Objectifying psychomental stress in the workplace--an example.

BACKGROUND: Psychomental stress is a major source of illness and reduced productivity. Data objectifying physiological stress responses are scarce. We studied salivary cortisol levels in a highly stressful environment, the pediatric critical care unit. The aim was to identify targets for organizational changes, to implement these changes and to assess their impact on cortisol levels. DESIGN: Repeated measurements observational cohort study (before and after intervention). SUBJECTS: 84 nurses working in two independent teams (A and B) in a 19 bed pediatric intensive care unit. Between study periods team A experienced a major exchange of experienced staff while the turnover rate in team B remained average. MEASUREMENTS AND INTERVENTIONS: Salivary cortisol samples were collected every 2 h and after stressful events. Nurses in study period I showed elevated cortisol levels at the beginning of the late shift, interpreted as an anticipatory stress reaction. To ease conditions during the early part of the late shift (conflicting tasks, noise and crowding), we postponed the afternoon ward round, limited non-urgent procedures and introduced a change in visiting hours. The early shift, which was not affected by the intervention, served as control. MAIN RESULTS: Both crude and adjusted analysis revealed a decrease of cortisol levels at the beginning of the late shift in team B (p = 0.0009), but not in team A (p = 0.464). The control situation showed no difference between teams and study periods. INTERPRETATION: We demonstrated reduced cortisol secretions in one team following organizational changes, which was probably overridden by the disruption of social coherence in the second team.

Prenatal diagnosis of facial clefts : evaluation of a specialised counseling

Résumé: Questions étudiées / principes: Le diagnostic prénatal des fentes faciales et palatines a soulevé maintes questions concernant la meilleure manière d'informer les parents et d'offrir une aide appropriée durant les semaines de grossesse restant, afin de faire de la naissance une expérience positive. Le conseil prénatal diffère selon la personne qui en est responsable et ses connaissances concernant les aspects pratiques des soins ainsi que l'impact de cette malformation sur la qualité de vie de l'enfant. Le but de cette étude est d'évaluer nos techniques actuelles et de les modifier de façon appropriée. Méthodes: 29 couples ayant bénéficié d'un diagnostic prénatal ont été priés de répondre rétrospectivement à un questionnaire. L'histoire obstétrique personnelle ainsi que l'histoire familiale, le déroulement des évènements, la qualité de l'information fournie et leurs impressions à la naissance ont été considérées. Résultats: Les parents utilisent de multiples sources d'information: l'obstétricien, le conseil du chirurgien pédiatrique au sein de I « équipe fente », les groupes de soutien de parents et Internet. 93% des parents se sont sentis bien préparés à la naissance de leur enfant, autant psychologiquement que concernant les aspects pratiques des soins. 54% ont été soulagés de voir leur enfant moins affecté qu'ils ne l'imaginaient. Finalement, 96% considèrent que le diagnostic prénatal est un bénéfice. Conclusion: Une information de base devrait être apportée rapidement après l'ultrason confirmant le diagnostic, suivie de discussions techniques progressivement plus détaillées durant le temps de grossesse restant. Summary: Questions under study / principles: Prenatal diagnosis of cleft lip and palate has raised many questions concerning the best way to inform the parents and offer appropriate support during the remaining pregnancy to help prepare a positive birth experience. Prenatal counseling differs according to whose is responsible and that person's knowledge of practical aspects of care and the impact of the malformation on the child's quality of life. The aim of the study was to evaluate our current techniques and modify them when appropriate. Methods: 29 couples having experienced prenatal diagnosis were asked to respond retrospectively to a questionnaire. Personal obstetric and family history, timing and quality of information provided and their impressions at birth were considered. Results: The parents used several sources of information: the obstetrician, the counsel by the cleft team surgeon, the parents support groups and Internet. 93% of the parents felt well prepared for the birth of their child psychologically and concerning practical aspects of care. 54% felt relieved that their child was less affected than imagined. 96% considered prenatal diagnosis a benefit. Conclusion: Basic information should be provided soon after ultrasound confirmation, followed by progressively more detailed technical discussions over the remaining pregnancy.

