56 resultados para survival of healthy and malignant cells


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Cross-sectional studies have indicated that alterations in social functioning, particularly interpersonal functioning, are associated with the occurrence of psychotic symptoms and experiences at different levels of the extended psychosis phenotype (ranging from population psychometric expression of liability to overt psychotic disorder). However, more research is needed on the development of this association over time

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Rates of overweight and obesity increase significantly whilst children and young people are in out-of-home care. This paper provides the protocol for a study, funded by the Australian Research Council (2012–2014), being conducted to evaluate the effectiveness of a Healthy Eating and Active Living intervention programme for adolescents who live in out-of-home residential care. This randomised trial will be conducted with 118 adolescents aged 13–17 years of age in out-of-home residential care and the residential staff who look after them. Adolescents' eating habits, physical activity levels, psychological well-being, body dissatisfaction and weight status will be assessed at baseline, immediately post the programme (which runs for 6 months), and again 12 months post baseline. Similar measures will be obtained from residential carers (across the same time points). If effective, this programme could be implemented as usual care to modify levels of obesity amongst these vulnerable young people.

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Granulocyte-colony stimulating factor (G-CSF) increases recovery of rodent skeletal muscles after injury, and increases muscle function in rodent models of neuromuscular disease. However, the mechanisms by which G-CSF mediates these effects are poorly understood. G-CSF acts by binding to the membrane spanning G-CSFR and activating multiple intracellular signaling pathways. Expression of the G-CSFR within the haematopoietic system is well known, but more recently it has been demonstrated to be expressed in other tissues. However, comprehensive characterization of G-CSFR expression in healthy and diseased skeletal muscle, imperative before implementing G-CSF as a therapeutic agent for skeletal muscle conditions, has been lacking. Here we show that the G-CSFR is expressed in proliferating C2C12 myoblasts, differentiated C2C12 myotubes, human primary skeletal muscle cell cultures and in mouse and human skeletal muscle. In mdx mice, a model of human Duchenne muscular dystrophy (DMD), G-CSF mRNA and protein was down-regulated in limb and diaphragm muscle, but circulating G-CSF ligand levels were elevated. G-CSFR mRNA in the muscles of mdx mice was up-regulated however steady-state levels of the protein were down-regulated. We show that G-CSF does not influence C2C12 myoblast proliferation, differentiation or phosphorylation of Akt, STAT3, and Erk1/2. Media change alone was sufficient to elicit increases in Akt, STAT3, and Erk1/2 phosphorylation in C2C12 muscle cells and suggest previous observations showing a G-CSF increase in phosphoprotein signaling be viewed with caution. These results suggest that the actions of G-CSF may require the interaction with other cytokines and growth factors in vivo, however these data provides preliminary evidence supporting the investigation of G-CSF for the management of muscular dystrophy.

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Novel TiO2 single crystalline nanorods were synthesized by electrospinning and hydrothermal treatment. The role of the TiO2 nanorods on TiO2 nanoparticle electrode in improvement of light harvesting and photovoltaic properties of dye-sensitized solar cells (DSSCs) was examined. Although the TiO2 nanorods had lower dye loading than TiO2 nanoparticle, they showed higher light utilization behaviour. Electron transfer in TiO2 nanorods received less resistance than that in TiO2 nanoparticle aggregation. By just applying a thin layer of TiO2 nanorods on TiO2 nanoparticle working electrode, the DSSC device light harvesting ability and energy conversion efficiency were improved significantly. The thickness of the nanorod layer in the working electrode played an important role in determining the photovoltaic property of DSSCs. An energy conversion efficiency as high as 6.6% was found on a DSSC device with the working electrode consisting of a 12 μm think TiO2 nanoparticle layer covered with 3 μm thick TiO2 nanorods. The results obtained from this study may benefit further design of highly efficient DSSCs.

