Fasciola hepatica:The therapeutic potential of a worm secretome

The success of helminth parasites is partly related to their ability to modulate host immune responses towards an anti-inflammatory/regulatory phenotype. This ability resides with the molecules contained in the secretome of various helminths that have been shown to interact with host immune cells and influence their function. Consequently, there exists a unique opportunity to exploit these molecules for the prophylactic and therapeutic treatment of human pro- and auto-inflammatory disorders (for example septic shock, transplant rejection and autoimmune disease). In this review, we describe the mechanisms used by the trematode parasite, Fasciola hepatica, to modulate the immune responses of its host and discuss the potent immune-modulatory effects of three individual molecules within the secretome; namely cathepsin L1, peroxiredoxin and helminth defence molecule. With a focus on the requirements from industry, we discuss the strategies by which these molecules may be clinically developed to control human immune responses in a way that is conducive to the prevention of immune-mediated diseases.

Does Job Search Monitoring Intensity Affect Unemployment? Evidence from Northern Ireland

Because unemployment benefit reforms typically package together a number of changes, few existing evaluations have been able to isolate the effects of changes in job search monitoring intensity on benefit recipient stocks or flows. Those few studies that do so draw mixed conclusions. This paper provides new estimates of monitoring impacts by exploiting plausibly exogenous periods where search monitoring has been temporarily withdrawn - with the regime otherwise unchanged - during a series of benefit office refurbishments in Northern Ireland. As we would expect from search theory, withdrawal of monitoring significantly increases the stock of unemployment benefit recipients via reduced outflows. © The London School of Economics and Political Science 2008.

Service preferences among family caregivers of the terminally ill

Objective: The ability of families to assume caregiving responsibilities is contingent on material, social, and professional support. Inadequate or inappropriate support to the terminally ill and their family caregivers can result in the misuse of resources and add burden to the family. In this report, we describe service preferences among informal caregivers of the terminally ill. Design: Three hundred seventy-three caregivers participated in telephone interviews at two points in time: when the terminally ill person was designated as palliative and 5 months subsequent to the first interview. In the case that the care recipient died during the study period, the caregiver participated in the interview three months after the death. Measures: After reviewing possible services received by the care recipients and caregivers, caregivers were asked to identify the five services they found most valuable and which services they would have liked to have had or received more of when caregiving. Results: The five services caregivers reported as most valuable included: in-home nursing care, (90.7%); family physicians, (45.6%); medical specialists, (46.4%); housekeeping, (23.6%); and, religious support, (11.3%). The five most frequently reported services that family caregivers would have liked to have received or had more available included: housekeeping, (13.1%); caregiver respite, (10.2%); in-home nursing care, (8.0%); personal support workers, (4.6%); and, self-help/support groups, (3.8%). Analyses revealed that most (64.8%) perceived service needs were of a supportive nature for caregivers. Caregiver perceptions of the value and perceived need of services were consistent over time and into bereavement. Logistic regression analyses suggested that younger caregivers who were not employed, reported higher levels of burden and cared for someone with a diagnosis of cancer had greater perceived service needs. Conclusions: The findings reported in this paper provide important insights into caregiver perceptions of valued services when caring for a terminally ill family member. These finding also highlight the stability of caregiver service perceptions over time and into bereavement.

Gender differences among Canadian spousal caregivers at the end of life

The purpose of this study was to examine gender differences in spousal caregiving at the end of life. The primary research question was to determine gender differences in caregiver strain among spousal caregivers. Secondary research questions investigated included (i) the presence of gender differences among spousal caregivers in the duration of care provided; (ii) gender differences among spousal caregivers in formal service use and unmet service needs; and (iii) whether support to care recipients in activities of daily living varied according to the gender of the spousal caregiver. The study was conducted over a 2-year period (2000-2002) in south-central Ontario, Canada. The study sample included 283 informal spousal caregivers (198 females, 85 males) each of whom were caring for a terminally ill spouse at the time they participated in a cross-sectional telephone survey. The analysis showed that females reported a significantly greater level of caregiving strain than males (t = -2.12, d.f. = 281, P = 0.035). When considering source of support in activities of daily living for the care recipient, differential assistance was noted on the basis of caregiver gender. Female caregivers had almost twice the odds of providing support in toileting-related tasks than male caregivers (odds ratio (OR) = 1.98, 95% confidence interval (CI) = 1.01-3.85, P = 0.044), while male caregivers had approximately twice the odds of providing support in mobility-related tasks (OR = 0.41, 95% CI = 0.21-0.81, P = 0.011). Care recipients who had a female caregiver had lower odds of receiving support from family and friends in tasks associated with personal care (OR = 0.17, 95% CI = 0.05-0.53, P = 0.002). To address gender differences in caregiving, a realistic home-based palliative care approach must take into account the importance of informal caregivers. © 2008 Blackwell Publishing Ltd.