Nitrosative stress and corneal transplant endothelial cell death during acute graft rejection.

BACKGROUND: Nitrosative stress takes place in endothelial cells (EC) during corneal acute graft rejection. The purpose of this study was to evaluate the potential role of peroxynitrite on corneal EC death. METHODS: The effect of peroxynitrite was evaluated in vivo. Fifty, 250, and 500 microM in 1.5 microL of the natural or denatured peroxynitrite in 50 microM NaOH, 50 microM NaOH alone, or balanced salt solution were injected into the anterior chamber of rat eyes (n=3/group). Corneal toxic signs after injection were assessed by slit-lamp, in vivo confocal imaging, pachymetry, and EC count. The effect of peroxynitrite was also evaluated on nitrotyrosine and leucocyte elastase inhibitor/LDNase II immunohistochemistry. Human corneas were incubated with peroxynitrite and the effect on EC viability was evaluated. A specific inducible nitric oxide synthase inhibitor (iNOS) was administered systemically in rats undergoing allogeneic corneal graft rejection and the effect on EC was evaluated by EC count. RESULTS: Rat eyes receiving as little as 50 microM peroxynitrite showed a specific dose-dependent toxicity on EC. We observed an intense nitrotyrosine staining of human and rat EC exposed to peroxynitrite associated with leucocyte elastase inhibitor nuclear translocation, a noncaspase dependent apoptosis reaction. Specific inhibition of iNOS generation prevented EC death and enhanced EC survival of the grafted corneas. However, inhibition of iNOS did not have a significant influence on the incidence of graft rejection. CONCLUSION: Nitrosative stress during acute corneal graft rejection in rat eyes induces a noncaspase dependent apoptotic death in EC. Inhibition of nitric oxide production during the corneal graft rejection has protective effects on the corneal EC survival.

Prenatal diagnosis of congenital lung malformations.

Prenatal diagnosis of congenital lung anomalies has increased in recent years as imaging methods have benefitted from technical improvements. The purpose of this pictorial essay is to illustrate typical imaging findings of a wide spectrum of congenital lung anomalies on prenatal US and MRI. Moreover, we propose an algorithm based on imaging findings to facilitate the differential diagnosis, and suggest a follow-up algorithm during pregnancy and in the immediate postnatal period.

Cx36 Is a Target of Beta2/NeuroD1, Which Associates with Prenatal Differentiation of Insulin-producing β Cells.

The insulin-producing β cells of pancreatic islets are coupled by connexin36 (Cx36) channels. To investigate what controls the expression of this connexin, we have investigated its pattern during mouse pancreas development, and the influence of three transcription factors that are critical for β-cell development and differentiation. We show that (1) the Cx36 gene (Gjd2) is activated early in pancreas development and is markedly induced at the time of the surge of the transcription factors that determine β-cell differentiation; (2) the cognate protein is detected about a week later and is selectively expressed by β cells throughout the prenatal development of mouse pancreas; (3) a 2-kbp fragment of the Gjd2 promoter, which contains three E boxes for the binding of the bHLH factor Beta2/NeuroD1, ensures the expression of Cx36 by β cells; and (4) Beta2/NeuroD1 binds to these E boxes and, in the presence of the E47 ubiquitous cofactor, transactivates the Gjd2 promoter. The data identify Cx36 as a novel early marker of β cells and as a target of Beta2/NeuroD1, which is essential for β-cell development and differentiation.

PPARβ/δ prevents endoplasmic reticulum stress-associated inflammation and insulin resistance in skeletal muscle cells through an AMPK-dependent mechanism.

