Pluripotent and Multipotent Stem Cells Display Distinct Hypoxic miRNA Expression Profiles

MicroRNAs are reported to have a crucial role in the regulation of self-renewal and differentiation of stem cells. Hypoxia has been identified as a key biophysical element of the stem cell culture milieu however, the link between hypoxia and miRNA expression in stem cells remains poorly understood. We therefore explored miRNA expression in hypoxic human embryonic and mesenchymal stem cells (hESCs and hMSCs). A total of 50 and 76 miRNAs were differentially regulated by hypoxia (2% O2) in hESCs and hMSCs, respectively, with a negligible overlap of only three miRNAs. We found coordinate regulation of precursor and mature miRNAs under hypoxia suggesting their regulation mainly at transcriptional level. Hypoxia response elements were located upstream of 97% of upregulated hypoxia regulated miRNAs (HRMs) suggesting hypoxia-inducible-factor (HIF) driven transcription. HIF binding to the candidate cis-elements of specific miRNAs under hypoxia was confirmed by Chromatin immunoprecipitation coupled with qPCR. Role analysis of a subset of upregulated HRMs identified linkage to reported inhibition of differentiation while a downregulated subset of HRMs had a putative role in the promotion of differentiation. MiRNA-target prediction correlation with published hypoxic hESC and hMSC gene expression profiles revealed HRM target genes enriched in the cytokine:cytokine receptor, HIF signalling and pathways in cancer. Overall, our study reveals, novel and distinct hypoxia-driven miRNA signatures in hESCs and hMSCs with the potential for application in optimised culture and differentiation models for both therapeutic application and improved understanding of stem cell biology

A renal colic fast track pathway to improve waiting times and outcomes for patients presenting to the emergency department

Introduction: Renal colic is commonly encountered in the emergency department (ED). We validated a fast track renal colic (FTRC) initiative to decrease patient waiting times and streamline patient flow. Method: The FTRC pathway was devised according to the National Institute for Health and Care Excellence clinical summary criteria for the management of patients with suspected renal colic. ED triage nurses use the pathway to identify patients with likely renal colic suitable for fast track to analgesia, investigation and management. Investigations, diagnosis and patient demographics were recorded for 1157 consecutive patients coded as renal colic at a single-center ED over 12 months. Results: Three hundred and two patients were suitable for the FTRC pathway (26.1%), while 855 were seen by the ED clinicians prior to onward referral. Also, 83.9% of patients underwent computed tomography scan. In the FTRC group, 57.3% of patients had radiologically confirmed calculi versus 53.8% in the non-FTRC group (p=0.31). Alternative diagnoses among FTRC patients (2.6%) included ovarian pathology (n=1), diverticulitis (n=2) and incidental renal cell carcinoma (n=2), while 26.1% had no identifiable pathology. No immediately life-threatening diagnoses were identified on imaging. Computed tomography scans performed in the non-FTRC group identified two ruptured abdominal aortic aneurysms and alternative diagnoses (2.57%) including ovarian pathology (n=7), cholecystitis (n=2), incidental renal cell carcinoma (n=3) and inflammatory bowel disease (n=1); 31.2% identified no pathology. Time in ED and time to radiologist-reported imaging were lower for the FTRC group versus non-FTRC group (p<0.0001). Conclusion: The FTRC pathway is a safe and efficacious method of reducing diagnostic delay and improving patient flow in the ED

Systematic review of studies of mental health nurses' experience of anger and of its relationships with their attitudes and practice

IntroductionEmotional regulation is important in mental health nursing practice but individual emotions may require different regulation strategies. There is ample evidence that nurses experience anger specifically during their work, for example when experiencing patient aggression. It is, therefore, important to consolidate what is known about how anger manifests in mental health nursing practice.AimWe aimed to systematically identify, evaluate, and synthesise results from studies about mental health nurses and anger, where anger was measured objectively.MethodsSystematic literature review based on PRISMA guidelines.Results.We identified 12 studies. A range of validated and non-validated instruments were used. Mental health nurses may have lower levels of anger than normative samples but anger is commonly reported as an issue for them. Anger was studied in relation to its links with i) clinical management of patients, notably violence containment; and ii) employment issues more generally, notably job motivation. Anger is related to nurses’ attitudes about the acceptability of coercion but there is no evidence that it results in more coercion.Implications for practiceNurses should be aware of the potential influence of anger on their practice. Anger, specifically, should be considered when supporting mental health nurses, for example in clinical supervision. Emotional regulation training should target anger

Toward optimal implementation of cancer prevention and control programs in public health: A study protocol on mis-implementation