Preferences for place of care and place of death among informal caregivers of the terminally ill

Objectives: (1) To determine informal caregivers perceptions about place of care and place of death; and (2) to identify variables associated with a home death among terminally ill individuals who received in-home support services in a publicly funded home care system. Participants and design: A total of 216 informal caregivers participated in a bereavement interview. Data collection included care recipient and informal caregiver characteristics, the use of and satisfaction with community services, and preferences about place of death. Results: Most caregivers reported that they and the care recipient had a preferred place of death (77 and 68%, respectively) with over 63% reporting home as the preferred place of death. Caregivers had a greater preference for an institutional death (14%) than care recipients (4.7%). While 30% of care recipients did not die in their preferred location, most caregivers (92%) felt, in retrospect, that where the care recipient died was the appropriate place of death. Most caregivers reported being satisfied with the care that was provided. The odds of dying at home were greater when the care recipient stated a preference for place of death (OR: 2.92; 95% CI: 1.25, 6.85), and the family physician made home visits during the care recipients last month of life (Univariate odds ratios (OR): 4.42; 95% CI: 1.46, 13.36). Discussion: The ethic of self-control and choice for the care recipient must be balanced with consideration for the well being of the informal caregiver and responsiveness of the community service system. © 2005 Edward Arnold (Publishers) Ltd.

Sleep disturbances in spousal caregivers of individuals with Alzheimer's disease

Background: Although sleep problems are commonly reported among dementia caregivers, the nature and frequency of caregiver sleep disruptions, and their relationship to health status, has received little empirical attention to date. Methods: The current study investigated the sleep situations of a sample of 60 spousal caregivers currently residing with a Alzheimer disease care recipient, including the frequency of nocturnal disruptions by the care recipient, and the reasons for these disruptions. In addition, exploratory correlations were computed between caregiver sleep variables and health outcomes. Results: Some 63% of spousal caregivers reported sleep disruptions due to the nocturnal behavior of the recipients of their care. Poorer caregiver sleep quality was associated with higher frequency of nocturnal disruptions by the care recipient, the care recipient needing to use the bathroom, and wandering, higher caregiver depressive symptoms, and higher levels of caregiver role burden. The frequency of nocturnal disruptions was associated with poorer mental health status and a greater number of depressive symptoms. Conclusions: Results suggest that nocturnal disruptions by the care recipient may have adverse health consequences for spousal caregivers, and that further study of the determinants of caregiver sleep quality and health outcomes are warranted. © 2007 International Psychogeriatric Association.

Interventions for late trabeculectomy bleb leak

BACKGROUND: Late trabeculectomy bleb leaks are a common complication after filtering glaucoma surgery. Although asymptomatic, late bleb leaks may lead to hypotony and are associated with bleb related infections.

OBJECTIVES: To assess the effects of interventions for late trabeculectomy bleb leak.

SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 7), MEDLINE (January 1946 to July 2012), EMBASE (January 1980 to July 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 18 July 2012.

SELECTION CRITERIA: We included randomised and quasi-randomised trials in which any treatments for eyes with late bleb leak (interventional and non-interventional) were compared with each other.

DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors when additional information was needed.

MAIN RESULTS: The review included one multicentre trial based in the USA with 30 eyes of 30 participants. The trial compared two surgical procedures (conjunctival advancement and amniotic membrane transplant) to cover a filtering bleb leak. Conjunctival advancement has been shown to be more effective in sealing filtering bleb leaks.

AUTHORS' CONCLUSIONS: Although a variety of treatments have been proposed for bleb leaks, there is no evidence of their comparative effectiveness.The evidence in this review was provided by a single trial that compared two surgical procedures (conjunctival advancement and amniotic membrane transplant). The trial did show a superiority of conjunctival advancement, which was regarded as standard treatment, to amniotic membrane transplantation. There is a need for more randomised trials to validate the findings of this single trial and provide more information on the different types of interventions, especially non-surgical treatments compared to surgical procedures. We recommend that any intervention should be compared to a standard procedure, which is to date conjunctival advancement.

A ten year audit of clinical psychology referrals in the regional Adult Cystic Fibrosis Unit in Northern Ireland

Objectives: A retrospective audit was conducted into Clinical Psychology referrals made by the adult cystic fibrosis (CF) team over a ten year period from 2001-2010. The aim of the audit was to examine the psychological difficulties referred to Clinical Psychology and identify any trends.
Methods: A database of all referrals received over a ten year period was created. A coding template was created by KR and AC which allowed for the categorisation of referrals into three main themes: Mood disturbance, CF related events and non-CF related events. The same coding template was used to categorise referrals to the children’s CF service. Descriptive statistics were used to interpret the data.
Results: In 2009/10, 11% of the adult CF population in Northern Ireland were referred to Clinical Psychology. In the past 10 years there were 200 referrals and 105 adults who accessed Clinical Psychology services. The majority of referrals (67%) were re-referrals (range 2-7). More females were referred and they were also more likely to be referred repeatedly The main reason for referral was anxiety. Depression, adherence and end of life/transplant issues also accounted for a large proportion of referrals. A small proportion of referrals were due to non CF related events. There were age and gender differences in the reasons for referral.
Conclusion: A minority of CF patients attending the regional unit were referred to Clinical Psychology. Those who accessed the services appear to be at increased risk of psychological morbidity as re-referral rates are high. The gender difference in referral and re-referral rates may reflect a difference in psychological morbidity or males not accessing services.

