998 resultados para drug transformation


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The behaviour of cells cultured within three-dimensional (3D) structures rather than onto two-dimensional (2D) culture plastic more closely reflects their in vivo responses. Consequently, 3D culture systems are becoming crucial scientific tools in cancer cell research. We used a novel 3D culture concept to assess cell-matrix interactions implicated in carcinogenesis: a synthetic hydrogel matrix equipped with key biomimetic features, namely incorporated cell integrin-binding motifs (e.g. RGD peptides) and the ability of being degraded by cell-secreted proteases (e.g. matrix metalloproteases). As a cell model, we chose epithelial ovarian cancer, an aggressive disease typically diagnosed at an advanced stage when chemoresistance occurs. Both cell lines used (OV-MZ-6, SKOV-3) proliferated similarly in 2D, but not in 3D. Spheroid formation was observed exclusively in 3D when cells were embedded within hydrogels. By exploiting the design flexibility of the hydrogel characteristics, we showed that proliferation in 3D was dependent on cell-integrin engagement and the ability of cells to proteolytically remodel their extracellular microenvironment. Higher survival rates after exposure to the anti-cancer drug paclitaxel were observed in cell spheroids grown in hydrogels (40-60%) compared to cell monolayers in 2D (20%). Thus, 2D evaluation of chemosensitivity may not reflect pathophysiological events seen in patients. Because of the design flexibility of their characteristics and their stability in long-term cultures (28 days), these biomimetic hydrogels represent alternative culture systems for the increasing demand in cancer research for more versatile, physiologically relevant and reproducible 3D matrices.

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This study investigated a novel drug delivery system (DDS), consisting of polycaprolactone (PCL) or polycaprolactone 20% tricalcium phosphate (PCL-TCP) biodegradable scaffolds, fibrin Tisseel sealant and recombinant bone morphogenetic protein-2 (rhBMP-2) for bone regeneration. PCL and PCL-TCP-fibrin composites displayed a loading efficiency of 70% and 43%, respectively. Fluorescence and scanning electron microscopy revealed sparse clumps of rhBMP-2 particles, non-uniformly distributed on the rods’ surface of PCL-fibrin composites. In contrast, individual rhBMP-2 particles were evident and uniformly distributed on the rods’ surface of the PCL-TCP-fibrin composites. PCL-fibrin composites loaded with 10 and 20 μg/ml rhBMP-2 demonstrated a triphasic release profile as quantified by an enzyme-linked immunosorbent assay (ELISA). This consisted of burst releases at 2 h, and days 7 and 16. A biphasic release profile was observed for PCL-TCP-fibrin composites loaded with 10 μg/ml rhBMP-2, consisting of burst releases at 2 h and day 14. PCL-TCP-fibrin composites loaded with 20 μg/ml rhBMP-2 showed a tri-phasic release profile, consisting of burst releases at 2 h, and days 10 and 21. We conclude that the addition of TCP caused a delay in rhBMP-2 release. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and alkaline phosphatase assay verified the stability and bioactivity of eluted rhBMP-2 at all time points

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Cancer-related fatigue (CRF) is one of themost debilitating symptoms in patients with cancer. It is prevalent at the time of diagnosis and during and after antineoplastic treatment and in patients with advanced disease. The multifactorial and complex nature of CRF makes it challenging for health professionals to identify a clear underlying mechanism and manage this symptom effectively. Often, the management plan for CRF (whether pharmacological or nonpharmacological) can be further complicated by the coexistence of other symptoms. This systematic review1 is therefore important in informing health professionals on the effectiveness of pharmacological management for CRF.

