Efficient T cell adoptive transfer in lymphoreplete hosts mediated by transient activation of Stat5 signaling.

Lymphodepleting pre-conditioning is a nearly universal component of T cell adoptive transfer protocols. The side effects of pre-conditioning regimens used in adoptive cell therapy are clinically significant and include pan-cytopenia, immune suppression, and reactive myelopoiesis. We conducted studies to test the hypothesis that the mechanisms underlying effective engraftment are cell autonomous and not dependent on a lymphodepleted host immune status. These studies leveraged mouse models to examine the role of Stat5 signaling during T cell adoptive transfer. We observed that, by transiently expressing a constitutively active mutamer of Stat5b during the process of adoptive transfer, we could completely obviate the need for lymphodepletion prior to adoptive transfer. Using several functional assays, we benchmark the function of the engrafted T cells against T cells transferred after conventional lymphodepletion. These studies identify a cell-autonomous mechanism driven by transient Stat5b signaling with lasting effects on T cell phenotype and function. Furthermore, the results presented suggest that adoptive T cell therapy could be improved by removing lymphodepletion protocols entirely and replacing them with RNA transfection of T cells with transcripts encoding active Stat5.

Medical Treatment of Vascular Anomalies.

The treatment of vascular malformations and vascular anomalies is often complex, combining various approaches in the art of medicine to provide best outcomes and quality of life for these patients. Treatment may include but is not limited to the following: local control with compression garments and attire, pain control, surgical procedures and debulking, laser therapy, sclerotherapy, and medical management. In this article, the authors discuss the aspects of medical management, visiting the history of medical treatment, and the recent utilization and success of enzymatic pathway inhibitors, specifically sirolimus and new therapies that hold promise for the future for these patients.

Exploring perinatal death with midwifery students' using a collaborative art project.

OBJECTIVE: To explore the influence of the Amulet artwork and exhibition on midwifery students' perceptions of caring for parents experiencing perinatal death. DESIGN: A descriptive qualitative design involving face-to-face semi-structured interviews following institutional ethical approval. SETTING: A regional Maternity Hospital in Ireland which hosted the National Artwork and Exhibition exploring the hidden world of infant death. PARTICIPANTS: A purposive sample of six consenting post registration midwifery students who had attended the Amulet artwork and exhibition. FINDINGS: Four core themes emerged and these were i) entering the mother's world and hearing her pain; ii) the journey of grief and connecting with the bereaved parent's unique experience; iii) facing the challenge of providing effective perinatal bereavement care; and iv) maintaining a journey of compassionate practice. CONCLUSION AND IMPLICATIONS FOR PRACTICE: Exposure to, and reflection on the Amulet artwork and exhibition increased students' awareness and insight into the non-linear nature of the grieving process, and to the importance of maintaining a journey of compassionate care for parents experiencing perinatal death. The findings suggest that the use of creative women-centered strategies promote affective learning in relation to perinatal death and so may be of use to educators and maternity care providers.