The central role of T-tubule and sarcoplasmic reticulum (SR) diadic junctions in excitation-contraction (EC) coupling in adult (AD) ventricular myocytes suggests that their absence in newborn (NB) cells may manifest as an altered EC coupling phenotype. We used confocal microscopy to compare fluo-3 [Ca2+]i transients in the subsarcolemmal space and cell center of field-stimulated NB and AD rabbit ventricular myocytes. Peak systolic [Ca2+]i occurred sooner and was higher in the subsarcolemmal space compared with the cell center in NB myocytes. In AD myocytes, [Ca2+]i rose and declined with similar profiles at the cell center and subsarcolemmal space. Disabling the SR (10 micromol/L thapsigargin) slowed the rate of rise and decline of Ca2+ in AD myocytes but did not alter Ca2+ transient kinetics in NB myocytes. In contrast to adults, localized SR Ca2+ release events ("Ca2+ sparks") occurred predominantly at the cell periphery of NB myocytes. Immunolabeling experiments demonstrated overlapping distributions of the Na(+)-Ca2+ exchanger and ryanodine receptors (RyR2) in AD myocytes. In contrast, RyR2s were spatially separated from the sarcolemma in NB myocytes. Confocal sarcolemmal imaging of di-8-ANEPPS-treated myocytes confirmed an extensive T-tubule network in AD cells, and that T-tubules are absent in NB myocytes. A mathematical model of subcellular Ca2+ dynamics predicts that Ca2+ flux via the Na(+)-Ca2+ exchanger during an action potential can account for the subsarcolemmal Ca2+ gradients in NB myocytes. Spatial separation of sarcolemmal Ca2+ entry from SR Ca2+ release channels may minimize the role of SR Ca2+ release during normal EC coupling in NB ventricular myocytes.

Background The school-age years, approximately ages 7 through 11, represent a natural transition when children begin assuming some responsibility for their asthma management. Previously, we designed a theoretically derived, tailored parent–child shared asthma management mobile health app prototype, Improving Asthma Care Together (IMPACT). Objective The purpose of this study was to use human-centered design (HCD) to iteratively refine IMPACT to optimize user experience and incorporate evidence-based longitudinal engagement strategies. Methods This study used a mixed methods design from December 2019 to April 2021. Our app refinement used the HCD process of research, ideation, design, evaluation, and implementation, including 6 cycles of design and evaluation. The design and evaluation cycles focused on core app functionality, child engagement, and overall refinement. Evaluation with parent–child dyads entailed in-person and remote concept testing and usability testing sessions, after which rapid cycle thematic analyses identified key insights that informed future design refinement. Results Twelve parent–child dyads enrolled in at least one round of this study. Eight of the 12 child participants were male with a mean age of 9.9 (SD 1.6) years and all parent participants were female. Throughout evaluation cycles, dyads selected preferred app layouts, gamification concepts, and overall features with a final design prototype emerging for full-scale development and implementation. Conclusions A theoretically derived, evidence-based shared asthma management app was co-designed with end users to address real-world pain points and priorities. An 8-week pilot study testing app feasibility, acceptability, and preliminary efficacy is forthcoming.

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BACKGROUND The school-age years, approximately ages seven through eleven, represent a natural transition when children begin assuming some responsibility for their asthma management. Previously, we designed a theoretically-derived, tailored parent-child shared asthma management mHealth application (app), Improving Asthma Care Together (IMPACT). OBJECTIVE The purpose of this study was to use human centered design (HCD) to refine IMPACT to ensure that a developmentally appropriate, engaging app emerged. METHODS This study used a mixed methods design from December 2019 through April 2021. Our app refinement used the HCD process of research, ideation, design, evaluation, and implementation, including six cycles of design and evaluation. The design and evaluation cycles focused on core app functionality, child engagement, and overall refinement. Evaluation with parent-child dyads entailed in-person and remote concept testing and usability testing sessions, after which rapid cycle thematic analyses identified key insights that informed future design refinement. RESULTS Twelve parent-child dyads enrolled in at least one round of this study. Eight of the 12 child participants were male with a mean age of 9.9 + 1.6 years and all parent participants were female. Throughout evaluation cycles, dyads selected preferred app layouts, gamification concepts, and overall features with a final design prototype emerging for full-scale development and implementation. CONCLUSIONS A theoretically-derived, evidence-based shared asthma management app was co-designed with end users to address real-world pain points and priorities. An eight-week pilot testing app feasibility, acceptability, and preliminary efficacy is forthcoming.

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