SEVERE OSTEOPOROSIS DUE TO SYSTEMIC MAST CELL DISEASE: SUCCESSFUL TREATMENT WITH INTERFERON ALPHA-2B

We describe a 33-yr-old man suffering from severe vertebral osteoporosis and urticaria pigmentosa due to systemic mast cell disease (SMCD). Because i.v. clodronate therapy could not prevent further vertebral fractures, an additional treatment with interferon alpha-2b was initiated. During 24 months of treatment, our patient had no further pain episodes, no new vertebral fractures were discovered, trabecular bone mineral density (BMD) increased significantly and urticarial symptoms improved. Nevertheless, the extent of skin lesions remained unchanged. On histological examination, a remarkable decrease of mast cells was observed in the bone marrow, but not in the skin. Five months after discontinuation of interferon alpha-2b, trabecular BMD decreased and urticarial symptoms deteriorated. These findings illustrate a beneficial effect of interferon alpha-2b on SMCD-induced osteoporosis as well as urticarial symptoms, and raise the question whether this treatment may have a diverse impact on mast cell populations in different tissue

Impact of climate change and development scenarios on flow patterns in the Okavango River

This paper lays the foundation for the use of scenario modelling as a tool for integrated water resource management in the Okavango River basin. The Pitman hydrological model is used to assess the impact of various development and climate change scenarios on downstream river flow. The simulated impact on modelled river discharge of increased water use for domestic use, livestock, and informal irrigation (proportional to expected population increase) is very limited. Implementation of all likely potential formal irrigation schemes mentioned in available reports is expected to decrease the annual flow by 2% and the minimum monthly flow by 5%. The maximum possible impact of irrigation on annual average flow is estimated as 8%, with a reduction of minimum monthly flow by 17%. Deforestation of all areas within a 1 km buffer around the rivers is estimated to increase the flow by 6%. However, construction of all potential hydropower reservoirs in the basin may change the monthly mean flow distribution dramatically, although under the assumed operational rules, the impact of the dams is only substantial during wet years. The simulated impacts of climate change are considerable larger that those of the development scenarios (with exception of the high development scenario of hydropower schemes) although the results are sensitive to the choice of GCM and the IPCC SRES greenhouse gas (GHG) emission scenarios. The annual mean water flow predictions for the period 2020-2050 averaged over scenarios from all the four GCMs used in this study are close to the present situation for both the A2 and B2 GHG scenarios. For the 2050-2080 and 2070-2099 periods the all-GCM mean shows a flow decrease of 20% (14%) and 26% (17%) respectively for the A2 (B2) GHG scenarios. However, the uncertainty in the magnitude of simulated future changes remains high. The simulated effect of climate change on minimum monthly flow is proportionally higher

"Kultur" als Form symbolischer Gewalt: Grenzziehungsprozesse im Kontext von Migration am Beispiel der Schweiz

Die Schweiz gilt international als Modell eines gelungenen Multikulturalismus, dann nämlich wenn es das Zusammenleben der vier Sprachgruppen (Romands, DeutschschweizerInnen, TessinerInnen, RäteromanInnen) betrifft. Ein sprachlicher wie auch religiöser Pluralismus ist und war stets ein Grundbaustein des Selbstverständnisses der „Willensnation“ Schweiz. Geht es aber um MigrantInnen präsentiert sich die Geschichte anders, denn in diesem Falle erscheinen religiöse und ethnisch-kulturelle Pluralität vorwiegend als problematisch. MigrantInnen gehören entsprechend den öffentlichen und politischen Diskursen nicht zum multikulturellen Staat, vielmehr sind Prozesse kollektiver Grenzziehungen und damit Schließungsmechanismen zu beobachten, in denen Ethnizität, Religion und Kultur zu den wichtigsten Differenzierungsmerkmale werden, wie Gemeinsamkeiten gegen innen (SchweizerInnen) und Barrieren gegen außen (Ausländer, Migranten, Muslims, etc.) hergestellt werden. Ich argumentiere in diesem Kapitel, dass sich dieser „Kulturdiskurs“ im letzten Jahrzehnt verstärkt hat und gleichzeitig semantischen Verschiebungen unterworfen war. Mittels der Grenzziehungsperspektive wird historisch nachvollzogen, wie Zuwanderung und Integration in politischen Debatten und Gesetz zunehmend kulturalisiert und ethnisiert wurden. Ein Fallbeispiel aus der Forschung dient mir anschließend der Veranschaulichung dieser theoretischen Perspektive und dieses „neuen“ Essentialismus

