Effect of Combination Folic Acid, Vitamin B6 , and Vitamin B12 Supplementation on Fracture Risk in Women: A Randomized, Controlled Trial.

Epidemiologic studies have demonstrated an association of elevated plasma homocysteine levels with greater bone resorption and fracture risk. Vitamins B12 , B6 , and folic acid are cofactors in homocysteine metabolism, and supplementation with B vitamins is effective in lowering homocysteine levels in humans. However, randomized trials of supplemental B vitamins for reduction of fracture risk have been limited. Therefore, we performed an ancillary study to the Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a large randomized trial of women with preexisting cardiovascular disease or three or more coronary risk factors, to test whether a daily B vitamin intervention including folic acid (2.5 mg/day), vitamin B6 (50 mg/day), and vitamin B12 (1 mg/day) reduces nonspine fracture risk over 7.3 years of treatment and follow-up. Among 4810 women, we confirmed 349 nonspine fracture cases by centralized review of medical records. In a substudy of 300 women (150 in treatment group and 150 controls) with paired plasma samples at randomization and follow-up (7.3 years later), we measured two bone turnover markers, including C-terminal cross-linking telopeptide of type I collagen (CTX) and intact type I procollagen N-propeptide (P1NP). In Cox proportional hazards models based on intention-to-treat, we found no significant effects of B vitamin supplementation on nonspine fracture risk (relative hazard = 1.08; 95% confidence interval, 0.88 to 1.34). In a nested case-cohort analysis, there were no significant effects of B vitamins on fracture risk among women with elevated plasma homocysteine levels, or low levels of vitamins B12 or B6 , or folate at baseline. Furthermore, treatment with B vitamins had no effect on change in markers of bone turnover. We found no evidence that daily supplementation with B vitamins reduces fracture risk or rates of bone metabolism in middle-aged and older women at high risk of cardiovascular disease. © 2017 American Society for Bone and Mineral Research

SAR-based Wind Resource Statistics in the Baltic Sea

Ocean winds in the Baltic Sea are expected to power many wind farms in the coming years. This study examines satellite Synthetic Aperture Radar (SAR) images from Envisat ASAR for mapping wind resources with high spatial resolution. Around 900 collocated pairs of wind speed from SAR wind maps and from 10 meteorological masts, established specifically for wind energy in the study area, are compared. The statistical results comparing in situ wind speed and SAR-based wind speed show a root mean square error of 1.17 m s−1, bias of −0.25 m s−1, standard deviation of 1.88 m s−1 and correlation coefficient of R2 0.783. Wind directions from a global atmospheric model, interpolated in time and space, are used as input to the geophysical model function CMOD-5 for SAR wind retrieval. Wind directions compared to mast observations show a root mean square error of 6.29° with a bias of 7.75°, standard deviation of 20.11° and R2 of 0.950. The scale and shape parameters, A and k, respectively, from the Weibull probability density function are compared at only one available mast and the results deviate ~2% for A but ~16% for k. Maps of A and k, and wind power density based on more than 1000 satellite images show wind power density values to range from 300 to 800 W m−2 for the 14 existing and 42 planned wind farms

Modelling Hot Spots of Soil Loss by Wind Erosion (SoLoWind) in Western Saxony, Germany

Land Degradation and Development published by John Wiley & Sons, Ltd. While it needs yet to be assessed whether or not wind erosion in Western Saxony is a major point of concern regarding land degradation and fertility, it has already been recognized that considerable off-site effects of wind erosion in the adjacent regions of Saxony-Anhalt and Brandenburg are connected to the spread of herbicides, pesticides and dust. So far, no wind erosion assessment for Western Saxony, Germany, exists. The wind erosion model previously applied for Germany (DIN standard 19706) is considering neither changes in wind direction over time nor influences of field size. This study aims to provide a first assessment of wind erosion for Western Saxony by extending the existing DIN model to a multidirectional model on soil loss by wind (SoLoWind) with new controlling factors (changing wind directions, soil cover, mean field length and mean protection zone) combined by fuzzy logic. SoLoWind is used for a local off-site effect evaluation in combination with high-resolution wind speed and wind direction data at a section of the highway A72. The model attributes 3·6% of the arable fields in Western Saxony to the very-high-wind erosion risk class. A relationship between larger fields (greater than 116 ha) and higher proportions (51·7%) of very-high-wind erosion risk can be observed. Sections of the highway A72 might be under high risk according to the modelled off-site effects of wind erosion. The presented applications showed the potential of SoLoWind to support and consult management for protection measures on a regional scale. © 2016 The Authors. Land Degradation and Development published by John Wiley & Sons, Ltd.The authors would like to thank Jürgen Heinrich and Gudrun Mayer for the technical revision of the model conception and the German Weather Service, the Saxon State Office for the Environment, Agriculture and Geology, the Saxon State Office for Road Construction and Traffic, the Saxon State Ministry of the Environment and Agriculture, the Saxon State Spatial Data and Land Survey Corporation, the Saxon Road Maintenance Depots, OpenStreetMap and the National Aeronautics and Space Administration for providing the datasets. We would also like to thank three anonymous reviewers for helpful comments.info:eu-repo/semantics/publishedVersio

