Objectives Intrauterine growth restriction (IUGR) is diagnosed when the estimated fetal weight remains below the 10th percentile of gestational age based on pathological restriction of growth and/or accompanying Doppler abnormalities. Endothelial dysfunction is a common pathogenetic pathway underlying IUGR etiology. Endocan (ESM-1) is a novel marker of endothelial dysfunction and inflammation found in the maternal circulation. This study was designed to compare plasma endocan levels between pregnancies complicated with IUGR and a control group.Study design Forty-four pregnancies complicated with IUGR and 47 healthy pregnancies were included. Maternal plasma endocan levels were detected by ELISA. Parametric data was studied by Student's t-test. Mann-Whitney U-test was used in analyzing non-parametric data. Categorical variables underwent chi-square test. ROC analysis was performed to define the cutoff value of endocan in detecting IUGR. Spearman correlation test was performed.Results Maternal plasma endocan level varied significantly between IUGR and healthy pregnancies and was 1.8 fold higher in the IUGR group (793.0 (IQR544.4-1896.0) ng/L vs. 441.8 (IQR 408.3-512.4) ng/L, p  less then  .001). There was a weak negative correlation between endocan level and 5th and 10th minute APGAR Scores (r =  -0.256; p = .015 and r =  -0.215; p = .042, respectively), a weak positive correlation with umbilical artery pulsatility index, and a moderate negative correlation with cerebroplacental ratio (r  =  0.394; p  less then  .001 and r =  -0.459; p  less then  .001, respectively).Conclusions There was a significant difference between endocan levels of IUGR and healthy pregnancies. Further studies might be designed to investigate the performance of endocan in predicting neonatal outcomes for pregnancies complicated with IUGR.Introduction Evidence is emerging that paracetamol is a safe and effective alternative therapy for haemodynamically significant patent ductus arteriosus (hsPDA). Although there is no consensus opinion on its routine use for PDA in preterm infants, paracetamol is being used increasingly in many centres to treat hsPDA.Objective We conducted a national survey to review the current practice in the UK and the prevalence of paracetamol use for hsPDA closure in preterm infants.Method A web-based and telephone survey on the use of paracetamol for hsPDA closure in preterm infants was conducted. All neonatal intensive care and local neonatal units across the UK were contacted between May and August 2018.Results 98% (143/146) neonatal units responded. The first-line medication for hsPDA closure was ibuprofen in 92% (131/143) units. 33% (47/143) of units used paracetamol; three units used it as first-line. The dose and duration of paracetamol varied greatly among the units with a dose of 15 mg/kg 6 hourly in 62% (29/47) units and a duration of 3 and 5 days in 33% (14/42) and 31% (13/42) of units, respectively.  https://www.selleckchem.com/products/liraglutide.html  44% (19/43) of units did routine blood investigations using paracetamol for monitoring patients on treatment and 21% (9/43) took paracetamol level in addition to other tests.Conclusion 33% of the neonatal units across the UK offered paracetamol to treat hsPDA in preterm infants. Currently, there is a variation in practice regarding the dose, duration of paracetamol and monitoring of infants during its use for hsPDA closure. One strategy would be to develop national guidance once strong evidence is established to support its routine use for hsPDA in preterm infants.Temozolomide is a drug approved for treating glioblastomas, which has 100% oral bioavailability but gets degraded at physiological pH thus having very short half-life and only 20-30% brain bioavailability. Due to its amphiphilic nature, reported nanoformulations exhibits poor drug loading. The objective of this work was to formulate lipid-based drug delivery systems to enhance the brain bioavailability by prolonging the drug release and circulation time of the drug to overcome the limitations of the existing therapies and possible reduction of side effects. The size of the nanocarriers obtained was less than 300 nm and the PDI obtained was less than 0.3. The designed formulation showed higher entrapment efficiency as compared to the other reported nanocarriers of temozolomide. The designed formulations showed prolonged drug release from 12 to 20 h compared to 6 h for the pure drug. About 95% of the pure drug was degraded at plasma pH at the end of 12 h, whereas only 68% and 77% was degraded when entrapped inside the lipid crystal nanoparticles and proliposomes respectively. Further, pharmacokinetic and animal studies can confirm the potential of these for improvement of brain bioavailability.BACKGROUND Medical therapy for heart failure with reduced ejection fraction evolved since trials validated the use of implantable cardioverter-defibrillators (ICDs). We sought to evaluate the performance of ICDs in reducing mortality in the era of modern medical therapy by means of a systematic review and meta-analysis of contemporary randomized clinical trials of drug therapy for heart failure with reduced ejection fraction. METHODS AND RESULTS We systematically identified randomized clinical trials that evaluated drug therapy in patients with heart failure with reduced ejection fraction that reported mortality. Studies that enrolled 40%, or patients in the acute phase of heart failure and study treatment with devices were excluded. We identified 8 randomized clinical trials, including 31 701 patients of whom 3631 (11.5%) had an ICD. ICDs were associated with a lower risk of all-cause mortality (relative risk [RR], 0.85; 95% CI, 0.78-0.94) and sudden cardiac death (RR, 0.49; 95% CI, 0.40-0.61). Results were consistent among studies published before and after 2010. In meta-regression analysis, the proportion of nonischemic etiology did not affect the associated benefit of ICD. CONCLUSIONS In our meta-analysis of contemporary randomized trials of drug therapy for heart failure with reduced ejection fraction, the rate of ICD use was low and associated with a decreased risk in both all-cause mortality and sudden cardiac death. This benefit was still present in trials with new medical therapy.