Ecology and neurophysiology of sleep in two wild sloth species

Study Objectives: Interspecific variation in sleep measured in captivity correlates with various physiological and environmental factors, including estimates of predation risk in the wild. However, it remains unclear whether prior comparative studies have been confounded by the captive recording environment. Herein we examine the impact of predation pressure on sleep in sloths living in the wild. Design: Comparison of two closely related sloth species, one exposed to predation and one free from predation. Setting: Panamanian mainland rainforest (predators present) and island mangrove (predators absent). Participants: Mainland (Bradypus variegatus, 5 males and 4 females) and island (Bradypus pygmaeus, 6 males) sloths. Interventions: None. Measurements and Results: EEG and EMG activity were recorded using a miniature data logger. Although both species spent between 9 and 10 hours per day sleeping, the mainland sloths showed a preference for sleeping at night, whereas island sloths showed no preference for sleeping during the day or night. EEG activity during NREM sleep showed lower low-frequency power, and increased spindle and higher frequency power in island sloths when compared to mainland sloths. Conclusions: In sloths sleeping in the wild, predation pressure influenced the timing of sleep, but not the amount of time spent asleep. The preference for sleeping at night in mainland sloths may be a strategy to avoid detection by nocturnal cats. The pronounced differences in the NREM sleep EEG spectrum remain unexplained, but might be related to genetic or environmental factors.

Impact of carotid plaque screening on smoking cessation and other cardiovascular risk factors: a randomized controlled trial.

BACKGROUND: Screening of peripheral atherosclerosis is increasingly used, but few trials have examined its clinical impact. We aimed to assess whether carotid plaque screening helps smokers to improve their health behaviors and cardiovascular risk factors. METHODS: We randomly assigned 536 smokers aged 40 to 70 years to carotid plaque ultrasonographic screening (US group) vs no screening (control group) in addition to individual counseling and nicotine replacement therapy for all participants. Smokers with at least 1 plaque received pictures of their plaques with a 7-minute structured explanation. The outcomes included biochemically validated smoking cessation at 12 months (primary outcome) and changes in cardiovascular risk factor levels and Framingham risk score. RESULTS: At baseline, participants (mean age, 51.1 years; 45.0% women) smoked an average of 20 cigarettes per day with a median duration of 32 years. The US group had a high prevalence of carotid plaques (57.9%). At 12 months, smoking cessation rates were high, but did not differ between the US and control groups (24.9% vs 22.1%; P = .45). In the US group, cessation rates did not differ according to the presence or absence of plaques. Control of cardiovascular risk factors (ie, blood pressure and low-density lipoprotein cholesterol and hemoglobin A(1c) levels in diabetic patients) and mean absolute risk change in Framingham risk score did not differ between the groups. The mean absolute risk change in Framingham risk score was +0.6 in the US group vs +0.3 in the control group (P = .56). CONCLUSION: In smokers, carotid plaque screening performed in addition to thorough smoking cessation counseling is not associated with increased rates of smoking cessation or control of cardiovascular risk factors. Trial Registration  clinicaltrials.gov Identifier: NCT00548665.

Multiple paternity and its consequences in the white campion " Silene latifolia "

