The Role of Peptidyl Prolyl Isomerases in Aging and Vascular Diseases

Peptidyl prolyl isomerases (PPIases) are proteins belonging to the immunophilin family and are characterised by their cis-trans isomerization activity at the X-Pro peptide bond, in addition to their tetratricopeptide repeat (TPR) domain, important for interaction with the molecular chaperone, Hsp90. Due to this unique structure these proteins are able to facilitate protein-protein interactions which can impact significantly on a range of cellular processes such as cell signalling, differentiation, cell cycle progression, metabolic activity and apoptosis. Malfunction and/or dysregulation of most members of this class of proteins promotes cellular damage and tissue/organ failure, predisposing to ageing and age-related diseases. Many individual genes within the PPIase family are associated with several age-related diseases including cardiovascular diseases (CVDs), atherosclerosis, type II diabetes (T2D), chronic kidney disease (CDK), neurodegeneration, cancer and age-related macular degeneration (AMD), in addition to the ageing process itself. This review will focus on the different roles of PPIases, and their therapeutic/biomarker potential in these age-related vascular diseases.

Appointment keeping for medical review among patients with selected chronic diseases in an urban area of Uganda

Introduction: proper management of chronic diseases is important for prevention of disease complications and yet some patients miss appointments for medical review thereby missing the opportunity for proper monitoring of their disease conditions. There is limited information on missed appointments among chronic disease patients in resource limited settings. This study aimed to determine the prevalence of missed appointments for medical review and associated factors among chronic disease patients in an urban area of Uganda.

Methods: patients or caregivers of children with chronic diseases were identified as they bought medicines from a community pharmacy. They were visited at home to access their medical documents and those whose chronic disease status was ascertained were enrolled. The data was collected using: questionnaires, review of medical documents, and in-depth interviews with chronic disease patients.

Results: the prevalence of missed appointments was 42% (95%CI=35-49%). The factors associated with missed appointments were: monthly income ?30US Dollars (OR=2.56, CI=1.25–5.26), affording less than half of prescribed drugs (OR=3.92, CI=1.64–9.40), not experiencing adverse events (OR=2.66, CI=1.26–5.61), not sure if treatment helps (OR=2.84, CI=1.047.77), not having a medicines administration schedule (OR=6.77, CI=2.11–21.68), and increasing number of drugs (OR=0.72, CI=0.53–0.98). Conclusion: patients missed appointments mainly due to: financial and health system barriers, conflicting commitments with appointments, and perceptions of the disease condition. Patients should be supported with accessible and affordable health services.

Clinical trial designs for rare diseases: Studies developed and discussed by the International Rare Cancers Initiative

BACKGROUND: The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research.

SETTINGS: The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional--usually randomized--clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed.

RESULTS: The IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider these for use in future trials and understand the choices made for each design.

INTERPRETATION: Trials can be designed using a wide array of possibilities. There is no 'one size fits all' solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases.

Traditions and transitions: teenagers’ perceptions of parading in Belfast

The purpose of this article is to explore and illuminate teenagers' experiences of, and attitudes to, parades in Belfast. The research draws on responses from 125 teenagers located in interface areas (areas where Catholics and Protestants live side by side but apart) to government supported attempts to rebrand Orangefest (traditional parade associated with Protestant/Unionist/Loyalist community) and St Patrick's Day (traditional parade associated with Catholic/Nationalist/Republican community) as all-inclusive community events. For the most part, young people access these parades in pre-existing, single identity peer groups and view these parades as either inclusive or exclusive calling into question the extent to which Belfast's city centre can be viewed as shared space.

Young teenagers' experiences of domestic abuse

This article reports on the first findings from the Boys to Men Research Project. In total, 1143 pupils aged 13–14 years completed a questionnaire to assess their experiences of domestic abuse as victims, witnesses and perpetrators. Overall, 45% of pupils who had been in a dating relationship reported having been victimised, 25% having perpetrated it, with the only difference in rates of victimisation and perpetration between boys and girls being in relation to sexual victimisation. Of the whole sample, 34% reported having witnessed it in their own family. There was a relationship between victimisation and perpetration with the vast majority of perpetrators (92%) also reporting experiencing abuse from a boyfriend/girlfriend. There was also a relationship between experiencing abuse and help seeking from adults, with those who have been victimised less likely to say they would seek help if they were hit by a partner than those who had yet to experience any abuse. The relationship between help seeking and experiences of abuse is further complicated by gender, with girls twice as likely to seek help than boys, but with girls who have previously hit a partner among the most reticent group. The paper concludes with highlighting the implications of these findings for those undertaking preventative work in schools.

Look and Tell: Using Photo-Elicitation Methods with Teenagers

This article reflects on the usefulness of photo elicitation in research with young people. As part of an Economic and Social Research Council-funded project exploring conflict and divisions in contested cities, teenagers living or attending schools in segregated areas of Belfast were presented with 11 photographs depicting the city's traditional ethno religious divisions, the new ‘post conflict’ consumerist city and youth subcultures. In response to each photo, the young people produced individual written comments and their opinions were fleshed out during follow-up focus group interviews. Drawing on these responses, the strengths and weaknesses of using photo elicitation in research with young people and its capacity to generate new insights into teenagers' spatial perceptions and experiences are outlined.

