Health interventions as vehicles for increased sport participation for women and girls: Socio-managerial insights from a Netball-for-Development Program in Tonga

Against the background of ever-rising non-communicable disease rates, an area that has received increased attention from sport-for-development practitioners and academics is sport-for-health (SFH). SFH projects attempt to contribute to the development of healthy lifestyle behavior and physically active societies through sport-related programs and interventions. The purpose of this paper was to explore the socio-managerial challenges and opportunities of a netball-based SFH program in Tonga. Based on local focus group and interview data, findings were grouped under five overarching themes: strategic management of volunteer network, sociocultural barriers, public space management, events and tournaments as incentives, and collaboration across local and national sports. In discussing these findings in context, we provide implications for managing culturally sensitive SFH projects in the Pacific region and beyond

Signaling Signatures and Functional Properties of Anti-Human CD28 Superagonistic Antibodies

Superagonistic CD28 antibodies (CD28SAs) activate T lymphocytes without concomitant perturbation of the TCR/CD3-complex. In rodents these reagents induce the preferential expansion of regulatory T cells and can be used for the treatment of autoimmune diseases. Unexpectedly, the humanized CD28 superagonist TGN1412 caused severe and life threatening adverse effects during a recently conducted phase I clinical trail. The underlying molecular mechanisms are as yet unclear. We show that TGN1412 as well as the commercially available CD28 superagonist ANC28.1 induce a delayed but extremely sustained calcium response in human naïve and memory CD4+ T cells but not in cynomolgus T lymphocytes. The sustained Ca++-signal was associated with the activation of multiple intracellular signaling pathways and together these events culminated in the rapid de novo synthesis of high amounts of pro-inflammatory cytokines, most notably IFN-γ and TNF-α. Importantly, sustained transmembranous calcium flux, activation of Src-kinases as well as activation of PI3K were found to be absolutely required for CD28SA-mediated production of IFN-γ and IL-2. Collectively, our data suggest a molecular basis for the severe side effects caused by TGN1412 and impinge upon the relevance of non-human primates as preclinical models for reagents that are supposed to modify the function of human T cells