Summary Several studies have demonstrated that the number of pollen donors siring seeds of individual fruits is frequently greater than one and, consequently, that plants have multiple mates. Multiple paternity can have important consequences at the population level. It influences the genetic variability of a population, the reproductive success of males and the fitness of females and future generations. It also influences male-male interactions for fertilization and it is fundamental in providing opportunity of female choice. I investigated the occurrence and the importance of multiple paternity within fruits in natural populations of the dioecious Silene latifolia using microsatellite DNA markers, especially developed for this study. I found that multiple paternity occurs in all populations investigated in the European range of the species, varying from one to nine sires per fruit with a mean of three, suggesting that multiple paternity is highly prevalent in natural populations. In the presence of multiple paternity I investigated if there was a female genotype influence on siring success of the males. I used the same pollen mixture from two males and applied it to three replicate females of different relatedness (two full sisters and one unrelated). I found female genotype influence in one of the two populations investigated, which might reflect different population history. Since these results suggested some degree of female choice, we investigated whether the occurrence of multiple paternity and post-pollination selection could provide opportunity for inbreeding avoidance. First, I measured inbreeding depression at different life-cycle stages for offspring obtained by single-donor crosses with brothers or unrelated males replicated on distinct flowers on the same female plant. To address inbreeding avoidance, I determined paternity in crosses using mixed pollen loads of the two males. I found significant inbreeding depression in the studied population, even under benign experimental conditions, and although the unrelated male did not sire significantly more offspring, there was an effect of genetic dissimilarity on paternity. This suggests that paternity is affected by relatedness among mates, but maybe additionally affected by other factors such as pollen competitive ability or male-female interactions. Using inbred and outbred crosses, I further investigated sex ratio bias inheritance in this species, and found that sex ratio bias of the parental generation was significantly correlated to pollen germination success of the F2 generation, which suggests that sex ratio bias in this species results from the specific X/Y combination and not only on Y performance. An effect of X and Y is consistent with sex chromosome meiotic drive. In conclusion, I found multiple paternity to be widespread in the study species and that females of similar genotype produce similar paternity shares. I found that inbreeding depression is substantial, therefore receiving pollen from several donors might lead to fewer inbred offspring, I also found an effect of genetic dissimilarity on paternity shares, which indicates that there is some ability to discriminate against related pollen, although this seems not to be the only determinant of paternity outcome. Finally I found sex ratio bias to be dependent on both X and Y chromosomes as predicted by sex chromosome meiotic drive. Résumé Plusieurs études ont démontré qu'il n'était pas rare que les graines contenues dans un même fruit soient issues de la fécondation par plusieurs pollens provenant de mâles différents, ce qui sous-entend que les plantes peuvent avoir plusieurs partenaires sexuels. La paternité multiple peut avoir d'importantes conséquences au niveau populationnel dans la mesure où elle peut influencer le degré de variabilité génétique de la population, le succès reproducteur des mâles, la fitness des femelles et des futures générations. La paternité multiple peut également avoir un impact sur les interactions mâle-mâle lors de la fertilisation et peut être considérée comme fondamentale vis-à-vis de la femelle, qui y trouve alors une opportunité de choisir son ou ses partenaires. Dans le cadre de ce travail de thèse j'ai cherché à déterminer si la paternité multiple était un phénomène observable et important dans les populations naturelles de l'espèce dioïque, Silene latifolia. Pour ce faire, j'ai utilisé des marqueurs microsatellites, spécialement développés pour cette étude. J'ai observé des phénomènes de paternité multiple dans toutes les populations de l'étude, réparties dans l'aire de distribution européenne de l'espèce. Le nombre de pères par fruit varie de un à neuf, avec un nombre moyen de trois, ce qui signifie que la paternité multiple est très répandue dans les populations naturelles. En raison de ces résultats, je me suis demandée si le génotype de la femelle influence le succès de paternité des mâles. J'ai alors réalisé des pollinisations manuelles sur la base d'un mélange de pollens issus de deux mâles, que j'ai appliqué sur trois femelles (réplicats) présentant différents degrés d'apparentement (deux soeurs. et une femelle étrangère). Il ressort de cette expérience que le génotype de la femelle peut influencer la paternité dans l'une des deux populations étudiées, ce qui pourrait refléter des différences en terme d'histoire des populations. Dans la mesure où ces résultats suggèrent un certain degré de choix chez la femelle, j'ai cherché à savoir si la paternité multiple et la sélection post-pollinisation pouvaient être des moyens d'éviter les croisements consanguins. Dans un premier temps, j'ai évalué la dépression de consanguinité à différentes étapes du cycle de vie chez des descendants issus de croisements à un seul donneur, celui-ci étant alternativement un frère ou un étranger, répliqués sur plusieurs fleurs d'une même plante femelle. Afin d'estimer l'évitement de croisements consanguins, j'ai effectué des croisements dont le pollen était un mélange des deux mâles (frère et étranger), puis j'ai déterminé la paternité dans les fruits obtenus. J'ai pu mettre en évidence un effet de dépression de consanguinité- significatif dans les populations étudiées, même dans des conditions expérimentales moins rudes qu'à l'extérieur. Bien que le mâle étranger n'ait pas engendré un nombre significativement plus important de graines, il y avait un effet de dissimilarité génétique sur la paternité. Ceci suggère que la paternité est affectée par le degré d'apparentement entre les partenaires, mais qu'elle peut aussi être affectée par d'autres facteurs tels que la compétitivité du pollen ou encore par les interactions mâles-femelles. L'utilisation de croisements consanguins et hybrides m'a également permis d'étudier l'héritabilité du biais de sex ratio chez cette espèce. Il s'est avéré que le biais de sex ratio de la génération parentale était significativement corrélé au succès de germination du pollen de la génération F2, ce qui signifie que, chez cette espèce, le biais de sex ratio résulte d'une combinaison spécifique de X/Y et non uniquement de la performance de Y. Un effet de X et Y est compatible avec l'hypothèse de distorsion de ségrégation méiotique des chromosomes sexuels. En conclusion, il ressort de mes résultats que la paternité multiple est un phénomène largement répandu chez S. latifolia et la paternité accomplie par un mâle est plus similaire entre soeurs qu'avec une femelle étrangère J'ai également mis en évidence que la dépression de consanguinité a un impact considérable; aussi, recevoir du pollen de plusieurs donneurs différents pourrait permettre à la femelle de produire moins de descendants consanguins. J'ai aussi trouvé un effet de la dissimilarité génétique sur le partage de paternité, ce qui indique que la discrimination contre le pollen d'apparentés est possible, bien que cela ne semble pas être le seul facteur déterminant dans le résultat de la paternité. Enfin, j'ai trouvé que le biais de sex ratio est dépendant des deux chromosomes X et Y, conformément à la théorie de distorsion de ségrégation méiotique des chromosomes sexuels.