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The pharmacological effects of hydroxamic acids are partially attributed to their ability to serve as HNO and/or NO donors under oxidative stress. Previously, it was concluded that oxidation of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) by the metmyoglobin/H2O2 reaction system releases NO, which was based on spin trapping of NO and accumulation of nitrite. Reinvestigation of this system demonstrates the accumulation of N2O, which is a marker of HNO formation, at similar rates under normoxia and anoxia. In addition, the yields of nitrite that accumulated in the absence and the presence of O2 did not differ, implying that the source of nitrite is other than autoxidation of NO. In this system metmyoglobin is instantaneously and continuously converted into compound II, leading to one-electron oxidation of SAHA to its respective transient nitroxide radical. Studies using pulse radiolysis show that one-electron oxidation of SAHA (pKa=9.56 ± 0.04) yields the respective nitroxide radical (pKa=9.1 ± 0.2), which under all experimental conditions decomposes bimolecularly to yield HNO. The proposed mechanism suggests that compound I oxidizes SAHA to the respective nitroxide radical, which decomposes bimolecularly in competition with its oxidation by compound II to form HNO. Compound II also oxidizes HNO to NO and NO to nitrite. Given that NO, but not HNO, is an efficient hypoxic cell radiosensitizer, we hypothesized that under an oxidizing environment SAHA might act as a NO donor and radiosensitize hypoxic cells. Preincubation of A549 and HT29 cells with 2.5 μM SAHA for 24h resulted in a sensitizer enhancement ratio at 0.01 survival levels (SER0.01) of 1.33 and 1.59, respectively. Preincubation of A549 cells with oxidized SAHA had hardly any effect and, with 2mM valproic acid, which lacks the hydroxamate group, resulted in SER0.01=1.17. Preincubation of HT29 cells with SAHA and Tempol, which readily oxidizes HNO to NO, enhanced the radiosensitizing effect of SAHA. Pretreatment with SAHA blocked A549 cells at the G1 stage of the cell cycle and upregulated γ-H2AX after irradiation. Overall, we conclude that SAHA enhances tumor radioresponse by multiple mechanisms that might also involve its ability to serve as a NO donor under oxidizing environments.

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BACKGROUND: Fiscal strategies are increasingly considered upstream nutrition promotion measures. However, few trials have investigated the effectiveness or cost effectiveness of pricing manipulations on diet in real-world settings. OBJECTIVE: We assessed the effects on fruit, vegetable, and beverage purchasing and consumption of a 20% price-reduction intervention, a tailored skills-based behavior-change intervention, and a combined intervention compared with a control condition. DESIGN: The Supermarket Healthy Eating for Life trial was a randomized controlled trial conducted over 3 mo [baseline (time 1) to postintervention (time 2) with a 6-mo follow-up (time 3)]. Female primary household shoppers in Melbourne, Australia, were randomly assigned to a 1) skill-building (n = 160), 2) price-reduction (n = 161), 3) combined skill-building and price-reduction (n = 160), or 4) control (n = 161) group. Supermarket transaction data and surveys were used to measure the following study outcomes: fruit, vegetable, and beverage purchases and self-reported fruit and vegetable consumption at each time point. RESULTS: At 3 mo (time 2), price reduction-alone participants purchased more total vegetables and frozen vegetables than did controls. Price reduction-alone and price reduction-plus-skill-building participants purchased more fruit than did controls. Relative to controls, in the price-reduction group, total vegetable consumption increased by 233 g/wk (3.1 servings or 15% more than at baseline), and fruit purchases increased by 364 g/wk (2.4 servings; 35% more than at baseline). Increases were not maintained 6 mo postintervention (time 3). Price reduction-alone participants showed a tendency for a slight increase in fruit consumption at time 2 (P = 0.09) that was maintained at time 3 (P = 0.014). No intervention improved purchases of bottled water or low-calorie beverages. CONCLUSIONS: A 20% price reduction in fruit and vegetables resulted in increased purchasing per household of 35% for fruit and 15% for vegetables over the price-reduction period. These findings show that price modifications can directly increase produce purchases. The Supermarket Healthy Eating for Life trial was registered at Current Controlled Trials Registration as ISRCTN39432901.

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OBJECTIVE: Given the high prevalence of overweight/obesity among young people in residential out-of-home care (OOHC), and as their carers are in loco parentis, this research aimed: 1) to examine the healthy lifestyle cognitions and behaviours of residential carers; and 2) to describe resources needed to improve diet and/or physical activity outcomes for residents. METHODS: Cross-sectional data were collected from 243 residential carers. Measures included: demographics; knowledge of dietary/physical activity recommendations; self-reported encouragement/importance of health behaviours; physical activity/screen time (at work); unit 'healthiness'; and necessary resources for creating a healthy environment. RESULTS: Staff placed importance on the residents eating well and being physically active. However, examination of carer knowledge found significant gaps in staff education. Three key priority areas were identified to help build a healthy food and activity environment in residential OOHC: funding, professional development and policy. CONCLUSION: Carer knowledge of healthy lifestyles can be improved and they need to be well resourced to ensure children in public care settings live in a healthy environment. IMPLICATIONS: These findings may inform the development of ongoing professional development to improve carers' health literacy, as well as policy to support dietary/activity guidelines for the OOHC sector.

