Dysfonction métabolique et stress chronique: un nouveau regard sur la pandémie de "diabésité" [Metabolic dysfunction and chronic stress: a new sight at "diabesity" pandemic]

Chronic stress in Western society can activate the autonomus, neuroendocrine and inflammatory/immunlogic systems. Chronic exposure to stressors can indeed stimulate the hypothalamic-pituitary-adrenal axis and induce a disbalance between anabolic and catabolic hormones, responsible of an increased in visceral fat and of insulin resistance. These metabolic consequences can lead to pre-diabetes. Exposure to chronic stress results in allostatic load and its pathophysiologic consequences. The knowledge of this mecanisms and the cardiovascular and metabolic risk related, should influence our way of thinking about patient care. To decrease allostatic load, practitioners can rely on therapeutic relation. Therapeutic education is one of the skill that can be use to create therapeutic relation.

Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death.

BACKGROUND: Subclinical hypothyroidism has been associated with systolic and diastolic cardiac dysfunction and an elevated cholesterol level, but data on cardiovascular outcomes and death are limited. METHODS: We studied 2730 men and women, aged 70 to 79 years, with baseline thyrotropin (TSH) measurements and 4-year follow-up data to determine whether subclinical hypothyroidism was associated with congestive heart failure (CHF), coronary heart disease, stroke, peripheral arterial disease, and cardiovascular-related and total mortality. After the exclusion of participants with abnormal thyroxine levels, subclinical hypothyroidism was defined as a TSH level of 4.5 mIU/L or greater, and was further classified according to TSH levels (4.5-6.9, 7.0-9.9, and > or = 10.0 mIU/L). RESULTS: Subclinical hypothyroidism was present in 338 (12.4%) of the participants. Compared with euthyroid participants, CHF events occurred more frequently among those with a TSH level of 7.0 mIU/L or greater (35.0 vs 16.5 per 1000 person-years; P = .006), but not among those with TSH levels between 4.5 and 6.9 mIU/L. In multivariate analyses, the risk of CHF was higher among those with high TSH levels (TSH of 7.0-9.9 mIU/L: hazard ratio, 2.58 [95% confidence interval, 1.19-5.60]; and TSH of > or = 10.0 mIU/L: hazard ratio, 3.26 [95% confidence interval, 1.37-7.77]). Among the 2555 participants without CHF at baseline, the hazard ratio for incident CHF events was 2.33 (95% confidence interval, 1.10-4.96; P = .03) in those with a TSH of 7.0 mIU/L or greater. Subclinical hypothyroidism was not associated with increased risk for coronary heart disease, stroke, peripheral arterial disease, or cardiovascular-related or total mortality. CONCLUSIONS: Subclinical hypothyroidism is associated with an increased risk of CHF among older adults with a TSH level of 7.0 mIU/L or greater, but not with other cardiovascular events and mortality. Further investigation is warranted to assess whether subclinical hypothyroidism causes or worsens preexisting heart failure.

Improvement of chronic congestive heart-failure by oral captopril

Catopril, an inhibitor of angiotensin converting enzyme, was given orally during cardiac catheterisation to 6 normotensive patients with refractory congestive heart-failure. 60--180 minutes after administration of 25 mg captopril, arterial pressure fell by 25%, cardiac index rose by 38%, and left-ventricular pressure and right-atrial pressure fell by 25% and 40% respectively. Plasma-renin activity rose while plasma noradrenaline and aldosterone fell. These data suggest that, in the short term, captopril can reduce both preload and afterload, and improve cardiac function, in refractory congestive heart-failure.

Deletion of hypothetical wall teichoic acid ligases in Staphylococcus aureus activates the cell wall stress response.