Cognitive and emotional effects of carotid stenosis.

PRINCIPLES: Patients with carotid artery stenosis (CAS) are at risk of ipsilateral stroke and chronic compromise of cerebral blood flow. It is under debate whether the hypo-perfusion or embolism in CAS is directly related to cognitive impairment. Alternatively, CAS may be a marker for underlying risk factors, which themselves influence cognition. We aimed to determine cognitive performance level and the emotional state of patients with CAS. We hypo-thesised that patients with high grade stenosis, bilateral stenosis, symptomatic patients and/or those with relevant risk factors would suffer impairment of their cognitive performance and emotional state. METHODS: A total of 68 patients with CAS of ≥70% were included in a prospective exploratory study design. All patients underwent structured assessment of executive functions, language, verbal and visual memory, motor speed, anxiety and depression. RESULTS: Significantly more patients with CAS showed cognitive impairments (executive functions, word production, verbal and visual memory, motor speed) and anxiety than expected in a normative sample. Bilateral and symptomatic stenosis was associated with slower processing speed. Cognitive performance and anxiety level were not influenced by the side and the degree of stenosis or the presence of collaterals. Factors associated with less co-gnitive impairment included higher education level, female gender, ambidexterity and treated hypercholesterolemia. CONCLUSIONS: Cognitive impairment and increased level of anxiety are frequent in patients with carotid stenosis. The lack of a correlation between cognitive functioning and degree of stenosis or the presence of collaterals, challenges the view that CAS per se leads to cognitive impairment.

Substitution of (R,S)-methadone by (R)-methadone: Impact on QTc interval.

Methadone is administered as a chiral mixture of (R,S)-methadone. The opioid effect is mainly mediated by (R)-methadone, whereas (S)-methadone blocks the human ether-à-go-go-related gene (hERG) voltage-gated potassium channel more potently, which can cause drug-induced long QT syndrome, leading to potentially lethal ventricular tachyarrhythmias. To investigate whether substitution of (R,S)-methadone by (R)-methadone could reduce the corrected QT (QTc) interval, (R,S)-methadone was replaced by (R)-methadone (half-dose) in 39 opioid-dependent patients receiving maintenance treatment for 14 days. (R)-methadone was then replaced by the initial dose of (R,S)-methadone for 14 days (n = 29). Trough (R)-methadone and (S)-methadone plasma levels and electrocardiogram measurements were taken. The Fridericia-corrected QT (QTcF) interval decreased when (R,S)-methadone was replaced by a half-dose of (R)-methadone; the median (interquartile range [IQR]) values were 423 (398-440) milliseconds (ms) and 412 (395-431) ms (P = .06) at days 0 and 14, respectively. Using a univariate mixed-effect linear model, the QTcF value decreased by a mean of -3.9 ms (95% confidence interval [CI], -7.7 to -0.2) per week (P = .04). The QTcF value increased when (R)-methadone was replaced by the initial dose of (R,S)-methadone for 14 days; median (IQR) values were 424 (398-436) ms and 424 (412-443) ms (P = .01) at days 14 and 28, respectively. The univariate model showed that the QTcF value increased by a mean of 4.7 ms (95% CI, 1.3-8.1) per week (P = .006). Substitution of (R,S)-methadone by (R)-methadone reduces the QTc interval value. A safer cardiac profile of (R)-methadone is in agreement with previous in vitro and pharmacogenetic studies. If the present results are confirmed by larger studies, (R)-methadone should be prescribed instead of (R,S)-methadone to reduce the risk of cardiac toxic effects and sudden death.

