Daily physical activities and sports in adult survivors of childhood cancer and healthy controls: a population-based questionnaire survey.

BACKGROUND: Healthy lifestyle including sufficient physical activity may mitigate or prevent adverse long-term effects of childhood cancer. We described daily physical activities and sports in childhood cancer survivors and controls, and assessed determinants of both activity patterns. METHODOLOGY/PRINCIPAL FINDINGS: The Swiss Childhood Cancer Survivor Study is a questionnaire survey including all children diagnosed with cancer 1976-2003 at age 0-15 years, registered in the Swiss Childhood Cancer Registry, who survived ≥5 years and reached adulthood (≥20 years). Controls came from the population-based Swiss Health Survey. We compared the two populations and determined risk factors for both outcomes in separate multivariable logistic regression models. The sample included 1058 survivors and 5593 controls (response rates 78% and 66%). Sufficient daily physical activities were reported by 52% (n = 521) of survivors and 37% (n = 2069) of controls (p<0.001). In contrast, 62% (n = 640) of survivors and 65% (n = 3635) of controls reported engaging in sports (p = 0.067). Risk factors for insufficient daily activities in both populations were: older age (OR for ≥35 years: 1.5, 95CI 1.2-2.0), female gender (OR 1.6, 95CI 1.3-1.9), French/Italian Speaking (OR 1.4, 95CI 1.1-1.7), and higher education (OR for university education: 2.0, 95CI 1.5-2.6). Risk factors for no sports were: being a survivor (OR 1.3, 95CI 1.1-1.6), older age (OR for ≥35 years: 1.4, 95CI 1.1-1.8), migration background (OR 1.5, 95CI 1.3-1.8), French/Italian speaking (OR 1.4, 95CI 1.2-1.7), lower education (OR for compulsory schooling only: 1.6, 95CI 1.2-2.2), being married (OR 1.7, 95CI 1.5-2.0), having children (OR 1.3, 95CI 1.4-1.9), obesity (OR 2.4, 95CI 1.7-3.3), and smoking (OR 1.7, 95CI 1.5-2.1). Type of diagnosis was only associated with sports. CONCLUSIONS/SIGNIFICANCE: Physical activity levels in survivors were lower than recommended, but comparable to controls and mainly determined by socio-demographic and cultural factors. Strategies to improve physical activity levels could be similar as for the general population.

Promise for plant pest control: root-associated pseudomonads with insecticidal activities.

Insects are an important and probably the most challenging pest to control in agriculture, in particular when they feed on belowground parts of plants. The application of synthetic pesticides is problematic owing to side effects on the environment, concerns for public health and the rapid development of resistance. Entomopathogenic bacteria, notably Bacillus thuringiensis and Photorhabdus/Xenorhabdus species, are promising alternatives to chemical insecticides, for they are able to efficiently kill insects and are considered to be environmentally sound and harmless to mammals. However, they have the handicap of showing limited environmental persistence or of depending on a nematode vector for insect infection. Intriguingly, certain strains of plant root-colonizing Pseudomonas bacteria display insect pathogenicity and thus could be formulated to extend the present range of bioinsecticides for protection of plants against root-feeding insects. These entomopathogenic pseudomonads belong to a group of plant-beneficial rhizobacteria that have the remarkable ability to suppress soil-borne plant pathogens, promote plant growth, and induce systemic plant defenses. Here we review for the first time the current knowledge about the occurrence and the molecular basis of insecticidal activity in pseudomonads with an emphasis on plant-beneficial and prominent pathogenic species. We discuss how this fascinating Pseudomonas trait may be exploited for novel root-based approaches to insect control in an integrated pest management framework.

Expression of a plant-derived peptide harboring water-cleaning and antimicrobial activities.