Penalized likelihood for sparse contingency tables with an application to full-length cDNA libraries

<p>Abstract</p> <p>Background</p> <p>The joint analysis of several categorical variables is a common task in many areas of biology, and is becoming central to systems biology investigations whose goal is to identify potentially complex interaction among variables belonging to a network. Interactions of arbitrary complexity are traditionally modeled in statistics by log-linear models. It is challenging to extend these to the high dimensional and potentially sparse data arising in computational biology. An important example, which provides the motivation for this article, is the analysis of so-called full-length cDNA libraries of alternatively spliced genes, where we investigate relationships among the presence of various exons in transcript species.</p> <p>Results</p> <p>We develop methods to perform model selection and parameter estimation in log-linear models for the analysis of sparse contingency tables, to study the interaction of two or more factors. Maximum Likelihood estimation of log-linear model coefficients might not be appropriate because of the presence of zeros in the table's cells, and new methods are required. We propose a computationally efficient ℓ₁-penalization approach extending the Lasso algorithm to this context, and compare it to other procedures in a simulation study. We then illustrate these algorithms on contingency tables arising from full-length cDNA libraries.</p> <p>Conclusion</p> <p>We propose regularization methods that can be used successfully to detect complex interaction patterns among categorical variables in a broad range of biological problems involving categorical variables.</p

Pro-inflammatory profile of preeclamptic placental mesenchymal stromal cells: new insights into the etiopathogenesis of preeclampsia.

The objective of the present study was to evaluate whether placental mesenchymal stromal cells (PDMSCs) derived from normal and preeclamptic (PE) chorionic villous tissue presented differences in their cytokines expression profiles. Moreover, we investigated the effects of conditioned media from normal and PE-PDMSCs on the expression of pro-inflammatory Macrophage migration Inhibitory Factor (MIF), Vascular Endothelial Growth Factor (VEGF), soluble FMS-like tyrosine kinase-1 (sFlt-1) and free β-human Chorionic Gonadotropin (βhCG) by normal term villous explants. This information will help to understand whether anomalies in PE-PDMSCs could cause or contribute to the anomalies typical of preeclampsia. METHODS: Chorionic villous PDMSCs were isolated from severe preeclamptic (n = 12) and physiological control term (n = 12) placentae. Control and PE-PDMSCs’s cytokines expression profiles were determined by Cytokine Array. Control and PE-PDMSCs were plated for 72 h and conditioned media (CM) was collected. Physiological villous explants (n = 48) were treated with control or PE-PDMSCs CM for 72 h and processed for mRNA and protein isolation. MIF, VEGF and sFlt-1 mRNA and protein expression were analyzed by Real Time PCR and Western Blot respectively. Free βhCG was assessed by immunofluorescent. RESULTS: Cytokine array showed increased release of pro-inflammatory cytokines by PE relative to control PDMSCs. Physiological explants treated with PE-PDMSCs CM showed significantly increased MIF and sFlt-1 expression relative to untreated and control PDMSCs CM explants. Interestingly, both control and PE-PDMSCs media induced VEGF mRNA increase while only normal PDMSCs media promoted VEGF protein accumulation. PE-PDMSCs CM explants released significantly increased amounts of free βhCG relative to normal PDMSCs CM ones. CONCLUSIONS: Herein, we reported elevated production of pro-inflammatory cytokines by PE-PDMSCs. Importantly, PE PDMSCs induced a PE-like phenotype in physiological villous explants. Our data clearly depict chorionic mesenchymal stromal cells as central players in placental physiopathology, thus opening to new intriguing perspectives for the treatment of human placental-related disorders as preeclampsia

Circadian elevation of IL-6 levels in Muckle-Wells syndrome: a disorder of the neuro-immune axis?

Muckle-Wells syndrome (MWS) is a rare autosomal dominant hereditary disorder characterized by chronic recurrent urticaria, arthralgia, sensorineural deafness, and in some cases nephropathy due to amyloidosis (AA type). We report a 21-year-old woman and her father, both suffering from this syndrome, in whom elevated serum levels of IL-6 could be documented during the flares of urticaria, and discuss the relevance of this finding for MWS