Chemical regulators of epithelial plasticity reveal a nuclear receptor pathway controlling myofibroblast differentiation

Plasticity in epithelial tissues relates to processes of embryonic development, tissue fibrosis and cancer progression. Pharmacological modulation of epithelial transitions during disease progression may thus be clinically useful. Using human keratinocytes and a robotic high-content imaging platform, we screened for chemical compounds that reverse transforming growth factor β (TGF-β)-induced epithelial-mesenchymal transition. In addition to TGF-β receptor kinase inhibitors, we identified small molecule epithelial plasticity modulators including a naturally occurring hydroxysterol agonist of the liver X receptors (LXRs), members of the nuclear receptor transcription factor family. Endogenous and synthetic LXR agonists tested in diverse cell models blocked α-smooth muscle actin expression, myofibroblast differentiation and function. Agonist-dependent LXR activity or LXR overexpression in the absence of ligand counteracted TGF-β-mediated myofibroblast terminal differentiation and collagen contraction. The protective effect of LXR agonists against TGF-β-induced pro-fibrotic activity raises the possibility that anti-lipidogenic therapy may be relevant in fibrotic disorders and advanced cancer

Factors involved in nurses' responses to burnout: a grounded theory study

BACKGROUND: Intense and long-standing problems in burn centers in Tehran have led nurses to burnout. This phenomenon has provoked serious responses and has put the nurses, patients and the organization under pressure. The challenge for managers and nurse executives is to understand the factors which would reduce or increase the nurses' responses to burnout and develop delivery systems that promote positive adaptation and facilitate quality care. This study, as a part of more extensive research, aims to explore and describe the nurses' perceptions of the factors affecting their responses to burnout. METHODS: Grounded theory was used as the method. Thirty- eight participants were recruited. Data were generated by unstructured interviews and 21 sessions of participant observations. Constant comparison was used for data analysis. RESULTS: Nurses' and patients' personal characteristics and social support influenced nurses' responses to burnout. Personal characteristics of the nurses and patients, especially when interacting, had a more powerful effect. They altered emotional, attitudinal, behavioral and organizational responses to burnout and determined the kind of caring behavior. Social support had a palliative effect and altered emotional responses and some aspects of attitudinal responses. CONCLUSIONS: The powerful effect of positive personal characteristics and its sensitivity to long standing and intense organizational pressures suggests approaches to executing stress reduction programs and refreshing the nurses' morale by giving more importance to ethical aspects of caring. Moreover, regarding palliative effect of social support and its importance for the nurses' wellbeing, nurse executives are responsible for promoting a work environment that supports nurses and motivates them

Human Cardiac-Derived Adherent Proliferating Cells Reduce Murine Acute Coxsackievirus B3-Induced Myocarditis

BACKGROUND: Under conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. We recently isolated and identified novel cardiac-derived cells from human cardiac biopsies: cardiac-derived adherent proliferating cells (CAPs). They have similarities with mesenchymal stromal cells, which are known for their anti-apoptotic and immunomodulatory properties. We explored whether CAPs application could be a novel strategy to improve acute Coxsackievirus B3 (CVB3)-induced myocarditis. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the safety of our approach, we first analyzed the expression of the coxsackie- and adenovirus receptor (CAR) and the co-receptor CD55 on CAPs, which are both required for effective CVB3 infectivity. We could demonstrate that CAPs only minimally express both receptors, which translates to minimal CVB3 copy numbers, and without viral particle release after CVB3 infection. Co-culture of CAPs with CVB3-infected HL-1 cardiomyocytes resulted in a reduction of CVB3-induced HL-1 apoptosis and viral progeny release. In addition, CAPs reduced CD4 and CD8 T cell proliferation. All CAPs-mediated protective effects were nitric oxide- and interleukin-10-dependent and required interferon-γ. In an acute murine model of CVB3-induced myocarditis, application of CAPs led to a decrease of cardiac apoptosis, cardiac CVB3 viral load and improved left ventricular contractility parameters. This was associated with a decline in cardiac mononuclear cell activity, an increase in T regulatory cells and T cell apoptosis, and an increase in left ventricular interleukin-10 and interferon-γ mRNA expression. CONCLUSIONS: We conclude that CAPs are a unique type of cardiac-derived cells and promising tools to improve acute CVB3-induced myocarditis

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Do decision support systems influence variation in prescription?

<p>Abstract</p> <p>Background</p> <p>Translating scientific evidence into daily practice is problematic. All kinds of intervention strategies, using educational and/or directive strategies, aimed at modifying behavior, have evolved, but have been found only partially successful. In this article the focus is on (computerized) decision support systems (DSSs). DSSs intervene in physicians' daily routine, as opposed to interventions that aim at influencing knowledge in order to change behavior. We examined whether general practitioners (GPs) are prescribing in accordance with the advice given by the DSS and whether there is less variation in prescription when the DSS is used.</p> <p>Methods</p> <p>Data were used from the Second Dutch National Survey of General Practice (DNSGP2), collected in 2001. A total of 82 diagnoses, 749811 contacts, 133 physicians, and 85 practices was included in the analyses. GPs using the DSS daily were compared to GPs who do not use the DSS. Multilevel analyses were used to analyse the data. Two outcome measures were chosen: whether prescription was in accordance with the advice of the DSS or not, and a measure of concentration, the Herfindahl-Hirschman Index (HHI).</p> <p>Results</p> <p>GPs who use the DSS daily prescribe more according to the advice given in the DSS than GPs who do not use the DSS. Contradictory to our expectation there was no significant difference between the HHIs for both groups: variation in prescription was comparable.</p> <p>Conclusion</p> <p>We studied the use of a DSS for drug prescribing in general practice in the Netherlands. The DSS is based on guidelines developed by the Dutch College of General Practitioners and implemented in the Electronic Medical Systems of the GPs. GPs using the DSS more often prescribe in accordance with the advice given in the DSS compared to GPs not using the DSS. This finding, however, did not mean that variation is lower; variation is the same for GPs using and for GPs not using a DSS. Implications of the study are that DSSs can be used to implement guidelines, but that it should not be expected that variation is limited.</p

