Novel Risk Factors for Progression of Diabetic and Nondiabetic CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

1. Download : Download high-res image (451KB)
2. Download : Download full-size image

     

Beta-catenin is temporally regulated during normal liver development

BACKGROUND & AIMS: beta-Catenin, a key component of the Wnt pathway, plays an important role in unregulated liver growth in liver tumors, in regulated growth during liver regeneration, and in ex vivo embryonic liver cultures. METHODS: We used developing livers from several stages of gestational development to examine beta-catenin expression, protein-protein interactions, localization, and regulation in prenatal and postnatal livers. RESULTS: Microarray, Northern, and protein analyses showed peak expression of beta-catenin during early liver development at Embryonic day 10 (E10)-E12, followed by a decrease and a complete loss of normal beta-catenin (97-kilodalton species) after E16 through the remaining prenatal period. At the early stages, beta-catenin localized to the cytoplasm and nuclei of resident cells in addition to its normal membranous localization, which was seen at all later stages and in adult liver. Decreases in beta-catenin levels at E14 onward coincided with its decreased gene expression and increased degradation, as seen by an increase in serine 45/threonine 41-phosphorylated beta-catenin and its other negative regulators, such as axin, adenomatous polyposis coli gene product (APC), and glycogen synthase kinase-3 beta. Finally, we showed an intact association of E-cadherin and beta-catenin despite the loss of beta-catenin at E16-E18, owing to the presence of membrane-associated smaller-molecular-weight beta-catenin species. CONCLUSIONS: We also identified a stage-specific expression and regulation of beta-catenin during liver development that might be crucial for physiological liver development. Nuclear and cytoplasmic beta-catenin corresponded to cell proliferation in liver development. Finally, a smaller-molecular-weight species of beta-catenin might be maintaining normal interactions at the membrane.     

Inflammatory, haemostatic, and rheological markers for incident peripheral arterial disease: Edinburgh Artery Study.

AIMS: Recently, markers of inflammation, haemostasis, and blood rheology have received much attention as risk factors for coronary heart disease and stroke. However, their role in peripheral arterial disease (PAD) is not well established and some of them, including the pro-inflammatory cytokine interleukin-6 (IL-6), have not been examined before in prospective epidemiological studies. METHODS AND RESULTS: In the Edinburgh Artery Study, we studied the development of PAD in the general population and evaluated 17 potential blood markers as predictors of incident PAD. At baseline (1987), 1519 men and women free of PAD aged 55-74 were recruited. After 17 years, 208 subjects had developed symptomatic PAD. In analysis adjusted for cardiovascular risk factors and baseline cardiovascular disease (CVD), only C-reactive protein, fibrinogen, lipoprotein (a), and haematocrit [hazard ratio (95% CI) corresponding to an increase equal to the inter-tertile range 1.30 (1.08, 1.56), 1.16 (1.05, 1.17), 1.22 (1.04, 1.44), 1.22 (1.08, 1.38)] were significantly (P < 0.01) associated with PAD. However, these markers provided very little prognostic information for incident PAD to that obtained by cardiovascular risk factors and the ankle brachial index. Other markers including IL-6, intracellular adhesion molecule 1, d-dimer, tissue plasminogen activator antigen, and plasma and blood viscosities showed weak associations, which were considerably attenuated when CVD risk factors were accounted for. CONCLUSIONS: Our prospective data showed that several inflammatory, haemostatic, and rheological markers are associated with incident PAD; however, their clinical utility is likely to be limited. Future research is necessary to validate the importance of these biomarkers explicitly on PAD and to address the causality of the reported associations.     

IMPACT Trial: angiographic and intravascular ultrasound observations of the first human experience with mycophenolic acid-eluting polymer stent system.

The purpose of the study was to examine the safety and efficacy of two different formulations of mycophenolic acid (MPA)-eluting Duraflex stents on coronary de novo lesions. Recent data indicate that local delivery of MPA in the porcine overstretch coronary model significantly reduces neointimal hyperplasia (NIH). Patients were divided into three consecutive groups. The first (n=50) and second (n=55) groups received moderate- and slow-release MPA-eluting Duraflex stent, respectively. The last group (n=50) received the bare metal Duraflex stent. Clinical, angiographic, and intravascular ultrasound analysis were performed at 6-month follow-up. All stents were successfully deployed and patients were discharged home without clinical events. Compared to controls, 6-month in-lesion and in-stent minimum luminal diameter as well as late lumen loss were not significantly different in the moderate- and slow-release treatment groups. At follow-up, percentage obstruction and NIH volume were also similar between the three groups. At 30 days and 6 and 12 months, there were no differences noted between the three groups with respect to major adverse cardiac events as well as the individual rates of mortality, myocardial infarction, or repeat revascularization. There were no cases of subacute or late thrombosis. In this feasibility trial, the MPA-eluting Duraflex stents in either slow- or moderate-release formulations were well tolerated, but showed no benefit for treatment of coronary lesions when compared to controls. Further testing with different drug dosing or delivery rate might improve these results.     

Clinical audits to improve critical care: Part 2: Analyse,benchmark and feedback

Clinical audits are an essential part of the cycle designed to ensure that patients receive the best quality of care. By measuring the care delivered against established best practice standards, it becomes possible to identify shortcomings and to plan targeted strategies and processes for continuous improvement. The success of a clinical audit depends upon defined goals, motivation of stakeholders, appropriate tools and resources, and clear communication.In part 1 of this series, an overview of the structures and processes needed to prepare and collect data for clinical audits in the critical care setting was provided [A.J. Ullman, G. Ray-Barruel, C.M. Rickard, M. Cooke, Clinical audits to improve critical care: Part 1 Prepare and collect data, Aust Crit Care, 2017, in press]. In part 2, we discuss how to analyse the collected audit data, benchmark findings with internal and external data sets, and feedback audit results to critical care clinicians to promote evidence-based practice and improve patient outcomes.