Matrix γ-carboxyglutamate (Gla) protein (MGP) is an important local inhibitor of vascular calcification, which can undergo two post-translational modifications: vitamin K-dependent γ-glutamate ...carboxylation and serine phosphorylation. While carboxylation is thought to have effects upon binding of calcium-ions, phosphorylation is supposed to affect the cellular release of MGP. Since both modifications can be exerted incompletely, various MGP species can be detected in the circulation. MGP levels were measured with two commercially available competitive and two novel sandwich assays in healthy controls, in patients with rheumatic disease, aortic valve disease, and end-stage renal disease, as well as in volunteers after vitamin K supplementation (VKS) and treatment with vitamin K antagonists (VKA). Major differences were found between the MGP assays, including significantly different behaviour with regard to vascular disease and the response to VKA and VKS. The dual-antibody assay measuring non-phosphorylated, non-carboxylated MGP (dp-ucMGP) was particularly sensitive for these changes and would be suited to assess the vascular vitamin K status. We conclude that the different assays for particular circulating MGP species allows the assessment of various aspects of the MGP system.
Summary Background Unruptured intracranial aneurysms (UIAs) are increasingly detected and are an important health-care burden. We aimed to assess the prevalence of UIAs according to family history, ...comorbidity, sex, age, country, and time period. Methods Through searches of PubMed, Embase, and Web of Science we updated our 1998 systematic review up to March, 2011. We calculated prevalences and prevalence ratios (PRs) with random-effects binomial meta-analysis. We assessed time trends with year of study as a continuous variable. Findings We included 68 studies, which reported on 83 study populations and 1450 UIAs in 94 912 patients from 21 countries. The overall prevalence was estimated as 3·2% (95% CI 1·9–5·2) in a population without comorbidity, with a mean age of 50 years, and consisting of 50% men. Compared with populations without the comorbidity, PRs were 6·9 (95% CI 3·5–14) for autosomal dominant polycystic kidney disease (ADPKD), 3·4 (1·9–5·9) for a positive family history of intracranial aneurysm of subarachnoid haemorrhage, 3·6 (0·4–30) for brain tumour, 2·0 (0·9–4·6) for pituitary adenoma, and 1·7 (0·9–3·0) for atherosclerosis. The PR for women compared with men was 1·61 (1·02–2·54), with a ratio of 2·2 (1·3–3·6) in study populations with a mean age of more than 50 years. Compared with patients older than 80 years, we found no differences by age, except for patients younger than 30 years (0·01, 0·00–0·12). Compared with the USA, PRs were similar for other countries, including Japan (0·8, 0·4–1·7) and Finland (1·0, 0·4–2·4). There was no statistically significant time trend. Interpretation The prevalence of UIAs is higher in patients with ADPKD or a positive family history of intracranial aneurysm of subarachnoid haemorrhage than in people without comorbidity. In Finland and Japan, the higher incidence of subarachnoid haemorrhage is not explained by a higher prevalence of UIAs, implicating higher risks of rupture. Funding Julius Centre for Health Sciences and Primary Care and Department of Neurology and Neurosurgery, University Medical Centre, Utrecht.
This study was originally conceived to test in a rigorous way the specificity of three major approaches to high-throughput array-based DNA methylation analysis: (1) MeDIP, or methylated DNA ...immunoprecipitation, an example of antibody-mediated methyl-specific fractionation; (2) HELP, or HpaII tiny fragment enrichment by ligation-mediated PCR, an example of differential amplification of methylated DNA; and (3) fractionation by McrBC, an enzyme that cuts most methylated DNA. These results were validated using 1466 Illumina methylation probes on the GoldenGate methylation assay and further resolved discrepancies among the methods through quantitative methylation pyrosequencing analysis. While all three methods provide useful information, there were significant limitations to each, specifically bias toward CpG islands in MeDIP, relatively incomplete coverage in HELP, and location imprecision in McrBC. However, we found that with an original array design strategy using tiling arrays and statistical procedures that average information from neighboring genomic locations, much improved specificity and sensitivity could be achieved, e.g., approximately 100% sensitivity at 90% specificity with McrBC. We term this approach "comprehensive high-throughput arrays for relative methylation" (CHARM). While this approach was applied to McrBC analysis, the array design and computational algorithms are fractionation method-independent and make this a simple, general, relatively inexpensive tool suitable for genome-wide analysis, and in which individual samples can be assayed reliably at very high density, allowing locus-level genome-wide epigenetic discrimination of individuals, not just groups of samples. Furthermore, unlike the other approaches, CHARM is highly quantitative, a substantial advantage in application to the study of human disease.