Pharmaceutical cost control in primary care: opinion and contributions by healthcare professionals

<p>Abstract</p> <p>Background</p> <p>Strategies adopted by health administrations and directed towards drug cost control in primary care (PC) can, according to earlier studies, generate tension between health administrators and healthcare professionals. This study collects and analyzes the opinions of general practitioners (GPs) regarding current cost control measures as well as their proposals for improving the effectiveness of these measures.</p> <p>Methods</p> <p>A qualitative exploratory study was carried out using 11 focus groups composed of GPs from the Spanish regions of Aragon, Catalonia and the Balearic Islands. A semi-structured guide was applied in obtaining the GPs' opinions. The transcripts of the dialogues were analyzed by two investigators who independently considered categorical and thematic content. The results were supervised by other members of the team, with overall responsibility assigned to the team leader.</p> <p>Results</p> <p>GPs are conscious of their public responsibility with respect to pharmaceutical cost, but highlight the need to spread responsibility for cost control among the different actors of the health system. They insist on implementing measures to improve the quality of prescriptions, avoiding mere quantitative evaluations of prescription costs. They also suggest moving towards the self-management of the pharmaceutical budget by each health centre itself, as a means to design personalized incentives to improve their outcomes. These proposals need to be considered by the health administration in order to pre-empt the feelings of injustice, impotence, frustration and lack of motivation that currently exist among GPs as a result of the implemented measures.</p> <p>Conclusion</p> <p>Future investigations should be oriented toward strategies that involve GPs in the planning and management of drug cost control mechanisms. The proposals in this study may be considered by the health administration as a means to move toward the rational use of drugs while avoiding concerns about injustice and feelings of impotence on the part of the GPs, which can lead to lack of interest in and disaffection with the current measures.</p

Developmental differences in children’s interpersonal emotion regulation

Previous research on interpersonal emotion regulation (ER) in childhood has been rather unsystematic, focusing mainly on children’s prosocial behaviour, and has been conducted in the absence of an integrative emotion theoretical framework. The present research relied on the interpersonal affect classification proposed by Niven, Totterdell, and Holman (2009) to investigate children’s use of different interpersonal ER strategies. The study drew on two samples: 180 parents of children aged between 3 and 8 years reported about a situation where their child was able to change what another person was feeling in order to make them feel better. In addition, 126 children between 3- and 8-years old answered two questions about how they could improve others’ mood. Results from both samples showed age differences in children’s use of interpersonal ER strategies. As expected, ‘affective engagement’ (i.e., focusing on the person or the problem) and ‘cognitive engagement’ (i.e., appraising the situation from a different perspective) were mainly used by 7-8 years-old, whereas ‘attention’ (i.e., distracting and valuing) was most used by 3-4 and 5-6 years-old. ‘Humor’ (i.e., laughing with the target) remained stable across the different age groups. The present research provides more information about the developmental patterns for each specific interpersonal emotion regulation strategy

Boost Camp’, a universal school-based transdiagnostic prevention program targeting adolescent emotion regulation; evaluating the effectiveness by a clustered RCT : a protocol paper

Abstract Background The transition from childhood into adolescence can be considered as a critical developmental period. Moreover, adolescence is associated with a decreased use of adaptive emotion regulation strategies and an increased use of maladaptive emotion regulation strategies increasing the risk of emotional problems. Targeting emotion regulation is therefore seen as an innovative prevention approach. The present study aims to evaluate the effectiveness of Boost camp, an innovative school-based prevention program targeting ER, on adolescents’ emotion regulation skills and emotional wellbeing. Also secondary outcomes and possible moderators will be included. Methods The aim is to reach 300 adolescents (16 class groups, 6 schools) in their first year of high school. A clustered Randomized Controlled Trial (RCT) with two conditions, intervention (n = 150) and control (n = 150), will be set up. Adolescents in the intervention condition will receive 14 lessons over the course of 2 days, followed by Booster sessions, and will be compared with adolescents in a non-intervention control group. The outcomes will be measured by self-report questionnaires at baseline, immediately after Boost camp, and at three and 6 months follow-up. Discussion Data-collection is planned to be completed in May 2018. Data-analyses will be finished the end of 2018. The presented paper describes the Boost camp program and the clustered RCT design to evaluate its effectiveness. It is expected that Boost camp will have beneficial effects. If found effective, Boost camp will have the potential to increase adolescent’s ER and well-being, and reduce the risk to become adults in need. The trials is registered on the 13th of June 2017 in ISRCTN registry [ISRCTN68235634]