The ACA training programme to improve communication between general practitioners and their palliative care patients: development and applicability

<p>Abstract</p> <p>We describe the development of a new training programme on GP-patient communication in palliative care, and the applicability to GPs and GP Trainees. This ‘ACA training programme’ focuses on <b> <it>A</it> </b><it>vailability</it> of the GP for the patient, <b> <it>C</it> </b><it>urrent issues</it> that should be raised by the GP, and <b> <it>A</it> </b><it>nticipating</it> various scenarios. Evaluation results indicate the ACA training programme to be applicable to GPs and GP Trainees. The ACA checklist was appreciated by GPs as useful both in practice and as a learning tool, whereas GP Trainees mainly appreciated the list for use in practice.</p

4D cardiovascular magnetic resonance velocity mapping of alterations of right heart flow patterns and main pulmonary artery hemodynamics in tetralogy of Fallot

<p>Abstract</p> <p>Background</p> <p>To assess changes in right heart flow and pulmonary artery hemodynamics in patients with repaired Tetralogy of Fallot (rTOF) we used whole heart, four dimensional (4D) velocity mapping (VM) cardiovascular magnetic resonance (CMR).</p> <p>Methods</p> <p>CMR studies were performed in 11 subjects with rTOF (5M/6F; 20.1 ± 12.4 years) and 10 normal volunteers (6M/4F; 34.2 ± 13.4 years) on clinical 1.5T and 3.0T MR scanners. 4D VM-CMR was performed using PC VIPR (Phase Contrast Vastly undersampled Isotropic Projection Reconstruction). Interactive streamline and particle trace visualizations of the superior and inferior vena cava (IVC and SVC, respectively), right atrium (RA), right ventricle (RV), and pulmonary artery (PA) were generated and reviewed by three experienced readers. Main PA net flow, retrograde flow, peak flow, time-to-peak flow, peak acceleration, resistance index and mean wall shear stress were quantified. Differences in flow patterns between the two groups were tested using Fisher's exact test. Differences in quantitative parameters were analyzed with the Kruskal-Wallis rank sum test.</p> <p>Results</p> <p>4D VM-CMR was successfully performed in all volunteers and subjects with TOF. Right heart flow patterns in rTOF subjects were characterized by (a) greater SVC/IVC flow during diastole than systole, (b) increased vortical flow patterns in the RA and in the RV during diastole, and (c) increased helical or vortical flow features in the PA's. Differences in main PA retrograde flow, resistance index, peak flow, time-to-peak flow, peak acceleration and mean wall shear stress were statistically significant.</p> <p>Conclusions</p> <p>Whole heart 4D VM-CMR with PC VIPR enables detection of both normal and abnormal right heart flow patterns, which may allow for comprehensive studies to evaluate interdependencies of post-surgically altered geometries and hemodynamics.</p

miR-125b Promotes Early Germ Layer Specification through Lin28/let-7d and Preferential Differentiation of Mesoderm in Human Embryonic Stem Cells

Unlike other essential organs, the heart does not undergo tissue repair following injury. Human embryonic stem cells (hESCs) grow indefinitely in culture while maintaining the ability to differentiate into many tissues of the body. As such, they provide a unique opportunity to explore the mechanisms that control human tissue development, as well as treat diseases characterized by tissue loss, including heart failure. MicroRNAs are small, non-coding RNAs that are known to play critical roles in the regulation of gene expression. We profiled the expression of microRNAs during hESC differentiation into myocardial precursors and cardiomyocytes (CMs), and determined clusters of human microRNAs that are specifically regulated during this process. We determined that miR-125b overexpression results in upregulation of the early cardiac transcription factors, GATA4 and Nkx2-5, and accelerated progression of hESC-derived myocardial precursors to an embryonic CM phenotype. We used an in silico approach to identify Lin28 as a target of miR-125b, and validated this interaction using miR-125b knockdown. Anti-miR-125b inhibitor experiments also showed that miR-125b controls the expression of miRNA let-7d, likely through the negative regulatory effects of Lin28 on let-7. We then determined that miR-125b overexpression inhibits the expression of Nanog and Oct4 and promotes the onset of Brachyury expression, suggesting that miR-125b controls the early events of human CM differentiation by inhibiting hESC pluripotency and promoting mesodermal differentiation. These studies identified miR-125b as an important regulator of hESC differentiation in general, and the development of hESC-derived mesoderm and cardiac muscle in particular. Manipulation of miR-125b-mediated pathways may provide a novel approach to directing the differentiation of hESC-derived CMs for cell therapy applications

Agrobacterium-mediated transformation systems of Primula vulgaris

Background: Genetic transformation is a valuable tool and an important procedure in plant functional genomics contributing to gene discovery, allowing powerful insights into gene function and genetically controlled characteristics. Primulaceae species provide one of the best-known examples of heteromorphic flower development, a breeding system which has attracted considerable attention, including that of Charles Darwin. Molecular approaches, including plant transformation give the best opportunity to define and understand the role of genes involved in floral heteromorphy in the common primrose, Primula vulgaris, along with other Primula species. Results: Two transformation systems have been developed in P. vulgaris. The first system, Agrobacterium-mediated vacuum infiltration of seedlings, enables the rapid testing of transgenes, transiently in planta. GUS expression was observed in the cotyledons, true leaves, and roots of Primula seedlings. The second system is based on Agrobacterium tumefaciens infection of pedicel explants with an average transformation efficiency of 4.6%. This transformation system, based on regeneration and selection of transformants within in vitro culture, demonstrates stable transgene integration and transmission to the next generation. Conclusion: The two transformation systems reported here will aid fundamental research into important traits in Primula. Although, stable integration of transgenes is the ultimate goal for such analyses, transient gene expression via Agrobacterium-mediated DNA transfer, offers a simple and fast method to analyse transgene functions. The second system describes, for the first time, stable Agrobacterium-mediated transformation of Primula vulgaris, which will be key to characterising the genes responsible for the control of floral heteromorphy

