Statins and psoriasis: Position statement by the Psoriasis Task Force of the European Academy of Dermatology and Venerology.

BACKGROUND: Psoriasis is associated with an increased mortality risk, with cardiovascular disease being the leading excess cause (in a dose-response manner with psoriasis severity). Statins have demonstrated a reduction in all-cause mortality with no excess of adverse events among the general population. The underuse of interventions in cardiovascular prevention, such as statins, for patients with psoriasis may be the result of an insufficient evaluation. OBJECTIVES: To provide the dermatologist with a tool for systematizing the treatment of dyslipidemia in psoriasis, which generally escapes the scope of dermatological practice, and to facilitate decision-making about the referral and treatment of patients. METHODS: The Psoriasis Task Force of the European Academy of Dermatology and Venereology performed this two-phase study to achieve a consensus and create recommendations on the use of statin therapy in patients with psoriasis. The first phase included a systematic review to identify a list of outline concepts and recommendations according to guidelines. The second phase consisted in a two-round Delphi study to evaluate those recommendations not literally taken from guidelines. RESULTS: A list of 47 concepts and recommendations to be followed by dermatologists involved in the treatment of patients with moderate-severe psoriasis was created. It included six main concepts about cardiovascular risk and psoriasis, six items related with the role of low-density lipoprotein cholesterol (LDL-c) and the benefits of statin treatment in psoriasis patients, eight recommendations about how cardiovascular risk should be assessed, three on the role of non-invasive cardiovascular imaging, three on LDL-c thresholds, eight key points related to statin prescription, 10 on statin treatment follow-up and three on patient referral to another specialist. CONCLUSIONS: The application of this position statement (close final list of concepts and recommendations) will help dermatologists to manage dyslipidemia and help psoriasis patients to reduce their cardiovascular risk.

Effect of supplementing rumen-protected methionine, lysine, and histidine to low-protein diets on the performance and nitrogen balance of dairy cows.

Lowering the dietary protein content can reduce N excretions and NH3 emissions from manure and increase milk N efficiency of dairy cows. However, milk yield (MY) and composition can be compromised due to AA deficiency. Methionine and Lys are known as first limiting EAA for dairy cows, and recently His is also mentioned as limiting, especially in grass-based or low-protein diets. To examine this, a trial was conducted with a 3-wk pre-experimental adaptation period (diet 16.5% crude protein), followed by a depletion period of 4 wk, in which 39 cows (average ± standard deviation: 116 ± 29.3 d in milk, 1.8 ± 1.2 lactations, 638 ± 73.2 kg of body weight, and 32.7 ± 5.75 kg MY/d) received a low-protein diet (CTRL) (14.5% crude protein). Then, taking into account parity, His plasma concentration, and MY, cows were randomly assigned to 1 of 3 treatment groups during the rumen-protected (RP) AA period of 7 wk; (1) CTRL; (2) CTRL + RP-Met + RP-Lys (MetLys); (3) CTRL + RP-Met + RP-Lys + RP-His (MetLysHis). Products were dosed, assuming requirements for digestible (d) Met, dLys, and dHis being, respectively, 2.4%, 7.0%, and 2.4% of intestinal digestible protein. In the cross-back period of 5 wk, all cows received the CTRL diet. During the last week of each period, a N balance was conducted by collecting total urine and spot samples of feces. Total feces production was calculated using the inert marker TiO2. Statistical analysis was performed with a linear mixed model with cow as random effect and data of the last week of the pre-experimental period used as covariate for the animal performance variables. No effect of supplementing RP-Met and RP-Lys nor RP-Met, RP-Lys, and RP-His on feed intake, milk performance, or milk N efficiency was observed. However, the plasma AA profile indicated additional supply of dMet, dLys, and dHis. Nevertheless, evaluation of the AA uptake relative to the cow's requirements showed that most EAA (exclusive Arg and Thr) were limiting over the whole experiment. Only dHis was sufficiently supplemented during the RP-AA period due to an overestimation of the diet's dMet and dLys supply in the beginning of the trial. The numerically increased milk urea N and urinary N excretion when RP-Met, RP-Lys, and RP-His were added to the low-protein diet suggest an increased catabolism of the excess His.

I22: SAXS/WAXS beamline at Diamond Light Source - an overview of 10 years operation.

