A horse, a horse, my kingdom for a horse. Saddle thrombosis of carotid bifurcation in acute stroke

Background: Saddle thrombosis is less frequently detected in carotid arteries than in peripheral arterial embolism. The clot and the distal vessel patency have to be promptly recognized in these cases, because if the carotid vessel is open distally, chances may arise for successful emergent surgical procedures to remove the thrombus. At conventional static imaging, mobile floating thrombi may be difficult to differentiate from thrombosis on carotid complicated lesions of atherosclerotic origin. High-resolution ultrasound (US), with its unique capability of real-time imaging, adds fundamental data for interpretation of the findings. Methods: Carotid ultrasound has been performed in acute stroke patients with high-resolution probes. Real-time clips are analyzed and imaging is presented. Results: Saddle carotid bifurcation thrombosis of cardiac origin has been identified in 2 patients with acute homolateral ischemic stroke, with prompt successful surgical removal in one case. Moreover, an example of a thrombus attached on the ruptured surface of a complicated atherosclerotic plaque in an acute symptomatic stroke patient that was successfully operated in emergency is presented. Conclusions: Early high-resolution ultrasound with real-time imaging can easily identify peculiar characteristics of carotid vulnerable diseases in acute stroke phase. Different clinical implications result from the early identification of these different conditions, modifying the therapeutical strategies. © 2012 Elsevier GmbH

Analgesic effectiveness and tolerability of oral oxycodone/naloxone and pregabalin in patients with lung cancer and neuropathic pain. An observational analysis

INTRODUCTION: Cancer-related pain has a severe negative impact on quality of life. Combination analgesic therapy with oxycodone and pregabalin is effective for treating neuropathic cancer pain. We investigated the efficacy and tolerability of a dose-escalation combination therapy with prolonged-release oxycodone/naloxone (OXN-PR) and pregabalin in patients with non-small-cell lung cancer and severe neuropathic pain. METHODS: This was a 4-week, open-label, observational study. Patients were treated with OXN-PR and pregabalin. Average pain intensity ([API] measured on a 0-10 numerical rating scale) and neuropathic pain (Douleur Neuropathique 4) were assessed at study entry and at follow-up visits. The primary endpoint was response to treatment, defined as a reduction of API at T28 ≥30% from baseline. Secondary endpoints included other efficacy measures, as well as patient satisfaction and quality of life (Brief Pain Inventory Short Form), Hospital Anxiety and Depression Scale, and Symptom Distress Scale; bowel function was also assessed. RESULTS: A total of 56 patients were enrolled. API at baseline was 8.0±0.9, and decreased after 4 weeks by 48% (4.2±1.9; P<0.0001 vs baseline); 46 (82.1%) patients responded to treatment. Significant improvements were also reported in number/severity of breakthrough cancer pain episodes (P=0.001), Brief Pain Inventory Short Form (P=0.0002), Symptom Distress Scale (P<0.0001), Hospital Anxiety and Depression Scale depression (P=0.0006) and anxiety (P<0.0001) subscales, and bowel function (P=0.0003). At study end, 37 (66.0%) patients were satisfied/very satisfied with the new analgesic treatment. Combination therapy had a good safety profile. CONCLUSION: OXN-PR and pregabalin were safe and highly effective in a real-world setting of severe neuropathic cancer pain, with a high rate of satisfaction, without interference on bowel function

Italian contribution to University Autonomy in Kazakhstan: the Erasmus+ project “Transition to University Autonomy in Kazakhstan” (TRUNAK)

University autonomy is the capacity of universities to be self-governin

mTOR regulation of metabolism in hematologic malignancies

Neoplastic cells rewire their metabolism, acquiring a selective advantage over normal cells and a protection from therapeutic agents. The mammalian Target of Rapamycin (mTOR) is a serine/threonine kinase involved in a variety of cellular activities, including the control of metabolic processes. mTOR is hyperactivated in a large number of tumor types, and among them, in many hematologic malignancies. In this article, we summarized the evidence from the literature that describes a central role for mTOR in the acquisition of new metabolic phenotypes for different hematologic malignancies, in concert with other metabolic modulators (AMPK, HIF1α) and microenvironmental stimuli, and shows how these features can be targeted for therapeutic purposes

Influence of autochthonous starter cultures on microbial dynamics and chemical-physical features of traditional fermented sausages of Basilicata region.

