Factors associated with depressive mood at the onset of multiple sclerosis - an analysis of 781 patients of the German NationMS cohort

BACKGROUND: Depression has a major impact on the disease burden of multiple sclerosis (MS). Analyses of overlapping MS and depression risk factors [smoking, vitamin D (25-OH-VD) and Epstein-Barr virus (EBV) infection] and sex, age, disease characteristics and neuroimaging features associated with depressive symptoms in early MS are scarce. OBJECTIVES: To assess an association of MS risk factors with depressive symptoms within the German NationMS cohort. DESIGN: Cross-sectional analysis within a multicenter observational study. METHODS: Baseline data of n = 781 adults with newly diagnosed clinically isolated syndrome or relapsing-remitting MS qualified for analysis. Global and region-specific magnetic resonance imaging (MRI)-volumetry parameters were available for n = 327 patients. Association of demographic factors, MS characteristics and risk factors [sex, age, smoking, disease course, presence of current relapse, expanded disability status scale (EDSS) score, fatigue (fatigue scale motor cognition), 25-OH-VD serum concentration, EBV nuclear antigen-1 IgG (EBNA1-IgG) serum levels] and depressive symptoms (Beck Depression Inventory-II, BDI-II) was tested as a primary outcome by multivariable linear regression. Non-parametric correlation and group comparison were performed for associations of MRI parameters and depressive symptoms. RESULTS: Mean age was 34.3 years (95% confidence interval: 33.6-35.0). The female-to-male ratio was 2.3:1. At least minimal depressive symptoms (BDI-II > 8) were present in n = 256 (32.8%), 25-OH-VD deficiency (<20 ng/ml) in n = 398 (51.0%), n = 246 (31.5%) participants were smokers. Presence of current relapse [coefficient (c) = 1.48, p = 0.016], more severe fatigue (c = 0.26, p < 0.0001), lower 25-OH-VD (c = -0.03, p = 0.034) and smoking (c = 0.35, p = 0.008) were associated with higher BDI-II scores. Sex, age, disease course, EDSS, month of visit, EBNA1-IgG levels and brain volumes at baseline were not. CONCLUSION: Depressive symptoms need to be assessed in early MS. Patients during relapse seem especially vulnerable to depressive symptoms. Contributing factors such as fatigue, vitamin D deficiency and smoking, could specifically be targeted in future interventions and should be investigated in prospective studies

Surface roughness of dental implants and treatment time using six different implantoplasty procedures.

OBJECTIVES To test whether or not one of six implantoplasty procedures is superior to the others rendering a minimal final implant surface roughness and a short treatment time. MATERIAL AND METHODS Forty-two one-piece implants were embedded in epoxy resin blocks with 6-mm rough implant surface exposed. The following implantoplasty polishing sequences were applied: Brownie(®) , Greenie(®) sequence (BG) (diamond rotary instruments 106-, 40-, 15-μm grit, Brownie(®) , Greenie(®) silicone polishers); Arkansas stone sequence (AS) (diamond 106-, 40-, 15-μm grit, Arkansas stone torpedo-shaped bur); Short diamond sequence (SD) (diamond 106-, 40-, 4-μm grit); Short diamond sequence with Greenie(®) (SDG) (diamond 106-, 40-, 4-μm grit, Greenie(®) ); Complete diamond sequence (CD) (diamond 106-, 40-, 15-, 8-, 4-μm grit); Complete diamond sequence with Greenie(®) (CDG) (106-, 40-, 15-, 8-, 4-μm grit, Greenie(®) ). The polished neck portion served as a positive control, the untreated sandblasted and acid-etched surface as negative control. Each implant was scanned with a contact profilometer rendering Ra values and Rz values as a measure of surface roughness. The time needed to polish the implant surface for each group was recorded. Simultaneous comparisons between more than two groups were done performing Kruskal-Wallis tests. Comparisons between two groups were analysed using Wilcoxon rank-sum tests. RESULTS Mean Ra values amounted to 0.32 ± 0.14 μm (BG), 0.39 ± 0.13 μm (AS), 0.59 ± 0.19 μm (SDG), 0.71 ± 0.22 μm (SD), 0.75 ± 0.26 μm (CDG), 0.98 ± 0.30 μm (CD), 0.10 ± 0.01 μm (PC) and 1.94 ± 0.47 μm (NC). Pairwise one-sided comparisons between the test group revealed statistically significant differences (P < 0.05). The shortest treatment time was recorded for group AS (13 ± 2 min) and the longest for CDG (21 ± 2 min) and BG (21 ± 4 min). CONCLUSIONS Considering final surface roughness and treatment duration, the use of rotary diamond burs in decreasing roughness, followed by an arkansas stone (group AS), appears to be an optimal treatment option

Modulation of dendritic cell properties by laquinimod as a mechanism for modulating multiple sclerosis

Laquinimod is an orally administered compound that is under investigation in relapsing-remitting multiple sclerosis. To understand the mechanism by which laquinimod exerts its clinical effects, we have performed human and murine studies assessing its immunomodulatory properties. In experimental autoimmune encephalomyelitis, the therapeutic administration of laquinimod beginning during the recovery of SJL mice, prevented further relapses as expected and strongly reduced infiltration of CD4 and CD8 T cells in the central nervous system. We hypothesized that this beneficial effect was mediated by dendritic cells, since we and others found a modulation of different dendritic cell subsets under treatment. According to the findings on antigen-presenting cells in the murine system, we found a reduced capacity of human monocyte-derived dendritic cells treated with therapeutic concentrations of laquinimod, upon maturation with lipopolysaccharide, to induce CD4 T cell proliferation and secretion of pro-inflammatory cytokines. Furthermore, laquinimod treatment of mature dendritic cells resulted in a decreased chemokine production by both murine and human dendritic cells, associated with a decreased monocyte chemo-attraction. In laquinimod-treated patients with multiple sclerosis we consistently found reduced chemokine and cytokine secretion by conventional CD1c dendritic cells upon lipopolysaccharide stimulation. Similarly to the animal model of relapsing-remitting multiple sclerosis, dendritic cell subsets were altered in patients upon laquinimod treatment, as the number of conventional CD1c and plasmacytoid CD303 dendritic cells were decreased within peripheral blood mononuclear cells. Moreover, laquinimod treatment in patients with multiple sclerosis and mice modified the maturation of dendritic cells demonstrated by an upregulation of CD86 expression in vivo. Our data suggest that inhibition of the NF-kappaB pathway is responsible for the changes observed in dendritic cell maturation and functions. These findings indicate that laquinimod exhibits its disease-modulating activity in multiple sclerosis by downregulating immunogenicity of dendritic cell responses. We suggest that monitoring dendritic cell properties in multiple sclerosis should be implemented in future therapeutic trials