Abstract Background Much of the cancer burden in the USA is preventable, through application of existing knowledge. State-level funders and public health practitioners are in ideal positions to affect programs and policies related to cancer control. Mis-implementation refers to ending effective programs and policies prematurely or continuing ineffective ones. Greater attention to mis-implementation should lead to use of effective interventions and more efficient expenditure of resources, which in the long term, will lead to more positive cancer outcomes. Methods This is a three-phase study that takes a comprehensive approach, leading to the elucidation of tactics for addressing mis-implementation. Phase 1: We assess the extent to which mis-implementation is occurring among state cancer control programs in public health. This initial phase will involve a survey of 800 practitioners representing all states. The programs represented will span the full continuum of cancer control, from primary prevention to survivorship. Phase 2: Using data from phase 1 to identify organizations in which mis-implementation is particularly high or low, the team will conduct eight comparative case studies to get a richer understanding of mis-implementation and to understand contextual differences. These case studies will highlight lessons learned about mis-implementation and identify hypothesized drivers. Phase 3: Agent-based modeling will be used to identify dynamic interactions between individual capacity, organizational capacity, use of evidence, funding, and external factors driving mis-implementation. The team will then translate and disseminate findings from phases 1 to 3 to practitioners and practice-related stakeholders to support the reduction of mis-implementation. Discussion This study is innovative and significant because it will (1) be the first to refine and further develop reliable and valid measures of mis-implementation of public health programs; (2) bring together a strong, transdisciplinary team with significant expertise in practice-based research; (3) use agent-based modeling to address cancer control implementation; and (4) use a participatory, evidence-based, stakeholder-driven approach that will identify key leverage points for addressing mis-implementation among state public health programs. This research is expected to provide replicable computational simulation models that can identify leverage points and public health system dynamics to reduce mis-implementation in cancer control and may be of interest to other health areas

The Role of Individual Variables, Organizational Variables and Moral Intensity Dimensions in Libyan Management Accountants’ Ethical Decision Making

This study investigates the association of a broad set of variables with the ethical decision making of management accountants in Libya. Adopting a cross-sectional methodology, a questionnaire including four different ethical scenarios was used to gather data from 229 participants. For each scenario, ethical decision making was examined in terms of the recognition, judgment and intention stages of Rest’s model. A significant relationship was found between ethical recognition and ethical judgment and also between ethical judgment and ethical intention, but ethical recognition did not significantly predict ethical intention—thus providing support for Rest’s model. Organizational variables, age and educational level yielded few significant results. The lack of significance for codes of ethics might reflect their relative lack of development in Libya, in which case Libyan companies should pay attention to their content and how they are supported, especially in the light of the under-development of the accounting profession in Libya. Few significant results were also found for gender, but where they were found, males showed more ethical characteristics than females. This unusual result reinforces the dangers of gender stereotyping in business. Personal moral philosophy and moral intensity dimensions were generally found to be significant predictors of the three stages of ethical decision making studied. One implication of this is to give more attention to ethics in accounting education, making the connections between accounting practice and (in Libya) Islam. Overall, this study not only adds to the available empirical evidence on factors affecting ethical decision making, notably examining three stages of Rest’s model, but also offers rare insights into the ethical views of practising management accountants and provides a benchmark for future studies of ethical decision making in Muslim majority countries and other parts of the developing world

Optimising management of patients with heart failure with preserved ejection fraction in primary care (OPTIMISE-HFpEF): rationale and protocol for a multi-method study

Background Heart failure with preserved ejection fraction (HFpEF) is less well understood than heart failure with reduced ejection fraction (HFrEF), with greater diagnostic difficulty and management uncertainty. Aim The primary aim is to develop an optimised programme that is informed by the needs and experiences of people with HFpEF and healthcare providers. This article presents the rationale and protocol for the Optimising Management of Patients with Heart Failure with Preserved Ejection Fraction in Primary Care (OPTIMISE-HFpEF) research programme. Design & setting This is a multi-method programme of research conducted in the UK. Method OPTIMISE-HFpEF is a multi-site programme of research with three distinct work packages (WPs). WP1 is a systematic review of heart failure disease management programmes (HF-DMPs) tested in patients with HFpEF. WP2 has three components (a, b, c) that enable the characteristics, needs, and experiences of people with HFpEF, their carers, and healthcare providers to be understood. Qualitative enquiry (WP2a) with patients and providers will be conducted in three UK sites exploring patient and provider perspectives, with an additional qualitative component (WP2c) in one site to focus on transitions in care and carer perspectives. A longitudinal cohort study (WP2b), recruiting from four UK sites, will allow patients to be characterised and their illness trajectory observed across 1 year of follow-up. Finally, WP3 will synthesise the findings and conduct work to gain consensus on how best to identify and manage this patient group. Results Results from the four work packages will be synthesised to produce a summary of key learning points and possible solutions (optimised programme) which will be presented to a broad spectrum of stakeholders to gain consensus on a way forward. Conclusion HFpEF is often described as the greatest unmet need in cardiology. The OPTIMISE-HFpEF programme aims to address this need in primary care, which is arguably the most appropriate setting for managing HFpEF

