Differential liver protein expression during schistosomiasis

The arrival of eggs in the liver during Schistosoma mansoni infection initiates a protective granulomatous response; however, as the infection progresses, this response results in chronic liver fibrosis. To better understand the impact of schistosomiasis on liver function, we used a proteomic approach to identify proteins whose expression was significantly altered in schistosome-infected mice 8 weeks postinfection. Identification of differentially expressed proteins by mass fingerprinting revealed that schistosome infection markedly reduced the abundance of proteins associated with several normal liver functions (i.e., citric acid cycle, fatty acid cycle, and urea cycle), while proteins associated with stress responses, acute phase reactants, and structural components were all significantly more abundant. The expression patterns of several immunity-related proteins (peroxiredoxin 1, arginase 1, and galectin 1) suggested that different protein forms are associated with schistosome infection. These findings indicate that acute schistosomiasis has a significant impact on specific liver functions and, moreover, that the alterations in specific protein isoforms and upregulation of unique proteins may be valuable as new markers of disease.     

A repetition suppression effect lasting several days within the semantic network

Performance in a semantic task is speeded up for repeated stimuli compared to novel stimuli. This conceptual priming effect is related to a decrease in functional activation within the left inferior prefrontal cortex for repeated stimulus exposure (repetition suppression). However, in contrast to perceptual priming which is known to be very robust over long periods of time, previous studies on semantic priming focused on short-term effects. The present study combined a behavioral and functional imaging experiment to investigate long-term conceptual repetition priming (retention interval 3 days). We found a highly significant decrease of reaction time for word stimuli which were presented repeatedly after 3 days both compared to initial presentation and to a matched word list. The functional magnetic resonance imaging data showed a repetition suppression within the left inferior (BA45, BA47) and middle (BA9) frontal gyrus for the comparison of known with unknown words. These data demonstrate that even over a period as long as 3 days, a repetition suppression within the left frontal network involved in semantic decision can be found. Thus, priming-related mechanisms in the semantic network may be robust over several days.     

Clostridium difficile toxins A and B directly stimulate human mast cells

Clostridium difficile toxins A and B (TcdA and TcdB) are the causative agents of antibiotic-associated pseudomembranous colitis. Mucosal mast cells play a crucial role in the inflammatory processes underlying this disease. We studied the direct effects of TcdA and TcdB on the human mast cell line HMC-1 with respect to degranulation, cytokine release, and the activation of proinflammatory signal pathways. TcdA and TcdB inactivate Rho GTPases, the master regulators of the actin cytoskeleton. The inactivation of Rho GTPases induced a reorganization of the actin cytoskeleton accompanied by morphological changes of cells. The TcdB-induced reorganization of the actin cytoskeleton in HMC-1 cells reduced the number of electron-dense mast cell-specific granules. Accordingly, TcdB induced the release of hexosaminidase, a marker for degranulation, in HMC-1 cells. The actin rearrangement was found to be responsible for degranulation since latrunculin B induced a comparable hexosaminidase release. In addition, TcdB as well as latrunculin B induced the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 and also resulted in a p38 MAPK-dependent increased formation of prostaglandins D(2) and E(2). The autocrine stimulation of HMC-1 cells by prostaglandins partially contributed to the degranulation. Interestingly, TcdB-treated HMC-1 cells, but not latrunculin B-treated HMC-1 cells, showed a strong p38 MAPK-dependent increase in interleukin-8 release. Differences in the mast cell responses to TcdB and latrunculin B are probably due to the presence of functionally inactive Rho GTPases in toxin-treated cells. Thus, the HMC-1 cell line is a promising model for studying the direct effects of C. difficile toxins on mast cells independently of the tissue context.     