Thyroid function and prevalent and incident metabolic syndrome in older adults: the Health, Ageing and Body Composition Study.

OBJECTIVE: Both subclinical hypothyroidism and the metabolic syndrome have been associated with increased risk of coronary heart disease events. It is unknown whether the prevalence and incidence of metabolic syndrome is higher as TSH levels increase, or in individuals with subclinical hypothyroidism. We sought to determine the association between thyroid function and the prevalence and incidence of the metabolic syndrome in a cohort of older adults. DESIGN: Data were analysed from the Health, Ageing and Body Composition Study, a prospective cohort of 3075 community-dwelling US adults. PARTICIPANTS: Two thousand one hundred and nineteen participants with measured TSH and data on metabolic syndrome components were included in the analysis. MEASUREMENTS: TSH was measured by immunoassay. Metabolic syndrome was defined per revised ATP III criteria. RESULTS: At baseline, 684 participants met criteria for metabolic syndrome. At 6-year follow-up, incident metabolic syndrome developed in 239 individuals. In fully adjusted models, each unit increase in TSH was associated with a 3% increase in the odds of prevalent metabolic syndrome (OR, 1.03; 95% CI, 1.01-1.06; P = 0.02), and the association was stronger for TSH within the normal range (OR, 1.16; 95% CI, 1.03-1.30; P = 0.02). Subclinical hypothyroidism with a TSH > 10 mIU/l was significantly associated with increased odds of prevalent metabolic syndrome (OR, 2.3; 95% CI, 1.0-5.0; P = 0.04); the odds of incident MetS was similar (OR 2.2), but the confidence interval was wide (0.6-7.5). CONCLUSIONS: Higher TSH levels and subclinical hypothyroidism with a TSH > 10 mIU/l are associated with increased odds of prevalent but not incident metabolic syndrome.

Encéphalite japonaise: risque pour les populations vivant en zones d'endémie et pour les voyageurs [The importance of Japanese encephalitis: for endemic populations and for travellers]

The importance of Japanese encephalitis (JE) in endemic populations and in travellers requires a balanced assessment. This disease represents an important public health problem in some endemic areas, which contrasts with the minimal risk for travellers to endemic areas. This is reflected by high numbers of infections mainly among children in endemic countries and by few case reports among tourists and even expatriates. The total number of case reports between 1978 and 2008 amounts to a risk of one to two cases per year. Nevertheless, some travelling groups may be at higher risk when visiting or working in high risk areas. A new vaccine against Japanese encephalitis will soon be registered in Switzerland. This paper contributes to the scarce data available for decision making whether or not to recommend the vaccination to tourists and expatriates.

Integration of olfactory information in a spatial representation enabling accurate arm choice in the radial arm maze

The aim of the present study was to determine whether and how rats can use local olfactory cues for spatial orientation. Rats were trained in an eight-arm radial maze under different conditions as defined by the presence or absence of supplementary olfactory cues marking each arm, the availability of distant visuospatial information, and the illumination of the maze (light or darkness). The different visual conditions were designed to dissociate among the effects of light per se and those of visuospatial cues, on the use of olfactory cues for accurate arm choice. Different procedures with modifications of the arrangement of olfactory cues were used to determine if rats formed a representation of the spatial configuration of the olfactory cues and if they could rely on such a representation for accurate arm choice in the radial maze. The present study demonstrated that the use of olfactory cues to direct arm choice in the radial arm maze was critically dependent on the illumination conditions and implied two different modes of processing of olfactory information according to the presence or the absence of light. Olfactory cues were used in an explicit manner and enabled accurate arm choice only in the absence of light. Rats, however, had an implicit memory of the location of the olfactory cues and formed a representation of the spatial position of these cues, whatever the lighting conditions. They did not memorize the spatial configuration of the olfactory cues per se but needed these cues to be linked to the external spatial frame of reference.

