Care improves self-reported daily functioning of adolescents with emotional and behavioural problems.

Emotional and behavioural problems (EBP) have a negative impact on various life domains of adolescents. Receiving care for EBP may improve the functioning of adolescents with EBP, but evidence on long-term outcomes in real-life settings is lacking. We, therefore, investigated self-reported functioning in different life domains of adolescents with various EBP, and the role of care during a three-year period. We used data from the TAKECARE study, which consist of a care and community cohort. We followed adolescents aged 12 and over (n = 733) during 3 years over five assessment rounds. Using the Strengths and Difficulties Questionnaire, self-reported functioning was measured in four life domains: home life, friendships, classroom learning and leisure activities. We categorized the respondents into four groups: (1) adolescents without emotional and behavioural problems (n = 298); (2) adolescents with emotional problems (n = 192); (3) adolescents with behavioural problems (n = 80); and (4) adolescents with both emotional and behavioural problems (n = 163). The development of functioning over time was analyzed using longitudinal ordinal (probit) regression analyses. Adolescents with both emotional and behavioural problems reported poorer functioning at baseline in all domains and adolescents who received care reported poorer functioning at baseline compared to adolescents who did not receive care. Regarding the change in functioning during the 3 years, adolescents who received care showed improved functioning in all domains. We found improved functioning after care, even if the problems may not have been solved. Psychosocial care can contribute to the functioning of adolescents with EBP, which can have major effects on their future life.

Trajectories of care for children and adolescents with psychosocial problems: a 3-year prospective cohort study.

BACKGROUND: Care for children and adolescents with psychosocial problems is aimed at reducing problems. There may be a relationship between the intensity and duration of care provision and improvement of these outcomes, but evidence on this issue is lacking. We therefore examined the association between care trajectories based on duration and intensity of care for children, and the reduction in psychosocial problems after 3 years. METHODS: We obtained a cohort of all children entering psychosocial care in one region (n = 1,378), the TAKECARE cohort, and followed it for 3 years, with five assessment rounds. Retention in the final round was 85.8%. Psychosocial problems were measured using the parent report of the Total Difficulty Score of the Strength and Difficulties Questionnaire (SDQ-TDS). We constructed trajectories for intensity of care using growth mixture modelling and assessed the association between duration and intensity of care trajectories and SDQ-TDS after 3 years. RESULTS: After 3 months 60.6% of children and adolescents were receiving care, after 1 year 38.7% were receiving care and after 3 years 26.0%. Regarding intensity of care, three trajectories were found: one with minimal intensity during all 3 years, a second with initially medium intensity and strong reduction within 1 year, and a third with high intensity and a reduction after 1 year. Although the psychosocial problems of children and adolescents were reduced during the 3-year period, the rate of decline was relatively less marked for children and adolescents with longer care trajectories. CONCLUSION: Overall, children and adolescents with psychosocial problems who received care had improved outcomes at follow-up. However, increased provision of care does not automatically lead to reduction of problems, and although overall psychosocial problems are reduced, a substantial subgroup has longer lasting problems.

Cardiac Progenitor Cell-Derived Extracellular Vesicles Reduce Infarct Size and Associate with Increased Cardiovascular Cell Proliferation.

Cell transplantation studies have shown that injection of progenitor cells can improve cardiac function after myocardial infarction (MI). Transplantation of human cardiac progenitor cells (hCPCs) results in an increased ejection fraction, but survival and integration are low. Therefore, paracrine factors including extracellular vesicles (EVs) are likely to contribute to the beneficial effects. We investigated the contribution of EVs by transplanting hCPCs with reduced EV secretion. Interestingly, these hCPCs were unable to reduce infarct size post-MI. Moreover, injection of hCPC-EVs did significantly reduce infarct size. Analysis of EV uptake showed cardiomyocytes and endothelial cells primarily positive and a higher Ki67 expression in these cell types. Yes-associated protein (YAP), a proliferation marker associated with Ki67, was also increased in the entire infarcted area. In summary, our data suggest that EV secretion is the driving force behind the short-term beneficial effect of hCPC transplantation on cardiac recovery after MI.

Exosomes from Cardiomyocyte Progenitor Cells and Mesenchymal Stem Cells Stimulate Angiogenesis Via EMMPRIN.

