Inhibition of human prolyl oligopeptidase activity by the Cyclotide Psysol 2 isolated from Psychotria solitudinum

Cyclotides are head-to-tail cyclized peptides comprising a stabilizing cystine-knot motif. To date, they are well known for their diverse bioactivities such as anti-HIV and immunosuppressive properties. Yet little is known about specific molecular mechanisms, in particular the interaction of cyclotides with cellular protein targets. Native and synthetic cyclotide-like peptides from Momordica plants are potent and selective inhibitors of different serine-type proteinases such as trypsin, chymotrypsin, matriptase, and tryptase-beta. This study describes the bioactivity-guided isolation of a cyclotide from Psychotria solitudinum as an inhibitor of another serine-type protease, namely, the human prolyl oligopeptidase (POP). Analysis of the inhibitory potency of Psychotria extracts and subsequent fractionation by liquid chromatography yielded the isolated peptide psysol 2 (1), which exhibited an IC50 of 25 μM. In addition the prototypical cyclotide kalata B1 inhibited POP activity with an IC50 of 5.6 μM. The inhibitory activity appeared to be selective for POP, since neither psysol 2 nor kalata B1 were able to inhibit the proteolytic activity of trypsin or chymotrypsin. The enzyme POP is well known for its role in memory and learning processes, and it is currently being considered as a promising therapeutic target for the cognitive deficits associated with several psychiatric and neurodegenerative diseases, such as schizophrenia and Parkinson's disease. In the context of discovery and development of POP inhibitors with beneficial ADME properties, cyclotides may be suitable starting points considering their stability in biological fluids and possible oral bioavailability

Health care for irregular migrants: pragmatism across Europe. A qualitative study

<p>Abstract</p> <p>Background</p> <p>Health services in Europe face the challenge of delivering care to a heterogeneous group of irregular migrants (IM). There is little empirical evidence on how health professionals cope with this challenge. This study explores the experiences of health professionals providing care to IM in three types of health care service across 16 European countries.</p> <p>Results</p> <p>Semi-structured interviews were conducted with health professionals in 144 primary care services, 48 mental health services, and 48 Accident & Emergency departments (total n = 240). Although legal health care entitlement for IM varies across countries, health professionals reported facing similar issues when caring for IM. These issues include access problems, limited communication, and associated legal complications. Differences in the experiences with IM across the three types of services were also explored. Respondents from Accident & Emergency departments reported less of a difference between the care for IM patients and patients in a regular situation than did respondents from primary care and mental health services. Primary care services and mental health services were more concerned with language barriers than Accident & Emergency departments. Notifying the authorities was an uncommon practice, even in countries where health professionals are required to do this.</p> <p>Conclusions</p> <p>The needs of IM patients and the values of the staff appear to be as important as the national legal framework, with staff in different European countries adopting a similar pragmatic approach to delivering health care to IM. While legislation might help to improve health care for IM, more appropriate organisation and local flexibility are equally important, especially for improving access and care pathways.</p

Evolution of educational inequalities in site-specific cancer mortality among Belgian men between the 1990s and 2000s using a “fundamental cause” perspective

Background: According to the "fundamental cause" theory, emerging knowledge on health-enhancing behaviours and technologies results in health disparities. This study aims to assess (trends in) educational inequalities in site-specific cancer mortality in Belgian men in the 1990s and the 2000s using this framework. Methods: Data were derived from record linkage between the Belgian censuses of 1991 and 2001 and register data on mortality. The study population comprised all Belgian men aged 50-79 years during follow-up. Both absolute and relative inequality measures have been calculated. Results: Despite an overall downward trend in cancer mortality, educational differences are observed for the majority of cancer sites in the 2000s. Generally, inequalities are largest for mortality from preventable cancers. Trends over time in inequalities are rather stable compared with the 1990s. Conclusions: Educational differences in site-specific cancer mortality persist in the 2000s in Belgium, mainly for cancers related to behavioural change and medical interventions. Policy efforts focussing on behavioural change and healthcare utilization remain crucial in order to tackle these increasing inequalities.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

