A multimodal aftercare intervention improves the outcome after kidney transplantation - results of the KTx360° aftercare program using claims data.

Background: The after-care treatment project KTx360° aimed to reduce graft failure and mortality after kidney transplantation (KTx). Methods: The study was conducted in the study centers Hannover, Erlangen and Hannoversch Muenden from May 2017 to October 2020 under the trial registration ISRCTN29416382. The program provided a multimodal aftercare program including specialized case management, telemedicine support, psychological and exercise assessments, and interventions. For the analysis of graft failure, which was defined as death, re-transplantation or start of long-term dialysis, we used longitudinal claims data from participating statutory health insurances (SHI) which enabled us to compare participants with controls. To balance covariate distributions between these nonrandomized groups we used propensity score methodology, in particular the inverse probability of treatment weighting (IPTW) approach. Findings: In total, 930 adult participants were recruited at three different transplant centres in Germany, of whom 320 were incident (enrolled within the first year after KTx) and 610 prevalent (enrolled >1 year after KTx) patients. Due to differences in the availability of the claims data, the claims data of 411 participants and 418 controls could be used for the analyses. In the prevalent group we detected a significantly lower risk for graft failure in the study participants compared to the matched controls (HR = 0.13, 95% CI = 0.04-0.39, p = 0.005, n = 389 observations), whereas this difference could not be detected in the incident group (HR = 0.92, 95% CI = 0.54-1.56, p = 0.837, n = 440 observations). Interpretation: Our findings suggest that a multimodal and multidisciplinary aftercare intervention can significantly improve outcome after KTx, specifically in patients later after KTx. For evaluation of effects on these outcome parameters in patients enrolled within the first year after transplantation longer observation times are necessary. Funding: The study was funded by the Global Innovation fund of the Joint Federal Committee of the Federal Republic of Germany, grant number 01NVF16009.

Altered histone acetylation patterns in pancreatic cancer cell lines induce subtype­specific transcriptomic and phenotypical changes.

Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at advanced tumor stages with chemotherapy as the only treatment option. Transcriptomic analysis has defined a classical and basal­like PDAC subtype, which are regulated by epigenetic modification. The present study aimed to determine if drug­induced epigenetic reprogramming of pancreatic cancer cells affects PDAC subtype identity and chemosensitivity. Classical and basal­like PDAC cell lines PaTu­S, Capan­1, Capan­2, Colo357, PaTu­T, PANC­1 and MIAPaCa­2, were treated for a short (up to 96 h) and long (up to 30 weeks) period with histone acetyltransferase (HAT) and histone deacetylase (HDAC) inhibitors. The cells were analyzed using gene expression approaches, immunoblot analysis, and various cell assays to assess cell characteristics, such as proliferation, colony formation, cell migration and sensitivity to chemotherapeutic drugs. Classical and basal­like PDAC cell lines showed pronounced epigenetic regulation of subtype­specific genes through acetylation of lysine 27 on Histone H3 (H3K27ac). Moreover, classical cell lines revealed a significantly decreased expression of HDAC2 and increased total levels of H3K27ac in comparison with the basal­like cell lines. Following HAT inhibitor treatment, classical cell lines exhibited a loss of epithelial marker gene expression, decreased chemotherapy response gene score and increased cell migration in vitro, indicating a tumor­promoting phenotype. HDAC inhibitor treatment, however, exerted minimal reprogramming effects in both subtypes. Epigenetic reprogramming of classical and basal­like tumor cells did not have a major impact on gemcitabine response, although the gemcitabine transporter gene SLC29A1 (solute carrier family 29 member 1) was epigenetically regulated.

Study on Health of Older People in Germany (Gesundheit 65+): objectives, design and implementation.