Tolerogenic effect of fiber tract injury: reduced EAE severity following entorhinal cortex lesion

Despite transient, myelin-directed adaptive immune responses in regions of fiber tract degeneration, none of the current models of fiber tract injuries evokes disseminated demyelination, implying effective mechanisms maintaining or re-establishing immune tolerance. In fact, we have recently detected CD95L upregulation accompanied by apoptosis of leukocytes in zones of axonal degeneration induced by entorhinal cortex lesion (ECL), a model of layer-specific axonal degeneration. Moreover, infiltrating monocytes readily transformed into ramified microglia exhibiting a phenotype of immature (CD86+/CD80−) antigen-presenting cells. We now report the appearance of the axonal antigen neurofilament-light along with increased T cell apoptosis and enhanced expression of the pro-apoptotic gene Bad in cervical lymph nodes after ECL. In order to test the functional significance of such local and systemic depletory/regulatory mechanisms on subsequent immunity to central nervous system antigens, experimental autoimmune encephalomyelitis was induced by proteolipid protein immunization 30 days after ECL. In three independent experiments, we found significantly diminished disease scores and infiltrates in lesioned compared to sham-operated SJL mice. This is consistent with a previous meta-statistical analysis (Goodin et al. in Neurology 52:1737–1745, 1999) rejecting the O-hypothesis that brain trauma causes or exacerbates multiple sclerosis. Conversely, brain injuries may involve long-term tolerogenic effects towards brain antigens. Leman Mutlu, Christine Brandt, Jon D. Laman, and Ingo Bechmann have contributed equally.     

Subjektive Qualitätskonzepte im Vergleich zu objektiven Qualitätskriterien

Background

The need for quality management in prevention and health promotion continues to grow. The role of the participants’ and course instructors’ views on quality in prevention and health promotion has been insufficiently considered. The aim of the present study was to examine the participants’ and course instructors’ views on quality in movement-related prevention and health promotion.

Methods

Four participants and four course instructors were questioned using semistructured interviews. The data were analyzed according to the structured content analysis according to Kuckartz.

Results

The views on quality of participants and course instructors were comparable. Within the participants’ and course instructors’ views on quality in movement-related prevention and health promotion the “individual relationship between therapist and patient”, “personal atmosphere”, and “class structure” were identified as important quality dimensions, while proof of effectiveness seemed to be less important. Moreover, the understanding of proof of effectiveness turned out to be inconsistent.

Conclusions

Compared to the prevention guideline of the German statutory health insurers, participants’ and course instructors’ views on quality point out the importance of process quality. In contrast, proof of effectiveness and the qualification of the course instructor play a minor role in subjective quality concepts.

     

Evaluation von organisierten Programmen zur Krebsfrüherkennung: Allgemeine Aspekte und aktueller Stand in Deutschland

In the past decades, it has been increasingly recognized that cancer screening is not always or not exclusively beneficial and, in the case of some measures, the negative effects may even outweigh the benefits. This has fundamentally changed the significance and emphasis placed on the evaluation of cancer screening programs. Generally, there is a distinction between an endpoint evaluation, which assesses the effectiveness or risk/benefit ratio, and a process evaluation, which aims to ensure optimum implementation of the program.Prior to the nationwide introduction of a screening measure, proof of effectiveness should ideally be provided by a randomized controlled trial (RCT), in which persons without a screening offer form the control group. From a scientific point of view, this study design is by far the best method to evaluate the endpoint, as it avoids biases that may distort the results in observational studies. RCT evidence on cancer screening measures currently offered by statutory health insurance providers in Germany – if available at all – originates exclusively from other countries.When mammography screening was introduced as the first organized screening program in Germany, comprehensive measures for process evaluation were taken. In April 2013, the legal basis for the transfer of colorectal and cervical cancer screening into organized programs was created. According to the legal provisions, both a process and an endpoint evaluation are planned for the new programs. It remains to be seen how the necessary data flows will be conceptualized and later implemented in practice.     

Gesichtsästhetik Teil 1: Die Bedeutung der Symmetrieebene des Gesichts

When humans observe a face, the eyes, mouth and nose regions are the preferred targets of the centre of gaze, with the outlines of eye position recordings approximating a triangle with vertices located in the centre of the eyes and mouth [31]. We studied the significance of cutaneous asymmetries inside and outside the Yarbus triangle on the basis of the assessment of digitally-manipulated images by 201 independent judges. We show that certain facial variations (such as naevi) are more attractive when asymmetrical than symmetrical (p<?0,001). They appear more attractive when located laterally rather than medially, particularly so when located outside the Yarbus triangle as compared to inside it (p<?0,001). The significance of facial symmetry increases significantly when approaching the Yarbus triangle or the midline, respectively.