Emotional reactivity at 12 months in very preterm infants born at <29 weeks of gestation.

The present study evaluated the socio-emotional development of very preterm born infants at 12 months corrected age. Forty-one infants born very preterm (<29 weeks of gestation) were compared to 22 infants born full term on a standardized behavioral assessment and a parental temperament questionnaire, both measuring emotional reactivity to joy, anger and fear, as well as sustained attention. The behavioral assessment showed that very preterm infants exhibited as much joy as full term infants during a joy-eliciting episode. However, they expressed a significantly higher reactivity in anger-eliciting situations and a reduced reactivity toward fear-eliciting situations. For all three emotion-eliciting situations, the preterm infants reacted with a higher level of motor activity. The preterm infants also exhibited a distinct attention pattern with a significantly higher initial attention level which declined rapidly throughout the episode. The questionnaire did not show any group differences. The clinical relevance of these results in terms of preliminary hallmarks of later behavioral difficulties such attention deficit/hyperactivity disorder are discussed as well as the inconsistencies observed between the questionnaire and the behavioral assessment.

Lu pour vous: Augmenter l'activité physique chez l'enfant: rien ne sert de faire courir ?

Résumé de: Metcalf B, et al. Effectiveness of intervention on physical activity of children: systematic review and meta-analysis of controlled trials with objectively measured outcomes (EarlyBird 54). BMJ. 2012 Sep 27;345:e5888. doi: 10.1136/bmj.e5888. PMID: 23044984.

5-HT2A and alpha1b-adrenergic receptors entirely mediate dopamine release, locomotor response and behavioural sensitization to opiates and psychostimulants.

Addictive properties of drugs of misuse are generally considered to be mediated by an increased release of dopamine (DA) in the ventral striatum. However, recent experiments indicated an implication of alpha1b-adrenergic receptors in behavioural responses to psychostimulants and opiates. We show now that DA release induced in the ventral striatum by morphine (20 mg/kg) is completely blocked by prazosin (1 mg/kg), an alpha1-adrenergic antagonist. However, morphine-induced increases in DA release in the ventral striatum were found to be similar in mice deleted for the alpha1b-adrenergic receptor (alpha1b-AR KO) and in wild-type (WT) mice, suggesting the presence of a compensatory mechanism. This acute morphine-evoked DA release was completely blocked in alpha1b-AR KO mice by SR46349B (1 mg/kg), a 5-HT2A antagonist. SR46349B also completely blocked, in alpha1b-AR KO mice, the locomotor response and the development of behavioural sensitization to morphine (20 mg/kg) and D-amphetamine (2 mg/kg). Accordingly, the concomitant blockade of 5-HT2A and alpha1b-adrenergic receptors in WT mice entirely blocked acute locomotor responses but also the development of behavioural sensitization to morphine, D-amphetamine or cocaine (10 mg/kg). We observed, nevertheless, that inhibitory effects of each antagonist on locomotor responses to morphine or D-amphetamine were more than additive (160%) in naïve WT mice but not in those sensitized to either drug. Because of these latter data and the possible compensation by 5-HT2A receptors for the genetic deletion of alpha1b-adrenergic receptors, we postulate the existence of a functional link between these receptors, which vanishes during the development of behavioural sensitization.

