PP.LB03.03

Abstract

e 517Objective: Distal tubular sodium retention is a potent driver of hypertension, with the thiazide sensitive sodium chloride cotransporter (NCC) and its phosphorylated form (pNCC) key players. The upstream modulators of NCC expression and phosphorylation are unclear, but some evidence suggests that mineralocorticoid receptor (MR) activation by aldosterone may be involved. The synthetic mineralocorticoid fludrocortisone is a potent MR agonist. In this project we aimed to quantify the magnitude and time course of changes in expression pNCC in human urinary exosomes, in response to activation of the MR by oral fludrocortisone administration.Design and method: Daily "spot" morning urine samples were collected from 20 patients undergoing fludrocortisone suppression testing (100mcg q6 h) to diagnose or exclude primary aldosteronism. Urinary exosomes were isolated by progressive ultracentrifugation and NCC and pNCC expression quantified by western blot, expressed as arbitrary units of optical density (OD) / mg creatinine. Results:A progressive rise in NCC and pNCC expression was observed, with median NCC increasing >3 fold, from 3.37 OD/ug to 11.38 OD/ug. Median pNCC increased >2 fold, from 5.29 OD/ug to 14.30 OD/ug. In a mixed effects model a change of +2.12 OD/ug per day (p < 0.0005) was estimated for NCC expression, and +2.32 OD/ug per day (p < 0.0005) for pNCC.Conclusions: MR activation causes a rapid (<24 hours) and progressive increase in NCC and pNCC expression in humans. This widens the potential role of aldosterone in regulating distal sodium handling and has implications regarding treatment options for hypertension with MR blockade.Objective: Single nucleotide polymorphisms (SNPs) can contribute to development and progression of cardiovascular disease (CVD). Left ventricular diastolic dysfunction (LVDD) is a well-recognized complication of hypertension and a predictor of CVD. However, the association between SNPs and LV function remains unclear. Therefore, we investigated the association between left ventricular diastolic function parameters and SNPs in Polish hypertensive cohort. Design and method:We studied 744 hypertensive patients (mean age 54.7 ± 13.6 years) from the Care North cohort. LV function was defined as left atrium size (LA), E/A, E' and E/E'. All subjects were genotyped for 25 SNPs previously shown to be associated with myocardial infarction and coronary artery disease. SNP with minor allele frequency (MAF)<5% and with missing values>10% were excluded (n = 3). Missing values of each SNP were imputed with random forest method. Linear regression assuming an additive model was applied to identify and compare the effect size of tested SNPs. Models were adjusted for age, 24-hr systolic and diastolic blood pressure, and heart rate. Results:The analysis showed 8 of 25 studied SNPs to be significantly associated with E, E/E' and LA. E -Early diastolic mitral flow velocity, E' -early diastolic mitral annulus velocity, LA -Left atrium area Conclusions: Our study reveals that SNPs previously linked to c...

Patching the patchwork: appraising the EU regulatory framework on cyber security breaches

“…82 In fact, as anticipated in Section 3.1, only a minority of national laws (20%) oblige reporting breaches affecting information confidentiality, or denial of service attacks not necessarily affecting the availability of the electronic communications. 83 ENISA noted that the number of malware-related attacks may be on the rise, in line with the results of statistics worldwide. 84 Despite their small reported incidence, malware-related incidents had the greatest impact: they last the longest (90 hours), and consequently entailed the highest number of user hours lost (81500).…”

“…85 The cost of insecurity appears therefore highbut how did the transposed Directive fare in terms of security? One fourth of the responding regulatory authorities believe that the requirements contained in Article 13a of the Framework Directive did not lead to stronger security measures; 45% declared not to know what impact the Directive had had on security, 86 a figure that appears disconcerting in itself, and all the more if compared with the 100% on disruption of service mentioned earlier.…”

“…57 The private sector has filled in the gap, be it in the form of privately financed studies, such as the one run by the Ponemon Institute, 58 or cyber-insurance 59 that, according to ENISA, has thus far limited adoption compared to other sectors, but may quickly develop with the entry into force of the GDPR and NIS Directives. 60 As a result, even though the instruments 61 and regulatory authorities 62 acknowledge the overlap between the risks to personal and non-personal data, and the fact that breaches can be triggered by cybercrime, there does not seem to be any methodology to survey the combined effect of cyber security breaches across the different sectors.…”

“…Unfortunately, however, as noted earlier the six instruments do not always provide metrics to evaluate the level of harm. 66 The Framework Directive does not clarify what constitutes a 'significant' impact; ENISA has elaborated some criteria 67 to assess the significance, which are however not mandatory. Moreover, "depending on the national implementation of Art.…”

“…As for availability, the regulatory authorities report that the Directive has attained 100% with respect to continuity/availability or disruption/outages of electronic communications networks and services. 78 Interestingly, only 5.1% (34) of the total number of incidents in 2016 was caused by malicious actions (a figure doubled compared to 2015), as opposed to 71% caused by system failures (hardware-related, and software bugs), 12.7 by human error, 79 and 5.1 by natural causes. 80 Denial of service attacks only accounted for 3% of incidents, and network traffic hijack for 1%.…”