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Immobility plus preexisting chronic disease or acute trauma can activate the coagulation system, thus increasing the risk for thromboembolic events. The effects of long-term bed-rest immobility and microgravity on the coagulation system of healthy persons (e.g., during crewed Mars missions) have not yet been studied. The main objective of the second Berlin BedRest Study (BBR2-2) "Coagulation Part" was to investigate adaptations of the hemostatic system during long-term bed rest (60 days) under simulated microgravity (6° head-down-tilt [6°HDT]) and after mobilization in three different volunteer groups (randomly assigned to CTR= inactive control group; RE= resistive exercise only group; and RVE= resistive exercise with whole-body vibration group). In 24 males (aged 21-45 years), before, during, and after long-term bed rest, key parameters of coagulation were measured from venous blood samples: D-dimer (DD), thrombin-antithrombin III complex (TAT), and prothrombin fragment F1 + 2 (PT-F1 + 2). Additionally, modified rotational thrombelastometry (ROTEM (®) ) analysis was performed. Times of exploratory analyses were as follows: baseline data collection 2 days before bed rest (BDC-2); eight different days of 6°HDT bed rest (HDT1-HDT60), and two different days after reambulation (R + 3 and R + 6). We found significant changes in DD, TAT, and PT-F1 + 2 over the total time course, but no consistent effect of physical interventions (RE, RVE) on these parameters. Notably, no parameter reached levels indicative of intravascular thrombin formation. All ROTEM® parameters remained within the normal range and no pathological traces were found. Sixty days of 6°HDT bed rest are not associated with pronounced activation of the coagulation system indicative of intravascular thrombus formation in healthy volunteers independent of the training type during the bed rest.

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Research Question/Issue: This study examines the relevance of currently accepted best practice recommendations regarding board structure on the survival likelihood of new economy initial public offering companies. We argue that industry context determines governance outcomes. Research Findings/Insights: We study 125 Australian new economy firms listed between 1994 and 2002. Each firm is tracked until the end of 2007 for monitoring their survival. We find that board independence is associated with an increase in the likelihood of corporate survival. We also find that the benefits of board independence increase at a decreasing rate. Theoretical/Academic Implications: The standard best practice recommendation of board independence stems from the monitoring role of directors and is based on agency theory. The results from our study suggest that the recommendation regarding board independence does not work well for new economy firms. While the agency theory based model implies a monotonic relation between board independence and performance, our research suggests that the relationship is nonlinear. This variation occurs because of increased monitoring costs faced by outsiders due to higher information asymmetry and complexity of new economy firms. Our empirical results suggest that inside directors play a complementary role to outsiders in mitigating firm failure. Practitioner/Policy Implications: Our research offers insights to policy makers who are interested in setting best practice standards regarding board structure. Our research suggests that firm/industry characteristics play a crucial role in determining the optimal board structure. In firms/industries where outsiders face significantly higher information processing costs, insiders can play a valuable complementary role to outsiders in enhancing the effectiveness of the board. Thus future hard or soft regulations related to board structure should consider industry context.

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The role of circulating tumor cells (CTCs) in disease diagnosis, prognosis, monitoring of the therapeutic efficacy, and clinical decision making is immense and has attracted tremendous focus in the last decade. We designed and fabricated simple, flat channel microfluidic devices polydimethylsiloxane (PDMS based) functionalized with locked nucleic acid (LNA) modified aptamers (targeting epithelial cell adhesion molecule (EpCAM) and nucleolin expression) for quick and efficient capture of CTCs and cancer cells. With optimized flow rates (10 μl/min), it was revealed that the aptamer modified devices offered reusability for up to six times while retaining optimal capture efficiency (>90%) and specificity. High capture sensitivity (92%) and specificity (100%) was observed in whole blood samples spiked with Caco-2 cells (10-100 cells/ml). Analysis of blood samples obtained from 25 head and neck cancer patients on the EpCAM LNA aptamer functionalized chip revealed that an average count of 5 ± 3 CTCs/ml of blood were captured from 22/25 samples (88%). EpCAM intracellular domain (EpICD) immunohistochemistry on 9 oral squamous cell carcinomas showed the EpICD positivity in the tumor cells, confirming the EpCAM expression in CTCs from head and neck cancers. These microfluidic devices also maintained viability for in vitro culture and characterization. Use of LNA modified aptamers provided added benefits in terms of cost effectiveness due to increased reusability and sustainability of the devices. Our results present a robust, quick, and efficient CTC capture platform with the use of simple PDMS based devices that are easy to fabricate at low cost and have an immense potential in cancer diagnosis, prognosis, and therapeutic planning.