Tolerogenic IL-10-engineered dendritic cell-based therapy to restore antigen-specific tolerance in T cell mediated diseases

Tolerogenic dendritic cells play a critical role in promoting antigen-specific tolerance via dampening of T cell responses, induction of pathogenic T cell exhaustion and antigen-specific regulatory T cells. Here we efficiently generate tolerogenic dendritic cells by genetic engineering of monocytes with lentiviral vectors co-encoding for immunodominant antigen-derived peptides and IL-10. These transduced dendritic cells (designated DCIL-10/Ag) secrete IL-10 and efficiently downregulate antigen-specific CD4+ and CD8+ T cell responses from healthy subjects and celiac disease patients in vitro. In addition, DCIL-10/Ag induce antigen-specific CD49b+LAG-3+ T cells, which display the T regulatory type 1 (Tr1) cell gene signature. Administration of DCIL-10/Ag resulted in the induction of antigen-specific Tr1 cells in chimeric transplanted mice and the prevention of type 1 diabetes in pre-clinical disease models. Subsequent transfer of these antigen-specific T cells completely prevented type 1 diabetes development. Collectively these data indicate that DCIL-10/Ag represent a platform to induce stable antigen-specific tolerance to control T-cell mediated diseases

Frequency and Coverage of trinucleotide repeats in eukaryotes.

In the aim to assess whether the tri-repeat shortage reported in vertebrates affects specific motifs, such as those causing neuromuscular diseases in man, we detected approximate di-, tri- and tetra-repeats (STR) longer than 25 bases in human chromosomes 21 and 22, and in some model organisms (M. musculus, D. melanogaster, C. elegans, A. thaliana and S. cerevisiae). We found that overall STR are more represented in mouse and in man than in the other organisms. However, tri-repeats are less represented than di- and tetra- in man and mouse, but show intermediate values between di- and tetra- in the other organisms. In man, ACG shows the lowest both frequency and coverage, ATC the highest coverage and AAT the highest frequency. In general, coverage and frequency of tri-repeats are linearly related, except for ACC, ATC, AAG, AGG motifs in man and AAG, AGG in mouse, which exhibit unexpectedly long repeats. Often their copy numbers exceed that found responsible for the dynamic mutations, set at around 40. The shortage in frequency and coverage of tri- vs. di- and tetra-repeats observed in man and mouse can be ascribed to a subset of the remaining tri-repeat motifs, but among them those recognized as dynamically mutable (AAG, AGC and CCG) are not the least represented. Possible constraints in tri-repeat expansion seem to be structural and conserved along the evolutionary scale: a motif-specific relaxation of the relevant controls may be responsible for the occasional expansions found in mouse and man

Navigating Adult Life from Emerging to Middle Adulthood: Patterns of Systemic Influences and Time Perspective in Migrants

This study emerges at the intersection of adult development and systems theory frameworks and their contributions to understanding migration experiences and associated cultural transitions. The adult development approach enables a deep understanding of the complexities that adults experience when they move from exploring themselves and their environment in emerging adulthood to establishing their identities and roles during middle adulthood. The systems theory framework, on the other hand, provides insights into the role of social and cultural dimensions in the lives of emerging and middle-adult immigrants who have navigated diverse cultures, roles, and identities. The study highlights the patterns and dynamic interactions of diverse systems of influences and their roles in shaping the self and relational identities of thirty emerging and middle-aged adults who have experienced migration

Approaches and strategies for understanding the career development needs of migrants and refugees: The potential of a systems-based narrative approach.

Addressing immigrants’ social and work inclusion is a priority at a time of increasing migration to Italy and Europe. Career counselors can identify the sense of self in transition, consider complex experiences and socio-cultural stories, and tailor actions for inclusion. This project enhances understanding of this process and the elements that impact the outcome and meaning of social inclusion and post-migration career development, providing suggestions for career guidance. We also explore the contribution of the Systems Theory Framework as a meta-theoretical and practical map and present case studies. Results underscore the potential of a narrative approach to support immigrants’ career development

Ultrasonic bone surgery in the treatment of impacted lower third molar associated to a complex odontoma: a case report

The removal of impacted mandibular third molar is a common surgical procedure entailing some risk of complications, especially when the tooth and the inferior alveolar nerve and/or lingual cortical plate are in close proximity. A technique that can reduce the possibility of damage is the Ultra Sonic Bone Surgery. The aim of this report is to present a paradigmatic case of an impacted mandibular third molar closely associated with a complex odontoma, which was treated with the Ultrasonic Bone Surgery (UBS) device. This technique appeared to be a valid alternative to manual or mechanical treatment, strongly minimizing trauma to the inferior alveolar nerve, vascular tissues, or surrounding dental tissues