Beamline I22 at Diamond Light Source is dedicated to the study of soft-matter systems from both biological and materials science. The beamline can operate in the range 3.7 keV to 22 keV for transmission SAXS and 14 keV to 20 keV for microfocus SAXS with beam sizes of 240 µm × 60 µm [full width half-maximum (FWHM) horizontal (H) × vertical (V)] at the sample for the main beamline, and approximately 10 µm × 10 µm for the dedicated microfocusing platform. There is a versatile sample platform for accommodating a range of facilities and user-developed sample environments. The high brilliance of the insertion device source on I22 allows structural investigation of materials under extreme environments (for example, fluid flow at high pressures and temperatures). I22 provides reliable access to millisecond data acquisition timescales, essential to understanding kinetic processes such as protein folding or structural evolution in polymers and colloids.

Tests and characterization of a laterally graded multilayer Montel mirror.

Multilayers are becoming an increasingly important tool in X-ray optics. The essential parameters to design a pair of laterally graded multilayer mirrors arranged in a Montel-type configuration for use as an X-ray collimating device are provided. The results of X-ray reflectometry tests carried out on the optics in addition to metrology characterization are also shown. Finally, using experimental data and combined with X-ray tracing simulations it is demonstrated that the mirror meets all stringent specifications as required for a novel ultra-high-resolution inelastic X-ray scattering spectrometer at the Advanced Photon Source.

Interaction of fluorescent dyes with DNA and spermine using fluorescence spectroscopy.

Oligonucleotides labelled with fluorescent dyes are widely used as probes for the identification of DNA sequences in detection methods using optical spectroscopies such as fluorescence and surface enhanced Raman scattering (SERS). Spermine is widely used in surface enhanced based assays as a charge reduction and aggregating agent as it interacts strongly with the phosphate backbone and has shown to enhance the signal of a labelled oligonucleotide. The fluorescence intensity of two commonly used labels, FAM and TAMRA, were compared when spermine was added under different experimental conditions. There was a marked difference upon conjugating the free dye to an oligonucleotide, when FAM was conjugated to an oligonucleotide there was around a six fold decrease in emission, compared to a six fold increase when TAMRA was conjugated to an oligonucleotide. Dye labelled single and double stranded DNA also behaved differently with double stranded DNA labelled with FAM being a much more efficient emitter in the mid pH range, however TAMRA becomes increasingly less efficient as the pH rises. Upon addition of the base spermine, signal enhancement from the FAM labelled oligonucleotide is observed. Increasing probe concentrations of TAMRA oligonucleotide above 0.5 µM led to signal reduction most likely through quenching, either by an interaction with guanine, or through self-quenching. By using different bases for comparison, spermine and triethylamine (TEA), different affects were observed in the measured fluorescence signals. When TEA was added to FAM, a reduction in the pH dependence of fluorescence was observed, which may be useful for mid pH range assays. With the drive to increase information content and decrease time and complexity of DNA assays it is likely that more assays will be carried out in complex media such as extracted DNA fragments and PCR product. This model study indicates that dye DNA and dye spermine interactions are dye specific and that extreme care with conditions is necessary particularly if it is intended to determine the concentrations of multiple analytes using probes labelled with different dyes.

Flemish network on rare connective tissue diseases (CTD): patient pathways in systemic sclerosis. First steps taken.

Despite the low prevalence of each rare disease, the total burden is high. Patients with rare diseases encounter numerous barriers, including delayed diagnosis and limited access to high-quality treatments. In order to tackle these challenges, the European Commission launched the European Reference Networks (ERNs), cross-border networks of healthcare providers and patients representatives. In parallel, the aims and structure of these ERNs were translated at the federal and regional levels, resulting in the creation of the Flemish Network of Rare Diseases. In line with the mission of the ERNs and to ensure equal access to care, we describe as first patient pathways for systemic sclerosis (SSc), as a pilot model for other rare connective and musculoskeletal diseases. Consensus was reached on following key messages: 1. Patients with SSc should have multidisciplinary clinical and investigational evaluations in a tertiary reference expert centre at baseline, and subsequently every three to 5 years. Intermediately, a yearly clinical evaluation should be provided in the reference centre, whilst SSc technical evaluations are permissionably executed in a centre that follows SSc-specific clinical practice guidelines. In between, monitoring can take place in secondary care units, under the condition that qualitative examinations and care including interactive multidisciplinary consultations can be provided. 2. Patients with early diffuse cutaneous SSc, (progressive) interstitial lung disease and/or pulmonary arterial hypertension should undergo regular evaluations in specialised tertiary care reference institutions. 3. Monitoring of patients with progressive interstitial lung disease and/or pulmonary (arterial) hypertension will be done in agreement with experts of ERN LUNG.

Hybrid diamond-silicon angular-dispersive x-ray monochromator with 0.25-meV energy bandwidth and high spectral efficiency.

