Graft versus host disease (GVHD), mediated by donor T cells, is a significant source of morbidity and mortality following allogeneic stem cell transplantation. Mesenchymal stem cells (MSC) can successfully treat ongoing graft versus host disease, presumably due to their ability to suppress donor T cell proliferation. Little is known about the potential of MSC to prevent GVHD. Here we show that bone marrow-isolated MSC can suppress the development of GVHD if given after donor T cell recognition of antigen. IFN-c was required to initiate MSC efficacy. Recipients of IFN-c -/-T cells did not respond to MSC treatment and succumbed to GVHD. MSC, pre-treated with IFN-c, became immediately active and could suppress GVHD more efficiently than a fivefold-greater number of MSC that were not activated. When given at the time of bone marrow transplantation, activated MSC could prevent GVHD mortality (100% survival, p=0.006). MSC activation was dependent on the magnitude of IFN-c exposure, with increased IFN-c exposure leading to increased MSC suppression of GVHD. Activated MSC present a new strategy for preventing GVHD using fewer MSC. Key words: Mesenchymal stem cell Á GVH disease Á IFN-c See accompanying commentary by Dazzi and Marelli-Berg IntroductionAllogeneic hematopoietic stem cell transplants have the potential to play a significant curative role in the treatment of malignant and non-malignant hematopoietic disorders, autoimmune diseases, and immunological deficiencies, and in the induction of transplantation tolerance [1][2][3][4][5][6][7][8][9][10]. Widespread application of this therapeutic modality is limited due to the morbidity and mortality of graft versus host disease (GVHD), which affects 50% of stem cell transplant recipients [11][12][13][14][15][16]. While grafts highly matched to the recipient, young donors, donor/recipient sex match, and posttransplant immunosuppression are strategies used to reduce the risk of GVHD [17], thus far, the greatest preventative measure has been intentional underutilization of stem cell transplantation. Theoretically, strategies aimed at preventing GVHD would target early initiating factors either during the inflammatory milieu created in the wake of tissue damage from conditioning regimens [18,19] or during T cell antigen recognition and proliferation [20,21]. Once the efferent effector phase occurs, donor T cell-mediated destruction of host tissues occurs and preventive strategies are replaced with treatment regimens [19].Mesenchymal stem cells (MSC) have been used in the efferent phase of GVHD to successfully treat ongoing, acute, steroidresistant GVHD [22,23]. In contrast, when given at the time of BM transplant, for the prevention of GVHD, the incidence of grade III/ IV GVHD was not significantly improved [24], suggesting the [26,27,29,30]. In addition, MSC do not suppress the modest T cell proliferative response to recall antigens [31]. These findings suggest MSC may exert their optimal effects during the events surrounding larger scale T cell activation and proliferat...

Background Diabetes is a serious worldwide public health challenge. The burden of diabetes, including prevalence and risk of complications, is greater for minorities, particularly African Americans. Internet-based immersive virtual worlds offer a unique opportunity to reach large and diverse populations with diabetes for self-management education and support. Objective The objective of the study was to examine the acceptability, usage, and preliminary outcome of a virtual world intervention, Diabetes Island, in low-income African Americans with type 2 diabetes. The main hypotheses were that the intervention would: (1) be perceived as acceptable and useful; and (2) improve diabetes self-care (eg, behaviors and barriers) and self-care related outcomes, including glycemic control (A1C), body mass index (BMI), and psychosocial factors (ie, empowerment and distress) over six months. Methods The evaluation of the intervention impact used a single-group repeated measures design, including three assessment time points: (1) baseline, (2) 3 month (mid intervention), and (3) 6 month (immediate post intervention). Participants were recruited from a university primary care clinic. A total of 41 participants enrolled in the 6 month intervention study. The intervention components included: (1) a study website for communication, feedback, and tracking; and (2) access to an immersive virtual world (Diabetes Island) through Second Life, where a variety of diabetes self-care education activities and resources were available. Outcome measures included A1C, BMI, self-care behaviors, barriers to adherence, eating habits, empowerment, and distress. In addition, acceptability and usage were examined. A series of mixed-effects analyses, with time as a single repeated measures factor, were performed to examine preliminary outcomes. Results The intervention study sample (N=41) characteristics were: (1) mean age of 55 years, (2) 71% (29/41) female, (3) 100% (41/41) African American, and (4) 76% (31/41) reported annual incomes below US $20,000. Significant changes over time in the expected direction were observed for BMI (P<.02); diabetes-related distress (P<.02); global (P<.01) and dietary (P<.01) environmental barriers to self-care; one physical activity subscale (P<.04); and one dietary intake (P<.01) subscale. The participant feedback regarding the intervention (eg, ease of use, interest, and perceived impact) was consistently positive. The usage patterns showed that the majority of participants logged in regularly during the first two months, and around half logged in each week on average across the six month period. Conclusions This study demonstrated promising initial results of an immersive virtual world approach to reaching underserved individuals with diabetes to deliver diabetes self-management education. This intervention model and method show promise and could be tailored for other populations. A large scale controlled trial is needed to further examine efficacy.

Purpose The purpose of this study was to evaluate the impact of an innovative intervention that utilized a certified medical assistant with specific diabetes training to work with a multidisciplinary diabetes care team to help provide basic diabetes education and self-care support in low-income minority populations with type 2 diabetes. Methods Enrolled participants were randomized to either the medical assistant coaching (MAC) group (N = 25) or the treatment as usual (TAU) group (N = 25). Deidentified data was obtained on a matched no contact control (NCC) group (N = 50). Results Analysis of covariance (ANCOVA) comparisons revealed no significant differences between the 3 groups on A1C, but a trend was observed. A1Cs decreased across time for the MAC group, while increasing for the TAU and NCC groups. ANCOVA comparisons also indicated that the MAC group experienced significantly greater increases in perceived empowerment and a larger, although non-significant, reduction in perceived diabetes related problems than the TAU group. Conclusions This randomized controlled pilot study suggests that the inclusion of a medical assistant self-care coach as part of the diabetes care team holds promise in improving outcomes and should be further examined in a large-scale study.

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