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The antigen-presenting dendritic cells (DCs) are key to the immunological response, with different functions ascribed ranging from cellular immune activation to induction of tolerance. Such immunological responses are involved in the pathophysiological mechanisms of cardiovascular diseases, with DCs shown to play a role in atherosclerosis, hypertension, and heart failure and most notably following heart transplantation. A better understanding of the interplay between the immune system and cardiovascular diseases will therefore be critical for developing novel therapeutic treatments as well as innovative monitoring tools for disease progression. As such, the present review will provide an overview of DCs involvement in the pathophysiology of cardiovascular diseases and how targeting these cells may have beneficial effects for the prognosis of patients.

Background. Pharmacodynamic biomarkers that detect changes of immunological functions have been recognized as a helpful tool to increase the efficacy of immunosuppressive drug therapies. However, physiological changes of immunological biomarkers following transplantation are not investigated. Therefore, we assessed frequently used immunological biomarkers of the circulating blood in the first year following heart transplantation (HTx).Methods. Activation markers CD25 and CD95, intracellular cytokines IL-2 and IFNγ, chemokines IP10 and MIG, and subsets of dendritic cells as well as antibodies against human leukocyte antigens (HLA) and major histocompatibility complex class I-related chain A (MICA) antigens were analyzed at different time points using flow cytometry and Luminex xMAP technology.Results. Expression of IL-2, IFNγ, and plasmacytoid dendritic cells (pDCs) significantly increasedp<0.01during the first year. Anti-HLA antibodies decreased continuously, while anti-MICA antibodies showed minor increase within the first year. An association between percentage of pDCs and anti-MICA antibody positivity was proven. pDCs, IFNγ-producing T cells, and IP10 concentration were associated in a stronger way with age and gender of HTx recipients than with antibodies against HLA or MICA.Conclusions. We conclude that certain immunological biomarkers of the circulating blood change during the first year after HTx. These changes should be considered for interpretation of biomarkers after transplantation.

Objective This pilot intervention study assessed the impact of a 3-week inpatient program for mothers with primary breast cancer and their children. The program combined rehabilitative treatment and preventive, psychosocial, child-centered interventions. Methods A total of 116 mothers (age 29–57 years, mean = 41.1) with primary, non-metastasized breast cancer completed standardized questionnaires before (Pre1), at the beginning of (Pre2), and at the end of (Post) a 3-week inpatient intervention. The standardized scales included mothers' and children's quality of life and children's psychological symptoms. Mothers' emotional functioning and their 116 children's (age 3–14 years, mean = 7.4; 47% female) psychological health and emotional symptoms were defined as primary outcome measures. A within-subject-control-group design was used to compare changes before the intervention (measurements Pre1–Pre2) to changes during the intervention (measurements Pre2–Post) via dependent one-sided t-tests. Additional exploratory analyses for further outcome variables were performed. Results Changes during the intervention period were significantly greater than changes during the waiting period for all primary outcome measures (mothers' emotional functioning: p

Ultra-intense femtosecond X-ray pulses from X-ray lasers permit structural studies on single particles and biomolecules without crystals. We present a large data set on inherently heterogeneous, polyhedral carboxysome particles. Carboxysomes are cell organelles that vary in size and facilitate up to 40% of Earth’s carbon fixation by cyanobacteria and certain proteobacteria. Variation in size hinders crystallization. Carboxysomes appear icosahedral in the electron microscope. A protein shell encapsulates a large number of Rubisco molecules in paracrystalline arrays inside the organelle. We used carboxysomes with a mean diameter of 115±26 nm from Halothiobacillus neapolitanus. A new aerosol sample-injector allowed us to record 70,000 low-noise diffraction patterns in 12 min. Every diffraction pattern is a unique structure measurement and high-throughput imaging allows sampling the space of structural variability. The different structures can be separated and phased directly from the diffraction data and open a way for accurate, high-throughput studies on structures and structural heterogeneity in biology and elsewhere.

