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Il fenomeno dei Neet, i giovani che non studiano e non lavorano, rappresenta la punta dell'iceberg di un malessere sociale decisamente più esteso e pervasivo di quanto i numeri, comunque alti, lascerebbero supporre. Dietro una persona che scivola al di fuori dei percorsi consueti di vita, c'è un cortocircuito che investe le principali istituzioni sociali: scuola, famiglia e mondo del lavoro. Il volume offre l'esito di un percorso di ricerca durato due anni e condotto, con metodologie qualitative, da un team multidisciplinare di scienziati sociali. Attraverso la raccolta di storie di vita, focus group, interviste in profondità è stato possibile individuare i tratti che accomunano i percorsi dei giovani Neet e anche ciò che li distingue. I Neet, infatti, non sono tutti uguali: per questo parlare del fenomeno in generale rappresenta una semplificazione non utile alla sua comprensione e soprattutto all'elaborazione di politiche efficaci per contrastarlo. Si è costruita un'analisi dei bisogni, comportamenti e orientamenti di valore dei giovani rispetto a formazione e mondo del lavoro, giungendo a elaborare una tipologia, che rende conto della disomogeneità del fenomeno. L'interdipendenza dei fattori culturali e socioeconomici rischia di schiacciare i più fragili tra i soggetti sociali e i Neet sono fra questi. Ascoltarne i bisogni e conoscere il loro mondo sociale è il primo e necessario passo per qualsiasi intervento.

Background & Aims Premenopausal women who are HCV positive (HCV+) have failing ovarian function, which is likely to impact their fertility. Thus, we investigated the reproductive history, risk of infertility, and pregnancy outcomes in women of childbearing age who were HCV+. Methods Three different groups were studied: (1) Clinical cohort: 100 women who were HCV+ and also had chronic liver disease (CLD), age matched with 50 women who were HBV+ with CLD and with 100 healthy women; all women were consecutively observed in three gastroenterology units in hospitals in Italy; (2) 1,998 women who were HCV+ and enrolled in the Italian Platform for the Study of Viral Hepatitis Therapies (PITER); (3) 6,085 women, who were mono-infected with HCV, and 20,415 women, who were HCV−, from a large de-identified insurance database from the USA. Measurements: total fertility rate (TFR) defined as the average number of children that a woman would bear during her lifetime. To define the reproductive stage of each participant, levels of anti-Müllerian hormone (AMH) and 17β-estradiol were measured. Results Clinical cohort: women who were either HCV+ or HBV+ had similar CLD severity and age at first pregnancy. Based on a multivariate analysis, women who were HCV+ had a higher risk of miscarriage than those who were HBV+ (odds ratio [OR] 6,905; 95% CI 1.771–26.926). Among women who were HCV+, incidence of miscarriage was correlated with median AMH level (1.0 ng/ml). Achieving a sustained virologic response (SVR) after antiviral treatment reduced the risk of miscarriage (OR 0.255; 95% CI 0.090–0.723). In the PITER-HCV cohort, miscarriage occurred in 42.0% of women (44.6% had multiple miscarriages). TFR for women who were HCV+ and between 15 and 49 years of age was 0.7 vs. 1.37 of Italian population of the same age range. In the US cohort: compared with women who were HCV−, women who were HCV+ positive were significantly more likely to have infertility (OR 2.439; 95% CI 2.130–2.794), premature birth (OR 1.34; 95% CI 1.060–1.690), gestational diabetes (OR 1.24; 95% CI 1.020–1.510), and pre-eclampsia (OR 1.206; 95% CI 0.935–1.556), and were less likely to have a live birth (OR 0.754; 95% CI 0.622–0.913). Conclusions Ovarian senescence in women of childbearing age who are HCV+ is associated with a lower chance of live birth, greater risk of infertility, gestational diabetes, pre-eclampsia and miscarriage. Such risks could be positively influenced by successful HCV cure. Lay summary Most new cases of HCV infection are among people who inject drugs, many of whom are young women in their childbearing years. Women of reproductive age who are HCV+ display markers of ovarian senescence. This is associated with an increased burden in terms of infertility and adverse pregnancy outcomes, including stillbirth, miscarriage, fewer live births, and gestational diabetes. Early viral suppression with therapy is likely to mitigate these risks.

