Communication, Coordination, and Security for People with Multiple Sclerosis (COCOS-MS): a randomised phase II clinical trial protocol.

INTRODUCTION: Patients with multiple sclerosis (MS) have complex needs that range from organising one's everyday life to measures of disease-specific therapy monitoring to palliative care. Patients with MS are likely to depend on multiple healthcare providers and various authorities, which are often difficult to coordinate. Thus, they will probably benefit from comprehensive cross-sectoral coordination of services provided by care and case management (CCM). Though studies have shown that case management improves quality of life (QoL), functional status and reduces service use, such benefits have not yet been investigated in severely affected patients with MS. In this explorative phase ll clinical trial, we evaluated a CCM with long-term, cross-sectoral and outreaching services and, in addition, considered the unit of care (patients and caregivers). METHODS AND ANALYSIS: Eighty patients with MS and their caregivers will be randomly assigned to either the control (standard care) or the intervention group (standard care plus CCM (for 12 months)). Regular data assessments will be done at baseline and then at 3-month intervals. As primary outcome, we will evaluate patients' QoL. Secondary outcomes are patients' treatment-related risk perception, palliative care needs, anxiety/depression, use of healthcare services, caregivers' burden and QoL, meeting patients' and caregivers' needs, and evaluating the CCM intervention. We will also evaluate CCM through individual interviews and focus groups. The sample size calculation is based on a standardised effect of 0.5, and one baseline and four follow-up assessments (with correlation 0.5). Linear mixed models for repeated measures will be applied to analyse changes in quantitative outcomes over time. Multiple imputation approaches are taken to assess the robustness of the results. The explorative approach (phase ll clinical trial) with embedded qualitative research will allow for the development of a final design for a confirmative phase lll trial. ETHICS AND DISSEMINATION: The trial will be conducted under the Declaration of Helsinki and has been approved by the Ethics Commission of Cologne University's Faculty of Medicine. Trial results will be published in an open-access scientific journal and presented at conferences. TRIAL REGISTRATION NUMBER: German Register for Clinical Studies (DRKS) (DRKS00022771).

Effect of boron on the expression of aluminium toxicity in Phaseolus vulgaris.

The interaction of boron (B) and aluminium (Al) was investigated in 5-day-old seedlings of soybean cv. Maple Arrow. Al treatment inhibited root elongation and callose formation in root tips particularly after 4-h Al treatment. After 10 and 24 h, both parameters indicated increasing recovery from Al stress. B deficiency aggravated Al toxicity compared with B sufficiency. B deficiency did lead to an increase in unmethylated pectin in the first 3 mm of the root tip. This increase in potential binding sites is reflected in generally higher Al contents in root tips of B-deficient plants. A fractionated extraction of Al from the root tips showed that citrate-exchangeable and non-exchangeable Al steeply increased up to 4 h, but then decreased after 10- and 24-h Al treatment faster in B-sufficient than in B-deficient plants. This decrease of Al contents can be explained by an Al-enhanced release of citrate from the root tips after 10-h Al treatment. However, the citrate exudation rate was the same (after 10 h) or even lower (after 24 h) in B-sufficient plants and thus cannot explain the faster decrease in Al contents of the root tips compared with the B-deficient plants. We, therefore, propose that under B deficiency, Al is more strongly bound by the pectic network of the cell wall of the root tips, which delays or prevents the recovery from initial Al stress through exudation of citrate, and thus explains the greater Al sensitivity of B-deficient common bean roots.

A possible role of sphingolipids in the aluminium resistance of yeast and maize.

