A follow up study on the efficacy of metadoxine in the treatment of alcohol dependence

BACKGROUND: We carried out a three months follow-up study on the efficacy of metadoxine in a cohort of alcoholics admitted to the Alcohol misuse Long-term Treatment (ALT) Unit – University of Pisa (Italy). We analyzed the clinical data, psychometric tests and blood tests of 160 alcoholics on admission and after 3 months of treatment. We compared 58 pts treated with metadoxine (MET) with 102 pts who did not receive (NULL) any drug as an adjunct to the psycho-educational interventions provided by the ALT Unit. RESULTS: At follow-up, the patients in treatment with metadoxine showed a significant improvement in the rate of complete abstinence (44.8% vs. 21.6%; chi square: 8.45, df = 1, p < 0.0037). Furthermore, the number of drop-outs at three months of treatment was also significantly lower in the MET than in the NULL group (17% vs. 57%; chi square of 23.22, df = 1, p < 0.001). CONCLUSION: Our findings support the use of metadoxine in the management of alcohol dependence. However, randomized clinical trials are necessary to confirm and replicate them. This study raises the importance of identifying new pharmacological compounds effective on the outcome of alcoholism in order to help patients to best adhere to treatment programs and to prevent the development of mental and physical complications due to chronic and heavy use of alcohol

Can dispersal investment explain why tall plant species achieve longer dispersal distances than short plant species?

Tall plant species disperse further distances than do short species, within and across dispersal syndromes, yet the driver underpinning this relationship is unclear. The ability of taller plants to invest more in dispersal structures may explain the positive relationship between plant height and dispersal distance. Here, we quantify the cross-species relationships between presence of dispersal structures, dispersal investment plant height and dispersal distance. Plant height, dispersal syndrome and dispersal investment data were collated for 1613 species from the literature, with dispersal distance data collated for 114 species. We find that species with high dispersal investment disperse further than do species with low dispersal investment. Tall species have a greater probability of having dispersal structures on their seeds compared with short species. For species with dispersal structures on their seeds, plant height is very weakly related to dispersal investment. Our results provide the first global confirmation of the dispersal investment–distance hypothesis, and show dispersal investment can be used for predicting species dispersal distances. However, our results and those of previous studies indicate plant height is still the best proxy for estimating species dispersal distances due to it being such a readily available plant trait

Stable isotope evidence for crustal recycling as recorded by superdeep diamonds

© 2015 Elsevier B.V. Sub-lithospheric diamonds from the Juina-5 and Collier-4 kimberlites and the Machado River alluvial deposit in Brazil have carbon isotopic compositions that co-vary with the oxygen isotopic compositions of their inclusions, which implies that they formed by a mixing process. The proposed model for this mixing process, based on interaction of slab-derived carbonate melt with reduced (carbide- or metal-bearing) ambient mantle, explains these isotopic observations. It is also consistent with the observed trace element chemistries of diamond inclusions from these localities and with the experimental phase relations of carbonated subducted crust. The 18O-enriched nature of the inclusions demonstrates that they incorporate material from crustal protoliths that previously interacted with seawater, thus confirming the subduction-related origin of superdeep diamonds. These samples also provide direct evidence of an isotopically anomalous reservoir in the deep (≥350 km) mantle

Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects

Background: High dose oral thiamine may have a role in treating diabetes, heart failure, and hypermetabolic states. The purpose of this study was to determine the pharmacokinetic profile of oral thiamine hydrochloride at 100 mg, 500 mg and 1500 mg doses in healthy subjects. Methods: This was a randomized, double-blind, single-dose, 4-way crossover study. Pharmacokinetic measures were calculated. Results: The $AUC_{0-10 hr}$ and $C_{max}$ values increased nonlinearly between 100 mg and 1500 mg. The slope of the $AUC_{0-10 hr}$ vs dose, as well as the $C_{max}$ vs dose, plots are steepest at the lowest thiamine doses. Conclusion: Our study demonstrates that high blood levels of thiamine can be achieved rapidly with oral thiamine hydrochloride. Thiamine is absorbed by both an active and nonsaturable passive process

