Multiperspectivity in organized sport in refugee sites : Sociological findings and pedagogical considerations

Refugee sites are a means to manage large-scale refugee movements, a recurring event in today’s world. Sport is supposed to have beneficial eects for the residents of such sites and is therefore an activity, which is standardly organized by the sites’ management. Moreover, many NGOs and “Sport for Development and Peace” programmes endorse the use of sport in emergency situations—including in refugee sites—to achieve several biopsychosocial objectives. There is a growing body of scientific literature, however, that is calling into question the beneficial eects of sport in this setting as well as the rationale behind this idea. Against this background, we explore the question “How does multiperspectivity influence sport in refugee sites?” based on two case studies. We use the ethnographic materials we were able to collect for the case studies to conduct a (sociological) analysis of multiperspectivity in sport and to develop (pedagogical) proposals on how to incorporate multiperspectivity when devising sports activities for refugees. The fact that the perspectives and motivations beyond the actual sports activities in the refugee site setting might be extremely homogenous leads us to conclude that multiperspectivity is key for planning, organizing and monitoring sports activities, and that refugees’ positions must also be acknowledged. We recommend programmes and practical ways of achieving these objectives with a focus on the role of trainers and coaches

Innovative cancer therapeutics based on polymers or biogenic drugs evaluated in murine tumor models

Cancer is a leading cause of death worldwide. Although several common treatment options exist, there is an urgent need for improved tumor therapeutics. Therefore, we evaluated three innovative anticancer approaches in vivo. These were newly synthesized siRNA polyplexes, novel myxobacterial anticancer compounds, and innovative polymeric melphalan formulations. We evaluated the in vivo characteristics of polymeric bound siRNA. We could demonstrate that the polymer FolA-PEG24-K(Stp4-C)2 is an efficient carrier for targeting siRNA to the folate receptor expressing tumor tissue of mice. Moreover, the siRNA was able to enter tumor cells and led to specific gene silencing. After systemic injection, the polyplexes did neither cause any toxic side effects nor accumulate in any healthy organ. With only 6 nm average diameter, polyplexes were very small, resulting in fast removal from blood circulation by renal clearance. Addition of larger PEG spacers to the initial polyplex led to an increased polyplex size. As a result, the renal clearance was decreased, and polyplex distribution in the body was optimized. These results show that the in vivo hurdles of siRNA delivery can be overcome by binding siRNA to the precise and multifunctional polymers. Natural compounds have broad therapeutic effects, and are basis for the production of various anticancer drugs. Myxobacterial products often target cell structures which are rarely targeted by other metabolites, and they exert novel modes of action. Therefore, they are of particular importance for the development of new anticancer drugs. In this thesis, we evaluated three novel myxobacterial compounds in vivo. Within our experimental settings, we could demonstrate for the first time that archazolid, pretubulysin and chondramide can impair the migration and colonization of breast cancer cells in mice. Concerning their impact on tumor growth reduction, the compounds have promising characteristics, but the experimental setups need further improvement. Cytostatic drugs, like melphalan play an important role in cancer therapy, but bear problems, such as a low therapeutic efficacy and strong toxic side effects. Immobilization of chemotherapeutics on polymers is an interesting option to reduce their toxicity and enhance their efficacy, mainly by passive tumor targeting. We evaluated three innovative polymer-melphalan formulations in cell viability and proliferation assays. The covalent conjugate of poly(oxyethylene H-phosphonate) with melphalan was additionally investigated in vivo. This polymeric immobilization of melphalan led to an improved therapeutic effect compared to the pure cytostatic drug, as the growth and regrowth of HuH7 tumors could be hampered effectively. In conclusion, this thesis deals with the in vivo evaluation of innovative cancer therapeutics, which were successfully investigated in murine tumor models. The results with the experimental agents, based on siRNA, polymers or biogenic drugs, are encouraging starting points for further anticancer research

Sport for Development and Peace in the United Nations: An Empirical Study on the Development of the Role of SDP in the UN in the Context of the Closure of the UNOSDP

In 2017, it was decided that the United Nations Office on Sport for Development and Peace (UNOSDP) is to be closed. This qualitative study aims to analyse the reasons for the closure as well as its effects on Sport for Development and Peace (SDP) in the United Nations. Against the background of the systems theory, we conducted interviews with participants from relevant organisations. It is shown that the way the UNOSDP worked underwent a change and that the new tasks as well as their fulfilment were viewed controversially. Additionally, broader changes in development policy set a new frame for SDP