Hyperhomocysteinemia is independently associated with albuminuria in the population-based CoLaus study.

Increased serum levels of homocysteine and uric acid have each been associated with cardiovascular risk. We analyzed whether homocysteine and uric acid were associated with glomerular filtration rate (GFR) and albuminuria independently of each other. We also investigated the association of MTHFR polymorphisms related to homocysteine with albuminuria to get further insight into causality. This was a cross-sectional population-based study in Caucasians (n = 5913). Hyperhomocysteinemia was defined as total serum homocysteine ≥ 15 μmol/L. Albuminuria was defined as urinary albumin-to-creatinine ratio > 30 mg/g. Uric acid was associated positively with homocysteine (r = 0.246 in men and r = 0.287 in women, P < 0.001). The prevalence of albuminuria increased across increasing homocysteine categories (from 6.4% to 17.3% in subjects with normal GFR and from 3.5% to 14.5% in those with reduced GFR, P for trend < 0.005). Hyperhomocysteinemia (OR = 2.22, 95% confidence interval: 1.60-3.08, P < 0.001) and elevated serum uric acid (OR = 1.27, 1.08-1.50, per 100 μmol/L, P = 0.004) were significantly associated with albuminuria, independently of hypertension and type 2 diabetes. The 2-fold higher risk of albuminuria associated with hyperhomocysteinemia was similar to the risk associated with hypertension or diabetes. MTHFR alleles related to higher homocysteine were associated with increased risk of albuminuria. In the general adult population, elevated serum homocysteine and uric acid were associated with albuminuria independently of each other and of renal function.

Housewife or working mum--each to her own? The relevance of societal factors in the association between social roles and alcohol use among mothers in 16 industrialized countries.

Aims To investigate whether differences in gender-income equity at country level explain national differences in the links between alcohol use, and the combination of motherhood and paid labour. Design Cross-sectional data in 16 established market economies participating in the Gender, Alcohol and Culture: An International Study (GenACIS) study. Setting Population surveys. Participants A total of 12 454 mothers (aged 25-49 years). Measurements Alcohol use was assessed as the quantity per drinking day. Paid labour, having a partner, gender-income ratio at country level and the interaction between individual and country characteristics were regressed on alcohol consumed per drinking day using multi-level modelling. Findings Mothers with a partner who were in paid labour reported consuming more alcohol on drinking days than partnered housewives. In countries with high gender-income equity, mothers with a partner who were in paid labour drank less alcohol per occasion, while alcohol use was higher among working partnered mothers living in countries with lower income equity. Conclusion In countries which facilitate working mothers, daily alcohol use decreases as female social roles increase; in contrast, in countries where there are fewer incentives for mothers to remain in work, the protective effect of being a working mother (with partner) on alcohol use is weaker. These data suggest that a country's investment in measures to improve the compatibility of motherhood and paid labour may reduce women's alcohol use.

Life design: Un paradigma per la costruzione della vita professionale nel XXI secolo

