Beyond deficiency:Potential benefits of increased intakesof vitamin K for bone and vascular health

Vitamin K is wellknown for its role in the synthesisof a number of blood coagulationfactors.During recent years vitaminK-dependent proteins werediscovered to be of vital importancefor bone and vascular health.Recommendations for dietary vitaminK intake have been made onthe basis of the hepatic requirementsfor the synthesis of bloodcoagulation factors.Accumulatingevidence suggests that the requirementsfor other functions thanblood coagulation may be higher.This paper is the result of a closedworkshop (Paris,November 2002)in which a number of Europeanvitamin K experts reviewed theavailable data and formulated theirstandpoint with respect to recommendeddietary vitamin K intakeand the use of vitamin K-containingsupplements

Role of RhoA and rho kinase in lysophosphatidic acid-induced endothelial barrier dysfunction.

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The anisotropy of granular materials

The effect of the anisotropy on the elastoplastic response of two dimensional packed samples of polygons is investigated here, using molecular dynamics simulation. We show a correlation between fabric coefficients, characterizing the anisotropy of the granular skeleton, and the anisotropy of the elastic response. We also study the anisotropy induced by shearing on the subnetwork of the sliding contacts. This anisotropy provides an explanation to some features of the plastic deformation of granular media.Comment: Submitted to PR

A quadrature filter approach for registration accuracy assessment of fundus images

This paper presents a method to automatically assess the accuracy of image registration. It is applicable to images in which vessels are the main landmarks such as fundus images and angiography. The method simultaneously exploits not only the position, but also the intensity profile across the vasculatures. The accuracy measure is defined as the energy of the odd component of the 1D vessel profile in the difference image divided by the total energy of the corresponding vessels in the constituting images. Scale and orientation-selective quadrature filter banks have been employed to analyze the 1D signal profiles. Subsequently, the relative energy measure has been calibrated such that the measure translates to a spatial misalignment in pixels. The method was validated on a fundus image dataset from a diabetic retinopathy screening program at the Rotterdam Eye Hospital. An evaluation showed that the proposed measure assesses the registration accuracy with a bias of -0.1 pixels and a precision (standard deviation) of 0.9 pixels. The small Fourier footprint of the orientation selective quadrature filters makes the method robust against noise

Development of a Synthetic Earth Gravity Model by 3D mass optimisation based on forward modelling

Several previous Synthetic Earth Gravity Model (SEGM) simulations are based on existing information about the Earth’s internal mass distribution. However, currently available information is insufficient to model the Earth’s anomalous gravity field on a global scale. The low-frequency information is missing when modelling only topography, bathymetry and crust (including the Mohorovičić discontinuity), but the inclusion of information on the mantle and core does not seem to significantly improve this situation. This paper presents a method to determine a more realistic SEGM by considering simulated 3D mass distributions within the upper mantle as a proxy for all unmodelled masses within the Earth.The aim is to improve an initial SEGM based on forward gravity modelling of the topography, bathymetry and crust such that the missing low-frequency information is now included. The simulated 3D mass distribution has been derived through an interactive and iterative mass model optimisation algorithm, which minimises geoid height differences with respect to a degree-360 spherical harmonic expansion of the EGM2008 global external gravity field model. We present the developed optimisation algorithm by applying it to the development of a global SEGM that gives a reasonably close fit to EGM2008, and certainly closer than a SEGM based only on the topography, bathymetry and crust

Possible mineral contributions to the diet and health of wild chimpanzees in three East African forests

For financial support, the authors acknowledge the Mohamed bin Zayed Species Conservation Fund grant numbers 0925272, 10251055, 11252562, 12254904, the Royal Zoological Society of Scotland, the Leverhulme Trust grant number ECF‐2013‐507, and the Boise Fund.We present new data on the ingestion of minerals from termite mound soil by East African chimpanzees (Pan troglodytes schweinfurthii) living in the Budongo Forest Reserve, Uganda, the Gombe National Park and the Mahale Mountains National Park, Tanzania. Termite mound soil is here shown to be a rich source of minerals, containing high concentrations of iron and aluminum. Termite mound soil is not, however, a source of sodium. The concentrations of iron and aluminum are the highest yet found in any of the mineral sources consumed. Levels of manganese and copper, though not so high as for iron and aluminum, are also higher than in other dietary sources. We focus on the contribution of termite mound soil to other known sources of mineral elements consumed by these apes, and compare the mineral content of termite soil with that of control forest soil, decaying wood, clay, and the normal plant‐based chimpanzee diet at Budongo. Samples obtained from Mahale Mountains National Park and Gombe National Park, both in Tanzania, show similar mineral distribution across sources. We suggest three distinct but related mechanisms by which minerals may come to be concentrated in the above‐mentioned sources, serving as potentially important sources of essential minerals in the chimpanzee diet.PostprintPeer reviewe

