Mitogen-induced stimulation and suppression of erythroid burst promoting activity production by human mononuclear cells

Exposure of human peripheral blood mononuclear cells or highly enriched monocytes to various plant lectins substantially alters their production of erythroid burst promoting activity (BPA). Neither unstimulated, nor mitogen stimulated, enriched T lymphocytes produced demonstrable BPA. Each of the lectins tested resulted in a different pattern of alteration of BPA production by mononuclear cells. Increasing concentrations of phytohaemagglutinin (PHA) caused a progressive increase in BPA production up to a plateau level at concentrations above 0·25–0·5 Μ1/ml. Concanavalin A (Con A) at concentrations of 0·05–0·1 Μg/ml stimulated BPA production, but Con A concentrations > 1 Μg/ml never augmented BPA production by mononuclear cells. Pokeweed mitogen inhibited BPA production by mononuclear cells in a concentration-dependent manner. Since PHA and Con A can bind to and stimulate both monocytes/macrophages and T lymphocytes, some production of BPA by stimulated T cells in the presence of monocytes cannot be ruled out. Earlier studies demonstrated that T cells augment monocyte production of BPA. Thus, monocyte–T cell interactions, as well as activation of monocytes and perhaps lymphocytes, play an important role in regulation of BPA production in vitro .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73808/1/j.1365-2141.1983.tb01232.x.pd

A trial protocol for the effectiveness of digital interventions for preventing depression in adolescents: The Future Proofing Study

BACKGROUND: Depression frequently first emerges during adolescence, and one in five young people will experience an episode of depression by the age of 18 years. Despite advances in treatment, there has been limited progress in addressing the burden at a population level. Accordingly, there has been growing interest in prevention approaches as an additional pathway to address depression. Depression can be prevented using evidence-based psychological programmes. However, barriers to implementing and accessing these programmes remain, typically reflecting a requirement for delivery by clinical experts and high associated delivery costs. Digital technologies, specifically smartphones, are now considered a key strategy to overcome the barriers inhibiting access to mental health programmes. The Future Proofing Study is a large-scale school-based trial investigating whether cognitive behaviour therapies (CBT) delivered by smartphone application can prevent depression. METHODS: A randomised controlled trial targeting up to 10,000 Year 8 Australian secondary school students will be conducted. In Stage I, schools will be randomised at the cluster level either to receive the CBT intervention app (SPARX) or to a non-active control group comparator. The primary outcome will be symptoms of depression, and secondary outcomes include psychological distress, anxiety and insomnia. At the 12-month follow-up, participants in the intervention arm with elevated depressive symptoms will participate in an individual-level randomised controlled trial (Stage II) and be randomised to receive a second CBT app which targets sleep difficulties (Sleep Ninja) or a control condition. Assessments will occur post intervention (both trial stages) and at 6, 12, 24, 36, 48 and 60 months post baseline. Primary analyses will use an intention-to-treat approach and compare changes in symptoms from baseline to follow-up relative to the control group using mixed-effect models. DISCUSSION: This is the first trial testing the effectiveness of smartphone apps delivered to school students to prevent depression at scale. Results from this trial will provide much-needed insight into the feasibility of this approach. They stand to inform policy and commission decisions concerning if and how such programmes should be deployed in school-based settings in Australia and beyond.Funding for this project came from a NHMRC Project Grant Awarded to HC (APP1120646), an Early-Mid Career Fellowship awarded to AW-S, an NHMRC Fellowship awarded to PJB (APP1158707) and a Sir Henry Wellcome fellowship awarded to S

Proposed Response Parameters for Twelve-Month Drug Trial in Juvenile Systemic Sclerosis: Results of the Hamburg International Consensus Meetings

Objective Juvenile systemic sclerosis (SSc) is an orphan disease, associated with high morbidity and mortality. New treatment strategies are much needed, but clearly defining appropriate outcomes is necessary if successful therapies are to be developed. Our objective here was to propose such outcomes. Methods This proposal is the result of 4 face-to-face consensus meetings with a 27-member multidisciplinary team of pediatric rheumatologists, adult rheumatologists, dermatologists, pediatric cardiologists, pulmonologists, gastroenterologists, a statistician, and patients. Throughout the process, we reviewed the existing adult data in this field, the more limited pediatric literature for juvenile SSc outcomes, and data from 2 juvenile SSc patient cohorts to assist in making informed, data-driven decisions. The use of items for each domain as an outcome measure in an open label 12-month clinical trial of juvenile SSc was voted and agreed upon using a nominal group technique. Results After voting, the domains agreed on were global disease activity, skin, Raynaud's phenomenon, digital ulcers, musculoskeletal, cardiac, pulmonary, renal, and gastrointestinal involvement, and quality of life. Fourteen outcome measures had 100% agreement, 1 item had 91% agreement, and 1 item had 86% agreement. The domains of biomarkers and growth/development were moved to the research agenda. Conclusion We reached consensus on multiple domains and items that should be assessed in an open label, 12-month clinical juvenile SSc trial as well as a research agenda for future development