eral action of irisin improves glucose homeostasis and increases energy expenditure, with no data on a central role of irisin in metabolism. These studies sought to examine 1) presence of irisin in human cerebrospinal fluid (CSF) and banked human hypothalamic tissue, 2) serum irisin in maternal subjects across varying adiposities with or without gestational diabetes (GDM), and 3) their respective neonate offspring. CSF, serum, and neonatal cord serum were collected from 91 pregnant women with and without GDM attending for an elective cesarean section [body mass index (BMI): 37.7 Ϯ 7.6 kg/m 2 ; age: 32 Ϯ 8.3 yr]. Irisin was assessed by ELISA and correlated with biochemical and anthropometric data. Irisin expression was examined in human hypothalamus by immunohistochemical staining. Serum irisin in pregnant women was significantly lower in nonobese compared with obese and GDM subjects, after adjusting for BMI, lipids, and glucose. Irisin was present in neonatal cord serum (237 Ϯ 8 ng/ml) and maternal CSF (32 Ϯ 1.5 ng/ml). CSF irisin correlated positively with serum irisin levels from nonobese and obese pregnant women (P Ͻ 0.01), with CSF irisin significantly raised in GDM subjects (P Ͻ 0.05). Irisin was present in human hypothalamic sections in the paraventricular neurons, colocalized with neuropeptide Y. Irisin was detectable in CSF and in paraventricular neurons. Maternal serum irisin was lower in nonobese pregnant women after adjusting for BMI and a number of metabolic parameters. These studies indicate that irisin may have a central role in metabolism in addition to the known peripheral role. Further studies investigating the central action of irisin in human metabolic disease are required.irisin; obesity; gestational diabetes mellitus; leptin EMERGING DATA SUGGEST THAT a newly discovered polypeptide hormone, irisin, a cleaved secreted form of fibronectin type III domain containing 5 (FNDC5), has the potential to increase energy expenditure and improve glucose homeostasis in humans (4,16,31,34). This is particularly significant, since irisin can induce the transformation of white adipocytes into "beige" or "brite" adipocytes, which can ultimately lead to increased mitochondrial respiration (4, 34), with implications for weight loss. Therefore, such studies suggest the potential therapeutic applications of irisin not only in use for weight loss but also to improve glucose metabolism (4). Subsequent research has also revealed that the function of irisin appears to fall beyond its original role noted in muscle (4,9,13,21,23), and the administration of exogenous irisin could theoretically increase energy expenditure during or after weight loss. Recent studies have shown that irisin may also act as an adipokine (21, 25) as well as a potential "neurokine" (9, 12). Although the role of irisin in the brain is unclear, analysis has revealed that FNDC5 knockdown in murine embryonic stem cells reduces neurogenesis (11), whereas pharmacological doses of irisin increase proliferation of mouse hippocampal neuronal cells (20...

Background Elevated triglycerides are a feature of the metabolic syndrome, maternal obesity, maternal vasculitis (i.e. systemic lupus erythematosus) and diabetes mellitus. These conditions are all known risk factors for pre-eclampsia. Hypertriglyceridaemia therefore may be associated with pre-eclampsia and indeed this may precede the presence of overt disease.Objective In this study we determine the association between hypertriglyceridaemia and pre-eclampsia in pregnant women. Selection criteria Two reviewers independently selected studies on pregnant women where triglycerides were measured and women were followed up until the development of pre-eclampsia or selected on the basis of presence of pre-eclampsia and compared with controls.Data collection and analysis We collected and meta-analysed the weighted mean differences (WMDs) of triglyceride levels from individual studies using a random effects model. Main resultsWe found strong evidence from meta-analysis of 24 case-control studies (2720 women) that pre-eclampsia is associated with higher levels of serum triglycerides (WMD 0.78 mmol/l, 95% confidence interval 0.6-0.96, P < 0.00001). This finding is also confirmed in five cohort studies, that recruited 3147 women in the second trimester before the onset of pre-eclampsia, which proves that hypertriglyceridaemia precedes the onset of pre-eclampsia (WMD 0.24 mmol/l, 95% confidence interval 0.13-0.34, P < 0.0001).Author's conclusions Hypertriglyceridaemia is associated with and precedes the onset of pre-eclampsia. Further research should focus on defining the prognostic accuracy of this test to identify women at risk and the beneficial effect of triglyceride-lowering therapies in pregnancy.

Background Covered stent correction of sinus venosus ASDs (SVASD) is a relatively new technique. Challenges include anchoring a sufficiently long stent in a nonstenotic superior vena cava (SVC) and expanding the stent at the wider SVC‐RA junction without obstructing the anomalous right upper pulmonary vein (RUPV). The 10‐zig covered Cheatham‐platinum (CCP) stent has the advantage of being available in lengths of 5–11 cm and dilatable to 34 mm in diameter. Methods An international registry reviewed the outcomes of 10‐zig CCP stents in 75 patients aged 11.4–75.9 years (median 45.4) from March 2016. Additional stents were used to anchor the stent in the SVC or close residual shunts in 33/75. An additional stent was placed in 4/5 (80%) with 5/5.5 cm CCPs, 18/29 (62%) with 6 cm CCPs, 5/18 (28%) with 7 cm CCPs, 5/22 (23%) with 7.5/8 cm CCPs and 0/1 with an 11 cm CCP. A “protective” balloon catheter was inflated in the RUPV in 17. Results Early stent embolization in two patients required surgical removal and defect repair and tamponade was drained in one patient. The CT at 3 months showed occlusion of the RUPV in one patient. Follow up is from 2 months to 5.1 years (median 1.8 years). QP:QS has reduced from 2.5 ± 0.5 to 1.2 ± 0.36 (p < .001) and RVEDVi from 149.1 ± 35.4 to 95.6 ± 21.43 ml/m2 (p < .001). Conclusions Ten‐zig CCPs of 7–8 cm appear to provide reliable SVASD closure with a low requirement for additional stents. Careful selection of patients and meticulous attention to detail is required to avoid complications.

