The well now course: a service evaluation of a health gain approach to weight management.

BACKGROUND: The Well Now health and weight course teaches body respect and health gain for all. The course validates peoples' lived experiences and knowledge through group activities and discussion with the aim of helping people to better understand their food and body stories. Well Now explores different ways of knowing, including the use and limits of body signals, like energy levels, hunger, taste and emotions and helps people keep food and behaviours in perspective by drawing attention to other factors that impact on health and wellbeing. This study undertook a service evaluation of the Well Now course to understand its acceptability for participants and its impact on diet quality, food preoccupation, physical activity and mental wellbeing. METHODS: This service evaluation combined quantitative pre- and post-course measures with telephone interviews with previous attendees. Paired t-tests were used to determine if there were statistically significant differences in the intended outcomes. Semi-structured qualitative telephone interviews were undertaken with previous attendees 6-12 months after attendance to understand how participants experienced the Well Now course. RESULTS: Significant improvements were demonstrated in diet quality, food preoccupation, physical activity and mental wellbeing outcomes. Medium effect sizes are demonstrated for mental wellbeing and diet quality, with smaller effect sizes shown for physical activity and food preoccupation. The weight and Body Mass Index (BMI) of attendees remained stable in this timeframe. The qualitative data corroborates and extends elements of the quantitative outcomes and highlights areas of the course that may benefit from further development and improvement. The findings further indicate that the Well Now approach is largely acceptable for attendees. CONCLUSIONS: Well Now's non-judgemental holistic approach facilitates change for those who complete the course, and for those who do not. This health gain approach upholds non-maleficence and beneficence, and this is demonstrated with this service evaluation for both completers and partial completers.

Protein tyrosine phosphatase PTPN22 regulates LFA-1 dependent Th1 responses.

A missense C1858T single nucleotide polymorphism within PTPN22 is a strong genetic risk factor for the development of multiple autoimmune diseases. PTPN22 encodes a protein tyrosine phosphatase that negatively regulates immuno-receptor proximal Src and Syk family kinases. Notably, PTPN22 negatively regulates kinases downstream of T-cell receptor (TCR) and LFA-1, thereby setting thresholds for T-cell activation. Alterations to the quality of TCR and LFA-1 engagement at the immune synapse and the regulation of downstream signals can have profound effects on the type of effector T-cell response induced. Here we describe how IFNγ+ Th1 responses are potentiated in Ptpn22-/- T-cells and in T-cells from mice expressing Ptpn22R619W (the mouse orthologue of the human genetic variant) as they age, or following repeated immune challenge, and explore the mechanisms contributing to the expansion of Th1 cells. Specifically, we uncover two LFA-1-ICAM dependent mechanisms; one T-cell intrinsic, and one T-cell extrinsic. Firstly, we found that in vitro anti-CD3/LFA-1 induced Th1 responses were enhanced in Ptpn22-/- T-cells compared to WT, whereas anti-CD3/anti-CD28 induced IFNy responses were similar. These data were associated with an enhanced ability of Ptpn22-/- T-cells to engage ICAM-1 at the immune synapse when incubated on planar lipid bilayers, and to form conjugates with dendritic cells. Secondly, we observed a T-cell extrinsic mechanism whereby repeated stimulation of WT OT-II T-cells with LPS and OVA323-339 pulsed Ptpn22-/- bone marrow derived dendritic cells (BMDCs) was sufficient to enhance Th1 cell development compared to WT BMDCs. Furthermore, this response could be reversed by LFA-1 blockade. Our data point to two related but distinct mechanisms by which PTPN22 regulates LFA-1 dependent signals to enhance Th1 development, highlighting how perturbations to PTPN22 function over time to regulate the balance of the immune response.