In questo inizio di secolo, la nuova organizzazione sociale del lavoro pone una serie di domande e di sfide ai ricercatori che intendono aiutare le persone a progettare la loro vita lavorativa. Nell'era della globalizzazione anche per quanto riguarda il career counseling, abbiamo deciso di affrontare queste problematiche e di dare delle risposte che si caratterizzassero come innovative attraverso la costituzione di un forum di discussione internazionale. Si è proceduto in questo modo per evitare le difficoltà che generalmente si incontrano quando si mettono a punto dei modelli e dei metodi in un Paese e poi si esportano in altre culture con l'intento di adattarli alle stesse. Questo articolo presenta i primi risultati della collaborazione che si è registrata - un modello e dei metodi per la consulenza di orientamento. Il modello per l'intervento nell'ambito dell'approccio Life Design si caratterizza per cinque presupposti relativi al modo di vedere le persone e la loro vita lavorativa. Essi riguardano le possibilità contestuali, i processi dinamici, i progressi non-lineari, le molteplici prospettive e la presenza di pattern personali. Partendo da questi cinque presupposti abbiamo messo a punto un modello basato sull'epistemologia del costruzionismo sociale, che sostiene che la conoscenza e l'identità di un individuo sono i prodotti dell'interazione sociale e che il significato è costruito attraverso il discorso. Questo approccio fa riferimento anche alla teoria della costruzione di sé di Guichard (2005) e della costruzione della vita professionale di Savickas (2005), che descrivono le azioni utili a facilitare la progettazione del proprio futuro. Particolare attenzione viene data agli interventi nel corso dell'arco di vita, olistici, contestuali e preventivi.

Subclinical thyroid dysfunction, cardiac function, and the risk of heart failure. The Cardiovascular Health study.

OBJECTIVES: The goal of this study was to determine whether subclinical thyroid dysfunction was associated with incident heart failure (HF) and echocardiogram abnormalities. BACKGROUND: Subclinical hypothyroidism and hyperthyroidism have been associated with cardiac dysfunction. However, long-term data on the risk of HF are limited. METHODS: We studied 3,044 adults>or=65 years of age who initially were free of HF in the Cardiovascular Health Study. We compared adjudicated HF events over a mean 12-year follow-up and changes in cardiac function over the course of 5 years among euthyroid participants, those with subclinical hypothyroidism (subdivided by thyroid-stimulating hormone [TSH] levels: 4.5 to 9.9, >or=10.0 mU/l), and those with subclinical hyperthyroidism. RESULTS: Over the course of 12 years, 736 participants developed HF events. Participants with TSH>or=10.0 mU/l had a greater incidence of HF compared with euthyroid participants (41.7 vs. 22.9 per 1,000 person years, p=0.01; adjusted hazard ratio: 1.88; 95% confidence interval: 1.05 to 3.34). Baseline peak E velocity, which is an echocardiographic measurement of diastolic function associated with incident HF in the CHS cohort, was greater in those patients with TSH>or=10.0 mU/l compared with euthyroid participants (0.80 m/s vs. 0.72 m/s, p=0.002). Over the course of 5 years, left ventricular mass increased among those with TSH>or=10.0 mU/l, but other echocardiographic measurements were unchanged. Those patients with TSH 4.5 to 9.9 mU/l or with subclinical hyperthyroidism had no increase in risk of HF. CONCLUSIONS: Compared with euthyroid older adults, those adults with TSH>or=10.0 mU/l have a moderately increased risk of HF and alterations in cardiac function but not older adults with TSH<10.0 mU/l. Clinical trials should assess whether the risk of HF might be ameliorated by thyroxine replacement in individuals with TSH>or=10.0 mU/l.

Association of major and minor ECG abnormalities with coronary heart disease events.