It has come to our attention that the PITER framework investigator, Alessandro Federico, was incorrectly listed as F. Alessandro in the original manuscript. Please note that the correct name of this author is Alessandro Federico (2nd University of Naples). The correct list of PITER investigators is in the footnote below.

Il saggio cerca di ricostruire la storia di un edificio di grande rilevanza storica a livello architettonico ed artistico, purtroppo sconosciuto ai più: la chiesa di San Michelino in Foro di Rimini. Dell’antica struttura, la cui origine è databile tra il IV e VI secolo, oggi è possibile vedere solo alcune porzioni, incastonate in edifici costruiti in epoche successive. Partendo dalle fonti documentarie e bibliografiche se ne ripercorre inizialmente la storia: da chiesa di competenza templare prima e giovannita poi, fino alla soppressione ed il passaggio a proprietà privata. Si propone quindi un breve studio svolto circa gli affreschi ritrovati fortuitamente nel 1993 nell’abside della chiesa con particolare riferimento all’immagine ancora conservata di una santa databile al XIII secolo. Tramite la lettura della stratigrafia delle murature viene in seguito ricostruita la storia dell’evoluzione del manufatto a livello architettonico. Infine, dopo aver analizzato lo stato di conservazione dell’edificio, si forniscono alcune linee guida di intervento per un progetto di restauro e valorizzazione della chiesa e dell’affresco al suo interno.

The pattern of RNA synthesis during status epilepticus was studied in the cerebral extrafocal cortex of cats. The results indicated a change in the pattern of RNA synthesis suggesting an inadequate processing of precursor RNA molecules into mature products. The newly synthesized cytoplasmic RNA was composed of discrete species whereas the corresponding RNA of the controls showed a heterogeneous distribution. Such discrete species might be involved in cellular processes of particular importance in this functional state.

Morrell (1959) described the appearance of a secondary epileptic focus in the rabbit cortical area contralateral and homotopic to a primary epileptic lesion induced by freezing. Such a secondary epileptic lesion is called mirror focus.

Colitis is the term used for chronic inflammatory bowel diseases at substantially increased risk of developing a form of colorectal cancer (CRC) known as colitis-associated cancer. In our study we synthesized core-shell polymeric micelles obtained by self-assembly of block copolymers for high efficiency delivery of anti-inflammatory and anti-cancer compounds to colonocytes and colon mucosa. We achieved an efficient intracellular delivery of these hydrophobic compounds (prednisone, retinoic acid and doxorubicin) to cultured colonocytes without cellular toxicity. The efficacy of retinoic acid and doxorubicin administration was significantly increased using these nanosized carriers. Moreover, these polymeric micelles have been shown to overcome the multidrug resistance efflux mechanism effectively delivering doxorubicin to multidrug-resistant colon cancer cells. These nanocarriers are also suitable for selective in vivo delivery of lipophilic drugs by enema administration to the inflamed colon tissue, specifically targeting the inflamed mucosa. From the Clinical Editor This team of investigators studied polymeric micelles as highly efficient drug delivery systems enabling intracellular delivery of hydrophobic compounds (prednisone, retinoic acid, and doxorubicin) to cultured colonocytes without cellular toxicity, also demonstrating beneficial in vivo effects.