In this study, a combination of a Lactobacillus sakei strain and a Staphylococcus equorumstrain was used as autochthonous starter for an experimental production of Basilicata fermented sausages. The influence of starter addition on the safety and quality parameters and microbiological and chemical-physical properties of the products was investigated. Microbial counts of safety indicators were lower in the samples with the addition of starter culture, and, at the end of ripening, Enterobacteriaceae and Gram negative bacteria were detected only in samples made without the starter addition. The addition of starter led to a final product with better microbiological and chemical-physical features, and a positive effect on flavor and aroma compounds formation by a good proteolytic and lipolytic activities. The use of autochthonous starter cultures allows to obtain products with the organoleptic characteristics expected and steady in time and to standardize the production process, improving the safety and quality, but preserving the essential character of the product

Inhibition of bromodomain and extra-terminal (BET) proteins increases NKG2D ligand MICA expression and sensitivity to NK cell-mediated cytotoxicity in multiple myeloma cells. role of cMYC-IRF4-miR-125b interplay

Background: Anticancer immune responses may contribute to the control of tumors after conventional chemotherapy and different observations have indicated that chemotherapeutic agents can induce immune responses resulting in cancer cell death and immune-stimulatory side effects. Increasing experimental and clinical evidence highlight the importance of Natural Killer (NK) cells in immune responses toward Multiple Myeloma (MM) and combination therapies able to enhance the activity of NK cells against MM are showing promise in treating this hematologic cancer. The epigenetic readers of acetylated histones Bromodomain and Extra-Terminal (BET) proteins are critical regulators of gene expression. In cancer, they can upregulate transcription of key oncogenes such as cMYC, IRF4, BCL-2 and others. In addition, the activity of these proteins can regulate the expression of osteoclastogenic cytokines during cancer progression. Here, we investigated the effect of BET-bromodomain proteins inhibition, on the expression of Natural Killer (NK) cell-activating ligands in Multiple Myeloma (MM) cells. Methods: Five MM cell lines [SKO-007(J3), U266, RPMI-8226, ARP-1, JJN3] and CD138+ MM cells isolated from MM patients were used to investigate the activity of BET bromodomain inhibitors (BETi) (JQ1 and I-BET-151) and of the selective BRD4-degrader PROTAC (Proteolysis Targeting Chimera) (ARV-825), on the expression and function of several NK cell activating ligands (NKG2DLs and DNAM-1Ls), using Flow Cytometry, Real-Time PCR, transient transfections and degranulation assays. Results: Our results indicate that inhibition of BET proteins via small molecule inhibitors or their degradation via a hetero-bifunctional Proteolysis Targeting Chimera (PROTAC) probe can enhance the expression of MICA, a ligand of the NKG2D receptor, in human MM cell lines and primary malignant plasma cells, rendering myeloma cells more efficient to activate NK cell degranulation. Noteworthy, similar results were obtained using selective CBP/EP300 bromodomain inhibition. Mechanistically, we found that BETi-mediated inhibition of cMYC correlates with the upregulation of miR-125b-5p and the downregulation of the cMYC/miR-125b-5p target gene IRF4, a transcriptional repressor of MICA. Conclusions: These findings provide new insights on the immuno-mediated antitumor activities of BETi and further elucidate the molecular mechanisms that regulate NK cell-activating ligand expression in MM

Quasi-static and low-velocity impact behavior of intraply hybrid flax/basalt composites

In an attempt to increase the low-velocity impact response of natural fiber composites, a new hybrid intraply woven fabric based on flax and basalt fibers has been used to manufacture laminates with both thermoplastic and thermoset matrices. The matrix type (epoxy or polypropylene (PP) with or without a maleated coupling agent) significantly affected the absorbed energy and the damage mechanisms. The absorbed energy at perforation for PP-based composites was 90% and 50% higher than that of epoxy and compatibilized PP composites, respectively. The hybrid fiber architecture counteracted the influence of low transverse strength of flax fibers on impact response, irrespective of the matrix type. In thermoplastic laminates, the matrix plasticization delayed the onset of major damage during impact and allowed a better balance of quasi-static properties, energy absorption, peak force, and perforation energy compared to epoxy-based composites