LONGITUDINAL STUDY OFRPE65-ASSOCIATED INHERITED RETINAL DEGENERATIONS

Purpose: To study the disease course ofRPE65-associated inherited retinal degenerations (IRDs) as a function of the genotype, define a critical age for blindness, and identify potential modifiers. Methods: Forty-five patients with IRD from 33 families with biallelicRPE65mutations, 28 stemming from a genetic isolate. We collected retrospective data from medical charts. Coexisting variants in 108 IRD-associated genes were identified with Molecular Inversion Probe analysis. Results: Most patients were diagnosed within the first years of life. Daytime visual function ranged from near-normal to blindness in the first four decades and met WHO criteria for blindness for visual acuity and visual field in the fifth decade. p.(Thr368His) was the most common variant (54%). Intrafamilial variability and interfamilial variability in disease severity and progression were observed. Molecular Inversion Probe analysis confirmed allRPE65variants and identified one additional variant inLRATand one inEYSin two separate patients. Conclusion: All patients withRPE65-associated IRDs developed symptoms within the first year of life. Visual function in childhood and adolescence varied but deteriorated inevitably toward blindness after age 40. In this study, genotype was not predictive of clinical course. The variance in severity of disease could not be explained by double hits in other IRD genes

A retrospective analysis of noise-induced hearing loss in the Dutch construction industry

Purpose Noise exposure is an important and highly prevalent occupational hazard in the construction industry. This study examines hearing threshold levels of a large population of Dutch construction workers and compares their hearing thresholds to those predicted by ISO-1999. Methods In this retrospective study, medical records of periodic occupational health examinations of 29,644 construction workers are analysed. Pure-tone audiometric thresholds of noise-exposed workers are compared to a non-exposed control group and to ISO-1999 predictions. Regression analyses are conducted to explore the relationship between hearing loss and noise intensity, noise exposure time and the use of hearing protection. Results Noise-exposed workers had greater hearing losses compared to their non-noise-exposed colleagues and to the reference population reported in ISO-1999. Noise exposure explained only a small proportion of hearing loss. When the daily noise exposure level rose from 80 dB(A) towards 96 dB(A), only a minor increase in hearing loss is shown. The relation of exposure time and hearing loss found was similar to ISO-1999 predictions when looking at durations of 10 years or more. For the first decade, the population medians show poorer hearing than predicted by ISO-1999. Discussion Duration of noise exposure was a better predictor than noise exposure levels, probably because of the limitations in noise exposure estimations. In this population, noise-induced hearing loss was already present at the beginning of employment and increased at the same rate as is predicted for longer exposure duration

Outcomes of rare patients with a primary cutaneous CD30(+) lymphoproliferative disorder developing extracutaneous disease

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Reduced Vitamin K Status as a Potentially Modifiable Risk Factor of Severe Coronavirus Disease 2019

BACKGROUND: Respiratory failure and thromboembolism are frequent in SARS-CoV-2-infected patients. Vitamin K activates both hepatic coagulation factors and extrahepatic endothelial anticoagulant protein S, required for thrombosis prevention. In times of vitamin K insufficiency, hepatic procoagulant factors are preferentially activated over extrahepatic proteins. Vitamin K also activates matrix Gla protein (MGP), which protects against pulmonary and vascular elastic fiber damage. We hypothesized that vitamin K may be implicated in coronavirus disease 2019 (COVID-19), linking pulmonary and thromboembolic disease. METHODS: 135 hospitalized COVID-19 patients were compared with 184 historical controls. Poor outcome was defined as invasive ventilation and/or death. Inactive vitamin K-dependent MGP (dp-ucMGP) and prothrombin (PIVKA-II) were measured, inversely related to extrahepatic and hepatic vitamin K status, respectively. Desmosine was measured to quantify the rate of elastic fiber degradation. Arterial calcification severity was assessed by computed tomography. RESULTS: Dp-ucMGP was elevated in COVID-19 patients compared to controls (p<0.001), with even higher dp-ucMGP in patients with poor outcomes (p<0.001). PIVKA-II was normal in 82.1% of patients. Dp-ucMGP was correlated with desmosine (p<0.001), and coronary artery (p=0.002) and thoracic aortic (p<0.001) calcification scores. CONCLUSIONS: Dp-ucMGP was severely increased in COVID-19 patients, indicating extrahepatic vitamin K insufficiency, which was related to poor outcome while hepatic procoagulant factor II remained unaffected. These data suggest a mechanism of pneumonia-induced extrahepatic vitamin K depletion leading to accelerated elastic fiber damage and thrombosis in severe COVID-19 due to impaired activation of MGP and endothelial protein S, respectively. A clinical trial could assess whether vitamin K administration improves COVID-19 outcomes