Background: The longitudinal population-based study Gesundheit 65+ aimed to close data gaps on health and well-being of older adults in Germany in times of the COVID-19 pandemic. Methods: The target population comprised persons 65 years and older permanently residing in Germany and with sufficient German language skills. Proxy interviews were possible and consent from legal representatives was obtained as necessary in order to enable participation of physically or cognitively impaired persons. A two-stage sampling process, was used to draw 128 primary sample points (PSUs) and within these PSUs sex- and age-stratified random samples were drawn from population registries. A mixed-mode design was applied to contact the study population and for data collection. Data were collected between June 2021 and April 2023. Participants were surveyed a total of four times at intervals of four months. At month 12 participants were offered a home visit including a non-invasive examination. Data on all-cause mortality and information on neighborhood social and built environment as well as health insurance data will be linked to primarily collected data at the individual level. Discussion: Results will inform health politicians and other stakeholders in the care system on health and health care needs of older people in Germany.

Fear of Falling Carries Over into Overprotection in Old Age: A Cross-Lagged Panel Analysis.

Fear of falling might result in overprotection by one's social environment. In turn, feeling dependent could increase fear of falling. However, the association between fear of falling and perceived overprotection and its temporal order is unknown. This longitudinal study explores this potential mutual longitudinal association. This study presents secondary analyses from a larger trial. We tested the association between fear of falling and perceived overprotection in a cross-lagged path model controlled for falls, health-related quality of life, age, gender, and trial condition. N = 310 participants (M = 70 years, range: 64-92) completed self-reports at Time 1, 7 (Time 2), and 11 weeks (Time 3) after baseline assessment. We found a positive association from fear of falling to perceived overprotection (ß = .12, 95% CI[0.02, 0.21], p = .02; ß = .10; [0.01, 0.18], p = .03). The reversed cross-lagged paths were not significant. Findings suggest higher fear of falling translates into perceived overprotection, which may in turn increase loss of independence in old age.

A Stepped Health Services Intervention to Improve Care for Mental and Neurological Diseases: Protocol for a Prospective Cohort Trial.

BACKGROUND: Mental and neurological disorders cause a large proportion of morbidity burden and require adequate health care structures. However, deficits in the German health care system like long waiting times for access to specialized care and a lack of coordination between health care providers lead to suboptimal quality of care and elevated health care costs. OBJECTIVE: To overcome these deficits, we implement and evaluate a unique stepped and coordinated model of care (the Neurologisch-psychiatrische und psychotherapeutische Versorgung [NPPV] program) for patients with mental and neurological diseases. METHODS: Patients included in the program receive an appropriate treatment according to medical needs in a multiprofessional network of ambulatory health care providers. The therapy is coordinated by a managing physician and complemented by additional therapy modules, such as group therapy, internet-based cognitive behavioral therapy, and a case management. Statutory health insurance (SHI) routine data and data from a longitudinal patient survey will be used to compare the program with regular care and evaluate SHI expenditures and patient-related outcomes. A health care provider survey will evaluate the quality of structure and processes and provider satisfaction. Finally, an analysis of ambulatory claims data and drug prescription data will be used to evaluate if health care providers follow a needs-led approach in therapy. Ethics approval for this trial was obtained from the ethics committee of the chamber of physicians in North Rhine (September 13, 2017, reference No. 2017287). RESULTS: Patient enrollment of NPPV ended in September 2021. Data analysis has been completed in 2022. The results of this study will be disseminated through scientific publications, academic conferences, and a publicly available report to the German Federal Joint Committee, which is expected to be available in the first half of 2023. CONCLUSIONS: The NPPV program is the first intervention to implement a stepped model of care for both mental and neurological diseases in Germany. The analysis of several data sources and a large sample size (more than 14,000 patients) enable a comprehensive evaluation of the NPPV program. TRIAL REGISTRATION: German Clinical Trials Register DRKS00022754; https://tinyurl.com/3mx9pz5z. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37569.

Health sensitivity in the daily lives of younger and older adults: correlates and longer-term change in health.

