Pedometry and 'peer support' in older Chinese adults: a 12-month cluster randomised controlled trial

Session - Exercise/RehabilitationResearch Dissemination ReportsThere is a need to increase physical activity to attenuate age-related morbidity. This 12-month factorial design cluster trial randomized 399 volunteers from 24 centres to buddy peer support, pedometry, or control group. Data were anaysed using last-observation carried-forward and intention-to-treat methods. Compared to the controls, participants in the pedometry group increased their levels of physical activity energy expenditure significantly, as did those in the buddy group. As recorded by the International Physical Activity Questionnaire [IPAQ], the respective increases amounted to 1820 (95% confidence interval [CI], 1360-2290) and 1260 (95% CI, 780-17 460) metabolic equivalent of task (MET).min.wk-1. The buddy group also had significantly improved aerobic fitness after adjustment for body weight (12%; 95% CI, 4-21%), but this did not attain significance in the pedometry group (7%; 95% CI, -1 to 15%). Our results suggest that recourse to pedometers and the buddy peer support system is simple means of increasing physical activity in older subjects.published_or_final_versio

Comparing Signal Setting Design Methods through emissions and fuel consumption performance indicators

In order to address the Signal Setting Design at urban level two main approaches may be pursued: the coordination and the synchronisation approaches depending on the steps considered for the optimisation of decision variables (two steps vs. one step). Furthermore, in terms of objective functions mono-criterion or multi-criteria may be adopted. In this paper the coordination approach is implemented considering the multi-criteria optimisation at single junctions and mono-criterion optimisation at network level whereas the synchronisation is implemented considering the mono-criterion optimisation. The main purpose of the paper is the evaluation of the performances of two strategies not only considering indicators such as the total delay, the queue length etc. but also considering other indicators such as the emissions and the fuel consumption. The methodological framework is composed by three stages: (i) the decision variables (green timings and offsets) computation through optimisation methods; (ii) the implementation of optimal signal settings in a microscopic traffic flow simulator (“Simulation of Urban MObility”-SUMO); (iii) the estimation of emissions and fuel consumption indicators

Friedreich ataxia patient tissues exhibit increased 5-hydroxymethylcytosine modification and decreased CTCF binding at the FXN locus

© 2013 Al-Mahdawi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Friedreich ataxia (FRDA) is caused by a homozygous GAA repeat expansion mutation within intron 1 of the FXN gene, which induces epigenetic changes and FXN gene silencing. Bisulfite sequencing studies have identified 5-methylcytosine (5 mC) DNA methylation as one of the epigenetic changes that may be involved in this process. However, analysis of samples by bisulfite sequencing is a time-consuming procedure. In addition, it has recently been shown that 5-hydroxymethylcytosine (5 hmC) is also present in mammalian DNA, and bisulfite sequencing cannot distinguish between 5 hmC and 5 mC.The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number 242193/EFACTS (CS), the Wellcome Trust [089757] (SA) and Ataxia UK (RMP) to MAP

DHODH modulates transcriptional elongation in the neural crest and melanoma

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation

PH-Sensitive polymer matrix with immobilized indicator ion pairs

A new sensor material for monitoring pH in aqueous solutions is described. It is based on lipophilic ion pairs consisting of an anionic pH indicator Bromocresol Green and a quaternary ammonium cation cetyltrimethylammonium. The ion pairs are homogeneously distributed inside the plasticized PVC membrane. The change of pH in an aqueous solution causes the change of optical property of the indicator immobilized on the plasticized PVC membrane. The plasticized PVC membrane is sensitive in a pH range from 4.0 to 6.0

The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

Peer reviewedPublisher PD

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation

Crystal Structure of a Novel Esterase Rv0045c from Mycobacterium tuberculosis

There are at least 250 enzymes in Mycobacterium tuberculosis (M. tuberculosis) involved in lipid metabolism. Some of the enzymes are required for bacterial survival and full virulence. The esterase Rv0045c shares little amino acid sequence similarity with other members of the esterase/lipase family. Here, we report the 3D structure of Rv0045c. Our studies demonstrated that Rv0045c is a novel member of α/β hydrolase fold family. The structure of esterase Rv0045c contains two distinct domains: the α/β fold domain and the cap domain. The active site of esterase Rv0045c is highly conserved and comprised of two residues: Ser154 and His309. We proposed that Rv0045c probably employs two kinds of enzymatic mechanisms when hydrolyzing C-O ester bonds within substrates. The structure provides insight into the hydrolysis mechanism of the C-O ester bond, and will be helpful in understanding the ester/lipid metabolism in M. tuberculosis

Psychometric assessment of HIV/STI sexual risk scale among MSM: A Rasch model approach

<p>Abstract</p> <p>Background</p> <p>Little research has assessed the degree of severity and ordering of different types of sexual behaviors for HIV/STI infection in a measurement scale. The purpose of this study was to apply the Rasch model on psychometric assessment of an HIV/STI sexual risk scale among men who have sex with men (MSM).</p> <p>Methods</p> <p>A cross-sectional study using respondent driven sampling was conducted among 351 MSM in Shenzhen, China. The Rasch model was used to examine the psychometric properties of an HIV/STI sexual risk scale including nine types of sexual behaviors.</p> <p>Results</p> <p>The Rasch analysis of the nine items met the unidimensionality and local independence assumption. Although the person reliability was low at 0.35, the item reliability was high at 0.99. The fit statistics provided acceptable infit and outfit values. Item difficulty invariance analysis showed that the item estimates of the risk behavior items were invariant (within error).</p> <p>Conclusions</p> <p>The findings suggest that the Rasch model can be utilized for measuring the level of sexual risk for HIV/STI infection as a single latent construct and for establishing the relative degree of severity of each type of sexual behavior in HIV/STI transmission and acquisition among MSM. The measurement scale provides a useful measurement tool to inform, design and evaluate behavioral interventions for HIV/STI infection among MSM.</p