Mind Your Steps

Abstract This thesis assesses the effectiveness of structured multi-professional medical ethical decision-making in diminishing problems experienced around medical ethical decisionmaking in the Erasmus MC NICU. Besides, it gives an overview of the patients discussed from 2009 to 2012, and their outcomes at two year follow-up. Patient care, especially in acute settings, is closely linked to emotional burden in nurses and physicians. The impacts of chronic and acute work-related stressors on moral distress, post-traumatic stress symptoms, anxiety, and depression were evaluated. The introduction illuminates the context and the pre-existing problems in the Erasmus MC NICU with respect to medical ethical decision-making. Besides, consequences of working in a highly demanding context for professionals’ well-being are presented against a practical and a theoretical background

Implementing structured, multiprofessional medical ethical decision-making in a neonatal intensive care unit

Background In neonatal intensive care, a child’s death is often preceded by a medical decision. Nurses, social workers and pastors, however, are often excluded from ethical case deliberation. If multiprofessional ethical case deliberations do take place, participants may not always know how to perform to the fullest. Setting A level-IIID neonatal intensive care unit of a paediatric teaching hospital in the Netherlands. Methods Structured multiprofessional medical ethical decision-making (MEDM) was implemented to help overcome problems experienced. Important features were: all professionals who are directly involved with the patient contribute to MEDM; a five-step procedure is used: exploration, agreement on the ethical dilemma/ investigation of solutions, analysis of solutions, decision-making, planning actions; meetings are chaired by an impartial ethicist. A 15-item questionnaire to survey staff perceptions on this intervention just before and 8 months after implementation was developed. Results Before and after response rates were 91/105 (87%) and 85/113 (75%). Factor analysis on the questionnaire suggested a four-factor structure: participants’ role; structure of MEDM; content of ethical deliberation; and documentation of decisions/ conclusions. Effect sizes were 1.67 (p<0.001), 0.69 (p<0.001) and 0.40 (p<0.01) for the first three factors respectively, but only 0.07 (p¼0.65) for the fourth factor. Nurses’ perceptions of improvement did not significantly exceed those of physicians. Conclusion Professionals involved in ethical case deliberation perceived that the process of decisionmaking had improved; they we

MiR-337-3p Promotes Adipocyte Browning by Inhibiting TWIST1

The prevalence of metabolic syndrome (MetS) and obesity is an alarming health issue worldwide. Obesity is characterized by an excessive accumulation of white adipose tissue (WAT), and it is associated with diminished brown adipose tissue (BAT) activity. Twist1 acts as a negative feedback regulator of BAT metabolism. Therefore, targeting Twist1 could become a strategy for obesity and metabolic disease. Here, we have identified miR-337-3p as an upstream regulator of Twist1. Increased miR-337-3p expression paralleled decreased expression of TWIST1 in BAT compared to WAT. Overexpression of miR-337-3p in brown pre-adipocytes provoked a reduction in Twist1 expression that was accompanied by increased expression of brown/mitochondrial markers. Luciferase assays confirmed an interaction between the miR-337 seed sequence and Twist1 3 0UTR. The inverse relationship between the expression of TWIST1 and miR-337 was finally validated in adipose tissue samples from non-MetS and MetS subjects that demonstrated a dysregulation of the miR-337-Twist1 molecular axis in MetS. The present study demonstrates that adipocyte miR-337-3p suppresses Twist1 repression and enhances the browning of adipocytes

Proton Pump Inhibitor Use, Fatigue, and Health-Related Quality of Life in Kidney Transplant Recipients:Results From the TransplantLines Biobank and Cohort Study

Rationale &amp; Objective: Prior studies report that the use of proton pump inhibitors (PPIs) can adversely affect gut microbiota and gastrointestinal uptake of micronutrients, in particular iron and magnesium, and are used frequently by kidney transplant recipients. Altered gut microbiota, iron deficiency, and magnesium deficiency have been implicated in the pathogenesis of chronic fatigue. Therefore, we hypothesized that PPI use may be an important and underappreciated cause of fatigue and reduced health-related quality of life (HRQoL) in this population. Study Design: Cross-sectional study. Setting &amp; Participants: Kidney transplant recipients (≥1 year after transplantation) enrolled in the TransplantLines Biobank and Cohort Study. Exposure: PPI use, PPI type, PPI dosage, and duration of PPI use. Outcome: Fatigue and HRQoL, assessed using the validated Checklist Individual Strength 20 Revised questionnaire and Short Form-36 questionnaire. Analytical Approach: Logistic and linear regression. Results: We included 937 kidney transplant recipients (mean age 56 ± 13 years, 39% female) at a median of 3 (1-10) years after transplantation. PPI use was associated with fatigue severity (regression coefficient 4.02, 95% CI, 2.18 to 5.85, P &lt; 0.001), a higher risk of severe fatigue (OR 2.05, 95% CI, 1.48 to 2.84, P &lt; 0.001), lower physical HRQoL (regression coefficient −8.54, 95% CI, −11.54 to −5.54, P &lt; 0.001), and lower mental HRQoL (regression coefficient −4.66, 95% CI, −7.15 to −2.17, P &lt; 0.001). These associations were independent of potential confounders including age, time since transplantation, history of upper gastrointestinal disease, antiplatelet therapy, and the total number of medications. They were present among all individually assessed PPI types and were dose dependent. Duration of PPI exposure was only associated with fatigue severity. Limitations: Residual confounding and inability to assess causal relationships. Conclusions: PPI use is independently associated with fatigue and lower HRQoL among kidney transplant recipients. PPI use might be an easily accessible target for alleviating fatigue and improving HRQoL among kidney transplant recipients. Further studies examining the effect of PPI exposure in this population are warranted. Plain-Language Summary: In this observational study, we investigated the association of proton pump inhibitors with fatigue and health-related quality of life among kidney transplant recipients. Our data showed that proton pump inhibitors were independently associated with fatigue severity, severe fatigue, and lower physical and mental health-related quality of life. These associations were present among all individually assessed proton pump inhibitor types and were dose dependent. While we await future studies on this topic, proton pump inhibitor use might be an easily accessible target for alleviating fatigue and improving health-related quality of life among kidney transplant recipients.</p

