Extracellular matrix molecules enhance the neurotrophic effect of schwann cell-like differentiated adipose-derived stem cells and increase cell survival under stress conditions.

Since the first reports of induction of adipose-derived stem cells (ASC) into neuronal and glial cell phenotypes, expectations have increased regarding their use in tissue engineering applications for nerve repair. Cell adhesion to extracellular matrix (ECM) is a basic feature of survival, differentiation, and migration of Schwann cells (SC) during nerve regeneration, and fibronectin and laminin are two key molecules of this process. Interaction between ECM and SC-like differentiated ASC (dASC) could potentially improve the neurotrophic potential of the stem cells. We have investigated the effect of ECM molecules on SC-like dASC in terms of proliferation, adhesion, and cell viability. Fibronectin and laminin did not affect the proliferation of dASC when compared with cell adherent tissue culture plastic, but significantly improved viability and cell attachment when dASC were exposed to apoptotic conditions. To assess the influence of the ECM molecules on dASC neurotrophic activity, dASC were seeded onto ECM-coated culture inserts suspended above dorsal root ganglia (DRG) sensory neurons. Neurite outgrowth of DRG neurons was enhanced when dASC were seeded on fibronectin and laminin when compared with controls. When DRG neurons and dASC were in direct contact on the various surfaces there was significantly enhanced neurite outgrowth and coculture with laminin-conditioned dASC produced the longest neurites. Compared with primary SCs, dASC grown on laminin produced similar levels of neurite outgrowth in the culture insert experiments but neurite length was shorter in the direct contact groups. Anti β1 integrin blocking antibody could inhibit baseline and dASC evoked neurite elongation but had no effect on outgrowth mediated by laminin-conditioned dASC. ECM molecules had no effect on the levels of nerve growth factor and brain-derived neurotrophic factor secretion from dASC. The results of the study suggest that ECM molecules can significantly improve the potential of dASC for nerve regeneration.

Prevalence of symptomatic and silent stress-induced perfusion defects in diabetic patients with suspected coronary artery disease referred for myocardial perfusion scintigraphy.

PURPOSE: Silent myocardial ischaemia--as evaluated by stress-induced perfusion defects on myocardial perfusion scintigraphy (MPS) in patients without a history of chest pain--is frequent in diabetes and is associated with increased rates of cardiovascular events. Its prevalence has been determined in asymptomatic diabetic patients, but remains largely unknown in diabetic patients with suspected coronary artery disease (CAD) in the clinical setting. In this study we therefore sought (a) to determine the prevalence of symptomatic and silent perfusion defects in diabetic patients with suspected CAD and (b) to characterise the eventual predictors of abnormal perfusion. METHODS: The patient population comprised 133 consecutive diabetic patients with suspected CAD who had been referred for MPS. Studies were performed with exercise (41%) or pharmacological stress testing (1-day protocol, (99m)Tc-sestamibi, 201Tl or both). We used semi-quantitative analysis (20-segment polar maps) to derive the summed stress score (SSS) and the summed difference score (SDS). RESULTS: Abnormal MPS (SSS> or =4) was observed in 49 (37%) patients (SSS=4.9+/-8.4, SDS=2.4+/-4.7), reversible perfusion defects (SDS> or =2) in 40 (30%) patients [SSS=13.3+/-10.9; SDS=8.0+/-5.6; 20% moderate to severe (SDS>4), 7% multivessel] and fixed defects in 21 (16%) patients. Results were comparable between patients with and patients without a history of chest pain. Of 75 patients without a history of chest pain, 23 (31%, 95% CI=21-42%) presented reversible defects (SSS=13.9+/-11.3; SDS=7.4+/-1.2), indicative of silent ischaemia. Reversible defects were associated with inducible ST segment depression during MPS stress [odds ratio (OR)=3.2, p<0.01). Fixed defects were associated with erectile dysfunction in males (OR=3.7, p=0.02) and lower aspirin use (OR=0.25, p=0.02). CONCLUSION: Silent stress-induced perfusion defects occurred in 31% of the patients, a rate similar to that in patients with a history of chest pain. MPS could identify these patients with a potentially increased risk of cardiovascular events.