The Role of Packing, Dispersion, Electrostatics, and Solvation in High‐Affinity Complexes of Cucurbit[ n ]urils with Uncharged Polar Guests

The rationalization of non-covalent binding trends is both of fundamental interest and provides new design concepts for biomimetic molecular systems. Cucurbit[n]urils (CBn) are known for a long time as the strongest synthetic binders for a wide range of (bio)organic compounds in water. However, their host-guest binding mechanism remains ambiguous despite their symmetric and simple macrocyclic structure and the wealth of literature reports. We herein report experimental thermodynamic binding parameters (ΔG, ΔH, TΔS) for CB7 and CB8 with a set of hydroxylated adamantanes, di-, and triamantanes as uncharged, rigid, and spherical/ellipsoidal guests. Binding geometries and binding energy decomposition were obtained from high-level theory computations. This study reveals that neither London dispersion interactions, nor electronic energies or entropic factors are decisive, selectivity-controlling factors for CBn complexes. In contrast, peculiar host-related solvation effects were identified as the major factor for rationalizing the unique behavior and record-affinity characteristics of cucurbit[n]urils

Association of Age at Menopause With Incident Heart Failure: A Prospective Cohort Study and Meta‐Analysis

BACKGROUND: Early age (<45 years) at menopause has been postulated to be associated with increased cardiovascular disease risk; however, evidence of its relation with heart failure (HF) incidence is limited. We examined whether age at menopause is associated inversely with HF incidence in the Atherosclerosis Risk In Communities (ARIC) study and summarized all existing data in a meta-analysis. METHODS AND RESULTS: In ARIC, data were obtained from 5629 postmenopausal women (mean age 56 years, 26% with bilateral oophorectomy) without HF. During a median follow-up of 21.4 years, 965 incident HF events occurred. In a Cox regression model adjusted for reproductive health and HF risk factors, the hazard ratios for incident HF across categories of age at menopause (<45, 45-49, 50-54, and ≥55 years) were 1.32, 1.17, 1.00 (referent), and 1.12, respectively. Compared with women with later onset of menopause (aged ≥45 years), those with early menopause had elevated HF risk (hazard ratio 1.20, 95% CI 1.01-1.43). For the meta-analysis, we searched Medline and Embase for articles published through December 2015 that prospectively evaluated age at menopause and HF risk. Summarized estimates from the 3 included studies (3568 events) showed higher HF risk among women with early menopause compared with those with later menopause (hazard ratio 1.33, 95% CI 1.15-1.53). CONCLUSIONS: These results provided evidence that early age at menopause is associated with a modestly greater risk of HF. Identification of women with early menopause offers a window of opportunity to implement interventions that will improve overall cardiovascular health during the postmenopausal years

Nanosized Multifunctional Polyplexes for Receptor-Mediated SiRNA Delivery

Although our understanding of RNAi and our knowledge on designing and synthesizing active and safe siRNAs significantly increased during the past decade, targeted delivery remains the major limitation in the development of siRNA therapeutics. On one hand, practical considerations dictate robust chemistry reproducibly providing precise carrier molecules. On the other hand, the multistep delivery process requires dynamic multifunctional carriers of substantial complexity. We present a monodisperse and multifunctional carrier system, synthesized by solid phase supported chemistry, for siRNA delivery in vitro and in vivo. The sequence-defined assembly includes a precise cationic (oligoethanamino)amide core, terminated at the ends by two cysteines for bioreversible polyplex stabilization, at a defined central position attached to a monodisperse polyethylene glycol chain coupled to a terminal folic acid as cell targeting ligand. Complexation with an endosomolytic influenza peptide-siRNA conjugate results in nanosized functional polyplexes of 6 nm hydrodynamic diameter. The necessity of each functional substructure of the carrier system for a specific and efficient gene silencing was confirmed. The nanosized polyplexes showed stability in vivo, receptor-specific cell targeting, and silencing of the EG5 gene in receptor-positive tumors. The nanosized appearance of these particles can be precisely controlled by the oligomer design (from 5.8 to 8.8 nm diameter). A complete surface charge shielding together with the high stability result in good tolerability in vivo and the absence of accumulation in nontargeted tissues such as liver, lung, or spleen. Due to their small size, siRNA polyplexes are efficiently cleared by the kidney