OBJECTIVES: How susceptible older adults' affect is to fluctuations in health (i.e., health sensitivity) indicates how well they adapt to everyday health challenges. Theory and evidence are inconsistent as to whether older adults are more or less health sensitive than younger adults. The role of health burden as correlate and outcome of health sensitivity and age differences therein is also unclear. We thus move the study of health sensitivity ahead from longitudinal inquiry to examine age differences, the role of health burden, and long-term implications of daily life health sensitivitMethods: We use data from COGITO where 101 younger adults (Mage = 25; range = 20-31) and 103 older adults (Mage = 71; range = 65-80) gave daily reports of physical symptoms and positive and negative affect during a ∼100-day micro-longitudinal phase, as well as reports of trait-level health two years before and after. RESULTS: Extending earlier reports, older age and higher health burden were (independently) associated with lower health sensitivity in positive but not negative affect. Health sensitivity was unrelated to long-term changes in health burden. CONCLUSION: We take our findings to indicate successful aging (older adults are not more emotionally vulnerable to health issues) and discuss habituation as a process underlying how age and health burden may reduce health sensitivity.

What makes implementation intentions (in)effective for physical activity among older adults?

OBJECTIVES: For most populations, implementation intentions (IIs) facilitate physical activity (PA). However, for older adults, previous studies found mixed evidence for the effectiveness of this behaviour change technique. To examine which characteristics of IIs predict successful enactment, the content of older participants' IIs formed within a self-regulatory intervention to prompt PA was analysed. DESIGN: A sample of N = 126 German speaking adults aged 64 and older formed up to six IIs for PA and reported their enactment 5 weeks later. METHODS: Controlling for age and sex, multilevel models tested associations between characteristics of IIs (e.g., chronological rank of II, hetero- and homogeneity, specificity, presence of certain cues) and enactment. RESULTS: Significantly related to enactment were: the chronological rank of an II (first IIs superior to last IIs), greater heterogeneity in activities, greater specificity of when-cues, and greater use of pre-existing routines. CONCLUSIONS: Participants were more likely to enact their IIs 5 weeks later if they planned different (heterogeneous) activities, created IIs with more specific when-cues (e.g., on Monday at 9 am), and in particular a routine (e.g., after breakfast). They also enacted the first three IIs (chronological rank of II) more often than the last three IIs. Future experimental studies should test whether providing instructions to create IIs based on the above significant characteristics lead to more effective health behaviour change among older adults.

Benefits of volunteering on psychological well-being in older adulthood: evidence from a randomized controlled trial.

Objectives: Long-term volunteering has been associated with better physical, mental, and cognitive health in correlational studies. Few studies, however, have examined the longitudinal benefits of volunteering with randomized experimental designs (e.g., intervention studies). Even fewer studies have examined whether such benefits can be shown after short-term volunteering. To fill this gap, we conducted four 1-hour volunteering intervention sessions to promote volunteering among a group of older adults with limited volunteering experience and examined the impact of volunteering on depressive symptoms, meaning in life, general self-efficacy, and perceived autonomy.Methods: A total of 384 participants aged 50-96 years were assigned at random to either an intervention group to promote volunteering behaviors or an active control group to promote physical activity. The participants' monthly volunteering minutes, depressive symptoms, meaning in life, general self-efficacy and perceived autonomy were measured at baseline and six weeks, three months, and six months after the intervention.Results: Being in the volunteering intervention condition was not directly associated with depressive symptoms, meaning in life, general self-efficacy, or perceived autonomy at the 6-week, 3-month, or 6-month follow-ups after the intervention. However, there was an indirect effect of the intervention on depressive symptoms: participants in the intervention group, who had increased their volunteering at the 3-month follow-up, reported fewer depressive symptoms at the 6-month follow-up.Discussion: Our randomized controlled trial suggests that short-term volunteering does not reliably lead to short-term changes in psychosocial health measures as correlational studies would suggest. Efforts need to be made to encourage older adults to maintain long-term volunteering.

Changes in views on aging in later adulthood: the role of cardiovascular events.