Effects of L-carnitine supplemented total parenteral nutrition on lipid and energy metabolism in postoperative stress.

During episodes of trauma carnitine-free total parenteral nutrition (TPN) may result in a reduction of the total body carnitine pool, leading to a diminished rate of fat oxidation. Sixteen patients undergoing esophagectomy were divided randomly in two equal isonitrogenous groups (0.2 g/kg.day). Both received TPN (35 kcal/kg.day; equally provided as long-chain triglycerides and glucose) over 11 days without (group A) and with (group B) L-carnitine supplementation (12 mg/kg.day = 75 mumol/kg.day). Compared with healthy controls, the total body carnitine pool prior to the operation was significantly reduced in both groups, suggesting a state of semistarvation and muscle wasting. In group A the plasma levels of total carnitine and its subfractions (free carnitine, short- and long-chain acylcarnitine) remained stable during the study whereas in group B the total plasma carnitine concentration rose mainly due to an increase in free carnitine. In group A the cumulative urinary carnitine losses were 11.5 +/- 2.6 mmol (= 15.5 +/- 3.1% of the estimated total body carnitine pool). In group B 3.1 +/- 1.9 mmol (= 11.1 +/- 7.6%) of the infused carnitine was retained in the immediate postoperative phase until day 6, but this amount was completely lost at completion of the study period. No significant differences in the respiratory quotient or in the plasma levels of triglycerides, free fatty acids, and ketone bodies were observed, between or within the groups, before the operation and after 11 days of treatment. It is concluded that the usefulness of carnitine supplementation during postoperative TPN was not apparent in the present patient material.

Analyse comparée de régimes institutionnels de gestion des réseaux urbains de l'eau en station touristique de montagne : les cas de Crans-Montana (Suisse) et de Morzine-Avoriaz (France)

