A series of 1,2,4-oxadiazole analogues has been shown to be potent and selective SH2 inhibitors of the tyrosine kinase ZAP-70, a potential therapeutic target for immune suppression. These compounds typically are 200-400-fold more potent than the native, monophosphorylated tetrapeptide sequences. When compared with the high-affinity zeta-1-ITAM peptide (Ac-NQL-pYNELNLGRREE-pYDVLD-NH(2), wherein pY refers to phosphotyrosine) some of the best 1,2, 4-oxadiazole analogues are approximately 1 order of magnitude less active. This series of compounds displays an unprecedented level of selectivity over the closely related tyrosine kinase Syk, as well as other SH2-containing proteins such as Src and Grb2. Gel shift studies using a protein construct consisting only of C-terminal ZAP-70 SH2 demonstrate that these compounds can effectively engage this particular SH2 domain.
IntroductionThe prevalence of pediatric obesity has increased over the past 3 decades and is a pressing public health program. New technology advancements that can encourage more physical in children are needed. The Zamzee program is an activity meter linked to a motivational website designed for children 8–14 years of age. The objective of the study was to use a collaborative approach between a medical center, the private sector and local school staff to assess the feasibility of using the Zamzee Program in the school-based setting to improve physical activity levels in children.MethodsThis was a pilot 8-week observational study offered to all children in one fifth grade classroom. Body mass index (BMI), the amount of physical activity by 3-day recall survey, and satisfaction with usability of the Zamzee Program were measured pre- and post-study.ResultsOut of 11 children who enrolled in the study, 7 completed all study activities. In those who completed the study, the median (interquartile range) total activity time by survey increased by 17 (1042) minutes and the BMI percentile change was 0 (8). Both children and their caregivers found the Zamzee Activity Meter (6/7) and website (6/7) “very easy” or “easy” to use.ConclusionThe Zamzee Program was found to be usable but did not significantly improve physical activity levels or BMI. Collaborative obesity intervention projects involving medical centers, the private sector and local schools are feasible but the effectiveness needs to be evaluated in larger-scale studies.
Context:Childhood obesity is epidemic in the United States, but low levels of physical activity and high levels of screen time are modifiable risk factors. An activity meter (AM) program, that utilizes an interactive child-focused website and measures the amount and intensity of physical activity, may promote activity and decrease BMI. Objective:The current study tests the feasibility of using an AM program with child-caregiver pairs in a primary care setting. We hypothesize that participants would rate the system as easy to use, would be motivated with their engagement in physical activity, and would continue to use and recommend to others. We hypothesize the AM system would increase children's physical activity levels and decrease engagement in screen time over the study period. We also measure changes in participants' body mass index (BMI). Design:Prospective study assessing ease of use and satisfaction with the AM program post-intervention and comparing physical activity and BMI changes in children and caregivers from pre-and post-intervention over a 4-month period.Setting: A primary care clinic in Rochester, Minnesota.Participants: Ten children ages 9-14 years with BMI over 85th percentile and their associated caregivers. Intervention: Zamzee AM and website.Main Measures: Child and caregiver satisfaction ratings, physical activity measured by AM and survey, screen time engagement measured by survey, and BMI.Results: Between September 2014 and February 2015, 10 child-caregiver pairs were enrolled, and one pair did not complete the study. Both children and caregivers were satisfied with the usability of the AM and website, were motivated to be more physically active and would continue use of the meter after the study. Six activity meters were lost and five were broken. There were no significant changes in physical activity, screen time, or BMI in either caregivers or children. Conclusion:This feasibility study suggests promise for use of an AM program in the primary care setting but no effectiveness in improving activity level, screen time or BMI over 4 months. Further study with attention to intervention refinement and larger sample sizes is warranted. Given the prevalence of children with overweight/obesity, innovative ideas to promote physical activity are required.
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