The deregulation of RNA polymerases I and III in tumours

RNA polymerases I and III are responsible for approximately 80% of all nuclear transcription. The activity of these enzymes is a major determinant of the biosynthetic capacity of cells, since they synthesise important products required for protein synthesis, such as tRNAs and rRNAs. Regulation of these polymerases is likely to be of fundamental importance, since their activity is controlled directly by two cardinal tumour suppressors, RB and p53. Cervical, breast and colorectal malignancies were investigated to assess if activity of RNA polymerases I and III is deregulated in these cancers. Expression studies of genes transcribed by these polymerases demonstrated that most of the tumour biopsies examined displayed deregulated transcriptional activity in comparison with matched normal tissue. In the cervical biopsy samples examined, the presence of human papillomavirus 16 correlated with dramatic and specific overexpression of genes transcribed by these polymerases. This may be explained by the fact that, upon integration into the host genome, this virus upregulates the levels of the oncoproteins E6 and E7, which are able to neutralise p53 and RB, respectively. Furthermore, Brf1, a subunit of TFIIIB, was also found to be overexpressed, and this correlated with the increased levels of RNA polymerase III transcripts in the human papillomavirus 16 infected samples. This subunit was also found to be elevated in some cases of the other tumour types tested. When other factors were investigated that may contribute to upregulated rates of transcription, it was found that in the breast tumour biopsies, upregulation of c-Myc closely correlated with increased levels of RNA polymerase I transcripts as well as MRP and 7SK transcripts. In the colon tumour biopsies, a correlation was observed between the c-Myc target, cyclin D2, and increased levels of RNA polymerase III transcripts. It was also found through comparison of a transformed and untransfomed cell line that RNA polymerase III transcription may be regulated through acetylation and deacetylation

Evidence-based primary health care and local research: a necessary but problematic partnership

Background Front-line NHS staff undertake small research projects to answer questions about local patients and services, but these projects often face considerable challenges. This paper reports on one such project. Aims and methods of study The study used structured interviews in order to find out about the knowledge of nutrition among Bangladeshis using an NHS Walk-in Centre. Development of the study Time constraints posed considerable difficulties in progressing and completing the study; flaws in the methodology emerged; and underpinning assumptions about health promotion and ethnic minority health beliefs were open to challenge. Learning from the study Despite this, some findings were valuable and have considerable potential as a stimulus to critical thinking among practitioners about their own attitudes, as well as raising issues that future research would find it useful to addres

Evidence-based primary health care and local research: a necessary but problematic partnership

Background: Front-line NHS staff undertake small research projects to answer questions about local patients and services, but these projects often face considerable challenges. This paper reports on one such project. Aims and methods of study:The study used structured interviews in order to find out about the knowledge of nutrition among Bangladeshis using an NHS Walk-in Centre. Development of the study: Time constraints posed considerable difficulties in progressing and completing the study; flaws in the methodology emerged; and underpinning assumptions about health promotion and ethnic minority health beliefs were open to challenge. Learning from the study: Despite this, some findings were valuable and have considerable potential as a stimulus to critical thinking among practitioners about their own attitudes, as well as raising issues that future research would find it useful to address

Comparison of the prognostic value of ECOG-PS, MGPS and BMI/WL: Implications for a clinically important framework in the assessment and treatment of advanced cancer