La station touristique représente un espace urbain consacré principalement au tourisme, tout en comprenant également une population résidente permanente. Du point de vue de la gestion des réseaux urbains de l'eau, cette caractéristique induit pour ce type de lieu des usages propres à tout espace urbain mais également des spécificités liées à la forte fluctuation saisonnière de la population résidente ou encore à la présence d'usages particuliers tels que l'irrigation des golfs, la production de neige artificielle ou le thermalisme. Dès lors, la planification de l'approvisionnement est délicate et peu prévisible. Ces difficultés sont renforcées par le fait que les concentrations temporelles de la demande coïncident généralement avec des périodes de stress hydrique notable. Dans le cas de stations balnéaires, les pics de fréquentation interviennent en général durant l'été lorsque la ressource en eau est peu disponible. Le problème est similaire dans les stations touristiques de montagne où l'eau est généralement indisponible car stockée sous forme de neige durant les mois de forte fréquentation. De plus, ces difficultés sont souvent renforcées par la localisation géographique des stations touristiques, fréquemment situées dans des espaces sensibles du point de vue de la ressource en eau, avec des situations de pénuries temporelles, voire structurelles. Ces problématiques propres à la plupart des stations touristiques mènent souvent à de fortes rivalités entre, d'une part, les différents usages touristiques de la ressource, et d'autre part, les usages autochtones et touristiques. Les particularités liées au tourisme tendent ainsi à renforcer les rivalités entre différents types de secteurs d'activité (approvisionnement en eau potable, tourisme, hydroélectricité, enneigement artificiel, irrigation, etc.). Ces différents usages de la ressource mis en concurrence nécessitent dès lors la mise en oeuvre de réglementations structurées à travers des politiques publiques ainsi que des droits de propriété et selon des composantes nationales, régionales et locales ; soit un cadre institutionnel que nous proposons d'appeler Régime Institutionnel de Ressource (RIR) (Knoepfel et al. 2001, 2007). A travers cette thèse de doctorat, nous répondons à différentes questions de recherche. Nous tentons d'abord de comprendre comment ces différents RIR sont-ils mis en oeuvre dans le cadre d'espaces touristiques ? Comment ceux-ci sont-ils concrétisés par les acteurs et quels sont leurs effets en termes de durabilité technique, environnementale, sociale et économique des réseaux urbains de l'eau ? Nous questionnons ensuite les effets du tourisme sur la gestion des infrastructures de réseau à l'échelle de la station touristique et de son bassin versant et nous interrogeons sur les effets du tourisme en termes de gestion des eaux urbaines. Nous portons notre attention sur deux stations touristiques situées dans deux contextes institutionnels différents (Crans-Montana en Suisse et Morzine-Avoriaz en France) et y étudions trois types de régimes institutionnels en particulier : la régie directe (gestion publique), l'affermage (gestion déléguée) et la gestion privée des infrastructures. Les résultats de cette thèse de doctorat indiquent tout d'abord dans quelle mesure le tourisme modifie de façon significative la perception et les modalités de gestion de la ressource en eau et des infrastructures. Ils montrent ensuite que l'espace fonctionnel de la gestion de ces infrastructures correspond rarement aux limites du réseau hydrographique naturel et quelles en sont les implications en termes de durabilité. Enfin, la comparaison de différents régimes institutionnels révèle les forces et les faiblesses de chaque modèle de gestion dans le cas spécifique des stations touristiques et également les différentes solutions adoptées localement pour la mise en oeuvre d'un arrangement institutionnel permettant un usage plus ou moins durable des infrastructures de réseau et du réseau hydrographique naturel. - Tourism resort represents an urban area mainly dedicated to tourism while including at the same time a permanent residential population. From the point of view of urban water networks, this characteristic induces a strong seasonal fluctuation of residential population and involves special water uses such as golf irrigation, production of artificial snow or functioning of thermal baths. Therefore, water supply planning can be tricky and difficult to predict. These difficulties are reinforced by the fact that temporary concentrations of water demand coïncidé generally with periods of water stress. In the case of seaside resorts, frequenting peaks arise in general during summer when water resource is less available. The problem is similar in mountainous tourist resorts where water is generally unavailable as it is stored as snow during months of highest frequenting. Furthermore, these difficulties are often reinforced by resorts' geographical localisations, which are often situated in sensitive areas in terms of temporary or structural water shortages. These problematic issues often lead to strong rivalries between tourists' water uses on the one hand, and between locals and tourists uses on the other hand. Thus, features of tourism tend to reinforce rivalries between different sectors of activity (supply of drinking water, tourism, hydroelectricity, artificial snow, irrigation, etc.). These different and competing water uses need the implementation of rules structured through public policies and property rights and through national, regional and local legal components; We propose to call this framework as an Institutional Resource Regime (IRR) (Knoepfel et al. 2001, 2007, 2009). Through this PhD thesis, we answer different research questions. We firstly aim to understand how those different IRR are implemented within tourism spaces? How do actors materialize them and what are their effects in term of technical, environmental, social and economical sustainability of urban water networks? We then, investigate effects of tourism on water networks infrastructures' management at the scale of the tourist resort and its river basin. We focus our attention on two tourist resorts situated within two different institutional contexts (Crans-Montana, Switzerland and Morzine-Avoriaz, France) and study three types of institutional regime in particular: public, delegated and private management of infrastructures. Results of this PhD thesis indicate firstly how tourism modifies in a significant way the perception and management modalities of water resource and infrastructures. Results also show that functional space of infrastructures management rarely matches with the limits of the natural river basin and indicates what it means in terms of sustainability. Finally, the comparison of different institutional regimes reveals the strengths and weakness of each management model in the specific case of tourist resorts and shows the different solutions in locally implementing an institutional arrangement for a more or less sustainable management of network infrastructures and natural water system.

Reduced learning ability as a consequence of evolutionary adaptation to nutritional stress in Drosophila melanogaster

1. Dietary conditions affect cognitive abilities of many species, but it is unclear to what extent this physiological effect translates into an evolutionary relationship. 2. A reduction of competitive ability under nutritional stress has been reported as a correlated response to selection for learning ability in Drosophila melanogaster. Here we test whether the reverse holds as well, i.e. whether an evolutionary adaptation to poor food conditions leads to a decrease in learning capacities. 3. Populations of D. melanogaster were: (i) not subject to selection (control), (ii) selected for improved learning ability, (iii) selected for survival and fast development on poor food, or (iv) subject to both selection regimes. 4. There was no detectable response to selection for learning ability. 5. Selection on poor food led to higher survival, faster development and smaller adult size as a direct response, and to reduced learning ability as a correlated response. This study supports the hypothesis that adaptation to poor nutrition is likely to trade off with the evolution of improved learning ability.