We report on the design, implementation, and performance of an x-ray monochromator with ultra-high energy resolution (ΔE/E ≃ 2.7 × 10(-8)) and high spectral efficiency using x rays with photon energies E ≃ 9.13 keV. The operating principle of the monochromator is based on the phenomenon of angular dispersion in Bragg back-diffraction. The optical scheme of the monochromator is a modification of a scheme reported earlier [Shvyd'ko et al., Phys. Rev. A 84, 053823 (2011)], where a collimator/wavelength selector Si crystal was replaced with a 100-µm-thick type IIa diamond crystal. This modification provides a very-small-energy bandwidth ΔE ≃ 0.25 meV, a 3-fold increase in the aperture of the accepted beam, a reduction in the cumulative angular dispersion rate of x rays emanating from the monochromator for better focusing on a sample, a sufficient angular acceptance matching the angular divergence of an undulator source (≈ 10 µrad), and an improved throughput due to low x-ray absorption in the thin diamond crystal. The measured spectral efficiency of the monochromator was ≈ 65% with an aperture of 0.3 × 1 mm(2). The performance parameters of the monochromator are suitable for inelastic x-ray spectroscopy with an absolute energy resolution ΔE < 1 meV.

Structural and electrical characterization of ultra-thin SrTiO3 tunnel barriers grown over YBa2Cu3O7 electrodes for the development of high Tc Josephson junctions.

The transport properties of ultra-thin SrTiO(3) (STO) layers grown over YBa(2)Cu(3)O(7) electrodes were studied by conductive atomic force microscopy at the nano-scale. A very good control of the barrier thickness was achieved during the deposition process. A phenomenological approach was used to obtain critical parameters regarding the structural and electrical properties of the system. The STO layers present an energy barrier of 0.9 eV and an attenuation length of 0.23 nm, indicating very good insulating properties for the development of high-quality Josephson junctions.

[Population-level changes to promote cardiovascular health]. / Zmeny na úrovni populace zamerené na podporu kardiovaskulárního zdraví

BACKGROUND: Cardiovascular diseases (CVD) cause 1.8 million premature (<75 years) death annually in Europe. The majority of these deaths are preventable with the most efficient and cost-effective approach being on the population level. The aim of this position paper is to assist authorities in selecting the most adequate management strategies to prevent CVD. DESIGN AND METHODS: Experts reviewed and summarized the published evidence on the major modifiable CVD risk factors: food, physical inactivity, smoking, and alcohol. Population-based preventive strategies focus on fiscal measures (e.g. taxation), national and regional policies (e.g. smoke-free legislation), and environmental changes (e.g. availability of alcohol). RESULTS: Food is a complex area, but several strategies can be effective in increasing fruit and vegetables and lowering intake of salt, saturated fat, trans-fats, and free sugars. Tobacco and alcohol can be regulated mainly by fiscal measures and national policies, but local availability also plays a role. Changes in national policies and the built environment will integrate physical activity into daily life. CONCLUSION: Societal changes and commercial influences have led to the present unhealthy environment, in which default option in life style increases CVD risk. A challenge for both central and local authorities is, therefore, to ensure healthier defaults. This position paper summarizes the evidence and recommends a number of structural strategies at international, national, and regional levels that in combination can substantially reduce CVD.

Cardiovascular determinants and prognostic significance of CC Chemokine Ligand-18 (CCL18/PARC) in patients with stable coronary artery disease.

Chemokines are important mediators of angiogenesis, hematopoiesis and leucocyte trafficking. CC Chemokine Ligand-18 (CCL18)/ pulmonary and activation-regulated chemokine (PARC) is a circulating chemokine that plays a role in injury healing, physiological homing of mononuclear blood cells and inflammatory responses. CCL18/PARC is also expressed in atherosclerotic plaques. We prospectively evaluated CCL18/PARC levels and their cardiovascular and biological determinants in a large cohort of 285 patients with stable coronary heart disease who were subsequently followed for 3 years for hard cardiac events. It was found that CCL18/PARC levels were associated with decreased cardiac function, decreased exercise capacity and increased inflammatory parameters including interleukin-6 (IL-6) and hs-CRP. More importantly high CCL18/PARC levels were an independent predictor of future cardiovascular events. Therefore, CCL18/PARC is a potential diagnostic and prognostic parameter in patients with stable coronary artery disease.

Mouse germline restriction of Oct4 expression by germ cell nuclear factor.

The POU-domain transcription factor Oct4 is essential for the maintenance of the mammalian germline. In this study, we show that the germ cell nuclear factor (GCNF), an orphan nuclear receptor, represses Oct4 gene activity by specifically binding within the proximal promoter. GCNF expression inversely correlates with Oct4 expression in differentiating embryonal cells. GCNF overexpression in embryonal cells represses Oct4 gene and transgene activities, and we establish a link to transcriptional corepressors mediating repression by GCNF. In GCNF-deficient mouse embryos, Oct4 expression is no longer restricted to the germ cell lineage after gastrulation. Our studies suggest that GCNF is critical in repressing Oct4 gene activity as pluripotent stem cells differentiate and in confining Oct4 expression to the germline.