The plasma membrane is most likely the major target for sensing of aluminium (Al), leading to inhibition of plant root-growth. As a result of high external Al, alterations in plasma membrane composition may be expected in order to maintain its properties. As sphingolipids are characteristic components of this membrane, their involvement in membrane adjustment to increased Al concentrations was investigated. Heterologous expression of a stereounselective long-chain base (LCB) (8E/Z)-desaturase from Arabidopsis thaliana, Brassica napus and Helianthus annuus in Saccharomyces cerevisiae improved the Al resistance of the transgenic yeast cells. This encouraged us to investigate whether Al affects the LCB composition, and whether genetic engineering of the LCB profile modifies the Al resistance of the Al-sensitive plant species maize (Zea mays, L.). Constitutive expression of the LCB (8E/Z)-desaturase from Arabidopsis thaliana in maize roots led to an 8- to 10-fold increase in (8E)-4-hydroxysphing-8-enine in total roots. Less marked but similar changes were observed in 3 mm root apices. Al treatment of the Al-sensitive maize cv Lixis resulted in a significant increase in the proportion of (8Z)-LCB and in the content of total LCBs in root tips, which was not observed in the Al-resistant cv ATP-Y. When root tips of transgenic plants were exposed to Al, only minor changes of both (8Z)- and (8E)-unsaturated LCBs as well as of the total LCB were observed. Al treatment of the wild type parental line H99 decreased the (8Z)-unsaturated LCBs and the total LCB content. Based on Al-induced callose production, a marker for Al sensitivity, the parental line H99 was as Al-resistant as cv ATP-Y, whereas the transgenic line became as sensitive as cv Lixis. Taken together, these data suggest that, in particular, the loss of the ability to down-regulate the proportion of (8Z)-unsaturated LCBs may be related to increased Al sensitivity.

Localization of aluminium in the maize root apex: can morin detect cell wall-bound aluminium?

Morin is a fluorochrome which forms a fluorescent complex with aluminium (Al) and is thus used to localize Al in plant tissues. However, reports about the cellular distribution of Al-apoplastic versus symplastic-based on morin staining are often conflicting. The objective of this work was to investigate whether Al localization with morin staining can show the proper cellular distribution of Al. Fresh root cross-sections were made from root apices of maize (cv. Lixis) treated with 25 muM Al for 6 h and stained with morin. Fluorescence microscopic investigation showed Al-morin fluorescence in the cytosol, but not in the cell wall. This is in contrast to the growing evidence which shows that Al mainly accumulates in the cell wall, especially bound to the pectin matrix. Therefore, in vitro analyses were carried out to study whether morin can form a fluorescent complex with Al, which is bound to pectin, cell wall, and other Al-binding ligands such as phosphate, galacturonate, DNA, and ATP. Compared with the control treatment without Al-binding ligands, fluorescence intensity was reduced by about 10-fold in the presence of pectin and isolated cell walls, but fairly unaffected in the presence of phosphate and galacturonate. Al associated with DNA and ATP also formed a fluorescent complex with morin. This implies that, although Al is mainly accumulated in the cell wall, it cannot be detected with morin as it is tightly bound to cell-wall pectin. Thus, morin staining should not be used to study the distribution of Al between cell compartments.

Apoplastic binding of aluminum is involved in silicon-induced amelioration of aluminum toxicity in maize.

The alleviating effect of silicon (Si) supply on aluminum (Al) toxicity was suggested to be based on ex or in planta mechanisms. In our experiments with the Al-sensitive maize (Zea mays) cultivar Lixis, Si treatment but not Si pretreatment ameliorated Al-induced root injury as revealed by less root-growth inhibition and callose formation. Si treatment did not affect monomeric Al concentrations in the nutrient solution, suggesting an in planta effect of Si on Al resistance. A fractionated analysis of Si and Al in the 1-cm root apices revealed that more than 85% of the root-tip Al was bound in the cell wall. Al contents in the apoplastic sap, the symplastic sap, and the cell wall did not differ between -Si and +Si plants. Si did not affect the Al-induced exudation of organic acid anions and phenols from the root apices. However, Al treatment greatly enhanced Si accumulation in the cell wall fraction, reducing the mobility of apoplastic Al. From our data we conclude that Si treatment leads to the formation of hydroxyaluminumsilicates in the apoplast of the root apex, thus detoxifying Al.