The effect of a curriculum-based physical activity intervention on accelerometer-assessed physical activity in schoolchildren: a non-randomised mixed methods controlled before-and-after study

Classroom-based physical activity (PA) interventions offer the opportunity to increase PA without disrupting the curriculum. We aimed to explore the feasibility and potential effectiveness of a classroom-based intervention on moderate to vigorous PA (MVPA) and total PA. The secondary aim was to assess the acceptability and sustainability of the intervention. In a mixed-methods, non-randomised, exploratory controlled before-and-after study, 152 children (10 ± 0.7 years) were recruited from five schools; two intervention (n = 72) and three control (n = 80) schools. School teachers delivered an 8-week classroom-based intervention, comprising of 10 minutes daily MVPA integrated into the curriculum. The control schools maintained their usual school routine. Mean daily MVPA (min), total PA (mean cpm), physical fitness, and health-related quality of life measurements were taken at baseline, end of intervention, and 4-weeks post-intervention (follow-up). Data were analysed using a constrained baseline longitudinal analysis model accounting for the hierarchical data structure. For the primary outcomes (MVPA and total PA) the posterior mean difference and 95% compatibility interval were derived using a semi-Bayesian approach with an explicit prior. The acceptability and sustainability of the intervention was explored via thematic content analysis of focus group discussions with teachers (n = 5) and children (n = 50). The difference in mean daily MVPA (intervention-control) was 2.8 (-12.5 to 18.0) min/day at 8 weeks and 7.0 (-8.8 to 22.8) min/day at follow-up. For total PA, the differences were -2 (-127 to 124) cpm at 8-weeks and 11 (-121 to 143) cpm at follow-up. The interval estimates indicate that meaningful mean effects (both positive and negative) as well as trivial effects are reasonably compatible with the data and design. The intervention was received positively with continuation reported by the teachers and children. Classroom-based PA could hold promise for increasing average daily MVPA, but a large cluster randomised controlled trial is required

Publication bias in gastroenterological research – a retrospective cohort study based on abstracts submitted to a scientific meeting

BACKGROUND: The aim of this study was to examine the determinants of publication and whether publication bias occurred in gastroenterological research. METHODS: A random sample of abstracts submitted to DDW, the major GI meeting (1992–1995) was evaluated. The publication status was determined by database searches, complemented by a mailed survey to abstract authors. Determinants of publication were examined by Cox proportional hazards model and multiple logistic regression. RESULTS: The sample included abstracts on 326 controlled clinical trials (CCT), 336 other clinical research reports (OCR), and 174 basic science studies (BSS). 392 abstracts (47%) were published as full papers. Acceptance for presentation at the meeting was a strong predictor of subsequent publication for all research types (overall, 54% vs. 34%, OR 2.3, 95% CI 1.7 to 3.1). In the multivariate analysis, multi-center status was found to predict publication (OR 2.8, 95% CI 1.6–4.9). There was no significant association between direction of study results and subsequent publication. Studies were less likely to be published in high impact journals if the results were not statistically significant (OR 0.5, 95 CI 95% 0.3–0.6). The author survey identified lack of time or interest as the main reason for failure to publish. CONCLUSIONS: Abstracts which were selected for presentation at the DDW are more likely to be followed by full publications. The statistical significance of the study results was not found to be a predictor of publication but influences the chances for high impact publication

Do Children and Adolescents with Anorexia Nervosa Display an Inefficient Cognitive Processing Style?

Objective: This study aimed to examine neuropsychological processing in children and adolescents with Anorexia Nervosa (AN). The relationship of clinical and demographic variables to neuropsychological functioning within the AN group was also explored.  Method: The performance of 41 children and adolescents with a diagnosis of AN were compared to 43 healthy control (HC) participants on a number of neuropsychological measures.  Results: There were no differences in IQ between AN and HC groups. However, children and adolescents with AN displayed significantly more perseverative errors on the Wisconsin Card Sorting Test, and lower Style and Central Coherence scores on the Rey Osterrieth Complex Figure Test relative to HCs.  Conclusion: Inefficient cognitive processing in the AN group was independent of clinical and demographic variables, suggesting it might represent an underlying trait for AN. The implications of these findings are discussed

Increased autophagy in EphrinB2-deficient osteocytes is associated with elevated secondary mineralization and brittle bone

Mineralized bone forms when collagen-containing osteoid accrues mineral crystals. This is initiated rapidly (primary mineralization), and continues slowly (secondary mineralization) until bone is remodeled. The interconnected osteocyte network within the bone matrix differentiates from bone-forming osteoblasts; although osteoblast differentiation requires EphrinB2, osteocytes retain its expression. Here we report brittle bones in mice with osteocyte-targeted EphrinB2 deletion. This is not caused by low bone mass, but by defective bone material. While osteoid mineralization is initiated at normal rate, mineral accrual is accelerated, indicating that EphrinB2 in osteocytes limits mineral accumulation. No known regulators of mineralization are modified in the brittle cortical bone but a cluster of autophagy-associated genes are dysregulated. EphrinB2-deficient osteocytes displayed more autophagosomes in vivo and in vitro, and EphrinB2-Fc treatment suppresses autophagy in a RhoA-ROCK dependent manner. We conclude that secondary mineralization involves EphrinB2-RhoA-limited autophagy in osteocytes, and disruption leads to a bone fragility independent of bone mass