► Ulva lactuca was characterized as feedstock for the acetone, butanol and ethanol fermentation. ► Hydrolysates were obtained using mild pretreatment conditions and commercial cellulases. ► Ulva ...lactuca hydrolysate was used as substrate for fermentation by two different strains. ► Rhamnose was utilized by C. beijerinckii for production of 1,2-propanediol.
Green seaweed Ulva lactuca harvested from the North Sea near Zeeland (The Netherlands) was characterized as feedstock for acetone, ethanol and ethanol fermentation. Solubilization of over 90% of sugars was achieved by hot-water treatment followed by hydrolysis using commercial cellulases. A hydrolysate was used for the production of acetone, butanol and ethanol (ABE) by Clostridium acetobutylicum and Clostridium beijerinckii. Hydrolysate-based media were fermentable without nutrient supplementation. C. beijerinckii utilized all sugars in the hydrolysate and produced ABE at high yields (0.35g ABE/g sugar consumed), while C. acetobutylicum produced mostly organic acids (acetic and butyric acids). These results demonstrate the great potential of U. lactuca as feedstock for fermentation. Interestingly, in control cultures of C. beijerinckii on rhamnose and glucose, 1,2 propanediol was the main fermentation product (9.7g/L).
This research proposes a periodic review multi-item two-layer inventory model. The main contribution is a novel approach to determine the can-order threshold in a two-layer model under time-dependent ...and uncertain demand and setup costs. The first layer consists of a learning mechanism to forecast demand and forecast setup costs. The second layer involves the coordinated replenishment of items, which is analysed as a Bayesian game with uncertain prior probability distribution. The research builds on the concept of the (
S
,
c
,
s
) policy, which is extended to the case of uncertain and time-dependent parameters.
Pivotal randomized trials demonstrating efficacy, safety and good tolerance, of two new potassium binders (patiromer and sodium zirconium cyclosilicate) led to their recent approval. A major hurdle ...to the implementation of these potassium-binders is understanding how to integrate them safely and effectively into the long-term management of cardiovascular and kidney disease patients using renin angiotensin aldosterone system inhibitors (RAASi), the latter being prone to induce hyperkalaemia.
A multidisciplinary academic panel including nephrologists and cardiologists was convened to develop consensus therapeutic algorithm(s) aimed at optimizing the use of the two novel potassium binders (patiromer and sodium zirconium cyclosilicate) in stable adults who require treatment with RAASi and experience(d) hyperkalaemia in a non-emergent setting.
Two dedicated pragmatic algorithms are proposed. The lowest intervention threshold (i.e. 5.1 mmol/L or greater) was the one used in the patiromer and sodium zirconium cyclosilicate) pivotal trials, both drugs being indicated to treat hyperkalaemia in a non -emergent setting. Acknowledging the heterogeneity across specialty guidelines in hyperkalaemia definition and thresholds to intervene when facing hyperkalaemia, we have been mindful to use soft language i.e. “it is to consider”, not necessarily “to do”.
Providing the clinical community with pragmatic algorithms may help optimize the management of high-risk patients by avoiding the risks of both hyper and hypokalaemia and of suboptimal RAASi therapy
In patients with iron deficiency anemia, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) allow high-dose iron repletion. While FCM is reported to induce hypophosphatemia, the frequency of ...hypophosphatemia after an equivalent dosage of FDI had not been assessed prospectively.
