Genome-wide analysis in a murine Dnmt1 knockdown model identifies epigenetically silenced genes in primary human pituitary tumors

DNA methylation at promoter CpG islands (CGI) is an epigenetic modification associated with inappropriate gene silencing in multiple tumor types. In the absence of a human pituitary tumor cell line, small interfering RNA-mediated knockdown of the maintenance methyltransferase DNA methyltransferase (cytosine 5)-1 (Dnmt1) was used in the murine pituitary adenoma cell line AtT-20. Sustained knockdown induced reexpression of the fully methylated and normally imprinted gene neuronatin (Nnat) in a time-dependent manner. Combined bisulfite restriction analysis (COBRA) revealed that reexpression of Nnat was associated with partial CGI demethylation, which was also observed at the H19 differentially methylated region. Subsequent genome-wide microarray analysis identified 91 genes that were significantly differentially expressed in Dnmt1 knockdown cells (10% false discovery rate). The analysis showed that genes associated with the induction of apoptosis, signal transduction, and developmental processes were significantly overrepresented in this list (P < 0.05). Following validation by reverse transcription-PCR and detection of inappropriate CGI methylation by COBRA, four genes (ICAM1, NNAT, RUNX1, and S100A10) were analyzed in primary human pituitary tumors, each displaying significantly reduced mRNA levels relative to normal pituitary (P < 0.05). For two of these genes, NNAT and S100A10, decreased expression was associated with increased promoter CGI methylation. Induced expression of Nnat in stable transfected AtT-20 cells inhibited cell proliferation. To our knowledge, this is the first report of array-based "epigenetic unmasking" in combination with Dnmt1 knockdown and reveals the potential of this strategy toward identifying genes silenced by epigenetic mechanisms across species boundaries.

Towards understanding self-development coaching programs

Self-development resources are a popular billion -dollar industry worldwide used to improve individuals quality of lives. However, there are insufficient studies for a contemporary conceptualization, especially when it comes to live self-development programs. This paper provides a literature review about current self-development definitions, ideology, concepts, and themes; quality of material provided; quality and characteristics of self-development providers; and the features of the participants who seek such programs. The paper will also discuss the relationsh ip between self-development and related disciplines including coaching, training, mentoring, and motivational speaking. Finally, a new definition will be proposed for self-development coaching programs. Gaps of knowledge are highlighted for further research.

Studying upper-limb kinematic using inertial sensors embedded in smartphones

Background: In recent years, there have been investigations concerning upper-limbs kinematics by various devices. The latest generation of smartphones often includes inertial sensors with subunits which can detect inertial kinematics. The use of smartphones is presented as a convenient and portable analysis method for studying kinematics in terms of angular mobility and linear acceleration Objective: The aim of this study was to study humerus kinematics through six physical properties that correspond to angular mobility and acceleration in the three axes of space, obtained by a smartphone. Methods: This cross-sectional study recruited healthy young adult subjects. Descriptive and anthropometric independent variables related to age, gender, weight, size, and BMI were included. Six physical properties were included corresponding to two dependent variables for each of three special axes: mobility angle (degrees) and lineal acceleration (meters/seconds2), which were obtained thought the inertial measurement sensor embedded in the iPhone4 smartphone equipped with three two elements for the detection of kinematic variables: a gyroscope and an accelerometer. Apple uses an LIS302DL accelerometer in the iPhone4. The application used to obtain kinematic data was xSensor Pro, Crossbow Technology, Inc., available at the Apple AppStore. The iPhone4 has storage capacity of 20MB. The data-sampling rate was set to 32 Hz, and the data for each analytical task was transmitted as email for analysis and postprocessing The iPhone4 was placed in the right half of the body of each subject located in the middle third of the humerus slightly posterior snugly secured by a neoprene fixation belt. Tasks were explained concisely and clearly. The beginning and the end were decided by a verbal order by the researcher. Participants were placed standing, starting from neutral position, performing the following analytical tasks: 180º right shoulder abduction (eight repetitions) and, after a break of about 3 minutes, 180º right shoulder flexion (eight repetitions). Both tasks were performed with the elbow extended, wrist in neutral position and the palmar area of the hand toward the midline at the beginning and end of the movement. Results: A total of 11 subjects (8 men, 3 woman) were measured, whose mean of age was 24.7 years (SD = 4.22 years) and their average BMI was 22.64 Kg/m2 (SD = 2.29 Kg/m2). The mean of angular mobility collected by the smartphone was bigger in pitch axis for flexion (= 157.28°, SD= 12.35°) and abduction (= 151.71°, SD= 9.70°). With regard to acceleration, the highest peak mean value was shown in the Y motion axis during flexion (= 19.5°/s2, SD = 0.8°/s2) and abduction (= 19.4°/s2, SD = 0.8°/s2). Also, descriptive graphics of analytical tasks performed were obtained. Conclusions: This study shows how humerus contributes to upper-limb motion and it identified movement patterns. Therefore, it supports smartphone as a useful device to analyze upper-limb kinematics. Thanks to this study it´s possible to develop a simple application that facilitates the evaluation of the patient.