Drinking water is currently a scarce world resource, the preparation of which requires complex treatments that include clarification of suspended particles and disinfection. Seed extracts of Moringa oleifera Lam., a tropical tree, have been proposed as an environment-friendly alternative, due to their traditional use for the clarification of drinking water. However, the precise nature of the active components of the extract and whether they may be produced in recombinant form are unknown. Here we show that recombinant or synthetic forms of a cationic seed polypeptide mediate efficient sedimentation of suspended mineral particles and bacteria. Unexpectedly, the polypeptide was also found to possesses a bactericidal activity capable of disinfecting heavily contaminated water. Furthermore, the polypeptide has been shown to efficiently kill several pathogenic bacteria, including antibiotic-resistant isolates of Staphylococcus, Streptococcus, and Legionella species. Thus, this polypeptide displays the unprecedented feature of combining water purification and disinfectant properties. Identification of an active principle derived from the seed extracts points to a range of potential for drinking water treatment or skin and mucosal disinfection in clinical settings.

TIE-2 and VEGFR Kinase Activities Drive Immunosuppressive Function of TIE-2-Expressing Monocytes in Human Breast Tumors.

PURPOSE: Tumor-associated TIE-2-expressing monocytes (TEM) are highly proangiogenic cells critical for tumor vascularization. We previously showed that, in human breast cancer, TIE-2 and VEGFR pathways control proangiogenic activity of TEMs. Here, we examine the contribution of these pathways to immunosuppressive activity of TEMs. EXPERIMENTAL DESIGN: We investigated the changes in immunosuppressive activity of TEMs and gene expression in response to specific kinase inhibitors of TIE-2 and VEGFR. The ability of tumor TEMs to suppress tumor-specific T-cell response mediated by tumor dendritic cells (DC) was measured in vitro. Characterization of TEM and DC phenotype in addition to their interaction with T cells was done using confocal microscopic images analysis of breast carcinomas. RESULTS: TEMs from breast tumors are able to suppress tumor-specific immune responses. Importantly, proangiogenic and suppressive functions of TEMs are similarly driven by TIE-2 and VEGFR kinase activity. Furthermore, we show that tumor TEMs can function as antigen-presenting cells and elicit a weak proliferation of T cells. Blocking TIE-2 and VEGFR kinase activity induced TEMs to change their phenotype into cells with features of myeloid dendritic cells. We show that immunosuppressive activity of TEMs is associated with high CD86 surface expression and extensive engagement of T regulatory cells in breast tumors. TIE-2 and VEGFR kinase activity was also necessary to maintain high CD86 surface expression levels and to convert T cells into regulatory cells. CONCLUSIONS: These results suggest that TEMs are plastic cells that can be reverted from suppressive, proangiogenic cells into cells that are able to mediate an antitumoral immune response. Clin Cancer Res; 19(13); 3439-49. ©2013 AACR.

Inhibition of glial cell proinflammatory activities by peroxisome proliferator-activated receptor gamma agonist confers partial protection during antimyelin oligodendrocyte glycoprotein demyelination in vitro.

Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a member of the nuclear hormone superfamily originally characterized as a regulator of adipocyte differentiation and lipid metabolism. In addition, PPAR-gamma has important immunomodulatory functions. If the effect of PPAR-gamma's activation in T-cell-mediated demyelination has been recently demonstrated, nothing is known about the role of PPAR-gamma in antibody-induced demyelination in the absence of T-cell interactions and monocyte/macrophage activation. Therefore, we investigated PPAR-gamma's involvement by using an in vitro model of inflammatory demyelination in three-dimensional aggregating rat brain cell cultures. We found that PPAR-gamma was not constitutively expressed in these cultures but was strongly up-regulated following demyelination mediated by antibodies directed against myelin oligodendrocyte glycoprotein (MOG) in the presence of complement. Pioglitazone, a selective PPAR-gamma agonist, partially protected aggregates from anti-MOG demyelination. Heat shock responses and the expression of the proinflammatory cytokine tumor necrosis factor-alpha were diminished by pioglitazone treatment. Therefore, pioglitazone protection seems to be linked to an inhibition of glial cell proinflammatory activities following anti-MOG induced demyelination. We show that PPAR-gamma agonists act not only on T cells but also on antibody-mediated demyelination. This may represent a significant benefit in treating multiple sclerosis patients.

Regulation of the DNA-binding and transcriptional activities of Xenopus laevis NFI-X by a novel C-terminal domain.

