Red clover increases micronutrient concentrations in red clover

Foraeg crops provide micronutrients as well as energy, protein and fibre to ruminants. However, the micronutrient concentrations of forage plant species differ, legumes generally having higher concentrations than grasses. In addition to that there are also strong effects of soil type. Typically, the concentrations of one or several micronutrients in forage are too low to meet the nutritional requirement of dairy cows. We hypothesized that the overall micronutrient (Co, Cu, Fe, Mn, Mo, Zn) concentrations of forage mixtures are affected by the red clover dry matter (DM) proportions and site effects. This hypothesis was tested at three contrasting sites. The results showed that increased red clover proportion increased the overall concentrations of several micronutrient in the mixtures at all sites. At the site with the widest range of red clover proportion (0-70 %) in the mixture, the Co, Cu and Fe concentrations more than doubled between the lowest and highest red clover DM proportions. At the other two sites a smaller increase in red clover proportion(from 10 % to 25 % or from 25 % to 50 %) also increased the overall concentrations of Co by up to 80 % but less for other micronutrients.  One of the sites generally had higher micronutrient concentrations in the crop and removed larger amounts of micronutrients with the harvested biomass compared to the other two sites.This could be explained by differences in pH and micronutrient concentrations of the soils at the sites. We conclude that increased red clover proportion in the sward has the potential to increase tha overall micronutrient concentrations but that the effect of the soil is also a controlling factor

Differential ketogenic diet-induced shift in CSF lipid/carbohydrate metabolome of pediatric epilepsy patients with optimal vs. no anticonvulsant response: a pilot study

Background: The low carbohydrate, high fat ketogenic diet can be an effective anticonvulsant treatment in some pediatric patients with pharmacoresistant epilepsy. Its mechanism(s) of action, however, remain uncertain. Direct sampling of cerebrospinal fluid before and during metabolic therapy may reveal key changes associated with differential clinical outcomes. We characterized the relationship between seizure responsiveness and changes in lipid and carbohydrate metabolites. Methods: We performed metabolomic analysis of cerebrospinal fluid samples taken before and during ketogenic diet treatment in patients with optimal response (100% seizure remission) and patients with no response (no seizure improvement) to search for differential diet effects in hallmark metabolic compounds in these two groups. Optimal responders and non-responders were similar in age range and included males and females. Seizure types and the etiologies or syndromes of epilepsy varied but did not appear to differ systematically between responders and non-responders. Results: Analysis showed a strong effect of ketogenic diet treatment on the cerebrospinal fluid metabolome. Longitudinal and between-subjects analyses revealed that many lipids and carbohydrates were changed significantly by ketogenic diet, with changes typically being of larger magnitude in responders. Notably, responders had more robust changes in glucose and the ketone bodies β-hydroxybutyrate and acetoacetate than non-responders; conversely, non-responders had significant increases in fructose and sorbose, which did not occur in responders. Conclusions: The data suggest that a differential and stronger metabolic response to the ketogenic diet may predict a better anticonvulsant response, and such variability is likely due to inherent biological factors of individual patients. Strategies to boost the metabolic response may be beneficial

Electrically Switchable Polymer Brushes for Protein Capture and Release in Biological Environments**

Interfaces functionalized with polymers are known for providing excellent resistance towards biomolecular adsorption and for their ability to bind high amounts of protein while preserving their structure. However, making an interface that switches between these two states has proven challenging and concepts to date rely on changes in the physiochemical environment, which is static in biological systems. Here we present the first interface that can be electrically switched between a high-capacity (>1 μg cm−2) multilayer protein binding state and a completely non-fouling state (no detectable adsorption). Switching is possible over multiple cycles without any regeneration. Importantly, switching works even when the interface is in direct contact with biological fluids and a buffered environment. The technology offers many applications such as zero fouling on demand, patterning or separation of proteins as well as controlled release of biologics in a physiological environment, showing high potential for future drug delivery in vivo

Modeling a Coronal Mass Ejection from an Extended Filament Channel. I. Eruption and Early Evolution