The Impact of Personality and Culture on the Job Demands-Control Model of Job Stress

Among the various work stress models, one of the most popular has been the job demands-control (JDC) model developed by Karasek (1979), which postulates that work-related strain is highest under work conditions characterized by high demands and low autonomy. The absence of social support at work further increases negative outcomes. This model, however, does not apply equally to all individuals and to all cultures. This review demonstrates how various individual characteristics, especially some personality dimensions, influence the JDC model and could thus be considered buffering or moderator factors. Moreover, we review how the cultural context impacts this model as suggested by results obtained in European, American, and Asian contexts. Yet there are almost no data from Africa or South America. More crosscultural studies including populations from these continents would be valuable for a better understanding of the impact of the cultural context on the JDC model.

Role for inducible cAMP early repressor in promoting pancreatic beta cell dysfunction evoked by oxidative stress in human and rat islets.

AIMS/HYPOTHESIS: Pro-atherogenic and pro-oxidant, oxidised LDL trigger adverse effects on pancreatic beta cells, possibly contributing to diabetes progression. Because oxidised LDL diminish the expression of genes regulated by the inducible cAMP early repressor (ICER), we investigated the involvement of this transcription factor and of oxidative stress in beta cell failure elicited by oxidised LDL. METHODS: Isolated human and rat islets, and insulin-secreting cells were cultured with human native or oxidised LDL or with hydrogen peroxide. The expression of genes was determined by quantitative real-time PCR and western blotting. Insulin secretion was monitored by EIA kit. Cell apoptosis was determined by scoring cells displaying pycnotic nuclei. RESULTS: Exposure of beta cell lines and islets to oxidised LDL, but not to native LDL raised the abundance of ICER. Induction of this repressor by the modified LDL compromised the expression of important beta cell genes, including insulin and anti-apoptotic islet brain 1, as well as of genes coding for key components of the secretory machinery. This led to hampering of insulin production and secretion, and of cell survival. Silencing of this transcription factor by RNA interference restored the expression of its target genes and alleviated beta cell dysfunction and death triggered by oxidised LDL. Induction of ICER was stimulated by oxidative stress, whereas antioxidant treatment with N-acetylcysteine or HDL prevented the rise of ICER elicited by oxidised LDL and restored beta cell functions. CONCLUSIONS/INTERPRETATION: Induction of ICER links oxidative stress to beta cell failure caused by oxidised LDL and can be effectively abrogated by antioxidant treatment.

The influence of attachment on perceived stress and cortisol response to acute stress in women sexually abused in childhood or adolescence.

The long-term implications of sexual abuse in childhood or adolescence (CSA) have been relatively well documented regarding attachment (disorganized attachment in childhood, unresolved trauma in adulthood), stress reactions (altered patterns of stress reactivity under experimental conditions), and psychopathology. Attachment has been shown to mediate the implications of CSA, namely on psychopathology. The implication of attachment on stress responses of abused persons has not been documented. Twenty-seven 20-46 years old women who had experienced episodes of CSA, and 17 controls have been interviewed using the Adult Attachment Interview. Sixty-three percent of abused women presented an unresolved trauma (12% for the controls). Thirty-six women (14 controls and 22 abused) came again to the laboratory for a session involving an experimental stress challenge (TSST). Subjects provided repeated appreciations of perceived stress on visual analogue scales and saliva samples were collected to assay cortisol levels. Whereas abused women with unresolved trauma showed the highest levels of perceived stress, they simultaneously presented the most suppressed cortisol reactions (there were significant post hoc differences between "unresolved abused" and controls on the increase of perceived stress and on cortisol recovery after the acute stress). It is suggested that important stressful experiences (such as CSA), especially when they have not been psychologically assimilated, may cause a disconnection, during subsequent mildly stressful circumstances, between the perception of stress and natural defensive body reactions.