Advance Care Planning in palliative care : a systematic literature review of the contextual factors influencing its uptake 2008-2012

Background: Advance Care Planning is an iterative process of discussion, decision-making and documentation about end-of-life care. Advance Care Planning is highly relevant in palliative care due to intersecting clinical needs. To enhance the implementation of Advance Care Planning, the contextual factors influencing its uptake need to be better understood. Aim: To identify the contextual factors influencing the uptake of Advance Care Planning in palliative care as published between January 2008 and December 2012. Methods: Databases were systematically searched for studies about Advance Care Planning in palliative care published between January 2008 and December 2012. This yielded 27 eligible studies, which were appraised using National Institute of Health and Care Excellence Quality Appraisal Checklists. Iterative thematic synthesis was used to group results. Results: Factors associated with greater uptake included older age, a college degree, a diagnosis of cancer, greater functional impairment, being white, greater understanding of poor prognosis and receiving or working in specialist palliative care. Barriers included having non-malignant diagnoses, having dependent children, being African American, and uncertainty about Advance Care Planning and its legal status. Individuals’ previous illness experiences, preferences and attitudes also influenced their participation. Conclusion: Factors influencing the uptake of Advance Care Planning in palliative care are complex and multifaceted reflecting the diverse and often competing needs of patients, health professionals, legislature and health systems. Large population-based studies of palliative care patients are required to develop the sound theoretical and empirical foundation needed to improve uptake of Advance Care Planning in this setting.

Integrated chronic disease management in primary-secondary care : a systematic literature review of the evidence

Introduction: Diabetes has traditionally been managed as a single chronic disease state, but it exists with co-morbidities such as depression and metabolic syndrome. Treatment is multifaceted, requiring both primary and secondary care, however, the delivery of diabetes care is often fragmented. Integrated chronic disease management is a growing model of interest, and is underpinned by the chronic care model (CCM), devised as a guide for primary care management of patients with chronic conditions. The model identifies six key elements for effective care, and has shown promise in improving the management of diabetes. Aim: To find empirical evidence of integrated care interventions targeted at co-morbidities including diabetes, across primary/secondary care. Method: A systematic review of peer reviewed literature from PubMed, CINAHL, Embase, Cochrane Library and Joanna Briggs was performed. Studies were reviewed according to inclusion criteria- studies published in English, between 2004-2014, empirical studies, studies with evidence of primary/secondary implementation, and those dealing with chronic co-morbid disease states. Results: 51 studies met the inclusion criteria. Included studies were mostly from the US (38), with five from Australia, UK (2), Canada (2), Netherlands (1), Norway (1), Ireland (1), and one multi-country study. It was found that all interventions adopted at least one (average 3-4) of the chronic care model, with the majority implementing delivery system redesign activities within the primary care practice/s. We found evidence of interventions which significantly reduced emergency department and hospital admissions, improved processes of care, patient health outcomes such as HbA1c, improved patient satisfaction, and reduced costs. Conclusion/Implications for practice: Diabetes exists as a co-morbid disease, requiring both primary and secondary care. We found that integrated care interventions adopting elements of the chronic care model positively impacted on patient outcomes, service utilisation, as well as costs. This review has highlighted that it may not be necessary to adopt all CCM elements to improve clinical outcomes, patient satisfaction and costs.

Nucleopolyhedrovirus introduction in Australia

Nucleopolyhedrovirus (NPV) has become an integral part of integrated pest management (IPM) in many Australian agricultural and horticultural crops. This is the culmination of years of work conducted by researchers at the Queensland Department of Primary Industries and Fisheries (QDPI&F) and Ag Biotech Australia Pty Ltd. In the early 1970’s researchers at QDPI&F identified and isolated a virus in Helicoverpa armigera populations in the field. This NPV was extensively studied and shown to be highly specific to Helicoverpa and Heliothis species. Further work showed that when used appropriately the virus could be used effectively to manage these insects in crops such as sorghum, cotton, chickpea and sweet corn. A similar virus was first commercially produced in the USA in the 1970’s. This product, Elcar®, was introduced into Australia in the late 1970’s by Shell Chemicals with limited success. A major factor contributing to the poor adoption of Elcar was the concurrent enormous success of the synthetic pyrethroids. The importance of integrated pest management was probably also not widely accepted at that time. Gradual development of insect resistance to synthetic pyrethroids and other synthetic insecticides in Australia and the increased awareness of the importance of IPM meant that researchers once again turned their attentions to environmentally friendly pest management tools such NPV and beneficial insects. In the 1990’s a company called Rhone-Poulenc registered an NPV for use in Australian sorghum, chickpea and cotton. This product, Gemstar®, was imported from the USA. In 2000 Ag Biotech Australia established an in-vivo production facility in Australia to produce commercial volumes of a product similar to the imported product. This product was branded, ViVUS®, and was first registered and sold commercially in Australia in 2003. The initial production of ViVUS used a virus identical to the American product but replicating it in an Australian Helicoverpa species, H. armigera. Subsequent research collaboration between QDPI&F and Ag Biotech reinvigorated interest in the local virus strain. This was purified and the production system adapted to produce it on a commercial scale. This new version of ViVUS, which was branded ViVUS Gold®, was first registered and sold commercially in 2004. Widespread insect resistance to insecticides and a greater understanding of integrated pest management is leading to increased adoption of technologies such NPV in Australian agriculture.