We present observations and modeling of the magnetic field configuration, morphology, and dynamics of a large-scale, high-latitude filament eruption observed by the Solar Dynamics Observatory. We analyze the 2015 July 9-10 filament eruption and the evolution of the resulting coronal mass ejection (CME) through the solar corona. The slow streamer-blowout CME leaves behind an elongated post-eruption arcade above the extended polarity inversion line that is only poorly visible in extreme ultraviolet (EUV) disk observations and does not resemble a typical bright flare-loop system. Magnetohydrodynamic (MHD) simulation results from our data-inspired modeling of this eruption compare favorably with the EUV and white-light coronagraph observations. We estimate the reconnection flux from the simulation's flare-arcade growth and examine the magnetic-field orientation and evolution of the erupting prominence, highlighting the transition from an erupting sheared-arcade filament channel into a streamer-blowout flux-rope CME. Our results represent the first numerical modeling of a global-scale filament eruption where multiple ambiguous and complex observational signatures in EUV and white light can be fully understood and explained with the MHD simulation. In this context, our findings also suggest that the so-called stealth CME classification, as a driver of unexpected or "problem" geomagnetic storms, belongs more to a continuum of observable/nonobservable signatures than to separate or distinct eruption processes.Peer reviewe

Regeneration of long-distance peripheral nerve defects after delayed reconstruction in healthy and diabetic rats is supported by immunomodulatory chitosan nerve guides

Background: Delayed reconstruction of transection or laceration injuries of peripheral nerves is inflicted by a reduced regeneration capacity. Diabetic conditions, more frequently encountered in clinical practice, are known to further impair regeneration in peripheral nerves. Chitosan nerve guides (CNGs) have recently been introduced as a new generation of medical devices for immediate peripheral nerve reconstruction. Here, CNGs were used for 45 days delayed reconstruction of critical length 15 mm rat sciatic nerve defects in either healthy Wistar rats or diabetic Goto-Kakizaki rats; the latter resembling type 2 diabetes. In short and long-term investigations, we comprehensively analyzed the performance of one-chambered hollow CNGs (hCNGs) and two-chambered CNGs (CFeCNGs) in which a chitosan film has been longitudinally introduced. Additionally, we investigated in vitro the immunomodulatory effect provided by the chitosan film. Results: Both types of nerve guides, i.e. hCNGs and CFeCNGs, enabled moderate morphological and functional nerve regeneration after reconstruction that was delayed for 45 days. These positive findings were detectable in generally healthy as well as in diabetic Goto-Kakizaki rats (for the latter only in short-term studies). The regenerative outcome did not reach the degree as recently demonstrated after immediate reconstruction using hCNGs and CFeCNGs. CFeCNG-treatment, however, enabled tissue regrowth in all animals (hCNGs: only in 80% of animals). CFeCNGs did further support with an increased vascularization of the regenerated tissue and an enhanced regrowth of motor axons. One mechanism by which the CFeCNGs potentially support successful regeneration is an immunomodulatory effect induced by the chitosan film itself. Our in vitro results suggest that the pro-regenerative effect of chitosan is related to the differentiation of chitosan-adherent monocytes into pro-healing M2 macrophages. Conclusions: No considerable differences appear for the delayed nerve regeneration process related to healthy and diabetic conditions. Currently available chitosan nerve grafts do not support delayed nerve regeneration to the same extent as they do after immediate nerve reconstruction. The immunomodulatory characteristics of the biomaterial may, however, be crucial for their regeneration supportive effects

The TOSCA Registry for Tuberous Sclerosis-Lessons Learnt for Future Registry Development in Rare and Complex Diseases.

Introduction: The TuberOus SClerosis registry to increase disease Awareness (TOSCA) is an international disease registry designed to provide insights into the clinical characteristics of patients with Tuberous Sclerosis Complex (TSC). The aims of this study were to identify issues that arose during the design, execution, and publication phases of TOSCA, and to reflect on lessons learnt that may guide future registries in rare and complex diseases. Methods: A questionnaire was designed to identify the strengths, weaknesses, and issues that arose at any stage of development and implementation of the TOSCA registry. The questionnaire contained 225 questions distributed in 7 sections (identification of issues during registry planning, during the operation of the registry, during data analysis, during the publication of the results, other issues, assessment of lessons learnt, and additional comments), and was sent by e-mail to 511 people involved in the registry, including 28 members of the Scientific Advisory Board (SAB), 162 principal investigators (PIs), and 321 employees of the sponsor belonging to the medical department or that were clinical research associate (CRA). Questionnaires received within the 2 months from the initial mailing were included in the analysis. Results: A total of 53 (10.4%) questionnaires were received (64.3% for SAB members, 12.3% for PIs and 4.7% for employees of the sponsor), and the overall completeness rate for closed questions was 87.6%. The most common issues identified were the limited duration of the registry (38%) and issues related to handling of missing data (32%). In addition, 25% of the respondents commented that biases might have compromised the validity of the results. More than 80% of the respondents reported that the registry improved the knowledge on the natural history and manifestations of TSC, increased disease awareness and helped to identify relevant information for clinical research in TSC. Conclusions: This analysis shows the importance of registries as a powerful tool to increase disease awareness, to produce real-world evidence, and to generate questions for future research. However, there is a need to implement strategies to ensure patient retention and long-term sustainability of patient registries, to improve data quality, and to reduce biases

