What’s Cooking? – Cognitive Training of Executive Function in the Elderly

Executive function involves the efficient and adaptive engagement of the control processes of updating, shifting, and inhibition (Miyake, 2000) to guide behavior toward a goal. It is associated with decrements in many other cognitive functions due to aging (West, 1996; Raz, 2000) with itself particularly vulnerable to the effect of aging (Treitz et al., 2007). Cognitive training in the form of structural experience with executive coordination demands exhibited effective enhancement in the elderly (Hertzog et al., 2008). The current study was thus aimed at the development and evaluation of a training regime for executive function in the elderly. The breakfast cooking task of Craik and Bialystok (2006) was adapted into a multitasking training task in a session (pre-test vs. post-test) by group (control vs. training). In the training condition, participants constantly switched, updated, and planned in order to control the cooking of several foods and concurrently performed a table setting secondary task. Training gains were exhibited on task related measures. Transfer effect was selectively observed on the letter–number sequencing and digit symbol coding test. The cooking training produced short term increase in the efficiency of executive control processing. These effects were interpreted in terms of the process overlap between the training and the transfer tasks

The p53-dependent apoptotic pathway of breast cancer cells (BC-M1) induced by the bis-type bioreductive compound aziridinylnaphthoquinone

INTRODUCTION: Several aziridinylbenzoquinone drugs have undergone clinical trials as potential antitumor drugs. These bioreductive compounds are designed to kill cells preferentially within the hypoxia tumor microenvironment. The bioreductive compound of bis-type naphthoquinone synthesized in our laboratory, 2-aziridin-1-yl-3-[(2-{2-[(3-aziridin-1-yl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)thio]ethoxy}ethyl)thio]naphthoquinone (AZ-1), had the most potent death effect on the breast cancer cells BC-M1 in our previous screening. In the present study, we determined that the mechanism of the death effect of BC-M1 cells induced by AZ-1 was mediated by the apoptosis pathway. METHODS: We evaluated the cytotoxicity of AZ-1 and the anti-breast cancer drugs tamoxifen and paclitaxel to BC-M1 cells and MCF-7 cells by the MTT assay and measured the apoptosis phenomena by Hoechst 33258 staining for apoptotic bodies. We also quantified the sub-G(1 )peak area and the ratio of the CH(2)/CH(3 )peak area of the cell membrane in BC-M1 cells by flow cytometry and (1)H-NMR spectra, respectively. The apoptosis-related protein expressions, including p53, p21, the RNA-relating protein T-cell restricted intracellular antigen-related protein, cyclin-dependent kinase 2 (cell cycle regulating kinase) and pro-caspase 3, were detected by western blot, and the caspase-3 enzyme activity was also quantified by an assay kit. RESULTS: AZ-1 induced two of the breast cancer cell lines, with IC(50 )= 0.51 μM in BC-M1 cells and with IC(50)= 0.57 μM in MCF-7 cells, and showed less cytotoxicity to normal fibroblast cells (skin fibroblasts) with IC(50)= 5.6 μM. There was a 10-fold difference between two breast cancer cell lines and normal fibroblasts. Of the two anti-breast cancer drugs, tamoxifen showed IC(50)= 0.12 μM to BC-M1 cells and paclitaxel had much less sensitivity than AZ-1. The expression of p53 protein increased from 0.5 to 1.0 μM AZ-1 and decreased at 2.0 μM AZ-1. The p21 protein increased from 0.5 μM AZ-1, with the highest at 2 μM AZ-1. Regarding the AZ-1 compound-induced BC-M1 cells mediating the apoptosis pathway, the apoptotic body formation, the sub-G(1 )peak area, the ratio of CH(2)/CH(3 )of phospholipids in the cell membrane and the enzyme activity of caspase-3 were all in direct proportion with the dose-dependent increase of the concentration of AZ-1. The death effect-related proteins, including T-cell restricted intracellular antigen-related protein, cyclin-dependent kinase 2, and pro-caspase-3, all dose-dependently decreased with AZ-1 concentration. CONCLUSIONS: The AZ-1-induced cell death of BC-M1 cells mediating the apoptosis pathway might be associated with p53 protein expression, and AZ-1 could have the chance to be a candidate drug for anti-breast cancer following more experimental evidence, such as animal models

The efficiency of endothelin receptor antagonist bosentan for pulmonary arterial hypertension associated with congenital heart disease: A systematic review and meta-analysis

