ABSTRACT
Introduction: Overweight and obesity in youth with serious emotional disturbance (SED) is exceedingly common. In 2015 the AHA called attention to mental illnesses in youth as important risk conditions for early CVD and the need for transformational change in management of overweight and obesity in this group. Our objective was to test a 12-month, innovative healthy weight intervention in youth with SED.Hypothesis: The active intervention is more effective than control in decreasing BMI Z-score compared at 12 m. Method(s): We conducted a two-arm randomized trial in 2 outpatient pediatric mental health settings in 112 youth, ages 8-18 yrs. The active intervention group was offered 12m of in-person and virtual individual weight management sessions led by health coaches who provided guidance on improving diet and increasing physical activity, and engaged parents. Result(s): At baseline, mean (SD) age was 13.0 (2.7) yrs with 46% ages 8-12 and 54% 13-18;55% were male, 46% Black, 39% had household income less than $50K/yr and 31% lived in a single-parent household. Primary diagnoses were ADHD (41%), major depression (23%), and anxiety (23%). Mean BMI Z-score (SD) was 2.0(0.4), BMI 30.4 (6.4) kg/m2.Mean(SD) psychotropic medications were 2.1(1.4).At 12m, 111 (99%) had a follow-up weight;42 were collected after the onset of the COVID pandemic). The intervention group compared to the control group had 0.15 decrease in BMI Z-Score (95% CI 0.26 to 0.04), p<0.007) between baseline and 12 m (Figure) and a 1.43 kg/m2 decrease in BMI (95% CI 2.43, 0.42, p<0.006). Estimated net effect on BMI Z-score for intervention vs. control was enhanced during the pandemic but not statistically different from net effects pre-pandemic (p=0.06). Conclusion(s): A weight control intervention designed for children with SED decreased BMI Z-score substantially over 12 months, including during the COVID-19 pandemic. These results provide empirical evidence in support of weight control programs in a population at high risk for early development of CVD risk factors.
ABSTRACT
The response of the adaptive immune system is augmented by multimeric presentation of a specific antigen, resembling viral particles. Several vaccines have been designed based on natural or designed protein scaffolds, which exhibited a potent adaptive immune response to antigens;however, antibodies are also generated against the scaffold, which may impair subsequent vaccination. In order to compare polypeptide scaffolds of different size and oligomerization state with respect to their efficiency, including anti-scaffold immunity, we compared several strategies of presentation of the RBD domain of the SARS-CoV-2 spike protein, an antigen aiming to generate neutralizing antibodies. A comparison of several genetic fusions of RBD to different nanoscaffolding domains (foldon, ferritin, lumazine synthase, and beta-annulus peptide) delivered as DNA plasmids demonstrated a strongly augmented immune response, with high titers of neutralizing antibodies and a robust T-cell response in mice. Antibody titers and virus neutralization were most potently enhanced by fusion to the small beta-annulus peptide scaffold, which itself triggered a minimal response in contrast to larger scaffolds. The beta-annulus fused RBD protein increased residence in lymph nodes and triggered the most potent viral neutralization in immunization by a recombinant protein. Results of the study support the use of a nanoscaffolding platform using the beta-annulus peptide for vaccine design.