Excess pressure as an analogue of blood flow velocity

INTRODUCTION: Derivation of blood flow velocity from a blood pressure waveform is a novel technique, which could have potential clinical importance. Excess pressure, calculated from the blood pressure waveform via the reservoir-excess pressure model, is purported to be an analogue of blood flow velocity but this has never been examined in detail, which was the aim of this study. METHODS: Intra-arterial blood pressure was measured sequentially at the brachial and radial arteries via fluid-filled catheter simultaneously with blood flow velocity waveforms recorded via Doppler ultrasound on the contralateral arm (n = 98, aged 61 ± 10 years, 72% men). Excess pressure was derived from intra-arterial blood pressure waveforms using pressure-only reservoir-excess pressure analysis. RESULTS: Brachial and radial blood flow velocity waveform morphology were closely approximated by excess pressure derived from their respective sites of measurement (median cross-correlation coefficient r = 0.96 and r = 0.95 for brachial and radial comparisons, respectively). In frequency analyses, coherence between blood flow velocity and excess pressure was similar for brachial and radial artery comparisons (brachial and radial median coherence = 0.93 and 0.92, respectively). Brachial and radial blood flow velocity pulse heights were correlated with their respective excess pressure pulse heights (r = 0.53, P < 0.001 and r = 0.43, P < 0.001, respectively). CONCLUSION: Excess pressure is an analogue of blood flow velocity, thus affording the opportunity to derive potentially important information related to arterial blood flow using only the blood pressure waveform

Functionalized α-Helical Peptide Hydrogels for Neural Tissue Engineering.

This is the final version of the article. Available from the American Chemical Society via the DOI in this record.Trauma to the central and peripheral nervous systems often lead to serious morbidity. Current surgical methods for repairing or replacing such damage have limitations. Tissue engineering offers a potential alternative. Here we show that functionalized α-helical-peptide hydrogels can be used to induce attachment, migration, proliferation and differentiation of murine embryonic neural stem cells (NSCs). Specifically, compared with undecorated gels, those functionalized with Arg-Gly-Asp-Ser (RGDS) peptides increase the proliferative activity of NSCs; promote their directional migration; induce differentiation, with increased expression of microtubule-associated protein-2, and a low expression of glial fibrillary acidic protein; and lead to the formation of larger neurospheres. Electrophysiological measurements from NSCs grown in RGDS-decorated gels indicate developmental progress toward mature neuron-like behavior. Our data indicate that these functional peptide hydrogels may go some way toward overcoming the limitations of current approaches to nerve-tissue repair.This work was supported by the Biotechnology and Biological Sciences Research Council (H01716X, D.N.W. and M.A.B.); the European Research Council (StG243261, BS; and ADG340764, D.N.W.); the Royal Society (UF051616, B.S.); the Medical Research Council (G1100623, A.D.R.); and the Engineering and Physical Sciences Research Council (Bristol Chemical Synthesis Centre for Doctoral Training, EP/G036764/1, K.L.H.). D.N.W. holds a Royal Society Wolfson Research Merit Award

Morphological characteristics of motor neurons do not determine their relative susceptibility to degeneration in a mouse model of severe spinal muscular atrophy

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality, resulting primarily from the degeneration and loss of lower motor neurons. Studies using mouse models of SMA have revealed widespread heterogeneity in the susceptibility of individual motor neurons to neurodegeneration, but the underlying reasons remain unclear. Data from related motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), suggest that morphological properties of motor neurons may regulate susceptibility: in ALS larger motor units innervating fast-twitch muscles degenerate first. We therefore set out to determine whether intrinsic morphological characteristics of motor neurons influenced their relative vulnerability to SMA. Motor neuron vulnerability was mapped across 10 muscle groups in SMA mice. Neither the position of the muscle in the body, nor the fibre type of the muscle innervated, influenced susceptibility. Morphological properties of vulnerable and disease-resistant motor neurons were then determined from single motor units reconstructed in Thy.1-YFP-H mice. None of the parameters we investigated in healthy young adult mice - including motor unit size, motor unit arbor length, branching patterns, motor endplate size, developmental pruning and numbers of terminal Schwann cells at neuromuscular junctions - correlated with vulnerability. We conclude that morphological characteristics of motor neurons are not a major determinant of disease-susceptibility in SMA, in stark contrast to related forms of motor neuron disease such as ALS. This suggests that subtle molecular differences between motor neurons, or extrinsic factors arising from other cell types, are more likely to determine relative susceptibility in SMA

The transformation of earth-system observations into information of socio-economic value in GEOSS

