ST1936, un nuovo agonista dei recettori 5-HT6: effetti sulla trasmissione dopaminergica e sulla dostribuzione del pERK nel Nucleo Accumbens Shell e Core e nella corteccia prefrontale del ratto

La funzione del recettore 5‐HT6, uno fra gli ultimi scoperti della superfamiglia dei recettori serotoninergici, è ampiamente sconosciuta e ciò è dovuto alla limitata conoscenza del loro meccanismo di trasduzione, alla mancanza di agonisti pieni attivi a livello centrale e all’inconsistenza degli effetti farmacologici e eurochimici degli antagonisti. Recentemente è stato reso disponibile un nuovo agonista pieno, ST1936, con affinità nanomolare per il recettore 5‐HT6. Riportiamo l’effetto acuto di ST1936 sul dializzato di dopamina (DA) e noradrenalina (NA) nella corteccia prefrontale (PFCX), nel nucleus accumbens (Acb), shell e core, e sull’espressione di phospho‐Extracellular signal Regulated Kinase (pERK) nelle stesse aree, come dimostrato con l’immunoistochimica. Riportiamo inoltre l’effetto di ST1936 quando somministrato in modo contingente da parte del ratto nel paradigma sperimentale di self‐administration (SA). La somministrazione sistemica acuta di ST1936 aumenta in modo dose‐dipendente il dializzato di DA, NA nella PFCX e nella AcbSh e in minor misura nel AcbC; questi effetti sono prevenuti per somministrazione istemica di due diversi antagonisti del recettore 5‐HT6. ST1936 aumenta anche il numero di neuroni pERK‐positivi nella corteccia prelimbica (PrL) e nella porzione mediale e intermedia della AcbSh ma non nella corteccia infralimbica (IL) e nel AcbC. Questi effetti sono prevenuti per somministrazione sistemica dell’antagonista selettivo dei recettori D1 SCH39166. ST1936 risulta capace di sostenere nel ratto un comportamento di SA, per via endovenosa. La risposta di autosomministrazione è ridotta significativamente per pretrattamento sistemico con antagonisti del recettore 5‐HT6. Queste proprietà di ST1936 suggeriscono che il recettore 5‐HT6 controlli l’attività dei neuroni dopaminergici e noradrenergici che proiettano alla PFCX e al Acb

Benzimidazole-2-Phenyl-Carboxamides as Dual-Target Inhibitors of BVDV Entry and Replication

Bovine viral diarrhea virus (BVDV), also known as Pestivirus A, causes severe infection mostly in cattle, but also in pigs, sheep and goats, causing huge economical losses on agricultural farms every year. The infections are actually controlled by isolation of persistently infected animals and vaccination, but no antivirals are currently available to control the spread of BVDV on farms. BVDV binds the host cell using envelope protein E2, which has only recently been targeted in the research of a potent and efficient antiviral. In contrast, RdRp has been successfully inhibited by several classes of compounds in the last few decades. As a part of an enduring antiviral research agenda, we designed a new series of derivatives that emerged from an isosteric substitution of the main scaffold in previously reported anti-BVDV compounds. Here, the new compounds were characterized and tested, where several turned out to be potent and selectively active against BVDV. The mechanism of action was thoroughly studied using a time-of-drug-addition assay and the results were validated using docking simulations

Human Enterovirus B: Selective Inhibition by Quinoxaline Derivatives and Bioinformatic RNA-Motif Identification as New Targets

The Enterovirus genus includes many viruses that are pathogenic in humans, including Coxsackie viruses and rhinoviruses, as well as the emerging enteroviruses D68 and A71. Currently, effective antiviral agents are not available for the treatment or prevention of enterovirus infections, which remain an important threat to public health. We recently identified a series of quinoxaline derivatives that were provento be potent inhibitors of coxsackievirus B5, the most common and a very important human pathogen belonging to the enterovirus genus. We have shown how most active derivatives interfere with the earliest stages of viral replication, blocking infection. Considering the broad antiviral spectrum, a very attractive property for an antiviral drug, we aimed to investigate the antiviral activity of the most promising compounds against other Enterovirus species. Here, we investigated the susceptibility of a panel of representatives of Enterovirus genus (enterovirus A71, belonging to A species; coxsackieviruses B4 and B3;echovirus 9, belonging to B species; and enterovirus D68, belonging to D species) to quinoxaline inhibitors. We also tested cytotoxicity and selectivity indices of the selected compounds, as well as their effects on virus yield.We also investigated their potential mechanism of action by a time course assay. In addition, a bioinformatic analysis was carried out to discover potential new conserved motifs in CVB3 and CVB4 compared to the other enterovirus species that can be used as new targets