The Staphylococcus aureus cell wall stress stimulon (CWSS) is activated by cell envelope-targeting antibiotics or depletion of essential cell wall biosynthesis enzymes. The functionally uncharacterized S. aureus LytR-CpsA-Psr (LCP) proteins, MsrR, SA0908 and SA2103, all belong to the CWSS. Although not essential, deletion of all three LCP proteins severely impairs cell division. We show here that VraSR-dependent CWSS expression was up to 250-fold higher in single, double and triple LCP mutants than in wild type S. aureus in the absence of external stress. The LCP triple mutant was virtually depleted of wall teichoic acids (WTA), which could be restored to different degrees by any of the single LCP proteins. Subinhibitory concentrations of tunicamycin, which inhibits the first WTA synthesis enzyme TarO (TagO), could partially complement the severe growth defect of the LCP triple mutant. Both of the latter findings support a role for S. aureus LCP proteins in late WTA synthesis, as in Bacillus subtilis where LCP proteins were recently proposed to transfer WTA from lipid carriers to the cell wall peptidoglycan. Intrinsic activation of the CWSS upon LCP deletion and the fact that LCP proteins were essential for WTA-loading of the cell wall, highlight their important role(s) in S. aureus cell envelope biogenesis.

Antecedents of Job Satisfaction, Organizational Commitment and Stress in a Public Hospital: A P-E Fit Perspective

This article tests different P-E fit dimensions in order to assess their impact on three work outcomes: job satisfaction; organizational commitment; and stress perception. Findings shows that P-E fit dimensions have differentiated effects on its dependent variables. This study contributes to several important academic discussions. The first concerns the model tested, which contains several P-E fit dimensions. The second scientific contribution is to consider P-E fit dimensions as antecedents of three job outcomes. The third contribution concerns the development and testing of a new P-E fit dimension called "person-reforms" fit.

Influence of Individual Characteristics on Work Engagement and Job Stress in a Sample of National and Foreign Workers in Switzerland

In most Western postindustrial societies today, the population is aging, businesses are faced with global integration, and important migration flows are taking place. Increasingly work organizations are hiring crossnational and multicultural workteams. In this situation it is important to understand the influence of certain individual and cultural characteristics on the process of professional integration. The present study explores the links between personality traits, demographic characteristics (age, sex, education, income, and nationality), work engagement, and job stress. The sample consisted of 618 participants, including 394 Swiss workers (200 women, 194 men) and 224 foreigners living and working in Switzerland (117 women, 107 men). Each participant completed the NEO-FFI, the UWES, and the GWSS questionnaires. Our results show an interaction between age and nationality with respect to work engagement and general job stress. The levels of work engagement and job stress appear to increase with age among national wotkers, whereas they decrease among foreign workers. In addition, work engagement was negatively associated with Neuroticism and positively with the other four personality dimensions. Finally, job stress was positively associated with Neuroticism and Conscientiousness, and negatively associated with Extraversion. However, the strength of these relationships appeared to vary according to the worker's nationality, age, sex, education, and income.

Minority quasispecies of drug-resistant HIV-1 that lead to early therapy failure in treatment-naive and -adherent patients.

BACKGROUND: Early virological failure of antiretroviral therapy associated with the selection of drug-resistant human immunodeficiency virus type 1 in treatment-naive patients is very critical, because virological failure significantly increases the risk of subsequent failures. Therefore, we evaluated the possible role of minority quasispecies of drug-resistant human immunodeficiency virus type 1, which are undetectable at baseline by population sequencing, with regard to early virological failure. METHODS: We studied 4 patients who experienced early virological failure of a first-line regimen of lamivudine, tenofovir, and either efavirenz or nevirapine and 18 control patients undergoing similar treatment without virological failure. The key mutations K65R, K103N, Y181C, M184V, and M184I in the reverse transcriptase were quantified by allele-specific real-time polymerase chain reaction performed on plasma samples before and during early virological treatment failure. RESULTS: Before treatment, none of the viruses showed any evidence of drug resistance in the standard genotype analysis. Minority quasispecies with either the M184V mutation or the M184I mutation were detected in 3 of 18 control patients. In contrast, all 4 patients whose treatment was failing had harbored drug-resistant viruses at low frequencies before treatment, with a frequency range of 0.07%-2.0%. A range of 1-4 mutations was detected in viruses from each patient. Most of the minority quasispecies were rapidly selected and represented the major virus population within weeks after the patients started antiretroviral therapy. All 4 patients showed good adherence to treatment. Nonnucleoside reverse-transcriptase inhibitor plasma concentrations were in normal ranges for all 4 patients at 2 separate assessment times. CONCLUSIONS: Minority quasispecies of drug-resistant viruses, detected at baseline, can rapidly outgrow and become the major virus population and subsequently lead to early therapy failure in treatment-naive patients who receive antiretroviral therapy regimens with a low genetic resistance barrier.

