Evaluation of a prostate cancer e-health-tutorial

Hintergrund: Angesichts verschiedener Behandlungsoptionen ist die Information und Therapieentscheidung beim lokalisierten Prostatakarzinom eine Herausforderung. Die digitale Informationstechnologie bietet im Vergleich zu gedruckten Informationen mehr Möglichkeiten, die Information und die Patientenkommunikation bedarfsgerecht zu gestalten. Ziele: Zur Unterstützung der Therapieentscheidung und der Kommunikation mit Patienten ist in der deutschsprachigen Schweiz ein Online-Tutorial in einem systematischen Prozess entwickelt und in einer Pilotstudie getestet worden. In der Evaluation interessierten die Nutzerzufriedenheit, die Erfüllung der Informationsbedürfnisse, die Vorbereitung auf die Therapieentscheidung und deren subjektive Qualität. Material und Methoden: Die Plattform wurde in einem iterativen Prozess mittels Fokusgruppen mit Ärzten und Patienten auf der Grundlage von Informationen aus bestehenden Broschüren entwickelt. Für den Test der Plattform wurden in 8 urologischen Kliniken 87 Patienten zur Teilnahme eingeladen. Die 56 Nutzer wurden 4 Wochen nach dem Login und 3 Monate nach dem Therapieentscheid online befragt, 48 Nutzer füllten beide Befragungen aus. Eingesetzte Instrumente waren die Preparation for Decision Making Scale (PDMS), die Decisional Conflict Scale (DCS) und die Decisional Regret Scale (DRS). Ergebnisse und Diskussion: Die Nutzenden sind mit der Plattform sehr zufrieden und finden ihre Informationsbedürfnisse gut erfüllt. Sie zeigen 3 Monate nach dem Entscheid eine gute Vorbereitung auf die Entscheidung (MW PDMS 75, SD 23) und berichten über niedrigen Entscheidungskonflikt (MW DCS 9.6, SD 11) und kaum Bedauern über die Entscheidung (MW DRS 6.4, SD 9.6). Basierend auf diesen Erkenntnissen kann die Plattform zur weiteren Nutzung empfohlen werden.Background: Due to the multitude of therapy options the treatment decision after diagnosis of a localised prostate cancer is challenging. Compared to printed booklets, web based information technology offers more possibilities to tailor information to patients’ individual needs. Objectives: To support the decision making process as well as the communication with patients we developed an online tutorial in a systematic process in the German speaking part of Switzerland and then tested it in a pilot study. The study investigated users’ satisfaction, the coverage of information needs, the preparation for decision making and the subjective quality of the decision. Materials and methods: Based on already existing information material the online tutorial was developed in an iterative process using focus groups with patients and urologists. For the following evaluation in eight clinics a total of 87 patients were invited to access the platform and participate in the study. From these patients 56 used the tutorial and 48 answered both surveys (the first one 4 weeks after the first login and the second one 3 months after treatment decision). The surveys used the Preparation for Decision Making Scale (PDMS), the Decisional Conflict Scale (DCS), and the Decisional Regret Scale (DRS). Results and Conclusion: Satisfaction with the tutorial is very high among patients with newly diagnosed localized prostate cancer. Users find their information needs sufficiently covered. Three months after the decision they felt that they were well prepared for the decision making (Mean PDMS 75, SD 23), they had low decisional conflict (Mean DCS 9.6, SD 11) and almost no decisional regret (Mean DRS 6.4, SD 9.6). Based on these findings the further use of the tutorial can be recommended

B Cell Depletion Reduces the Number of Autoreactive T Helper Cells and Prevents Glucose-6-Phosphate Isomerase-Induced Arthritis

The therapeutic benefit of B cell depletion in patients with rheumatoid arthritis has provided proof of concept that B cells are relevant for the pathogenesis of arthritis. It remains unknown which B cell effector functions contribute to the induction or chronification of arthritis. We studied the clinical and immunological effects of B cell depletion in glucose-6-phosphate isomerase-induced arthritis. We targeted CD22 to deplete B cells. Mice were depleted of B cells before or after immunization with glucose-6-phosphate isomerase (G6PI). The clinical and histological effects were studied. G6PI-specific antibody responses were measured by ELISA. G6PI-specific T helper (Th) cell responses were assayed by polychromatic flow cytometry. B cell depletion prior to G6PI-immunization prevented arthritis. B cell depletion after immunization ameliorated arthritis, whereas B cell depletion in arthritic mice was ineffective. Transfer of antibodies from arthritic mice into B cell depleted recipients did not reconstitute arthritis. B cell depleted mice harbored much fewer G6PI-specific Th cells than control animals. B cell depletion prevents but does not cure G6PI-induced arthritis. Arthritis prevention upon B cell depletion is associated with a drastic reduction in the number of G6PI-specific effector Th cells

Antimicrobial peptides of the Cecropin-family show potent antitumor activity against bladder cancer cells

