Precision feedback: A conceptual model.

Introduction: When performance data are provided as feedback to healthcare professionals, they may use it to significantly improve care quality. However, the question of how to provide effective feedback remains unanswered, as decades of evidence have produced a consistent pattern of effects-with wide variation. From a coaching perspective, feedback is often based on a learner's objectives and goals. Furthermore, when coaches provide feedback, it is ideally informed by their understanding of the learner's needs and motivation. We anticipate that a "coaching"-informed approach to feedback may improve its effectiveness in two ways. First, by aligning feedback with healthcare professionals' chosen goals and objectives, and second, by enabling large-scale feedback systems to use new types of data to learn what kind of performance information is motivating in general. Our objective is to propose a conceptual model of precision feedback to support these anticipated enhancements to feedback interventions. Methods: We iteratively represented models of feedback's influence from theories of motivation and behavior change, visualization, and human-computer interaction. Through cycles of discussion and reflection, application to clinical examples, and software development, we implemented and refined the models in a software application to generate precision feedback messages from performance data for anesthesia providers. Results: We propose that precision feedback is feedback that is prioritized according to its motivational potential for a specific recipient. We identified three factors that influence motivational potential: (1) the motivating information in a recipient's performance data, (2) the surprisingness of the motivating information, and (3) a recipient's preferences for motivating information and its visual display. Conclusions: We propose a model of precision feedback that is aligned with leading theories of feedback interventions to support learning about the success of feedback interventions. We plan to evaluate this model in a randomized controlled trial of a precision feedback system that enhances feedback emails to anesthesia providers.

Blockade of the Wnt/ß-catenin pathway attenuates bleomycin-induced pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease and characterized by abnormal growth of fibroblasts and lung scarring. While the pathogenesis of IPF is not clearly understood, activation of transforming growth factor-ß (TGF-ß) and disruption of alveolar basement membrane seem to play important roles in leading to excess disruption of the matrix, which is associated with activated matrix metalloproteinase (MMP) and aberrant proliferation of myofibroblasts. The Wnt/ß-catenin pathway is an important regulator of cellular proliferation and differentiation and abnormal activation of Wnt/ß-catenin signal was observed in IPF. We examined whether inhibition of the Wnt/ß-catenin pathway could attenuate pulmonary fibrosis in a bleomycin-induced murine model of pulmonary fibrosis. Pulmonary fibrosis was induced in C57BL/6N mice by intratracheal instillation of bleomycin. To inhibit the Wnt/ß-catenin pathway, small interfering RNA (siRNA) for ß-catenin was administered into trachea 2 h before bleomycin instillation and every 48 h afterward until sacrifice on day 14. The level of ß-catenin expression was increased in the epithelial cells of bleomycin-administered mice. Intratracheal treatment with ß-catenin siRNA significantly reduced ß-catenin expression, pulmonary fibrosis and collagen synthesis in bleomycin-administered mice compared with controls, with no significant effect on the inflammatory response. The ß-catenin-targeted siRNA also significantly decreased the levels of MMP-2 (P<0.01) and TGF-ß (P<0.01) expression in the lung tissue. Blockade of the Wnt/ß-catenin pathway by ß-catenin siRNA decreased bleomycin-induced pulmonary fibrosis in the murine model. These findings suggest that targeting Wnt/ß-catenin signaling may be an effective therapeutic approach in the treatment of IPF.

Senescence mechanisms of nucleus pulposus chondrocytes in human intervertebral discs.

