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Objective The aim of this study was to develop an open-source and reproducible digital quantitative analysis (DIA) of somatostatin receptor subtype 2a (SST2) staining in formalin-fixed paraffin-embedded tissues of pancreatic neuroendocrine tumors (panNETs) and growth hormone (GH)-secreting pituitary adenomas (GHomas). Design SST2 immunostaining of 18 panNETs and 39 GHomas was assessed using a novel DIA protocol and compared with a widely used semi-quantitative immunoreactivity score (IRS). Methods The DIA software calculates the staining intensity/area and the percentage of positive cells (%PC). Four representative images were selected for each sample by two independent selectors (S1 and S2), with the analysis performed by two independent analyzers (A1 and A2). Agreement between observers was calculated using the concordance correlation coefficient (CCC). Results In panNETs, the CCC ranged 0.935–0.977 for intensity/area and 0.942–0.983 for %PC. In GHomas, the CCC ranged 0.963–0.997 for intensity/area and 0.979–0.990 for %PC. In both panNETs and GHomas, the DIA staining intensity was strongly correlated with the IRS (Spearman rho: 0.916–0.969, P P 2 expression, evaluated both as DIA intensity/area (Spearman rho: −0.448 to −0.527, P = 0.007–0.004) and DIA %PC (Spearman rho: −0.558 to −0.644, P ≤ 0.001). Conclusions The DIA has an excellent inter-observer agreement and showed a strong correlation with the widely used semi-quantitative IRS. The DIA protocol is an open-source, highly reproducible tool and provides a reliable quantitative evaluation of SST2 immunohistochemistry.

Acromegaly is a disease characterized by elevated growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels. Surgery is the only curative treatment, while medical therapies are administered life-long. To date, almost 30% of patients treated with the currently available medical therapies do not achieve biochemical control.This review focuses on new drugs in development for acromegaly. In detail, we provide an overview of the new molecules designed to improve disease control rate (such as novel somotostatin receptor ligands and antisense oligonucleotides), as well as the new formulations of existing medications aiming to improve patients' compliance (e.g. oral or long-acting subcutaneous octreotide).The constant progresses in the medical treatment of acromegaly could lead to an individualized therapy based on tumor, as well as patient's characteristics. Besides disease control, patient's need represents a major target of medical treatment in chronic diseases such as acromegaly, in order to improve compliance to therapy and patients' quality of life.

Soil seed banks serve as reservoirs of taxonomic and genetic diversity and can buffer the effect of perturbations on plant communities, and thus are critical for community resilience. We studied the relationship of seed bank abundance and richness with different hydrological attributes, evaluated beta diversity patterns among wetlands in the Middle Parana River floodplain, and experimentally explored soil seed bank germination after a drought period. Seed abundance was positively related to drought intensity and, along with richness, negatively related to drought and flood frequency. Turnover and balanced variation in abundance greatly contributed to the total beta diversity probably associated with the environmental heterogeneity of the floodplain; nestedness had a lower contribution probably associated with different dispersal abilities of species. Germination behavior varied between rooted and free-floating plants. In conclusion, the soil seed banks studied are highly variable among habitats; drought and flood frequency, and drought intensity are related with the seed banks abundance and richness; and the germination responses after a drought phase differ among broad ecological groups of wetland plants.

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.

PURPOSE Acromegaly is a severe chronic endocrine disease. Achieving biochemical control often needs a multimodal treatment approach, including prolonged medical treatment. Aim of the study is to evaluate the burden of treatment direct costs with respect to the different therapeutic strategies, disease control, and follow-up length. METHODS Single center retrospective study on 73 acromegaly patients. Costs of acromegaly treatments were computed based on a detailed revision of patients' clinical charts. RESULTS Median total treatment cost/patient was €47,343 during the entire follow-up (8 years), while median treatment cost/patient/year was €6811. The majority of patients received medical therapy (71/73, 97.3%). Median cost for first-line medical treatment (first-generation somatostatin receptor ligands) was lower compared to second-line treatments (pegvisomant monotherapy or combination therapies), considering both total (€22,824 vs €76,140; p

The mixture of water extracts from Tanacetum parthenium and Salix alba was studied in an ex vivo assessment of neurotoxicity constituted by isolated mouse cortex specimens challenged with K+ 60 mM Krebs–Ringer buffer (neurotoxicity stimulus). The effects of the mixture on lactate dehydrogenase (LDH), nitrite and serotonin levels were investigated. The phytochemical profile of the mixture was also evaluated. A docking approach was conducted to predict, albeit partially, the putative mechanism underlying the observed effects. The extracts displayed a good profile of polyphenolic compounds (22 chromatographic peaks detected), with caftaric acid and epicatechin being the prominent phenols. In isolated cortex, the association of T. parthenium and S. alba extracts was effective in reducing the K+ 60 mM-induced levels of LDH and nitrites, whereas the neurotoxicity stimulus-induced serotonin depletion was prevented by the treatment. Regarding the inhibition of serotonin catabolism, epicatechin (44.65 µg/mg) and caftaric acid (10.51 µg/mg) were putatively the main compounds involved in the inhibition of monoamineoxidase-A, which is known to play a master role in serotonin turnover. Collectively, the results of the present study point to the efficacy of the present extract mixture as an innovative pharmacological tool to prevent the onset of migraine.

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.

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 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 eco-hydrological 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.

Toxicants on fish may induce genetic alterations that can be used as genotoxic markers. We evaluated DNA damage using alkaline comet assay applied on erythrocytes after in vivo exposure of Prochilodus lineatus to different concentrations of Cypermethrin (0.300, 0.150, 0.075 and 0.000 µg/L) as a probable chemical mutagen. The results revealed a significantly higher level of DNA damage at all concentrations of Cypermethrin tested compared to control and background level (p