Peptidylarginine deiminase and deiminated proteins are detected throughout early halibut ontogeny - Complement components C3 and C4 are post-translationally deiminated in halibut (Hippoglossus hippoglossus L.)

Post-translational protein deimination is mediated by peptidylarginine deiminases (PADs), which are calcium dependent enzymes conserved throughout phylogeny with physiological and pathophysiological roles. Protein deimination occurs via the conversion of protein arginine into citrulline, leading to structural and functional changes in target proteins. In a continuous series of early halibut development from 37 to 1050° d, PAD, total deiminated proteins and deiminated histone H3 showed variation in temporal and spatial detection in various organs including yolksac, muscle, skin, liver, brain, eye, spinal cord, chondrocytes, heart, intestines, kidney and pancreas throughout early ontogeny. For the first time in any species, deimination of complement components C3 and C4 is shown in halibut serum, indicating a novel mechanism of complement regulation in immune responses and homeostasis. Proteomic analysis of deiminated target proteins in halibut serum further identified complement components C5, C7, C8 C9 and C1 inhibitor, as well as various other immunogenic, metabolic, cytoskeletal and nuclear proteins. Post-translational deimination may facilitate protein moonlighting, an evolutionary conserved phenomenon, allowing one polypeptide chain to carry out various functions to meet functional requirements for diverse roles in immune defences and tissue remodelling

Individual risk assessment and information technology to optimise screening frequency for diabetic retinopathy.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.AIMS/HYPOTHESIS: The aim of this study was to reduce the frequency of diabetic eye-screening visits, while maintaining safety, by using information technology and individualised risk assessment to determine screening intervals. METHODS: A mathematical algorithm was created based on epidemiological data on risk factors for diabetic retinopathy. Through a website, www.risk.is , the algorithm receives clinical data, including type and duration of diabetes, HbA(1c) or mean blood glucose, blood pressure and the presence and grade of retinopathy. These data are used to calculate risk for sight-threatening retinopathy for each individual's worse eye over time. A risk margin is defined and the algorithm recommends the screening interval for each patient with standardised risk of developing sight-threatening retinopathy (STR) within the screening interval. We set the risk margin so that the same number of patients develop STR within the screening interval with either fixed annual screening or our individualised screening system. The database for diabetic retinopathy at the Department of Ophthalmology, Aarhus University Hospital, Denmark, was used to empirically test the efficacy of the algorithm. Clinical data exist for 5,199 patients for 20 years and this allows testing of the algorithm in a prospective manner. RESULTS: In the Danish diabetes database, the algorithm recommends screening intervals ranging from 6 to 60 months with a mean of 29 months. This is 59% fewer visits than with fixed annual screening. This amounts to 41 annual visits per 100 patients. CONCLUSION: Information technology based on epidemiological data may facilitate individualised determination of screening intervals for diabetic eye disease. Empirical testing suggests that this approach may be less expensive than conventional annual screening, while not compromising safety. The algorithm determines individual risk and the screening interval is individually determined based on each person's risk profile. The algorithm has potential to save on healthcare resources and patients' working hours by reducing the number of screening visits for an ever increasing number of diabetic patients in the world

A systematic review on health resilience to economic crises

Background The health effects of recent economic crises differ markedly by population group. The objective of this systematic review is to examine evidence from longitudinal studies on factors influencing resilience for any health outcome or health behaviour among the general population living in countries exposed to financial crises. Methods We systematically reviewed studies from six electronic databases (EMBASE, Global Health, MEDLINE, PsycINFO, Scopus, Web of Science) which used quantitative longitudinal study designs and included: (i) exposure to an economic crisis; (ii) changes in health outcomes/behaviours over time; (iii) statistical tests of associations of health risk and/or protective factors with health outcomes/behaviours. The quality of the selected studies was appraised using the Quality Assessment Tool for Quantitative Studies. PRISMA reporting guidelines were followed. Results From 14,584 retrieved records, 22 studies met the eligibility criteria. These studies were conducted across 10 countries in Asia, Europe and North America over the past two decades. Ten socio-demographic factors that increased or protected against health risk were identified: gender, age, education, marital status, household size, employment/occupation, income/ financial constraints, personal beliefs, health status, area of residence, and social relations. These studies addressed physical health, mortality, suicide and suicide attempts, mental health, and health behaviours. Women’s mental health appeared more susceptible to crises than men’s. Lower income levels were associated with greater increases in cardiovascular disease, mortality and worse mental health. Employment status was associated with changes in mental health. Associations with age, marital status, and education were less consistent, although higher education was associated with healthier behaviours. Conclusions Despite widespread rhetoric about the importance of resilience, there was a dearth of studies which operationalised resilience factors. Future conceptual and empirical research is needed to develop the epidemiology of resilience