Sound objects in time, space and action

SOUND OBJECTS IN TIME, SPACE AND ACTIONThe term "sound object" describes an auditory experience that is associated with an acoustic event produced by a sound source. At cortical level, sound objects are represented by temporo-spatial activity patterns within distributed neural networks. This investigation concerns temporal, spatial and action aspects as assessed in normal subjects using electrical imaging or measurement of motor activity induced by transcranial magnetic stimulation (TMS).Hearing the same sound again has been shown to facilitate behavioral responses (repetition priming) and to modulate neural activity (repetition suppression). In natural settings the same source is often heard again and again, with variations in spectro-temporal and spatial characteristics. I have investigated how such repeats influence response times in a living vs. non-living categorization task and the associated spatio-temporal patterns of brain activity in humans. Dynamic analysis of distributed source estimations revealed differential sound object representations within the auditory cortex as a function of the temporal history of exposure to these objects. Often heard sounds are coded by a modulation in a bilateral network. Recently heard sounds, independently of the number of previous exposures, are coded by a modulation of a left-sided network.With sound objects which carry spatial information, I have investigated how spatial aspects of the repeats influence neural representations. Dynamics analyses of distributed source estimations revealed an ultra rapid discrimination of sound objects which are characterized by spatial cues. This discrimination involved two temporo-spatially distinct cortical representations, one associated with position-independent and the other with position-linked representations within the auditory ventral/what stream.Action-related sounds were shown to increase the excitability of motoneurons within the primary motor cortex, possibly via an input from the mirror neuron system. The role of motor representations remains unclear. I have investigated repetition priming-induced plasticity of the motor representations of action sounds with the measurement of motor activity induced by TMS pulses applied on the hand motor cortex. TMS delivered to the hand area within the primary motor cortex yielded larger magnetic evoked potentials (MEPs) while the subject was listening to sounds associated with manual than non- manual actions. Repetition suppression was observed at motoneuron level, since during a repeated exposure to the same manual action sound the MEPs were smaller. I discuss these results in terms of specialized neural network involved in sound processing, which is characterized by repetition-induced plasticity.Thus, neural networks which underlie sound object representations are characterized by modulations which keep track of the temporal and spatial history of the sound and, in case of action related sounds, also of the way in which the sound is produced.LES OBJETS SONORES AU TRAVERS DU TEMPS, DE L'ESPACE ET DES ACTIONSLe terme "objet sonore" décrit une expérience auditive associée avec un événement acoustique produit par une source sonore. Au niveau cortical, les objets sonores sont représentés par des patterns d'activités dans des réseaux neuronaux distribués. Ce travail traite les aspects temporels, spatiaux et liés aux actions, évalués à l'aide de l'imagerie électrique ou par des mesures de l'activité motrice induite par stimulation magnétique trans-crânienne (SMT) chez des sujets sains. Entendre le même son de façon répétitive facilite la réponse comportementale (amorçage de répétition) et module l'activité neuronale (suppression liée à la répétition). Dans un cadre naturel, la même source est souvent entendue plusieurs fois, avec des variations spectro-temporelles et de ses caractéristiques spatiales. J'ai étudié la façon dont ces répétitions influencent le temps de réponse lors d'une tâche de catégorisation vivant vs. non-vivant, et les patterns d'activité cérébrale qui lui sont associés. Des analyses dynamiques d'estimations de sources ont révélé des représentations différenciées des objets sonores au niveau du cortex auditif en fonction de l'historique d'exposition à ces objets. Les sons souvent entendus sont codés par des modulations d'un réseau bilatéral. Les sons récemment entendus sont codé par des modulations d'un réseau du côté gauche, indépendamment du nombre d'expositions. Avec des objets sonores véhiculant de l'information spatiale, j'ai étudié la façon dont les aspects spatiaux des sons répétés influencent les représentations neuronales. Des analyses dynamiques d'estimations de sources ont révélé une discrimination ultra rapide des objets sonores caractérisés par des indices spatiaux. Cette discrimination implique deux représentations corticales temporellement et spatialement distinctes, l'une associée à des représentations indépendantes de la position et l'autre à des représentations liées à la position. Ces représentations sont localisées dans la voie auditive ventrale du "quoi".Des sons d'actions augmentent l'excitabilité des motoneurones dans le cortex moteur primaire, possiblement par une afférence du system des neurones miroir. Le rôle des représentations motrices des sons d'actions reste peu clair. J'ai étudié la plasticité des représentations motrices induites par l'amorçage de répétition à l'aide de mesures de potentiels moteurs évoqués (PMEs) induits par des pulsations de SMT sur le cortex moteur de la main. La SMT appliquée sur le cortex moteur primaire de la main produit de plus grands PMEs alors que les sujets écoutent des sons associée à des actions manuelles en comparaison avec des sons d'actions non manuelles. Une suppression liée à la répétition a été observée au niveau des motoneurones, étant donné que lors de l'exposition répétée au son de la même action manuelle les PMEs étaient plus petits. Ces résultats sont discuté en termes de réseaux neuronaux spécialisés impliqués dans le traitement des sons et caractérisés par de la plasticité induite par la répétition. Ainsi, les réseaux neuronaux qui sous-tendent les représentations des objets sonores sont caractérisés par des modulations qui gardent une trace de l'histoire temporelle et spatiale du son ainsi que de la manière dont le son a été produit, en cas de sons d'actions.

Myosin Vs organize actin cables in fission yeast.

Myosin V motors are believed to contribute to cell polarization by carrying cargoes along actin tracks. In Schizosaccharomyces pombe, Myosin Vs transport secretory vesicles along actin cables, which are dynamic actin bundles assembled by the formin For3 at cell poles. How these flexible structures are able to extend longitudinally in the cell through the dense cytoplasm is unknown. Here we show that in myosin V (myo52 myo51) null cells, actin cables are curled, bundled, and fail to extend into the cell interior. They also exhibit reduced retrograde flow, suggesting that formin-mediated actin assembly is impaired. Myo52 may contribute to actin cable organization by delivering actin regulators to cell poles, as myoV defects are partially suppressed by diverting cargoes toward cell tips onto microtubules with a kinesin 7-Myo52 tail chimera. In addition, Myo52 motor activity may pull on cables to provide the tension necessary for their extension and efficient assembly, as artificially tethering actin cables to the nuclear envelope via a Myo52 motor domain restores actin cable extension and retrograde flow in myoV mutants. Together these in vivo data reveal elements of a self-organizing system in which the motors shape their own tracks by transporting cargoes and exerting physical pulling forces.

