the potential to identify biomarkers that define calf sepsis in terms of combined clinical, physiological, and pathobiological abnormalities. To our knowledge, this is the first study presenting an NMR- (nuclear magnetic resonance-) based plasma metabolomics at set intervals in neonatal septic calves. Twenty neonatal dairy calves with severe sepsis and ten healthy calves were used. Hematological and biochemical health profiles were gathered in plasma samples at set intervals. Similarly, NMR spectra were acquired. All diseased animals (except one) died after 72 hours. Clinical and laboratory results were in accordance with those of severe septic animals. Multivariate analysis on NMR plasma spectra proved to be an excellent tool for faster identification of calves with severe sepsis from healthy animals. The NMR-based metabolomic profile may contribute to the better understanding of severe sepsis in newborn calves.
Project description:The effective performance of fetal cardiac examination using spatiotemporal image correlation (STIC) technology requires 2 essential steps: volume acquisition and postprocessing. An important prerequisite is training sonologists to acquire high-quality volume data sets so that when analyzed, such volumes are informative. This article is part 2 of a series on 4-dimensional sonography with STIC. Part 1 focused on STIC technology and its features, the importance of operator training/experience and acquisition of high-quality STIC volumes, factors that affect STIC volume acquisition rates, and general recommendations on performing 4D sonography with STIC. In part 2, we discuss a detailed and practical stepwise approach for STIC volume acquisition, along with methods to determine whether such volumes are appropriate for analysis.
Project description:Four-dimensional sonography with spatiotemporal image correlation (STIC) technology allows acquisition of a fetal cardiac volume data set and displays a cine loop of a complete single cardiac cycle in motion. Part 1 of this 2-part article reviews STIC technology and its features, the importance of operator training/experience, and acquisition of high-quality STIC volumes, as well as factors that affect STIC volume acquisition rates. We also propose a detailed and practical stepwise approach to performing 4-dimensional sonography with STIC and begin herein by providing general recommendations. Part 2 will discuss specifics of the approach, along with how to determine whether such volumes are appropriate for analysis.
Project description:This Article presents, for the first time to our knowledge, an untargeted nuclear magnetic resonance (NMR) metabolomic characterization of the polar intracellular metabolic adaptations of human adipose-derived mesenchymal stem cells during osteogenic differentiation. The use of mesenchymal stem cells (MSCs) for bone regeneration is a promising alternative to conventional bone grafts, and untargeted metabolomics may unveil novel metabolic information on the osteogenic differentiation of MSCs, allowing their behavior to be understood and monitored/guided toward effective therapies. Our results unveiled statistically relevant changes in the levels of just over 30 identified metabolites, illustrating a highly dynamic process with significant variations throughout the whole 21-day period of osteogenic differentiation, mainly involving amino acid metabolism and protein synthesis; energy metabolism and the roles of glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation; cell membrane metabolism; nucleotide metabolism (including the specific involvement of O-glycosylation intermediates and NAD+); and metabolic players in protective antioxidative mechanisms (such as glutathione and specific amino acids). Different metabolic stages are proposed and are supported by putative biochemical explanations for the metabolite changes observed. This work lays the groundwork for the use of untargeted NMR metabolomics to find potential metabolic markers of osteogenic differentiation efficacy.
Project description:IntroductionThe immune compartment within fetal chorionic villi is comprised of fetal Hofbauer cells (HBC) and invading placenta-associated maternal monocytes and macrophages (PAMM). Recent studies have characterized the transcriptional profile of the first trimester (T1) placenta; however, the phenotypic and functional diversity of chorionic villous immune cells at term (T3) remain poorly understood.MethodsTo address this knowledge gap, immune cells from human chorionic villous tissues obtained from full-term, uncomplicated pregnancies were deeply phenotyped using a combination of flow cytometry, single-cell RNA sequencing (scRNA-seq, CITE-seq) and chromatin accessibility profiling (snATAC-seq).ResultsOur results indicate that, relative to the first trimester, the frequency of fetal macrophages (HBC, proliferating HBC) is significantly reduced, whereas that of infiltrating maternal monocytes/macrophages (PAMM1b, PAMM1a, PAMM2, MAC_1) increased in T3. PAMM1b and HBCs exhibit the most phagocytic capacity at term highlighting their regulatory role in tissue homeostasis in late pregnancy. The transcriptional profiles of resident villous immune subsets exhibit a heightened activation state relative to the relative to T1, likely to support labor and parturition. Additionally, we provide one of the first insights into the chromatin accessibility profile of villous myeloid cells at term. We next stratified our findings by pre-pregnancy BMI since maternal pregravid obesity is associated with several adverse pregnancy outcomes. Pregravid obesity increased inflammatory gene expression, particularly among HBC and PAMM1a subsets, but dampened the expression of antimicrobial genes, supporting a tolerant-like phenotype of chorionic villous myeloid cells. We report a decline in HBC abundance accompanied by an increase in infiltrating maternal macrophages, which aligns with reports of heightened chorionic villous inflammatory pathologies with pregravid obesity. Finally, given the shared fetal yolk-sac origin of HBCs and microglia, we leveraged an in vitro model of umbilical cord blood-derived microglia to investigate the impact of pregravid obesity on fetal neurodevelopment. Our findings reveal increased expression of activation markers albeit dampened phagocytic capacity in microglia with pregravid obesity.DiscussionOverall, our study highlights immune adaptations in the fetal chorionic villous with gestational age and pregravid obesity, as well as insight towards microglia dysfunction possibly underlying poor neurodevelopmental outcomes in offspring of women with pregravid obesity.