BACKGROUND: Oral bosentan has been widely applied in pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD). A systemic review and meta-analysis was conducted for a therapeutic evaluation of oral bosentan in both adult and pediatric patients with PAH-CHD. The acute responses and a long-term effect were respectively assessed in a comparison with baseline characteristics, and the improvement of exercise tolerance was analyzed. METHODS: PubMed, Medline, Embase, and Cochrane Central Register of clinical controlled trails or observational studies have been searched for a recording of bosentan effects on the PAH-CHD participants. For mortality and rate of adverse events (AEs), it was described in detail. Randomized-effects model or fixed-effects model was used to calculate different effective values with a sensitivity analysis. RESULTS: Seventeen studies were pooled in this review, and 3 studies enrolled the pediatric patients. Among all studies, 456 patients were diagnosed with PAH-CHD, and 91.7% were treated with oral bosentan. With a term less than 6 months of bosentan therapy, there existed a significant improvement in 6-minute walk distance (6MWD) and the World Health Organization functional class (WHO-FC), but no such differences in Borg dyspnea index scores (BDIs) and the resting oxygen saturation (SpO2). Although with a prolonged treatment, not only 6MWD and FC, but also the resting SpO2 and heart rate were changed for a better exercise capability. Additionally, compared with the basic cardiopulmonary hemodynamics, it showed a statistically significant difference in mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance index (PVRi). Although a limitation of pooled studies with comparative outcomes of different terms, outcomes presented a lower WHO-FC which contributes to a success in a prolonged treatment. CONCLUSIONS: Bosentan in PAH-CHD is well established and still requires clinical trials for an identification of its efficiency on CHD patients for an optimized period lessening a serious complication and the common AEs

Reconstruction of phyletic trees by global alignment of multiple metabolic networks

Background: In the last decade, a considerable amount of research has been devoted to investigating the phylogenetic properties of organisms from a systems-level perspective. Most studies have focused on the classification of organisms based on structural comparison and local alignment of metabolic pathways. In contrast, global alignment of multiple metabolic networks complements sequence-based phylogenetic analyses and provides more comprehensive information. Results: We explored the phylogenetic relationships between microorganisms through global alignment of multiple metabolic networks. The proposed approach integrates sequence homology data with topological information of metabolic networks. In general, compared to recent studies, the resulting trees reflect the living style of organisms as well as classical taxa. Moreover, for phylogenetically closely related organisms, the classification results are consistent with specific metabolic characteristics, such as the light-harvesting systems, fermentation types, and sources of electrons in photosynthesis. Conclusions: We demonstrate the usefulness of global alignment of multiple metabolic networks to infer phylogenetic relationships between species. In addition, our exhaustive analysis of microbial metabolic pathways reveals differences in metabolic features between phylogenetically closely related organisms. With the ongoing increase in the number of genomic sequences and metabolic annotations, the proposed approach will help identify phenotypic variations that may not be apparent based solely on sequence-based classification.National Institutes of Health (U.S.) (Grant GM081871

Validation of bidimensional measurement in nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>Our previous study showed a close relationship between computed tomography (CT)-derived bidimensional measurement of primary tumor and retropharyngeal nodes (BDMprn) and gross tumor volume of primary tumor and retropharyngeal nodes (GTVprn) in nasopharyngeal carcinoma (NPC) and better prognosis for NPC patients with smaller BDMprn. In this study, we report the results on of a study to validate the use of BDM in a separate cohort of NPC patients.</p> <p>Methods</p> <p>We retrospectively reviewed 103 newly diagnosed NPC cases who were treated with radiotherapy/concurrent chemoradiotherapy (CCRT) or CCRT with adjuvant chemotherapy from 2002 to 2009. We used magnetic resonance imaging (MRI) to measure BDMprn. We calculated overall survival, recurrence-free and distant metastasis-free survival curves and set a BDMprn cut off point to categorize patients into a high- or low-risk group. We then used Cox proportional hazard model to evaluate the prognostic influence of BDMprn after correcting age, gender and chemotherapy status.</p> <p>Results</p> <p>After adjusting for age, gender, and chemotherapy status, BDMprn remained an independent prognostic factor for distant metastasis [Hazard ratio (HR) = 1.046; <it>P </it>= 0.042] and overall survival (HR = 1.012; <it>P </it>= 0.012). Patients with BDMprn < 15 cm²had a greater 3-year overall survival rate than those with BDMprn ≧ 15 cm²(92.3% vs. 73.7%; <it>P </it>= 0.009). They also had a greater 3-year distant metastasis-free survival (94% vs.75%; <it>P </it>= 0.034).</p> <p>Conclusion</p> <p>The predictive ability of BDMprn was validated in a separate NPC cohort. A BDMprn of 15 cm²can be used to separate NPC patients into high- and low-risk groups and predict survival rates and metastasis potential. It can, therefore, be used as a reference to design clinical trials, predict prognosis, and make treatment decisions.</p