Introduction: The availability of interferon-sparing therapy with direct acting antivirals (DAAs) has expanded the pool of patients eligible for treatment. Despite this, data on the efficacy and safety of these treatments in elderly are lacking. Aim: To evaluate the efficacy and safety of the treatment with DAA-based regimens in HCV patients aged ≥65 years with advanced fibrosis/cirrhosis in a real life clinical setting. Methods: Retrospective data of elderly patients treated with DAAs from January to November 2015 in 7 tertiary referral center of Emilia-Romagna Region (Italy) were collected. Patients received: sofosbuvir (SOF) [n = 35], SOF + simeprevir (SMV) [n = 78], SOF + daclatasvir (DCV) [n = 21], SOF + ledipasvir [n = 17], SMV + DCV [n = 4], ombitasvir/paritaprevir/ritonavir only [n = 3] or with dasasbuvir [n = 42]. Ribavirin was added at the physician's discretion according weight. The primary efficacy endpoint was sustained virological response 12 weeks after the last dose of study drug (SVR12). Results: Overall, 200 consecutive elderly patients were treated. The median age was 74 years (range: 65-85) and 90 (45%) aged ≥75 years; 49% were male, 50.5% were treatment experienced and 85% had cirrhosis. The majority (76%) had genotype (GT) 1b. To date, 155 patients completed treatment. Two cirrhotics died during the therapy and were excluded from final analysis because the cause of death was unrelated to the treatment. Overall, 94 have reached week 12 of post-treatment and the SVR12 was 91.5% (86/94). According to GT, the SVR12 was achieved in 69/73 (94.5%) with GT1, in 16/18 (88.9%) with GT2 and in 1/3 (33.4%) with GT4 infection. Relapse occurred more commonly in cirrhotic patients. No serious adverse events have been reported until now. Complete safety data for the cohort and updated SVR data will be presented. Conclusions: This preliminary data indicate that DAA-based regimen have a similar efficacy compared to registrative studies and without significant side effects in HCV elderly patients in a real-world setting.

Introduction: Non-interferon-based therapy with direct acting antiviral agents (DAA) have become an integral component of treatment for HCV infection but little is known about their real-world effectiveness. Aim: To evaluate the efficacy and safety of the treatment with DAA-based regimen in HCV patients with advanced fibrosis/cirrhosis in a real life clinical setting. Methods: Retrospective data of patients treated with DAA from January to November 2015 in 7 tertiary referral centers in the Emilia-Romagna Region (Italy) were collected. Patients on the waiting list for orthotopic liver transplantation and with HIV co-infection were excluded. Patients received: sofosbuvir (SOF) [n = 74], SOF + simeprevir (SMV) [n = 149], SOF + daclatasvir (DCV) [n = 69], SOF + ledipasvir [n = 43], SMV + DCV [n = 4], ombitasvir/paritaprevir/ritonavir only [n = 11] or with dasasbuvir [n = 84]. Ribavirin was added at the physician's discretion according to weight. The primary efficacy endpoint was sustained virological response 12 weeks after the last dose of study drug (SVR12). Results: Overall, 435 consecutive patients were treated. The median age was 63 years (range: 29–85); 60% were male, 55.2% were treatment experienced and 81.1% had cirrhosis. The majority (56.6%) had genotype (GT) 1b, 12.4% GT1a, 11.3% GT2, 12.6% GT3 and 7.1% GT4. To date, 347 patients completed treatment and 179 the week 12 of post-treatment follow-up. Three cirrhotics died during treatment and were excluded from analysis. Overall, the SVR12 was 88.8% (159/179). According to GT, the SVR12 was achieved in 17/19 (89.5%) GT1a, in 100/111 (90.1%) GT1b, in 24/26 (92.3%) GT2, in 9/11 (81.8%) GT3 and in 9/12 (75%) GT4. Patients with cirrhosis had a lower response rate than those with advanced fibrosis (86.7% vs 97.2%; p = 0.082). Complete safety data for the entire cohort, updated SVR12 will be presented. Conclusions: The DAA-based regimen was efficacious with low relapse rates in HCV patients in a real-world setting. Patients with cirrhosis seems to respond less well to the different regimens used.