A number of longitudinal studies have pointed to the long-term impact of different views on aging (VoA) on health in later life, whereas the reverse relationship has rarely been examined. Serious cardiovascular events such as myocardial infarction or stroke are life-threatening events which might in turn lead to changes in VoA. The present longitudinal study examined the effect of a cardiovascular event (CVE) on VoA over a three-year period using pooled data from three waves of the German Ageing Survey (2008, 2011, 2014, age range: 40-95 years). In order to account for alternative explanations for changes in VoA, individuals without CVE (n = 200) were matched to individuals who experienced a CVE (n = 202) using a propensity score matching procedure. Compared to individuals without CVE, individuals who experienced a CVE showed adverse changes in three VoA indicators (self-perceptions of aging as associated with physical losses/with ongoing development; subjective age). These results suggest that CVE can in fact change how individuals view their own aging. According to previous studies, this can lead to future health changes and thus become a health-related downward spiral. Health promotion programs could, therefore, profit by adding specific VoA interventions for individuals who experienced a CVE.

Promoting Volunteering Among Older Adults in Hong Kong: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Volunteering has consistently been associated with better mental, physical, and cognitive health in older adulthood. However, the volunteering rate of older adults in Hong Kong is much lower than in Western countries. Few studies have examined whether interventions can be effective in motivating older adults to volunteer in Hong Kong. To fill this gap, we conducted a randomized controlled trial to examine the impact of a theory-based social-cognitive intervention on volunteering. RESEARCH DESIGN AND METHODS: A total of 264 community-dwelling older adults in Hong Kong (Mage = 69.95 years, SDage = 6.90 years, 81.06% female) were randomly assigned to either an experimental group or an active control group. Participants in the experimental group received 4 weekly 1-hr face-to-face volunteering intervention sessions. Those in the active control group received parallel sessions targeting physical activity instead of volunteering. The time spent on volunteering per month was self-reported and measured at baseline, 6 weeks, 3 months, and 6 months after the intervention. Self-efficacy, intention, action planning, and self-monitoring of volunteering were measured as mediators. RESULTS: Monthly volunteering minutes increased among participants in the experimental group when compared with the active control group at 6-week, 3-month, and 6-month follow-ups. Self-efficacy, intention, and action planning consistently mediated the effect of the intervention on volunteering minutes. DISCUSSION AND IMPLICATIONS: The findings demonstrate the effectiveness of the intervention on volunteering behavior in older adults in Hong Kong through well-established behavior change techniques.

Study protocol of a multi-center RCT testing a social-cognitive intervention to promote volunteering in older adults against an active control.

BACKGROUND: Volunteering could be a win-win opportunity for older adults: Links between volunteering and societal improvements as well as older adults' own health and longevity are found in several observational studies. RCTs to increase volunteering in older adults are however sparse, leaving the question of causality unanswered. This study protocol describes a theory-based social-cognitive intervention with multiple behavior change techniques to increase volunteering among community-dwelling older adults in Hong Kong. METHODS: In a parallel group, two-arm, randomized controlled trial, an initial N = 360 are assigned to receive either the volunteering intervention or the active control intervention (parallel content targeting physical activity). The primarily outcome measure is self-reported volunteering minutes per month at baseline, six weeks, three months and six months after the intervention. Participants in the treatment group are expected to increase their weekly volunteering minutes over time as compared to participants in the control group. Possible active ingredients of the intervention as well as mental and physical health outcomes of increased volunteering are investigated by means of mediation analyses. DISCUSSION: Like many industrialized nations, Hong Kong faces a rapid demographic change. An effective psychological intervention to encourage retirees to engage in formal volunteering would alleviate some of the societal challenges a growing proportion of older adults entails. TRIAL REGISTRATION: Primary Registry and Trial Identifying Number ChiCTR-IIC-17010349 , secondary CCRB trial number CUHK_CCRB00543, registration date 2016/12/28.

Are self-perceptions of ageing modifiable? Examination of an exercise programme with vs. without a self-perceptions of ageing-intervention for older adults.