Mantle thermal pulses below the Mid-Atlantic Ridge and temporal variations in the formation of oceanic lithosphere

A 20-Myr record of creation of oceanic lithosphere is exposed along a segment of the central Mid-Atlantic Ridge on an uplifted sliver of lithosphere. The degree of melting of the mantle that is upwelling below the ridge, estimated from the chemistry of the exposed mantle rocks, as well as crustal thickness inferred from gravity measurements, show oscillations of 3–4 Myr superimposed on a longer-term steady increase with time. The time lag between oscillations of mantle melting and crustal thickness indicates that the mantle is upwelling at an average rate of 25 mm yr-1, but this appears to vary through time. Slow-spreading lithosphere seems to form through dynamic pulses of mantle upwelling and melting, leading not only to along-axis segmentation but also to across-axis structural variability. Also, the central Mid-Atlantic Ridge appears to have become steadily hotter over the past 20 Myr, possibly owing to north–south mantle flow

A Helicity-Based Method to Infer the CME Magnetic Field Magnitude in Sun and Geospace: Generalization and Extension to Sun-Like and M-Dwarf Stars and Implications for Exoplanet Habitability

Patsourakos et al. (Astrophys. J. 817, 14, 2016) and Patsourakos and Georgoulis (Astron. Astrophys. 595, A121, 2016) introduced a method to infer the axial magnetic field in flux-rope coronal mass ejections (CMEs) in the solar corona and farther away in the interplanetary medium. The method, based on the conservation principle of magnetic helicity, uses the relative magnetic helicity of the solar source region as input estimates, along with the radius and length of the corresponding CME flux rope. The method was initially applied to cylindrical force-free flux ropes, with encouraging results. We hereby extend our framework along two distinct lines. First, we generalize our formalism to several possible flux-rope configurations (linear and nonlinear force-free, non-force-free, spheromak, and torus) to investigate the dependence of the resulting CME axial magnetic field on input parameters and the employed flux-rope configuration. Second, we generalize our framework to both Sun-like and active M-dwarf stars hosting superflares. In a qualitative sense, we find that Earth may not experience severe atmosphere-eroding magnetospheric compression even for eruptive solar superflares with energies ~ 10^4 times higher than those of the largest Geostationary Operational Environmental Satellite (GOES) X-class flares currently observed. In addition, the two recently discovered exoplanets with the highest Earth-similarity index, Kepler 438b and Proxima b, seem to lie in the prohibitive zone of atmospheric erosion due to interplanetary CMEs (ICMEs), except when they possess planetary magnetic fields that are much higher than that of Earth.Comment: http://adsabs.harvard.edu/abs/2017SoPh..292...89

Age-associated modifications of intestinal permeability and innate immunity in human small intestine

The physical and immunological properties of the human intestinal epithelial barrier in aging are largely unknown. Ileal biopsies from young (7–12 years), adult (20–40 years) and aging (67–77 years) individuals not showing symptoms of gastrointestinal (GI) pathologies were used to assess levels of inflammatory cytokines, barrier integrity and cytokine production in response to microbial challenges. Increased expression of interleukin (IL)-6, but not interferon (IFN)γ, tumour necrosis factor (TNF)-α and IL-1β was observed during aging; further analysis showed that cluster of differentiation (CD)11c+ dendritic cells (DCs) are one of the major sources of IL-6 in the aging gut and expressed higher levels of CD40. Up-regulated production of IL-6 was accompanied by increased expression of claudin-2 leading to reduced transepithelial electric resistance (TEER); TEER could be restored in in vitro and ex vivo cultures by neutralizing anti-IL-6 antibody. In contrast, expression of zonula occludens-1 (ZO-1), occludin and junctional-adhesion molecule-A1 did not vary with age and overall permeability to macromolecules was not affected. Finally, cytokine production in response to different microbial stimuli was assessed in a polarized in vitro organ culture (IVOC). IL-8 production in response to flagellin declined progressively with age although the expression and distribution of toll-like receptor (TLR)-5 on intestinal epithelial cells (IECs) remained unchanged. Also, flagellin-induced production of IL-6 was less pronounced in aging individuals. In contrast, TNF-α production in response to probiotics (VSL#3) did not decline with age; however, in our experimental model probiotics did not down-regulate the production of IL-6 and expression of claudin-2. These data suggested that aging affects properties of the intestinal barrier likely to impact on age-associated disturbances, both locally and systemically