ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a complex disease of the central nervous system. As new drugs are becoming available, knowledge on diagnosis and treatment must continuously evolve. There is therefore a need for a reference tool compiling current data on benefit and safety, to aid professionals in treatment decisions and use of resources across Europe. The European Committee of Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN) have joined forces to meet this need. The objective was to develop an evidence-based clinical practice guideline for the pharmacological treatment of people with MS to guide healthcare professionals in the decision-making process. METHODS: This guideline has been developed using the GRADE methodology and following the recently updated EAN recommendations for guideline development. Clinical questions were formulated in PICO format (patient, intervention, comparator, outcome) and outcomes were prioritized according to their relevance to clinical practice. An exhaustive literature search up to December 2016 was performed for each question and the evidence is presented narratively and, when possible, combined in a meta-analysis using a random-effects model. The quality of evidence for each outcome was rated into four categories - very high, high, low and very low - according to the risk of bias. GRADE evidence profiles were created using GRADEprofiler (GRADEpro) software (Version 3.6). The recommendations with assigned strength (strong, weak) were formulated based on the quality of evidence and the risk-benefit balance. Consensus between the panellists was reached by use of the modified nominal group technique. RESULTS: A total of 10 questions have been agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency at the time of publication. A total of 20 recommendations were agreed by the guideline working group members after three rounds of consensus.

Assess, compare and enhance the status of Persons with Multiple Sclerosis (MS) in Europe: a European Register for MS.

OBJECTIVES: Persons with multiple sclerosis (PwMS) experience health-related quality of life (HRQoL) problems greatly differing across Europe, and the European Union (EU) faces deep inequalities in MS management from country to country. Through the establishment of a European MS Register (EUReMS), an effective action is proposed to improve the overall knowledge on MS and support effective intervention programmes at EU and national political level. EUReMS aims to achieve consensus on its mission and vision, to define existing data providers, to develop models driving future MS health policies and research, to develop an information technology (IT) infrastructure for a data set, to develop a European shared governance and to secure providers' data provision into EUReMS. MATERIALS AND METHODS: EUReMS is meant to build on a minimum set of core data from existing national and regional population-based MS registries and from PwMS' perspectives. EUReMS' main partner is the European MS Platform (EMSP) acting in collaboration with associated and collaborating European partners. RESULTS: EUReMS was launched in July 2011. A Consensus Statement on purposes, vision, mission and strategies was produced in December 2011, and a comprehensive survey on existing MS data collections in Europe has been performed, and the EUReMS data mask is currently being discussed. CONCLUSIONS: EUReMS will represent a tool to provide up to date, comparable and sustainable MS data through an effective and credible register, which will encourage extensive knowledge building of MS, more equitable policies and higher standards in MS treatment and services.

In plants a putative isovaleryl-CoA-dehydrogenase is located in mitochondria.

In plants the degradation pathways of branched-chain amino acids have remained somewhat unclear with respect to both their biochemistry and their intracellular location. While biochemical evidence has localized some of the catabolic enzymes in peroxisomes/glyoxysomes, others cofractionate with mitochondria. We have now identified a candidate protein and corresponding cDNA for an enzyme of the leucine catabolic pathway, the isovaleryl-CoA-dehydrogenase (IVD). This polypeptide is a member of the acyl-CoA-dehydrogenase (ACDH) family and is encoded in the nuclear genome of Arabidopsis thaliana. Expression of the putative IVD gene in pea seedlings is documented by western blot analyses with an antibody against the mammalian IVD. Subcellular fractionation identifies the putative IVD enzyme in the mitochondrion. This localization suggests that in plants mitochondria contain at least part of the branched-chain amino acid degradation pathway(s).

Correlation of nonanucleotide motifs with transcript initiation of 18S rRNA genes in mitochondria of pea, potato and Arabidopsis.

Transcription initiation sites for the mitochondrial 18S rRNA genes in the dicot plants Arabidopsis thaliana, potato and pea were identified by a combination of in vitro capping, primer extension and S-1 analyses. These promoters contain a nonanucleotide motif and an AT-rich sequence similar to many mRNA and tRNA promoters in dicot mitochondria. In Arabidopsis and potato, active promoters are located within 120 nucleotides upstream of the 18S rRNA genes, as in Oenothera. The nucleotide sequence in the corresponding region in pea mitochondria is well conserved, but is not used as promoter in this plant. Instead a novel promoter sequence is used that lies several hundred nucleotides upstream. These results show that rRNAs can be transcribed from the same promoter types as mRNAs and tRNAs in plant mitochondria. However, the sequence features presently attributed to plant mitochondrial promoters-the conserved nonanucleotide and the upstream AT-rich box-do not allow to deduce the presence of an active promoter from genomic sequence data alone.

Transcription of potato mitochondrial 26S rRNA is initiated at its mature 5' end.

Transcription initiation sites in plant mitochondria can be located by in vitro capping of primary 5' transcript termini. Direct sequencing of a cap-labelled mitochondrial RNA from potato shows its sequence to be identical to the 5' terminal part of the 26S rRNA. Primer extension analysis indicates the mature 5' end to be the sole detectable 5' transcript terminus. In potato mitochondria the mature 5' end of the 26S rRNA is thus created by transcription initiation without any further 5' processing. The nucleotide sequence surrounding this transcription initiation site shows only limited similarity to other putative promoter sequences from dicot plant mitochondria suggesting the possibility that divergent RNA polymerases, and/or transcription initiation factors, are present in plant mitochondria.