How young people cope with chronic kidney disease:Literature review

Background: Chronic kidney disease (CKD) is a complex, long-term condition occurring in all age groups. It has been reported that the incidence of renal replacement therapy in young people is 7-8 per million population. Notwithstanding those individuals who may receive a donor kidney, many individuals may be disenfranchised by perceptions of helplessness and feelings of powerlessness against a backdrop of diminished health outlook, consequently impacting on capacity for effective coping. Aim: The aim of this review is to explore how young people cope with CKD. Methods: Three hundred and thirty-seven abstracts were identified. Sixty-three papers were cross-examined using a Critical Appraisal Skills Checklist Tool. Results: Young people face various demands; these may be episodic or ongoing, depending on health and circumstance. The themes this review uncovers are: 'Lack of a Coping Definition'; 'Coping Strategies in Young People'; and 'Barriers to the Understanding of Coping in Young People'. Conclusion: More qualitative research is vital to retrieve 'real-life' perceptions from young people coping with kidney disease to identify how care should be made more explicit for them. © 2012 European Dialysis and Transplant Nurses Association/European Renal Care Association.

A literature review of end-stage renal disease and cachexia:Understanding experience to inform evidence-based healthcare

Introduction: Cachexia is a major cause of morbidity and mortality in people who have end-stage renal disease (ESRD). The majority of research into cachexia in ESRD has focused on the biological aspects of the syndrome and potential treatment modalities. While this research is necessary, it predominately focuses on the physical impact of cachexia in ESRD. The multi-dimensional psychosocial ramifications of this syndrome have been highlighted in other end-stage illness trajectories, but have not been systematically explored in persons who have ESRD. Aim: This paper discusses why this research is necessary, alongside further studies to help define the pathophysiology of this syndrome. Conclusion: The rich insightful data gained from understanding the patients' illness experience will positively contribute to the limited knowledge base available and inform future holistic patient-centred care delivery which recognises and responds to not only the biological but also the psychosocial impact of cachexia. © 2013 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Transfer of amiprophosmethyl resistance from a Nicotiana plumbaginifolia mutant by somatic hybridisation

Transfer of resistance to the phosphorothioamidate herbicide, amiprophosmethyl (APM), from the P-tubulin mutant of Nicotiana plumbaginifolia to the interspecific N, plumbaginifolia (+) N, sylvestris is and to the intertribal N, plumbaginifolia (+) Atropa belladonna somatic hybrids has been demonstrated. Transfer to the recipient species was accomplished by: (1) symmetric hybridisation and (2) asymmetric hybridisation using gamma-irradiation of donor protoplasts. Cytogenetic analysis confirmed the hybrid origin of the hybrids obtained. It was established that most of them typically inherited no more than three donor chromosomes, although it was possible to obtain symmetric hybrids in the case of symmetric fusion. Immunofluorescent microscopy analysis has shown that protoplasts of the mutant, and of the N. plumbagini-folia (+) N. sylvestris and N. plumbaginifolia (+) A. belladonna hybrids, retained the normal structure of interphase microtubule (MT) arrays and mitotic figures after treatment with 5 mu M APM, whereas MTs of protoplasts of the recipients were destroyed under these conditions. It was also shown that hybrid clones contained an altered beta-tubulin isoform originating from the N. plumbaginifolia mutant. The selected hybrid clones were characterised by cross-resistance to trifluralin, a dinitroaniline herbicide with the same mode of anti-MT action. Some of the somatic hybrids which could flower were fertile. It was established that seeds of some fertile hybrids were able to germinate in the presence of 5 mu M APM. The results obtained thus support the conclusion that the technique of somatic hybridisation, especially asymmetric fusion, can be used to transfer APM resistance from the N. plumbaginifolia mutant to different (related and remote) plant species of the Solanaceae, including important crops.

