Neurofilament light chain as a biomarker in multiple sclerosis

Due to the unpredictable course and heterogenous treatment response in multiple sclerosis (MS), there is a clear need for biomarkers that reflect disease activity in the clinical follow-up of these patients. Neurofilaments are neuron-specific components of the cytoskeleton that can be assayed in different body compartments. They have been explored as potential biomarkers for many years. Neurofilament light chain (NF-L) appears the most promising biomarker in MS patients, and there is now little doubt that NF-L should have a role in the follow-up of MS patients. Newer assays and techniques for NF-L detection available in serum samples confirms the usefulness of NF-L as a biomarker. Nevertheless, there is still a need for prospective studies, and studies to determine clinical useful cut-off values. This review evaluates the strengths and weaknesses of NF-L as a biomarker in patients with MS.publishedVersio

Wearing-off at the end of natalizumab dosing interval and risk of MS disease activity: A prospective 1-year follow-up study

Natalizumab effectively prevents disease activity in relapsing-remitting multiple sclerosis by binding α4 integrin and inhibiting leukocyte migration to the central nervous system. We recently reported an association between low natalizumab receptor occupancy and subjective wearing-off symptoms at the end of the 4-week dosing interval. Here, we aimed to evaluate the short-term risk of disease activity in a 1-year prospective follow-up of the same patient cohort (n = 40). We found that all patients available for follow-up after one year (n = 35) fulfilled the criteria for no evidence of disease activity (NEDA). Thus, wearing-off symptoms were not associated with increased short-term risk of disease activity. Longer follow-up in a larger patient cohort is required to establish whether therapeutic efficacy is maintained in patients with wearing-off symptoms.publishedVersio

Neurofilament Light Chain as a Biomarker in Multiple Sclerosis

Due to the unpredictable course and heterogenous treatment response in multiple sclerosis (MS), there is a clear need for biomarkers that reflect disease activity in the clinical follow-up of these patients. Neurofilaments are neuron-specific components of the cytoskeleton that can be assayed in different body compartments. They have been explored as potential biomarkers for many years. Neurofilament light chain (NF-L) appears the most promising biomarker in MS patients, and there is now little doubt that NF-L should have a role in the follow-up of MS patients. Newer assays and techniques for NF-L detection available in serum samples confirms the usefulness of NF-L as a biomarker. Nevertheless, there is still a need for prospective studies, and studies to determine clinical useful cut-off values. This review evaluates the strengths and weaknesses of NF-L as a biomarker in patients with MS

The autoimmune disease-associated SNP rs917997 of IL18RAP controls IFNγ production by PBMC

AbstractType 1 Diabetes (T1D) is an autoimmune disorder characterized by aberrant T cell responses. Innate immune activation defects may facilitate a T helper 1 (Th1) phenotype. The cytokine IL-18 synergizes with IL-12 to induce IFNγ production and Th1 differentiation. The IL-18R subunit (IL18RAP) SNP rs917997 has been linked to decreased IL18RAP gene expression. Prior reports link rs917997 allele A with protection from T1D, and conversely with susceptibility to Celiac disease. However, few studies have investigated the IL-18 pathway in T1D. In this study, we analyzed responsiveness to IL-18 in T1D, and the effect of rs917997 genotype on IL18RAP gene expression post-activation. Upon IL-12 and IL-18 treatment, peripheral blood mononuclear cells from subjects carrying susceptibility alleles at rs917997 produced higher levels of IFNγ than those with protective genotypes. Additionally, the SNP modified IL18RAP surface protein expression by NK cells and gene expression in activated T cells. Taken together, these data suggest that the disease-associated rs917997 allele G permits hyperresponsiveness to IL-18, providing a novel target for therapeutic intervention in T1D

