Health status of returnees to Kosovo: do living conditions during asylum make a difference?

OBJECTIVE: From August 1999 to July 2001, asylum seekers who had come to Switzerland from Kosovo were repatriated. The present study aimed to assess the relationship between living conditions during asylum in Switzerland and health status among returnees. STUDY DESIGN: Cross-sectional survey of 319 ethnic Albanian families in Kosovo, selected from a list of 12900 heads of households who had received repatriation aid. METHODS: Consenting household members aged 16 years or more who had received asylum in Switzerland were interviewed during the autumn of 2001. Questions explored living conditions during asylum, present socio-economic conditions (World Bank Kosovo Poverty Assessment Survey), subjective physical and mental health [Medical Outcomes Study 36-item Short Form Health Survey (SF-36)], traumatic events (Harvard Trauma Questionnaire) and symptoms of post-traumatic stress disorder (PTSD; Mini International Neuropsychiatric Interview). RESULTS: Ninety-four per cent of selected households were located. Among the 580 participants, 25.5% suffered from PTSD and 65% lived in extreme poverty. Subjective health scores, measured by SF-36, were low, particularly for those affected by PTSD. Among living conditions in the host country, duration of stay longer than 26 weeks was associated with lower mental health scores, particularly among people with PTSD. CONCLUSIONS: Two years after the conflict, returnees had low health scores. The association between duration of stay and lower mental health scores may reflect the stress of adapting to asylum or the consequence of compulsory repatriation. This study has implications for the emerging healthcare system in Kosovo and for policies of asylum in host countries.     

Guanine polynucleotides are self‐antigens for human natural autoantibodies and are significantly reduced in the human genome

In the course of investigating anti‐DNA autoantibodies, we examined IgM and IgG antibodies to poly‐G and other oligonucleotides in the sera of healthy persons and those diagnosed with systemic lupus erythematosus (SLE), scleroderma (SSc), or pemphigus vulgaris (PV); we used an antigen microarray and informatic analysis. We now report that all of the 135 humans studied, irrespective of health or autoimmune disease, manifested relatively high amounts of IgG antibodies binding to the 20‐mer G oligonucleotide (G20); no participants entirely lacked this reactivity. IgG antibodies to homo‐nucleotides A20, C20 or T20 were present only in the sera of SLE patients who were positive for antibodies to dsDNA. The prevalence of anti‐G20 antibodies led us to survey human, mouse and Drosophila melanogaster (fruit fly) genomes for runs of T20 and G20 or more: runs of T20 appear > 170 000 times compared with only 93 runs of G20 or more in the human genome; of these runs, 40 were close to brain‐associated genes. Mouse and fruit fly genomes showed significantly lower T20/G20 ratios than did human genomes. Moreover, sera from both healthy and SLE mice contained relatively little or no anti‐G20 antibodies; so natural anti‐G20 antibodies appear to be characteristic of humans. These unexpected observations invite investigation of the immune functions of anti‐G20 antibodies in human health and disease and of runs of G20 in the human genome.     

Mode of interaction of TRIP13 AAA-ATPase with the Mad2-binding protein p31comet and with mitotic checkpoint complexes

The AAA-ATPase thyroid hormone receptor interacting protein 13 (TRIP13), jointly with the Mad2-binding protein p31^comet, promotes the inactivation of the mitotic (spindle assembly) checkpoint by disassembling the mitotic checkpoint complex (MCC). This checkpoint system ensures the accuracy of chromosome segregation by delaying anaphase until correct bipolar attachment of chromatids to the mitotic spindle is achieved. MCC inhibits the anaphase-promoting complex/cyclosome (APC/C), a ubiquitin ligase that targets for degradation securin, an inhibitor of anaphase initiation. MCC is composed of the checkpoint proteins Mad2, BubR1, and Bub3, in association with the APC/C activator Cdc20. The assembly of MCC in active checkpoint is initiated by the conversion of Mad2 from an open (O-Mad2) to a closed (C-Mad2) conformation, which then binds tightly to Cdc20. Conversely, the disassembly of MCC that takes place when the checkpoint is turned off involves the conversion of C-Mad2 back to O-Mad2. Previously, we found that the latter process is mediated by TRIP13 together with p31^comet, but the mode of their interaction remained unknown. Here, we report that the oligomeric form of TRIP13 binds both p31^comet and MCC. Furthermore, p31^comet and checkpoint complexes mutually promote the binding of each other to oligomeric TRIP13. We propose that p31^comet bound to C-Mad2–containing checkpoint complex is the substrate for the ATPase and that the substrate-binding site of TRIP13 is composed of subsites specific for p31^comet and C-Mad2–containing complex. The simultaneous occupancy of both subsites is required for high-affinity binding to TRIP13.Thyroid hormone receptor interacting protein 13 (TRIP13 ) is an AAA-ATPase that is required for the inactivation of the mitotic (spindle assembly) checkpoint (1, 2). This checkpoint system delays anaphase until correct bipolar attachment of sister chromatids to the mitotic spindle is achieved and thus ensures accuracy of chromosome segregation in mitosis (3–5). When the mitotic checkpoint system is on, it inhibits the action of the anaphase-promoting complex/cyclosome (APC/C), a ubiquitin ligase that targets for degradation specific cell cycle regulatory proteins, such as securin, an inhibitor of anaphase initiation (6). APC/C is inhibited by the mitotic checkpoint complex (MCC), which is composed of the checkpoint proteins Mad2, BubR1, and Bub3, in association with the APC/C activator Cdc20. The active checkpoint converts Mad2 from an open (O-Mad2) to a closed (C-Mad2) conformation, and the latter associates with Cdc20 in a very tight complex. It is thought that the C-Mad2–Cdc20 (MC) subcomplex associates with BubR1-Bub3 to form the MCC (4, 5).In studying the mechanisms of the disassembly of MCC, we found that ATP hydrolysis is required for this process (7). ATP was also required for the action of p31^comet, a Mad2-binding protein involved in the exit from the mitotic checkpoint (8) and in MCC dissociation (9). Subsequently, we purified a factor that promotes ATP- and p31^comet-dependent release of Mad2 from MC and MCC and identified it as the TRIP13 ATPase (1). The role of TRIP13 in checkpoint inactivation was corroborated by in vivo results of other investigators indicating that TRIP13 knockdown delays metaphase–anaphase transition (2). We proposed that the energy of ATP hydrolysis is used by the TRIP13 ATPase to promote conformational transition of C-Mad2 to O-Mad2, thus leading to its release from MCC or MC (1). The action of TRIP13 to convert C-Mad2 to O-Mad2 was recently demonstrated by direct methods (10).The question arose concerning what is the role of p31^comet in the action of the TRIP13 ATPase. Because it had been suggested by a proteomic data-mining study that TRIP13 interacts with p31^comet (11) and because p31^comet specifically binds to the closed conformation of Mad2 (12), it seemed reasonable to assume that p31^comet serves as an adaptor protein that targets the TRIP13 AAA-ATPase to C-Mad2–containing checkpoint complexes. However, in our previous experiments on immunodepletion of TRIP13 or p31^comet from checkpoint extracts, using antibodies directed against either protein, we could not detect coimmunodepletion of either protein with its presumed partner (1). The present investigation was initiated to solve this problem and to gain insight into the role of p31^comet in TRIP13 action. We find that p31^comet and checkpoint complexes mutually stimulate the binding of each other to the oligomeric form of the TRIP13 ATPase. We propose that p31^comet bound to C-Mad2–containing checkpoint complex is the substrate for the ATPase and that the substrate-binding site of TRIP13 is composed of subsites specific for p31^comet and the C-Mad2 moiety of the checkpoint complex. The simultaneous binding of p31^comet and C-Mad2 to these subsites is required for their high-affinity interaction with TRIP13.     