AIM/HYPOTHESIS: Endoplasmic reticulum (ER) stress, which is involved in the link between inflammation and insulin resistance, contributes to the development of type 2 diabetes mellitus. In this study, we assessed whether peroxisome proliferator-activated receptor (PPAR)β/δ prevented ER stress-associated inflammation and insulin resistance in skeletal muscle cells. METHODS: Studies were conducted in mouse C2C12 myotubes, in the human myogenic cell line LHCN-M2 and in skeletal muscle from wild-type and PPARβ/δ-deficient mice and mice exposed to a high-fat diet. RESULTS: The PPARβ/δ agonist GW501516 prevented lipid-induced ER stress in mouse and human myotubes and in skeletal muscle of mice fed a high-fat diet. PPARβ/δ activation also prevented thapsigargin- and tunicamycin-induced ER stress in human and murine skeletal muscle cells. In agreement with this, PPARβ/δ activation prevented ER stress-associated inflammation and insulin resistance, and glucose-intolerant PPARβ/δ-deficient mice showed increased phosphorylated levels of inositol-requiring 1 transmembrane kinase/endonuclease-1α in skeletal muscle. Our findings demonstrate that PPARβ/δ activation prevents ER stress through the activation of AMP-activated protein kinase (AMPK), and the subsequent inhibition of extracellular-signal-regulated kinase (ERK)1/2 due to the inhibitory crosstalk between AMPK and ERK1/2, since overexpression of a dominant negative AMPK construct (K45R) reversed the effects attained by PPARβ/δ activation. CONCLUSIONS/INTERPRETATION: Overall, these findings indicate that PPARβ/δ prevents ER stress, inflammation and insulin resistance in skeletal muscle cells by activating AMPK.

Effects of corticosterone pellets on baseline and stress-induced corticosterone and corticosteroid-binding-globulin.

Exogenous administration of glucocorticoids is a widely used and efficient tool to investigate the effects of elevated concentrations of these hormones in field studies. Because the effects of corticosterone are dose and duration-dependent, the exact course of plasma corticosterone levels after exogenous administration needs to be known. We tested the performance of self-degradable corticosterone pellets (implanted under the skin) in elevating plasma corticosterone levels. We monitored baseline (sampled within 3min after capture) total corticosterone levels and investigated potential interactions with corticosteroid-binding-globulin (CBG) capacity and the endogenous corticosterone response to handling in Eurasian kestrel Falco tinnunculus and barn owl Tyto alba nestlings. Corticosterone pellets designed for a 7-day-release in rodents elevated circulating baseline total corticosterone during only 2-3 days compared to placebo-nestlings. Highest levels occurred 1-2days after implantation and levels decreased strongly thereafter. CBG capacity was also increased, resulting in a smaller, but still significant, increase in baseline free corticosterone levels. The release of endogenous corticosterone as a response to handling was strong in placebo-nestlings, but absent 2 and 8 days after corticosterone pellet implantation. This indicates a potential shut-down of the hypothalamo-pituitary-adrenal axis after the 2-3 days of elevated baseline corticosterone levels. 20 days after pellet implantation, the endogenous corticosterone response to handling of nestlings implanted with corticosterone pellets attained similar levels as in placebo-nestlings. Self-degradable pellets proved to be an efficient tool to artificially elevate circulating baseline corticosterone especially in field studies, requiring only one intervention. The resulting peak-like elevation of circulating corticosterone, the concomitant elevation of CBG capacity, and the absence of an endogenous corticosterone response to an acute stressor have to be taken into account.

Pelvic organ prolapse surgery with and without tension-free vaginal tape in women with occult or asymptomatic urodynamic stress incontinence: a randomised controlled trial.

