Social threat exposure in juvenile mice promotes cocaine-seeking by altering blood clotting and brain vasculature

Childhood maltreatment is associated with increased severity of substance use disorder and frequent relapse to drug use following abstinence. However, the molecular and neurobiological substrates that are engaged during early traumatic events and mediate the greater risk of relapse are poorly understood and knowledge of risk factors is to date extremely limited. In this study, we modeled childhood maltreatment by exposing juvenile mice to a threatening social experience (social stressed, S-S). We showed that S-S experience influenced the propensity to reinstate cocaineseeking after periods of withdrawal in adulthood. By exploring global gene expression in blood leukocytes we found that this behavioral phenotype was associated with greater blood coagulation. In parallel, impairments in brain microvasculature were observed in S-S mice. Furthermore, treatment with an anticoagulant agent during withdrawal abolished the susceptibility to reinstate cocaine-seeking in S-S mice. These findings provide novel insights into a possible molecular mechanism by which childhood maltreatment heightens the risk for relapse in cocaine-dependent individuals

Response to Cummins and Finaret (2019)

We thank Joseph Cummins and Amelia Finaret for their interest in our article (Comandini et al., 2019) and their insightful comments, which allowed us to further discuss the issue of age imprecision in nutritional studies. In this response, we aim to stress some points that interfere with the analysis of the three major concerns highlighted by the authors

Clinical evaluation of switching from immediate-release to prolonged-release lithium in bipolar patients, poorly tolerant to lithium immediate-release treatment: A randomized clinical trial

open13Aim: The effect of switching from lithium immediate release (Li-IR) to lithium prolonged release (Li-PR) on lithium-induced tremor after 1 and 12 weeks of treatment was evaluated in a randomized, multicenter, open trial, in bipolar patients from the participating sites with a tremor severity ≥2 (Udvalg for Kliniske Undersøgelser [UKU] rating scale) despite optimal lithium titration. Methods: The primary endpoint was the evaluation of tremor by means of the UKU scale after 1 week of treatment. Secondary endpoints included manic Young Mania Rating Scale (YMRS) and depressive symptoms (Montgomery-Asberg Depression Rating Scale), a global assessment of the patient's status (Clinical Global Impression), polyuria/polydipsia (UKU item 3.8) and patient-reported outcomes. Results: Owing to difficulties in including suitable patients the enrollment phase was closed when 73 patients were randomized. Notwithstanding the lower number of patients, in the modified intention-to-treat population (n = 70) the primary endpoint was statistically significant: tremor improved after 1 week in 62.9% in Li-PR group against 20.0% of patients in Li-IR group (p = .0006; two-tailed Fisher's exact test). The difference remained statistically significant after 4 (p = .0031) and 12 weeks (p = .0128). The same analysis performed in the PP population confirmed these results. Among the secondary endpoints, only the factor convenience of the treatment satisfaction questionnaire showed a statistically significant difference between groups. There were no apparent differences in the safety profile of the two formulations. Conclusions: This study is the first comparative documentation of a potential benefit of the prolonged-release formulation in reducing the symptom tremor, a well-known adverse effect of lithium therapy. Indeed, the study results should be interpreted taking into account the sample size lower than planned.openPelacchi, Federica; Dell'Osso, Liliana; Bondi, Emi; Amore, Mario; Fagiolini, Andrea; Iazzetta, Paolo; Pierucci, Daniela; Gorini, Manuela; Quarchioni, Elisa; Comandini, Alessandro; Salvatori, Enrica; Cattaneo, Agnese; Pompili, MaurizioPelacchi, Federica; Dell'Osso, Liliana; Bondi, Emi; Amore, Mario; Fagiolini, Andrea; Iazzetta, Paolo; Pierucci, Daniela; Gorini, Manuela; Quarchioni, Elisa; Comandini, Alessandro; Salvatori, Enrica; Cattaneo, Agnese; Pompili, Maurizi

A randomized, double-blind study comparing the efficacy and safety of trazodone once-a-day and venlafaxine extended-release for the treatment of patients with major depressive disorder

This double-blind, randomized study evaluated the efficacy and safety of trazodone OAD (once-a-day) in comparison with venlafaxine XR (extended-release) in 324 patients (166 trazodone and 158 venlafaxine) with major depressive disorder (MDD). The primary efficacy endpoint was the mean change from baseline in the 17-item Hamilton Depression Rating Scale (HAM-D) at week 8. Both treatments were effective in reducing the HAM-D-17 total score at week 8 vs. baseline (intent-to-treat: trazodone -12.9, venlafaxine -14.7; per protocol: trazodone -15.4, venlafaxine -16.4). Patients in the venlafaxine group achieved better results after 8 weeks, whereas the trazodone group achieved a statistically significant reduction in HAM-D-17 following only 7 days of treatment. The most frequent adverse events (AEs) were dizziness and somnolence in the trazodone group, and nausea and headache in the venlafaxine group. Most AEs were mild-to-moderate in severity. This study confirmed that both venlafaxine XR and trazodone OAD may represent a valid treatment option for patients with MDD

