Association of c-Raf expression with survival and its targeting with antisense oligonucleotides in ovarian cancer

c-Raf is an essential component of the extracellular related kinase (ERK) signal transduction pathway. Immunohistochemical staining indicated that c-Raf was present in 49/53 ovarian adenocarcinomas investigated and high c-Raf expression correlated significantly with poor survival (P = 0.002). c-Raf protein was detected in 15 ovarian cancer cell lines. Antisense oligodeoxynucleotides (ODNs) (ISIS 5132 and ISIS 13650) reduced c-Raf protein levels and inhibited cell proliferation in vitro. Selectivity was demonstrated by the lack of effect of ISIS 5132 on A-Raf or ERK, while a random ODN produced only minor effects on growth and did not influence c-Raf expression. ISIS 5132 produced enhanced apoptosis and cells accumulated in S and G 2/M phases of the cell cycle. In vivo, ISIS 5132 inhibited growth of the s.c. SKOV-3 xenograft while a mismatch ODN had no effect. These data indicate that high levels of c-Raf expression may be important in ovarian cancer and use of antisense ODNs targeted to c-Raf could provide a strategy for the treatment of this disease. © 2001 Cancer Research Campaign http://www.bjcancer.co

The place and barriers of evidence based practice: knowledge and perceptions of medical, nursing and allied health practitioners in malaysia

<p>Abstract</p> <p>Background</p> <p>Despite a recent increase in activities to promote evidence-based practice (EBP), it was unclear how Malaysian hospital practitioners received this new approach in medicine. This study examines their confidence and perceptions on EBP.</p> <p>Findings</p> <p>We conducted cross-sectional surveys using a self-administered questionnaire during two EBP training courses in two Malaysian hospitals in January and June 2007. Our subjects (n = 144) were doctors and nursing and allied health staff (NAH) participating in the EBP courses. Our questionnaire covered three domains: confidence and understanding (six items), attitude (five items) and barriers to practice (four items). We presented simple descriptive statistics, including the sum ratings and the proportions with different responses for each item, and compared different groups using Mann-Whitney U test for scaled ratings and Chi-square test for dichotomous responses.</p> <p>Ninety-two doctors and 52 NAH staff completed the surveys. Overall, doctors expressed slightly higher confidence on EBP compared to NAH staff. Out of a maximum sum rating of 27 over six items, doctors reported an average of 18.3 (SD 3.2) and NAH staff reported an average of 16.0 (SD 3.4), p = 0.002. Doctors were also more positive in their views on EBP. For example, 67.4% of doctors disagreed, but 61% of NAH staff agreed that "the importance of EBP in patient care is exaggerated", and 79.3% of doctors disagreed, but 46.2% of NAH staff agreed that "EBP is too tedious and impractical". Similar responses were observed for other items in the domain.</p> <p>Doctors and NAH staff shared similar concerns on barriers to evidence-based practice. The highest proportions considered poor facilities to access evidence a barrier (76% of doctors and 90% of NAH), followed by poor awareness of evidence (62% of doctors and 70% of NAH) and time constraints (63% of doctors and 68% of NAH), p = 0.09 for the combined rating of four items in the domain.</p> <p>Conclusions</p> <p>The findings of our survey suggest a need for greater efforts in promoting EBP among Malaysian hospital practitioners especially for NAH staff. From the responses based on the barriers to EBP, improving facilities for accessing evidence and promoting more user-friendly resources to address time constraints appear to be the priorities.</p

Recovering Dietary Information from Extant and Extinct Primates Using Plant Microremains

When reconstructing the diets of primates, researchers often rely on several well established methods, such as direct observation, studies of discarded plant parts, and analysis of macrobotanical remains in fecal matter. Most of these studies can be performed only on living primate groups, however, and the diets of extinct, subfossil, and fossil groups are known only from proxy methods. Plant microremains, tiny plant structures with distinctive morphologies, can record the exact plant foods that an individual consumed. They can be recovered from recently deceased and fossil primate samples, and can also be used to supplement traditional dietary analyses in living groups. Here I briefly introduce plant microremains, provide examples of how they have been successfully used to reconstruct the diets of humans and other species, and describe methods for their application in studies of primate dietary ecology