Biometal muscle to restore atrial transport function in a permanent atrial fibrillation animal model: a potential tool in the treatment of end-stage heart failure.

BACKGROUND: Half of the patients with end-stage heart failure suffer from persistent atrial fibrillation (AF). Atrial kick (AK) accounts for 10-15% of the ejection fraction. A device restoring AK should significantly improve cardiac output (CO) and possibly delay ventricular assist device (VAD) implantation. This study has been designed to assess the mechanical effects of a motorless pump on the right chambers of the heart in an animal model. METHODS: Atripump is a dome-shaped biometal actuator electrically driven by a pacemaker-like control unit. In eight sheep, the device was sutured onto the right atrium (RA). AF was simulated with rapid atrial pacing. RA ejection fraction (EF) was assessed with intracardiac ultrasound (ICUS) in baseline, AF and assisted-AF status. In two animals, the pump was left in place for 4 weeks and then explanted. Histology examination was carried out. The mean values for single measurement per animal with +/-SD were analysed. RESULTS: The contraction rate of the device was 60 per min. RA EF was 41% in baseline, 7% in AF and 21% in assisted-AF conditions. CO was 7+/-0.5 l min(-1) in baseline, 6.2+/-0.5 l min(-1) in AF and 6.7+/-0.5 l min(-1) in assisted-AF status (p<0.01). Histology of the atrium in the chronic group showed chronic tissue inflammation and no sign of tissue necrosis. CONCLUSIONS: The artificial muscle restores the AK and improves CO. In patients with end-stage cardiac failure and permanent AF, if implanted on both sides, it would improve CO and possibly delay or even avoid complex surgical treatment such as VAD implantation.

Structural characterization of Turtle Mountain anticline (Alberta, Canada) and impact on rock slope failure

his paper proposes a structural investigation of the Turtle Mountain anticline (Alberta, Canada) to better understand the role of the different tectonic features on the development of both local and large scale rock slope instabilities occurring in Turtle Mountain. The study area is investigated by combining remote methods with detailed field surveys. In particular, the benefit of Terrestrial Laser Scanning for ductile and brittle tectonic structure interpretations is illustrated. The proposed tectonic interpretation allows the characterization of the fracturing pattern, the fold geometry and the role of these tectonic features in rock slope instability development. Ten discontinuity sets are identified in the study area, their local variations permitting the differentiation of the study zone into 20 homogenous structural domains. The anticline is described as an eastern verging fold that displays considerable geometry differences along its axis and developed by both flexural slip and tangential longitudinal strain folding mechanisms. Moreover, the origins of the discontinuity sets are determined according to the tectonic phases affecting the region (pre-folding, folding, post-folding). The localization and interpretation of kinematics of the different instabilities revealed the importance of considering the discrete brittle planes of weakness, which largely control the kinematic release of the local instabilities, and also the rock mass damage induced by large tectonic structures (fold hinge, thrust).

Effects of corticosterone on innate and humoral immune functions and oxidative stress in barn owl nestlings.