To date, cellular transplantation therapy has not yet fulfilled its high expectations for cardiac repair. A major limiting factor is lack of long-term engraftment of the transplanted cells. Interestingly, transplanted cells can positively affect their environment via secreted paracrine factors, among which are extracellular vesicles, including exosomes: small bi-lipid-layered vesicles containing proteins, mRNAs, and miRNAs. An exosome-based therapy will therefore relay a plethora of effects, without some of the limiting factors of cell therapy. Since cardiomyocyte progenitor cells (CMPC) and mesenchymal stem cells (MSC) induce vessel formation and are frequently investigated for cardiac-related therapies, the pro-angiogenic properties of CMPC and MSC-derived exosome-like vesicles are investigated. Both cell types secrete exosome-like vesicles, which are efficiently taken up by endothelial cells. Endothelial cell migration and vessel formation are stimulated by these exosomes in in vitro models, mediated via ERK/Akt-signaling. Additionally, these exosomes stimulated blood vessel formation into matrigel plugs. Analysis of pro-angiogenic factors revealed high levels of extracellular matrix metalloproteinase inducer (EMMPRIN). Knockdown of EMMPRIN on CMPCs leads to a diminished pro-angiogenic effect, both in vitro and in vivo. Therefore, CMPC and MSC exosomes have powerful pro-angiogenic effects, and this effect is largely mediated via the presence of EMMPRIN on exosomes.

Cohort Profile: Tracing Achievements, Key processes and Efforts in professional care for Children and Adolescents REsearch; TAKECARE.

TAKECARE is a prospective cohort study designed in The Netherlands to obtain evidence on the care chain for children and adolescents with psychosocial problems, and its long-term outcomes. Little is known about the content of care as offered and on whether the care is adequate. The cohort consists of children and adolescents entering care for psychosocial problems (care sample, n = 1382) and a random sample of the general population (community sample, n = 666). Children were eligible for participation if they were aged 4-18 years (inclusive) and had estimated IQs of 70 and over. The care sample covers the fields of Preventive Child Healthcare (PCH), Child and Adolescent Social Care (CASC) and Child and Adolescent Mental Healthcare (CAMH). Children, parents or guardians and involved practitioners completed five questionnaires (baseline, and at 3, 12, 24 and 36 months thereafter). The main categories of data concern the sociodemographic characteristics of children and their parents or guardians, the characteristics of entry into care and care content, and intermediate and final treatment outcomes. Information about data access can be requested by e-mail: c4youth@umcg.nl.

Epicardial application of cardiac progenitor cells in a 3D-printed gelatin/hyaluronic acid patch preserves cardiac function after myocardial infarction.

Cardiac cell therapy suffers from limitations related to poor engraftment and significant cell death after transplantation. In this regard, ex vivo tissue engineering is a tool that has been demonstrated to increase cell retention and survival. The aim of our study was to evaluate the therapeutic potential of a 3D-printed patch composed of human cardiac-derived progenitor cells (hCMPCs) in a hyaluronic acid/gelatin (HA/gel) based matrix. hCMPCs were printed in the HA/gel matrix (30 × 10(6) cells/ml) to form a biocomplex made of six perpendicularly printed layers with a surface of 2 × 2 cm and thickness of 400 µm, in which they retained their viability, proliferation and differentiation capability. The printed biocomplex was transplanted in a mouse model of myocardial infarction (MI). The application of the patch led to a significant reduction in adverse remodeling and preservation of cardiac performance as was shown by both MRI and histology. Furthermore, the matrix supported the long-term in vivo survival and engraftment of hCMPCs, which exhibited a temporal increase in cardiac and vascular differentiation markers over the course of the 4 week follow-up period. Overall, we developed an effective and translational approach to enhance hCMPC delivery and action in the heart.

Microvesicles and exosomes for intracardiac communication.

The heart is an organ with a complex mixture of well-organized interactions of different cell types that facilitate proper myocardial contractility, sufficient perfusion, balanced myocardial extracellular stiffness, and controlled functioning of the immune system. Several cell types, including cardiomyocytes, endothelial cells, smooth muscle cells, fibroblasts, immune cells, and cardiac-derived stem cells, need a well-controlled communication system to use the complex orchestra of signalling molecules. The intercellular communication includes direct cell-cell contact, cell-matrix interaction, long-range signals, and electrical and extracellular chemical molecules. In addition to the extracellular molecules that cells can use to influence their environment, more and more attention is focused on the release of extracellular membrane vesicles by cells. These vesicles were always thought to be cell debris derivatives, but it appeared that these vesicles are used for horizontal transfer of information between cells, containing proteins, peptides, several classes of RNA molecules, and sometimes DNA. The main populations of released vesicles are classified on their (intra)cellular origin and include apoptotic bodies, microvesicles, and exosomes. Here, we provide an overview on the role of vesicles in cardiac communication and their use as potential therapeutics and biomarkers.