Quality of life in multiple sclerosis: translation in French Canadian of the MSQoL-54.

Background: Multiple Sclerosis (MS) is a neurodegenerative disease which runs its course for the remainder of the patient's life frequently causing disability of varying degrees. Negative effects on Health-related quality of life (HRQOL) are well documented and a subject of clinical study. The Multiple Sclerosis QOL 54 (MSQOL-54) questionnaire was developed to measure HRQOL in patients with MS. It is composed of 54 items, and is a combination of the SF-36 and 18 diseasespecific items. Objective: The objective of this project was to translate the MSQOL-54 into French Canadian, and to make it available to the Canadian scientific community for clinical research and clinical practice. Methods: Across all French speaking regions, there are occurrences of variation. They include the pronunciation, sentence structure, and the lexicon, where the differences are most marked. For this reason, it was decided to translate the US original MSQOL-54 into French Canadian instead of adapting the existing French version. The SF-36 has been previously validated and published in French Canadian, therefore the translation work was performed solely on the 18 MS specific items. The translation followed an internationally accepted methodology into 3 steps: forward translation, backward translation, and patients' cognitive debriefing. Results: Instructions and Items 38, 43, 45 and 49 were the most debated. Problematic issues mainly resided in the field of semantics. Patients' testing (n = 5) did not reveal conceptual problems. The questionnaire was well accepted, with an average time for completion of 19 minutes. Conclusion: The French Canadian MSQOL-54 is now available to the Canadian scientific community and will be a useful tool for health-care providers to assess HRQOL of patients with MS as a routine part of clinical practice. The next step in the cultural adaptation of the MSQOL-54 in French Canadian will be the evaluation of its psychometric properties.The authors gratefully acknowledge the grant provided for this study by Aventis Pharma Canada, and Dr Barbara Vickrey for her support

Predicting Important Residues and Interaction Pathways in Proteins Using Gaussian Network Model: Binding and Stability of HLA Proteins

A statistical thermodynamics approach is proposed to determine structurally and functionally important residues in native proteins that are involved in energy exchange with a ligand and other residues along an interaction pathway. The structure-function relationships, ligand binding and allosteric activities of ten structures of HLA Class I proteins of the immune system are studied by the Gaussian Network Model. Five of these models are associated with inflammatory rheumatic disease and the remaining five are properly functioning. In the Gaussian Network Model, the protein structures are modeled as an elastic network where the inter-residue interactions are harmonic. Important residues and the interaction pathways in the proteins are identified by focusing on the largest eigenvalue of the residue interaction matrix. Predicted important residues match those known from previous experimental and clinical work. Graph perturbation is used to determine the response of the important residues along the interaction pathway. Differences in response patterns of the two sets of proteins are identified and their relations to disease are discussed

Protein misfolding and dysregulated protein homeostasis in autoinflammatory diseases and beyond.

Cells have a number of mechanisms to maintain protein homeostasis, including proteasome-mediated degradation of ubiquitinated proteins and autophagy, a regulated process of ‘self-eating’ where the contents of entire organelles can be recycled for other uses. The unfolded protein response prevents protein overload in the secretory pathway. In the past decade, it has become clear that these fundamental cellular processes also help contain inflammation though degrading pro-inflammatory protein complexes such as the NLRP3 inflammasome. Signaling pathways such as the UPR can also be co-opted by toll-like receptor and mitochondrial reactive oxygen species signaling to induce inflammatory responses. Mutations that alter key inflammatory proteins, such as NLRP3 or TNFR1, can overcome normal protein homeostasis mechanisms, resulting in autoinflammatory diseases. Conversely, Mendelian defects in the proteasome cause protein accumulation, which can trigger interferon-dependent autoinflammatory disease. In non-Mendelian inflammatory diseases, polymorphisms in genes affecting the UPR or autophagy pathways can contribute to disease, and in diseases not formerly considered inflammatory such as neurodegenerative conditions and type 2 diabetes, there is increasing evidence that cell intrinsic or environmental alterations in protein homeostasis may contribute to pathogenesis

Recent advances in ankylosing spondylitis: understanding the disease and management

The term spondyloarthritis refers to a group of immune-mediated diseases characterised by inflammation of the axial skeleton, peripheral joints, and entheses. Ankylosing spondylitis (AS) is the most common and characteristic of these entities and even though it was first described over two centuries ago, the understanding of the underlying disease mechanism remains incomplete. It is known that around 40% of patients with AS have subclinical bowel inflammation, suggesting that the origin of the disease could be in the gut. Also, more genes and new molecules have demonstrated a role in the pathogenesis of AS. In this review, we analyse the latest therapies for spondyloarthritis and the most relevant discoveries over the last three years, together with their implications for different aspects of the disease