The nuclear factor I (NFI) family consists of sequence-specific DNA-binding proteins that activate both transcription and adenovirus DNA replication. We have characterized three new members of the NFI family that belong to the Xenopus laevis NFI-X subtype and differ in their C-termini. We show that these polypeptides can activate transcription in HeLa and Drosophila Schneider line 2 cells, using an activation domain that is subdivided into adjacent variable and subtype-specific domains each having independent activation properties in chimeric proteins. Together, these two domains constitute the full NFI-X transactivation potential. In addition, we find that the X. laevis NFI-X proteins are capable of activating adenovirus DNA replication through their conserved N-terminal DNA-binding domains. Surprisingly, their in vitro DNA-binding activities are specifically inhibited by a novel repressor domain contained within the C-terminal part, while the dimerization and replication functions per se are not affected. However, inhibition of DNA-binding activity in vitro is relieved within the cell, as transcriptional activation occurs irrespective of the presence of the repressor domain. Moreover, the region comprising the repressor domain participates in transactivation. Mechanisms that may allow the relief of DNA-binding inhibition in vivo and trigger transcriptional activation are discussed.

Playing Second Fiddle: Expert Advice and Decision-Making in Switzerland

This thesis concerns the role of scientific expertise in the decision-making process at the Swiss federal level of government. It aims to understand how institutional and issue-specific factors influence three things: the distribution of access to scientific expertise, its valuation by participants in policy for- mulation, and the consequence(s) its mobilization has on policy politics and design. The theoretical framework developed builds on the assumption that scientific expertise is a strategic resource. In order to effectively mobilize this resource, actors require financial and organizational resources, as well as the conviction that it can advance their instrumental interests within a particular action situation. Institutions of the political system allocate these financial and organizational resources, influence the supply of scientific expertise, and help shape the venue of its deployment. Issue structures, in turn, condition both interaction configurations and the way in which these are anticipated by actors. This affects the perceived utility of expertise mobilization, mediating its consequences. The findings of this study show that the ability to access and control scientific expertise is strongly concentrated in the hands of the federal administration. Civil society actors have weak capacities to mobilize it, and the autonomy of institutionalized advisory bodies is limited. Moreover, the production of scientific expertise is undergoing a process of professionalization which strengthens the position of the federal administration as the (main) mandating agent. Despite increased political polarization and less inclu- sive decision-making, scientific expertise remains anchored in the policy subsystem, rather than being used to legitimate policy through appeals to the wider population. Finally, the structure of a policy problem matters both for expertise mobilization and for the latter's impact on the policy process, be- cause it conditions conflict structures and their anticipation. Structured problems result in a greater overlap between the principal of expertise mobilization and its intended audience, thereby increasing the chance that expertise shapes policy design. Conversely, less structured problems, especially those that involve conflicts about values and goals, reduce the impact of expertise.

Using group role-playing games with gifted children and adolescents: A psychosocial intervention model

Gifted children develop asynchronously, often advanced for their age cognitively, but at or between their chronological and mental ages socially and emotionally (Robinson, 2008). In order to help gifted children and adolescents develop and practice social and emotional self-regulation skills, we investigated the use of an Adlerian play therapy approach during pen-and-paper role-playing games. Additionally, we used Goffman's (1961, 1974) social role identification and distance to encourage participants to experiment with new identities. Herein, we propose a psychosocial model of interactions during role-playing games based on Goffman's theory and Adlerian play therapy techniques, and suggest that role-playing games are an effective way of intervening with gifted children and adolescents to improve their intra- and interpersonal skills. We specifically targeted intrapersonal skills of exercising creativity, becoming self-aware, and setting individual goals by raising participants' awareness of their privately logical reasons for making decisions and their levels of social interest. We also targeted their needs and means of seeking significance in the group to promote collaboration and interaction skills with other gifted peers through role analysis, embracement, and distancing. We report results from a case study and conclude that role-playing games deserve more attention, both from researchers and clinical practitioners, because they encourage change while improving young clients' social and emotional development.

Spinal modulations accompany peripheral fatigue during prolonged tennis playing.

