Ionizing Radiation Alters Human Embryonic Stem Cell Properties and Differentiation Capacity by Diminishing the Expression of Activin Receptors.

Exposure of the embryo to ionizing radiation (IR) is detrimental as it can cause genotoxic stress leading to immediate and latent consequences such as functional defects, malformations, or cancer. Human embryonic stem (hES) cells can mimic the preimplantation embryo and help to assess the biological effects of IR during early development. In this study, we describe the alterations H9 hES cells exhibit after X-ray irradiation in respect to cell cycle progression, apoptosis, genomic stability, stem cell signaling, and their capacity to differentiate into definitive endoderm. Early postirradiation, hES cells responded with an arrest in G2/M phase, elevated apoptosis, and increased chromosomal aberrations. Significant downregulation of stem cell signaling markers of the TGF beta-, Wnt-, and Hedgehog pathways was observed. Most prominent were alterations in the expression of activin receptors. However, hES cells responded differently depending on the culture conditions chosen for maintenance. Enzymatically passaged cells were less sensitive to IR than mechanically passaged ones showing fewer apoptotic cells and fewer changes in the stem cell signaling 24 h after irradiation, but displayed higher levels of chromosomal aberrations. Even though many of the observed changes were transient, surviving hES cells, which were differentiated 4 days postirradiation, showed a lower efficiency to form definitive endoderm than their mock-irradiated counterparts. This was demonstrated by lower expression levels of SOX17 and microRNA miR-375. In conclusion, hES cells are a suitable tool for the IR risk assessment during early human development. However, careful choice of the culture methods and a vigorous monitoring of the stem cell quality are mandatory for the use of these cells. Exposure to IR influences the stem cell properties of hES cells even when immediate radiation effects are overcome. This warrants consideration in the risk assessment of radiation effects during the earliest stages of human development.

The hierarchy of work pursuits of public health managers.

How public health is managed in various settings is an important but under-examined issue. We examine themes in the management literature, contextualize issues facing public health managers and investigate the relative importance placed on their various work pursuits using a 14-activity management model empirically derived from studies of clinician-managers in hospitals. Ethnographic case studies of 10 managers in nine diverse public health settings were conducted. The case study accounts of managers' activities were content analysed, and substantive words encapsulating their work were categorized using the model. Managerial activities of the nine public health managers were ranked according to the number of words describing each activity. Kendall's coefficient of concordance yielded W = 0.710, P < 0.000, revealing significant similarity between the activity patterns of the public health managers. A rank order correlation between the activity patterns of the average ranks for the public health sample and for the hospital clinician-managers (n = 52) was R = 0.420, P = 0.131, indicating no significant relationship between relative activity priorities of the two groups. Public health managers put less emphasis on pursuits associated with structure, hierarchy and education, and more on external relations and decision-making. The model of hospital clinician-managers' managerial activities is applicable to public health managers while identifying differences in the way the two groups manage. The findings suggest that public health management work is more managerialist than previously thought.