Objective: Characterize association between hydrocortisone receipt and hospital outcomes of infants with persistent pulmonary hypertension of the newborn (PPHN). Study design: Cohort study of infants ≥34 weeks with PPHN who received inhaled nitric oxide at <7 days of age (2010–2016). We generated propensity scores, and performed inverse probability weighted regression to estimate hydrocortisone effect on outcomes: death, chronic lung disease (CLD), oxygen at discharge. Results: Of 2743 infants, 30% received hydrocortisone, which was associated with exposure to mechanical ventilation, sedatives, paralytics, or vasopressors (p<0.001). There was no difference in death, CLD, or oxygen at discharge. In infants with meconium aspiration syndrome, hydrocortisone was associated with decreased oxygen at discharge (odds ratio 0.56; 95% confidence interval 0.21, 0.91). Conclusions: There was no association between hydrocortisone receipt and death, CLD, or oxygen at discharge in our cohort. Prospective studies are needed to evaluate the effectiveness of hydrocortisone in infants with PPHN.

This study aimed to investigate the changes in abomasum transcriptome and the associated microbial community structure in young calves with artificially dosed, adult rumen contents. Eight young bull calves were randomly dosed with freshly extracted rumen contents from an adult cow (high efficiency (HE), n = 4), or sterilized rumen content (Con, n = 4). The dosing was administered within 3 days of birth, then at 2, 4, and 6 weeks following the initial dosing. Abomasum tissues were collected immediately after sacrifice at 8 weeks of age. Five genera (Tannerella, Desulfovibrio, Deinococcus, Leptotrichia, and Eubacterium; P < 0.05) showed significant difference in abundance between the treatments. A total of 975 differentially expressed genes were identified (P < 0.05, fold-change > 1.5, mean read-counts > 5). Pathway analysis indicated that up-regulated genes were involved in immune system process and defense response to virus, while the down-regulated genes involved in ion transport, ATP biosynthetic process, and mitochondrial electron transport. Positive correlation (r > 0.7, P < 0.05) was observed between TRPM4 gene and Desulfovibrio, which was significantly higher in the HE group. TRPM4 had a reported role in the immune system process. In conclusion, the dosing of adult rumen contents to calves can alter not only the composition of active microorganisms in the abomasum but also the molecular mechanisms in the abomasum tissue, including reduced protease secretion and decreased hydrochloric acid secretion.

Diet-induced acidosis imposes a health risk to young calves. In this study, we aimed to investigate the host jejunum transcriptome changes, along with its microbial community variations, using our established model of feed-induced ruminal acidosis in young calves. Eight bull calves were randomly assigned to two diet treatments beginning at birth (a starch-rich diet, Aci; a control diet, Con). Whole-transcriptome RNA sequencing was performed on the jejunum tissues collected at 17 weeks of age. Ribosomal RNA reads were used for studying microbial community structure variations in the jejunum. A total of 853 differentially expressed genes were identified (402 upregulated and 451 downregulated) between the two groups. The cell cycle and the digestion and absorption of protein in jejunal tissue were affected by acidosis. Compared to the control, genera of Campylobacter, Burkholderia, Acidaminococcus, Corynebacterium, and Olsenella significantly increased in abundance in the Aci group, while Lachnoclostridium and Ruminococcus were significantly lower in the Aci group. Expression changes in the AXL gene were associated with the abundance variations of a high number of genera in jejunum. Our study provided a snapshot of the transcriptome changes in the jejunum and its associated meta-transcriptome changes in microbial communities in young calves with feed-induced acidosis.

Lipid-related metabolic disorders (LRMD) are prevalent in early lactation dairy cows, and have detrimental effects on productivity and health. Our objectives were to identify cows resistant or susceptible to LRMD using a ketosis induction protocol (KIP) to discover differentially expressed liver genes and metabolic pathways associated with disposition. Clustering cows based on postpartum lipid metabolite concentrations within dietary treatments identified cows more or less susceptible (MS vs. LS) to LRMD within the control treatment, and more or less resistant (MR vs. LR) within the KIP treatment. Whole-transcriptome RNA sequencing was performed on liver samples (−28, +1, and +14 days relative to calving) to assess differential gene and pathway expression (LS vs. MS; MR vs. LR; n = 3 cows per cluster). Cows within the MS and LR clusters had evidence of greater blood serum β-hydroxybutyrate concentration and liver triglyceride content than the LS and MR clusters, respectively. The inferred metabolism of differentially expressed genes suggested a role of immune response (i.e., interferon-inducible proteins and major histocompatibility complex molecules). Additionally, unique roles for glutathione metabolism and eicosanoid metabolism in modulating susceptibility and resistance, respectively, were implicated. Overall, this research provides novel insight into the role of immunometabolism in LRMD pathology, and suggests the potential for unique control points for LRMD progression and severity.