BACKGROUND AND AIMS:The systemic inflammatory response is associated with the loss of lean tissue, anorexia, weakness, fatigue and reduced survival in patients with advanced cancer and therefore is important in the definition of cancer cachexia. The aim of the present study was to carry out a direct comparison of the prognostic value of Eastern Cooperative Oncology Group Performance Status (ECOG-PS), modified Glasgow Prognostic Score (mGPS) and Body Mass Index/Weight Loss Grade (BMI/WL grade) in patients with advanced cancer. METHOD:All data were collected prospectively across 18 sites in the UK and Ireland. Patient's age, sex, ECOG-PS, mGPS and BMI/WL grade were recorded, as were details of underlying disease including metastases. Survival data were analysed using univariate and multivariate Cox regression. RESULTS:A total of 730 patients were assessed. The majority of patients were male (53%), over 65 years of age (56%), had an ECOG-PS>0/1 (56%), mGPS≥1 (56%), BMI≥25 (51%), <2.5% weight loss (57%) and had metastatic disease (86%). On multivariate cox regression analysis ECOG-PS (HR 1.61 95%CI 1.42-1.83, p < 0.001), mGPS (HR 1.53, 95%CI 1.39-1.69, p < 0.001) and BMI/WL grade (HR 1.41, 95%CI 1.25-1.60, p < 0.001) remained independently associated with overall survival. In patients with a BMI/WL grade 0/1 both ECOG and mGPS remained independently associated with overall survival. CONCLUSION:The ECOG/mGPS framework may form the basis of risk stratification of survival in patients with advanced cancer

Towards a Full Life: An Evaluation of Family Support Programmes for People with a Disability in Ireland

For the past five decades,there has been an increasing awareness of the need for service and societal responses to people with disabilities to be addressed through a person-centered approach. A person-centered approach is one which seeks to put the person first. The principle of person-centeredness, which is identified as one of the four key principles underpinning Irish health policy, is based in the belief that in order to meet the desires and needs of an individual, their "unique identity...particular gifts and wounds...right to choose, and...capacity to develop, participate and contribute" must be maintained centre stage. Furthermore, it is recognised that person-centered approaches must take account, not only of the person with disability, but also of the family, as their role may be key in ensuring that true person-centerednessis achieved This is particularly relevant to the establishment and maintenance of the person's circle of support beyond professional services. Thus, whereas person-centerednessis rightly focused on the person, there is a need for service providers to also have a family-centred focus, which is aimed at supporting family to support their family member who has a disability.In 2010, Genio grant aided four family focused initiatives with a focus on building capacity in a variety of stakeholders in order to promote and support the inclusion of people with disabilities. The initiatives involved training and capacity building with families of people with disability, including people with severe and complex disabilities. The general aim of the initiatives was to increase family members' knowledge and skills and enable them to plan better lives for their family member and to advocate on their behalf. In 2012, Genio commissioned a team of researchers, from Trinity College Dublin, to conduct an evaluation of the four grant-aided family-focused initiatives from the perspectives of families of people with disabilities and services/organisations. The evaluation employed a multi-method approach using qualitative and quantitative methods to provide a comprehensive evaluation. Data was collected using individual interviews, surveys and documentary analysis

Computed tomography diagnosed cachexia and sarcopenia in 725 oncology patients: is nutritional screening capturing hidden malnutrition?

Background: Nutrition screening on admission to hospital is mandated in many countries, but to date, there is no consensus on which tool is optimal in the oncology setting. Wasting conditions such as cancer cachexia (CC) and sarcopenia are common in cancer patients and negatively impact on outcomes; however, they are often masked by excessive adiposity. This study aimed to inform the application of screening in cancer populations by investigating whether commonly used nutritional screening tools are adequately capturing nutritionally vulnerable patients, including those with abnormal body composition phenotypes (CC, sarcopenia, and myosteatosis). Methods: A prospective study of ambulatory oncology outpatients presenting for chemotherapy was performed. A detailed survey incorporating clinical, nutritional, biochemical, and quality of life data was administered. Participants were screened for malnutrition using the Malnutrition Universal Screening Tool (MUST), Malnutrition Screening Tool (MST), and the Nutritional Risk Index (NRI). Computed tomography (CT) assessment of body composition was performed to diagnose CC, sarcopenia, and myosteatosis according to consensus criteria. Results: A total of 725 patients (60% male, median age 64 years) with solid tumours participated (45% metastatic disease). The majority were overweight/obese (57%). However, 67% were losing weight, and CT analysis revealed CC in 42%, sarcopenia in 41%, and myosteatosis in 46%. Among patients with CT-identified CC, the MUST, MST, and NRI tools categorized 27%, 35%, and 7% of them as ‘low nutritional risk’, respectively. The percentage of patients with CT-identified sarcopenia and myosteatosis that were categorised as ‘low nutritional risk’ by MUST, MST and NRI were 55%, 61%, and 14% and 52%, 50%, and 11%, respectively. Among these tools, the NRI was most sensitive, with scores <97.5 detecting 85.8%, 88.6%, and 92.9% of sarcopenia, myosteatosis, and CC cases, respectively. Using multivariate Cox proportional hazards models, NRI score < 97.5 predicted greater mortality risk (hazard ratio 1.8, confidence interval: 1.2–2.8, P = 0.007). Conclusions: High numbers of nutritionally vulnerable patients, with demonstrated abnormal body composition phenotypes on CT analysis, were misclassified by MUST and MST. Caution should be exercised when categorizing the nutritional risk of oncology patients using these tools. NRI detected the majority of abnormal body composition phenotypes and independently predicted survival. Of the tools examined, the NRI yielded the most valuable information from screening and demonstrated usefulness as an initial nutritional risk grading system in ambulatory oncology patients