OBJECTIVE: Longitudinal studies have consistently shown beneficial effects of positive self-perceptions of ageing (SPA) on health. However, SPA are more often negative than positive, particularly in older adults. For this reason, the present study tested the effectiveness of an intervention to promote more positive SPA in the context of an exercise programme for older adults. DESIGN: Eighty-four community-dwelling older adults (66-88 years; M(SD)=76.8(5.29)) were randomly assigned to a group-based exercise programme over 12 weeks with (n = 46) or without (n = 38) a psychological intervention to change SPA, consisting of four intervention units over the programme period. MAIN OUTCOME MEASURES: A gain- and a loss-related domain of SPA were assessed at baseline, after the first half of the programme, directly after the programme and in a follow-up four weeks later. RESULTS: Latent change score models showed an improvement of participants' SPA in the intervention group in both SPA domains after the programme, whereas SPA did not change in the control group. Both groups showed an improvement in physical performance, however, only the IG showed additional improvements in mental health. CONCLUSION: The implementation of an SPA intervention is a promising approach in regular health promotion programmes for older adults.

Perceived somatic and affective barriers for self-efficacy and physical activity.

According to Bandura's social-cognitive theory, perceptions of somatic and affective barriers are sources of self-efficacy. This longitudinal study compares general indicators of health barriers with measures of perceived somatic and affective barriers to predict self-efficacy and accelerometer-assessed physical activity in a subsample of n = 153 (selected at random from N = 310) community-dwelling German older adults. Perceived somatic and affective barriers longitudinally predicted physical activity mediated by self-efficacy, whereas general health barriers did not. Perceived health barriers to physical activity might be more important than more objective health barriers for older adults' physical activity levels.

Positive Self-perceptions of Aging Promote Healthy Eating Behavior Across the Life Span via Social-Cognitive Processes.

OBJECTIVES: Negative self-perceptions of aging (SPA) have been shown to result in lower levels of preventive behavior, health, and longevity. This study focuses on the understudied SPA effects on healthy eating across the life span. Moreover, it aims to provide longitudinal evidence of the psychological mechanisms behind this relationship. METHOD: We investigated whether SPA (T1) can predict changes in eating behavior (T3) over 1 year in 1,321 participants (T1), aged 18-92 years. The explanatory role of social-cognitive processes (T1, T2) was tested via a two-step mediation analysis with multigroup modeling for different age and education levels. RESULTS: Baseline positive SPA predicted more healthy eating at T3 (b = 0.68, SE = 0.24, p = .01), controlling for baseline eating (T1), age, education, gender, BMI, and illnesses. Self-efficacy (T1) and intention to eat healthily (T2) serially mediated this effect, indirect effect: b = 0.04, p = .02, 95% CI (0.02, 0.08). SPA had stronger effects in older and less educated participants. DISCUSSION: This study provides important insights into the mechanisms behind positive SPA fueling successful health behavior change dynamics. Fostering more positive SPA through interventions might be especially important for vulnerable groups. Addressing SPA already in younger ages might help establish health-promoting life-span dynamics.

CCSchool: a multicentre, prospective study on improving continuum of care in children and adolescents with mental health problems associated with school problems in Germany.

BACKGROUND: Most psychiatric disorders in childhood and adolescence cause impairment in academic performance. Early interventions in school are thought to reduce the burden of disorder and prevent chronicity of disorder, while a delay in reachable help may result in more severe symptoms upon first time presentation, often then causing upon first-time presentation immediate need of inpatient care. METHODS: The study aims at reducing hospitalization rates and increasing social participation and quality of life among children and adolescents by establishing collaborations between schools, mental health care services and youth welfare services. CCSchool offers children and adolescents, aged six to 18 years, who present with psychiatric problems associated to school problems, a standardized screening and diagnostic procedure as well as treatment in school if necessary. Students can participate in CCSchool in three federal states of Germany if they a) show symptoms vindicating a mental health diagnosis, b) present with confirmed school problems and c) have a level of general functioning below 70 on the children global assessment of Functioning (C-GAF). Intervention takes place in three steps: module A (expected n = 901, according to power calculation) with standardized diagnostic procedures; module B (expected n = 428) implies a school-based assessment followed by a first intervention; module C (expected n = 103) offering school-based interventions with either four to six sessions (basic, 80% of patients) or eight to 12 sessions (intensive, 20% of patients). Primary aim is to evaluate the effectiveness of CCSchool, in reducing the need of hospitalization in children with mental health problems. The analyses will be conducted by an independent institute using mainly data collected from patients and their caregivers during study participation. Additionally, claims data from statutory health insurances will be analysed. Relevant confounders will be controlled in all analyses. DISCUSSION: Evaluation may show if CCSchool can prevent hospitalizations, enhance social participation and improve quality of life of children and adolescents with mental health problems by providing early accessible interventions in the school setting. TRIAL REGISTRATION: Deutsches Register Klinischer Studien, Trial registration number: DRKS00014838 , registered on 6th of June 2018.