Early-Life Insults Impair Parvalbumin Interneurons via Oxidative Stress: Reversal by N-Acetylcysteine.

BACKGROUND: A hallmark of the pathophysiology of schizophrenia is a dysfunction of parvalbumin-expressing fast-spiking interneurons, which are essential for the coordination of neuronal synchrony during sensory and cognitive processing. Oxidative stress as observed in schizophrenia affects parvalbumin interneurons. However, it is unknown whether the deleterious effect of oxidative stress is particularly prevalent during specific developmental time windows. METHODS: We used mice with impaired synthesis of glutathione (Gclm knockout [KO] mice) to investigate the effect of redox dysregulation and additional insults applied at various periods of postnatal development on maturation and long-term integrity of parvalbumin interneurons in the anterior cingulate cortex. RESULTS: A redox dysregulation, as in Gclm KO mice, renders parvalbumin interneurons but not calbindin or calretinin interneurons vulnerable and prone to exhibit oxidative stress. A glutathione deficit delays maturation of parvalbumin interneurons, including their perineuronal net. Moreover, an additional oxidative challenge in preweaning or pubertal but not in young adult Gclm KO mice reduces the number of parvalbumin-immunoreactive interneurons. This effect persists into adulthood and can be prevented with the antioxidant N-acetylcysteine. CONCLUSIONS: In Gclm KO mice, early-life insults inducing oxidative stress are detrimental to immature parvalbumin interneurons and have long-term consequences. In analogy, individuals carrying genetic risks to redox dysregulation would be potentially vulnerable to early-life environmental insults, during the maturation of parvalbumin interneurons. Our data support the need to develop novel therapeutic approaches based on antioxidant and redox regulator compounds such as N-acetylcysteine, which could be used preventively in young at-risk subjects.

Anastomotic longitudinal stress due to modification of arterial longitudinal properties after anastomosis.

BACKGROUND: In our hands, in vivo segmental vessel length changes up to 5% because of blood pressure: increasing in arterial pressure is associated to decrease in segmental vessel length. METHODS AND MATERIAL: Using two piezoelectric crystals sutured on vessel wall and a high fidelity pressure probe, we recorded artery length variations as function of blood pressure, before and after an end-to-end anastomosis on four pigs carotid arteries. RESULTS: Mean arterial pressure before anastomosis = 73 mmHg (+/- 12); mean arterial pressure after anastomosis = 91 mmHg (+/- 14); mean crystals displacement before anastomosis during systole = -0.21 mm; mean crystals displacement after anastomosis during systole = +0.24 mm; mean distance between crystals before anastomosis = 12.3 mm (+/- 0.8) and after anastomosis = 11.2 mm (+/- 0.5). CONCLUSIONS: In the acute phase following an end-to-end anastomosis, an increase in blood pressure causes increasing in vessel length, with an exponential correlation. The anastomosis is constantly subjected to a longitudinal traction whose magnitude depends on blood pressure.

Anxiety and Psychological Stress Before Prenatal Screening in First-Time Mothers Who Conceived Through IVF/ICSI or Spontaneously.

Mothers' general anxiety, anxiety about the well-being of the child and psychological stress before prenatal testing was studied by comparing women who conceived through in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) with women who conceived naturally. Before the first trimester screening test for Down's syndrome, a group of 51 women who conceived through IVF/ICSI and a group of 54 women who conceived spontaneously completed the State Scale of the State-Trait Anxiety Inventory (S-Anxiety; Spielberger, 1983), the Fear of Bearing a Physically or Mentally Handicapped Child Subscale of the Pregnancy-related Anxiety Questionnaire (PRAQ-R; Huizink et al., 2004), the Psychological Stress Measure (PSM; Lemyre & Tessier, 1988), and the Prenatal Psychosocial Profile (PPP; Curry, Campbell, & Christian, 1994). Women who conceived through IVF/ICSI had more elevated levels of general anxiety and psychological stress than the women who conceived naturally; however, no difference was observed between the two groups for anxiety specifically related to the health of the child. These results underline the need to monitor women's emotional state after conception via IVF/ICSI-when counseling usually ends-and around the time of the first trimester screening. Counseling might thus be extended.