Troubles sexuels masculins et obésité [Male sexual dysfunction and obesity].

Obesity concerns more than 200 million people in the world, with an increasing prevalence in western countries. It is closely related to multiple medical conditions, such as diabetes and hypertension. It was recently shown that testosterone deficiency syndrome and erectile dysfunction (ED) are also linked to male obesity. In this group of patients, ED may be due to defects in corpus cavernosum relaxation, endocrine modifications and nerve signal alterations. Weight loss and increased physical activities can improve erectile function in 30% of obese patients. Additional medical treatments of ED enhance erectile function in more than 80% of patients. Self image improvement associated with appropriate erectile dysfunction medical treatment allow better sexual life and potentially increased motivation for weight loss.

Energy cost of walking and gait instability in healthy 65- and 80-yr-olds.

This study tested whether the lower economy of walking in healthy elderly subjects is due to greater gait instability. We compared the energy cost of walking and gait instability (assessed by stride to stride changes in the stride time) in octogenarians (G80, n = 10), 65-yr-olds (G65, n = 10), and young controls (G25, n = 10) walking on a treadmill at six different speeds. The energy cost of walking was higher for G80 than for G25 across the different walking speeds (P < 0.05). Stride time variability at preferred walking speed was significantly greater in G80 (2.31 +/- 0.68%) and G65 (1.93 +/- 0.39%) compared with G25 (1.40 +/- 0.30%; P < 0.05). There was no significant correlation between gait instability and energy cost of walking at preferred walking speed. These findings demonstrated greater energy expenditure in healthy elderly subjects while walking and increased gait instability. However, no relationship was noted between these two variables. The increase in energy cost is probably multifactorial, and our results suggest that gait instability is probably not the main contributing factor in this population. We thus concluded that other mechanisms, such as the energy expenditure associated with walking movements and related to mechanical work, or neuromuscular factors, are more likely involved in the higher cost of walking in elderly people.

Reciprocal regulation of brain and muscle Arnt-like protein 1 and peroxisome proliferator-activated receptor alpha defines a novel positive feedback loop in the rodent liver circadian clock.

Recent evidence has emerged that peroxisome proliferator-activated receptor alpha (PPARalpha), which is largely involved in lipid metabolism, can play an important role in connecting circadian biology and metabolism. In the present study, we investigated the mechanisms by which PPARalpha influences the pacemakers acting in the central clock located in the suprachiasmatic nucleus and in the peripheral oscillator of the liver. We demonstrate that PPARalpha plays a specific role in the peripheral circadian control because it is required to maintain the circadian rhythm of the master clock gene brain and muscle Arnt-like protein 1 (bmal1) in vivo. This regulation occurs via a direct binding of PPARalpha on a potential PPARalpha response element located in the bmal1 promoter. Reversely, BMAL1 is an upstream regulator of PPARalpha gene expression. We further demonstrate that fenofibrate induces circadian rhythm of clock gene expression in cell culture and up-regulates hepatic bmal1 in vivo. Together, these results provide evidence for an additional regulatory feedback loop involving BMAL1 and PPARalpha in peripheral clocks.

Inconspicuous assessment of diet-induced thermogenesis using whole-body indirect calorimetry.

We report a novel technique for computing diet-induced thermogenesis using data from 24-h respiration chamber measurements of 76 subjects. Physical activity (PA) was determined using a radar system to assess its duration and an accelerometer to evaluate its intensity. The regression line relating PA and energy expenditure facilitated calculation of the integrated thermogenic response to the total energy ingested (11.4% ± 3.8%), which is consistent with the values classically reported in the literature (10%) at the group level.

A fast-track program reduces complications and length of hospital stay after open colonic surgery.

