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OBJECTIVES: To examine the effects of decreasing hospital length of stay (HLOS) on change in functioning from prehospital admission to posthospital discharge in older cohorts.DESIGN: Cohort-sequential design.SETTING: Nationwide, older population-based Longitudinal Aging Study Amsterdam (LASA).PARTICIPANTS: Individuals aged 68 and older with any hospital admission according to national medical registry data: two 10-year age groups (68-77 (younger-old) and 78-87 (older-old)) in two periods (1996-99 (Period 1) and 2006-09 (Period 2)) (N = 1,212).MEASUREMENTS: HLOS was the main independent variable in multinomial logistic models, dichotomized as 1 to 5 days (short) and 6 days or longer (long). Outcomes were change scores in mobility and activities in daily living (ADLs). Respondents who died during the 3-year period were assigned to a third outcome category.RESULTS: Results for both age groups showed more hospital admissions and shorter median HLOS in Period 2 than Period 1 (P < .05). Lower odds of decline in physical functioning were found in respondents with short HLOS than in those with long HLOS (for mobility: odds ratio (OR) = 0.36, 95% confidence interval (CI) = 0.23-0.54 (younger-old) and OR = 0.47, 95% CI = 0.30-0.72 (older-old); for ADLs: OR = 0.30, 95% CI = 0.19-0.48 (younger-old) and OR = 0.30, 95% CI = 0.18-0.53 (older-old)). Adjusting for confounders did not significantly change these estimates. Period did not modify these associations.CONCLUSION: Because the associations of HLOS with change in mobility and ADLs were the same in both periods, hospitalized older adults had neither advantage nor disadvantage from the decrease in HLOS. In addition, in both age groups, a greater percentage experienced the better functional outcomes and lower mortality associated with short admissions, which suggests an advantage of the decrease in HLOS.

A major challenge in neuroscience is to identify genes that influence specific behaviors and to understand the intermediary neuronal mechanisms. One approach is to identify so-called endophenotypes at different levels of neuronal organization from synapse to brain activity. An endophenotype is a quantitative trait that is closer to the gene action than behavior, and potentially a marker of neuronal mechanisms underlying behavior. Hippocampal activity and, in particular, hippocampal oscillations have been suggested to underlie various cognitive and motor functions. To identify quantitative traits that are potentially useful for identifying genes influencing hippocampal activity, we measured gamma oscillations and spontaneous activity in acute hippocampal slices from eight inbred mouse strains under three experimental conditions. We estimated the heritability of more than 200 quantitative traits derived from this activity. We observed significant differences between the different mouse strains, particularly in the amplitude of the activity and the correlation between activities in different hippocampal subregions. Interestingly, these traits had a low genetic correlation between the three experimental conditions, which suggests that different genetic components influence the activity in different conditions. Our findings show that several traits of hippocampal gamma oscillations and spontaneous activity are heritable and could thus be potentially useful in gene-finding strategies based on endophenotypes. © Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Objective. To compose an inventory of instruments that have been described to measure foot function (i.e., pressure and/or gait parameters), foot pain, and foot-related disability in rheumatoid arthritis (RA), and to investigate the clinimetric quality of these measures. Methods. A systematic search was conducted in Medline, CINAHL, EMBase, and Sportdiscus. Standardized criteria, extended with levels of evidence, were applied to assess the quality of the clinimetric studies and the properties (i.e., reliability, validity, and responsiveness) of the described instruments. Results. A variety of measurement instruments were identified. Only 16 instruments have been studied for their measurement properties in RA patients: 7 for assessing foot function, 3 for measuring foot-related disability, and 6 for measuring both foot pain and foot-related disability. Thirteen instruments were rated for reliability, of which 10 were rated positively on different levels of evidence. No positive rating for absolute measurement error was applicable for any of the tests. Internal consistency was reported for 7 instruments; 3 assigned a positive rating. For 2 instruments, Rasch analysis was used to assess the methodologic quality. A positive rating was reported for goodness-of-fit only, not for item calibration. Seven instruments were rated for construct validity, and 3 assigned a positive rating. Only 2 instruments were rated positively for responsiveness. Conclusion. This review offers a basis for choosing the most appropriate instruments for measuring foot function, foot pain, and foot-related disability in RA patients, both for clinical practice and for research. Further research on the quality of these measures is urgently needed.