INTRODUCTION: We set out to determine if insertion of a retropubic tension-free vaginal tape (TVT) sling at the time of pelvic organ prolapse surgery improves continence outcomes in women with pre-operative occult stress incontinence (OSI) or asymptomatic urodynamic stress incontinence (USI). METHODS: We conducted a randomised controlled study of prolapse surgery with or without a TVT midurethral sling. The pre- and post-operative assessment at 6 months included history, physical examination and urodynamic testing. Quality of life (QOL) and treatment success was assessed with the UDI-6 SF, IIQ-7 SF and a numerical success score. The primary outcome was symptomatic stress urinary incontinence (SUI) requiring continence surgery (TVT) at 6 months. Long-term follow-up continued to a minimum of 24 months. Secondary outcomes were quality of life parameters. RESULTS: Eighty women received prolapse surgery alone (n = 43) or prolapse surgery with concurrent TVT (n = 37). Six months following prolapse surgery 3 out of 43 (7 %) patients in the no TVT group requested sling surgery compared with 0 out of 37 (0 %) in the TVT group (ARR 7 % [95 %CI: 3 to 19 %], p = 0.11). After 24 months there was one further participant in the no TVT group who received a TVT for treatment of SUI compared with none in the TVT group (4 out of 43, 9.3 % versus 0 out of 37; ARR 9.3 % [95 %CI: -1 to 22 %], p = 0.06). Both groups showed improvement in QOL difference scores for within-group analysis, without difference between groups. CONCLUSION: These results support a policy that routine insertion of a sling in women with OSI at the time of prolapse repair is questionable and should be subject to shared decision-making between clinician and patient.

Stress Perception in Public Organizations: Expanding the Job Demands - Job Resources Model by Including Public Service Motivation

Although stress has been a longstanding issue in organizations and management studies, it has never been studied in relation to Public Service Motivation. This article therefore aims to integrate PSM into the job demands-job resources model of stress in order to determine whether PSM might contribute to stress in public organizations. Drawing upon original data from a questionnaire in a Swiss municipality, this study unsurprisingly shows that "red tape" is an antecedent of stress perception, whereas satisfaction with organizational support, positive feedback, and recognition significantly decrease the level of perceived stress. Astonishingly, the empirical results show that PSM is positively and significantly related to stress perception. By increasing individuals' expectations towards their jobs, PSM might thus contribute to increased pressure on public agents. Ultimately, this article investigates the "dark side" of PSM, which has been neglected by the literature thus far.

Oxidative stress and inflammation response after nanoparticle exposure : differences between human lung cell monocultures and an advanced three-dimensional model of the human epithelial airways

Combustion-derived and manufactured nanoparticles (NPs) are known to provoke oxidative stress and inflammatory responses in human lung cells; therefore, they play an important role during the development of adverse health effects. As the lungs are composed of more than 40 different cell types, it is of particular interest to perform toxicological studies with co-cultures systems, rather than with monocultures of only one cell type, to gain a better understanding of complex cellular reactions upon exposure to toxic substances. Monocultures of A549 human epithelial lung cells, human monocyte-derived macrophages and monocyte-derived dendritic cells (MDDCs) as well as triple cell co-cultures consisting of all three cell types were exposed to combustion-derived NPs (diesel exhaust particles) and to manufactured NPs (titanium dioxide and single-walled carbon nanotubes). The penetration of particles into cells was analysed by transmission electron microscopy. The amount of intracellular reactive oxygen species (ROS), the total antioxidant capacity (TAC) and the production of tumour necrosis factor (TNF)-a and interleukin (IL)-8 were quantified. The results of the monocultures were summed with an adjustment for the number of each single cell type in the triple cell co-culture. All three particle types were found in all cell and culture types. The production of ROS was induced by all particle types in all cell cultures except in monocultures of MDDCs. The TAC and the (pro-)inflammatory reactions were not statistically significantly increased by particle exposure in any of the cell cultures. Interestingly, in the triple cell co-cultures, the TAC and IL-8 concentrations were lower and the TNF-a concentrations were higher than the expected values calculated from the monocultures. The interplay of different lung cell types seems to substantially modulate the oxidative stress and the inflammatory responses after NP exposure. [Authors]

Selective and powerful stress gene expression in Arabidopsis in response to malondialdehyde.