Assessing knowledge of human papillomavirus and collecting data on sexual behavior: computer assisted telephone versus face to face interviews

<p>Abstract</p> <p>Background</p> <p>Education campaigns seeking to raise awareness of human papillomavirus (HPV) and promoting HPV vaccination depend on accurate surveys of public awareness and knowledge of HPV and related sexual behavior. However, the most recent population-based studies have relied largely on computer-assisted telephone interviews (CATI) as opposed to face to face interviews (FTFI). It is currently unknown how these survey modes differ, and in particular whether they attract similar demographics and therefore lead to similar overall findings.</p> <p>Methods</p> <p>A comprehensive survey of HPV awareness and knowledge, including sexual behavior, was conducted among 3,045 Singaporean men and women, half of whom participated via CATI, the other half via FTFI.</p> <p>Results</p> <p>Overall levels of awareness and knowledge of HPV differed between CATI and FTFI, attributable in part to demographic variations between these survey modes. Although disclosure of sexual behavior was greater when using CATI, few differences between survey modes were found in the actual information disclosed.</p> <p>Conclusion</p> <p>Although CATI is a cheaper, faster alternative to FTFI and people appear more willing to provide information about sexual behavior when surveyed using CATI, thorough assessments of HPV awareness and knowledge depend on multiple survey modes.</p

STAT-1 decoy oligodeoxynucleotide inhibition of acute rejection in mouse heart transplants

During acute rejection of cardiac transplants endothelial cell–leukocyte interaction fuelled by co-stimulatory molecules like CD40/CD154 may ultimately lead to graft loss. One key player in up-regulating the expression of such pro-inflammatory gene products is the interferon-γ-dependent transcription factor STAT-1. Hence down-regulating interferon-γ-stimulated pro-inflammatory gene expression in the graft endothelial cells by employing a decoy oligodeoxynucleotide (dODN) neutralising STAT-1 may protect the graft. To verify this hypothesis, heterotopic mouse heart transplantation was performed in the allogeneic B10.A(2R) to C57BL/6 and syngeneic C57BL/6 to C57BL/6 strain combination without immunosuppression. Graft vessels were pre-treated with STAT-1 dODN, mutant control ODN (10 μM each) or vehicle (Ringer solution). Cellular rejection (vascular and interstitial component) was graded histologically and CD40, ICAM-1, VCAM-1, MCP-1, E-selectin and RANTES expression in the graft monitored by real time PCR 24 h and 9 days post-transplantation. Nine days after transplantation both rejection scores were significantly diminished by 85 and 70%, respectively, in STAT-1 dODN-treated allografts as compared to mutant control ODN-treated allografts. According to immunohistochemistry analysis, this was accompanied by a reduced infiltration of monocyte/macrophages and T cells into the graft myocardium. In addition, pro-inflammatory gene expression was strongly impaired by more than 80% in STAT-1 dODN-treated allografts 24 h post-transplantation but not in mutant control ODN or vehicle-treated allografts. This inhibitory effect on pro-inflammatory gene expression was no longer detectable 9 days post-transplantation. Single periprocedural treatment with a STAT-1 dODN thus effectively reduces cellular rejection in mouse heart allografts. This effect is associated both with an early decline in pro-inflammatory gene expression and a later drop in mononuclear cell infiltration