The Group on Earth Observations System of Systems, GEOSS, is a co-ordinated initiative by many nations to address the needs for earth-system information expressed by the 2002 World Summit on Sustainable Development. We discuss the role of earth-system modelling and data assimilation in transforming earth-system observations into the predictive and status-assessment products required by GEOSS, across many areas of socio-economic interest. First we review recent gains in the predictive skill of operational global earth-system models, on time-scales of days to several seasons. We then discuss recent work to develop from the global predictions a diverse set of end-user applications which can meet GEOSS requirements for information of socio-economic benefit; examples include forecasts of coastal storm surges, floods in large river basins, seasonal crop yield forecasts and seasonal lead-time alerts for malaria epidemics. We note ongoing efforts to extend operational earth-system modelling and assimilation capabilities to atmospheric composition, in support of improved services for air-quality forecasts and for treaty assessment. We next sketch likely GEOSS observational requirements in the coming decades. In concluding, we reflect on the cost of earth observations relative to the modest cost of transforming the observations into information of socio-economic value

A thin layer angiogenesis assay: a modified basement matrix assay for assessment of endothelial cell differentiation

BACKGROUND: Basement matrices such as Matrigel™ and Geltrex™ are used in a variety of cell culture assays of anchorage-dependent differentiation including endothelial cell tube formation assays. The volumes of matrix recommended for these assays (approximately 150 μl/cm(2)) are costly, limit working distances for microscopy, and require cell detachment for subsequent molecular analysis. Here we describe the development and validation of a thin-layer angiogenesis (TLA) assay for assessing the angiogenic potential of endothelial cells that overcomes these limitations. RESULTS: Geltrex™ basement matrix at 5 μl/cm(2) in 24-well (10 μl) or 96-well (2 μl) plates supports endothelial cell differentiation into tube-like structures in a comparable manner to the standard larger volumes of matrix. Since working distances are reduced, high-resolution single cell microscopy, including DIC and confocal imaging, can be used readily. Using MitoTracker dye we now demonstrate, for the first time, live mitochondrial dynamics and visualise the 3-dimensional network of mitochondria present in differentiated endothelial cells. Using a standard commercial total RNA extraction kit (Qiagen) we also show direct RNA extraction and RT-qPCR from differentiated endothelial cells without the need to initially detach cells from their supporting matrix. CONCLUSIONS: We present here a new thin-layer assay (TLA) for measuring the anchorage-dependent differentiation of endothelial cells into tube-like structures which retains all the characteristics of the traditional approach but with the added benefit of a greatly lowered cost and better compatibility with other techniques, including RT-qPCR and high-resolution microscopy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12860-014-0041-5) contains supplementary material, which is available to authorized users

Improving the use of research evidence in guideline development: 12. Incorporating considerations of equity

BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the 12(th )of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: We reviewed the literature on incorporating considerations of equity in guidelines and recommendations. METHODS: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: We found few directly relevant empirical methodological studies. These answers are based largely on logical arguments. When and how should inequities be addressed in systematic reviews that are used as background documents for recommendations? • The following question should routinely be considered: Are there plausible reasons for anticipating differential relative effects across disadvantaged and advantaged populations? • If there are plausible reasons for anticipating differential effects, additional evidence should be included in a review to inform judgments about the likelihood of differential effects. What questions about equity should routinely be addressed by those making recommendations on behalf of WHO? • The following additional questions should routinely be considered: • How likely is it that the results of available research are applicable to disadvantaged populations and settings? • How likely are differences in baseline risk that would result in differential absolute effects across disadvantaged and advantaged populations? • How likely is it that there are important differences in trade-offs between the expected benefits and harms across disadvantaged and advantaged populations? • Are there different implications for disadvantaged and advantaged populations, or implications for addressing inequities? What context specific information is needed to inform adaptation and decision making in a specific setting with regard to impacts on equity? • Those making recommendations on behalf of WHO should routinely consider and offer advice about the importance of the following types of context specific data that might be needed to inform adaptation and decision making in a specific setting: • Effect modifiers for disadvantaged populations and for the likelihood of differential effects • Baseline risk in relationship to social and economic status • Utilization and access to care in relationship to social and economic status • Costs in relationship to social and economic status • Ethics and laws that may impact on strategies for addressing inequities • Availability of resources to address inequities What implementation strategies are likely be needed to ensure that recommendations are implemented equitably? • Organisational changes are likely to be important to address inequities. While it may only be possible to consider these in relationship to specific settings, consideration should be given to how best to provide support for identifying and addressing needs for organisational changes. In countries with pervasive inequities institutional, cultural and political changes may first be needed. • Appropriate indicators of social and economic status should be used to monitor the effects of implementing recommendations on disadvantaged populations and on changes in social and economic status