MiR-205 is progressively down-regulated in lymph node metastasis but fails as a prognostic biomarker in high-risk prostate cancer

The treatment of high-risk prostate cancer (HRPCa) is a tremendous challenge for uro-oncologists. The identification of predictive moleculobiological markers allowing risk assessment of lymph node metastasis and systemic progression is essential in establishing effective treatment. In the current study, we investigate the prognostic potential of miR-205 in HRPCa study and validation cohorts, setting defined clinical endpoints for both. We demonstrate miR-205 to be significantly down-regulated in over 70% of the HRPCa samples analysed and that reconstitution of miR-205 causes inhibition of proliferation and invasiveness in prostate cancer (PCa) cell lines. Additionally, miR-205 is increasingly down-regulated in lymph node metastases compared to the primary tumour indicating that miR-205 plays a role in migration of PCa cells from the original location into extraprostatic tissue. Nevertheless, down-regulation of miR-205 in primary PCa was not correlated to the synchronous presence of metastasis and failed to predict the outcome for HRPCa patients. Moreover, we found a tendency for miR-205 up-regulation to correlate with an adverse outcome of PCa patients suggesting a pivotal role of miR-205 in tumourigenesis. Overall, we showed that miR-205 is involved in the development and metastasis of PCa, but failed to work as a useful clinical biomarker in HRPCa. These findings might have implications for the use of miR-205 as a prognostic or therapeutic target in HRPCa.

Asthma and allergies: is the farming environment (still) protective in Poland? The GABRIEL Advanced Studies

BACKGROUND Evidence exists that a farming environment in childhood may provide protection against atopic respiratory disease. In the GABRIEL project based in Poland and Alpine regions of Germany, Austria and Switzerland, we aimed to assess whether a farming environment in childhood is protective against allergic diseases in Poland and whether specific exposures explain any protective effect. METHODS In rural Poland, 23 331 families of schoolchildren completed a questionnaire enquiring into farming practices and allergic diseases (Phase I). A subsample (n = 2586) participated in Phase II involving a more detailed questionnaire on specific farm exposures with objective measures of atopy. RESULTS Farming differed between Poland and the Alpine centres; in the latter, cattle farming was prevalent, whereas in Poland 18% of village farms kept ≥1 cow and 34% kept ≥1 pig. Polish children in villages had lower prevalences of asthma and hay fever than children from towns, and in the Phase II population, farm children had a reduced risk of atopy measured by IgE (aOR = 0.72, 95% CI 0.57, 0.91) and skin prick test (aOR = 0.65, 95% CI 0.50, 0.86). Early-life contact with grain was inversely related to the risk of atopy measured by IgE (aOR = 0.66, 95% CI 0.47, 0.92) and appeared to explain part of the farming effect. CONCLUSION While farming in Poland differed from that in the Alpine areas as did the exposure-response associations, we found in communities engaged in small-scale, mixed farming, there was a protective farming effect against objective measures of atopy potentially related to contact with grain or associated farm activities.

Health-related quality of life in rural children living in four European countries: the GABRIEL study

OBJECTIVE Measuring children's health-related quality of life (HRQOL) is of growing importance given increasing chronic diseases. By integrating HRQOL questions into the European GABRIEL study, we assessed differences in HRQOL between rural farm and non-farm children from Germany, Austria, Switzerland and Poland to relate it to common childhood health problems and to compare it to a representative, mostly urban German population sample (KIGGS). METHODS The parents of 10,400 school-aged children answered comprehensive questionnaires including health-related questions and the KINDL-R questions assessing HRQOL. RESULTS Austrian children reported highest KINDL-R scores (mean: 80.9; 95 % CI [80.4, 81.4]) and Polish children the lowest (74.5; [73.9, 75.0]). Farm children reported higher KINDL-R scores than non-farm children (p = 0.002). Significantly lower scores were observed in children with allergic diseases (p < 0.001), with sleeping difficulties (p < 0.001) and in overweight children (p = 0.04). The German GABRIEL sample reported higher mean scores (age 7-10 years: 80.1, [79.9, 80.4]; age 11-13 years: 77.1, [74.9, 79.2]) compared to the urban KIGGS study (age 7-10 years: 79.0, [78.7-79.3]; age 11-13 years: 75.1 [74.6-75.6]). Socio-demographic or health-related factors could not explain differences in HRQOL between countries. CONCLUSIONS Future increases in chronic diseases may negatively impact children's HRQOL.