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Purpose - The cumulative impacts of the knowledge economy together with the emerging dominance of knowledge-intensive sectors, have led to an unprecedented period of socio-economic and spatial restructuring. As a result, the paradigm of knowledge-based urban development (KBUD) has emerged as a development strategy to guide knowledge-based economic transformation (Knight, 1995; Yigitcanlar, 2007). Notwithstanding widespread government commitment and financial investment, in many cases providing the enabling circumstances for KUBUD has proven a complicated task as institutional barriers remain. Researchers and practitioners advocate that the way organisations work and their institutional relationships, policies and programs, will have a significant impact on a regions capacity to achieve KBUD (Savitch, 1998; Savitch and Kantor, 2002; Keast and Mandell, 2009). In this context, building organisational capacity is critical to achieving institutional change and bring together all of the key actors and sources, for the successful development, adoption, and implementation of knowledge-based development of a city (Yigitcanlar, 2009). Design/methodology/approach - There is a growing need to determine the complex inter-institutional arrangements and intra-organisational interactions required to advance urban development within the knowledge economy. In order to design organisational capacity-building strategies, the associated attributes of good capacity must first be identified. The paper, with its appraisal of knowledge-based urban development, scrutinises organisational capacity and institutional change in Brisbane. As part of the discussion of the case study findings, the paper describes the institutional relationships, policies, programs and funding streams, which are supporting KBUD in the region. Originality/value - In consideration that there has been limited investigation into the institutional lineaments required to provide the enabling circumstances for KBUD, the broad aim of this paper is to discover some good organisational capacity attributes, achieved through a case study of Brisbane. Practical implications - It is anticipated that the findings of the case study will contribute to moving the discussion on the complex inter-institutional arrangements and intra-organisaational interactions required for KBUD, beyond a position of rhetoric.

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A range of interventions are being implemented in Australia to apprehend and deter drug driving behaviour, in particular the recent implementation of random roadside drug testing procedures in Queensland. Given this countermeasure has a strong deterrence foundation, it is of interest to determine whether deterrence-based perceptual factors are influencing this offending behaviour or whether self-reported drug driving is heavily dependent upon illicit substance consumption levels and past offending behaviour. This study involves a sample of Queensland motorists (N = 898) who completed a self-report questionnaire that collected a range of information, including drug driving and drug consumption practices, conviction history, and perceptual deterrence factors. The aim was to examine what factors influence current drug driving behaviours. Analysis of the collected data revealed that approximately 20% of participants reported drug driving at least once in the last six months. Overall, there was considerable variability in the respondents' perceptions regarding the certainty, severity and swiftness of legal sanctions, although the largest proportion of the sample did not consider such sanctions to be certain, severe or swift. In regard to predicting those who intended to drug drive again in the future, a combination of perceptual and behavioural-based factors were associated with such intentions. However, a closer examination revealed that behaviours, rather than perceptions, proved to have a greater level of influence on the current sample's future intentions to offend. This paper further outlines the major findings of the study and highlights that multi-modal interventions are most likely required to reduce the prevalence of drug driving on public roads.

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A consistent finding in the literature is that males report greater usage of drugs and subsequently greater amounts of drug driving. Research also suggests that vicarious influences may be more pertinent to males than to females. Utilising Stafford and Warr’s (1993) reconceptualization of deterrence theory, this study sought to determine if the relative deterrent impact of zero-tolerance drug driving laws is disparate between genders. A sample of motorists’ (N = 899) completed a self-report questionnaire assessing participants frequency of drug driving and personal and vicarious experiences with punishment and punishment avoidance. Results show that males were significantly more likely to report future intentions of drug driving. Additionally, vicarious experiences of punishment avoidance was a more influential predictor of future drug driving instances for males with personal experiences of punishment avoidance a more influential predictor for females. These findings can inform gender sensitive media campaigns and interventions for convicted drug drivers.

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Several key issues need to be resolved before an efficient and reproducible Agrobacterium-mediated sugarcane transformation method can be developed for a wider range of sugarcane cultivars. These include loss of morphogenetic potential in sugarcane cells after Agrobacterium-mediated transformation, effect of exposure to abiotic stresses during in vitro selection, and most importantly the hypersensitive cell death response of sugarcane (and other nonhost plants) to Agrobacterium tumefaciens. Eight sugarcane cultivars (Q117, Q151, Q177, Q200, Q208, KQ228, QS94-2329, and QS94-2174) were evaluated for loss of morphogenetic potential in response to the age of the culture, exposure to Agrobacterium strains, and exposure to abiotic stresses during selection. Corresponding changes in the polyamine profiles of these cultures were also assessed. Strategies were then designed to minimize the negative effects of these factors on the cell survival and callus proliferation following Agrobacterium-mediated transformation. Some of these strategies, including the use of cell death protector genes and regulation of intracellular polyamine levels, will be discussed.