A window beneath the skin: how computed tomography assessment of body composition can assist in the identification of hidden wasting conditions in oncology that profoundly impact outcomes?

Advancements in image-based technologies and body composition research over the past decade has led to increased understanding of the importance of muscle abnormalities, such as low muscle mass (sarcopenia), and more recently low muscle attenuation (MA), as important prognostic indicators of unfavourable outcomes in patients with cancer. Muscle abnormalities can be highly prevalent in patients with cancer (ranging between 10 and 90 %), depending on the cohort under investigation and diagnostic criteria used. Importantly, both low muscle mass and low MA have been associated with poorer tolerance to chemotherapy, increased risk of post-operative infectious and non-infectious complications, increased length of hospital stay and poorer survival in patients with cancer. Studies have shown that systemic antineoplastic treatment can exacerbate losses in muscle mass and MA, with reported loss of skeletal muscle between 3 and 5 % per 100 d, which are increased exponentially with progressive disease and proximity to death. At present, no effective medical intervention to improve muscle mass and MA exists. Most research to date has focused on treating muscle depletion as part of the cachexia syndrome using nutritional, exercise and pharmacological interventions; however, these single-agent therapies have not provided promising results. Rehabilitation care to modify body composition, either increasing muscle mass and/or MA should be conducted, and its respective impact on oncology outcomes explored. Although the optimal timing and treatment strategy for preventing or delaying the development of muscle abnormalities are yet to be determined, multimodal interventions initiated early in the disease trajectory appear to hold the most promise

A 58-Year-Old Woman with Abdominal Symptoms and Elevated C-Reactive Protein

Babak Javid and colleagues discuss the differential diagnosis, investigation, and management of a woman with abdominal symptoms and a raised C-reactive protein

The Summer Of The Pivot: Prioritizing Equity In Remote Instruction Through A Multidisciplinary Community Of Practice Initiative At A Canadian University

This article is about the multidisciplinary Community of Practice (CoP) initiative that was implemented in the summer of 2020- summer of the pivot- at a Canadian post-secondary institution to prepare faculty, staff, and students for remote teaching and learning while navigating pandemic conditions created by COVID-19. The CoP as a case study using Critical Theory as a theoretical framework examines the experiences of a collective group of faculty and staff from different disciplines leading a multidisciplinary university-wide initiative and the implications of the approach for promoting effective pedagogies for teaching and learning remotely. Findings based on feedback from workshop attendees, reflections from the CoP facilitators, and comments forwarded to senior administrators about the impact and the effectiveness of the program indicate positive results. It is recommended that although the CoP initiative was originally conceived as a response to the summer of the pivot, it should become an integral approach to promoting dialogue and innovative strategies to advance equitable practices in higher education by cultivating community networks. The findings serve to continue constructive dialogues and discussions about how universities can transition, pivot, and mobilize innovatively and creatively to prioritize equitable teaching and learning conditions that challenge the status quo. This requires a long-term commitment by higher education institutions to break away from historically normalized practices and invest in innovative ways to identify and meet the needs of various stakeholders