Parent-Reported Usability of a Patient Portal-Based Asthma Care Tool for Parents of Children With Asthma.

INTRODUCTION: This study evaluates our new EHR-integrated patient portal for asthma care (PAC) management module for parents of children with asthma. The module includes a previsit asthma intake questionnaire via the portal. The parent answers are integrated into the providers clinic progress note to support clinical decision-making. Our goals were to measure the functionality and usability of the PAC module and to understand facilitators and barriers to its use for parents. METHODS: Parents of children ages 0-11 years old (n = 45) completed the PAC modules asthma intake questionnaires prior to their upcoming pediatric pulmonology clinic visit. To assess functionality, provider progress notes were manually reviewed to measure the amount of key asthma-related data captured. Differences in percent data captured with and without the PAC module were compared. Electronic surveys capture demographics, usability data (the System Usability Scale [SUS]), and open-ended experiential feedback about the module. Analysis included descriptive statistics for demographics and usability, as well as the constant comparative method for open-ended feedback. RESULTS: The PAC module at this early stage of design significantly improved the capture of key asthma data in physician notes, increasing from 77% to 92% (p < 0.001). The average SUS score (83.8) indicated high usability. Favorable aspects of the module that were identified included time savings and ease of use. CONCLUSION: Our PAC module enhanced data capture of key asthma management elements and demonstrated high parental usability. We will continue to refine the module through an iterative approach based on end-user feedback, with future expansion planned for broader patient populations

Manipulating the onset of cell cycle withdrawal in differentiated erythroid cells with cyclin-dependent kinases and inhibitors

Abstract Terminal differentiation of erythroid cells results in terminal cell divisions followed by irreversible cell cycle withdrawal of hemoglobinized cells. The mechanisms leading to cell cycle withdrawal were assessed in stable transfectants of murine erythroleukemia cells, in which the activities of cyclin-dependent kinases (CDKs) and CDK inhibitors (CDKIs) could be tightly regulated during differentiation. Cell cycle withdrawal of differentiating cells is mediated by induction of several CDKIs, thereby leading to inhibition of CDK2 and CDK4. Manipulation of CDK activity in differentiating cells demonstrates that the onset of cell cycle withdrawal can be either greatly accelerated or greatly delayed without affecting hemoglobin levels. Extending the proliferation of differentiating cells requires the synergistic action of CDK2 and CDK4. Importantly, CDK6 cannot substitute for CDK4 in this role, which demonstrates that the 2 cyclin D–dependent kinases are functionally different. The results show that differentiating hemoglobinized cells can be made to proliferate far beyond their normal capacity to divide.</jats:p

Reprogramming leukemic cells to terminal differentiation by inhibiting specific cyclin-dependent kinases in G ₁

Some tumor cells can be stimulated to differentiate and undergo terminal cell division and loss of tumorigenicity. The in vitro differentiation of murine erythroleukemia (MEL) cells is a dramatic example of tumor-cell reprogramming. We found that reentry of MEL cells into terminal differentiation is accompanied by an early transient decline in the activity of cyclin-dependant kinase (CDK) 2, followed by a decline of CDK6. Later, as cells undergo terminal arrest, CDK2 and CDK4 activities decline. By analyzing stable MEL-cell transfectants containing vectors directing inducible expression of specific CDK inhibitors, we show that only inhibitors that block the combination of CDK2 and CDK6 trigger differentiation. Inhibiting CDK2 and CDK4 does not cause differentiation. Importantly, we also show that reprogramming through inhibition of CDKs is restricted to G 1 phase of the cell cycle. The results imply that abrogation of normal cell-cycle controls in tumor cells contributes to their inability to differentiate fully and that restoration of such controls in G 1 can lead to resumption of differentiation and terminal cell division. The results also indicate that CDK4 and CDK6 are functionally distinct and support our hypothesis that the two CDKs regulate cell division at different stages of erythroid maturation. </jats:p

Manipulating the onset of cell cycle withdrawal in differentiated erythroid cells with cyclin-dependent kinases and inhibitors

Terminal differentiation of erythroid cells results in terminal cell divisions followed by irreversible cell cycle withdrawal of hemoglobinized cells. The mechanisms leading to cell cycle withdrawal were assessed in stable transfectants of murine erythroleukemia cells, in which the activities of cyclin-dependent kinases (CDKs) and CDK inhibitors (CDKIs) could be tightly regulated during differentiation. Cell cycle withdrawal of differentiating cells is mediated by induction of several CDKIs, thereby leading to inhibition of CDK2 and CDK4. Manipulation of CDK activity in differentiating cells demonstrates that the onset of cell cycle withdrawal can be either greatly accelerated or greatly delayed without affecting hemoglobin levels. Extending the proliferation of differentiating cells requires the synergistic action of CDK2 and CDK4. Importantly, CDK6 cannot substitute for CDK4 in this role, which demonstrates that the 2 cyclin D–dependent kinases are functionally different. The results show that differentiating hemoglobinized cells can be made to proliferate far beyond their normal capacity to divide.</jats:p

Reversal of tumorigenicity and the block to differentiation in erythroleukemia cells by GATA-1. Cancer Res

ABSTRACT Oncogenic transformation usually inhibits normal cell differentiation processes. Certain chemical agents can force some tumor cells to resume their differentiation program and undergo cell cycle arrest, an approach termed differentiation therapy. Mouse erythroleukemia (MEL) cells represent an important cell culture model system for investigating the principles of differentiation therapy. MEL cells are malignant erythroblasts that are blocked from differentiating into mature erythroid cells because of inappropriate expression of the transcription factor PU.1, which binds to and represses GATA-1, a key transcriptional stimulator of red blood cell differentiation. We report here that the block to differentiation in MEL cells can be overcome by providing the cells with additional GATA-1. A conditionally active form of GATA-1 can trigger the cells to differentiate, undergo terminal cell division, and lose their tumorigenicity. We also show that the gene for the cell cycle inhibitor p21 is transcriptionally regulated by GATA-1 and is a likely downstream effector of GATA-1 that helps to promote differentiation and proliferation arrest