Hypertension Is Associated with Marked Alterations in Sphingolipid Biology: A Potential Role for Ceramide

Background Hypertension is, amongst others, characterized by endothelial dysfunction and vascular remodeling. As sphingolipids have been implicated in both the regulation of vascular contractility and growth, we investigated whether sphingolipid biology is altered in hypertension and whether this is reflected in altered vascular function. Methods and Findings In isolated carotid arteries from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats, shifting the ceramide/S1P ratio towards ceramide dominance by administration of a sphingosine kinase inhibitor (dimethylsphingosine) or exogenous application of sphingomyelinase, induced marked endothelium-dependent contractions in SHR vessels (DMS: 1.4±0.4 and SMase: 2.1±0.1 mN/mm; n = 10), that were virtually absent in WKY vessels (DMS: 0.0±0.0 and SMase: 0.6±0.1 mN/mm; n = 9, p Conclusions Hypertension is associated with marked alterations in vascular sphingolipid biology such as elevated ceramide levels and signaling, that contribute to increased vascular tone

The Renin-Angiotensin-Aldosterone system in patients with depression compared to controls – a sleep endocrine study

BACKGROUND: Hypercortisolism as a sign of hypothamamus-pituitary-adrenocortical (HPA) axis overactivity and sleep EEG changes are frequently observed in depression. Closely related to the HPA axis is the renin-angiotensin-aldosterone system (RAAS) as 1. adrenocorticotropic hormone (ACTH) is a common stimulus for cortisol and aldosterone, 2. cortisol release is suppressed by mineralocorticoid receptor (MR) agonists 3. angiotensin II (ATII) releases CRH and vasopressin from the hypothalamus. Furthermore renin and aldosterone secretion are synchronized to the rapid eyed movement (REM)-nonREM cycle. METHODS: Here we focus on the difference of sleep related activity of the RAAS between depressed patients and healthy controls. We studied the nocturnal plasma concentration of ACTH, cortisol, renin and aldosterone, and sleep EEG in 7 medication free patients with depression (1 male, 6 females, age: (mean +/-SD) 53.3 ± 14.4 yr.) and 7 age matched controls (2 males, 5 females, age: 54.7 ± 19.5 yr.). After one night of accommodation a polysomnography was performed between 23.00 h and 7.00 h. During examination nights blood samples were taken every 20 min between 23.00 h and 7.00 h. Area under the curve (AUC) for the hormones separated for the halves of the night (23.00 h to 3.00 h and 3.00 h to 7.00 h) were used for statistical analysis, with analysis of co variance being performed with age as a covariate. RESULTS: No differences in ACTH and renin concentrations were found. For cortisol, a trend to an increase was found in the first half of the night in patients compared to controls (p < 0.06). Aldosterone was largely increased in the first (p < 0.05) and second (p < 0.01) half of the night. Cross correlations between hormone concentrations revealed that in contrast to earlier findings, which included only male subjects, in our primarily female sample, renin and aldosterone secretion were not coupled and no difference between patients and controls could be found, suggesting a gender difference in RAAS regulation. No difference in conventional sleep EEG parameters were found in our sample. CONCLUSION: Hyperaldosteronism could be a sensitive marker for depression. Further our findings point to an altered renal mineralocorticoid sensitivity in patients with depression

All-sky search for gravitational-wave bursts in the second joint LIGO-Virgo run

We present results from a search for gravitational-wave bursts in the data collected by the LIGO and Virgo detectors between July 7, 2009 and October 20, 2010: data are analyzed when at least two of the three LIGO-Virgo detectors are in coincident operation, with a total observation time of 207 days. The analysis searches for transients of duration < 1 s over the frequency band 64-5000 Hz, without other assumptions on the signal waveform, polarization, direction or occurrence time. All identified events are consistent with the expected accidental background. We set frequentist upper limits on the rate of gravitational-wave bursts by combining this search with the previous LIGO-Virgo search on the data collected between November 2005 and October 2007. The upper limit on the rate of strong gravitational-wave bursts at the Earth is 1.3 events per year at 90% confidence. We also present upper limits on source rate density per year and Mpc^3 for sample populations of standard-candle sources. As in the previous joint run, typical sensitivities of the search in terms of the root-sum-squared strain amplitude for these waveforms lie in the range 5 10^-22 Hz^-1/2 to 1 10^-20 Hz^-1/2. The combination of the two joint runs entails the most sensitive all-sky search for generic gravitational-wave bursts and synthesizes the results achieved by the initial generation of interferometric detectors.Comment: 15 pages, 7 figures: data for plots and archived public version at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=70814&version=19, see also the public announcement at http://www.ligo.org/science/Publication-S6BurstAllSky

Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Background: Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories.Methods: We used data from 1990 to 2019 on people aged 30-79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age.Findings: The number of people aged 30-79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306-359) million women and 317 (292-344) million men in 1990 to 626 (584-668) million women and 652 (604-698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55-62) of women and 49% (46-52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43-51) of women and 38% (35-41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20-27) for women and 18% (16-21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran.Interpretation: Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings.Copyright (C) 2021 World Health Organization; licensee Elsevier.</p

Bodemdegradatie

Ondanks verbeteringen van het milieu in Europa op een aantal terreinen, is een aangescherpt milieubeleid in de Europese Unie noodzakelijk om de gezondheidsschade en het natuurverlies te beperken. Een kosten-batenanalyse wijst uit dat zo'n beleid robuust is en dat de macro-economische gevolgen beheersbaar zijn. Belangrijke prioriteiten voor het EU-milieubeleid zijn klimaatverandering, stikstof-eutrofiering, fijn stof, ozon en biodiversiteit. Dit zijn de belangrijkste bevindingen van een internationaal studieconsortium onder leiding van het RIVM. De studie is verricht in samenwerking met EFTEC (UK), NTUA (Griekenland), IIASA (Oostenrijk). Daarnaast hebben TNO en TME bijdragen geleverd. Ook is in het kader van de studie intensief samengewerkt met het Europese Milieuagentschap in Kopenhagen. De studie is verricht op verzoek van de Europese Commissie als bijdrage voor het zesde Milieu-Actieprogramma, dat door de Europese Commissie is gepresenteerd. In de studie stonden vijf vragen centraal: Is het huidige beleid adequaat genoeg? Kan technologie de geconstateerde beleidstekorten oplossen? Zijn ambitieusere milieudoelstellingen te realiseren? Zo ja, zijn deze doelen ook in economische zin verstandig? Welke beleidsreacties en -instrumenten zijn aan te bevelen? Deze vijf vragen zijn geanalyseerd voor twaalf Europese milieuproblemen, zoals klimaatverandering, biodiversiteit en chemische risico's. De analyse bestaat uit een analyse van de kosten van vermeden schade, milieu-uitgaven, risicoschattingen, publieke opinie, sociale gevolgen en duurzaamheid. De studie bevat ook informatie over milieudoelstellingen, scenario's en beleidsopties en - maatregelen, inclusief de kosten en baten hiervan. Dit rapport is het technische achtergrondrapport dat behoort bij het hoofdrapport. Er zijn twaalf technische achtergrondrapporten opgesteld, waarvan negen een specifiek milieuprobleem behandelen (analyse van het probleem, scenarios, kosten-batenanalyse en beleidsopties). Daarnaast zijn er drie algemene achtergrondrapporten opgesteld over de macro-economische gevolgen, de uitbreiding van de EU en de gehanteerde batenmethodiek.The economic assessment of priorities for a European environmental policy plan focuses on twelve identified Prominent European Environmental Problems such as climate change, chemical risks and biodiversity. The study, commissioned by the European Commission (DG Environment) to a European consortium led by RIVM, provides a basis for priority setting for European environmental policy planning in support of the sixth Environmental Action Programme as follow-up of the current fifth Environmental Action Plan called 'Towards Sustainability'. The analysis is based on an examination of the cost of avoided damage, environmental expenditures, risk assessment, public opinion, social incidence and sustainability. The study incorporates information on targets, scenario results, and policy options and measures including their costs and benefits. Main findings of the study are the following. Current trends show that if all existing policies are fully implemented and enforced, the European Union will be successful in reducing pressures on the environment. However, damage to human health and ecosystems can be substantially reduced with accelerated policies. The implementation costs of these additional policies will not exceed the environmental benefits and the impact on the economy is manageable. This requires future policies to focus on least-cost solutions and follow an integrated approach. Nevertheless, these policies will not be adequate for achieving all policy objectives. Remaining major problems are the excess load of nitrogen in the ecosystem, exceedance of air quality guidelines (especially particulate matter), noise nuisance and biodiversity loss. This report is one of a series supporting the main report: European Environmental Priorities: an Integrated Economic and Environmental Assessment. The areas discussed in the main report are fully documented in the various Technical reports. A background report is presented for each environmental issue giving an outline of the problem and its relationship to economic sectors and other issues; the benefits and the cost-benefit analysis; and the policy responses. Additional reports outline the benefits methodology, the EU enlargement issue and the macro-economic consequences of the scenarios. This report documents the Soil Degradation issue.European Commssio