BACKGROUND: Erosive reflux disease (ERD) and non-erosive reflux disease (NERD) are often regarded as part of the spectrum of the same disease. AIM: To elucidate molecular features that characterise NERD and ERD at the protein level. METHODS: A total of 56 consecutive subjects were enrolled: 10 healthy subjects, 24 with NERD and 22 with ERD. Eight specimens were taken from macroscopically normal mucosa at 5 cm of gastro-oesophageal junction. Four were processed for the proteins extraction and four for evaluation using haematoxylin-eosin and immunohistochemistry. We used shotgun proteomics to identify tentative disease molecular features for ERD or NERD. Candidate distinctive proteins were verified using immunohistochemistry. RESULTS: Shotgun proteomics analysis revealed 33 differentially expressed proteins in NERD vs. ERD samples, involved in cellular proliferation, keratinisation, stress responses and sugar metabolism. Based on a gene ontology meta-analysis, seven of them were further analysed using Western blotting (WB) and four also using immunohistochemistry. We identified novel candidate disease molecular features for GERD and few distinctive proteins to discriminate NERD and ERD. In particular, Transitional Endoplasmic Reticulum ATPase (TER ATPase), GAPDH, Alpha 1 Acid Glycoprotein 1, Annexin A1, Calmodulin and 14-3-3 proteins were confirmed at WB analysis. CONCLUSIONS: Non-erosive reflux disease and ERD are distinct disease entities at the protein level. This study proposes an array of candidate biomarkers possibly useful to discriminate between NERD and ERD.

BACKGROUND: Cannabinoid (CB) receptors have been located in brain areas involved in the triggering of TLESRs as well as in the nodose ganglion from which vagal afferents emanate. The distribution of CB(1) receptors has been investigated in the human gastrointestinal mucosa, as expression of inflammatory process. AIM: To evaluate the CB(1) expression in oesophageal mucosa. METHODS: A total of 87 consecutive subjects were enrolled: 10 controls, 39 NERD and 38 erosive oesophagitis. Eight specimens were taken from macroscopically normal mucosa. Five were processed by haematoxylin-eosin, MIB1/CB(1) evaluation and three for the RNA and proteins extraction. RESULTS: The mean MIB1-LI value was 31% and 22% in NERD and ERD patients, respectively, compared to 68% in the healthy subjects. Mean CB(1)mRNA/GUSB mRNA value of the controls was 0.66, while in GERD patients, it was 0.28. In NERD and ERD, the mean values of CB(1)/GUSB were 0.38 and 0.17, respectively, with highly significant differences between the NERD vs. ERD groups. Semi-quantitative analysis of CB(1) expression, performed with WB, shows in NERD patients a higher CB(1) receptor expression than ERD patients. CONCLUSIONS: With this study, we showed for the first time the presence of CB(1) receptors in the human oesophageal epithelium.

Overexpressed cyclooxygenase-2 (COX-2) strongly contributes to the growth and invasiveness of tumoral cells in patients affected by colorectal cancer (CRC). It has been demonstrated that COX-2 overexpression depends on different cellular pathways involving both transcriptional and post-transcriptional regulations. We assumed that COX-2 expression could be regulated also by microRNAs (miRNAs) since these short RNA molecules participate to the fine regulation of several genes implicated in cell growth and differentiation. In this paper, we report the inverse correlation between COX-2 and miR-101 expression in colon cancer cell lines and we demonstrated in vitro the direct inhibition of COX-2 mRNA translation mediated by miR-101. Moreover, this correlation was supported by data collected ex vivo, in which colon cancer tissues and liver metastases derived from CRC patients were analyzed. These findings provide a novel molecular insight in the modulation of COX-2 at post-transcriptional level by miR-101 and strengthen the observation that miRNAs are highly implicated in the control of gene expression. An impairment of miR-101 levels could represent one of the leading causes of COX-2 overexpression in colon cancer cells.