To examine the time course of alteration in neural process (spinal loop properties) during prolonged tennis playing, 12 competitive players performed a series of neuromuscular tests every 30 min during a 3-h match protocol. Muscle activation (twitch interpolation) and normalized EMG activity were assessed during maximal voluntary contraction (MVC) of plantar flexors. Spinal reflexes and M-waves were evoked at rest (i.e., H(max) and M(max) , respectively) and during MVC (i.e., H(sup) , V-wave, M(sup) , respectively). MVC torque declined significantly (P<0.001) across the match protocol, due to decrease (P<0.001) in muscle activation and in normalized EMG activity. The impairment in MVC was significantly correlated (r=0.77; P<0.05) with the decline in muscle activation. H(max) /M(max) (P<0.001), H(sup) /M(sup) (P<0.01) and V/M(sup) (P<0.05) ratios were depressed with fatigue and decreased by ∼80%, 46% and 61% at the end of exercise, respectively. Simultaneously, peak twitch torque and M-wave amplitude were significantly (P<0.01) altered with exercise, suggesting peripheral alterations. During prolonged tennis playing, the compromised voluntary strength capacity is linked to a reduced neural input to the working muscles. This central activation deficit partly results from a modulation in spinal loop properties.

Position of indapamide , a diuretic with vasorelaxant activities, in antihypertensive therapy.

Introduction: Diuretics play a pivotal role in the management of hypertension. A large experience has been accumulated with indapamide , a long-acting thiazide-like diuretic that lowers blood pressure (BP) primarily through its natriuretic diuretic effect. Some of its long-term antihypertensive efficacy may be due to calcium antagonist-like vasorelaxant activities. Indapamide has protecting effects in a variety of conditions associated with high cardiovascular risk, such as diabetes, left ventricular hypertrophy, nephropathy and stroke. It is highly effective in lowering BP, whether given alone or in combination. Indapamide is well tolerated and has the advantage of having no adverse impact on glucose and lipid metabolism. Today, thiazide-like diuretics are regarded more and more as preferred drugs, when diuretic therapy is required to lower BP. Areas covered: The aim of this paper is to review the experience accumulated with indapamide. It is limited to clinical studies that are relevant for the everyday management of hypertensive patients, whether or not they exhibit cardiovascular or renal disease. Expert opinion: Indapamide, because of its well-documented beneficial effects on cardiovascular and renal outcomes, represents a safe and valuable option for treating patients with high BP. There is, however, still room for new trials evaluating the combination of this diuretic with other types of antihypertensive drugs, in particular a calcium antagonist such as amlodipine. There is also the need to compare the indapamide-perindopril and indapamide-amlodipine combinations, in terms of antihypertensive efficacy, tolerability and effects on target organ damage and, ideally, on cardiovascular mortality.

Microbiological activities in moonmilk monitored using isothermal microcalorimetry (cave of Vers Chez le Brandt, Neuchatel, Switzerland)

Studies of the influence of microbial communities on calcium carbonate deposits mostly rely on classical or molecular microbiology, isotopic analyses, and microscopy. Using these techniques, it is difficult to infer microbial activities in such deposits. In this context, we used isothermal microcalorimetry, a sensitive and nondestructive tool, to measure microbial activities associated with moonmilk ex-situ. Upon the addition of diluted LB medium and other carbon sources to fresh moonmilk samples, we estimated the number of colony forming units per gram of moonmilk to be 4.8 3 105 6 0.2 3 105. This number was close to the classical plate counts, but one cannot assume that all active cells producing metabolic heat were culturable. Using a similar approach, we estimated the overall growth rate and generation time of the microbial community associated with the moonmilk upon addition of various carbon sources. The range of apparent growth rates of the chemoheterotrophic microbial community observed was between 0.025 and 0.067 h21 and generation times were between 10 and 27 hours. The highest growth rates were observed for citrate and diluted LB medium, while the highest carbon-source consumption rates were observed for low molecular weight organic acids (oxalate and acetate) and glycerol. Considering the rapid degradation of organic acids, glucose, and other carbon sources observed in the moonmilk, it is obvious that upon addition of nutrients during snow melting or rainfall these communities can have high overall activities comparable to those observed in some soils. Such communities can influence the physico-chemical conditions and participate directly or indirectly to the formation of moonmilk.