Sulla ‘Oratio ad adolescentes’ di Basilio Magno

This work of Basil’s addresses the Christian school, but also the cultural pagan circles and their prejudices against the monastic lifestyle. Basil’s pedagogy seems to be inspired by Origenes’ thinking

Ancora sui nuovi frammenti origeniani (PSI inv. 2101)

New readings in the papyrus text published by the same scholar in “Prometheus” 4, 1978, 97-108

Nuovi frammenti origeniani (PSI inv. 2101)

First edition (with photos) of several papyrus fragments preserved in Florence, at the Istituto Papirologico “G. Vitelli”: PSI inv. 2101 preserves parts of two columns (fr. A) and three other fragments (fr. 1, 2, 3) – all of them with recto and verso – from a Commentary on the Gospel according St. John, probably a work by Origenes

Nuovi frammenti del Vangelo di Matteo

Edition and commentary of two papyrus fragments preserved at the Papyrological Institute “G. Vitelli” in Florence (CNR 419 and 420, with 4 photographs). These damaged fragments hand down part of 15 verses of the Gospel according St. Matthew (Mt. 2.13-16, 2.22-3.1; 24.3-6, 12-15)

Efficient Tet-dependent expression of human factor IX in vivo by a new self-regulating lentiviral vector.

Regulation of gene expression represents a long-sought goal of gene therapy. However, most viral vectors pose constraints on the incorporation of drug-dependent transcriptional regulatory systems. Here, by optimizing the design of self-regulating lentiviral vectors based on the tetracycline system, we have been able to overcome the limitations of previously reported constructs and to reach both robust expression and efficient regulation from a single vector. The improved performance allows us to report for the first time effective long-term in vivo regulation of a human clotting Factor IX (hF.IX) transgene upon systemic administration of a single vector to SCID mice. We showed that hF.IX expression in the plasma could be expressed to therapeutically significant concentrations, adjusted to different set levels by varying the tetracycline dose, rapidly turned off and on, and completely recovered after each treatment cycle. The new vector design was versatile, as it successfully incorporated a tissue-specific promoter that selectively targeted regulated expression to hepatocytes. Robust transgene expression in the systemic circulation coupled to the ability to switch off and even adjust the expression level may open the way to safer gene-based delivery of therapeutics

442. LV Expressing MR Reporter Genes Allows In Vivo Monitoring of Stem Cell Gene Therapy

Somatic stem cells (SSC) have raised interest because of their therapeutic potential in both cell-based and gene therapy applications. Towards this goal, tracking the fate of either delivered cells or of genetically modified endogenous cells is of utmost importance. Diverse imaging approaches are available for cell tracking and among these MRI shows a greater resolution and allows direct anatomic correlation and long-term studies of dynamic cell migration on living animals. Superparamagnetic iron oxide (SPIO) has been used to label SSC in vitro and to make them detectable in vivo upon transplantation. However, major limitations of this approach are the progressive dilution of the contrast media among cell progeny and the need for ex vivo SPIO loading. We thus explored an alternative strategy based on the combination of lentiviral vectors (LV), which efficiently transduce SSC both ex vivo and in vivo and allow long-term expression in their progeny, and MR reporter genes, able to increase iron uptake and accumulation into different cell types

Generation of Potent and Stable Human CD4+ T Regulatory Cells by Activation-independent Expression of FOXP3

Therapies based on enhancing the numbers and/or function of T regulatory cells (Tregs) represent one of the most promising approaches to restoring tolerance in many immune-mediated diseases. Several groups have investigated whether human Tregs suitable for cellular therapy can be obtained by in vitro expansion, in vitro conversion of conventional T cells into Tregs, or gene transfer of the FOXP3 transcription factor. To date, however, none of these approaches has resulted in a homogeneous and stable population of cells that is as potently suppressive as ex vivo Tregs. We developed a lentivirus-based strategy to ectopically express high levels of FOXP3 that do not fluctuate with the state of T-cell activation. This method consistently results in the development of suppressive cells that are as potent as Tregs and can be propagated as a homogeneous population. Moreover, using this system, both naive and memory CD4+ T cells can be efficiently converted into Tregs. To date, this is the most efficient and reliable protocol for generating large numbers of suppressive CD4+ Tregs, which can be used for further biological study and developed for antigen-specific cellular therapy applications

Sclerotherapy with 3% polidocanol foam to treat second-degree haemorrhoidal disease. Three-year follow-up of a multicentre, single arm, IDEAL phase 2b trial

Background Sclerotherapy with 3% polidocanol foam is becoming increasingly popular for the treatment of symptomatic I-II or III degree haemorrhoidal disease (HD). However, there are no studies that have reported a follow-up of more than 1 year. The purpose of this study was to analyse the long-term outcomes of sclerotherapy with 3% polidocanol foam in the treatment of II-degree HD. Methods This was an open label, single-arm, phase 2b trial conducted in 10 tertiary referral centres for HD. A total of 183 patients with II-degree HD, aged between 18 and 75 years with symptomatic HD according to the Goligher classification and unresponsive to medical treatment, were included in the study and underwent sclerotherapy with 3% polidocanol foam. The efficacy was evaluated in terms of bleeding score, haemorrhoidal disease symptom score (HDSS) and short health scale for HD (SHS-HD) score. Successful treatment was defined as the complete absence of bleeding episodes after 7 days (T1) according to the bleeding score. Results The overall success rate ranged from 95.6% (175/183) at 1 year to 90.2% (165/183) after the final 3 year follow-up. The recurrence rate, based on the primary outcome, ranged from 12% (15/125) to 28% (35/125). The greatest increase in recurrence (15) was recorded between 12 and 18 months of follow-up, then another five between 18 and 24 months. Both the HDSS and the SHS score remained statistically significant (p < 0.001) from a median preoperative value of 11 (10-13) and 18 (15-20) to 0 (0-2) and 4 (0-4), respectively. Symptom-free (HDSS = 0) patients, excluding patients converted to surgery, increased from 55.5% (101/182) at 1 year to 65.1% at 3 years (110/169). There were no intraoperative complications in redo-sclerotherapy nor additional adverse events (AEs) compared to the first 12 months. Conclusions Sclerotherapy with 3% polidocanol foam is gradually establishing itself in the treatment of bleeding HD due to its repeatability, safety, convenience in terms of direct and indirect costs with the absence of discomfort for the patient as well as AEs rather than an excellent overall success rate

Systemic and targeted delivery of semaphorin 3A inhibits tumor angiogenesis and progression in mouse tumor models

The role of semaphorins in tumor progression is still poorly understood. In this study, we aimed at elucidating the regulatory role of semaphorin 3A (SEMA3A) in primary tumor growth and metastatic dissemination