AFR implantation was feasible and safe in all patients with PAH. There was a significant improvement of symptoms, six-minute walk distance, cardiac index and systemic oxygen transport. The device maintained patency in short-term follow-up and the resultant hypoxia was tolerated well.

Background and Aims: Studies in South Asian population show that low maternal vitamin B12 associates with insulin resistance and small for gestational age in the offspring. Low vitamin B12 status is attributed to vegetarianism in these populations. It is not known whether low B12 status is associated with metabolic risk of the offspring in whites, where the childhood metabolic disorders are increasing rapidly. Here, we studied whether maternal B12 levels associate with metabolic risk of the offspring at birth. Methods: This is a cross-sectional study of 91 mother-infant pairs (n = 182), of white Caucasian origin living in the UK. Blood samples were collected from white pregnant women at delivery and their newborns (cord blood). Serum vitamin B12, folate, homocysteine as well as the relevant metabolic risk factors were measured. Results: The prevalence of low serum vitamin B12 (<191 ng/L) and folate (<4.6 μg/L) were 40% and 11%, respectively. Maternal B12 was inversely associated with offspring’s Homeostasis Model Assessment 2-Insulin Resistance (HOMA-IR), triglycerides, homocysteine and positively with HDL-cholesterol after adjusting for age and BMI. In regression analysis, after adjusting for likely confounders, maternal B12 is independently associated with neonatal HDL-cholesterol and homocysteine but not triglycerides or HOMA-IR. Conclusions: Our study shows that low B12 status is common in white women and is independently associated with adverse cord blood cholesterol.

No abstract

Recently soluble CD163 (sCD163), a cleaved form of the macrophage receptor CD163, was identified as a macrophage-specific risk-predictor for developing Type 2 Diabetes. Here, we investigate circulating levels of sCD163 in gestational diabetes mellitus (GDM). Furthermore, given the role of the placenta in the pathogenesis of GDM, we assessed placental contribution to sCD163 secretion. Paired maternal (venous) and umbilical vein blood samples from GDM (n = 18) and Body Mass Index (BMI) matched control women (n = 20) delivered by caesarean section at 39–40 week gestation were assessed for circulating levels of sCD163, Tumour necrosis factor alpha (TNF-α) and Interleukin 6 (IL-6). Media from explant culture of maternal subcutaneous fat and corresponding placental tissues were assayed for these same molecules. CD163 positive cell numbers were determined in placental and adipose tissues of GDM and control women. We found significantly elevated circulating sCD163 levels in GDM mothers (688.4±46.9 ng/ml vs. 505.6±38.6 ng/ml) and their offspring (418.2±26.6 ng/ml vs. 336.3±24.4 ng/ml [p<0.05 for both]) as compared to controls, together with elevated circulating TNF-α and IL-6 levels. Moreover, both GDM placentae (268.1±10.8 ng/ml/mg vs. 187.6±20.6 ng/ml/mg) and adipose explants (41.1±2.7 ng/ml/mg vs. 26.6±2.4 ng/ml/mg) released significantly more sCD163 than controls. Lastly, significantly more CD163 positive cells were observed in GDM placentae (25.7±1.1 vs. 22.1±1.2) and adipose tissue (19.1±1.1 vs 12.7±0.9) compared to controls. We describe elevated sCD163 levels in GDM and identify human placenta as a novel source of sCD163 suggesting that placental tissues might contribute to the increased levels of circulating sCD163 in GDM pregnancies.

Background: There is a recent interest in nonsurgical correction of superior sinus venosus defects. Patient selection is currently based on advanced imaging and printing technologies. Simple clinical tools to select patients will expand its applicability in developing countries. Methods: Defects caudally extending toward the oval fossa and right upper pulmonary veins draining beyond the cavoatrial junction on transesophageal echocardiography were excluded. Balloon interrogation of cavoatrial junction confirmed complete occlusion of the defect with unobstructed pulmonary venous drainage to left atrium. Single long covered stents or overlapping covered stents were used to exclude sinus venosus defects. Closure of left-to-right interatrial shunt without causing pulmonary vein occlusion was confirmed on follow-up imaging. Results: Forty-four patients selected after transesophageal echocardiography underwent balloon interrogation with monitoring of right upper pulmonary vein. Eighteen out of 44 patients were ineligible. Twenty-four eligible patients with closure of left-to-right interatrial shunt without pulmonary vein occlusion underwent covered stent exclusion using single long stents in 15 and overlapping stents in the rest, while 2 patients are awaiting the procedure. Four patients aged 6 to 16 years received stents that were 18 mm or larger. Three patients had stent embolization that required surgical correction in 2 but in the last patient was managed nonsurgically with an overlapping covered stent with good final outcomes. Procedure was successful in 22 patients. At a median follow-up of 20 months (range, 3–54 months), there were no adverse events. Follow-up imaging showed trivial left-to-right shunt in 4 and unobstructed pulmonary veins in all patients. Conclusions: Transesophageal echocardiography and balloon interrogation identified 60% of the patients with sinus venosus defects to be eligible for catheter closure. Overlapping stents are an alternative to custom-made long stents. Transesophageal echocardiography confirms procedural success on follow-up. Advanced imaging and printing technologies are not essential for successful outcomes and thus simple tests increase the feasibility in developing countries.