No abstract

Background: Physical function decline is associated with dementia, which might either be mediated by the coexisting sarcopenia or directly related to the impaired cognition. Our objectives are to examine the relationship between cognitive function and performance-based physical function and to test the hypothesis that cognitive function is related to poor physical function independent of muscle mass. Methods: We measured muscle strength, performance-based physical function and muscle mass using dual-energy X-ray absorptiometry and cognitive function using the cognitive part of the Community Screening Instrument of Dementia (CSI-D) in 4,000 community-dwelling Chinese elderly aged >65 years. A CSI-D cognitive score of >28.40 was considered as cognitively impaired. The effect of cognitive impairment on muscle strength and physical function was analyzed by multivariate analysis with adjustment for age, appendicular skeletal mass (ASM), the Physical Activity Scale for the Elderly (PASE) and other comorbidities. Results: In both genders, the cognitively impaired (CSI-D cognitive score >28.40) group had a weaker grip strength (–5.10 kg, p < 0.001 in men; –1.08 kg in women, p < 0.001) and performed worse in the two physical function tests (in men, 6-meter walk speed, –0.13 m/s, p < 0.001, chair stand test, 1.42 s, p < 0.001; in women, 6-meter walk speed, –0.08 m/s, p < 0.001, chair stand test, 1.48 s, p < 0.001). After adjustment for age, ASM, PASE and other comorbidities, significant differences in grip strength (–2.60 kg, p < 0.001 in men; –0.49 kg, p = 0.011 in women) and the two physical function tests persisted between the cognitively impaired and nonimpaired group (in men, 6-meter walk speed, –0.072 m/s, p < 0.001, chair stand test, 0.80 s, p = 0.045; in women, 6-meter walk speed, –0.049 m/s, p < 0.001, chair stand test, 0.98 s, p < 0.001). Conclusions: Poor physical function and muscle strength coexisted with cognitive impairment. This relationship was independent of muscle mass. It is likely therefore that the functional decline in dementia might be related directly to factors resulting in cognitive impairment independently of the coexisting sarcopenia.

The Wnt pathway regulates cell fate, proliferation, and apoptosis, and defects in the pathway play a key role in many cancers. Although Wnts act to stabilize ␤-catenin levels in the cytosol and nucleus, a multiprotein complex containing adenomatous polyposis coli, glycogen synthase kinase 3␤, and Axin1 or its homolog Axin2/Axil/conductin promotes ␤-catenin phosphorylation and subsequent proteasomal degradation. We found that the rat Axil gene was strongly induced upon neoplastic transformation of RK3E cells by mutant ␤-catenin or ␥-catenin or after ligand-induced activation of a ␤-catenin-estrogen receptor fusion protein. Expression of Wnt1 in murine breast epithelial cells activated the conductin gene, and human cancers with defective ␤-catenin regulation had elevated AXIN2 gene and protein expression. Expression of AXIN2/Axil was strongly repressed in cancer cells by restoration of wild type adenomatous polyposis coli function or expression of a dominant negative form of T cell factor (TCF)-4. TCF binding sites in the AXIN2 promoter played a key role in the ability of ␤-catenin to activate AXIN2 transcription. In contrast to AXIN2/Axil, expression of human or rat Axin1 homologs was nominally affected by ␤-catenin-TCF. Because Axin2 can inhibit ␤-catenin abundance and function, the data implicate AXIN2 in a negative feedback pathway regulating Wnt signaling. Additionally, although Axin1 and Axin2 have been thought to have comparable functions, the observation that Wnt pathway activation elevates AXIN2 but not AXIN1 expression suggests that there may be potentially significant functional differences between the two proteins.

In most urban public transit rail systems, passengers may need to make several interchanges between different lines to reach their destination. The design of coordinated timetables that enable smooth interchanges with minimal delay for all passengers is a very difficult task. This paper presents a mixed-integer-programming optimization model for this schedule synchronization problem for nonperiodic timetables that minimizes the interchange waiting times of all passengers. A novelty in our formulation is the use of binary variables that enable the correct representation of the waiting times to the “next available” train at the interchange stations. By adjusting trains' run times and station dwell times during their trips and their dispatch times, turnaround times at the terminals, and headways at the stations, our model can construct high-quality timetables that minimize transfer waiting times. We also discuss an optimization-based heuristic for the model. We have tested our algorithm for the Mass Transit Railway (MTR) system in Hong Kong, which runs six railway lines with many cross-platform interchange stations. Preliminary numerical results indicate that our approach improves the synchronization significantly compared with the current practice of using fixed headways and trip times. We also explore the trade-offs among different operational parameters and flexibility and their impact on overall passenger waiting times.

WOO, JEAN, JASON LEUNG, AND TIMOTHY KWOK. BMI, body composition, and physical functioning in older adults. Obesity. 2007;15:1886 -1894. Objective: Recent studies have emphasized the importance of muscle and fat mass in relation to age-related decline in physical function. Our objective was to determine whether BMI, as a surrogate measurement of fat mass, may be used as a measure of risk factor for physical functioning in older adults and whether body composition measurements confer any advantage over BMI. Research Methods and Procedures:Four thousand men and women Ն65 years of age living in the community, stratified by age and sex, underwent the following measurements: body composition by DXA; grip strength; and timed 6-m walk. Subjects were grouped into five categories of BMI using Asian criteria for health-related risks, and between-group differences in physical performance measures and body composition were analyzed using analysis of covariance adjusting for age, physical activity level, and presence of chronic disease. Results: Subjects in the two obese categories had a significantly greater number of instrumental activities of daily living (IADL) impairments compared with the underweight and normal-weight groups. Those with BMI Ն30 kg/m 2 had the worst walking performance, and the groups with BMI in the normal and overweight range had optimal performance. Fat mass, but not appendicular muscle mass, was associated with walking speed after adjusting for BMI. Discussion: Fat mass seems to be a more important factor than appendicular muscle mass in determining walking speed in community-living older adults, even after adjusting for BMI.