Ages of crystalline rocks from fra mauro.

Crystallization ages for six rocks from Fra Mauro have been measured by the argon-40-argon-39 method. All six rocks give an age of 3.77 +/- 0.15 x 10(9) years, which is the same as for fragmental rocks from this site. It is concluded that the Imbrium event and the crystallization of a significant portion of the pre-Imbrian basalts were essentially contemporaneous.

Age of a lunar anorthosite.

The crystallization age of an Apollo 15 anorthosite rock, 15415,9, returned from the lunar highlands has been measured to be (4.09 +/- 0.19) x 10(9) years. The primitive lunar crust must have been formed in the first 300 to 400 x 10(6) years. The results give some credence to the hypothesis that the primitive lunar surface was molten and large-scale fractional crystallization occurred in the early history of the moon.

Authigenic potassium feldspar in cambrian carbonates: evidence of alleghanian brine migration.

The shallow-water limestones and dolostones of the Conococheague Limestone (Upper Cambrian) of western Maryland contain large amounts of authigenic potassium feldspar. The presence of halite daughter crystals in breached fluid inclusions, low whole-rock ratios of chlorine to bromine, and thermochemical data suggest that the potassium feldspar formed at low temperature by the reaction of connate brines with intercalated siliciclastic debris. Analyses of argon age spectra indicate that the authigenic feldspar probably formed during Late Pennsylvanian to Early Permian time. These results may indicate mobilization and migration of connate brines brought about by Alleghanian folding. The widespread occurrence of authigenic potassium feldspar in Cambrian and Ordovician carbonate rocks throughout the Appalachians suggests that this may have occurred throughout the entire basin.

Early miocene subglacial basalts, the East antarctic ice sheet, and uplift of the transantarctic mountains.

Subglacially erupted volcanic rocks from Mount Early and Sheridan Bluff, Antarctica, yield whole-rock potassium-argon dates and argon-40/argon-39 release spectra of Early Miocene age. Field associations suggest the existence of the East Antarctic ice sheet and significant uplift of the Transantarctic Mountains by that time.

40Ar-39Ar Dating of the Manson Impact Structure: A Cretaceous-Tertiary Boundary Crater Candidate.

The mineralogy of shocked mineral and lithic grains in the Cretaceous-Tertiary (K-T) boundary claystone worldwide is most consistent with a bolide impact on a continent. Both the concentrations and sizes of these shocked grains are greatest in the western interior of North America. These data suggest that the Manson impact structure in north-central Iowa is a viable candidate for the K-T boundary impact event. Argon-40-argon-39 age spectrum dating of shocked microcline from the crystalline central uplift of the Manson impact structure indicates that there was severe argon-40 loss at 65.7 +/- 1.0 million years ago, an age that is indistinguishable from that of the K-T boundary, within the limits of analytical precision.

Botanical and geological significance of potassium-argon dates from the juan fernandez islands.

Potassium-argon dating of five basalts from the three main islands of the Juan Fernández (or Robinson Crusoe) Islands of Chile in the southeastern Pacific gives ages of 1.01 +/- 0.12 and 2.44 +/- 0.14 million years for Masafuera, 3.79 +/- 0.20 and 4.23 +/- 0.16 for Masatierra, and 5.8 +/- 2.1 for Santa Clara. These ages are much younger than that of the underlying oceanic plate and are consistent with the origin of the island-seamount chain from a mantle hot spot beneath the eastward moving Nazca plate. The young age for the archipelago suggests that speciation within endemic genera has occurred within the past 4 to 5 million years. Endemic genera of apparently more ancient origins, such as Lactoris and Thyrsopteris, have apparently dispersed to the islands and survive refugially.

[Guidelines on cardiovascular disease prevention in clinical practice. Belgian Working Group on Cardiovascular Prevention and Rehabilitation]. / Recommandations relatives a la prévention des maladies cardiovasculaires en pratique clinique. Groupe de travail belge de prévention des maladies cardiovasculaires.

Since more than 15 years, expert groups and various European Scientific Societies have written Guidelines on Cardiovascular Disease Prevention. Because of the rapid evolution of science, it is necessary to adapt regularly these guidelines. The last version dates from 2007 and has been written by the " Fourth Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in Clinical Practice ". In this issue, the more recent Guidelines are summarised and we focus on highlighting the aspects of these Guidelines that have changed since the previous version published in this journal in 2005.