CONTEXT: In populations of older adults, prediction of coronary heart disease (CHD) events through traditional risk factors is less accurate than in middle-aged adults. Electrocardiographic (ECG) abnormalities are common in older adults and might be of value for CHD prediction. OBJECTIVE: To determine whether baseline ECG abnormalities or development of new and persistent ECG abnormalities are associated with increased CHD events. DESIGN, SETTING, AND PARTICIPANTS: A population-based study of 2192 white and black older adults aged 70 to 79 years from the Health, Aging, and Body Composition Study (Health ABC Study) without known cardiovascular disease. Adjudicated CHD events were collected over 8 years between 1997-1998 and 2006-2007. Baseline and 4-year ECG abnormalities were classified according to the Minnesota Code as major and minor. Using Cox proportional hazards regression models, the addition of ECG abnormalities to traditional risk factors were examined to predict CHD events. MAIN OUTCOME MEASURE: Adjudicated CHD events (acute myocardial infarction [MI], CHD death, and hospitalization for angina or coronary revascularization). RESULTS: At baseline, 276 participants (13%) had minor and 506 (23%) had major ECG abnormalities. During follow-up, 351 participants had CHD events (96 CHD deaths, 101 acute MIs, and 154 hospitalizations for angina or coronary revascularizations). Both baseline minor and major ECG abnormalities were associated with an increased risk of CHD after adjustment for traditional risk factors (17.2 per 1000 person-years among those with no abnormalities; 29.3 per 1000 person-years; hazard ratio [HR], 1.35; 95% CI, 1.02-1.81; for minor abnormalities; and 31.6 per 1000 person-years; HR, 1.51; 95% CI, 1.20-1.90; for major abnormalities). When ECG abnormalities were added to a model containing traditional risk factors alone, 13.6% of intermediate-risk participants with both major and minor ECG abnormalities were correctly reclassified (overall net reclassification improvement [NRI], 7.4%; 95% CI, 3.1%-19.0%; integrated discrimination improvement, 0.99%; 95% CI, 0.32%-2.15%). After 4 years, 208 participants had new and 416 had persistent abnormalities. Both new and persistent ECG abnormalities were associated with an increased risk of subsequent CHD events (HR, 2.01; 95% CI, 1.33-3.02; and HR, 1.66; 95% CI, 1.18-2.34; respectively). When added to the Framingham Risk Score, the NRI was not significant (5.7%; 95% CI, -0.4% to 11.8%). CONCLUSIONS: Major and minor ECG abnormalities among older adults were associated with an increased risk of CHD events. Depending on the model, adding ECG abnormalities was associated with improved risk prediction beyond traditional risk factors.

Obstructive Sleep Apnea Severity and Overnight Body Fluid Shift before and after Hemodialysis.

BACKGROUND AND OBJECTIVES: Obstructive sleep apnea is associated with significantly increased cardiovascular morbidity and mortality. Fluid overload may promote obstructive sleep apnea in patients with ESRD through an overnight fluid shift from the legs to the neck soft tissues. Body fluid shift and severity of obstructive sleep apnea before and after hemodialysis were compared in patients with ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Seventeen patients with hemodialysis and moderate to severe obstructive sleep apnea were included. Polysomnographies were performed the night before and after hemodialysis to assess obstructive sleep apnea, and bioimpedance was used to measure fluid overload and leg fluid volume. RESULTS: The mean overnight rostral fluid shift was 1.27±0.41 L prehemodialysis; it correlated positively with fluid overload volume (r=0.39; P=0.02) and was significantly lower posthemodialysis (0.78±0.38 L; P<0.001). There was no significant difference in the mean obstructive apnea-hypopnea index before and after hemodialysis (46.8±22.0 versus 42.1±18.6 per hour; P=0.21), but obstructive apnea-hypopnea index was significantly lower posthemodialysis (-10.1±10.8 per hour) in the group of 12 patients, with a concomitant reduction of fluid overload compared with participants without change in fluid overload (obstructive apnea-hypopnea index +8.2±16.1 per hour; P<0.01). A lower fluid overload after hemodialysis was significantly correlated (r=0.49; P=0.04) with a lower obstructive apnea-hypopnea index. Fluid overload-assessed by bioimpedance-was the best predictor of the change in obstructive apnea-hypopnea index observed after hemodialysis (standardized r=-0.68; P=0.01) in multivariate regression analysis. CONCLUSIONS: Fluid overload influences overnight rostral fluid shift and obstructive sleep apnea severity in patients with ESRD undergoing intermittent hemodialysis. Although no benefit of hemodialysis on obstructive sleep apnea severity was observed in the whole group, the change in obstructive apnea-hypopnea index was significantly correlated with the change in fluid overload after hemodialysis. Moreover, the subgroup with lower fluid overload posthemodialysis showed a significantly lower obstructive sleep apnea severity, which provides a strong incentive to further study whether optimizing fluid status in patients with obstructive sleep apnea and ESRD will improve the obstructive apnea-hypopnea index.

