Background/objectives: To develop an online patient education resource for use in spinal cord injury rehabilitation. Participants: The development process involved more than 100 subject-matter experts (SMEs) (rehabilitation professionals and consumers) from across Canada. Preliminary evaluation was conducted with 25 end-users. Methods: An iterative development process was coordinated by a project team; SMEs (including patients) developed the content in working groups using wiki-based tools. Multiple rounds of feedback based on early prototypes helped improve the courses during development. Results: Five courses were created, each featuring more than 45 minutes of video content and hundreds of media assets. Preliminary evaluation results indicate that users were satisfied by the courses and perceived them to be effective. Conclusions: This is an effective process for developing multimedia patient education resources; the involvement of patients in all parts of the process was particularly helpful. Future work will focus on implementation, integration into clinical practice and other delivery formats (smart phones, tablets).

BCR-ABL induces chronic myeloid leukemia (CML) through the aberrant regulation of multiple signaling substrates. Previous research has shown that BCR-ABL mediates down-modulation of CBL-B protein levels. A murine bone marrow transplantation (BMT) study was performed to assess the contribution of Cbl-b to BCR-ABL-induced disease. The predominant phenotype in the Cbl-b(-/-) recipients was a CML-like myeloproliferative disease (MPD) similar to that observed in the wild-type animals, but with a longer latency, diminished circulating leukocyte numbers and reduced spleen weights. Despite the decreased leukemic burden in comparison to their wild-type counterparts, the Cbl-b(-/-) animals displayed enhanced numbers of Gr-1(+)/Mac-1(+) spleen cells and neutrophilia. On the basis of prior evidence of CBL-B-dependent motility toward SDF-1α, we hypothesized that Cbl-b deficiency might impair bone marrow localization during transplantation. Homing experiments showed reduced migration of Cbl-b(-/-) cells to the bone marrow. Intrafemoral transplantation of BCR-ABL-transduced Cbl-b(-/-) cells revealed equivalent latency of disease development to the wild-type transplants, supporting the conclusion that Cbl-b deficiency diminishes homing of leukemic cells to the bone marrow, and perturbs the proliferation of BCR-ABL-expressing malignant clones during CML development.

Background/Objective: People with spinal cord injury (SCI) access educational resources during their inpatient rehabilitation, but they can be overwhelmed by the amount of information they need to assimilate during ever-shorter stays. This project created e-learning courses to fill the knowledge needs of SCI consumers and evaluated user satisfaction and knowledge transfer. Methods/Overview: A needs assessment of 83 consumers and 99 staff identified information needs for people with SCI (Toronto Rehabilitation Institute-UHN and CPAO, 2008). Key topics were selected for the creation of 10 online patient education courses, collectively called Spinal Cord Injury-University (SCI-U), and housed on the Spinal Cord Connections website (www.spinalcordconnections.ca/sci-u). Course content was developed collaboratively by over 100 consumers and professionals, from healthcare and community service organizations across Canada. Each course uses adult learning principles and presents key information on healthy living with SCI, in an accessible and engaging way. A team of professionals created multimedia courses using Articulate software, incorporating video, animation and interactivity. The courses show the positive faces of SCI, each one featuring 3 video presenters (all people with SCI), and video testimonials where consumers talk about their experience living with SCI and managing their health. Users are encouraged to complete course quizzes to reinforce their learning. A pilot study enrolled consumers and clinicians (n = 25) and evaluated knowledge acquisition and retention, as well as perceived utility and satisfaction with the first 3 courses in the series: SCI and You, Bladder and Bowel. Results: Knowledge acquisition and retention: across-group mean pre-course, post-course and 1-month postcourse scores were "

One of the prominent tyrosine phosphorylated substrates of BCR-ABL identified in cells from chronic-phase Chronic Myeloid Leukemia (CML) patients is the Cbl ubiquitin ligase and adaptor protein. Bone marrow transplantation studies have revealed that Cbl is dispensable for CML development, as animals receiving Cbl-deficient bone marrow cells expressing BCR-ABL develop a myeloproliferative disease (MPD) with a similar latency and phenotype as wild type bone marrow recipients (Dinulescu et al. 22: 8852–60, 2003). Cbl belongs to a family of E3 ubiquitin ligases that also contains Cbl-b and Cbl-3. In contrast to the equivalent Cbl protein expression displayed in hematopoietic cell lines expressing BCR-ABL, addition of the oncogene leads to a decreased expression of the related family member, Cbl-b. The objective of this study was to determine whether Cbl-b is a critical signaling intermediate downstream of BCR-ABL. To investigate this objective, we performed retroviral transduction of wild type- and Cbl-b- deficient bone marrow with BCR-ABL and utilized these cells for bone marrow transplantation of lethally irradiated mice. Recipients of wild type donor cells transduced with the p210 isoform of BCR-ABL, succumb to a rapidly fatal CML-like MPD, while the lack of Cbl-b produces a significant delay in morbidity (average latency of 32 days as compared with 18 days for recipients of wild-type marrow). Expansion of differentiated neutrophils, as visualized by histopathological analysis, is evident in the peripheral blood, bone marrow and spleen of all transplanted animals. However, circulating white blood cells are augmented in number (average wbc count for Cbl-b(+/+), 150 × 106 cells / mL; Cbl-b(−/−), 83 × 106 cells / mL) and enhanced spleen size is observed in Cbl-b(+/+) mice (35 mg / g of body mass) as compared to Cbl-b(−/−) (19 mg/g) animals. Liver masses were comparable between the two transplants. In depth flow cytometric studies of splenic cells reveals the characteristic decrease in B and T cells and enhanced myeloid lineages. Notably, an increased number of granulocytes (Gr-1+/Mac-1+ cells) is observed in the Cbl-b-knockout animals, suggesting enhanced migration but decreased survival of leukemic cells in the Cbl-b−/− spleen. In support of this hypothesis, fibroblasts deficient in Cbl-b display enhanced chemotactic migration toward Fetal Calf Serum. As migration is a key determinant of cellular retention in the bone marrow, the loss of Cbl-b could ultimately be affecting cell localization. Therefore, our data supports a continued study of Cbl-b as a motility regulator in BCR-ABL-dependent CML progression.