The costs of coping with stressful situations are traded-off against other functions such as immune responses. This trade-off may explain why corticosterone secretion reduces immune reactions. Corticosterone differentially affects various immunity components. However, which component is suppressed varies between studies. It remains unclear whether the trade-off in energy, nutrition, autoimmunity or oxidative stress accounts for differential immunosuppression. In this study, we investigated whether corticosterone differentially affects the constitutive innate and humoral acquired immunity. We used barn owl nestlings, implanting 50% with a corticosterone-releasing pellet and the other 50% with a placebo pellet. To measure the effect on humoral immunity we vaccinated 50% of the corticosterone-nestlings and 50% of the placebo-nestlings with the antigens 'Tetravac' and the other 50% were injected with PBS. To assess the costs of elevated corticosterone, we measured body mass and resistance to oxidative stress. Administration of corticosterone increased corticosterone levels whereas vaccination induced the production of antibodies. Corticosterone reduced the production of antibodies, but it did not significantly affect the constitutive innate immunity. Corticosterone reduced body growth and resistance to oxidative stress. Under stressful conditions barn owl nestlings seem to keep the constitutive innate immunity, whereas elevated corticosterone levels negatively affected inducible immune responses. We found evidence that mounting a humoral immune reaction is not costly in terms of growth, but reduces the resistance to oxidative stress independently of corticosterone administration. We suggest that humoral immunity is suppressed because the risk of immunopathologies may be disproportionately high when mounting an antibody response under stressful situations.

Acute hemodynamic effect of a vascular antagonist of vasopressin in patients with congestive heart failure.

To assess the role of arginine vasopressin (AVP) in congestive heart failure (CHF), 10 patients with CHF refractory to conventional treatment were studied before and 60 minutes after intravenous administration of 5 micrograms/kg of d(CH2)5Tyr(Me)AVP, a specific antagonist of AVP at the vascular receptor level. Heart rate, systemic arterial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac index by thermodilution and cutaneous blood flow by laser-Doppler technique were measured. In 9 patients with no significant hemodynamic and cutaneous blood flow response to the AVP antagonist, baseline values (mean +/- standard deviation) were: heart rate, 77 +/- 14 beats/min; systemic arterial pressure, 120/79 +/- 18/8 mm Hg; pulmonary arterial pressure, 42/21 +/- 12/8 mm Hg; pulmonary capillary wedge pressure, 19 +/- 7 mm Hg; cardiac index, 2.2 +/- 0.6 liters/min/m2; plasma AVP, 2.3 +/- 0.8 pg/ml; and plasma osmolality, 284 +/- 14 mosm/kg H2O. The tenth patient had the most severe CHF. His plasma AVP level was 55 pg/ml and plasma osmolality was 290 mosm/kg. He responded to the AVP antagonist with a decrease in systemic arterial pressure from 115/61 to 79/41 mm Hg, in pulmonary arterial pressure from 58/31 to 33/13 mm Hg and in pulmonary capillary wedge pressure from 28 to 15 mm Hg. Simultaneously, cardiac index increased from 1.1 to 2.2 liters/min/m2 and heart rate from 113 to 120 beats/min; cutaneous blood flow increased 5-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Copeptin, a stable peptide derived from the vasopressin precursor, correlates with the individual stress level.

BACKGROUND: During stress, vasopressin is a potent synergistic factor of CRH as a hypothalamic stimulator of the HPA axis. The measurements of CRH and vasopressin levels are cumbersome because of their instability and short half-life. Copeptin is a more stable peptide stoichiometrically released from the same precursor molecule. The aim of our study was to compare copeptin and cortisol levels in different stress situations. METHODS: Three groups of patients with increasing stress levels were investigated: a) healthy controls without apparent stress (n=20), b) hospitalized medical patients with moderate stress (n=25) and c) surgical patients 30 minutes after extubation, with maximal stress (n=29). In all patients we assessed cortisol and copeptin levels. Copeptin levels were measured with a new sandwich immunoassay. RESULTS: Cortisol levels in controls were (median, IQ range, 486 [397-588] nmol/L), not significantly different as compared to medical patients (438 [371-612] nmol/L, p=0.69). Cortisol levels in surgical patients after extubation were higher (744 [645-1062] nmol/L p<0.01 vs controls and medical patients). Copeptin levels in controls were 4.3 [3.2-5.5] pmol/L, which was lower as compared to medical patients (17.5 [6.4-24.1], p<0.001) and surgical patients after extubation (67.5 [37.8-110.0] pmol/L, p<0.001). The correlation between copeptin levels and cortisol was r=0.46, p<0.001. CONCLUSION: Copeptin is a novel marker of the individual stress level. It more subtly mirrors moderate stress as compared to cortisol values.