Item does not contain fulltext AIMS: Tumour necrosis factor (TNF)-receptor associated factor 2 (TRAF2) is an adaptor molecule involved in nuclear factor (NF)-kappaB activation, which is characteristic of in vitro activated B-cell (ABC)-like diffuse large B-cell lymphomas (DLBCL) and may result in expression of anti-apoptotic genes and poor response to chemotherapy. TRAF2 also has direct anti-apoptotic properties via interference with the apoptosis signalling cascade. The aim was to determine whether TRAF2 is preferentially expressed in ABC-like DLBCL, and whether expression correlates with clinical outcome. METHODS AND RESULTS: TRAF2 was expressed in nine of 20 tested ABC-like DLBCLs and in only one of 13 tested germinal centre B-lymphocyte (GCB)-like DLBCLs. High TRAF2 expression was correlated with high International Prognostic Index at time of presentation, high chance of relapse and short progression-free survival time in 44 tested DLBCLs. Furthermore, when analysis was restricted to ABC-like DLBCL only, TRAF2 expression was significantly associated with poor progression-free survival time. CONCLUSIONS: TRAF2 might be involved in activation of NF-kappaB in a subset of ABC-like DLBCL, and its expression is associated with a particularly poor outcome in primary nodal DLBCL patients. Because of its possible effect on to chemotherapy resistance, resistance, TRAF2 might be an attractive candidate as a molecular target for TRAF2+ DLBCL.

Item does not contain fulltext Two distinct primary cutaneous large B cell lymphomas are recognized: primary cutaneous follicle centre lymphoma (PCFCL), characterized by an excellent prognosis, and primary cutaneous large B cell lymphoma, leg-type (PCLBCL leg-type), with an unfavourable prognosis. To determine whether inhibition of the apoptosis pathways may underlie the difference in clinical outcome between PCFCL and PCLBCL leg-type, we investigated the expression of only apoptosis-related genes by microarray expression profiling. Unsupervised cluster analysis was carried out using 169 genes involved in apoptosis on a group of 21 previously untreated patients diagnosed with primary cutaneous large B cell lymphoma. Cluster analysis resulted in two separate groups which showed large overlap with the PCFCL and PCLBCL leg-type. One group was characterized by high expression levels of pro- and anti-apoptotic genes. The other group was characterized by high expression levels of apoptosis-inducing cytotoxic effector genes, possibly reflecting a cellular cytotoxic immune response. Our results suggest that the clinically favourable PCFCLs are characterized by a relatively intense cellular cytotoxic immune response and that PCLBCL leg-types are characterized by constitutive activation of the intrinsic mediated apoptosis pathway, with concomitant downstream inhibition of this apoptosis pathway. Thus, strategies neutralizing the function of apoptosis-inhibiting proteins might be effective in PCLBCL leg-type.

Dendritic cells (DC) have gained much interest in the field of anticancer vaccine development because of their central function in immune regulation. However, the clinical application of ex vivo cultured DC has significant disadvantages. A vaccine that targets dendritic cells in vivo and enhances antigen presentation would be of great benefit. Because of its DC-restricted expression pattern, and its function as an antigen uptake receptor, DC-SIGN is an interesting candidate target structure for human immature DC. Here, we studied whether modification of the melanoma differentiation antigen gp100 with DC-SIGN-interacting glycans enhances targeting to human DC. A high-mannose form of gp100, as protein or as tumor lysate, not only interacted specifically with DC through DC-SIGN but also resulted in an enhanced antigen presentation to gp100-specific CD4(+) T cells. Our results indicate that glycan modification of tumor antigens to target C-type lectin receptors, such as DC-SIGN, is a new way to develop in vivo targeting DC strategies that simultaneously enhance the induction of tumor-specific T cells.