Sleep in vitro : Erk pathway regulates sleep duration and sleep related genes

To date, for most biological and physiological phenomena, the scientific community has reach a consensus on their related function, except for sleep, which has an undetermined, albeit mystery, function. To further our understanding of sleep function(s), we first focused on the level of complexity at which sleep-like phenomenon can be observed. This lead to the development of an in vitro model. The second approach was to understand the molecular and cellular pathways regulating sleep and wakefulness, using both our in vitro and in vivo models. The third approach (ongoing) is to look across evolution when sleep or wakefulness appears. (1) To address the question as to whether sleep is a cellular property and how this is linked to the entire brain functioning, we developed a model of sleep in vitro by using dissociated primary cortical cultures. We aimed at simulating the major characteristics of sleep and wakefulness in vitro. We have shown that mature cortical cultures display a spontaneous electrical activity similar to sleep. When these cultures are stimulated by waking neurotransmitters, they show a tonic firing activity, similar to wakefulness, but return spontaneously to the "sleep-like" state 24h after stimulation. We have also shown that transcriptional, electrophysiological, and metabolic correlates of sleep and wakefulness can be reliably detected in dissociated cortical cultures. (2) To further understand at which molecular and cellular levels changes between sleep and wakefulness occur, we have used a pharmacological and systematic gene transcription approach in vitro and discovered a major role played by the Erk pathway. Indeed, pharmacological inhibition of this pathway in living animals decreased sleep by 2 hours per day and consolidated both sleep and wakefulness by reducing their fragmentation. (3) Finally, we tried to evaluate the presence of sleep in one of the most primitive species with a neural network. We set up Hydra as a model organism. We hypothesized that sleep as a cellular (neuronal) property may occur with the appearance of the most primitive nervous system. We were able to show that Hydra have periodic rest phases amounting to up to 5 hours per day. In conclusion, our work established an in vitro model to study sleep, discovered one of the major signaling pathways regulating vigilance states, and strongly suggests that sleep is a cellular property highly conserved at the molecular level during evolution. -- Jusqu'à ce jour, la communauté scientifique s'est mise d'accord sur la fonction d'une majorité des processus physiologiques, excepté pour le sommeil. En effet, la fonction du sommeil reste un mystère, et aucun consensus n'est atteint le concernant. Pour mieux comprendre la ou les fonctions du sommeil, (1) nous nous sommes d'abord concentré sur le niveau de complexité auquel un état ressemblant au sommeil peut être observé. Nous avons ainsi développé un modèle du sommeil in vitro, (2) nous avons disséqué les mécanismes moléculaires et cellulaires qui pourraient réguler le sommeil, (3) nous avons cherché à savoir si un état de sommeil peut être trouvé dans l'hydre, l'animal le plus primitif avec un système nerveux. (1) Pour répondre à la question de savoir à quel niveau de complexité apparaît un état de sommeil ou d'éveil, nous avons développé un modèle du sommeil, en utilisant des cellules dissociées de cortex. Nous avons essayé de reproduire les corrélats du sommeil et de l'éveil in vitro. Pour ce faire, nous avons développé des cultures qui montrent les signes électrophysiologiques du sommeil, puis quand stimulées chimiquement passent à un état proche de l'éveil et retournent dans un état de sommeil 24 heures après la stimulation. Notre modèle n'est pas parfait, mais nous avons montré que nous pouvions obtenir les corrélats électrophysiologiques, transcriptionnels et métaboliques du sommeil dans des cellules corticales dissociées. (2) Pour mieux comprendre ce qui se passe au niveau moléculaire et cellulaire durant les différents états de vigilance, nous avons utilisé ce modèle in vitro pour disséquer les différentes voies de signalisation moléculaire. Nous avons donc bloqué pharmacologiquement les voies majeures. Nous avons mis en évidence la voie Erkl/2 qui joue un rôle majeur dans la régulation du sommeil et dans la transcription des gènes qui corrèlent avec le cycle veille-sommeil. En effet, l'inhibition pharmacologique de cette voie chez la souris diminue de 2 heures la quantité du sommeil journalier et consolide l'éveil et le sommeil en diminuant leur fragmentation. (3) Finalement, nous avons cherché la présence du sommeil chez l'Hydre. Pour cela, nous avons étudié le comportement de l'Hydre pendant 24-48h et montrons que des périodes d'inactivité, semblable au sommeil, sont présentes dans cette espèce primitive. L'ensemble de ces travaux indique que le sommeil est une propriété cellulaire, présent chez tout animal avec un système nerveux et régulé par une voie de signalisation phylogénétiquement conservée.