TNF promoter polymorphisms and modulation of growth retardation and disease severity in pediatric Crohn's disease

OBJECTIVES: Delayed growth is common in pediatric Crohn's disease (CD). Multiple factors have been shown to affect growth in this situation, the most prominent being the presence and severity of inflammation and inadequate nutritional intake. Inflammation, anorexia, and weight loss are all manifestations of circulating TNF-alpha, which is elevated in CD. The ability to secrete TNF-alpha may be affected by polymorphisms in the TNF-alpha promoter. The aim of our study was to determine whether growth retardation and disease severity in pediatric onset CD are affected by TNF promoter genotype. METHODS: Genotyping for TNF-alpha and NOD2/CARD15 single nucleotide polymorphisms was performed in 87 patients with detailed growth records. Parameters including disease location and disease severity were recorded, and the effect of these polymorphisms on Z-scores for height and weight at disease onset and during follow-up were analyzed. RESULTS: Lower age of onset was linked to more height retardation, while the presence of colonic disease and the absence of ileal disease were more likely to predict the absence of growth retardation. The presence of two polymorphisms thought to decrease circulating TNF-alpha was associated with higher mean Z-scores for height and a trend toward less growth retardation. Two other polymorphisms were modestly associated with disease severity. CONCLUSION: Polymorphisms in the TNF-alpha promoter may independently modulate growth and disease severity in pediatric onset CD. The effect of these polymorphisms does not appear to be mediated via weight loss, and is relatively modest.     

Improving nursing management and practice through quality circles

Health care in general, and nursing in particular, is experiencing dramatic changes in worker values, economic realities, and management theory. All three areas of change move toward actively involving employees in organizational decision making. Although nursing managers have implemented a variety of systems to gain employee participation, "Quality Circles" seems to be the most promising method currently available. This article describes some techniques for effectively implementing Quality Circles within a nursing organization.     

Development of color association in normal and neurologically impaired children

Color association, defined as the ability to identify the characteristic color of familiar objects, was studied in 2 groups of brain-damaged children with language or nonlanguage impairment and in a group of control patients. The performance of the 16 control children, 3.5-4.5 years of age, was compared with that of 31 patients, 4.5-5.5 years of age; their scores were 52.4 +/- 31.3 (mean +/- SD) and 85.9 +/- 13.1, respectively (p less than 0.005). Seventeen dysphasic, brain-damaged children and 11 age-matched children with neurologic deficits but without language delay were examined. Their scores were 57.7 +/- 11.7 and 70.6 +/- 21.9, respectively (p less than 0.05). Finally, each of the brain-damaged groups was compared with age-matched controls. Although the control children performed far better than the dysphasic children (77.6 +/- 20.9 and 57.5 +/- 11.7, respectively, p less than 0.001), there was no significant difference between controls and neurologically impaired children without language delay (77.6 +/- 20.9 and 70.6 +/- 21.9, respectively). We conclude that color association in normal children is already operative at 3.5 years and approaches maturity by 4.5-5.5 years. This function was preserved in neurologically impaired children without language delay but was significantly distrubed in the dysphasic children; therefore, the use of color should be assessed in the habilitation of children.