Natural history of markers of collagen turnover in patients with early diastolic dysfunction and impact of eplerenone

OBJECTIVES: This study was designed to evaluate the impact of eplerenone on collagen turnover in preserved systolic function heart failure (HFPSF).

BACKGROUND: Despite growing interest in abnormal collagen metabolism as a feature of HFPSF with diastolic dysfunction, the natural history of markers of collagen turnover and the impact of selective aldosterone antagonism on this natural history remains unknown.

METHODS: We evaluated 44 patients with HFPSF, randomly assigned to control (n = 20) or eplerenone 25 mg daily (n = 24) for 6 months, increased to 50 mg daily from 6 to 12 months. Serum markers of collagen turnover and inflammation were analyzed at baseline and at 6 and 12 months and included pro-collagen type-I and -III aminoterminal peptides, matrix metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha. Doppler-echocardiographic assessment of diastolic filling indexes and tissue Doppler analyses were also obtained.

RESULTS: The mean age of the patients was 80 +/- 7.8 years; 46% were male; 64% were receiving an angiotensin-converting enzyme inhibitor, 34% an angiotensin-II receptor blocker, and 68% were receiving beta-blocker therapy. Pro-collagen type-III and -I aminoterminal peptides, matrix metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha increased with time in the control group. Eplerenone treatment had no significant impact on any biomarker at 6 months but attenuated the increase in pro-collagen type-III aminoterminal peptide at 12 months (p = 0.006). Eplerenone therapy was associated with modest effects on diastolic function without any impact on clinical variables or brain natriuretic peptide.

CONCLUSIONS: This study demonstrates progressive increases in markers of collagen turnover and inflammation in HFPSF with diastolic dysfunction. Despite high background utilization of renin-angiotensin-aldosterone modulators, eplerenone therapy prevents a progressive increase in pro-collagen type-III aminoterminal peptide and may have a role in management of this disease. (The Effect of Eplerenone and Atorvastatin on Markers of Collagen Turnover in Diastolic Heart Failure; NCT00505336).

The potential contributions of concept maps for learning website to assessment for learning practices

The purpose of this paper is to examine the promising contributions of the Concept Maps for Learning (CMfL) website to assessment for learning practices. The CMfL website generates concept maps from relatedness degree of concepts pairs through the Pathfinder Scaling Algorithm. This website also confirms the established principles of effective assessment for learning, for it is capable of automatically assessing students' higher order knowledge, simultaneously identifying strengths and weaknesses, immediately providing useful feedback and being user-friendly. According to the default assessment plan, students first create concept maps on a particular subject and then they are given individualized visual feedback followed by associated instructional material (e.g., videos, website links, examples, problems, etc.) based on a comparison of their concept map and a subject matter expert's map. After studying the feedback and instructional material, teachers can monitor their students' progress by having them create revised concept maps. Therefore, we claim that the CMfL website may reduce the workload of teachers as well as provide immediate and delayed feedback on the weaknesses of students in different forms such as graphical and multimedia. For the following study, we will examine whether these promising contributions to assessment for learning are valid in a variety of subjects.

Real-time PCR demonstrates high prevalence of Schistosoma japonicum in the Philippines:implications for surveillance and control

BACKGROUND: The Philippines has a population of approximately 103 million people, of which 6.7 million live in schistosomiasis-endemic areas with 1.8 million people being at risk of infection with Schistosoma japonicum. Although the country-wide prevalence of schistosomiasis japonica in the Philippines is relatively low, the prevalence of schistosomiasis can be high, approaching 65% in some endemic areas. Of the currently available microscopy-based diagnostic techniques for detecting schistosome infections in the Philippines and elsewhere, most exhibit varying diagnostic performances, with the Kato-Katz (KK) method having particularly poor sensitivity for detecting low intensity infections. This suggests that the actual prevalence of schistosomiasis japonica may be much higher than previous reports have indicated.

METHODOLOGY/PRINCIPAL FINDINGS: Six barangay (villages) were selected to determine the prevalence of S. japonicum in humans in the municipality of Palapag, Northern Samar. Fecal samples were collected from 560 humans and examined by the KK method and a validated real-time PCR (qPCR) assay. A high S. japonicum prevalence (90.2%) was revealed using qPCR whereas the KK method indicated a lower prevalence (22.9%). The geometric mean eggs per gram (GMEPG) determined by the qPCR was 36.5 and 11.5 by the KK. These results, particularly those obtained by the qPCR, indicate that the prevalence of schistosomiasis in this region of the Philippines is much higher than historically reported.

CONCLUSIONS/SIGNIFICANCE: Despite being more expensive, qPCR can complement the KK procedure, particularly for surveillance and monitoring of areas where extensive schistosomiasis control has led to low prevalence and intensity infections and where schistosomiasis elimination is on the horizon, as for example in southern China.

Threat Analysis of BlackEnergy Malware for Synchrophasor based Real-time Control and Monitoring in Smart Grid

The BlackEnergy malware targeting critical infrastructures has a long history. It evolved over time from a simple DDoS platform to a quite sophisticated plug-in based malware. The plug-in architecture has a persistent malware core with easily installable attack specific modules for DDoS, spamming, info-stealing, remote access, boot-sector formatting etc. BlackEnergy has been involved in several high profile cyber physical attacks including the recent Ukraine power grid attack in December 2015. This paper investigates the evolution of BlackEnergy and its cyber attack capabilities. It presents a basic cyber attack model used by BlackEnergy for targeting industrial control systems. In particular, the paper analyzes cyber threats of BlackEnergy for synchrophasor based systems which are used for real-time control and monitoring functionalities in smart grid. Several BlackEnergy based attack scenarios have been investigated by exploiting the vulnerabilities in two widely used synchrophasor communication standards: (i) IEEE C37.118 and (ii) IEC 61850-90-5. Specifically, the paper addresses reconnaissance, DDoS, man-in-the-middle and replay/reflection attacks on IEEE C37.118 and IEC 61850-90-5. Further, the paper also investigates protection strategies for detection and prevention of BlackEnergy based cyber physical attacks.