Thermomechanical couplings in shape memory alloy materials

In this work we address several theoretical and computational issues which are related to the thermomechanical modeling of shape memory alloy materials. More specifically, in this paper we revisit a non-isothermal version of the theory of large deformation generalized plasticity which is suitable for describing the multiple and complex mechanisms occurring in these materials during phase transformations. We also discuss the computational implementation of a generalized plasticity based constitutive model and we demonstrate the ability of the theory in simulating the basic patterns of the experimentally observed behavior by a set of representative numerical examples

Influence of oral beclomethasone dipropionate on early non-infectious pulmonary outcomes after allogeneic hematopoietic cell transplantation: results from two randomized trials.

Early non-infectious pulmonary complications represent a significant cause of mortality after hematopoietic cell transplantation (HCT). We tested the hypothesis that oral beclomethasone dipropionate (BDP) is effective for preventing early non-infectious pulmonary complications after allogeneic HCT. We retrospectively reviewed the medical records of 120 patients, 60 in each treatment arm, to identify non-infectious and infectious pulmonary events and pulmonary function test results from all patients who participated in two randomized trials of oral BDP for treatment of acute gastrointestinal GVHD. 17-Beclomethasone monopropionate (17-BMP), the active metabolite of BDP, was evaluated in blood from the right atrium in four patients. Thirty-three of 42 (79%) placebo-treated patients experienced a decrease of the DL(CO) from pretransplant to day 80 after transplant, compared with 27 of 49 (55%) BDP-treated patients (P=0.02). In the first 200 days after randomization, there were no cases of non-infectious pulmonary complications in BDP-treated patients, vs four cases among placebo-treated patients (P=0.04). Levels of 17-BMP were detected in atrial blood at steady state. Delivery of a potent glucocorticoid such as 17-BMP to the pulmonary artery after oral dosing of BDP may be useful in modulating pulmonary inflammation and preventing the development of non-infectious pulmonary complications after allogeneic HCT.Bone Marrow Transplantation advance online publication, 29 June 2009; doi:10.1038/bmt.2009.129

Vimentin restrains regulatory T-cell suppression of graft-versus-host disease

Regulatory T-cells (Treg) are critical for maintaining immune homeostasis. However, current Treg immunotherapies do not optimally treat inflammatory diseases in patients. Understanding the cellular processes that control Treg function may allow for the augmentation of therapeutic efficacy. In contrast to activated conventional T-cells, where protein kinase C-T (PKC-T) localizes to the contact-point between T-cells and antigen-presenting cells, in Treg, PKC-T localizes to the opposite end of the cell in the distal pole complex (DPC). Here, using a phosphoproteomic screen, we identified the intermediate filament vimentin as a PKC-T phosphotarget and show that vimentin forms a DPC superstructure on which PKC-T accumulates. Treatment of Treg with either a clinically relevant PKC-T inhibitor or vimentin siRNA disrupted vimentin and enhanced Treg metabolic and suppressive activity. Moreover, vimentin-disrupted Treg were significantly better than controls in suppressing alloreactive T-cell priming in graftversus-host disease, and graft-versus-host disease lethality. Interestingly, vimentin disruption augmented suppressor function of PKC-T-deficient Treg. This suggests that enhanced Treg activity after PKC-T inhibition is secondary to effects on vimentin, not just PKC-T kinase activity inhibition. Our data demonstrated that vimentin is a key metabolic and functional controller of Treg activity, and provide proof-of-principle that disrupting vimentin is a feasible, translationally relevant method to enhance Treg potency

Systematic review of cytokines and growth factors for the management of oral mucositis in cancer patients

<p>The aim of this project was to review the literature and define clinical practice guidelines for the use of cytokines and growth factor agents for the prevention or treatment of oral mucositis induced by cancer chemotherapy or radiotherapy.</p><p>A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: Recommendation, Suggestion, No guideline possible.</p><p>Sixty-four clinical studies across 11 interventions were evaluated. A recommendation was made for the use of recombinant human KGF-1 (palifermin) at a dose of 60 mu g/kg per day for 3 days prior to conditioning treatment and for 3 days post-transplant for prevention of oral mucositis in patients receiving high-dose chemotherapy and total body irradiation followed by autologous stem cell transplantation for hematological malignancies. A suggestion was made against using granulocyte macrophage colony-stimulating factor mouthwash for the prevention of oral mucositis in the setting of high-dose chemotherapy followed by autologous or allogeneic stem cell transplantation. No guideline was possible for any other cytokine or growth factor agents due to inconclusive evidence.</p><p>Of the cytokine and growth factor agents studied for oral mucositis, the evidence only supports use of palifermin in the specific population listed above. Additional well-designed research is needed on other cytokine and growth factor interventions and in other cancer treatment settings.</p>