Mediamusic (E-Journal)
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    Generation and Differentiation of Adult Tissue-Derived Human Thyroid Organoids

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    Total thyroidectomy as part of thyroid cancer treatment results in hypothyroidism requiring lifelong daily thyroid hormone replacement. Unbalanced hormone levels result in persistent complaints such as fatigue, constipation, and weight increase. Therefore, we aimed to investigate a patient-derived thyroid organoid model with the potential to regenerate the thyroid gland. Murine and human thyroidderived cells were cultured as organoids capable of self-renewal and which expressed proliferation and putative stem cell and thyroid characteristics, without a change in the expression of thyroid tumor-related genes. These organoids formed thyroid-tissue-resembling structures in culture. (Xeno-)transplantation of 600,000 dispersed organoid cells underneath the kidney capsule of a hypothyroid mouse model resulted in the generation of hormone-producing thyroid-resembling follicles. This study provides evidence that thyroid-lineagespecific cells can form organoids that are able to self-renew and differentiate into functional thyroid tissue. Subsequent (xeno-)transplantation of these thyroid organoids demonstrates a proof of principle for functional miniature gland formation.</p

    Measurement of Protein Mobility in Listeria monocytogenes Reveals a Unique Tolerance to Osmotic Stress and Temperature Dependence of Diffusion

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    Protein mobility in the cytoplasm is essential for cellular functions, and slow diffusion may limit the rates of biochemical reactions in the living cell. Here, we determined the apparent lateral diffusion coefficient (D L ) of GFP in Listeria monocytogenes as a function of osmotic stress, temperature, and media composition. We find that D L is much less affected by hyperosmotic stress in L. monocytogenes than under similar conditions in Lactococcus lactis and Escherichia coli. We find a temperature optimum for protein diffusion in L. monocytogenes at 30°C, which deviates from predicted trends from the generalized Stokes-Einstein equation under dilute conditions and suggests that the structure of the cytoplasm and macromolecular crowding vary as a function of temperature. The turgor pressure of L. monocytogenes is comparable to other Gram-positive bacteria like Bacillus subtilis and L. lactis but higher in a knockout strain lacking the stress-inducible sigma factor SigB. We discuss these findings in the context of how L. monocytogenes survives during environmental transmission and interaction with the human host.</p

    The subtle spreading of sexist norms

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    Even when overt sexism and prejudice become rarer, social norms that perpetuate inequality are remarkably persistent. The present research lays out one of the subtle ways in which sexist norms may spread through society, by pointing to the role of responses to sexism. We investigate how third parties infer social norms about sexism when observing social interactions. In three studies among male students (Studies 1 and 2) and male and female students (Study 3), we demonstrate that subtle variations in how people respond to a sexist statement can have a substantial influence on inferences third parties make about sexist norms. Specifically, when a sexist statement is made and the conversation continues in a smoothly flowing fashion, third parties infer that this opinion is shared among interaction partners, perceived as appropriate, and that sexism is normative among them. However, when a sexist statement is followed by a brief silence that disrupts the flow of the conversation, observers think that it is contentious and that sexism is neither shared nor normative. Importantly, the effects of the manipulation generalized to the perception of sexist descriptive norms among male students in general. We conclude that social and cultural norms are not just inferred from conversation content, but also from conversational flow.</p

    Development, validation and evaluation of a patient information booklet for rectal cancer survivors with a stoma:A three-step approach

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    OBJECTIVE: Quantitatively measure the degree of patient satisfaction and perceived acquired knowledge through the development of a patient information booklet for rectal cancer survivors with a stoma, according to a novel three-step approach.METHODS: The study included a systematic literature review to identify relevant information for the booklet, which was validated by experts based on relevance, clarity and essentiality. It underwent testing on quality, readability, and layout and design and was quantitatively evaluated by rectal cancer survivors with a stoma.RESULTS: In total, 145 articles were used for the development of the booklet. It scored 91% for relevance according to 17 experts, 70% for readability, 75.63% for quality and 23 out of 32 for design. The mean score of patient satisfaction was 8.03 out of 10. All 20 patients found the booklet 'useful' and 95% felt better informed.CONCLUSIONS: The booklet scored high for patient satisfaction and increased perceived acquired information. It ensured satisfactory levels of quality, readability, and layout and design.PRACTICE IMPLICATIONS: This study offers a novel three-step approach for development of informational tools for cancer survivors, assuring that a variety of newly created written patient materials would be of increased quality and relevance to any target population.</p

    Immediate single-tooth implant placement with simultaneous bone augmentation versus delayed implant placement after alveolar ridge preservation in bony defect sites in the esthetic region:A 5-year randomized controlled trial