The Updated version of SF Box: A method for soil quality classification as a basis for applicable site-specific environmental risk assessment of contaminated soils

This technical note summarises major changes in the updated version of SF Box, which is part of the SCORE – the Multi-Criteria Decision Analysis method for decision support in soil remediation projects. SCORE stands for the Sustainable Choice Of REmediation and SF Box stands for Soil Function toolBox. The SF Box tool has been developed for soil function assessment to complement environmental risk assessments, in order to increase awareness of decision-makers for inherent soil qualities other than concentration of contaminants and their availability/mobility, which are critical for proper soil functioning, e.g. availability of water and nutrients for soil organisms, but often ignored in remediation projects (driven by protection of the soil environment with ambition to recover ecosystem functions) in Sweden. The tool is based on a scoring method using soil quality indicators (SQIs) for assessing (I) the soil’s capacity to perform its functions in its own reference state of being ‘clean’, i.e. “what can this soil do and can it perform its functions well, assuming that it is free of contaminants?”, and (II) the effects of the remedial actions themselves on soil functions, i.e. “can the remediated soil continue to perform these functions well?”. The earlier version of SF Box addresses the soil functions associated with Primary Production. By (i) taking into consideration the perspectives of soil microbiology, soil fauna and vegetation, (ii) slightly modifying the set of SQIs (consisting of soil texture, content of coarse material, organic carbon/matter, available water, C/N ratio, pH and available phosphorus), and (iii) revisiting the curves for scoring of soil performances on each SQI, the SF Box tool has been updated to assess the soils’ capacity to function as a basis for Life and Habitat of flora and fauna. This updated version is therefore aimed to provide an improved basis for site-specific environmental risk assessment by means of (1) differentiating between the effects of contamination on soil biota and the effects of soil capability to function as a host to these species in its own reference state free from contaminants, and (2) classification of the soils (usually characterized by heterogeneity at contaminated sites) in accordance with their overall performance on the selected SQIs for further analysis of ecotoxicological risks in each soil class

Liposomi rivastigmina za isporuku u mozak intranazalnim putem

The present study is mainly aimed at delivering a drug into the brain via the intranasal route using a liposomal formulation. For this purpose, rivastigmine, which is used in the management of Alzheimer’s disease, was selectd as a model drug. Conventional liposomes were formulated by lipid layer hydration method using cholesterol and soya lecithin as lipid components. The concentration of rivastigmine in brain and plasma was studied in rat models after intranasal and oral administration of liposomes and free drug. A significantly higher level of drug was found in the brain with intranasal liposomes of rivastigmine compared to the intranasal free drug and the oral route. Intranasal liposomes had a longer half-life in the brain than intranasally or orally administered free drug. Delivering rivastigmine liposomes through the intranasal route for the treatment of Alzheimer’s disease might be a new approach to the management of this condition.Glavni cilj rada je razvoj liposoma za intranazalnu primjenu za isporuku lijeka u mozak. U tu svrhu izabran je rivastigmin kao modelni lijek koji se upotrebljava u terapiji Alzheimerove bolesti. Liposomi su pripravljeni metodom hidratacije lipidnog sloja koristeći kolesterol i lecitin iz soje kao lipidne komponente. Praćena je koncentracija rivastigmina u mozgu i plazmi nakon intranazalne i peroralne primjene liposoma i slobodnog lijeka. S intranazalnim liposomima rivastigmina postignuta je značajno veća koncentracija lijeka u mozgu. Osim toga intranazalni liposomi imaju dulje vrijeme poluživota u mozgu. Intranazalna primjena liposoma rivastigmina mogla bi predstavljati novi pristup terapiji Alzheimerove bolesti