Murine polyomavirus-like particles induce maturation of bone marrow-derived dendritic cells and proliferation of T cells

We analysed the effects of murine polyomavirus-like particles (PLPs) on bone marrow-derived dendritic cells (BMDCs) and T cells in vitro. BMDCs activated with PLPs up-regulated CD40, CD80, CD86 and major histocompatibility complex (MHC) class II surface markers and produced proinflammatory cytokines. Chimeric PLPs [expressing the ovalbumin (OVA)-peptides OVA(257-264) or OVA(323-339)], but not wildtype PLPs, activated OVA-specific CD8 T cells and OVA-specific CD4 T cells, respectively, indicating both MHC class I and II presentation of the peptides by antigen-presenting cells. Our results suggest that PLPs may be used as vaccine adjuvants priming dendritic cells to induce potent T cell responses.     

CD83 is a regulator of murine B cell function in vivo

The transmembrane glycoprotein CD83 has been described as a specific maturation marker for dendritic cells and several lines of evidence suggest that CD83 regulates thymic T cell maturation as well as peripheral T cell activation. Here we show for the first time that CD83 is involved also in the regulation of B cell function. CD83 is up-regulated on activated B cells in vivo, specifically in the draining lymph nodes of Leishmania major-infected mice. The ubiquitous transgenic (Tg) expression of CD83 interferes with Leishmania-specific T cell-dependent and with T cell-independent antibody production. This defect is restricted to the B cell population since the antigen-specific T cell response of CD83Tg mice to L. major infection is unchanged. The defective immunoglobulin (Ig) response is due to Tg expression of CD83 on the B cells because wild-type B cells display normal antigen-specific responses in CD83Tg hosts and CD83Tg B cells do not respond to immunization in a mixed wild-type/CD83Tg bone marrow chimera. Finally, the treatment of non-Tg C57BL/6 mice with anti-CD83 mAb induces a dramatic increase in the antigen-specific IgG response to immunization, thus demonstrating a regulatory role for naturally induced CD83 on wild-type B cells.     

Measurement Properties of the Modified Spinal Function Sort (M-SFS): Is It Reliable and Valid in Workers with Chronic Musculoskeletal Pain?

Purpose To analyze the reliability and validity of a picture-based questionnaire, the Modified Spinal Function Sort (M-SFS). Methods Sixty-two injured workers with chronic musculoskeletal disorders (MSD) were recruited from two work rehabilitation centers. Internal consistency was assessed by Cronbach’s alpha. Construct validity was tested based on four a priori hypotheses. Structural validity was measured with principal component analysis (PCA). Test–retest reliability and agreement was evaluated using intraclass correlation coefficient (ICC) and measurement error with the limits of agreement (LoA). Results Total score of the M-SFS was 54.4 (SD 16.4) and 56.1 (16.4) for test and retest, respectively. Item distribution showed no ceiling effects. Cronbach’s alpha was 0.94 and 0.95 for test and retest, respectively. PCA showed the presence of four components explaining a total of 74% of the variance. Item communalities were >0.6 in 17 out of 20 items. ICC was 0.90, LoA was ±12.6/16.2 points. The correlations between the M-SFS were 0.89 with the original SFS, 0.49 with the Pain Disability Index, ?0.37 and ?0.33 with the Numeric Rating Scale for actual pain, ?0.52 for selfreported disability due to chronic low back pain, and 0.50, 0.56–0.59 with three distinct lifting tests. No a priori defined hypothesis for construct validity was rejected. Conclusions The M-SFS allows reliable and valid assessment of perceived self-efficacy for work-related tasks and can be recommended for use in patients with chronic MSD. Further research should investigate the proposed M-SFS score of <56 for its predictive validity for non-return to work.     

Infection of cells expressing CXCR4 mutants lacking N-glycosylation at the N-terminal extracellular domain is enhanced for R5X4-dualtropic human immunodeficiency virus type-1

Background  

Infection with human immunodeficiency virus type-1 (HIV-1) requires binding of the viral envelope gp120 to CD4 and to the CXCR4 coreceptor. Both, gp120 and CXCR4 are subject to N-glycosylation. Here we investigated the influence of the N-linked glycans g1 and g2 present on CXCR4 for HIV-1 infection.     

Emergency Medical Care of Multiple Sclerosis Patients: Primary Data from the Mount Sinai Resource Utilization in Multiple Sclerosis Project

Background and Purpose

There has been no systematic analysis of emergency department (ED) utilization in the multiple sclerosis (MS) population. We investigated the acute-care needs of MS patients using ED as a route for entry into healthcare services.

Methods

ED visits made by MS patients were identified. Data extracted included demographics, medical/neurological history, and workup/management in the ED.

Results

The Mount Sinai ED received 569 visits from 224 MS patients during a 3-year period, of whom 33.5% were covered by Medicaid and 12.9% were uninsured. Patients with an Expanded Disability Status Scale score of ≥6 accounted for 54%, 50.5% of relapsing remitting MS patients were being treated with disease-modifying therapies, and 74.5% of the ED visits were non-neurological. Patients with mild-to-moderate MS were more likely to present to the ED for issues directly related to MS such as acute exacerbations, while those with severe MS presented more often due to medical issues indirectly related to MS, such as urinary tract infections (p<0.0001).

