ABSTRACT. The effect of glucocorticoids in regulating liver angiotensinogen gene expression was studied in chronically instrumented fetal sheep during the last trimester of gestation and was compared with the expression of other hepatic genes (prothrombin, factor IX, and albumin). Four sets of twins were studied at 118 d of gestation, and three sets were studied at 138 d of gestation (term, 145 d). One of each set of twins was infused intraperitoneally with cortisol (5 pmol.mL-'.h-') for 48 h, whereas the other twin received the same volume (1 mL/h) of normal saline. Plasma cortisol concentration increased from 0.32 f 0.12 and 2.7 f 0.12 nmo1/100 mL to 44.2 f 20.0 and 37.7 f 8.2 nmo1/100 mL in 118-and 138-d fetuses, respectively, during the cortisol infusion; no changes were observed in fetuses infused with saline alone. At the end of the infusion period, the animals were anesthetized, the fetal liver was removed, and total cellular RNA was isolated and probed for angiotensinogen, prothrombin, factor IX, and albumin. The results demonstrated that cortisol infusion decreased angiotensinogen mRNA by 61% in 138-d fetuses and albumin mRNA expression by 2.4-fold in 118-d fetuses and by 3.4-fold in 138-d fetuses. On the other hand, cortisol had no effect on fetal factor IX gene expression but increased prothrombin mRNA levels by 65% in 118-d fetuses and 62% in 138-d fetuses. Taken together, our results suggest that, during fetal life, angiotensinogen gene expression is negatively regulated by glucocorticoids. This effect is not universal because cortisol increases fetal prothrombin gene expression. (Pediatr Res 30: 256-260, 1991) Abbreviations SSPE, sodium chloride, sodium phosphate, EDTA creases during the last trimester of gestation but has been shown to decrease in the 1st wk after birth (5).Studies in mature rats have demonstrated that multiple factors, including glucocorticoids, can modulate liver angiotensinogen gene expression (6-9). Less is known about regulation of angiotensinogen mRNA levels in the fetus, but it has been suggested that glucocorticoid hormones play an important role in organ maturation and enzyme induction during fetal life (10, 11). In vitro studies with cultured rat fetal hepatocytes (12) have shown that addition of dexamethasone to culture media causes fetal hepatocytes to express adult levels of mRNA for albumin, tyrosine aminotransferase, and transfemn while decreasing the level of a-fetoprotein mRNA. Information about glucocorticoid effects on gene expression in fetal liver in vivo is more limited and differs from results obtained in vitro. Johnson et al. (13) have shown that tyrosine aminotransferase mRNA is not affected by glucocorticoids in near-term fetal rats but that hormone responsiveness develops postnatally.In an effort to determine if glucocorticoids play a role in the expression of liver angiotensinogen gene during fetal life, we studied the effect of cortisol on the hepatic expression of angiotensinogen gene in chronically instrumented fetal sheep. We also compared the e...

Objectives: There is a paucity of evidence on how to facilitate shared decision-making under real-world conditions and, in particular, whether interventions should target patients, health care providers, or both groups. Our objectives were to assess the comparative effectiveness, feasibility, and acceptability of patient- and provider-targeted interventions for improving shared decision-making about contraceptive methods in a pragmatic trial that prioritised applicability to real-world care. Design: The study design was a 2X2 factorial cluster randomized controlled trial with four arms: (1) video + prompt card ("video"), (2) decision aids + training ("decision aids"), (3) dual interventions ("dual"), and (4) usual care. Clusters were 16 primary and/or reproductive health care clinics that deliver contraceptive care in the Northeast United States. Participants: Participants were people who had completed a health care visit at a participating clinic, were assigned female sex at birth, were aged 15-49 years, were able to read and write English or Spanish, and had not previously participated in the study. Participants were enrolled for 13 weeks before interventions were implemented in clinics (pre-implementation cohort) and for 26 weeks after interventions were implemented in clinics (post-implementation cohort). 5,018 participants provided data on at least one study outcome. Interventions: Interventions were a video and prompt card that encourage patients to ask three specific questions in the health care visit and a suite of decision aids on contraceptive methods and training for providers in how to use them to facilitate shared decision-making with patients in the health care visit. Main outcome measures: The primary outcome was shared decision-making about contraceptive methods. Secondary outcomes spanned psychological, behavioural, and health outcomes. All outcomes were patient-reported via surveys administered immediately, four weeks, and six months after the health care visit. Results: We did not observe any between-arm difference in the differences in shared decision-making between the pre- and post-implementation cohorts for the sample as a whole (video vs. usual care: adjusted odds ratio (AOR)=1.23 (95% confidence interval (CI): 0.82 to 1.85), p=0.80; decision aids vs. usual care: AOR=1.47 (95% CI: 0.98 to 2.18), p=0.32; dual vs. video: AOR=0.95 (95% CI: 0.64 to 1.41), p=1.00; dual vs. decision aids: AOR=0.80 (95% CI: 0.54 to 1.17), p=0.72) or for participants with adequate health literacy. Among participants with limited health literacy, the difference in shared decision-making between the pre- and post-implementation cohorts was different in the video arm from the usual care arm (AOR=2.40 (95% CI: 1.01 to 5.71), p=.047) and was also different in the decision aids arm from the usual care arm (AOR=2.65 (95% CI: 1.16 to 6.07), p=.021), however these differences were not robust to adjustment for multiple comparisons. There were no intervention effects on the secondary outcomes among all participants nor among prespecified subgroups. With respect to intervention feasibility, rates of participant-reported exposure to the relevant intervention components were 9.4% for the video arm, 31.5% for the decision aids arm, and 5.0% for the dual arm. All interventions were acceptable to most patients. Conclusions: The interventions studied are unlikely to have a meaningful population-wide impact on shared decision-making or other outcomes in real-world contraceptive care without additional strategies to promote and support implementation. Selective use of the interventions among patients with limited health literacy may be more promising and, if effective, could reduce disparities in shared decision-making. Trial registration: ClinicalTrials.gov NCT02759939.

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