Context: Several assays of monitoring immune cell function have been developed to enhance therapeutic drug monitoring.Objective: An in vitro-validated whole-blood assay of phosphorylated ribosomal protein S6 (pS6RP) was evaluated for confounders to monitor the mTOR-inhibitor everolimus (ERL).Materials and methods: Whole blood samples from 87 heart transplant recipients were analyzed for pS6RP-expression in CD3-positive T-cells by phospho-flow analysis.Results: ERL blood concentration, laboratory parameters, co-medications, demographic and clinical data were reviewed.Conclusion: Evaluating the pS6RP-assay revealed that pS6RP is influenced by cyclosporine A (CsA) blood concentration, duration of ERL treatment, co-medication with thiazide diuretics and different metabolic parameters.

We overcome two of the most daunting challenges in single-particle diffractive imaging: collecting many high-quality diffraction patterns on a small amount of sample and separating components from mixed samples. We demonstrate this on carboxysomes, which are polyhedral cell organelles that vary in size and facilitate up to 40% of Earth's carbon fixation. A new aerosol sample-injector allowed us to record 70,000 low-noise diffraction patterns in 12 min with the Linac Coherent Light Source running at 120 Hz. We separate different structures directly from the diffraction data and show that the size distribution is preserved during sample delivery. We automate phase retrieval and avoid reconstruction artefacts caused by missing modes. We attain the highest-resolution reconstructions on the smallest single biological objects imaged with an X-ray laser to date. These advances lay the foundations for accurate, high-throughput structure determination by flash-diffractive imaging and offer a means to study structure and structural heterogeneity in biology and elsewhere.

In the last years many studies have been designed to predict risk of acute rejection and to adapt the immunosuppressive therapy. The importance of dendritic cells (DCs) in the immune response, especially their role in tolerance is known. Thus, we investigated the influence of tacrolimus (TAC)-based and of cyclosporine A (CsA)-based immunosuppressive therapies on dendritic cells and the incidence of rejection in heart transplant recipients.Groups consisted of 14 CsA treated and 15 TAC treated patients. At different study time points (0, 3 and 6 months after study begin) peripheral blood from the patients was drawn to analyse (1) blood concentration of CsA or TAC (trough value) and (2) percentages of plasmacytoid and myeloid DC (p and mDC) subsets using flow cytometry. Histological rejection grading was performed of endomyocardial biopsies.TAC treated patients had significantly higher values of pDCs (CsA group 53.9%±13.0%; TAC group 67.5%±8.4%; p0.05) and significantly lower values of mDCs than CsA treated patients (CsA group 58%±19.0%; TAC group 45.2%±10.7%; p0.05). In general, HTx patients with rejection grade of ≥2 had significant lower values of pDCs (55.1%±16.2%) compared to patients without rejection (63.6%±10.5%; p0.05). TAC-treated patients had significantly less rejections CsA-treated patients (CsA group 0.86±0.95; TAC group 0.2±0.4; p0.05).Our results showed that HTx patients with high pDCs had a lower risk for rejection and that TAC-treated patients had higher pDCs values compared to CsA-treated patients. Future studies need to define individual pDC values to predict acute cellular rejection.

