Bivalent Epigenetic Control of Oncofetal Gene Expression in Cancer

Multiple mechanisms of epigenetic control that include DNA methylation, histone modification, noncoding RNAs, and mitotic gene bookmarking play pivotal roles in stringent gene regulation during lineage commitment and maintenance. Experimental evidence indicates that bivalent chromatin domains, i.e., genome regions that are marked by both H3K4me3 (activating) and H3K27me3 (repressive) histone modifications, are a key property of pluripotent stem cells. Bivalency of developmental genes during the G1 phase of the pluripotent stem cell cycle contributes to cell fate decisions. Recently, some cancer types have been shown to exhibit partial recapitulation of bivalent chromatin modifications that are lost along with pluripotency, suggesting a mechanism by which cancer cells reacquire properties that are characteristic of undifferentiated, multipotent cells. This bivalent epigenetic control of oncofetal gene expression in cancer cells may offer novel insights into the onset and progression of cancer and may provide specific and selective options for diagnosis as well as for therapeutic intervention

Effectiveness of a new model of primary care management on knee pain and function in patients with knee osteoarthritis: Protocol for THE PARTNER STUDY

© 2018 The Author(s). Background: To increase the uptake of key clinical recommendations for non-surgical management of knee osteoarthritis (OA) and improve patient outcomes, we developed a new model of service delivery (PARTNER model) and an intervention to implement the model in the Australian primary care setting. We will evaluate the effectiveness and cost-effectiveness of this model compared to usual general practice care. Methods: We will conduct a mixed-methods study, including a two-arm, cluster randomised controlled trial, with quantitative, qualitative and economic evaluations. We will recruit 44 general practices and 572 patients with knee OA in urban and regional practices in Victoria and New South Wales. The interventions will target both general practitioners (GPs) and their patients at the practice level. Practices will be randomised at a 1:1 ratio. Patients will be recruited if they are aged =45 years and have experienced knee pain =4/10 on a numerical rating scale for more than three months. Outcomes are self-reported, patient-level validated measures with the primary outcomes being change in pain and function at 12 months. Secondary outcomes will be assessed at 6 and 12 months. The implementation intervention will support and provide education to intervention group GPs to deliver effective management for patients with knee OA using tailored online training and electronic medical record support. Participants with knee OA will have an initial GP visit to confirm their diagnosis and receive management according to GP intervention or control group allocation. As part of the intervention group GP management, participants with knee OA will be referred to a centralised multidisciplinary service: the PARTNER Care Support Team (CST). The CST will be trained in behaviour change support and evidence-based knee OA management. They will work with patients to develop a collaborative action plan focussed on key self-management behaviours, and communicate with the patients' GPs. Patients receiving care by intervention group GPs will receive tailored OA educational materials, a leg muscle strengthening program, and access to a weight-loss program as appropriate and agreed. GPs in the control group will receive no additional training and their patients will receive usual care. Discussion: This project aims to address a major evidence-to-practice gap in primary care management of OA by evaluating a new service delivery model implemented with an intervention targeting GP practice behaviours to improve the health of people with knee OA. Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12617001595303, date of registration 1/12/2017

Análisis histórico del componente urbano arquitectónico del campus de la Universidad Francisco de Paula Santander sede central Cúcuta, en el marco del programa de fortalecimiento institucional y crecimiento de la infraestructura física. (Archivo Electrónico)

El análisis del que es objeto esta investigación, es aplicado en la Sede central de la Universidad Francisco de Paula Santander, ubicada en el barrio Colsag, en la ciudad de San José de Cúcuta, teniendo en cuenta su afectación en el contexto inmediato y regional. El estudio se hace a partir de la documentación histórica recolectada en este proceso, con un enfoque de análisis urbano arquitectónico, para comprender los procesos de crecimiento físico que ha tenido la universidad desde su fundación hasta hoy, y qué factores incidieron en los acontecimientos más relevantes. La investigación de estos acontecimientos, se hace revisando documentos dispersos en diferentes dependencias de la universidad, principalmente, documentos que contienen los planes de desarrollo; extrayendo datos históricos relevantes, variantes que determinaron importantes decisiones constructivas y comparando los registros de las proyecciones físicas, con la ejecución histórica de las mismas. En complemento del análisis histórico y a partir del mismo, se realizan 33 fichas de inventario de bienes donde se describen aspectos técnicos (planimetrías, cuadros de áreas, condiciones físicas) históricos (reseña y autores) y financieros (avalúos) de cada edificio, datos que fueron tomados de la investigación documental y del trabajo de campo hecho para este trabajo. Finalmente se aporta una matriz de análisis urbano-arquitectónico con datos de análisis relevantes para los procesos de planeación y acreditación de la universidad.PregradoArquitecto(a

Thrombelastography does not predict clinical response to rtPA for acute ischemic stroke.