A semi-automated algorithm for hypothalamus volumetry in 3 Tesla magnetic resonance images.

The hypothalamus, a small diencephalic gray matter structure, is part of the limbic system. Volumetric changes of this structure occur in psychiatric diseases, therefore there is increasing interest in precise volumetry. Based on our detailed volumetry algorithm for 7 Tesla magnetic resonance imaging (MRI), we developed a method for 3 Tesla MRI, adopting anatomical landmarks and work in triplanar view. We overlaid T1-weighted MR images with gray matter-tissue probability maps to combine anatomical information with tissue class segmentation. Then, we outlined regions of interest (ROIs) that covered potential hypothalamus voxels. Within these ROIs, seed growing technique helped define the hypothalamic volume using gray matter probabilities from the tissue probability maps. This yielded a semi-automated method with short processing times of 20-40 min per hypothalamus. In the MRIs of ten subjects, reliabilities were determined as intraclass correlations (ICC) and volume overlaps in percent. Three raters achieved very good intra-rater reliabilities (ICC 0.82-0.97) and good inter-rater reliabilities (ICC 0.78 and 0.82). Overlaps of intra- and inter-rater runs were very good (≥ 89.7%). We present a fast, semi-automated method for in vivo hypothalamus volumetry in 3 Tesla MRI.

Regional Impact of Population Aging on Changes in Individual Self-perceptions of Aging: Findings From the German Ageing Survey.

Background and Objectives: The importance of self-perceptions of aging (SPA) for health and longevity is well documented. Comparably little is known about factors that contribute to SPA. Besides individual factors, the context a person lives in may shape SPA. Research has so far focused on country-level differences in age stereotypes, indicating that rapid population aging accompanies more negative age stereotypes. The present study expands previous research by investigating the impact of district-specific population aging within one country on different facets of SPA. Research Design and Methods: Based on a large representative survey in Germany, the study investigates changes in SPA as ongoing development as well as the SPA of physical loss over a 12-year period in adults aged 40+. The study uses several indicators of population aging (e.g., population development, average age, greying index), to identify four clusters differing in their pace of population aging. Based on three-level latent change models, these clusters were compared in their impact on changes in SPA. Results: Compared to districts with an average rate of population aging, the study shows that persons living in regions with a fast population aging rate (C1) hold more negative SPA in both facets (ps = .01). Districts with slow population aging (C2) have significantly higher SPA ongoing development (p = .03). Discussion and Implications: The study underlines the importance for regional differences in population aging on the development of SPA. In particular, societies should be aware that fast population aging may result in more negative SPA.

Response shift in self-rated health after serious health events in old age.

OBJECTIVE: Although health generally deteriorates with advancing age, how older adults evaluate their health status (i.e., their self-rated health, SRH) remains rather positive. So far, however, little is known about how SRH in old age may change in the face of an abrupt health decline. Because change/stability in SRH may reflect not only change/stability in health but also changes in the meaning people assign to the concept of "health", response shift effects in SRH for people with and without a serious health event are investigated in the present study in the older general population. METHOD: Longitudinal data from 1764 participants of the German Ageing Survey aged 65 + assessed at two occasions three years apart was used to investigate changes in SRH and three types of response shift: recalibration (change in standards for good health), reprioritization (change in the importance of different factors for health), and reconceptualization (omission/inclusion of new factors). The so-called "then-test" was used to examine recalibration response shift and path analyses, to examine reprioritization and reconceptualization response shift. RESULTS: SRH declined between the two measurement occasions. As expected, people who experienced a serious health event indicated stronger declines in SRH. The study found evidence of two types of response shift. Regardless of whether they experienced a serious health event or not, individuals on average retrospectively overestimated their baseline health relative to the concurrent rating (recalibration). Furthermore, the predictive importance of depressive symptoms and optimism for SRH increased for individuals who experienced a serious health event (reprioritization). CONCLUSION: The results indicate that older adults maintain stable SRH by using two types of response shift: recalibration and, when faced with a serious health event, reprioritization response shift.

Relations between views on ageing and perceived age discrimination: a domain-specific perspective.

This study investigates the relation between age stereotypes and perceived age discrimination. Existing evidence for such a relation is notoriously ambiguous with regard to its direction-age stereotypes can predict (perceived) discrimination, but experiencing discrimination may also change views on ageing-which is why we used a dataset with two waves to disentangle the direction of the associations. Considering research on the multi-dimensionality of views on ageing and perceived age discrimination, we addressed this question from a domain- and age group-specific perspective. Drawing on data from two measurement points of the German Ageing Survey (DEAS; t1: 2008, t2: 2011; age range at t1: 40-93 years, n = 6092 participants at t1), we examined reciprocal relations between views on ageing and perceived age discrimination. Cross-lagged models revealed that domain-specific views on ageing predict subsequent changes in perceived discrimination in corresponding domains: Negative views on ageing regarding personal competence, physical decline, and social interactions were associated with increases in perceived discrimination in the domains of work, medical care, and social life, respectively. However, we did not find evidence for a reciprocal effect of perceived age discrimination on views on ageing. In sum, results indicate that negative views on ageing act as self-fulfilling prophecies by predisposing people to categorize other people's behaviour as age discrimination or to act themselves in a way that might elicit ageist behaviour in others.

Generation and functional characterization of MDSC-like cells.

Myeloid-derived suppressor cells (MDSC) are critical in regulating immune responses by suppressing antigen presenting cells (APC) and T cells. We previously observed that incubation of peripheral blood monocytes with interleukin (IL)-10 during their differentiation to monocyte-derived dendritic cells (moDCs) results in the generation of an APC population with a CD14+HLA-DRlowphenotype (IL-10-APC) with reduced stimulatory capacity similar to human MDSC. Co-incubation experiments now revealed that the addition of IL-10-APC to moDC caused a reduction of DC-induced T-cell proliferation, of the expression of maturation markers, and of secreted cytokines and chemokines such as TNF-α, IL-6, MIP-1α and Rantes. Addition of IL-10-APC increased the immunosuppressive molecule osteoactivin and its corresponding receptor syndecan-4 on moDC. Moreover, CD14+HLA-DRlow MDSC isolated from healthy donors expressed high levels of osteoactivin, which was even further upregulated by the auxiliary addition of IL-10. Using transcriptome analysis, we identified a set of molecules and pathways mediating these effects. In addition, we found that IL-10-APC as well as human isolated MDSC expressed higher levels of programmed death (PD)-1, PD-ligand-1 (PD-L1), glucocorticoid-induced-tumor-necrosis-factor-receptor-related-protein (GITR) and GITR-ligand. Inhibition of osteoactivin, syndecan-4, PD-1 or PD-L1 on MDSC by using blocking antibodies restored the stimulatory capacity of DC in co-incubation experiments. Activation of MDSC with Dectin-1 ligand curdlan reduced the expression of osteoactivin and PD-L1. Our results demonstrate that osteoactivin/syndecan-4 and PD-/PD-L1 are key molecules that are profoundly involved in the inhibitory effects of MDSC on DC function and might be promising tools for clinical application.