The provenance, half-life and biological activity of malondialdehyde (MDA) were investigated in Arabidopsis thaliana. We provide genetic confirmation of the hypothesis that MDA originates from fatty acids containing more than two methylene-linked double bonds, showing that tri-unsaturated fatty acids are the in vivo source of up to 75% of MDA. The abundance of the combined pool of free and reversibly bound MDA did not change dramatically in stress, although a significant increase in the free MDA pool under oxidative conditions was observed. The half-life of infiltrated MDA indicated rapid metabolic turnover/sequestration. Exposure of plants to low levels of MDA using a recently developed protocol powerfully upregulated many genes on a cDNA microarray with a bias towards those implicated in abiotic/environmental stress (e.g. ROF1 and XERO2). Remarkably, and in contrast to the activities of other reactive electrophile species (i.e. small vinyl ketones), none of the pathogenesis-related (PR) genes tested responded to MDA. The use of structural mimics of MDA isomers suggested that the propensity of the molecule to act as a cross-linking/modifying reagent might contribute to the activation of gene expression. Changes in the concentration/localisation of unbound MDA in vivo could strongly affect stress-related transcription.

The AP-1 transcription factor c-Jun prevents stress-imposed maladaptive remodeling of the heart.

Systemic hypertension increases cardiac workload and subsequently induces signaling networks in heart that underlie myocyte growth (hypertrophic response) through expansion of sarcomeres with the aim to increase contractility. However, conditions of increased workload can induce both adaptive and maladaptive growth of heart muscle. Previous studies implicate two members of the AP-1 transcription factor family, junD and fra-1, in regulation of heart growth during hypertrophic response. In this study, we investigate the function of the AP-1 transcription factors, c-jun and c-fos, in heart growth. Using pressure overload-induced cardiac hypertrophy in mice and targeted deletion of Jun or Fos in cardiomyocytes, we show that c-jun is required for adaptive cardiac hypertrophy, while c-fos is dispensable in this context. c-jun promotes expression of sarcomere proteins and suppresses expression of extracellular matrix proteins. Capacity of cardiac muscle to contract depends on organization of principal thick and thin filaments, myosin and actin, within the sarcomere. In line with decreased expression of sarcomere-associated proteins, Jun-deficient cardiomyocytes present disarrangement of filaments in sarcomeres and actin cytoskeleton disorganization. Moreover, Jun-deficient hearts subjected to pressure overload display pronounced fibrosis and increased myocyte apoptosis finally resulting in dilated cardiomyopathy. In conclusion, c-jun but not c-fos is required to induce a transcriptional program aimed at adapting heart growth upon increased workload.

Abus sexuel, psychopathologie et réponses psycho-endocriniennes au stress

Résumé : Des événements traumatiques précoces peuvent favoriser le développement ultérieur de psychopathologies telles que les troubles anxieux ou dépressifs. Dans quelle mesure ces événements influencent-ils la réaction d'un sujet à un stress aigu ? Objectif : comparer la prévalence de troubles psychiatriques et déterminer la différence de réaction au stress à l'âge adulte de femmes ayant ou non subi un traumatisme de type abus sexuel dans leur enfance. Participants : 46 femmes âgées de 22 à 48 ans recrutées entre juin 2004 et juillet 2006 réparties en 2 groupes (groupe contrôle de 16 sujets, groupe traumatisé de 30 sujets). L'étude se déroule dans l'Unité de recherche du SUPEA, rue du Bugnon 25A, 1005 Lausanne. Mesures : hormone adrenocorticotropiqué (ACTI-I), cortisol plasmatique et salivaire, fréquence cardiaque au cours du TSST (test psychosocial de stress standardisé), réponses aux questionnaires standardisés VAS (visual analog scale) et MDBF (Mehrdimensionale Befindlichkeitsfragebogen), MINI (mini international neuropsychiatric interview), ETI (early trauma inventory). Les différences de cóncentration d'ACTH et de cortisol, du rythme cardiaque, et des réponses aux questionnaires VAS et MDBF entre des groupes contrôle et abus ont été analysés (ANOVA, ANalysis Of VAriance). Lorsque les résultats montraient une grande hétérogénéité, nous .avons également appliqué les tests de Mann-Whitney et de Kruskal-Wallis: Résultats principaux : les personnes abusées dans leur enfance souffrent à l'âge adulte plus fréquemment de troubles psychiatriques selon les critères du MINI DSM-IV. Ces personnes réagissent fortement au stress, mais seules leurs réponses subjectives montrent des différences significatives par rapport à un groupe de contrôle.