The homocysteine controversy

Mild to moderate hyperhomocysteinemia has been identified as a strong predictor of cardiovascular disease, independent from classical atherothrombotic risk factors. In the last decade, a number of large intervention trials using B vitamins have been performed and have shown no benefit of homocysteine-lowering therapy in high-risk patients. In addition, Mendelian randomization studies failed to convincingly demonstrate that a genetic polymorphism commonly associated with higher homocysteine levels (methylenetetrahydrofolate reductase 677 C>T) is a risk factor for cardiovascular disease. Together, these findings have cast doubt on the role of homocysteine in cardiovascular disease pathogenesis, and the homocysteine hypothesis has turned into a homocysteine controversy. In this review, we attempt to find solutions to this controversy. First, we explain that the Mendelian randomization analyses have limitations that preclude final conclusions. Second, several characteristics of intervention trials limit interpretation and generalizability of their results. Finally, the possibility that homocysteine lowering is in itself beneficial but is offset by adverse side effects of B vitamins on atherosclerosis deserves serious attention. As we explain, such side effects may relate to direct adverse effects of the B-vitamin regimen (in particular, the use of high-dose folic acid) or to proinflammatory and proproliferative effects of B vitamins on advanced atherosclerotic lesions

Translational models for vascular cognitive impairment: a review including larger species.

BACKGROUND: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited. METHODS: We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, hyperhomocysteinemia, high-salt/high-fat diet) or reproduce genetic causes of VCI (CADASIL-causing Notch3 mutations). CONCLUSIONS: We concluded that (1) translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; (2) rodent models of VCI are limited by paucity of white matter; and (3) further translational models, and improved cognitive testing instruments, are required

Inflammation, genetic background and longevity

Ageing is an inexorable intrinsic process that affects all cells, tissues, organs and individuals. Due to a diminished homeostasis and increased organism frailty, ageing causes a reduction of the response to environmental stimuli and, in general, is associated to an increased predisposition to illness and death. Actually, it is characterized by a state of reduced ability to maintain health and general homeodynamics of the organism.Alarge part of the ageing phenotype is explained by an imbalance between inflammatory and anti-inflammatory networks, which results in the low grade chronic pro-inflammatory status of ageing, ‘‘inflamm-ageing’’. It is strictly linked to immunosenescence, and on the whole they are the major contributory factors to the increased frequency of morbidity and mortality among elderly. Inflammageing is compatible with longevity; even if centenarians have an increased level of inflammatory mediators in comparison to old subjects and they are very frail, they also have high level of anti-inflammatory cytokines together with protective genotypes. Actually, data on case control studies performed in Italian centenarians suggest that a pro-inflammatory genotype is unfavourable to reach extreme longevity in good health and likely favours the onset of age-related diseases such as cardiovascular diseases and Alzheimer’s disease, the leading causes of mortality and disability in the elderly. However, many associations between gene variants and longevity have been found only in Italian population. This should not be unexpected, since ageing and longevity are complex traits resulting not only and not exclusively from genetics, but rather from the interactions between genetics, environment and chance

Folic acid fortification and public health: Report on threshold doses above which unmetabolised folic acid appear in serum

