The VNTR polymorphism of the endothelial nitric oxide synthase gene and blood pressure in women at the end of pregnancy

ObjectiveExamine the association of the 4a/4b polymorphism of endothelial nitric oxide synthase (eNOS) with blood pressure in women at late pregnancy.Materials and methodsBlood pressure before pregnancy and at the end of gestation (37–40-week term) was measured in 588 women of the Russian ancestry. The women were divided into groups according to the body mass index and the presence of preeclampsia at late pregnancy. The 4a/4b polymorphism of the eNOS gene was genotyped using PCR with subsequent screening of amplified fragment length polymorphisms.ResultsThe 4a4a eNOS genotype was associated with higher levels of diastolic blood pressure in pregnant women and with more pronounced dynamics of the diastolic and mean arterial pressure in the development of pregnancy (p = 0.02–0.03). Pregnant women with the 4a4a genotype and increased body mass index had higher systolic, diastolic, and mean arterial pressure (p = 0.001–0.009). In pregnant women with preeclampsia, the 4a4a genotype was associated with higher level of diastolic blood pressure at the end of pregnancy (p = 0.04), whereas in the women without preeclampsia this genotype was associated with more pronounced changes of blood pressure at pregnancy (p = 0.02).ConclusionThe results of our study suggest that the genotype 4a4a of the eNOS gene is associated with higher levels of blood pressure in women at the end of pregnancy.     

Comprehensive Women-Centered Treatment for Psychoactive Substance Use in the Republic of Georgia: Outcomes of a Randomized Clinical Trial

This study aimed to assess the impact of a culturally sensitive, comprehensive women-centered intervention on psychoactive substance use among women in the Republic of Georgia. Study participants included 128 women who had injected psychoactive substance(s) in the past 30 days and had enrolled in a randomized controlled trial that compared Reinforcement-Based Treatment and the Women’s CoOp (RBT+WC) to usual care (UC). RBT+WC provided a structured 12-session intervention designed to reduce HIV/HCV risk and psychoactive substance and alcohol use, and to improve mental and physical health, whereas UC provided information booklets on the same topics and case management for 12 sessions. Urine drug screening was conducted at baseline, treatment completion, and 3-month follow-up. The findings showed that RBT+WC was not more effective than UC, although both treatments positively impacted opioid, benzodiazepine, and amphetamine/methamphetamine use. The findings suggest that RBT+WC represents a promising comprehensive women-centered intervention for reducing substance use and HIV risks for Georgian women who use substances.     

Magnetic resonance venography and liver transplant complications

Hepatic vein stenosis is a rare but serious complication following liver transplantation.Multiple modalities can be utilized to image the hepatic vasculature.Magnetic resonance venography(MRV)provides certain advantages over ultrasound,computed tomography angiography and digital subtraction venography.MRV utilizes the same imaging principles of magnetic resonance angiography in order to image the venous system.Blood pool contrast agents,specifically gadofosveset trisodium,allow for steady state imaging up to 1 h following injection,with improved visualisation of vital venous structures by utilising delayed steady state imaging.Additionally,the inherent physics properties of magnetic resonance imaging also provide excellent soft tissue detail and thus help define the extent of complications that often plague the post-liver transplant patient.This case report describes the use of gadofosveset trisodium in a patient with hepatic venous stenosis following liver transplantation.Initial venography failed to outline the stenoses and thus MRV using a blood pool contrast agent was utilised in order to delineate the anatomy and plan a therapeutic endovascular procedure.     

Successful lung donation at the age of 6 weeks: Challenges and lessons learned

A clinical case of successful procurement and transplantation of bilateral lungs from 6‐week‐old infant with sepsis secondary to bacterial meningitis is reported. Forty‐one‐day‐old male infant (height 60 cm, weight 4 kg) died of cerebral edema secondary to Escherichia coli meningitis and bacteremia. Preretrieval assessment included the following: arterial gases; pO₂ 50.4 kPa (378 mm Hg), pCO₂ 4.9 kPa (37 mm Hg), on FiO₂ 100%, PEEP 5 cm H₂O. Fiberoptic bronchoscopy showed no secretions nor mucosal inflammation; CXR revealed clear lung fields and pleural spaces. Inspection revealed dense adhesions in pericardial cavity and purulent left hemithorax effusion (urgent Gram‐stain came back as negative) but there was no consolidation in the lung. Good compliance of the lungs on inflation/deflation test was observed. The lungs were retrieved using the technique described. The recipient was a 4‐month‐old infant with alveolar capillary dysplasia and malaligned pulmonary veins. Implantation of the lungs was performed via bilateral thoracosternotomy on cardiopulmonary bypass, cooling to 30°C. Elective support with nitric oxide was used postoperatively. Two years after the transplantation, the recipient doing well with normal lung function. Lung procurement from a 6‐week donor with infectious complications and prolonged ventilation is a challenging undertaking but can be successful and should be attempted whenever possible given the paucity of organs available for pediatric recipients.     

In search for geroprotectors: in silico screening and in vitro validation of signalome-level mimetics of young healthy state

Populations in developed nations throughout the world are rapidly aging, and the search for geroprotectors, or anti-aging interventions, has never been more important. Yet while hundreds of geroprotectors have extended lifespan in animal models, none have yet been approved for widespread use in humans. GeroScope is a computational tool that can aid prediction of novel geroprotectors from existing human gene expression data. GeroScope maps expression differences between samples from young and old subjects to aging-related signaling pathways, then profiles pathway activation strength (PAS) for each condition. Known substances are then screened and ranked for those most likely to target differential pathways and mimic the young signalome. Here we used GeroScope and shortlisted ten substances, all of which have lifespan-extending effects in animal models, and tested 6 of them for geroprotective effects in senescent human fibroblast cultures. PD-98059, a highly selective MEK1 inhibitor, showed both life-prolonging and rejuvenating effects. Natural compounds like N-acetyl-L-cysteine, Myricetin and Epigallocatechin gallate also improved several senescence-associated properties and were further investigated with pathway analysis. This work not only highlights several potential geroprotectors for further study, but also serves as a proof-of-concept for GeroScope, Oncofinder and other PAS-based methods in streamlining drug prediction, repurposing and personalized medicine.