Catalysis for the transformation of biomass in value-added products

2017 - 2018The present doctoral thesis is focused on the catalytic conversion of bioglycidol into value-added products... [edited by Author]XXXI cicl

Una lettura ecosistemica e la prospettiva di un learnfare capacitante: L’Osservatorio sui Processi Formativi e l’Analisi Territoriale come modello pedagogico di resilienza trasformativa

The article aims to testify to the ten-year experience of research-action and training carried out by the Observatory on Training Processes and Territorial Analysis of the University of Salerno, founded and directed by Prof. E. Mannese. Starting from the examination of this experience and through reflection on the methodological framework and the projects implemented, the characterizing elements that have ensured its stability and success are identified in order to propose a hypothesis of a training ecosystem. Pedagogical model of transformative resilience outlined is structured around six principles: multipolar agency, generativity and transformativity, territories conceived as learningland, learning and territorial capital, capabilities for the development of talents and territories, the metaphor of the border. These principles are consistent with a series of fundamental characteristics common to the main theoretical and educational approaches present in the literature. They are the basis of the definition of a core set aimed at guiding the promotion and development of generative pedagogical devices, transformative research-action models and capability learnfare systems, for the development of talents and territories.L’articolo intende testimoniare l’esperienza ormai decennale di ricerca-azione e formazione messa in campo dall’Osservatorio sui Processi Formativi e l’Analisi Territoriale dell’Università degli Studi di Salerno, fondato e diretto dalla prof.ssa E. Mannese. A partire dall’esame di tale esperienza e attraverso la riflessione sull’impianto metodologico e le progettualità realizzate, si identificano gli elementi caratterizzanti che ne hanno assicurato tenuta e successo per proporre un’ipotesi di ecosistema formativo. Il modello pedagogico di resilienza trasformativa delineato fonda la sua struttura su sei principi: agency multipolare, generatività e trasformatività, territori pensati come learningland, apprendimento e capitale territoriale, capacitazioni per lo sviluppo dei talenti e dei territori, la metafora del confine. Si tratta di principi che presentano una notevole coerenza con una serie di caratteri fondamentali comuni ai principali approcci teorici e formativi presenti in letteratura e che costituiscono la base per la definizione di un core set teso ad orientare la promozione e lo sviluppo di dispositivi pedagogici di tipo generativo, modelli di ricerca-azione trasformativi e sistemi di learnfare capacitanti, per lo sviluppo dei talenti e dei territori

The IMiDs targets IKZF-1/3 and IRF4 as novel negative regulators of NK cell-activating ligands expression in multiple myeloma

Immunomodulatory drugs (IMiDs) have potent anti-tumor activities in multiple myeloma (MM) and are able to enhance the cytotoxic function of natural killer (NK) cells, important effectors of the immune response against MM. Here, we show that these drugs can enhance the expression of the NKG2D and DNAM-1 activating receptor ligands MICA and PVR/CD155 in human MM cell lines and primary malignant plasma cells. Depletion of cereblon (CRBN) by shRNA interference strongly impaired upregulation of these ligands and, more interestingly, IMiDs/CRBN-mediated downregulation of the transcription factors Ikaros (IKZF1), Aiolos (IKZF3) and IRF4 was critical for these regulatory mechanisms. Indeed, shRNA knockdown of IKZF1 or IKZF3 expression was both necessary and sufficient for the upregulation of MICA and PVR/CD155 expression, suggesting that these transcription factors can repress these genes; accordingly, the direct interaction and the negative role of IKZF1 and IKZF3 proteins on MICA and PVR/CD155 promoters were demonstrated. Finally, MICA expression was enhanced in IRF4-silenced cells, indicating a specific suppressive role of this transcription factor on MICA gene expression in MM cells. Taken together, these findings describe novel molecular pathways involved in the regulation of MICA and PVR/CD155 gene expression and identify the transcription factors IKZF-1/IKZF-3 and IRF4 as repressors of these genes in MM cells