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    Background It is unclear if an intact buccal bony plate is a prerequisite for immediate implant placement in post-extraction sockets. The aim of this 5-year randomized controlled trial was therefore comparison of peri-implant soft and hard tissue parameters, esthetic ratings, and patient-reported satisfaction of immediate implant placement in post-extraction sockets with buccal bony defects of &gt;= 5 mm in the esthetic zone, with delayed implant placement after ridge preservation.Methods Patients presenting a failing tooth in the esthetic region and a buccal bony defect of &gt;= 5 mm after extraction were randomly assigned to immediate (Immediate group, n = 20) or delayed (Delayed group, n = 20) implant placement. Second-stage surgery and placement of a provisional restoration occurred 3 months after implant placement in both groups, followed by definitive restorations 3 months thereafter. The follow-up was 5 years. Marginal bone level (primary outcome), buccal bone thickness, soft tissue parameters, esthetics, and patient-reported satisfaction were recorded.Results Mean marginal bone level change was -0.71 +/- 0.35 mm and -0.54 +/- 0.41 mm in respectively the Immediate group and the Delayed group after 5 years (P = 0.202). This difference, and in other variables, was not significant.Conclusions Marginal bone level changes, buccal bone thickness, clinical outcomes, esthetics, and patients' satisfaction following immediate implant placement, in combination with bone augmentation in post-extraction sockets with buccal bony defects of &gt;= 5 mm, were comparable to those following delayed implant placement after ridge preservation in the esthetic zone.</p

    Basal cognition:Multicellularity, neurons and the cognitive lens

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    Economics of Youth Mental Health:essays on Juvenile Delinquency, Education and Policy

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    Mental health problems largely originate during youth and affect one out of five individuals worldwide. The corresponding individual disease burden lead to significant societal costs, as youth mental health problems have a long-lasting impact over the life-cycle. Through an economic lens youth mental health can be seen as a pivotal element of human capital, associated with educational progress and labour market participation, required to produce economic value. Despite the relevance of youth mental health from both a health and economic perspective, there is still an imperative need for research to reduce the burden of mental health for future generations. In this thesis we have focused on one piece of the puzzle, i.e. the lack of data-driven evaluation strategies to identify (cost-)effective youth mental health interventions. One of the challenges is the fact that in many cases, experiments (i.e., randomized controlled trials) remain difficult or impossible to implement, for financial, political, or ethical reasons, or because the population of interest is too small. Therefore, I demonstrate in this thesis that observational data could be used to provide crucial insights for clinical and policy decision-making in order to make more optimal budget allocations. We were able to identify the role of policies in youth mental health trajectories (chapter 2), the effect of mental health interventions on societal outcomes (chapter 3), the relationship between monitoring compliance to compulsory education and student’s test scores (chapter 4), and the long-run return to government expenditures in special education (chapter 5)

    The Importance of Radiation Dose to the Atherosclerotic Plaque in the Left Anterior Descending Coronary Artery for Radiation-Induced Cardiac Toxicity of Breast Cancer Patients?

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    IMPORTANCE: Radiation-induced acute coronary events (ACEs) may occur as treatment-related late side effect of breast cancer (BC) radiation. However, the underlying mechanisms behind this radiation-induced cardiac disease remains to be determined.OBJECTIVE: The objective of this study was to test the hypothesis that radiation dose to calcified atherosclerotic plaques in the left anterior descending coronary artery (LAD) is a better predictor for ACEs than radiation dose to the whole heart or left ventricle in BC patients treated with radiotherapy (RT).DESIGN, SETTING, PARTICIPANTS, AND MAIN OUTCOMES AND MEASURES: The study cohort consisted of 910 BC patients treated with postoperative RT after breast conserving surgery. In total, 163 patients had an atherosclerotic plaque in the LAD. The endpoint was the occurrence of an ACE after treatment. For each individual patient, the mean heart dose (MHD), volume of the left ventricle receiving ≥ 5 Gy (LV-V5), mean LAD dose and mean dose to calcified atherosclerotic plaques in the LAD, if present, were acquired based on planning CT-scans. Cox-regression analysis was used to analyse the effects on the cumulative incidence of ACEs.RESULTS: The median follow-up time was 9.2 years (range: 0.1-14.3 years). In total, 38 patients (4.2%) developed an ACE during follow-up. For patients with an atherosclerotic plaque (n=163) the mean dose to the atherosclerotic plaque was the strongest predictor for ACE, even after correction for cardiovascular risk factors (HR: 1.269 (95% CI: 1.090-1.477), P=0.002). The LV-V5 was associated with ACEs in patients without atherosclerotic plaques in the LAD (n=680) (hazard ratio (HR): 1.021 (95% CI: 1.003-1.039; P=0.023).CONCLUSION AND RELEVANCE: The results of this study suggest that radiation dose to pre-existing calcified atherosclerotic plaques in the LAD is strongly associated with the development of ACEs in BC patients.</p

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