Casimir Force on a Micrometer Sphere in a Dip: Proposal of an Experiment

The attractive Casimir force acting on a micrometer-sphere suspended in a spherical dip, close to the wall, is discussed. This setup is in principle directly accessible to experiment. The sphere and the substrate are assumed to be made of the same perfectly conducting material.Comment: 11 pages, 1 figure; to appear in J. Phys. A: Math. Ge

Precaution or Integrated Responsibility Approach to Nanovaccines in Fish Farming? A Critical Appraisal of the UNESCO Precautionary Principle

Nanoparticles have multifaceted advantages in drug administration as vaccine delivery and hence hold promises for improving protection of farmed fish against diseases caused by pathogens. However, there are concerns that the benefits associated with distribution of nanoparticles may also be accompanied with risks to the environment and health. The complexity of the natural and social systems involved implies that the information acquired in quantified risk assessments may be inadequate for evidence-based decisions. One controversial strategy for dealing with this kind of uncertainty is the precautionary principle. A few years ago, an UNESCO expert group suggested a new approach for implementation of the principle. Here we compare the UNESCO principle with earlier versions and explore the advantages and disadvantages by employing the UNESCO version to the use of PLGA nanoparticles for delivery of vaccines in aquaculture. Finally, we discuss whether a combined scientific and ethical analysis that involves the concept of responsibility will enable approaches that can provide a supplement to the precautionary principle as basis for decision-making in areas of scientific uncertainty, such as the application of nanoparticles in the vaccination of farmed fish

Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients

Objective:to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients.Methods:We genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 patients. The best associated SNPs of the Italian GWAS were replicated in silico in Scandinavian and Belgian populations, and meta-analyzed.Results:HLA-DRB1*15 is associated with OCB+: p = 0.03, Odds Ratio (OR) = 1.6, 95% Confidence Limits (CL) = 1.1-2.4. None of the 52 non-HLA MS susceptibility loci was associated with OCB, except one SNP (rs2546890) near IL12B gene (OR: 1.45; 1.09-1.92). The weighted Genetic Risk Score mean was significantly (p = 0.0008) higher in OCB+ (7.668) than in OCB- (7.412) patients. After meta-analysis on the three datasets (Italian, Scandinavian and Belgian) for the best associated signals resulted from the Italian GWAS, the strongest signal was a SNP (rs9320598) on chromosome 6q (p = 9.4×10-7) outside the HLA region (65 Mb).Discussion:genetic factors predispose to the development of OCB

Sitting and standing performance in a total population of children with cerebral palsy: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Knowledge of sitting and standing performance in a total population of children with cerebral palsy (CP) is of interest for health care planning and for prediction of future ability in the individual child. In 1994, a register and a health care programme for children with CP in southern Sweden was initiated. In the programme information on how the child usually sits, stands, stands up and sits down, together with use of support or assistive devices, is recorded annually.</p> <p>Methods</p> <p>A cross-sectional study was performed, analysing the most recent report of all children with CP born 1990-2005 and living in southern Sweden during 2008. All 562 children (326 boys, 236 girls) aged 3-18 years were included in the study. The degree of independence, use of support or assistive devices to sit, stand, stand up and sit down was analysed in relation to the Gross Motor Function Classification System (GMFCS), CP subtype and age.</p> <p>Result</p> <p>A majority of the children used standard chairs (57%), could stand independently (62%) and could stand up (62%) and sit down (63%) without external support. Adaptive seating was used by 42%, external support to stand was used by 31%, to stand up by 19%, and to sit down by 18%. The use of adaptive seating and assistive devices increased with GMFCS levels (p < 0.001) and there was a difference between CP subtypes (p < 0.001). The use of support was more frequent in preschool children aged 3-6 (p < 0.001).</p> <p>Conclusion</p> <p>About 60% of children with CP, aged 3-18, use standard chairs, stand, stand up, and sit down without external support. Adding those using adaptive seating and external support, 99% of the children could sit, 96% could stand and 81% could stand up from a sitting position and 81% could sit down from a standing position. The GMFCS classification system is a good predictor of sitting and standing performance.</p