Brodalumab for the treatment of plaque psoriasis in a real-life setting: a 3 years multicenter retrospective study—IL PSO (Italian landscape psoriasis)

Introduction: Brodalumab is a monoclonal antibody that targets the subunit A of the interleukin-17A receptor (IL17RA), inhibiting the signaling of various isoforms of the IL-17 family. It has been approved for the treatment of moderate-to-severe plaque psoriasis after being evaluated in three Phase-3 trials. However, long-term data on brodalumab in a real-life setting are still limited

Real-life effectiveness of tildrakizumab in chronic plaque psoriasis: A 52-week multicentre retrospective study—IL PSO (Italian landscape psoriasis)

Background: Tildrakizumab is a humanized monoclonal antibody that binds selectively the p19 subunit of interleukin-23. It is approved for treatment of moderate– severe chronic plaque psoriasis. Objectives: We conducted a 52-week retrospective study to assess the effectiveness and safety of tildrakizumab in a real-life setting. Methods: Our retrospective study included 237 consecutive adults with moderateto-severe plaque psoriasis, enrolled in 10 different Italian centres, treated with tildrakizumab up to Week 52. Patient characteristics, comorbidities, previous treatmentsand the PASI (Psoriasis Area and Severity Index) score at each visit (baseline, Week 16, Week 28 and Week 52) were retrieved from the electronic medical records. The percentages of patients achieving 75%, 90% and 100% (PASI 75, PASI 90 and PASI 100) improvement in PASI with respect to baseline PASI were registered. Results: At Week 52, 90.91%, 73.55% and 58.68% of patients achieved a PASI reduction ≥75% (PASI 75), PASI 90 and PASI 100, respectively. An absolute PASI≤2 was reached by 85.95% at Week 52. Compared with Phase 3 clinical trials, we observed similar rates of PASI 75/90 responses and higher percentages of patients achieving PASI 100. Patients who had not responded to previous biologic treatments and patients with cardio-metabolic comorbidities were significantly more likely to achieve PASI 100 at Week 28 and PASI 90 at Week 52. The higher body mass index did not interfere with the odds of reaching PASI 75/90/100 at each time point. No significant safety findings were recorded throughout the study, and none of the patients had to interrupt the treatment because of adverse events. Conclusion: Our data suggest that the efficacy of tildrakizumab for plaque psoriasis in ‘real-life’ clinical practice is comparable with Phase 3 clinical trials with higher percentages of patients achieving complete skin clearance (PASI 100) at Weeks 16, 28 and 52

Effectiveness, Tolerability, and Drug Survival of Risankizumab in a Real-World Setting: A Three-Year Retrospective Multicenter Study—IL PSO (ITALIAN LANDSCAPE PSORIASIS)

Background: Risankizumab is a humanized monoclonal antibody that selectively inhibits interleukin-23. It has been approved for moderate-to-severe plaque psoriasis and has shown efficacy and safety in clinical trials and real-world experiences. This study aimed to evaluate the long-term effectiveness, safety, and drug survival of risankizumab in a real-life setting. Materials and Methods: We included patients treated with risankizumab from January 2019 to February 2023. A Psoriasis Area and Severity Index score (PASI) was collected at weeks 0, 16, 28, 52, 104, and 156, when available. The occurrence of any adverse events was recorded at each visit. Results: We enrolled 1047 patients. At week 52, a ≥90% improvement in PASI was observed in 81.44% of patients, with a continuous improvement throughout the study (88.99% and 99.07% at weeks 104 and 156, respectively). After three years of treatment, all patients involving the scalp, palms/soles, and genitalia and 95% of patients with nail psoriasis achieved a complete or almost complete skin clearance. No significant safety findings were observed, and 90.73% of the patients were still on treatment after 36 months. Conclusions: This study supports the long-term effectiveness and safety of risankizumab in a real- world setting, even in patients involving difficult-to-treat areas

Traian and the Danubian Provinces. The political, economic and religious life in the Danubian Provinces: Proceedings of the 4th International Conference on the Roman Danubian Provinces, Zagreb, 15th - 17th November 2017.

