In 2011, the European Council stressed the significance of water quality for sustainable development in Europe and emphasized the need for better integration of the water policy objectives into the Common Agriculture Policy Water Policy 15 (2013) 830-849 reform in rural areas. Since 2000, the Water Framework Directive (WFD) has required the EU Member States to target good ecological status for their water bodies. However, the implementation of the Directive for the numerous Mediterranean temporary streams has been delayed indicating the need for elaboration of the tools and methods that address the special characteristics of such water bodies. This requirement has been addressed by the recently completed MIRAGE project. In the context of the recent publication of the European Commission's Blueprint to Safeguard Europe's Waters, the MIRAGE-proposed framework for the characterization of the ecohydrological dynamics and the systematic description of the measured impact for temporary rivers could bring considerable added value to the EU revision of all relevant water policies. The project recommends additions to WFD articles including an explicit definition of temporary rivers, adaptation of environmental objectives to their peculiarities and establishment of a proper method to determine the initial status and specific actions in River Basin Management Plans.

AMH should replace FSH in the evaluation of gonadal reserve in pre-menopausal thyroid cancer women. At present, age is the only predictor of AMH levels. About one out of two women with a history of thyroid cancer suffers from menstrual dysregulation, but infertility must be considered a low risk.

This epidemiological study on acromegaly carried out using a large GP-based database, documented a disease prevalence of about 7 cases per 100,000 inhabitants. As expected, acromegaly was associated with a number of comorbidities (mainly hypertension and type II diabetes mellitus) and a high rate of patients' hospitalization.

Acromegaly is a rare and severe disease caused by an increased and autonomous secretion of growth hormone (GH), thus resulting in high circulating levels of insulin-like growth factor 1 (IGF-1). Comorbidities and mortality rate are closely related to the disease duration. However, in most cases achieving biochemical control means reducing or even normalizing mortality and restoring normal life expectancy. Current treatment for acromegaly includes neurosurgery, radiotherapy and medical therapy. Transsphenoidal surgery often represents the recommended first-line treatment. First-generation somatostatin receptor ligands (SRLs) are the drug of choice in patients with persistent disease after surgery and are suggested as first-line treatment for those ineligible for surgery. However, only about half of patients treated with octreotide (or lanreotide) achieve biochemical control. Other available drugs approved for clinical use are the second-generation SRL pasireotide, the dopamine agonist cabergoline, and the GH-receptor antagonist pegvisomant. In the present paper, we revised the current literature about the management of acromegaly, aiming to highlight the most relevant and recent therapeutic strategies proposed for patients resistant to first-line medical therapy. Furthermore, we discussed the potential molecular mechanisms involved in the variable response to first-generation SRLs. Due to the availability of different medical therapies, the choice for the most appropriate drug can be currently based also on the peculiar clinical characteristics of each patient.

Background Pasireotide is a second-generation somatostatin (SRIF) receptor ligand (SRL), approved for medical treatment of acromegaly and Cushing's disease (CD). The molecule is a stable cyclohexapeptide synthetized based on SRIF structure. Differently from first-generation SRLs (e.g. octreotide), preferentially binding somatostatin receptor (SST) subtype 2 (SST 2 ), pasireotide has high affinity for multiple SSTs (SST 5 > SST 2 > SST 3 > SST 1 ). Interestingly, early preclinical studies demonstrated that pasireotide shows distinct functional properties compared to SRIF and first-generation SRLs when binding SSTs. Methods We aimed to highlight the differential receptor-targeted action of pasireotide in the treatment of somatotroph and corticotroph adenomas, throughout the critical revision of preclinical studies carried out on acromegaly and CD models. Results Different authors demonstrated that the antisecretory effect of pasireotide in somatotroph adenoma cell cultures is comparable to that of the SST 2 -preferential agonist octreotide. Some reports even show a direct correlation between SST 2 mRNA expression and GH reduction after pasireotide treatment, thus laying for a predominant role of SST 2 in driving pasireotide efficacy in somatotropinomas in vitro. On the other hand, the inhibitory effect of pasireotide on ACTH secretion in corticotropinoma cells seems to be mainly mediated by SST 5 . Indeed, most reports show a higher potency and efficacy of pasireotide compared to SST 2 preferential agonists, while functional studies confirm the pivotal role of SST 5 targeting in corticotroph cells. Conclusions The analysis of preclinical studies carried out in somatotroph and corticoph adenomas points out that pasireotide shows a cell-specific activity, exerting its biological effects via different SSTs in the different adenoma histotypes.