Perspectives about exercise from adults with venous leg ulcers : an exploratory study

Objective Exercise has the potential to offer a range of health benefits in addition to improving healing outcomes for people with venous leg ulcers. However despite evidence based recommendations, most of these individuals do not engage in regular exercise. The aim of this study was to gain an understanding of the perspectives of adults with venous leg ulcers, in relation to exercise. Method This was a qualitative design using semi-structured interviews and discussions. Ten participants with venous leg ulceration volunteered to participate. Recruitment was through a specialist wound clinic. Verbatim data were collected by an experienced moderator using a semi-structured guide. Data saturation was reached after three group discussions and two interviews. A random selection of transcripts was sent back to the participants for verification. Thematic content analysis was used to determine major themes and categories. Two transcripts were independently analysed, categories and themes independently developed, cross checked and found comparable. Remaining transcripts were analysed using developed categories and codes. Results Regardless of their current exercise routine, participants reported exercising prior to venous leg ulceration and expressed an interest in either becoming active or maintaining an active lifestyle. Overall four themes emerged from the findings: i) participant understanding of the relationship between chronic venous insufficiency and exercise patterns, ii) fear of harm impacts upon positive beliefs and attitudes to exercise, iii) perceived factors limit exercise and iv) structured management facilitates exercise. Conclusion The value of exercise in improving outcomes in venous leg ulcers lies in its capacity to promote venous return and reduce the risk of secondary conditions in this population. Despite motivation and interest in being exercise active, people with venous leg ulcers report many obstacles. Further exploration of mechanisms that assist this patient population and promote understanding about management of barriers, coupled with promotion of enabling factors is vital for improving their exercise participation.

Retrospective observational study of patients who present to Australian rural emergency departments with undifferentiated chest pain

Aim To identify the demographic and clinical characteristics of patients who present to Australian rural emergency departments with chest pain. Design Retrospective, observational study Setting Rural emergency departments (ED) in Queensland, Australia Participants 337 consecutive adult patients with undifferentiated chest pain that presented between 1st September 2013 and 30th November 2013. Main outcome measures Service indicators, discharge diagnoses and disposition Results Presentations for undifferentiated chest pain represented 3.5% of all patient presentations during the sampling period. The mean age of patients was 48 years and 54% were male. Overall, 92% of patients left the ED within the 4-hour NEAT target. The majority of presentations were related to cardiac concerns (39%), followed by non-cardiac chest pain (17%), musculoskeletal (15%) and respiratory (10%) conditions. More than half of these patients were discharged at the completion of the ED service (52.8%), 40.6% were admitted, 3.3% left at own risk, 2.4% did not wait and less than 1% of patients required transfer to another hospital directly from the ED. Conclusions This study has provided information on the characteristics and processes of care for patients presenting to Australian rural EDs with undifferentiated chest pain that will inform service planning and further research to evaluate the effectiveness of care for these patients.

Can mothers accurately describe their toddler’s weight? Results from the NOURISH cohort

A mother’s perception of her child’s weight may be more important in determining how she feeds her child, than the child’s actual weight status. Use of controlling feeding practices, prompted by perceptions and concerns about weight, may disrupt the child’s innate self-regulation of energy intake. This can promote overeating and overweight (Costanzo & Woody, 1985). This study describes mother’s perception of her child’s weight relative to the child’s actual weight. Mothers in the control group of NOURISH (n=276) were asked to describe their child as underweight, normal weight, or somewhat/very overweight via self-administered questionnaire when children were aged 12-16 months (Daniels et al, 2009). Child’s weight and length were measured by study staff. At assessment, mean age (sd) was 13.7(1.3) months, mean weight-for-age z-score (sd) was 0.6(0.8) (WHO standards, 2008), and 51% were male. Twenty-seven children were perceived as underweight (10%) and twelve children were perceived as overweight (4%). ANOVA revealed significant differences in weight-for-age z-scores across each category of weight perception, mean (sd) -0.2(0.5), 0.6(0.8) and 1.8(0.7) for underweight, normal weight and overweight respectively F(4, 288)= 15.6, (p<0.00). Based on WHO criteria only one of the 27 children was correctly perceived as underweight (WHO 2008). Similarly while 12 children were perceived as overweight, 88 were actually overweight/at risk. At group level, children of mothers who perceived their child as underweight were indeed leaner. However at the individual level mothers could not accurately describe their child’s weight, tending to over-identify underweight and perceive overweight children as normal weight.