The “Department of Archaeology“ of the Faculty of Humanities and Social Sciences of the University of Zagreb gladly hosted the 4th International Conference on the Roman Danubian Provinces in 2017. The Conference was organized with the support of the Faculty of Humanities and Social Sciences of the University of Zagreb, the Croatian Archaeological Society, and the Croatian Science Foundation through the project 6505 Between the Danube and the Mediterranean. Exploring the role of Roman military in the mobility of people and goods in Croatia during the Roman Era. Since it was organized in Zagreb, the Conference remained in Pannonia, not far from Siscia, the capital of Pannonia Savia, and in the territory of the Res publica Andautoniensium. The main topic of the Conference was Traian and the Roman Danubian Provinces or, more specifically, the political, economic and religious life in the Danubian Provinces.(from the Foreword)The “Department of Archaeology“ of the Faculty of Humanities and Social Sciences of the University of Zagreb gladly hosted the 4th International Conference on the Roman Danubian Provinces in 2017. The Conference was organized with the support of the Faculty of Humanities and Social Sciences of the University of Zagreb, the Croatian Archaeological Society, and the Croatian Science Foundation through the project 6505 Between the Danube and the Mediterranean. Exploring the role of Roman military in the mobility of people and goods in Croatia during the Roman Era. Since it was organized in Zagreb, the Conference remained in Pannonia, not far from Siscia, the capital of Pannonia Savia, and in the territory of the Res publica Andautoniensium. The main topic of the Conference was Traian and the Roman Danubian Provinces or, more specifically, the political, economic and religious life in the Danubian Provinces.(from the Foreword

Traian and the Danubian Provinces. The political, economic and religious life in the Danubian Provinces: Proceedings of the 4th International Conference on the Roman Danubian Provinces, Zagreb, 15th - 17th November 2017.

The “Department of Archaeology“ of the Faculty of Humanities and Social Sciences of the University of Zagreb gladly hosted the 4th International Conference on the Roman Danubian Provinces in 2017. The Conference was organized with the support of the Faculty of Humanities and Social Sciences of the University of Zagreb, the Croatian Archaeological Society, and the Croatian Science Foundation through the project 6505 Between the Danube and the Mediterranean. Exploring the role of Roman military in the mobility of people and goods in Croatia during the Roman Era. Since it was organized in Zagreb, the Conference remained in Pannonia, not far from Siscia, the capital of Pannonia Savia, and in the territory of the Res publica Andautoniensium. The main topic of the Conference was Traian and the Roman Danubian Provinces or, more specifically, the political, economic and religious life in the Danubian Provinces.(from the Foreword)The “Department of Archaeology“ of the Faculty of Humanities and Social Sciences of the University of Zagreb gladly hosted the 4th International Conference on the Roman Danubian Provinces in 2017. The Conference was organized with the support of the Faculty of Humanities and Social Sciences of the University of Zagreb, the Croatian Archaeological Society, and the Croatian Science Foundation through the project 6505 Between the Danube and the Mediterranean. Exploring the role of Roman military in the mobility of people and goods in Croatia during the Roman Era. Since it was organized in Zagreb, the Conference remained in Pannonia, not far from Siscia, the capital of Pannonia Savia, and in the territory of the Res publica Andautoniensium. The main topic of the Conference was Traian and the Roman Danubian Provinces or, more specifically, the political, economic and religious life in the Danubian Provinces.(from the Foreword

Supervised Topic-Based Message Polarity Classification using Cognitive Computing

This paper describes a supervised approach we have designed for the topic-based message polarity classification. Given a message and a topic, we aim at (i) classifying the message on a two point scale, that is positive or negative sentiment toward that topic and (ii) classifying the message on a five-point scale, that is the message conveyed by that tweet toward the topic on a more fine-grained range. These two tasks have been proposed as subtasks of SemEval-2017 task 4. We have targeted them with the employment of IBM Watson that we leveraged to extract concepts and categories to enrich the vectorial space we have modeled to train our classifiers. We have used different classifiers for the two tasks on the provided training set and obtained good accuracy and F1-score values comparable to the SemEval 2017 competitors of those tasks

Modeling real-time data and contextual information from workouts in eCoaching platforms to predict users’ sharing behavior on Facebook

eCoaching platforms have become powerful tools to support users in their day-to-day physical routines. More and more research works show that motivational factors are strictly linked with the user inclination to share her fitness achievements on social media platforms. In this paper, we tackle the problem of analyzing and modeling users' contextual information and real-time training data by exploiting state-of-the-art classification algorithms, to predict if a user will share her current running workout on Facebook. By analyzing user's performance, collected by means of an eCoaching platform for runners, and crossing them with contextual information such as the weather, we are able to predict with a high accuracy if the user will post or not on Facebook. Given the positive impact that social media posts have in these scenarios, understanding what are the conditions that lead a user to post or not, can turn the output of the classification process into actionable knowledge. This knowledge can be exploited inside eCoaching platforms to model user behavior in broader and deeper ways, to develop novel forms of intervention and favor users' motivation on the long term