Neutralizing TNFα restores glucocorticoid sensitivity in a mouse model of neutrophilic airway inflammation.

Asthma is a heterogeneous disorder, evidenced by distinct types of inflammation resulting in different responsiveness to therapy with glucocorticoids (GCs). Tumor necrosis factor α (TNFα) is involved in asthma pathogenesis, but anti-TNFα therapies have not proven broadly effective. The effects of anti-TNFα treatment on steroid resistance have never been assessed. We investigated the role of TNFα blockade using etanercept in the responsiveness to GCs in two ovalbumin-based mouse models of airway hyperinflammation. The first model is GC sensitive and T helper type 2 (Th2)/eosinophil driven, whereas the second reflects GC-insensitive, Th1/neutrophil-predominant asthma subphenotypes. We found that TNFα blockade restores the therapeutic effects of GCs in the GC-insensitive model. An adoptive transfer indicated that the TNFα-induced GC insensitivity occurs in the non-myeloid compartment. Early during airway hyperinflammation, mice are GC insensitive specifically at the level of thymic stromal lymphopoietin (Tslp) transcriptional repression, and this insensitivity is reverted when TNFα is neutralized. Interestingly, TSLP knockout mice displayed increased inflammation in the GC-insensitive model, suggesting a limited therapeutic application of TSLP-neutralizing antibodies in subsets of patients suffering from Th2-mediated asthma. In conclusion, we demonstrate that TNFα reduces the responsiveness to GCs in a mouse model of neutrophilic airway inflammation. Thus antagonizing TNFα may offer a new strategy for therapeutic intervention in GC-resistant asthma.

Prediction from ultrasonographic measurements of the expected delivery date in two species of bottlenosed dolphin (Tursiops truncatus and Tursiops aduncus).

Ultrasonographic measurements were made at least once a month during 14 gestations in seven Tursiops truncatus and 12 gestations in five Tursiops aduncus (bottlenosed dolphins). The 121 measurements of the fetal biparietal diameter and 139 measurements of the fetal thoracic diameter in T truncatus and the 97 measurements of the biparietal diameter and 97 measurements of the thoracic diameter in Taduncus were used to establish regression lines for the increases in the diameter of the head and thorax of the fetus with time. From these relationships an easy-to-use computer program was developed to predict the date of birth of the two species of bottlenosed dolphin, and its predictions were compared with the actual dates of birth of other calves of both species. The births occurred within the range of predicted dates, and even when only a few measurements were available, the program provided accurate predictions.

The choice of child delivery is a European human right.

In a judgment of 14 December 2010, in the case of Madam Ternovszky v. Hungary, the European Court of Human Rights has considered that a State should provide an adequate regulatory scheme concerning the right to choose in matters of child delivery (at home or in a hospital). In the context of homebirth, regarded as a matter of personal choice of the mother, this implies that the mother is entitled to a legal and institutional environment that enables her choice. This contribution stresses in which sense the regulatory schemes in the Member States Belgium, Germany, the Netherlands, France and the UK concerning the choice of child delivery are in accordance with Article 8 ECHR, the right to respect for the private life. Do the Member States provide the legal certainty to a mother that the midwife can legally assist a homebirth? Or are restrictions made in interests of public health?