Circulating miRNAs in Women with Polycystic Ovary Syndrome: A Longitudinal Cohort Study.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) often change their metabolic profile over time to decrease levels of androgens while often gaining a propensity for the development of the metabolic syndrome. Recent discoveries indicate that microRNAs (miRNAs) play a role in the development of PCOS and constitute potential biomarkers for PCOS. We aimed to identify miRNAs associated with the development of an impaired metabolic profile in women with PCOS, in a follow-up study, compared with women without PCOS. METHODS AND MATERIALS: Clinical measurements of PCOS status and metabolic disease were obtained twice 6 years apart in a cohort of 46 women with PCOS and nine controls. All participants were evaluated for degree of metabolic disease (hypertension, dyslipidemia, central obesity, and impaired glucose tolerance). MiRNA levels were measured using Taqman® Array cards of 96 pre-selected miRNAs associated with PCOS and/or metabolic disease. RESULTS: Women with PCOS decreased their levels of androgens during follow-up. Twenty-six of the miRNAs were significantly changed in circulation in women with PCOS during the follow-up, and twenty-four of them had decreased, while levels did not change in the control group. Four miRNAs were significantly different at baseline between healthy controls and women with PCOS; miR-103-3p, miR-139-5p, miR-28-3p, and miR-376a-3p, which were decreased in PCOS. After follow-up, miR-28-3p, miR-139-5p, and miR-376a-3p increased in PCOS women to the levels observed in healthy controls. Of these, miR-139-5p correlated with total testosterone levels (rho = 0.50, padj = 0.013), while miR-376-3p correlated significantly with the waist-hip ratio at follow-up (rho = 0.43, padj = 0.01). Predicted targets of miR-103-3p, miR-139-5p, miR-28-3p, and miR-376a-3p were enriched in pathways associated with Insulin/IGF signaling, interleukin signaling, the GNRH receptor pathways, and other signaling pathways. MiRNAs altered during follow-up in PCOS patients were enriched in pathways related to immune regulation, gonadotropin-releasing hormone signaling, tyrosine kinase signaling, and WNT signaling. CONCLUSIONS: These studies indicate that miRNAs associated with PCOS and androgen metabolism overall decrease during a 6-year follow-up, reflecting the phenotypic change in PCOS individuals towards a less hyperandrogenic profile.

A randomised, controlled, crossover study of the effect of diet on angiopoietin-like protein 4 (ANGPTL4) through modification of the gut microbiome.

Angiopoietin-like protein 4 (ANGPTL4) is a lipoprotein lipase inhibitor that is involved in lipid metabolism and angiogenesis. Animal studies have suggested that the ANGPTL4 protein is modulated by the gut microbiota, possibly through increased concentrations of SCFA, such as C4, found in whole-fat milk or as a result of fermentation of inulin. This study investigated whether a standardised diet either high in fat content or supplemented with inulin powder would increase plasma ANGPTL4 in overweight men and whether this increase was mediated through a compositional change of the gut microbiota. The study had a crossover design with three arms, where participants were given a standardised isoenergetic diet supplemented with inulin powder, whole-fat milk or water (control). Plasma and urine samples were collected before and after each intervention period. Faecal samples and adipose tissue biopsies were collected after each intervention period. The study included twenty-one participants of whom eighteen completed the study. The dietary interventions did not change ANGPTL4 plasma concentration, nor was plasma ANGPTL4 associated with plasma lipids, TAG or NEFA concentration. The relative abundance of bifidobacteria following the inulin diet was higher, compared with the control diet. However, the changes in microbiota were not associated with plasma ANGPTL4 and the overall composition of the microbiota did not change between the dietary periods. Although weight was maintained throughout the dietary periods, weight was negatively associated with plasma ANGPTL4 concentration. In the adipose tissue, ANGPTL4 expression was correlated with leptin expression, but not with hypoxia-inducible factor 1α (HIF-1α) expression.

Neurocognitive outcomes of off-pump versus on-pump coronary artery bypass: a prospective randomized controlled trial.

BACKGROUND: Preliminary reports have documented the safety of off-pump coronary artery bypass graft compared with conventional coronary artery bypass graft surgery. Whereas off-pump coronary artery bypass graft surgery may be associated with improvement in some short-term outcomes, longer-term outcomes and influence on neurocognitive function have not been fully assessed. We examined short-term and intermediate-term neurocognitive and index admission morbidity and mortality after coronary artery bypass surgery performed with and without the use of extracorporeal circulation. METHODS: We prospectively randomly assigned 201 patients undergoing nonemergent isolated coronary artery bypass graft surgery to conventional coronary artery bypass graft surgery (n = 102) or off-pump coronary artery bypass graft surgery (n = 99). The primary end points of the study were neurocognitive function assessed using a 19-test neurocognitive battery at baseline, discharge, and 6 months. Neurocognitive deficit was defined as a 20% or greater reduction from baseline in at least 20% of the tests. Secondary end points included index admission mortality, stroke, low-output cardiac failure, return to the operating room for bleeding, and postoperative troponin release. Risk ratios and 95% confidence intervals were calculated based on intention-to-treat analysis. RESULTS: There was no difference in neurocognitive deficit at discharge (discharge versus preoperative: risk ratio, 0.83; 95% confidence interval, 0.65 to 1.07) or at 6 months (6 months versus preoperative: risk ratio, 0.94; 95% confidence interval, 0.70 to 1.28). There was no significant difference in mortality or morbidity between the two groups. The off-pump coronary artery bypass graft group had fewer patients with troponin release than the conventional coronary artery bypass graft group. CONCLUSIONS: Off-pump coronary artery bypass graft surgery did not result in decreased frequency of neurocognitive deficit. Off-pump coronary artery bypass graft surgery was associated with substantially lower levels of troponin release after surgery.