BACKGROUND & AIMS: A fast-track program is a multimodal approach for patients undergoing colonic surgery that combines stringent regimens of perioperative care (fluid restriction, optimized analgesia, forced mobilization, and early oral feeding) to reduce perioperative morbidity, hospital stay, and cost. We investigated the impact of a fast-track protocol on postoperative morbidity in patients after open colonic surgery. METHODS: A randomized trial of patients in 4 teaching hospitals in Switzerland included 156 patients undergoing elective open colonic surgery who were assigned to either a fast-track program or standard care. The primary end point was the 30-day complication rate. Secondary end points were severity of complications, hospital stay, and compliance with the fast-track protocol. RESULTS: The fast-track protocol significantly decreased the number of complications (16 of 76 in the fast-track group vs 37 of 75 in the standard care group; P = .0014), resulting in shorter hospital stays (median, 5 days; range, 2-30 vs 9 days, respectively; range, 6-30; P < .0001). There was a trend toward less severe complications in the fast-track group. A multiple logistic regression analysis revealed fluid administration greater than the restriction limits (odds ratio, 4.198; 95% confidence interval, 1.7-10.366; P = .002) and a nonfunctioning epidural analgesia (odds ratio, 3.365; 95% confidence interval, 1.367-8.283; P = .008) as independent predictors of postoperative complications. CONCLUSIONS: The fast-track program reduces the rate of postoperative complications and length of hospital stay and should be considered as standard care. Fluid restriction and an effective epidural analgesia are the key factors that determine outcome of the fast-track program.

Ambulatory monitoring of physical activities in patients with Parkinson's disease.

A new ambulatory method of monitoring physical activities in Parkinson's disease (PD) patients is proposed based on a portable data-logger with three body-fixed inertial sensors. A group of ten PD patients treated with subthalamic nucleus deep brain stimulation (STN-DBS) and ten normal control subjects followed a protocol of typical daily activities and the whole period of the measurement was recorded by video. Walking periods were recognized using two sensors on shanks and lying periods were detected using a sensor on trunk. By calculating kinematics features of the trunk movements during the transitions between sitting and standing postures and using a statistical classifier, sit-to-stand (SiSt) and stand-to-sit (StSi) transitions were detected and separated from other body movements. Finally, a fuzzy classifier used this information to detect periods of sitting and standing. The proposed method showed a high sensitivity and specificity for the detection of basic body postures allocations: sitting, standing, lying, and walking periods, both in PD patients and healthy subjects. We found significant differences in parameters related to SiSt and StSi transitions between PD patients and controls and also between PD patients with and without STN-DBS turned on. We concluded that our method provides a simple, accurate, and effective means to objectively quantify physical activities in both normal and PD patients and may prove useful to assess the level of motor functions in the latter.

The Lausanne cohort Lc65+: a population-based prospective study of the manifestations, determinants and outcomes of frailty

BACKGROUND: Frailty is a relatively new geriatric concept referring to an increased vulnerability to stressors. Various definitions have been proposed, as well as a range of multidimensional instruments for its measurement. More recently, a frailty phenotype that predicts a range of adverse outcomes has been described. Understanding frailty is a particular challenge both from a clinical and a public health perspective because it may be a reversible precursor of functional dependence. The Lausanne cohort Lc65+ is a longitudinal study specifically designed to investigate the manifestations of frailty from its first signs in the youngest old, identify medical and psychosocial determinants, and describe its evolution and related outcomes. METHODS/DESIGN: The Lc65+ cohort was launched in 2004 with the random selection of 3054 eligible individuals aged 65 to 70 (birth year 1934-1938) in the non-institutionalized population of Lausanne (Switzerland). The baseline data collection was completed among 1422 participants in 2004-2005 through questionnaires, examination and performance tests. It comprised a wide range of medical and psychosocial dimensions, including a life course history of adverse events. Outcomes measures comprise subjective health, limitations in activities of daily living, mobility impairments, development of medical conditions or chronic health problems, falls, institutionalization, health services utilization, and death. Two additional random samples of 65-70 years old subjects will be surveyed in 2009 (birth year 1939-1943) and in 2014 (birth year 1944-1948). DISCUSSION: The Lc65+ study focuses on the sequence "Determinants --> Components --> Consequences" of frailty. It currently provides information on health in the youngest old and will allow comparisons to be made between the profiles of aging individuals born before, during and at the end of the Second World War.

Kernohan's notch and misdiagnosis of disorders of consciousness.

A 69-year-old man presented with a sudden headache followed by unconsciousness. There was no head injury. The Glasgow Coma Scale (GCS) score was 3/15 and there was a left mydriasis, unreactive to light. The CT-scan showed a left acute subdural haematoma causing a remarkable mass effect. A supratentorial hemispheric craniotomy was performed. Nevertheless, after several weeks at the intensive care unit (ICU), the patient was still unresponsive to external stimuli and did not show any motor activity. A comfort care attitude was decided on with the family and the patient was extubated. However, a few days later, the patient subsequently showed a surprisingly favourable course, with improved wakefulness. Indeed, the GCS score improved, and the treatment plan was modified so that the patient benefited from rehabilitation. The MRI showed a right cerebral peduncle lesion, consistent with a Kernohan-Woltman notch phenomenon (KWNP). Six months later, the patient was able to walk and live quite normally.