Spelling improvement through letter-sound and whole-word training in two multilingual Greek- and English- speaking children

Case studies of two children with spelling difficulty are reported. LK was multilingual and ED bilingual. A training programme that targeted phonic decoding (or sublexical) spelling processes was conducted with both children. Immediate and delayed post-training assessments showed improvement in spelling nonwords for LK but not for ED. Training that targeted whole word (or lexical) spelling processes was then conducted with ED. Improvement in spelling of irregular words (a marker for lexical spelling processes) was observed. Research into literacy difficulties with multilingual children is sparse, although multilingualism is increasingly widespread. Up to now theoretically based training studies have focused on monolingual children and results were promising. The present findings indicate that theoretically based training programmes for literacy difficulties can also be effective for multilingual children

Civic Participation and Other Interventions That Promote Children\u2019s Tolerance of Migrants

In this chapter, we begin by providing a definition of \u2018tolerance\u2019, illustrating the wide range of attributes associated with the concept in the literature. Second, we identify some key paths through which tolerance can develop at different stages of an individual\u2019s development. Through a literature review, we will track some of the factors that can increase tolerance toward migrants during early and late stages development. Finally, we will conclude by presenting an overview of methodological approaches that practitioners have at their disposal to promote tolerance toward migrants

When Are New Hippocampal Neurons, Born in the Adult Brain, Integrated into the Network That Processes Spatial Information?

Adult-born neurons in the dentate gyrus (DG) functionally integrate into the behaviorally relevant hippocampal networks, showing a specific Arc-expression response to spatial exploration when mature. However, it is not clear when, during the 4- to 6-week interval that is critical for survival and maturation of these neurons, this specific response develops. Therefore, we characterized Arc expression after spatial exploration or cage control conditions in adult-born neurons from rats that were injected with BrdU on one day and were sacrificed 1, 7, 15, 30, and 45 days post-BrdU injection (PBI). Triple immunostaining for NeuN, Arc, and BrdU was analyzed through the different DG layers. Arc protein expression in BrdU-positive cells was observed from day 1 to day 15 PBI but was not related to behavioral stimulation. The specific Arc-expression response to spatial exploration was observed from day 30 and 45 in about 5% of the BrdU-positive cell population. Most of the BrdU-positive neurons expressing Arc in response to spatial exploration (∼90%) were located in DG layer 1, and no Arc expression was observed in cells located in the subgranular zone (SGZ). Using the current data and that obtained previously, we propose a mathematical model suggesting that new neurons are unlikely to respond to exploration by expressing Arc after they are 301 days old, and also that in a 7-month-old rat the majority (60%) of the neurons that respond to exploration must have been born during adulthood; thus, suggesting that adult neurogenesis in the DG is highly relevant for spatial information processing

Designing clinical trials for assessing the effects of cognitive training and physical activity interventions on cognitive outcomes: The Seniors Health and Activity Research Program Pilot (SHARP-P) Study, a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The efficacy of non-pharmacological intervention approaches such as physical activity, strength, and cognitive training for improving brain health has not been established. Before definitive trials are mounted, important design questions on participation/adherence, training and interventions effects must be answered to more fully inform a full-scale trial.</p> <p>Methods</p> <p>SHARP-P was a single-blinded randomized controlled pilot trial of a 4-month physical activity training intervention (PA) and/or cognitive training intervention (CT) in a 2 × 2 factorial design with a health education control condition in 73 community-dwelling persons, aged 70-85 years, who were at risk for cognitive decline but did not have mild cognitive impairment.</p> <p>Results</p> <p>Intervention attendance rates were higher in the CT and PACT groups: CT: 96%, PA: 76%, PACT: 90% (p=0.004), the interventions produced marked changes in cognitive and physical performance measures (p≤0.05), and retention rates exceeded 90%. There were no statistically significant differences in 4-month changes in composite scores of cognitive, executive, and episodic memory function among arms. Four-month improvements in the composite measure increased with age among participants assigned to physical activity training but decreased with age for other participants (intervention*age interaction p = 0.01). Depending on the choice of outcome, two-armed full-scale trials may require fewer than 1,000 participants (continuous outcome) or 2,000 participants (categorical outcome).</p> <p>Conclusions</p> <p>Good levels of participation, adherence, and retention appear to be achievable for participants through age 85 years. Care should be taken to ensure that an attention control condition does not attenuate intervention effects. Depending on the choice of outcome measures, the necessary sample sizes to conduct four-year trials appear to be feasible.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00688155">NCT00688155</a></p

