Das enttäuschte Versprechen der Integration: Migrantennachkommen in Frankreich und Deutschland

Dieser Beitrag beschäftigt sich mit den sozialstrukturellen Voraussetzungen, die der Dynamik bzw. dem Ausbleiben von Protestverhalten zu Grunde liegen. Ausgehend von drei theoretischen Erklärungsansätzen wird empirisch anhand von repräsentativen Mikrodaten gezeigt, dass die Konzeption der Integration der Migrantennachkommen durch die Staatsbürgerschaft und die Schule in Frankreich als ein Versprechen der Integration verstanden werden kann, das im Übergang auf den Arbeitsmarkt strukturell enttäuscht wird. Demgegenüber setzt die Ausgrenzung von Migrantennachkommen in Deutschland schon im Bildungssystem ein, so dass größere Erwartungshaltungen gar nicht erst entstehen. Die Revolten der jungen MigrantInnen in Frankreich können damit u.a. als Ergebnis von strukturell enttäuschten Erwartungen interpretiert werden.Integration, Zweite Generation, Migration, Deutschland, Frankreich

Apoptosis and p53 expression in rat adjuvant arthritis

INTRODUCTION: RA is a chronic inflammatory disorder that is characterized by inflammation and proliferation of synovial tissue. The amount of DNA fragmentation is significantly increased in rheumatoid synovium. Only low numbers of apoptotic cells are present in rheumatoid synovial tissue, however. The proportion of cells with DNA strand breaks is so great that this disparity suggests impaired apoptosis. Therefore, the development of novel therapeutic strategies that are aimed at inducing apoptosis in rheumatoid synovial tissue is an attractive goal. Although animal models for arthritis only approximate RA, they provide a useful test system for the evaluation of apoptosis-inducing therapies. AA in rats is among the most commonly used animal models for RA. For the interpretation of such studies, it is essential to characterize the extent to which apoptosis occurs during the natural course of the disease. Therefore, we evaluated the number of apoptotic cells and the expression of p53 in various phases of AA. MATERIALS AND METHODS: In order to generate the AA rat model, Lewis rats were immunized with Mycobacterium tuberculosis in mineral oil on day 0. Paw swelling usually started around day 10. For the temporal analysis rats were sacrificed on days 0, 5 (prearthritis), 11 (onset of arthritis), 17 (accelerating arthritis), or 23 (chronic arthritis). For the detection of apoptotic cells, the hind paws were harvested on days 0(n=6),5 (n=6), 11 (n=6), 17 (n=6), or 23 (n=4). The right ankle joints were fixed in formalin, decalcified in ethylenediaminetetra-acetic acid, embedded in paraffin, and sectioned. The TUNEL method was applied. The percentage of TUNEL-positive cells of the total inflammatory cell infiltrate was noted. For Western blot analysis, hind paws were harvested on days 0 (n=2), 5 (n=3), 11 (n=4), 17 (n=4), or 23 (n=4). In addition, hind paws of normal rats (n=2) were studied. The right ankle joints were snap frozen and pulverized. Synovial tissue was also obtained by arthroscopy of three patients with longstanding (>5 years) RA. After protein extraction in lysis buffer, equal amounts of protein samples from lysates were pooled and examined by Western bolt analysis using anti-p53 monoclonal antibody D07, which recognizes wild-type and mutant p53 from rodents and humans. For immunohistochemical analysis, six rats were sacrificed on day 23 after immunization and synovial tissue of the right ankle joints was snap frozen and evaluated by immunohistochemistry using anti-p53-pan. The sections were evaluated semi-quantitatively using a 0-4 scale. The kruskal-Wallis test for several group means was used to compare the percentage of TUNEL-positive cells at different time points. RESULTS: The percentages of TUNEL-positive cells were strongly dependent on the stage of the disease. Very few TUNEL-positive cells were detected in normal rats or in the early phases of AA; the number of TUNEL-positive cells was 1% or less of the total cell infiltrate, including neutrophils, from days 0-17 (Table 1). On day 23, however, the percentage of TUNEL-positive cells was significantly increased [15.8±5.1% (mean ± standard error of the mean); P=0.01]. TUNEL-positive cells were observed in the intimal lining layer and synovial sublining of the invasive front, as well as in the articular cartilage (Fig. 1). Subsequently, we examined expression of the tumor suppressor gene p53, because this is a key regulator of apoptosis. Expression of p53 in pooled rat AA joint extracts gradually increased from day 0 (6 arbitrary units) to day 23 (173 arbitrary units), which was markedly higher than p53 levels in RA synovium (32 arbitrary units; Table 1). Overexpression of p53 protein on day 23 was confirmed by immunohistochemistry in a separate experiment in six rats with AA. Overexpression of p53 was observed in the intimal lining layer and synovial sublining in all rats on day 23. In all cases a semiquantitative score of 4 was assigned, indicating that 51% or more of the cells were positive, whereas control sections were negative. DISCUSSION: The results presented here reveal that the number of TUNEL-positive cells remained very low until chronic arthritis developed. This indicates that, although there was sufficient DNA damage to cause an increment in p53 expression in the early phases, DNA strand breaks that can be detected by TUNEL assays only occurred in chronic AA. The observation that TUNEL-positive cells were nearly absent in early AA clearly indicates that only very few cells were undergoing programmed cell death. This is an important observation, which makes it possible to study the effects of apoptosis-inducing therapies in situ in early and accelerating AA. An effective therapy would obviously increase the number of TUNEL-positive cells. There is already some overexpression of p53 in the preclinical phase and during the onset of the arthritis, with an additional increment in p53 expression during accelerating and chronic arthritis. Presumably, this is wild-type p53, because the disease duration is likely too short to allow for the development of p53 mutations. Transcription of p53 is probably increased in response to the toxic environment of the inflamed joint. The increased expression of p53 in the joints of rats with chronic AA was even greater than that observed in synovial tissue of RA patients with long-standing disease. Overexpression of p53 and increased numbers of apoptotic cells did not occur simultaneously in this model; rather p53 overexpression preceded increased apoptosis. Activation of p53 leads to induction of cell growth arrest, allowing time for DNA repair. It appears that DNA damage is only extensive enough to induce apoptosis in the latter stages of AA. Factors other than p53 may also play an important role in the actual induction of apoptosis Taken together, significant apoptosis only occurs late in AA and it follows marked p53 overexpression, making it a useful model for testing proapoptotic therapies. AA is not the best model for p53 gene therapy, however, because dramatic p53 overexpression occurs in the latter stages of the disease