Thrombelastography (TEG) measures coagulation in venous blood. We hypothesized that TEG, by reflecting clot subtype and ex vivo fibrinolysis, might predict fibrinolytic response to tPA as reflected by rapid clinical improvement or hemorrhagic transformation of the infarct. 171 acute ischemic stroke patients treated with tPA were prospectively enrolled. Venous blood for TEG was drawn before and 10 min after tPA bolus. We measured rapid clinical improvement (RCI = 8 point improvement on NIHSS or total NIHSS of 0, 1 at 36 h), Hemorrhagic transformation (HT = any blood on imaging within 36 h), and hyperdense middle cerebral artery sign (HDMCA = biomarker for erythrocyte-rich clot). Multivariable regression models compared TEG parameters after adjusting for potential confounders. No differences in pre- or post-tPA TEG were found between patients with or without RCI. Also, there was no correlation between TEG and HDMCA. Clotting was slightly prolonged in patients with HT (p = 0.046). We failed to find a robust association between TEG and clinical response to tPA. It is likely that arterial clot lysis is determined by factors unrelated to coagulation status as measured by TEG in the venous circulation. It is unlikely that TEG will be useful to predict clinical response to tPA, but may help predict bleeding

Tree diversity effects on soil microbial biomass and respiration are context dependent across forest diversity experiments

Aim Soil microorganisms are essential for the functioning of terrestrial ecosystems. Although soil microbial communities and functions are linked to tree species composition and diversity, there has been no comprehensive study of the generality or context dependence of these relationships. Here, we examine tree diversity–soil microbial biomass and respiration relationships across environmental gradients using a global network of tree diversity experiments. Location Boreal, temperate, subtropical and tropical forests. Time period 2013. Major taxa studied Soil microorganisms. Methods Soil samples collected from 11 tree diversity experiments were used to measure microbial respiration, biomass and respiratory quotient using the substrate-induced respiration method. All samples were measured using the same analytical device, method and procedure to reduce measurement bias. We used linear mixed-effects models and principal components analysis (PCA) to examine the effects of tree diversity (taxonomic and phylogenetic), environmental conditions and interactions on soil microbial properties. Results Abiotic drivers, mainly soil water content, but also soil carbon and soil pH, significantly increased soil microbial biomass and respiration. High soil water content reduced the importance of other abiotic drivers. Tree diversity had no effect on the soil microbial properties, but interactions with phylogenetic diversity indicated that the effects of diversity were context dependent and stronger in drier soils. Similar results were found for soil carbon and soil pH. Main conclusions Our results indicate the importance of abiotic variables, especially soil water content, for maintaining high levels of soil microbial functions and modulating the effects of other environmental drivers. Planting tree species with diverse water-use strategies and structurally complex canopies and high leaf area might be crucial for maintaining high soil microbial biomass and respiration. Given that greater phylogenetic distance alleviated unfavourable soil water conditions, reforestation efforts that account for traits improving soil water content or select more phylogenetically distant species might assist in increasing soil microbial functions

Ottawa Panel Evidence-Based Clinical Practice Guidelines for the Management of Osteoarthritis in Adults Who Are Obese or Overweight

Background and Purpose. The objective of this review was to construct an updated evidence-based clinical practice guideline on the use of physical activity and diet for the management of osteoarthritis (OA) in adults (\u3e18 years of age) who are obese or overweight (body mass index ≥25 kg/m2). Data Sources. Articles were extracted from the following databases: MEDLINE, EMBASE (Current Contents), SPORTDiscus, SUM, Scopus, CINAHL, AMED, BIOMED, PubMed, ERIC, the Cochrane Controlled Trials, and PEDro. Study Selection. The Ottawa Panel and research assistance team strictly applied the inclusion and exclusion criteria from previous Ottawa Panel publications. Data Extraction. An a priori literature search was conducted for articles related to obesity and OA of the lower extremities that were published from January 1, 1966, to November 30, 2010. Inclusion criteria and the methods to grade the recommendations were created by the Ottawa Panel. Data Synthesis. Recommendations were graded based on the strength of evidence (A, B, C, C+ D, D+ or D-as well as experimental design (I for randomized controlled trials and II for nonrandomized studies). In agreement with previous Ottawa Panel methods, Cochrane Collaboration methods were utilized for statistical analysis. Clinical significance was established by an improvement of ≥15% in the experimental group compared with the control group. There were a total of 79 recommendations from 9 articles. From these recommendations, there were 36 positive recommendations: 21 grade A and 15 grade C+ There were no grade B recommendations, and all recommendations were of clinical benefit. Limitations. Further research is needed, as more than half of the trials were of low methodological quality. Conclusions. This review suggests that physical activity and diet programs are beneficial, specifically for pain relief (9 grade A recommendations) and improved functional status (6 grade A and 7 grade C+ recommendations), for adults with OA who are obese or overweight. The Ottawa Panel was able to demonstrate that when comparing physical activity alone, diet alone, physical activity combined with diet, and control groups, the intervention including physical activity and diet produced the most beneficial results. © 2011 American Physical Therapy Association