Immunological responses to social stress: Dependence on social environment and coping abilities

Social interactions as a consequence of the social position represent stressful conditions for the individual. Manipulation of social conditions or forming long-term social hierarchies by colony aggregation allow to investigate the regulation of immune defense mechanisms under seminatural circumstances. The present paper describes the effects of dyadic social interaction in male rats with or without direct aggressive interactions on some indices of humoral and cellular immunity. In addition, for comparative and reference purposes, in one experiment the conventional stressor of inescapable footshock was used as well. Primary humoral immune response to sheep red blood cell antigen is suppressed by repeated experience of both defeat and inescapable footshock. At individual level the social stressor is as effective as the conventional stressor of inescapable footshock, less individual rats show suppression following the social than after the conventional stress. The social stressors, i.e. being exposed to a resident or intruder of the territory, facilitate lymphocyte proliferation in the spleen by the mitogen ConA and PHA independently of the presence or absence of direct aggressive interaction. Finally, the different social stressors have some impact on the lymphocyte subpopulation in the spleen. Social stimulation without aggressive interactions increases the relative number of T(helper) cells, whereas defeat leads to an increase in the T(suppressor/cytotoxic) subpopulation. The data suggest multiple and differential effects of social stress on immune system functioning in the rat. Individual characteristics of the coping with stress, the social environment, and the immune indices under investigation determine the magnitude and direction of the changes in immune functioning

Pro-osteogenic trophic effects by PKA activation in human mesenchymal stromal cells

Human mesenchymal stromal cells (hMSCs) are able to differentiate into a wide variety of cell types, which makes them an interesting source for tissue engineering applications. On the other hand, these cells also secrete a broad panel of growth factors and cytokines that can exert trophic effects on surrounding tissues. In bone tissue engineering applications, the general assumption is that direct differentiation of hMSCs into osteoblasts accounts for newly observed bone formation in vivo. However, the secretion of bone-specific growth factors, but also pro-angiogenic factors, could also contribute to this process. We recently demonstrated that secretion of bone specific growth factors can be enhanced by treatment of hMSCs with the small molecule db-cAMP (cAMP) and here we investigate the biological activity of these secreted factors. We demonstrate that conditioned medium contains a variety of secreted growth factors, with differences between medium from basic-treated and cAMP-treated hMSCs. We show that conditioned medium from cAMP-treated hMSCs increases proliferation of various cell types and also induces osteogenic differentiation, whereas it has differential effects on migration. Microarray analysis on hMSCs exposed to conditioned medium confirmed upregulation of pathways involved in proliferation as well as osteogenic differentiation. Our data suggests that trophic factors secreted by hMSCs can be tuned for specific applications and that a good balance between differentiation on the one hand and secretion of bone trophic factors on the other, could potentially enhance bone formation for bone tissue engineering applications. (C) 2011 Elsevier Ltd. All rights reserved

Work-related critical incidents in hospital-based health care providers and the risk of post-traumatic stress symptoms, anxiety, and depression: A meta-analysis

This meta-analysis reviewed existing data on the impact of work-related critical incidents in hospital-based health care professionals. Work-related critical incidents may induce post-traumatic stress symptoms or even post-traumatic stress disorder (PTSD), anxiety, and depression and may negatively affect health care practitioners' behaviors toward patients. Nurses and doctors often cope by working part time or switching jobs. Hospital administrators and health care practitioners themselves may underestimate the effects of work-related critical incidents. Relevant online databases were searched for original research published from inception to 2009 and manual searches of the Journal of Traumatic Stress, reference lists, and the European Traumatic Stress Research Database were conducted. Two researchers independently decided on inclusion and study quality. Effect sizes were estimated using standardized mean differences with 95% confidence intervals. Consistency was evaluated, using the I2-statistic. Meta-analysis was performed using the random effects model. Eleven studies, which included 3866 participants, evaluated the relationship between work-related critical incidents and post-traumatic stress symptoms. Six of these studies, which included 1695 participants, also reported on the relationship between work-related critical incidents and symptoms of anxiety and depression. Heterogeneity among studies was high and could not be accounted for by study quality, character of the incident, or timing of data collection. Pooled effect sizes for the impact of work-related critical incidents on post-traumatic stress symptoms, anxiety, and depression were small to medium. Remarkably, the effect was more pronounced in the longer than in the shorter term. In conclusion, this meta-analysis supports the hypothesis that work-related critical incidents are positively related to post-traumatic stress symptoms, anxiety, and depression in hospital-based health care professionals. Health care workers and their supervisors should be aware of the harmful effects of critical incidents and take preventive measures.Post-traumatic Stress disorders Work-stress Nurses Physicians Health care professionals