Teenagers' Perceptions and Experiences of Belfast as a Divided City

In this ‘research project’ case study, we provide an empirical example of how quantitative and qualitative methods were combined within a single study and discuss some of the strengths and weaknesses of our combined methodology which included questionnaires, photo-prompts and focus-group interviews. Our intention in using mixed methods was to enhance understandings of the meanings of space, place and territory on the everyday lives of young people growing up in Belfast. How do young people negotiate space in politically divided cities such as Belfast? Is territory important, and if so, why is it important? How do we construct an appropriate and relevant study design that can not only describe, but explain what place, space and territory mean to young people, and more importantly, how it impacts on their everyday lives? How useful is it to apply a mixed-methods approach to finding answers to these questions? We explain why and how we used a mixed-methods approach and illuminate some of the issues we encountered. We demonstrate how mixed methods can provide not just complementary but also new insights into the topic under investigation. We hope that the case study encourages you to experiment, or at least consider, the potential of using mixed methods.

The macroeconomic impact of non-communicable diseases in China and India: Estimates, projections, and comparisons

This study provides estimates of the macroeconomic impact of non-communicable diseases (NCDs) inChina and India for the period 2012–2030. Our estimates are derived using the World Health Organization’sEPIC model of economic growth, which focuses on the negative effects of NCDs on labor supply andcapital accumulation. We present results for the five main NCDs (cardiovascular disease, cancer, chronicrespiratory disease, diabetes, and mental health). Our undiscounted estimates indicate that the cost ofthe five main NCDs will total USD 23.03 trillion for China and USD 4.58 trillion for India (in 2010 USD).For both countries, the most costly domain is cardiovascular disease. Our analyses also reveal that thecosts are much larger in China than in India mainly because of China’s higher and steeper income trajectory,and to a lesser extent its older population. Rough calculations also indicate that WHO’s best buys foraddressing the challenge of NCDs are highly cost-beneficial

Abundant genetic overlap between blood lipids and immune-mediated diseases indicates shared molecular genetic mechanisms

Epidemiological studies suggest a relationship between blood lipids and immune-mediated diseases, but the nature of these associations is not well understood. We used genome-wide association studies (GWAS) to investigate shared single nucleotide polymorphisms (SNPs) between blood lipids and immune-mediated diseases. We analyzed data from GWAS (n~200,000 individuals), applying new False Discovery Rate (FDR) methods, to investigate genetic overlap between blood lipid levels [triglycerides (TG), low density lipoproteins (LDL), high density lipoproteins (HDL)] and a selection of archetypal immune-mediated diseases (Crohn's disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, psoriasis and sarcoidosis). We found significant polygenic pleiotropy between the blood lipids and all the investigated immune-mediated diseases. We discovered several shared risk loci between the immune-mediated diseases and TG (n = 88), LDL (n = 87) and HDL (n = 52). Three-way analyses differentiated the pattern of pleiotropy among the immune-mediated diseases. The new pleiotropic loci increased the number of functional gene network nodes representing blood lipid loci by 40%. Pathway analyses implicated several novel shared mechanisms for immune pathogenesis and lipid biology, including glycosphingolipid synthesis (e.g. FUT2) and intestinal host-microbe interactions (e.g. ATG16L1). We demonstrate a shared genetic basis for blood lipids and immune-mediated diseases independent of environmental factors. Our findings provide novel mechanistic insights into dyslipidemia and immune-mediated diseases and may have implications for therapeutic trials involving lipid-lowering and anti-inflammatory agents.

Economics of Non-Communicable Diseases in Indonesia

The Economics of Non-Communicable Diseases in Indonesia provides new data on the economic burden of NCDs in the country, and puts it in perspective by drawing a comparison with India and China. With this new addition to the series on the economics of NCDs, the World Economic Forum aims to advance the understanding of the expected economic output loss at the country level, particularly in countries in economic and epidemiological transition. The evidence presented provides a starting point in reorienting the dialogue on investing in healthy living and NCD prevention in Indonesia towards the view that a healthy population is an important factor for sustainable growth.

Understanding the help seeking behaviour of teenagers who experience relationship abuse (dating violence) from a feminist intersectional approach.

This presentation aims to raise issues related to teenage relationship abuse (TRA-dating violence) and help seeking behaviour from an intersectional approach. Even though teenage relationship abuse has been raised as an issue since the 80’s there is still an absence of an intersectional theoretical conceptualization of TRA. Existing conceptualizations are based on incorrect assumptions of sameness of teenagers experiences of TRA which ignore the unique developmental stages of teenagers as well as youth’s diverse lived experiences due to their sexual orientation, ethnicity, class, disability as well as other structural divisions. TRA exists in a social context of inequalities. For the individual survivor, this social context is created not only through romantic relationships, but also through relationships with families, peers, friends, classmates and others. Their experiences are constructed through these relationships which form part of the social context into which TRA needs to be analysed. The analytical framework of intersectionality can provide a framework of understanding how these lived experiences are enacted and negotiated contextually. Emphasis will be given to the help seeking behaviour of diverse youths. This presentation will explore the diverse lived experiences contextually. Methods and Findings: This presentation is based on a research project in Northern Ireland currently underway, thus, it will offer a preliminary conceptualisation of TRA from an intersectional approach. The findings will be contextualized taking into account the high rate of homophobia that exists in Northern Ireland amongst other things. Conclusion/Recommendation: Intersectionality needs to be the analytical framework through which teenagers’ relationship’s experience are analysed since the lived experiences of LGTB, BME and disabled youth cannot be analysed apart from the structural divisions, social location and the context they are experienced. This presentation argues that the intersectional approach of theorizing is congruent and contributes to anti-oppressive social work practice.