Personality,psychosocial and health-related predictors of quality of life in old age

Objectives: Beyond its well-documented association with depressive symptoms across the lifespan, at an individual level, quality of life may be determined by multiple factors: psychosocial characteristics, current physical health and long-term personality traits.

Method: Quality of life was assessed in two distinct community-based age groups (89 young adults aged 36.2 ± 6.3 and 92 older adults aged 70.4 ± 5.5 years), each group equally including adults with and without acute depressive symptoms. Regression models were applied to explore the association between quality of life assessed with the World Health Organization Quality of Life - Bref (WHOQOL-Bref) and depression severity, education, social support, physical illness, as well as personality dimensions as defined by the Five-Factor Model.

Results: In young age, higher quality of life was uniquely associated with lower severity of depressive symptoms. In contrast, in old age, higher quality of life was related to both lower levels of depressive mood and of physical illness. In this age group, a positive association was also found between quality of life and higher levels of Openness to experience and Agreeableness personality dimensions.

Conclusion: Our data indicated that, in contrast to young cohorts, where acute depression is the main determinant of poor quality of life, physical illness and personality dimensions represent additional independent predictors of this variable in old age. This observation points to the need for concomitant consideration of physical and psychological determinants of quality of life in old age.     

Fabrication of porous scaffolds by three‐dimensional plotting of a pasty calcium phosphate bone cement under mild conditions

The major advantage of hydroxyapatite (HA)‐forming calcium phosphate cements (CPCs) used as bone replacement materials is their setting under physiological conditions without the necessity for thermal treatment that allows the incorporation of biological factors. In the present study, we have combined the biocompatible consolidation of CPCs with the potential of rapid prototyping (RP) techniques to generate calcium phosphate‐based scaffolds with defined inner and outer morphology. We demonstrate the application of the RP technique three‐dimensional (3D) plotting for the fabrication of HA cement scaffolds. This was realized by utilizing a paste‐like CPC (P‐CPC) which is stable as a malleable paste and whose setting reaction is initiated only after contact with aqueous solutions. The P‐CPC showed good processability in the 3D plotting process and allowed the fabrication of stable 3D structures of different geometries with adequate mechanical stability and compressive strength. The cytocompatibility of the plotted P‐CPC scaffolds was demonstrated in a cell culture experiment with human mesenchymal stem cells. The mild conditions during 3D plotting and post‐processing and the realization of the whole procedure under sterile conditions make this approach highly attractive for fabrication of individualized implants with respect to patient‐specific requirements by simultaneous plotting of biological components. Copyright © 2012 John Wiley & Sons, Ltd.     

Impact of oral ibandronate 150 mg once monthly on bone structure and density in post-menopausal osteoporosis or osteopenia derived from in vivo μCT

The effect of ibandronate 150 mg/once monthly in the treatment of post-menopausal osteopenia and osteoporosis on bone micro-structure at the distal tibia and radius has not been considered to date. Seventy post-menopausal women with osteoporosis or osteopenia were recruited. All subjects received calcium and vitamin D supplementation and were randomized to either a group which took 150 mg ibandronate oral monthly or a placebo group over a 12-month period. μCT measures of the distal tibia and radius were conducted every three months, with DXA lumbar spine and hip measurements conducted only pre and post and serum markers of bone formation and resorption measured every 6 months. After 12-months no significant impact of ibandronate on the primary outcome measures bone-volume to tissue-volume and trabecular separation at the distal tibia (p ≥ 0.15) was found. Further multiple regression analyses of the primary end-points indicated a significant effect favoring the ibandronate intervention (p = 0.045). Analysis of secondary end-points showed greater increases in distal tibia cortical thickness, cortical density and total density (p ≤ 0.043) with ibandronate and no significant effects at the distal radius, but greater increases of hip DXA-BMD and lumbar spine DXA-BMD (p ≤ 0.017). Ibandronate use resulted in a marked reduction in bone turnover (p < 0.001). While ibandronate resulted in greater mineralization of bone, this effect differed from one body region to another. There was some impact of ibandronate on bone structure (cortical thickness) at the distal tibia, but not on bone-volume to tissue-volume or trabecular separation.     

Generation and Preclinical Characterization of a Fc-optimized GITR-Ig Fusion Protein for Induction of NK Cell Reactivity Against Leukemia

Natural killer (NK) cells are cytotoxic lymphocytes that largely contribute to the efficacy of therapeutic strategies like allogenic stem cell transplantation in acute myeloid leukemia (AML) and application of Rituximab in chronic lymphocytic leukemia (CLL). The tumor necrosis factor (TNF) family member GITR ligand (GITRL) is frequently expressed on leukemia cells in AML and CLL and impairs the reactivity of NK cells which express GITR and upregulate its expression following activation. We developed a strategy to reinforce NK anti-leukemia reactivity by combining disruption of GITR–GITRL interaction with targeting leukemia cells for NK antibody-dependent cellular cytotoxicity (ADCC) using GITR-Ig fusion proteins with modified Fc moieties. Neutralization of leukemia-expressed GITRL by the GITR domain enhanced cytotoxicity and cytokine production of NK cells depending on activation state with NK reactivity being further largely dependent on the engineered affinity of the fusion proteins to the Fc receptor. Compared with wild-type GITR-Ig, treatment of primary AML and CLL cells with mutants containing a S239D/I332E modification potently increased cytotoxicity, degranulation, and cytokine production of NK cells in a target-antigen–dependent manner with additive effects being observed with CLL cells upon parallel exposure to Rituximab. Fc-optimized GITR-Ig may thus constitute an attractive means for immunotherapy of leukemia that warrants clinical evaluation.