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Stipo Jurcevic,1 Pierre-Eric Juif,2 Colleen Hamid,3 Roseanna Greenlaw,3 Daniele D’Ambrosio,2 Jasper Dingemanse2 1Department of Biomedical Sciences, University of Westminster, London, UK; 2Department of Clinical Pharmacology, Actelion Pharmaceuticals Ltd, Allschwil, Switzerland; 3Division of Transplantation Immunology & Mucosal Biology, King’s College London, London, UK Abstract: This study investigated the effects of ponesimod, a selective S1P1 receptor modulator, on T lymphocyte subsets in 16 healthy subjects. Lymphocyte subset proportions and absolute numbers were determined at baseline and on Day 10, after once-daily administration of ponesimod (10 mg, 20 mg, and 40 mg each consecutively for 3 days) or placebo (ratio 3:1). The overall change from baseline in lymphocyte count was -1,292±340×106 cells/L and 275±486×106 cells/L in ponesimod- and placebo-treated subjects, respectively. This included a decrease in both T and B lymphocytes following ponesimod treatment. A decrease in naïve CD4+ T cells (CD45RA+CCR7+) from baseline was observed only after ponesimod treatment (-113±98×106 cells/L, placebo: 0±18×106 cells/L). The number of T-cytotoxic (CD3+CD8+) and T-helper (CD3+CD4+) cells was significantly altered following ponesimod treatment compared with placebo. Furthermore, ponesimod treatment resulted in marked decreases in CD4+ T-central memory (CD45RA-CCR7+) cells (-437±164×106 cells/L) and CD4+ T-effector memory (CD45RA-CCR7-) cells (-131±57×106 cells/L). In addition, ponesimod treatment led to a decrease of -228±90×106 cells/L of gut-homing T cells (CLA-integrin β7+). In contrast, when compared with placebo, CD8+ T-effector memory and natural killer (NK) cells were not significantly reduced following multiple-dose administration of ponesimod. In summary, ponesimod treatment led to a marked reduction in overall T and B cells. Further investigations revealed that the number of CD4+ cells was dramatically reduced, whereas CD8+ and NK cells were less affected, allowing the body to preserve critical viral-clearing functions. Keywords: ponesimod, multiple dose, S1P1 receptor, lymphocyte subsets, CD45RA/CCR7

Background. To determine if a lifestyle change program can modify behavior to reduce sleep and stress disorders. Methods. Analyses are based on 2,624 individuals aged 30 to 80 years from the Rockford, Illinois metropolitan area who completed a lifestyle evaluation at baseline and again after four weeks, following participation in a 40-hour educational course given over a four-week period. Participants receive instruction on the importance of making better lifestyle choices related to making long-term improvements in nutrition and physical activity and they learn ways to improve sleep and reduce stress in their lives. Results. Significant percent decreases were observed in the number experiencing selected sleep or stress disorders from baseline to four weeks later for "sleeps restlessly" (-59%), "suffers from insomnia" (-64%), "feels under pressure" (-37%), "easily emotionally upset" (-52%), and "feels fearful or depressed" (-61%). Experiencing a selected sleep or stress disorder after four weeks among those who had the disorder at baseline was significantly more likely in those not physically active and/or not having lowered their BMI after four weeks. Changes in alcohol consumption and smoking did not significantly contribute to changes in the disorders. Those who failed to lower their coffee/tea use after four weeks were significantly more likely to have a sleep disorder and be easily emotionally upset. Conclusions. Changes in lifestyle behaviors after attending an educational program significantly reduced sleep and stress disorders in as little as four weeks, primarily explained by decreasing BMI and/or increasing exercise. [ABSTRACT FROM AUTHOR]

PARKSERVICE is a telemedical application currently being validated in the EU. The objectives are to provide a combination of home clinical and social support for people with Parkinson's disease with a revolutionary walking aid that uses “visual cues” to enable improved mobility. Early results are presented and the outlook of home telemedicine and visual cueing for people with PD is discussed. [ABSTRACT FROM AUTHOR]

The greatest potential to improve public health lies in the ability of individuals to adopt healthful behaviors. The purpose of this study was to determine whether participation in a facilitator-based video version of the Coronary Health Improvement Project (CHIP) would improve health behaviors and significantly reduce employee health risks. Employees (n = 442) from six worksites in metropolitan Rockford, Illinois, were used in a pretest/posttest design. Employees self-selected to participate in a facilitator-based, CHIP video program. Participants received instruction twice a week, for 8 weeks, via 15 videos shown at each participating worksite. Demographic and biometric data (body weight, body mass index, blood lipids, blood pressure, and fasting blood glucose) were evaluated at baseline and at 8 weeks. All sites individually and collectively demonstrated significant and meaningful reductions in body weight, body mass index, total cholesterol, low-density lipoprotein cholesterol, triglycerides, and fasting blood glucose. Men demonstrated greater improvement than women, and individuals with higher baseline health risks experienced the greatest reductions in risk. The CHIP video program appears to be an effective method of lowering employee health risks. Future research is needed to determine how long these reductions may persist. [ABSTRACT FROM AUTHOR]

An edge ranking of a graph is a labeling of the edges using positive integers such that all paths between two edges with the same label contain an intermediate edge with a higher label. An edge ranking is optimal if the highest label used is as small as possible. The edge-ranking problem has applications in scheduling the manufacture of complex multipart products; it is equivalent to finding the minimum height edge-separator tree. In this paper we give the first polynomial-time algorithm to find an optimal edge ranking of a tree, placing the problem in P. An interesting feature of the algorithm is an unusual greedy procedure that allows us to narrow an exponential search space down to a polynomial search space containing an optimal solution. An NC algorithm is presented that finds an optimal edge ranking for trees of constant degree. We also prove that a natural decision problem emerging from our sequential algorithm is P-complete. [ABSTRACT FROM AUTHOR]