Conclusions

Most MS patients seeking ED care suffer from acute non-neurological problems. The MS patients presenting to the ED tended to be underinsured, had high levels of disability, and were undertreated with disease-modifying therapies. The acute-care needs of MS patients evolve over the disease course, as do the resources that must be utilized in providing emergency care across the spectrum of MS severity. Understanding the characteristics, problems, and needs of MS patients utilizing the ED is an important step in improving care in this population from both clinical and public health perspectives.     

Innere Arbeitsmodelle von Bindung und aversive Kindheitserfahrungen bei Psychotherapeuten in Ausbildung

In this paper first results of a study about competence development of psychotherapists in training in Germany are presented. In particular, the current mental processing of early relationship experiences and adversive childhood experiences of 90 trainees from three psychotherapies were examined at the beginning of their training. The internal working models of attachment and adversive early childhood experiences were assessed with the Adult Attachment Interview (AAI). The quantitative data analysis was supplemented by qualitative content analysis of four interviews to examine how trainees have dealt with adversive experiences and to work out if and how those are related to their decision to become psychotherapists. The AAIs analysis with respect to the attachment representation revealed by a first analysis of 50 interviews an overrepresentation of secure attachment patterns (78?%) and thus a significantly higher proportion of secure internal working models in comparison to former studies. Psychotherapists in training seem as burdened as the general population in terms of adversive childhood experiences. The qualitative analysis suggests a high degree of self-efficacy-enhancing parentification. The results are discussed in relation to previous psychotherapy experience, therapeutic school, age and sex of trainees.     

Preserved bioactivity and tunable release of a SDF1-GPVI bi-specific protein using photo-crosslinked PEGda hydrogels

Chemokine-induced stem cell recruitment is a promising strategy for post myocardial infarction treatment. Injection of stromal cell-derived factor 1 (SDF1) has been shown to attract bone marrow-derived progenitor cells (BMPCs) from the blood that have the potential to differentiate into cardiovascular cells, which support angiogenesis, enabling the improvement of myocardial function. SDF1-GPVI bi-specific protein contains a glycoprotein VI (GPVI)-domain that serves as an anchor for collagen type I (Col I) and III, which are exposed in the wall of injured vasculature. In this study, we generated a cytocompatible hydrogel via photo-crosslinking of poly(ethylene glycol) diacrylate that serves as a reservoir for SDF1-GPVI. Controlled and sustained release of SDF1-GPVI was demonstrated over a period of 7 days. Release features were modifiable depending on the degree of the crosslinking density. Functionality of the GPVI-domain was investigated using a GPVI-binding ELISA to Col I. Activity of the SDF1-domain was tested for its CXCR4 binding potential. Preserved functionality of SDF1-GPVI bi-specific protein after photo-crosslinking and controllable release was successfully demonstrated in vitro supporting the implementation of this drug delivery system as a powerful tool for therapeutic protein delivery in the treatment of cardiovascular ischemic disease.     

Fundamental Investigations of Bond Behaviour of High-Strength Micro Steel Fibres in Ultra-High Performance Concrete under Cyclic Tensile Loading

The objective of the contribution is to understand the fatigue bond behaviour of brass-coated high-strength micro steel fibres embedded in ultra-high performance concrete (UHPC). The study contains experimental pullout tests with variating parameters like load amplitude, fibre orientation, and fibre-embedded length. The test results show that fibres are generally pulled out of the concrete under monotonic loading and rupture partly under cyclic tensile loading. The maximum tensile stress per fibre is approximately 1176 N/mm², which is approximately one third of the fibre tensile strength (3576 N/mm²). The load-displacement curves under monotonic loading were transformed into a bond stress-slip relationship, which includes the effect of fibre orientation. The highest bond stress occurs for an orientation of 30° by approximately 10 N/mm². Under cyclic loading, no rupture occurs for fibres with an orientation of 90° within 100,000 load changes. Established S/N-curves of 30°- and 45°-inclined fibres do not show fatigue resistance of more than 1,000,000 load cycles for each tested load amplitude. For the simulation of fibre pullout tests with three-dimensional FEM, a model was developed that describes the local debonding between micro steel fibre and the UHPC-matrix and captures the elastic and inelastic stress-deformation behaviour of the interface using plasticity theory and a damage formulation. The model for the bond zone includes transverse pressure-independent composite mechanisms, such as adhesion and micro-interlocking and transverse pressure-induced static and sliding friction. This allows one to represent the interaction of the coupled structures with the bond zone. The progressive cracking in the contact zone and associated effects on the fibre load-bearing capacity are the decisive factors concerning the failure of the bond zone. With the developed model, it is possible to make detailed statements regarding the stress-deformation state along the fibre length. The fatigue process of the fibre-matrix bond with respect to cyclic loading is presented and analysed in the paper.