Proceedings of the Fifth Italian Conference on Computational Linguistics CLiC-it 2018

On behalf of the Program Committee, a very warm welcome to the Fifth Italian Conference on Computational Linguistics (CLiC-­‐it 2018). This edition of the conference is held in Torino. The conference is locally organised by the University of Torino and hosted into its prestigious main lecture hall “Cavallerizza Reale”. The CLiC-­‐it conference series is an initiative of the Italian Association for Computational Linguistics (AILC) which, after five years of activity, has clearly established itself as the premier national forum for research and development in the fields of Computational Linguistics and Natural Language Processing, where leading researchers and practitioners from academia and industry meet to share their research results, experiences, and challenges

EVALITA Evaluation of NLP and Speech Tools for Italian - December 17th, 2020

Welcome to EVALITA 2020! EVALITA is the evaluation campaign of Natural Language Processing and Speech Tools for Italian. EVALITA is an initiative of the Italian Association for Computational Linguistics (AILC, http://www.ai-lc.it) and it is endorsed by the Italian Association for Artificial Intelligence (AIxIA, http://www.aixia.it) and the Italian Association for Speech Sciences (AISV, http://www.aisv.it)

Synchronous GISTs associated with multiple sporadic tumors: a case report

Gastrointestinal stromal tumors (GISTs) are rare neoplasms, but they also represent the most common mesenchymal tumors of the gastrointestinal tract originating from the cell of Cajal. GIST incidence ranges around 1% of all gastrointestinal malignancies. Approximately 5% of all GISTs have a hereditary etiology. The remaining 95% of GISTs are considered sporadic events, with up to 75% of cases driven by a constitutional activation of the c-KIT proto-oncogene. GISTs are generally solitary lesions. Nonetheless, multiple sporadic GISTs can occur and present as synchronous or metachronous tumors, usually associated with familial GIST. Here, we report a case of primary prostate and lung tumors associated with gastric and small bowel GISTs, unrelated to any known hereditary syndrome. Also, in the case we describe, the prostatic tumor came before the GISTs, while the lung tumor occurred later in time and led to pulmonary lobectomy plus lymphoadenectomy, with a diagnosis of nonsmall cell lung cancer. With the exception of a slight difference in lymphoid infiltration, the abdominal and gastric GIST nodules shared the same proliferative MIB1 index and mitotic count. However, the genetic analysis revealed that the gastric GIST and abdominal tumors were characterized by two different c-KIT mutations. This molecular heterogeneity supported the hypothesis of two different synchronous GISTs arising from stomach and ileum. At present, the patient is disease free and has already completed the third year of adjuvant therapy with imatinib. This case supports the importance of the analysis of c-KIT mutational status to distinguish metastases from synchronous multicentric GISTs, with relevant implications in therapeutic decisions, as well as the importance of a dedicated multidisciplinary team and of a radiological follow-up after the diagnosis of a primary GIST, to discover a relapse of the GIST or, possibly, additional malignancies

Prulifloxacin Effectiveness in Moderate-to-Severe Acute Exacerbations of Chronic Bronchitis: Α Noninterventional, Multicentre, Prospective Study in Real-Life Clinical Practice—The “AIOLOS” Study

Real-world evidence regarding the effectiveness of prulifloxacin in the treatment of acute exacerbations of chronic bronchitis (AECB) is limited. Therefore, this study aimed to assess the rates and time to symptom improvement and resolution in patients with moderate-to-severe AECB who were given prulifloxacin in the routine care in Greece. This observational, prospective study, conducted in 15 hospital-based clinics across Greece, enrolled outpatients >40 years old, with moderate-to-severe AECB, for whom the physician had decided to initiate treatment with prulifloxacin. Data were collected at prulifloxacin onset (baseline), 7–10 days after baseline, and at least 28 days after therapy completion. Between 23 November 2015 and 27 January 2018, 305 patients (males: 76.4%; mean (standard deviation) (SD) age: 69.7 (9.8) years; Anthonisen type I/II: 94.8%; chronic bronchitis duration >10 years: 24.9%) were consecutively enrolled. At baseline, >80% had increased sputum volume, cough, dyspnoea, and sputum purulence. Prulifloxacin improved symptoms in 99.7% of the patients after a mean (SD) of 5.47 (3.57) days, while symptoms fully recovered after a mean (SD) of 10.22 (5.00) days in 95.4%. The rate of adverse events related to prulifloxacin was 1.3% (serious: 0.7%). In the routine care in Greece, prulifloxacin was highly effective in moderate-to-severe AECB, while displaying a predictable safety profile