In the prospective, single-center, double-blind HOMe aFers study, 26 women with iron deficiency anemia (hemoglobin < 12 g/dL plus either plasma ferritin ≤ 100 ng/mL or a plasma ferritin ≤ 300 ng/mL and transferrin saturation (TSAT) ≤ 30%) were randomized to a single intravenous infusion of 20 mg/kg body weight (up to a maximum of 1000 mg) FCM or FDI. The primary endpoint was the incidence of hypophosphatemia (plasma phosphorus levels < 2.0 mg/dL at day 1, day 7 ± 2, and/or day 35 ± 2 after the infusion). In order to investigate potential skeletal and cardiovascular implications, we assessed changes in other components of mineral and bone metabolism, left ventricular function, and arrhythmias.
Hypophosphatemia occurred more frequently in women treated with FCM (9 out of 12 75%) than in those treated with FDI (1 out of 13 8%; p = 0.001). Within 24 h after iron supplementation, women in the FCM group had significant higher plasma intact FGF23 (p < 0.001) and lower plasma 1.25-dihydroxyvitamin D (p < 0.001). As an indicator of urinary phosphorus losses, urinary fractional phosphorus excretion was higher in the FCM group (p = 0.021 at day 7 ± 2 after iron supplementation). We did not observe differences in skeletal and cardiovascular markers, potentially because of the limited number of participants.
While both FCM and FDI provide efficient iron repletion in participants with iron deficiency anemia, FCM induced hypophosphatemia more often than FDI.
Clinical Trials.gov NCT02905539. Registered on 8 September 2016. 2015-004808-36 (EudraCT Number) U1111-1176-4563 (WHO Universal Trial Number) DRKS00010766 (Deutsches Register Klinischer Studien).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
A study on the scalability of discharge characteristics of a single-filament dielectric barrier discharge (DBD) to a spatially one-dimensional multi-filament arrangement driven by the same ...high-voltage (HV) pulses was performed for a gas mixture of 0.1 vol% O
2
in N
2
at 1 bar. Both arrangements feature a 1 mm gap with dielectric-covered electrodes featuring two hemispherical alumina caps for the single-filament and two parallel alumina-tubes for the multi-filament arrangement. The DBDs were characterised by electrical measurements (for peak current, energy, and power) accompanied by iCCD and streak imaging to determine the filament number and the discharge development in the gas gap and on the surfaces. It was found that the electrical quantities scale with a constant factor between the single- and multi-filament arrangement, which is expected to be related to the filament number. In the multi-filament arrangement, the pulsed operation leads to filament formation in the entire gap in lateral direction within less than 2 ns. Furthermore, particular breakdown or discharge inception regimes were identified for the multi-filament DBDs. These regimes could be generated at the falling slope of asymmetrical HV pulses featuring e.g. a double-streamer propagation, which was previously reported for single-filament DBDs. Consequently, it was proven that the discharge manipulation by varying the HV pulse widths obtained for single-filament DBDs can also be applied in a one-dimensional multi-filament arrangement, i.e. an upscaling based on the knowledge for single-filament DBDs seems to be generally possible.
We have studied exclusive, radiative B meson decays to charmless mesons in 9.7x10(6) B decays accumulated with the CLEO detector. We measure B(B0-->K(*0)(892)gamma) = (4.55(+0.72)(-0. ...68)+/-0.34)x10(-5) and B(B+-->K(*+)(892)gamma) = (3.76(+0.89)(-0. 83)+/-0.28)x10(-5). We have searched for CP asymmetry in B-->K(*)(892)gamma decays and measure A(CP) = +0.08+/-0.13+/-0.03. We report the first observation of B-->K(*)(2)(1430)gamma decays with a branching fraction of (1.66(+0.59)(-0.53)+/-0.13)x10(-5). No evidence for the decays B-->rhogamma and B0-->omegagamma is found and we limit B(B-->(rho/omega)gamma)/B(B-->K(*)(892)gamma)<0.32 at 90% C.L.
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