Impact of the Rome II paediatric criteria on the appropriateness of the upper and lower gastrointestinal endoscopy in children.

BACKGROUND: The demand for paediatric gastrointestinal (GI) endoscopy has increased, resulting in a significant rise of overall costs. AIM: To assess the clinical impact of the Rome II criteria for functional gastrointestinal disorders when selecting paediatric patients who underwent GI endoscopy. METHODS: The indications and findings of GI endoscopic procedures performed before and after the publication of the Rome II criteria were evaluated retrospectively. RESULTS: Upper GI endoscopy was performed in 1124 children, whereas colonoscopy was performed in 500 subjects. A total of 607 (54%) oesophago-gastro-duodenoscopies (OGDs) were positive and 517 (46%) were negative, whereas 306 (61.1%) colonoscopies were positive and 194 (38.9%) were negative. Of the 1624 procedures, 26% were considered inappropriate according to the Rome II criteria. Inappropriate procedures decreased significantly after publication of the Rome II criteria (OR, 3.7; 95% CI, 1.8-7.5). Of 1202 appropriate GI endoscopies, 502 OGD (62.7%) were significantly contributive, compared with only 105 (32.5%) of the 323 inappropriate procedures (OR, 3.5; 95% CI, 2.6-4.6), whereas 265 (65.8%) colonoscopies were significantly contributive, compared with only 41 (42.3%) of the 97 inappropriate procedures (OR, 2.6; 95% CI, 1.6-4.1). CONCLUSIONS: The use of the criteria for functional gastrointestinal disorders makes a significant positive impact, they should reduce unnecessary paediatric GI endoscopy

The Neuroprotective Effects of 17β-Estradiol Pretreatment in a Model of Neonatal Hippocampal Injury Induced by Trimethyltin

Hippocampal dysfunction plays a central role in neurodevelopmental disorders, resulting in severe impairment of cognitive abilities, including memory and learning. On this basis, developmental studies represent an important tool both to understanding the cellular and molecular phenomena underlying early hippocampal damage and to study possible therapeutic interventions, that may modify the progression of neuronal death. Given the modulatory role played by 17β-estradiol (E2) on hippocampal functions and its neuroprotective properties, the present study investigates the effects of pretreatment with E2 in a model of neonatal hippocampal injury obtained by trimethyltin (TMT) administration, characterized by neuronal loss in CA1 and CA3 subfields and astroglial and microglial activation. At post-natal days (P)5 and P6 animals received E2 administration (0.2 mg/kg/die i.p.) or vehicle. At P7 they received a single dose of TMT (6.5 mg/kg i.p.) and were sacrificed 72 h (P10) or 7 days after TMT treatment (P14). Our findings indicate that pretreatment with E2 exerts a protective effect against hippocampal damage induced by TMT administration early in development, reducing the extent of neuronal death in the CA1 subfield, inducing the activation of genes involved in neuroprotection, lowering the neuroinflammatory response and restoring neuropeptide Y- and parvalbumin- expression, which is impaired in the early phases of TMT-induced damage. Our data support the efficacy of estrogen-based neuroprotective approaches to counteract early occurring hippocampal damage in the developing hippocampus

Integrin α7 Is a Functional Marker and Potential Therapeutic Target in Glioblastoma

Functionally relevant markers of glioblastoma stem-like cells (GSCs) have potential for therapeutic targeting to treat this aggressive disease. Here we used generation and screening of thousands of monoclonal antibodies to search for receptors and signaling pathways preferentially enriched in GSCs. We identified integrin α7 (ITGA7) as a major laminin receptor in GSCs and in primary high-grade glioma specimens. Analyses of mRNA profiles in comprehensive datasets revealed that high ITGA7 expression negatively correlated with survival of patients with both low- and high-grade glioma. In vitro and in vivo analyses showed that ITGA7 plays a key functional role in growth and invasiveness of GSCs. We also found that targeting of ITGA7 by RNAi or blocking mAbs impaired laminin-induced signaling, and it led to a significant delay in tumor engraftment plus a strong reduction in tumor size and invasion. Our data, therefore, highlight ITGA7 as a glioblastoma biomarker and candidate therapeutic target

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements