Different epigenetic states define syncytiotrophoblast and cytotrophoblast nuclei in the trophoblast of the human placenta.

INTRODUCTION: The syncytiotrophoblast (STB) epithelial covering of the villous tree in the human placenta is a multi-nucleated syncytium that is sustained by continuous incorporation of differentiating cytotrophoblast (CTB) cells. STB nuclei display a variety of morphologies, but are generally more condensed in comparison to CTB nuclei. Here, we consider whether this condensation is a feature of epigenetic regulation of chromatin structure. METHODS: Semi-quantitative immunohistochemical investigations of a panel of histone modifications were performed to determine the relative proportions in CTB and STB nuclear populations. We also investigated the patterns of DNA methylation and distribution of DNA methyltransferases enzymes in these populations. RESULTS: Unexpectedly DNA methylation, and H3K9me3 and H3K27me3, which are modifications associated with heterochromatin, are present at lower levels in STB nuclei compared to CTB, despite the intensive condensation in the former nuclear population and the progenitor state of the latter. By contrast, STB nuclei are enriched for H4K20me3, which is also associated with repressive states. 5'hydroxymethylcytosine immunoreactivity is higher in STB, with intense staining observed in the highly condensed nuclei within syncytial knots. DISCUSSION: Cell-type specific epigenetic states exist within the trophoblast populations potentially regulating their different functions and developmental properties and suggesting non-canonical epigenetic states associated with the properties of these cells.This work was funded by a studentship from the Anatomical Society of Great Britain and Ireland. The study was also supported by the Centre for Trophoblast Research.This is the accepted manuscript. The final version is available at http://www.sciencedirect.com/science/article/pii/S0143400415009248

When pharmacotherapeutic recommendations may lead to the reverse effect on physician decision-making

For long the medical literature has shown that patients do not always receive appropriate care, including pharmacotherapeutic treatment. To achieve improved patient care, a number of physician-oriented interventions are being delivered internationally in an attempt to implement evidence based medicine in routine daily practice of medical practitioners. The pharmacy profession has taken an active role in the delivery of intervention strategies aimed at promoting evidence based prescribing and improved quality and safety of medicine use. However, the medical literature also supports the notion that valid clinical care recommendations do not always have the desired impact on physician behaviour. We argue that the well-established theory of psychological reactance might at least partially explain instances when physicians do not act upon such recommendations. Reactance theory suggests that when recommended to take a certain action, a motivational state compels us to react in a way that affirms our freedom to choose. Often we choose to do the opposite of what the recommendation is proposing that we do or we just become entrenched in our initial position. The basic concepts of psychological reactance are universal and likely to be applicable to the provision of recommendations to physicians. Making recommendations regarding clinical care, including pharmacotherapy, may carry with it implied threats, as it can be perceived as an attempt to restrict one’s freedom of choice potentially generating reactance and efforts to avoid them. By identifying and taking into account factors likely to promote reactance, physician-oriented interventions could become more effective

Stress in nurses : stress-related affect and its determinants examined over the nursing day

Peer reviewedPostprin

Medication safety in community pharmacy: a qualitative study of the sociotechnical context

<p>Abstract</p> <p>Background</p> <p>While much research has been conducted on medication safety, few of these studies have addressed primary care, despite the high volume of prescribing and dispensing of medicines that occurs in this setting. Those studies that have examined primary care dispensing emphasised the need to understand the role of sociotechnical factors (that is, the interactions between people, tasks, equipment and organisational structures) in promoting or preventing medication incidents. The aim of this study was to identify sociotechnical factors that community pharmacy staff encounter in practice, and suggest how these factors might impact on medication safety.</p> <p>Methods</p> <p>Sixty-seven practitioners, working in the North West of England, took part in ten focus groups on risk management in community pharmacy. The data obtained from these groups was subjected to a qualitative analysis to identify recurrent themes pertaining to sociotechnical aspects of medication safety.</p> <p>Results</p> <p>The findings indicated several characteristics of participants' work settings that were potentially related to medication safety. These were broadly classified as relationships involving the pharmacist, demands on the pharmacist and management and governance of pharmacists.</p> <p>Conclusion</p> <p>It is recommended that the issues raised in this study be considered in future work examining medication safety in primary care.</p

Healthcare Staff Wellbeing, Burnout, and Patient Safety: A Systematic Review

Objective To determine whether there is an association between healthcare professionals’ wellbeing and burnout, with patient safety. Design Systematic research review. Data Sources PsychInfo (1806 to July 2015), Medline (1946 to July 2015), Embase (1947 to July 2015) and Scopus (1823 to July 2015) were searched, along with reference lists of eligible articles. Eligibility Criteria for Selecting Studies Quantitative, empirical studies that included i) either a measure of wellbeing or burnout, and ii) patient safety, in healthcare staff populations. Results Forty-six studies were identified. Sixteen out of the 27 studies that measured wellbeing found a significant correlation between poor wellbeing and worse patient safety, with six additional studies finding an association with some but not all scales used, and one study finding a significant association but in the opposite direction to the majority of studies. Twenty-one out of the 30 studies that measured burnout found a significant association between burnout and patient safety, whilst a further four studies found an association between one or more (but not all) subscales of the burnout measures employed, and patient safety. Conclusions Poor wellbeing and moderate to high levels of burnout are associated, in the majority of studies reviewed, with poor patient safety outcomes such as medical errors, however the lack of prospective studies reduces the ability to determine causality. Further prospective studies, research in primary care, conducted within the UK, and a clearer definition of healthcare staff wellbeing are needed. Implications This review illustrates the need for healthcare organisations to consider improving employees’ mental health as well as creating safer work environments when planning interventions to improve patient safety

Four Regional Marine Biodiversity Studies: Approaches and Contributions to Ecosystem-Based Management

We compare objectives and approaches of four regional studies of marine biodiversity: Gulf of Maine Area Census of Marine Life, Baltic Sea History of Marine Animal Populations, Great Barrier Reef Seabed Biodiversity Project, and Gulf of Mexico Biodiversity Project. Each program was designed as an "ecosystem" scale but was created independently and executed differently. Each lasted 8 to 10 years, including several years to refine program objectives, raise funding, and develop research networks. All resulted in improved baseline data and in new, or revised, data systems. Each contributed to the creation or evolution of interdisciplinary teams, and to regional, national, or international science-management linkages. To date, there have been differing extents of delivery and use of scientific information to and by management, with greatest integration by the program designed around specific management questions. We evaluate each research program's relative emphasis on three principal elements of biodiversity organization: composition, structure, and function. This approach is used to analyze existing ecosystem-wide biodiversity knowledge and to assess what is known and where gaps exist. In all four of these systems and studies, there is a relative paucity of investigation on functional elements of biodiversity, when compared with compositional and structural elements. This is symptomatic of the current state of the science. Substantial investment in understanding one or more biodiversity element(s) will allow issues to be addressed in a timely and more integrative fashion. Evaluating research needs and possible approaches across specific elements of biodiversity organization can facilitate planning of future studies and lead to more effective communication between scientists, managers, and stakeholders. Building a general approach that captures how various studies have focused on different biodiversity elements can also contribute to meta-analyses of worldwide experience in scientific research to support ecosystem-based management