miR-21 and its target gene CCL20 are both highly overexpressed in the microenvironment of colorectal tumors: significance of their regulation

Recently, we reported a functional interaction between miR-21 and its identified chemokine target CCL20 in colorectal cancer (CRC) cell lines. Here, we investigated whether such functional interactions are permitted at the cellular level which would require an inverse correlation of expression and also co-expression of miR-21 and CCL20 in the same cell. Expression profiling was performed using qPCR, and ELISA, in situ hybridization and immunohistochemistry were applied for the presentation of their cellular localization. We demonstrated that miR-21 as well as CCL20 were both significantly upregulated in CRC tissues; thus, showing no antidromic expression pattern. This provided an initial clue that miR-21 and CCL20 may not be expressed in the same cell. In addition, we located miR-21 expression at the cellular level predominantly in stromal cells such as tumor-associated fibroblasts and to a minor degree in immune cells such as macrophages and lymphocytes. Likewise, CCL20 expression was primarily detected in tumor-infiltrating immune cells. Thus, investigating the cellular localization of miR-21 and its target CCL20 revealed that both molecules are expressed predominantly in the microenvironment of CRC tumors.

Das Schulhaus als geheimer Miterzieher. Normative Debatten in der Schweiz von 1830 bis 1930

Der Schulhausbau ist im 19. Jahrhundert einem starken Wandel unterworfen. In diesem Buch wird erstmals der Frage nachgegangen, wie und weshalb Normen für den Schulhausbau in der Schweiz von 1830 bis 1930 generiert und in formale Regelungen umgesetzt werden. Die Annahme, Erneuerungen im Schulhausbau betreffend Hygiene, Ergonomie, Ästhetik und Pädagogik hätten erst seit der Wende zum 20. Jahrhundert, insbesondere unter dem Einfluss der Reformpädagogik, stattgefunden, lässt das 19. Jahrhundert in Sachen Schulhausbau als rückständig erscheinen. Dabei wird vergessen, dass in dieser Zeit, gerade was die Zahl der gebauten Schulhäuser und die Entwicklung von Normen betrifft, eine intensive Arbeit geleistet wurde, die unter den historischen Umständen innovativ war. Die Organisation des Unterrichts, Licht und Luft im Schulzimmer und die Gesundheit der Schulkinder haben bereits das frühe 19. Jahrhundert normativ, praktisch und technisch beschäftigt. Gegen Ende des 19. Jahrhunderts findet eine über institutionelle und kantonale Grenzen hinausgehende öffentliche Diskussion statt, die breit rezipiert und professionalisiert wird. Verschiedene professionelle Akteure knüpfen an vorangegangene normative Debatten, staatliche Regulative, bestehende Traditionen und historische Kontexte an, um unterschiedlich motivierte, von Professionalisierungsprozessen beeinflusste Ansprüche an den Schulhausbau zu legitimieren, bis das Schulhaus zum „geheimen Miterzieher“ stilisiert wird.

"Mir hei e Verein": Eine Studie über Vereine, Sozialkapital und Wohlstand im Kanton Bern

In diesem Beitrag untersuchen wir den Zusammenhang zwischen dem Sozialkapitalbestand der 382 Gemeinden des Kantons Bern und deren wirtschaftlichen Prosperität. Als Indikator für das Sozialkapital verwenden wir die Anzahl an Vereinen. Nach unseren Recherchen gibt es im Kanton Bern insgesamt 10 130 Vereine. Die statistischen Analysen zeigen, dass selbst unter Kontrolle von weiteren Merkmalen Gemeinden mit vielen Vereinen über ein höheres Einkommen pro Einwohner verfügen. In einer Unterstichprobe von 100 Gemeinden wurde zusätzlich eine schriftliche Befragung von 2 577 Vereinen durchgeführt. Die Resultate ergeben, dass für den Wohlstand der Gemeinden insbesondere die Anzahl an aktiven Mitgliedern ausschlaggebend ist. Vereine mit Fokussierung auf das Gemeinwohl (Putnam-Vereine) haben zudem eine grössere Bedeutung für den Wohlstand als Vereine, die eher Partikularinteressen vertreten (Olson-Vereine). Insgesamt bestätigen die Ergebnisse die Sozialkapitalthese.