A multinational cross-sectional survey of the management of patient medication adherence by European healthcare professionals

Objectives To examine which interventions healthcare professionals use to support patients with taking medicines and their perceptions about the effectiveness of those actions. Design Cross-sectional multinational study. Setting Online survey in Austria, Belgium, England, France, Germany, Hungary, The Netherlands, Poland, Portugal and Switzerland. Participants A total of 3196 healthcare professionals comprising doctors (855), nurses (1047) and pharmacists (1294) currently registered and practising in primary care and community settings. Main outcome measures Primary outcome: Responses to the question ‘I ask patients if they have missed any doses of their medication’ for each profession and in each country. Secondary outcome: Responses to 50 items concerning healthcare professional behaviour to support patients with medication-taking for each profession and in each country. Results Approximately half of the healthcare professionals in the survey ask patients with long-term conditions whether they have missed any doses of their medication on a regular basis. Pharmacists persistently report that they intervene less than the other two professions to support patients with medicines. No country effects were found for the primary outcome. Conclusions Healthcare professionals in Europe are limited in the extent to which they intervene to assist patients having long-term conditions with medication adherence. This represents a missed opportunity to support people with prescribed treatment. These conclusions are based on the largest international survey to date of healthcare professionals’ management of medication adherence

ESPACOMP Medication Adherence Reporting Guideline (EMERGE)

Research on assessing or managing medication adherence applies approaches from observational, interventional, and implementation science that spans many disciplines and demands coherent conceptualization, valid methods, appropriate analyses, and complete and accurate reporting. To ensure such reporting, the European Society for Patient Adherence, COMpliance, and Persistence (ESPACOMP) Medication Adherence Reporting Guideline (EMERGE) recommends standard reporting approaches based on an accepted taxonomy. This guideline is derived from a literature review, a reactive Delphi study with 26 medication adherence experts from many countries and disciplines, and feedback from ESPACOMP members. It is designed to supplement existing guidelines for health research reporting and is structured around 4 minimum reporting criteria and 17 items reflecting best reporting practice. By enhancing and harmonizing research reporting, EMERGE aims to advance research and, ultimately, patient outcomes

Predictors of self-reported adherence to antihypertensive medicines: a multinational, cross-sectional survey

Background: Nonadherence to antihypertensive medicines limits their effectiveness, increases the risk of adverse health outcome, and is associated with significant health care costs. The multiple causes of nonadherence differ both within and between patients and are influenced by patients’ care settings. Objectives: The objective of this article was to identify determinants of patient nonadherence to antihypertensive medicines, drawing from psychosocial and economic models of behavior. Methods: Outpatients with hypertension from Austria, Belgium, England, Germany, Greece, Hungary, The Netherlands, Poland, and Wales were recruited to a cross-sectional online survey. Nonadherence to medicines was assessed using the Morisky Medication Adherence Scale (primary outcome) and the Medication Adherence Rating Scale. Associations with adherence and nonadherence were tested for demographic, clinical, and psychosocial factors. Results: A total of 2595 patients completed the questionnaire. The percentage of patients classed as nonadherent ranged from 24% in The Netherlands to 70% in Hungary. Low age, low self-efficacy, and respondents’ perceptions of their illness and cost-related barriers were associated with nonadherence measured on the Morisky Medication Adherence Scale across several countries. In multilevel, multivariate analysis, low self-efficacy (odds ratio = 0.73; 95% confidence interval 0.70–0.77) and a high number of perceived barriers to taking medicines (odds ratio = 1.70; 95% confidence interval 1.38–2.09) were the main significant determinants of nonadherence. Country differences explained 11% of the variance in nonadherence. Conclusions: Among the variables measured, patients’ adherence to antihypertensive medicines is influenced primarily by their self-efficacy, illness beliefs, and perceived barriers. These should be targets for interventions for improving adherence, as should an appreciation of differences among the countries in which they are being delivered