BACKGROUND: All flour in the USA is fortified with folic acid at a level of 140 μg/100 g which is estimated to supply an extra 100 μg daily to the average diet. Some researchers have advocated that this be increased to double and even four times this amount. Based on previous research these higher levels are likely to lead to the appearance of unmetabolised vitamin in the circulation, which may have safety implications for sub-groups of the population. The UK and the Republic of Ireland will likely introduce mandatory fortification also in the next year or so. The aim of this study was to capture the short-term effect of folic acid fortification on unmetabolised folic acid in serum after chronic consumption of folic acid. METHODS: After pre-saturation with 400 μg folic acid supplements daily for 14-weeks, healthy folate replete adults (n = 20) consumed folic acid fortified bread, at three different levels (400 μg, 200 μg, 100 μg) over a period of one week each. The dose was administered in two-equal sized slices consumed at 09.00 hrs and 13.00 hrs. Serum samples for total folate and folic acid were collected at baseline, after 14-weeks of supplementation, and pre and post (at 1, 2, 3 and 4 hours) each dose tested. RESULTS: Unmetabolised folic acid was detected after the 14-week supplementation period. Folic acid was not detected in either the 200 μg or 100 μg (current US regime) doses tested but was present at the highest level (400 μg) tested. CONCLUSION: Our findings suggest that persons exposed to the current US fortification programme supplying an average of 100 μg per day or less are unlikely to have unmetabolised folic acid in serum. It also seems that daily consumption of the higher level of 200 μg or less is unlikely to be problematic. Increasing the level however to 400 μg on the other hand is likely to lead to unmetabolised folic acid appearance

Variation in flexural, morphological, and biochemical leaf properties of eelgrass (Zostera marina) along the European Atlantic climate regions

Seagrasses need to withstand hydrodynamic forces; therefore, mechanical properties such as flexibility or breaking resistance are beneficial for survival. The co-variation of leaf breaking properties with biochemical traits in seagrasses has been documented, but it is unknown if the same patterns apply to leaf flexural properties. To interpret changes in the ecological function of seagrass ecosystems based on acclimation responses to environmental changes, it is necessary to understand the factors that affect flexural leaf properties. Here, morphological and flexural leaf properties of the perennial type of Zostera marina across different environmental conditions along European Atlantic climate regions are presented together with C:N ratio and neutral detergent fibre content as descriptors of biochemical leaf composition. Eelgrass leaves from cold regions were similar to threefold more elastic and similar to tenfold more flexible, were also narrower (1.7-fold), and contained similar to 1.9-fold higher fibre content than from plants growing in warmer regions. Eelgrass also showed acclimation to local conditions such as seasonality, water depth, and hydrodynamic exposure. Leaves collected from exposed or shallower locations or during winter were more flexible, suggesting an avoidance strategy to hydrodynamic forcing, which is generally higher under those conditions. Flexural rigidity was almost equally controlled by bending modulus (35%) and leaf thickness (37%), indicating functional differences compared to leaf breaking described in the literature. Overall, the findings indicate that Zostera marina has a high flexural plasticity and high acclimation capacity to some climate change effects such as sea level rise and increase in storm frequency and intensity.German Science FoundationGerman Research Foundation (DFG) [PA 2547/1-1]Royal Swedish Academy of Sciences (KVA travel grant)FCT-Foundation for Science and TechnologyPortuguese Foundation for Science and Technology [UID/Multi/04326/2019, SFRH/BPD/119344/2016

Stromal gene signatures in large-B-cell lymphomas.

BACKGROUND: The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear. METHODS: We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression-based survival-predictor model derived from a training group was tested in a validation group. RESULTS: A multivariate model created from three gene-expression signatures--termed germinal-center B-cell, stromal-1, and stromal-2 --predicted survival both in patients who received CHOP and patients who received R-CHOP. The prognostically favorable stromal-1 signature reflected extracellular-matrix deposition and histiocytic infiltration. By contrast, the prognostically unfavorable stromal-2 signature reflected tumor blood-vessel density. CONCLUSIONS: Survival after treatment of diffuse large-B-cell lymphoma is influenced by differences in immune cells, fibrosis, and angiogenesis in the tumor microenvironment

A Pivotal Role of Vitamin B9 in the Maintenance of Regulatory T Cells In Vitro and In Vivo

Dietary factors regulate immunological function, but the underlying mechanisms remain elusive. Here we show that vitamin B9 is a survival factor for regulatory T (Treg) cells expressing high levels of vitamin B9 receptor (folate receptor 4). In vitamin B9-reduced condition in vitro, Treg cells could be differentiated from naïve T cells but failed to survive. The impaired survival of Treg cells was associated with decreased expression of anti-apoptotic Bcl2 and independent of IL-2. In vivo depletion of dietary vitamin B9 resulted in the reduction of Treg cells in the small intestine, a site for the absorption of dietary vitamin B9. These findings provide a new link between diet and the immune system, which could maintain the immunological homeostasis in the intestine