DNA vaccination efficiently induces antibodies to Nogo-A and does not exacerbate experimental autoimmune encephalomyelitis.

Antibodies against the neurite outgrowth inhibitor Nogo-A enhance axonal regeneration following spinal cord injury. However, antibodies directed against myelin components can also enhance CNS inflammation. The present study was designed to assess the efficacy of DNA vaccination for generating antibodies against Nogo-A and to study their pathogenic potential in a mouse model for multiple sclerosis. Mice were immunized by a single i.m. injection of a plasmid expression vector encoding either full length membrane-integral Nogo-A equipped with a signal peptide or two versions of its large N-terminal extramembrane region. The presence of serum antibodies to Nogo-A was measured 4 weeks after injection by ELISA, Western blotting and immunohistochemistry. DNA vaccination efficiently induced production of Nogo-A-specific antibodies that recognized recombinant, intracellular Nogo-A in cell culture but also stained native Nogo-A on the oligodendrocyte surface. Experimental autoimmune encephalomyelitis was induced in DNA-vaccinated mice by immunization with proteolipid peptide (a.a. 139-154). In contrast to vaccination with DNA encoding myelin oligodendrocyte glycoprotein that exacerbates this disease, Nogo-A DNA vaccination did not enhance clinical severity of disease. In summary, DNA vaccination is a simple and efficient method for generating an antibody response to Nogo-A. No pathogenicity was observed even during a full-blown inflammatory response of the central nervous system

Analysis of FoxP3+ T-regulatory cells and CD8+ T-cells in ovarian carcinoma: location and tumor infiltration patterns are key prognostic markers.

Tumor infiltrating CD4+CD25+FoxP3+ regulatory immune cells (Treg) have been associated with impaired anti-tumor immune response and unfavorable prognosis for patients affected by ovarian carcinoma, whereas CD8+ T-cells have been found to positively influence survival rates in a large panel of solid tumors. Recently, density, location and tumor infiltration patterns of the respective immune cell subtypes have been identified as key prognostic factors for different types of tumors.We stained 210 human ovarian carcinoma samples immunhistochemically for FoxP3 and CD8 to identify the impact different immune cell patterns have on generally accepted prognostic variables as well as on overall survival.We found that FoxP3+ cells located within lymphoid aggregates surrounding the tumor were strongly associated with reduced survival time (P = 0.007). Central accumulation of CD8+ effector cells within the tumor bed shows a positive effect on survival (P = 0,001).The distribution pattern of immune cells within the tumor environment strongly influences prognosis and overall survival time of patients with ovarian carcinoma

Cannula and circuit management in peripheral extracorporeal membrane oxygenation: An international survey of 45 countries

Effective and safe practices during extracorporeal membrane oxygenation (ECMO) including infection precautions and securement of lines (cannulas and circuits) are critical to prevent life-threatening patient complications, yet little is known about the practices of bedside clinicians and data to support best practice is lacking. Therefore, the aim of this study was to identify and describe common line-related practices for patients supported by peripheral ECMO worldwide and to highlight any gaps for further investigation. An electronic survey was conducted to examine common line practices for patients managed on peripheral ECMO. Responses were obtained from 45 countries with the majority from the United States (n = 181) and United Kingdom (n = 32). Standardised infection precautions including hand hygiene, maximal barrier precautions and skin antisepsis were commonplace for cannulation. The most common antisepsis strategies included alcohol-based chlorhexidine gluconate (CHG) for cannula insertion (53%) and maintenance (54%), isopropyl alcohol on circuit access ports (39%), and CHG-impregnated dressings to cover insertion sites (36%). Adverse patient events due to line malposition or dislodgement were reported by 34% of respondents with most attributable to ineffective securement. Centres 'always' suturing peripheral cannula sites were more likely to experience a cannula adverse event than centres that 'never' sutured (35% [95% CI 30, 41] vs 0% [95% CI 0, 28]; Chi-square 4.40; p = 0.04) but this did not meet the a priori significance level o