Chronic NSAIDs Therapy and Upper Gastrointestinal Tract – Mechanism of Injury, Mucosal Defense, Risk Factors for Complication Development and Clinical Management

Non steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed medications worldwide because of their analgesic and anti-inflammatory properties. In fact, NSAIDs are generally prescribed for pain management in musculoskeletal or osteoarticolar pathologies and for rheumatic diseases, very common diseases in the general population. About twenty million US patients were prescribed NSAIDs every year. Although NSAIDs are generally well tolerated, chronic therapy is responsible for a significant morbidity and mortality rate; in fact, the incidence of GI events is significantly higher (about four fold) in patients receiving NSAIDs chronic therapy. Adverse gastrointestinal events related to NSAIDs therapy occur in a little but significant amount of patients, resulting in an important morbidity and mortality. In the US more than 150 per 100.000 patients were admitted every year for NSAIDs related adverse events, resulting in about 15000 deaths. The chapter covers the mechanism of NSAIDs related injury, mucosal defense, risk factors for complication development and the clinical management

BIM e beni architettonici. Verso una metodologia operativa per la conoscenza e la gestione del patrimonio culturale

Lo studio intende rispondere alla crescente ne- cessità di organizzare in maniera virtuosa gli ap- parati informativi relativi al Patrimonio Culturale, attraverso una metodologia che integri processi multidisciplinari di interazione con l’informazio- ne, finalizzati al rilievo, documentazione, gestio- ne, conoscenza e valorizzazione del Bene. È necessario ripercorrere, attualizzandolo, il pro- cesso di acquisizione strumentale dell’informa- zione, di normalizzazione e di strutturazione dei dati acquisti in un modello semantico tridimen- sionale e la successiva rappresentabilità e la frui- bilità del modello e della banca dati associata. Se nel campo della progettazione l’utilizzo del Buil- ding Information Modeling ha visto negli ultimi anni un consolidamento nelle procedure e l’indi- viduazione di metodologie standard, nell’ambito dei Beni Culturali, la sfida volta all’individuazione di metodologie operative è ancora aperta.The study aims to answer the growing need for virtuously organize informational apparatuses related to Cultural Heritage. We propose a me- thodology that integrates multidisciplinary pro- cesses of interaction with information aimed at survey, documentation, management, knowled- ge and enhancement of historic artifacts. It is needed to review and update the procedu- re of instrumental data acquisition, standardi- zation and structuring of the acquired data in a three-dimensional semantic model as well as the subsequent representability and accessibility of the model and the related database. If the use of Building Information Modeling has in recent years seen a consolidation in the procedures and the identification of standard methods in design process, nevertheless in the field of architectural heritage, the challenge to identify operational methodologies for the conservation, manage- ment and process enhancement is still open

Production and characterization of CSSI003 (2961) human induced pluripotent stem cells (iPSCs) carrying a novel puntiform mutation in RAI1 gene, Causative of Smith–Magenis syndrome

Smith-Magenis syndrome (SMS) is a complex genetic disorder characterized by developmental delay, behavioural problems and circadian rhythm dysregulation. About 90% of SMS cases are due to a 17p11.2 deletion containing retinoic acid induced1 (RAI1) gene, 10% are due to heterozygousmutations affecting RAI1 coding region. Little is known about RAI1 role

Copy number variations in healthy subjects. Case study: iPSC line CSSi005-A (3544) production from an individual with variation in 15q13.3 chromosome duplicating gene CHRNA7

CHRNA7, encoding the neuronal alpha7 nicotinic acetylcholine receptor (a7nAChR), is highly expressed in the brain, particularly in the hippocampus. It is situated in the 15q13.3 chromosome region, frequently associated with a Copy Number Variation (CNV), which causes its duplication or deletion. The clinical significance of CHRNA7 duplications is unknown so far, but there are several research data suggesting that they may be pathogenic, with reduced penetrance. We have produced an iPS cell line from a single healthy donor's fibroblasts carrying a 15q13.3 CNV, including CHRNA7 in order to study the exact role of this CNV during the neurodevelopment

Molecular and Clinical Links between Drug-Induced Cholestasis and Familial Intrahepatic Cholestasis

Idiosyncratic Drug-Induced Liver Injury (iDILI) represents an actual health challenge, accounting for more than 40% of hepatitis cases in adults over 50 years and more than 50% of acute fulminant hepatic failure cases. In addition, approximately 30% of iDILI are cholestatic (drug-induced cholestasis (DIC)). The liver's metabolism and clearance of lipophilic drugs depend on their emission into the bile. Therefore, many medications cause cholestasis through their interaction with hepatic transporters. The main canalicular efflux transport proteins include: 1. the bile salt export pump (BSEP) protein (ABCB11); 2. the multidrug resistance protein-2 (MRP2, ABCC2) regulating the bile salts' independent flow by excretion of glutathione; 3. the multidrug resistance-1 protein (MDR1, ABCB1) that transports organic cations; 4. the multidrug resistance-3 protein (MDR3, ABCB4). Two of the most known proteins involved in bile acids' (BAs) metabolism and transport are BSEP and MDR3. BSEP inhibition by drugs leads to reduced BAs' secretion and their retention within hepatocytes, exiting in cholestasis, while mutations in the ABCB4 gene expose the biliary epithelium to the injurious detergent actions of BAs, thus increasing susceptibility to DIC. Herein, we review the leading molecular pathways behind the DIC, the links with the other clinical forms of familial intrahepatic cholestasis, and, finally, the main cholestasis-inducing drugs

RNAs competing for microRNAs mutually influence their fluctuations in a highly non-linear microRNA-dependent manner in single cells

We used an experimental design based on two bidirectional plasmids and flow cytometry measurements of cotransfected mammalian cells. We validated a stochastic gene interaction model that describes how mRNAs can influence each other’s fluctuations in a miRNA-dependent manner in single cells. We show that miRNA–target correlations eventually lead to either bimodal cell population distributions with high and low target expression states, or correlated fluctuations across targets when the pool of unbound targets and miRNAs are in near-equimolar concentration. We found that there is an optimal range of conditions for the onset of cross-regulation, which is compatible with 10–1000 copies of targets per cell

BIM e beni architettonici: verso una metodologia operativa per la conoscenza e la gestione del patrimonio culturale - BIM and architectural heritage: towards an operational methodology for the knowledge and the management of Cultural Heritage

Lo studio intende rispondere alla crescente necessità di organizzare in maniera virtuosa gli apparati informativi relativi al Patrimonio Culturale, attraverso una metodologia che integri processi multidisciplinari di interazione con l’informazione, conoscenza e valorizzazione del Bene. È necessario ripercorrere, attualizzandolo, il processo di acquisizione strumentale dell’informazione, di normalizzazione e di strutturazione dei dati acquisti in un modello semantico tridimensionale e la successiva rappresentabilità e la fruibilità del modello e della banca dati associata. Se nel campo della progettazione l’utilizzo del Building Information Modeling ha visto negli ultimi anni un consolidamento nelle procedure e l’individuazione di metodologie standard, nell’ambito dei Beni Culturali, la sfida volta all’individuazione di metodologie operative è ancora aperta