This pilot intervention study assessed the impact of a 3-week inpatient program for mothers with primary breast cancer and their children. The program combined rehabilitative treatment and preventive, psychosocial, child-centered interventions.A total of 116 mothers (age 29-57 years, mean = 41.1) with primary, non-metastasized breast cancer completed standardized questionnaires before (Pre1), at the beginning of (Pre2), and at the end of (Post) a 3-week inpatient intervention. The standardized scales included mothers' and children's quality of life and children's psychological symptoms. Mothers' emotional functioning and their 116 children's (age 3-14 years, mean = 7.4; 47% female) psychological health and emotional symptoms were defined as primary outcome measures. A within-subject-control-group design was used to compare changes before the intervention (measurements Pre1-Pre2) to changes during the intervention (measurements Pre2-Post) via dependent one-sided t-tests. Additional exploratory analyses for further outcome variables were performed.Changes during the intervention period were significantly greater than changes during the waiting period for all primary outcome measures (mothers' emotional functioning: p 0.0001; children's psychological health: p = 0.0035; and children's emotional symptoms: p = 0.0005).Data suggest that the family-oriented intervention 'getting well together' seems to be beneficial to mothers' and children's quality of life and psychological well-being. Combining oncological rehabilitation and preventive child-centered interventions might be a feasible approach to supporting breast cancer patients and their children and improving their emotional state. Further research is warranted.

When a parent has a serious somatic illness, children suffer grave distress, their risk to develop a mental disorder increases. Sick mothers, in comparison to patients without children, experience additional strain, e. g. because they worry about their children. Although many studies focus on the quality of life of breast cancer patients, little is known about the special situation of young mothers with breast cancer. Currently, a prospective study with four assessment points (pre, post, 3- and 12-months-follow-up) is conducted on a large sample of women taking part in the family-oriented inpatient rehabilitation program "gemeinsam gesund werden'. In this paper a longitudinal sample of 173 women and 153 children, their quality of life and psychological impairment prior to, after and in the course of one year after the rehabilitation is presented. Compared to the general population, the children as well as the mothers are considerably impaired, especially in regard to Psychological Health/Emotional Functioning. These impairments improve markedly within the survey period. One year after the rehabilitation, the children show no more impairment than the reference groups. The mothers improve significantly as well, however, after one year their quality of life scores are still lower than those of the general population. In conclusion, a considerable impairment of the analyzed group of mothers with breast cancer and their children, the necessity of special supportive measures as well as the effectiveness of the model rehabilitation program can be shown.

Data concerning the effectiveness of naturalistic treatments (treatment-as-usual) in child and adolescent psychiatric (CAP) services are scarce. The purpose of this prospective observational study was to examine the effectiveness of CAP treatments in a naturalistic outpatient setting. Three hundred six patients (attention-deficit/hyperactivity disorder, ADHD, n=94; conduct disorder, CD, n=57; anxiety disorder, AD, n=53; depressive disorder, DD, n=38; other diagnostic categories, n=64), from nine child and adolescent psychiatric practices in Germany, were evaluated. Treatment effects were compared between patients who received frequent treatment and patients who only participated in diagnostics and short interventions. Since randomization was not feasible, propensity score analysis methods were used. Regarding the total sample, no significant treatment effects were found. However, a subgroup analysis of the four most frequent disorders (ADHD, CD, AD, DD) showed small to moderate treatment effects in patients with ADHD and AD. In CD and DD subgroups, no significant treatment effects could be found. “Real-world” CAP outpatient treatment seems to produce significant effects for ADHD and AD, but not for CD and DD. Compared to efficacy studies, our results show that naturalistic treatment might be better than expected.