Somatic hybrids of higher plants obtained from amiprophosmethyl-resistant mutant Nicotiniana plumbaginifolia

Interspecific and intertribal somatic hybrids were obtained to study the composition and function of microtubules in hybrid plants. The amiprophosmethyl-resistant mutant Nicotiana plumbaginifolia L. was used as donor; canamycin-resistant mutants N. sylvestris L. and Atropa belladonna served as recipients. Cytogenetic analysis confirmed the hybrid nature of the clones selected. Immunoflourescent analysis showed that constitutions of mitotic spindles in regenerating protoplast, isolated from the hybrid NpAb-107 and the mutant N. plunbaginifolia, show no change after a 2-hour treatment with 5 mu M of amiprophosmethyl; in A. belladonna, the division spindle is completely destroyed under these conditions. Tubulin was isolated from the hybrid NpAb-107 and separated by two-dimensional electrophoresis. The results showed that NpAb-107 has the beta-tubulin isoform specific for N. plumbaginifolia in addition to all isoforms of A. belladonna.

Lipoxidation products as biomarkers of oxidative damage to proteins during lipid peroxidation reactions

Oxidative stress is implicated in the pathogenesis of numerous disease processes including diabetes mellitus, atherosclerosis, ischaemia reperfusion injury and rheumatoid arthritis. Chemical modification of amino acids in protein during lipid peroxidation results in the formation of lipoxidation products which may serve as indicators of oxidative stress in vivo. The focus of the studies described here was initially to identify chemical modifications of protein derived exclusively from lipids in order to assess the role of lipid peroxidative damage in the pathogenesis of disease. Malondialdehye (MDA) and 4-hydroxynonenal (HNE) are well characterized oxidation products of polyunsaturated fatty acids on low-density lipoprotein (LDL) and adducts of these compounds have been detected by immunological means in atherosclerotic plaque. Thus, we first developed gas chromatography-mass spectrometry assays for the Schiff base adduct of MDA to lysine, the lysine-MDA-lysine diimine cross-link and the Michael addition product of HNE to lysine. Using these assays, we showed that the concentrations of all three compounds increased significantly in LDL during metal-catalysed oxidation in vitro. The concentration of the advanced glycation end-product N epsilon-(carboxymethyl)lysine (CML) also increased during LDL oxidation, while that of its putative carbohydrate precursor the Amadori compound N epsilon-(1-deoxyfructose-1-yl)lysine did not change, demonstrating that CML is a marker of both glycoxidation and lipoxidation reactions. These results suggest that MDA and HNE adducts to lysine residues should serve as biomarkers of lipid modification resulting from lipid peroxidation reactions, while CML may serve as a biomarker of general oxidative stress resulting from both carbohydrate and lipid oxidation reactions.

Survival in dialysis patients is different between patients with diabetes as primary renal disease and patients with diabetes as a co-morbid condition.

AIMS/HYPOTHESIS:

A previous study in Dutch dialysis patients showed no survival difference between patients with diabetes as primary renal disease and those with diabetes as a co-morbid condition. As this was not in line with our hypothesis, we aimed to verify these results in a larger international cohort of dialysis patients.

METHODS:

For the present prospective study, we used data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry. Incident dialysis patients with data on co-morbidities (n?=?15,419) were monitored until kidney transplantation, death or end of the study period (5 years). Cox regression was performed to compare survival for patients with diabetes as primary renal disease, patients with diabetes as a co-morbid condition and non-diabetic patients.

RESULTS:

Of the study population, 3,624 patients (24%) had diabetes as primary renal disease and 1,193 (11%) had diabetes as a co-morbid condition whereas the majority had no diabetes (n?=?10,602). During follow-up, 7,584 (49%) patients died. In both groups of diabetic patients mortality was higher compared with the non-diabetic patients. Mortality was higher in patients with diabetes as primary renal disease than in patients with diabetes as a co-morbid condition, adjusted for age, sex, country and malignancy (HR 1.20, 95% CI 1.10, 1.30). An analysis stratified by dialysis modality yielded similar results.

CONCLUSIONS/INTERPRETATION:

Overall mortality was significantly higher in patients with diabetes as primary renal disease compared with those with diabetes as a co-morbid condition. This suggests that survival in diabetic dialysis patients is affected by the extent to which diabetes has induced organ damage.

Raiffeisenism abroad: why did German cooperative banking fail in Ireland but prosper in the Netherlands?

Why did imitations of Raiffeisen’s rural cooperative savings and loans associations work well in some European countries, but fail in others? This article considers the example of Raiffeisenism in Ireland and in the Netherlands. Raiffeisen banks arrived in both places at the same time, but had drastically different fates. In Ireland they were almost wiped out by the early 1920s, while in the Netherlands they proved to be a long-lasting institutional transplant. Raiffeisen banks were successful in the Netherlands because they operated in niche markets with few competitors, while rural financial markets in Ireland were unsegmented and populated by long- established incumbents, leaving little room for new players, whatever their institu- tional advantages. Dutch Raiffeisen banks were largely self-financing, closely integrated into the wider rural economy, and able to take advantage of economic and religious divisions in rural society. Their Irish counterparts were not.