BACKGROUND CONTEXT: The population of senescent disc cells has been shown to increase in degenerated or herniated discs. However, the mechanism and signaling pathway involved in the senescence of nucleus pulposus (NP) chondrocytes are unknown. PURPOSE: To demonstrate the mechanisms involved in the senescence of NP chondrocytes. STUDY DESIGN/SETTING: Senescence-related markers were assessed in the surgically obtained human NP specimens. PATIENT SAMPLE: NP specimens remaining in the central region of the intervertebral disc were obtained from 25 patients (mean: 49 years, range: 20-75 years) undergoing discectomy. Based on the preoperative magnetic resonance images, there were 3 patients with Grade II degeneration, 17 patients with Grade III degeneration, and 5 patients with Grade IV degeneration. OUTCOME MEASURES: We examined cell senescence markers (senescence-associated beta-galactosidase [SA-beta-gal], telomere length, telomerase activity, p53, p21, pRB, and p16) and the hydrogen peroxide (H(2)O(2)) content as a marker for an oxidative stress in the human NP specimens. METHODS: SA-beta-gal expression, telomere length, telomerase activity, and H(2)O(2) content as well as their relationships with age and degeneration grades were analyzed. For the mechanism involved in the senescence of NP chondrocytes, expressions of p53, p21, pRB, and p16 in these cells were assessed with immunohistochemistry and Western blotting. RESULTS: The percentages of SA-beta-gal-positive NP chondrocytes increased with age (r=.82, p<.001), whereas the telomere length and telomerase activity declined (r=-.41, p=.045; r=-.52, p=.008, respectively) However, there was no significant correlation between age and H(2)O(2) contents (p=.18). The NP specimens with Grade III or Grade IV degeneration showed significantly higher percentages of SA-beta-gal-positive NP chondrocytes than those with Grade II degeneration (p=.01 and p=.025, respectively). Immunohistochemistry showed that the senescent NP chondrocytes in all the specimens expressed p53, p21, and pRB, but a few NP chondrocytes in only two specimens expressed p16. Western blotting showed that the expressions of p53, p21, and pRB displayed a corresponding pattern, that is, a strong p53 expression led to strong p21 and pRB expressions and vice versa. CONCLUSIONS: Our in vivo study demonstrated that senescent NP chondrocytes increased or accumulated in the NP with increasing age and advancing disc degeneration. The NP chondrocytes in the aging discs exhibited characteristic senescent features such as an increased SA-beta-gal expression, shortened telomeres, and decreased telomerase activity. We further demonstrated that the telomere-based p53-p21-pRB pathway, rather than the stress-based p16-pRB pathway, plays a more important role in the senescence of NP chondrocytes in an in vivo condition. Our results suggest that prevention or reversal of the senescence of NP chondrocytes can be a novel therapeutic target for human disc degeneration.

Expressions of membrane-type I matrix metalloproteinase, Ki-67 protein, and type II collagen by chondrocytes migrating from cartilage endplate into nucleus pulposus in rat intervertebral discs: a cartilage endplate-fracture model using an intervertebral disc organ culture.

STUDY DESIGN: Immunohistochemistry was performed in organ-cultured intact and cartilage endplate (CE)-fractured rat intervertebral discs (IVDs). OBJECTIVES: To demonstrate biologic events associated with migration of chondrocytes from hyaline CE into nucleus pulposus (NP). SUMMARY OF BACKGROUND DATA: It was recently revealed that the transition from a notochordal NP to a fibrocartilaginous NP in the rabbit IVD is accomplished exogenously by chondrocytes migrating from CEs into the NP. This observation has not been studied in other animal models, and the biologic events associated with chondrocyte migration have not been elucidated in the literature. METHODS: IVDs including cranial and caudal CEs were obtained from 4-week, 6-month, 12-month, and 18-month old Wistar rats. To accelerate chondrocyte migration, CEs of IVDs were fractured and cultured for 48 hours. IVDs without CE-fracture were used as a control for each age group. Expressions of membrane-type I matrix metalloproteinase (MT1-MMP, as a marker for cell migration and extracellular matrix digestion) and Ki-67 protein (as a proliferation marker) and pericellular deposition of type II collagen (as a marker for fibrocartilaginous matrix) by the chondrocytes migrating from CE into NP were examined immunohistochemically. RESULTS: In the control groups, chondrocyte migration limited only along the periphery of the notochordal NP and no chondrocytes were inside the NP proper. However, all the IVDs in the CE-fracture groups showed direct and more extensive migration of chondrocytes from CEs into the NP proper. The migrating chondrocytes in both control and CE-fracture groups expressed MT1-MMP and Ki-67 protein and deposited type II collagen in the NP. CONCLUSIONS: This report demonstrates the chondrocyte migration from CE into NP in the organ-cultured rat IVDs. This phenomenon is accelerated in the presence of CE fracture. The chondrocytes migrating from CEs into the NP expressed MT1-MMP and Ki-67 protein and deposited type II collagen. These biologic strategies probably enable chondrocytes of the hyaline CE to migrate into the ectopic NP region, replace notochordal cells, and change the notochordal tissue into fibrocartilage. These results suggest that similar biologic mechanisms may be involved in the natural transition from the notochordal NP to the fibrocartilaginous NP in other animal models, including human.