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Background: A State-based industry in Australia is in the process of developing a programme to prevent AOD impairment in the workplace. The objective of this study was to determine whether the Theory of Planned Behaviour can help explain the mechanisms by which behaviour change occurs with regard to AOD impairment in the workplace. ---------- Method: A survey of 1165 employees of a State-based industry in Australia was conducted, and a response rate of 98% was achieved. The survey included questions relevant to the Theory of Planned Behaviour: behaviour; behavioural intentions; attitude; perceptions of social pressure; and perceived behavioural control with regard to workplace AOD impairment. ---------- Findings: Less than 3% of participants reported coming to work impaired by AODs. Fewer than 2% of participants reported that they intended to come to work impaired by AODs. The majority of participants (over 80%) reported unfavourable attitudes toward AOD impairment at work. Logistic regression analyses suggest that, consistent with the theory of planned behaviour: attitudes, perceptions of social pressure, and perceived behavioural control with regard to workplace AOD impairment, all predict behavioural intentions (P < .001); and behavioural intentions predict (self-reported) behaviour regarding workplace AOD impairment (P < .001). ---------- Conclusions: The Theory of Planned Behaviour appears to assist with understanding the mechanisms by which behaviour change occurs with regard to AOD impairment in the workplace. An occupational AOD programme which targets those mechanisms for change may improve its impact in preventing workplace AOD impairment.

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Objective: The global implementation of oral random roadside drug testing is relatively limited, and correspondingly, the literature that focuses on the effectiveness of this intervention is scant. This study aims to provide a preliminary indication of the impact of roadside drug testing in Queensland. Methods: A sample of Queensland motorists’ (N= 922) completed a self-report questionnaire to investigate their drug driving behaviour, as well as examine the perceived affect of legal sanctions (certainty, severity and swiftness) and knowledge of the countermeasure on their subsequent offending behaviour. Results: Analysis of the collected data revealed that approximately 20% of participants reported drug driving at least once in the last six months. Overall, there was considerable variability in respondent’s perceptions regarding the certainty, severity and swiftness of legal sanctions associated with the testing regime and a considerable proportion remained unaware of testing practices. In regards to predicting those who intended to drug driving again in the future, perceptions of apprehension certainty, more specifically low certainty of apprehension, were significantly associated with self-reported intentions to offend. Additionally, self-reported recent drug driving activity and frequent drug consumption were also identified as significant predictors, which indicates that in the current context, past behaviour is a prominent predictor of future behaviour. To a lesser extent, awareness of testing practices was a significant predictor of intending not to drug drive in the future. Conclusion: The results indicate that drug driving is relatively prevalent on Queensland roads, and a number of factors may influence such behaviour. Additionally, while the roadside testing initiative is beginning to have a deterrent impact, its success will likely be linked with targeted intelligence-led implementation in order to increase apprehension levels as well as the general deterrent effect.

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Background: There is a growing trend for individuals to seek health information from online sources. Alcohol and other drug (AOD) use is a significant health problem worldwide, but access and use of AOD websites is poorly understood. ----- ----- Objective: To investigate content and functionality preferences for AOD and other health websites. Methods: An anonymous online survey examined general Internet and AOD-specific usage and search behaviors, valued features of AOD and health-related websites (general and interactive website features), indicators of website trustworthiness, valued AOD website tools or functions, and treatment modality preferences. ----- ----- Results: Surveys were obtained from 1214 drug (n = 766) and alcohol website users (n = 448) (mean age 26.2 years, range 16-70). There were no significant differences between alcohol and drug groups on demographic variables, Internet usage, indicators of website trustworthiness, or on preferences for AOD website functionality. A robust website design/navigation, open access, and validated content provision were highly valued by both groups. While attractiveness and pictures or graphics were also valued, high-cost features (videos, animations, games) were minority preferences. Almost half of respondents in both groups were unable to readily access the information they sought. Alcohol website users placed greater importance on several AOD website tools and functions than did those accessing other drug websites: online screening tools (χ²2 = 15.8, P < .001, n = 985); prevention programs (χ²2 = 27.5, P < .001, n = 981); tracking functions (χ²2 = 11.5, P = .003, n = 983); self help treatment programs (χ²2 = 8.3, P = .02, n = 984); downloadable fact sheets for friends (χ²2 = 11.6, P = .003, n = 981); or family (χ²2 = 12.7, P = .002, n = 983). The most preferred online treatment option for both the user groups was an Internet site with email therapist support. Explorations of demographic differences were also performed. While gender did not affect survey responses, younger respondents were more likely to value interactive and social networking features, whereas downloading of credible information was most highly valued by older respondents. ----- ----- Conclusions: Significant deficiencies in the provision of accessible information on AOD websites were identified, an important problem since information seeking was the most common reason for accessing these websites, and, therefore, may be a key avenue for engaging website users in behaviour change. The few differences between AOD website users suggested that both types of websites may have similar features, although alcohol website users may more readily be engaged in screening, prevention and self-help programs, tracking change, and may value fact sheets more highly. While the sociodemographic differences require replication and clarification, these differences support the notion that the design and features of AOD websites should target specific audiences to have maximal impact.