2008. “Trends in socioeconomic mortality inequalities in a southern European urban setting at the turn of the 21st century.” Journal of Epidemiology and Community Health 62(3

ABSTRACT Objective: To analyse trends in mortality inequalities by educational level for main causes of death among men and women in Barcelona, Spain, at the turn of the 21st century (1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003). Methods: The population of reference was all Barcelona residents older than 19 years. All deaths between 1992-2003 were included. Educational level was obtained through record linkage between the mortality register and the municipal census of Barcelona city. Variables studied were age, sex, educational level, period of death (four periods of 3 years) and cause of death. Age-standardised mortality rates for each educational level, sex and period were calculated. Poisson regression models were fitted to obtain relative index of inequality (RII) for educational level, adjusted for age for the time-periods. Results: RII for all causes of death was constant (around 1.5), but rate differences were higher in 1995-7 (715.6 per 100 000 in men and 352.8 in women) than in other periods and tended to decrease in men over the periods. Analysis of inequality trends by specific causes of death shows a stable trend for the majority of causes, with higher mortality among those with less education for all causes of death except lung cancer and breast cancer among women having RII below 1. Conclusions: Relative inequalities in total mortality by sex in Barcelona did not change during the 12 years studied, whereas absolute inequalities tended to decrease in men. Our study fills an important gap in southern Europe and Spanish literature on trends during this period

Good practice in emergency care: views from practitioners

Migrants make up a growing share of European populations. However, all too often their situation is compounded by problems with accessing health and other basic services. There is a need for tailored health policies, but robust data on the health needs of migrants and how best these needs can be met are scarce.Written by a collaboration of authors from three key international organisations (the European Observatory on Health Systems and Policies, the EUPHA Section on Migrant and Ethnic Minority Health, and the International Organization for Migration), as well as leading researchers from across Europe, the book thoroughly explores the different aspects of migration and health in the EU and how they can be addressed by health systems.Structured into five easy-to-follow sections, the volume includes: Contributions from experts from across Europe Key topics such as: access to human rights and health care; health issues faced by migrants; and the national and European policy response so far Conclusions drawn from the latest available evidence Comprehensive information on different aspects of health and migration and how they can best be addressed by health systems is still not easy to find. This book addresses this shortfall and will be of major value to researchers, students, policy-makers and practitioners concerned with migration and health in an increasingly diverse Europe

Cognitive function and emotional vulnerability in metastatic breast cancer: moderating effects of age and social support

Objective: Previous literature has established a relationship between cognitive function and symptoms of anxiety, depression, and post‐traumatic stress in primary breast cancer, but not in metastatic breast cancer (MBC). The current study examined the relationship between cognitive function and symptoms of anxiety, depression, and post‐traumatic stress as well as the moderating effects of age, time since MBC diagnosis, and social support. Methods: Subjective and objective measures of cognitive function as well as self‐ reports of emotional vulnerability were completed by 59 women diagnosed with MBC who were recruited through social media and support groups. Results: Emotional vulnerability scores were associated with perceived measures of cognitive function. Additionally, low levels of perceived cognitive function were met with increased levels of depression with social support moderating this relationship buffering against depression. Age was found to moderate the relationship between cognitive function and post‐traumatic stress with younger women at a greater risk of vulnerability. Out of all the emotional vulnerability measures, only anxiety negatively correlated with objective task performance. Conclusions: This study established a relationship between cognitive function and emotional vulnerability in MBC patients. It emphasised how vulnerable younger MBC women are to post‐traumatic stress, and the importance of the combined effects of cognitive function and social support in buffering against depression. Our results have important implications for developing new interventions and treatment plans that consider the roles of these factors in ensuring a better quality of life in MBC