Comet-FISH for the evaluation of plant DNA damage after mutagenic treatments

The aim of this study was to perform a comparative investigation of the actions of three mutagens that are widely used in plant mutagenesis using the comet-FISH technique. The comet-FISH technique was used for the analysis of DNA damage and the kinetics of repair within specific DNA sequences. FISH with rDNA and telomeric/centromeric DNA probes was applied to comets that were obtained from an alkaline/neutral comet assay. Migration within specific DNA sequences was analysed after treatment with two chemical mutagens-maleic hydrazide (MH) and N-nitroso-N-methylurea (MNU), and γ-rays. Barley was used as a model plant in this study. The possible utility of specific DNA sequences in a comparative assessment of the distribution of DNA damage within a plant genome was evaluated. This study proved that the comet-FISH technique is suitable for a detailed quantification of DNA damage and repair within specific DNA sequences in plant mutagenesis. The analysis of FISH signals demonstrated that the involvement of specific DNA sequences in DNA damage was different and was dependent on the mutagen used. We showed that 5S rDNA and telomeric DNA sequences are more sensitive to mutagenic treatment, which was expressed by a stronger fragmentation and migration in comparison to the other probes used in the study. We found that 5S rDNA and telomeric DNA probes are more suitable for testing the genotoxicity of environmental factors. A comparison of the involvement of specific chromosome domains in direct DNA breakage/repair and in chromosome aberration formation after mutagen treatment indicates the compatibility of the results

Diamondites: evidence for a distinct tectono-thermal diamond-forming event beneath the Kaapvaal craton

The petrogenesis and relationship of diamondite to well-studied monocrystalline and fibrous diamonds are poorly understood yet would potentially reveal new aspects of how diamond-forming fluids are transported through the lithosphere and equilibrate with surrounding silicates. Of 22 silicate- and oxide-bearing diamondites investigated, most yielded garnet intergrowths (n = 15) with major element geochemistry (i.e. Ca–Cr) classifying these samples as low-Ca websteritic or eclogitic. The garnet REE patterns fit an equilibrium model suggesting the diamond-forming fluid shares an affinity with high-density fluids (HDF) observed in fibrous diamonds, specifically on the join between the saline–carbonate end-members. The δ13C values for the diamonds range from − 5.27 to − 22.48‰ (V-PDB) with δ18O values for websteritic garnets ranging from + 7.6 to + 5.9‰ (V-SMOW). The combined C–O stable isotope data support a model for a hydrothermally altered and organic carbon-bearing subducted crustal source(s) for the diamond- and garnet-forming media. The nitrogen aggregation states of the diamonds require that diamondite-formation event(s) pre-dates fibrous diamond-formation and post-dates most of the gem monocrystalline diamond-formation events at Orapa. The modelled fluid compositions responsible for the precipitation of diamondites match the fluid-poor and fluid-rich (fibrous) monocrystalline diamonds, where all grow from HDFs within the saline-silicic-carbonatitic ternary system. However, while the nature of the parental fluid(s) share a common lithophile element geochemical affinity, the origin(s) of the saline, silicic, and/or carbonatitic components of these HDFs do not always share a common origin. Therefore, it is wholly conceivable that the diamondites are evidence of a distinct and temporally unconstrained tectono-thermal diamond-forming event beneath the Kaapvaal craton