Ascorbic acid attenuates endothelial permeability triggered by cell-free hemoglobin

Background

Increased endothelial permeability is central to shock and organ dysfunction in sepsis but therapeutics targeted to known mediators of increased endothelial permeability have been unsuccessful in patient studies. We previously reported that cell-free hemoglobin (CFH) is elevated in the majority of patients with sepsis and is associated with organ dysfunction, poor clinical outcomes and elevated markers of oxidant injury. Others have shown that Vitamin C (ascorbate) may have endothelial protective effects in sepsis. In this study, we tested the hypothesis that high levels of CFH, as seen in the circulation of patients with sepsis, disrupt endothelial barrier integrity.

混合线性模型下猪群间遗传联系的度量

采用关联指数(IC)和决定系数(CD)两种方法,度量混合线性模型遗传评估下 猪群体间的遗传关联性。结果表明,加拿大安大略省的大约克夏猪、长白猪、杜洛克猪和汉普夏猪4个主要品种群体间具有良好的遗传联系。CD法既组合了数据结构和信息量,又考虑了预测误差方差和遗传变异性,是一个选择判断遗传评估精度的好方法。 Abstract:Two criteria for the measures of genetic connectedness in mixed linear model of genetic evaluation are used:the degree of connectedness(IC)and the generalized coefficient of determination(CD).The results indicated that the data of four dominant swine breeds:Yorkshire,Landrace,Duroc and Hampshire in Ontario,Canada are well connected.The CD,which combines data structure and amount of information and also accounts for both prediction error variance and genetic variability,is a good method to select for judging the precision of a genetic evaluation.     

Motile sperm organelle morphology examination (MSOME): intervariation study of normal sperm and sperm with large nuclear vacuoles

Background  

Although the motile sperm organelle morphology examination (MSOME) was developed only as a selection criterion, its application as a method for classifying sperm morphology may represent an improvement in evaluation of semen quality, with potential clinical repercussions. The present study aimed to evaluate individual variations in the motile sperm organelle morphology examination (MSOME) analysis after a time interval.     

The many roles of small RNAs in leaf development

Leaf development involves many complex genetic interactions,signals between adjacent cells or between more distant tissues and consequent changes in cell fate.This review describes three stages in leaf development where regulation by small RNAs have been used to modulate gene expression patterns.     

Cavotricuspid Isthmus Anatomy Determines The Success Of Remote Controlled Magnetic Bidirectional Block: A Comparsion Between Magnetic 8-mm Solid Tip And 3.5-mm Magnetic Irrigated Tip Catheter

Background

Cavotricuspid isthmus (CTI) anatomy is associated with a great inter-individual variability. The aim of this study was to compare the magnetic 8-mm tip catheter versus the novel 3.5-mm magnetic irrigated tip catheter in achieving bidirectional right atrial isthmus block and to evaluate the impact of the underlying CTI anatomy on success rate.

Methods

A detailed remote controlled 3-dimensional electroanatomic (3D EA) right atrial reconstruction was performed using the magnetic navigation system with special emphasis to the CTI. CTI anatomy was evaluated utilizing the 3D EA map and classified into (A) simple (flat), (B) complex (pouch-like recess or concave shape) or (C) highly complex (pouch-like recess and concave shape). Patients were treated either with the magnetic 8-mm tip catheter (group I) or the open irrigated magnetic 3.5-mm tip catheter (group II). Primary endpoint was defined as acute bidirectional CTI block utilizing exclusively the remote controlled magnetic navigation system. Secondary endpoint was any procedure related complication and procedure time.

Results

In group I (n=10, 10 males, mean age: 65 ± 9 years) the primary endpoint was achieved in 80% (8/10 pts) requiring a median (Q1; Q3) RF application time of 37.1 min (22.8; 71.5) and a median (Q1;Q3) cumulative energy (CE) of 70.68 kJ (kilo Joule). (10.76;40.59). In group II (n=13, 10 males, mean age: 60 ± 7 years) the primary endpoint was achieved in 92 % (12/13) with a median (Q1; Q3) RF application time of 21.9 min (13.0; 27.0; p value=0.036) and a CE of 33.54 KJ (26.59; 49.22; p value=0.015). Variable CTI anatomy was identified for group I (type A: n=5 pts, type B: n=5 pts, type C: n=0 pts) and group for II (type A: n=4 pts, type B: n=7 pts, type C: n=2 pts). In group I magnetic ablation failure was associated with type B CTI anatomy (n=2 pts) and in group II with type C CTI (n=1). No procedure related complications were observed.

Conclusion

Remote controlled catheter ablation of typical atrial flutter using the magnetic navigation system appears to be safe and feasible. CTI anatomy determines remote controlled magnetic ablation success. Use of the magnetic 3.5 mm irrigated tip catheter should be considered in patients with complex CTI anatomy.     

Novel and selective DNA methyltransferase inhibitors: Docking-based virtual screening and experimental evaluation

The DNA methyltransferase (DNMT) enzyme family consists of four members with diverse functions and represents one of the most promising targets for the development of novel anticancer drugs. However, the standard drugs for DNMT inhibition are non-selective cytosine analogues with considerable cytotoxic side-effects that have been developed several decades ago. In this work, we conducted a virtual screening of more than 65,000 lead-like compounds selected from the National Cancer Institute collection using a multistep docking approach with a previously validated homology model of the catalytic domain of human DNMT1. Experimental evaluation of top-ranked molecules led to the discovery of novel small molecule DNMT1 inhibitors. Virtual screening hits were further evaluated for DNMT3B inhibition revealing several compounds with selectivity towards DNMT1. These are the first small molecules reported with biochemical selectivity towards an individual DNMT enzyme capable of binding in the same pocket as the native substrate cytosine, and are promising candidates for further rational optimization and development as anticancer drugs. The availability of enzyme-selective inhibitors will also be of great significance for understanding the role of individual DNMT enzymes in epigenetic regulation.     

Factors affecting the accuracy of urine-based biomarkers of BSE

Background  

Transmissible spongiform encephalopathy diseases are untreatable, uniformly fatal degenerative syndromes of the central nervous system that can be transmitted both within as well as between species. The bovine spongiform encephalopathy (BSE) epidemic and the emergence of a new human variant of Creutzfeldt-Jakob disease (vCJD), have profoundly influenced beef production processes as well as blood donation and surgical procedures. Simple, robust and cost effective diagnostic screening and surveillance tools are needed for both the preclinical and clinical stages of TSE disease in order to minimize both the economic costs and zoonotic risk of BSE and to further reduce the risk of secondary vCJD.     

Evaluation of zona pellucida birefringence intensity during in vitro maturation of oocytes from stimulated cycles

Background  

This study evaluated whether there is a relationship between the zona pellucida birefringence (ZP-BF) intensity and the nuclear (NM) and cytoplasmic (CM) in vitro maturation of human oocytes from stimulated cycles.