Eine schwere korperliche Erkrankung der Eltern stellt fur Kinder eine grose Belastung dar, sie tragen ein erhohtes Risiko psychische Storungen zu entwickeln. Kranke Mutter erfahren im Vergleich zu kinderlosen Patienten zusatzliche Belastungen, da sie sich z. B. um ihre Kinder sorgen. Obwohl uber die Lebensqualitat von Brustkrebspatientinnen viele Studien vorliegen, weis man wenig uber die spezielle Situation junger Mutter mit Brustkrebs. Im Rahmen einer prospektiven Studie mit vier Messzeitpunkten (Pra, Post, 3-, und 12-Monats-Follow-up) zur Evaluation der familienorientierten Modell-Rehabilitationsmasnahme „gemeinsam gesund werden“ werden z. Z. Daten einer grosen Stichprobe erhoben; in der vorliegenden Arbeit wird eine Langsschnittstichprobe von 173 Frauen und 153 Kindern hinsichtlich ihrer Lebensqualitat und psychischen Beeintrachtigung vor der Rehabilitation und im Verlauf eines Jahres vorgestellt. Sowohl Kinder als auch Mutter sind im Vergleich zur Allgemeinbevolkerung vor der Rehabilitation erheblich beeintrachtigt, das betrifft insbesondere die Bereiche Psychische/Emotionale Gesundheit und Funktionsfahigkeit. Diese Beeintrachtigungen verbessern sich im Erhebungszeitraum. Die Kinder sind nach einem Jahr in keinem der erfassten Bereiche auffalliger als Vergleichsgruppen aus der Allgemeinbevolkerung, auch die Mutter verbessern sich deutlich, sind jedoch im Vergleich zur Allgemeinbevolkerung weiterhin eingeschrankt. Durch die Studie kann somit eine erhebliche Beeintrachtigung der untersuchten brustkrebskranken Mutter und ihrer Kinder, die Notwendigkeit spezieller Unterstutzungsangebote sowie die Effektivitat des Modellprojekts aufgezeigt werden Schlagworter Kinder korperlich kranker Eltern – Kind beeintrachtigter Eltern – Brustkrebs – Lebensqualitat – Rehabilitation When a parent has a serious somatic illness, children suffer grave distress, their risk to develop a mental disorder increases. Sick mothers, in comparison to patients without children, experience additional strain, e. g. because they worry about their children. Although many studies focus on the quality of life of breast cancer patients, little is known about the special situation of young mothers with breast cancer. Currently, a prospective study with four assessment points (pre, post, 3- and 12-months-follow-up) is conducted on a large sample of women taking part in the family-oriented inpatient rehabilitation program “gemeinsam gesund werden”. In this paper a longitudinal sample of 173 women and 153 children, their quality of life and psychological impairment prior to, after and in the course of one year after the rehabilitation is presented. Compared to the general population, the children as well as the mothers are considerably impaired, especially in regard to Psychological Health/Emotional Functioning. These impairments improve markedly within the survey period. One year after the rehabilitation, the children show no more impairment than the reference groups. The mothers improve significantly as well, however, after one year their quality of life scores are still lower than those of the general population. In conclusion, a considerable impairment of the analyzed group of mothers with breast cancer and their children, the necessity of special supportive measures as well as the effectiveness of the model rehabilitation program can be shown. Keywords children of somatically ill parents – child of impaired parents – breast cancer – quality of life - rehabilitation

p53 family proteins carry on a wide spectrum of biological functions from differentiation, cell cycle arrest, apoptosis and chemosensitivity of tumors. Conversely, N-terminally truncated p73 (DNp73) functions as a potent inhibitor of all these tumor suppressor properties, implicating its participation in malignant transformation and oncogenesis. Several reports indicated considerable up-regulation of DNp73 in hepatocellular carcinoma (HCC) that correlates with reduced survival of patients, but little is known about the functional significance of DNp73 to tumorigenesis in vivo due to the lack of an appropriate model. To address this, we generated transgenic mice in which DNp73 expression is directed to the liver by the albumin promoter. Gene expression was tested by mRNA and protein analyses. Transgenic mice exhibited prominent hepatic histological abnormalities including increased hepatocyte proliferation resulting in preneoplastic lesions (liver cell adenomas) at 3-4 months. Among 12- to 20-month-old mice, 83% of animals developed hepatic carcinoma. HCC displayed a significant increase of hyperphosphorylated inactive retinoblastoma, whereas p53-regulated inhibitors of cell cycle progression were down-regulated in the tumors. Our data firmly establish the unique oncogenic capability of DNp73 to drive hepatocarcinogenesis in vivo, supporting its significance as a marker for disease severity in patients and as target for cancer prevention. This model offers new opportunities to further delineate DNp73-mediated liver oncogenesis but may also enable the development of more effective cancer therapies.