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Somatic embryogenesis and transformation systems are indispensable modern plant breeding components since they provide an alternative platform to develop control strategies against the plethora of pests and diseases affecting many agronomic crops. This review discusses some of the factors affecting somatic embryogenesis and transformation, highlights the advantages and limitations of these systems and explores these systems as breeding tools for the development of crops with improved agronomic traits. The regeneration of non-chimeric transgenic crops through somatic embryogenesis with introduced disease and pest-resistant genes for instance, would be of significant benefit to growers worldwide.

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Poly(lactide-co-glycolide) (PLGA) beads have been widely studied as a potential drug/protein carrier. The main shortcomings of PLGA beads are that they lack bioactivity and controllable drug-delivery ability, and their acidic degradation by-products can lead to pH decrease in the vicinity of the implants. Akermanite (AK) (Ca(2) MgSi(2) O(7) ) is a novel bioactive ceramic which has shown excellent bioactivity and degradation in vivo. This study aimed to incorporate AK to PLGA beads to improve the physiochemical, drug-delivery, and biological properties of PLGA beads. The microstructure of beads was characterized by SEM. The effect of AK incorporating into PLGA beads on the mechanical strength, apatite-formation ability, the loading and release of BSA, and the proliferation, and differentiation of bone marrow stromal cells (BMSCs) was investigated. The results showed that the incorporation of AK into PLGA beads altered the anisotropic microporous structure into homogenous one and improved their compressive strength and apatite-formation ability in simulated body fluids (SBF). AK neutralized the acidic products from PLGA beads, leading to stable pH value of 7.4 in biological environment. AK led to a sustainable and controllable release of bovine serum albumin (BSA) in PLGA beads. The incorporation of AK into PLGA beads enhanced the proliferation and alkaline phosphatase activity of BMSCs. This study implies that the incorporation of AK into PLGA beads is a promising method to enhance their physiochemical and biological property. AK/PLGA composite beads are a potential bioactive drug-delivery system for bone tissue repair.

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Business transformations are large-scale organizational change programs that, evidence suggests, are often unsuccessful. Our interest is in identifying the management capabilities required for the successful execution of these projects. We advance a service-oriented view of the enterprise, which suggests that different management services need to be identified and integrated in order to execute business transformation. In order to identify those management services that require integration, we conducted an exploratory empirical study of the demand for management services in US and Asia, and we show that two archetypes of management services exist in business transformation initiatives: transactional and transformational management services. We identify the relevant set of transactional and transformational services and discuss what the demand for these services implies for the execution of business transformations.

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This article is a study of the arts in early childhood as a way of learning, for both children and their teachers. The author suggests that drawing can be a powerful tool for collaborative approaches to pedagogy. When teachers draw with children, pathways of communication can be opened, and the collaborative exercise can trigger processes of transformation for both adult and child. In order to present challenges to more traditional, hands-off pedagogical practices in arts education, this article is an account of reflexive arts pedagogies, and how they can work to improve communication and understandings between adults and children. Within the educational contexts of Australian preschooling and primary schooling, the author examines the process of collaborative drawing, and how this can enable a process of transformation. Her analysis, and the accompanying examples of reflexive practices, combine complementary lenses, socio-cultural and postmodern, that she sees as working in harmony to produce new possibilities, in arts education in particular, and, more broadly, in early childhood education.