The ubiquitin-proteasome system in retinal health and disease

The ubiquitin–proteasome system (UPS) is the main intracellular pathway for modulated protein turnover, playing an important role in the maintenance of cellular homeostasis. It also exerts a protein quality control through degradation of oxidized, mutant, denatured, or misfolded proteins and is involved in many biological processes where protein level regulation is necessary. This system allows the cell to modulate its protein expression pattern in response to changing physiological conditions and provides a critical protective role in health and disease. Impairments of UPS function in the central nervous system (CNS) underlie an increasing number of genetic and idiopathic diseases, many of which affect the retina. Current knowledge on the UPS composition and function in this tissue, however, is scarce and dispersed. This review focuses on UPS elements reported in the retina, including ubiquitinating and deubiquitinating enzymes (DUBs), and alternative proteasome assemblies. Known and inferred roles of protein ubiquitination, and of the related, SUMO conjugation (SUMOylation) process, in normal retinal development and adult homeostasis are addressed, including modulation of the visual cycle and response to retinal stress and injury. Additionally, the relationship between UPS dysfunction and human neurodegenerative disorders affecting the retina, including Alzheimer's, Parkinson's, and Huntington's diseases, are dealt with, together with numerous instances of retina-specific illnesses with UPS involvement, such as retinitis pigmentosa, macular degenerations, glaucoma, diabetic retinopathy (DR), and aging-related impairments. This information, though still basic and limited, constitutes a suitable framework to be expanded in incoming years and should prove orientative toward future therapy design targeting sight-affecting diseases with a UPS underlying basis.

A metasynthesis of qualitative studies regarding opinions and perceptions about barriers and determinants of health services’ accessibility in economic migrants

Background: Access to health services is an important health determinant. New research in health equity is required, especially amongst economic migrants from developing countries. Studies conducted on the use of health services by migrant populations highlight existing gaps in understanding which factors affect access to these services from a qualitative perspective. We aim to describe the views of the migrants regarding barriers and determinants of access to health services in the international literature (1997–2011). Methods: A systematic review was conducted for Qualitative research papers (English/Spanish) published in 13 electronic databases. A selection of articles that accomplished the inclusion criteria and a quality evaluation of the studies were carried out. The findings of the selected studies were synthesised by means of metasynthesis using different analysis categories according to Andersen’s conceptual framework of access and use of health services and by incorporating other emergent categories. Results: We located 3,025 titles, 36 studies achieved the inclusion criteria. After quality evaluation, 28 articles were definitively synthesised. 12 studies (46.2%) were carried out in the U.S and 11 studies (42.3%) dealt with primary care services. The participating population varied depending mainly on type of host country. Barriers were described, such as the lack of communication between health services providers and migrants, due to idiomatic difficulties and cultural differences. Other barriers were linked to the economic system, the health service characteristics and the legislation in each country. This situation has consequences for the lack of health control by migrants and their social vulnerability. Conclusions: Economic migrants faced individual and structural barriers to the health services in host countries, especially those with undocumented situation and those experimented idiomatic difficulties. Strategies to improve the structures of health systems and social policies are needed.

Assessment of the Association of Health with the Liberalisation of Trade in Services under the World Trade Organisation

Background: The liberalisation of trade in services which began in 1995 under the General Agreement on Trade in Services (GATS) of the World Trade Organisation (WTO) has generated arguments for and against its potential health effects. Our goal was to explore the relationship between the liberalisation of services under the GATS and three health indicators – life expectancy (LE), under-5 mortality (U5M) and maternal mortality (MM) - since the WTO was established. Methods and Findings: This was a cross-sectional ecological study that explored the association in 2010 and 1995 between liberalisation and health (LE, U5M and MM), and between liberalisation and progress in health in the period 1995–2010, considering variables related to economic and social policies such as per capita income (GDP pc), public expenditure on health (PEH), and income inequality (Gini index). The units of observation and analysis were WTO member countries with data available for 2010 (n = 116), 1995 (n = 114) and 1995–2010 (n = 114). We conducted bivariate and multivariate linear regression analyses adjusted for GDP pc, Gini and PEH. Increased global liberalisation in services under the WTO was associated with better health in 2010 (U5M: 20.358 p,0.001; MM: 20.338 p = 0.001; LE: 0.247 p = 0.008) and in 1995, after adjusting for economic and social policy variables. For the period 1995–2010, progress in health was associated with income equality, PEH and per capita income. No association was found with global liberalisation in services. Conclusions: The favourable association in 2010 between health and liberalisation in services under the WTO seems to reflect a pre-WTO association observed in the 1995 data. However, this liberalisation did not appear as a factor associated with progress in health during 1995–2010. Income equality, health expenditure and per capita income were more powerful determinants of the health of populations.

Health-related quality of life and determinant factors in celiac disease. A population-based analysis of adult patients in Spain

Background: Celiac disease (CD) has a negative impact on the health-related quality of life (HRQL) of affected patients. Although HRQL and its determinants have been examined in Spanish CD patients specifically recruited in hospital settings, these aspects of CD have not been assessed among the general Spanish population. Methods: An observational, transversal study of a non-randomized, representative sample of adult celiac patients throughout all of Spain's Autonomous Regions. Subjects were recruited through celiac patient associations. A Spanish version of the self-administered Celiac Disease-Quality of Life (CD-QOL) questionnaire was used. Determinant factors of HRQL were assessed with the aid of multivariate analysis to control for confounding factors. Results: We analyzed the responses provided by 1,230 patients, 1,092 (89.2%) of whom were women. The overall mean value for the CD-QOL index was 56.3 ± 18.27 points. The dimension that obtained the most points was dysphoria, with 81.3 ± 19.56 points, followed by limitations with 52.3 ± 23.43 points; health problems, with 51.6 ± 26.08 points, and inadequate treatment, with 36.1 ± 21.18 points. Patient age and sex, along with time to diagnosis, and length of time on a gluten-free diet were all independent determinant factors of certain dimensions of HRQL: women aged 31 to 40 expressed poorer HRQL while time to diagnosis and length of time on a gluten-free diet were determinant factors for better HRQL scores. Conclusions: The HRQL of adult Spanish celiac subjects is moderate, improving with the length of time patients remain on a gluten-free diet.

Self-rated health and mortality: a follow-up study of a Spanish population

Objectives: Self-rated health (SRH) is known to be a valid indicator for the prediction of health outcomes. The aims of this study were to describe and analyse the associations between SRH and health status, socio-economic and demographic characteristics; and between SRH and mortality in a Spanish population. Study design: Longitudinal study. Methods: A sample of 5275 adults (age ≥21 years) residing in the Valencian Community (Spanish Mediterranean region) was surveyed in 2005 and followed for four years. SRH was categorized into good and poor health. The response variable was mortality (dead/alive), obtained from the local mortality register. Logistic regression models were adjusted in order to analyse the associations between SRH and health status, socio-economic and demographic characteristics; odds ratios were calculated to measure the associations. Poisson regression models were adjusted in order to analyse the associations between mortality and explanatory variables; the relative risk of death was calculated to measure the associations. Results: Poor SRH was reported by 25.9% of respondents, and the mortality rate after four years of follow-up was 3.6%. An association was found between SRH and the presence of chronic disease and disability in men and women. A perception of poor health vs good health led to a mortality risk of 3.0 in men and 2.7 in women. SRH was predictive of mortality, even after adjusting for all other variables. In men and women, the presence of disability provided additional predictive ability. Conclusions: SRH was predictive of mortality in both men and women, and acted as a mediator between socio-economic, demographic and health conditions and mortality.