<p>Abstract</p> <p>Background</p> <p>This study evaluated the cytotoxic and antiproliferative efficacy of two well-characterized members of the Cecropin-family of antimicrobial peptides against bladder tumor cells and benign fibroblasts.</p> <p>Methods</p> <p>The antiproliferative and cytotoxic potential of the Cecropins A and B was quantified by colorimetric WST-1-, BrdU- and LDH-assays in four bladder cancer cell lines as well as in murine and human fibroblast cell lines. IC₅₀values were assessed by logarithmic extrapolation, representing the concentration at which cell viability was reduced by 50%. Scanning electron microscopy (SEM) was performed to visualize the morphological changes induced by Cecropin A and B in bladder tumor cells and fibroblasts.</p> <p>Results</p> <p>Cecropin A and B inhibit bladder cancer cell proliferation and viability in a dose-dependent fashion. The average IC₅₀values of Cecropin A and B against all bladder cancer cell lines ranged between 73.29 μg/ml and 220.05 μg/ml. In contrast, benign fibroblasts were significantly less or not at all susceptible to Cecropin A and B. Both Cecropins induced an increase in LDH release from bladder tumor cells whereas benign fibroblasts were not affected. SEM demonstrated lethal membrane disruption in bladder cancer cells as opposed to fibroblasts.</p> <p>Conclusion</p> <p>Cecropin A and B exert selective cytotoxic and antiproliferative efficacy in bladder cancer cells while sparing targets of benign murine or human fibroblast origin. Both peptides may offer novel therapeutic strategies for the treatment of bladder cancer with limited cytotoxic effects on benign cells.</p

Network Analysis of Oyster Transcriptome Revealed a Cascade of Cellular Responses during Recovery after Heat Shock

Oysters, as a major group of marine bivalves, can tolerate a wide range of natural and anthropogenic stressors including heat stress. Recent studies have shown that oysters pretreated with heat shock can result in induced heat tolerance. A systematic study of cellular recovery from heat shock may provide insights into the mechanism of acquired thermal tolerance. In this study, we performed the first network analysis of oyster transcriptome by reanalyzing microarray data from a previous study. Network analysis revealed a cascade of cellular responses during oyster recovery after heat shock and identified responsive gene modules and key genes. Our study demonstrates the power of network analysis in a non-model organism with poor gene annotations, which can lead to new discoveries that go beyond the focus on individual genes

Intravenous apoptotic spleen cell infusion induces a TGF-beta-dependent regulatory T-cell expansion.: Apoptosis and regulatory T cells

International audienceApoptotic leukocytes are endowed with immunomodulatory properties that can be used to enhance hematopoietic engraftment and prevent graft-versus-host disease (GvHD). This apoptotic cell-induced tolerogenic effect is mediated by host macrophages and not recipient dendritic cells or donor phagocytes present in the bone marrow graft as evidenced by selective cell depletion and trafficking experiments. Furthermore, apoptotic cell infusion is associated with TGF-beta-dependent donor CD4+CD25+ T-cell expansion. Such cells have a regulatory phenotype (CD62L(high) and intracellular CTLA-4+), express high levels of forkhead-box transcription factor p3 (Foxp3) mRNA and exert ex vivo suppressive activity through a cell-to-cell contact mechanism. In vivo CD25 depletion after apoptotic cell infusion prevents the apoptotic cell-induced beneficial effects on engraftment and GvHD occurrence. This highlights the role of regulatory T cells in the tolerogenic effect of apoptotic cell infusion. This novel association between apoptosis and regulatory T-cell expansion may also contribute to preventing deleterious autoimmune responses during normal turnover

Paracrine IL-33 Stimulation Enhances Lipopolysaccharide-Mediated Macrophage Activation

BACKGROUND: IL-33, a member of the IL-1 family of cytokines, provokes Th2-type inflammation accompanied by accumulation of eosinophils through IL-33R, which consists of ST2 and IL-1RAcP. We previously demonstrated that macrophages produce IL-33 in response to LPS. Some immune responses were shown to differ between ST2-deficient mice and soluble ST2-Fc fusion protein-treated mice. Even in anti-ST2 antibody (Ab)-treated mice, the phenotypes differed between distinct Ab clones, because the characterization of such Abs (i.e., depletion, agonistic or blocking Abs) was unclear in some cases. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the precise role of IL-33, we newly generated neutralizing monoclonal Abs for IL-33. Exogenous IL-33 potentiated LPS-mediated cytokine production by macrophages. That LPS-mediated cytokine production by macrophages was suppressed by inhibition of endogenous IL-33 by the anti-IL-33 neutralizing mAbs. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that LPS-mediated macrophage activation is accelerated by macrophage-derived paracrine IL-33 stimulation

HIV-1 Nef Targets MHC-I and CD4 for Degradation Via a Final Common β-COP–Dependent Pathway in T Cells

To facilitate viral infection and spread, HIV-1 Nef disrupts the surface expression of the viral receptor (CD4) and molecules capable of presenting HIV antigens to the immune system (MHC-I). To accomplish this, Nef binds to the cytoplasmic tails of both molecules and then, by mechanisms that are not well understood, disrupts the trafficking of each molecule in different ways. Specifically, Nef promotes CD4 internalization after it has been transported to the cell surface, whereas Nef uses the clathrin adaptor, AP-1, to disrupt normal transport of MHC-I from the TGN to the cell surface. Despite these differences in initial intracellular trafficking, we demonstrate that MHC-I and CD4 are ultimately found in the same Rab7+ vesicles and are both targeted for degradation via the activity of the Nef-interacting protein, β-COP. Moreover, we demonstrate that Nef contains two separable β-COP binding sites. One site, an arginine (RXR) motif in the N-terminal α helical domain of Nef, is necessary for maximal MHC-I degradation. The second site, composed of a di-acidic motif located in the C-terminal loop domain of Nef, is needed for efficient CD4 degradation. The requirement for redundant motifs with distinct roles supports a model in which Nef exists in multiple conformational states that allow access to different motifs, depending upon which cellular target is bound by Nef