Somatic deletion in exon 10 of aryl hydrocarbon receptor gene in human GH-secreting pituitary tumors

Objective/Purpose: The aryl hydrocarbon receptor (AHR) pathway plays a critical role in the biology of Growth Hormone (GH)-secreting pituitary tumor (somatotropinoma). Germline rs2066853 AHR variant was found to be more frequent among acromegaly patients and associated with a more severe disease with larger invasive somatropinoma, and with resistance to somatostatin analogs treatment in patients living in polluted areas. However, no somatic changes in AHR gene have been reported so far in acromegaly patients. On that basis, the aim of the study was to assess at the somatic level the AHR gene status encompassing exon 10 region, also because of the high rate of variants found in this genomic region. Methods: A cohort of 13 patients aged 20\u201376 years with biochemical, clinical and histological diagnosis of somatotropinoma was studied. DNA and RNA from pituitary tumor histological samples have been extracted and analyzed by PCR and direct sequencing for AHR gene variants, and compared with corresponding patients\u2019 germline DNA as well as normal pituitary tissue as reference control. Results: A degenerated letter codes in the region corresponding to AHR exon 10 (c.1239-c.2056) was detected in somatotropinomas-derived DNA but not in that of matched germline and pituitary normal tissue. By multiple PCR and sequencing analysis, we observed amplification only before codon 1246 and after codon 1254, confirming the presence of a tumor-restricted somatic deletion in the 5\u2019 upstream region of AHR exon 10. Analysis of PCR-amplified cDNA revealed a wildtype sequence of exon 9 and 10 in normal pituitary tissue, and a wildtype sequence of exon 9 and 10 up to codon 1246 and no sequence after the deletion region (c.1246-c.1254) in 6 out of 9 tumor samples. Patients carrying the germline rs2066853 AHR variant showed no somatic LOH at the corresponding genetic locus. Conclusion: This is the first demonstration of a recurrent somatic deletion in the exon 10 of the AHR gene in somatotropinomas. The functional impact of this genetic finding needs to be clarifie

Notulae to the Italian native vascular flora: 8

In this contribution, new data concerning the distribution of native vascular flora in Italy are presented. It includes new records, confirmations, exclusions, and status changes to the Italian administrative regions for taxa in the genera Ajuga, Chamaemelum, Clematis, Convolvulus, Cytisus, Deschampsia, Eleocharis, Epi- pactis, Euphorbia, Groenlandia, Hedera, Hieracium, Hydrocharis, Jacobaea, Juncus, Klasea, Lagurus, Leersia, Linum, Nerium, Onopordum, Persicaria, Phlomis, Polypogon, Potamogeton, Securigera, Sedum, Soleirolia, Stachys, Umbilicus, Valerianella, and Vinca. Nomenclatural and distribution updates, published elsewhere, and corrigenda are provided as Suppl. material

Social cognition in people with schizophrenia: A cluster-analytic approach

Background The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. Method A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. Results We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. Conclusions If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person

Effectiveness and Safety of rhIGF-1 Therapy in Children: The European Increlex® Growth Forum Database Experience.

BACKGROUND/AIMS: We report data from the EU Increlex® Growth Forum Database (IGFD) Registry, an ongoing, open-label, observational study monitoring clinical practice use of recombinant human insulin-like growth factor-1 (rhIGF-1) therapy in children. METHODS: Safety and effectiveness data on rhIGF-1 treatment of 195 enrolled children with growth failure were collected from December 2008 to September 2013. RESULTS: Mean ± SD (95% CI) height velocity during first year of rhIGF-1 treatment was 6.9 ± 2.2 cm/year (6.5; 7.2) (n = 144); in prepubertal patients naïve to treatment, this was 7.3 ± 2.0 cm/year (6.8; 7.7) (n = 81). Female sex, younger age at start of rhIGF-1 therapy, and lower baseline height SDS predicted first-year change in height SDS. The most frequent targeted treatment-emergent adverse events (% patients) were hypoglycemia (17.6%, predictors: young age, diagnosis of Laron syndrome, but not rhIGF-1 dose), lipohypertrophy (10.6%), tonsillar hypertrophy (7.4%), injection site reactions (6.4%), and headache (5.9%). Sixty-one serious adverse events (37 related to rhIGF-1 therapy) were reported in 31 patients (16.5%). CONCLUSION: Safety and effectiveness data on use of rhIGF-1 in a 'real-world' setting were similar to those from controlled randomized trials. Severe growth phenotype and early start of rhIGF-1 improved height response and predicted risk of hypoglycemia

Immunohistochemical expression of glypican-3 in adrenocortical carcinoma: A potential cause of diagnostic pitfalls

no abstract availabl