Development of an activity index for adult eosinophilic esophagitis: international experts propose dysphagia, withish exudates on endoscopy and peripheral eosinophilia as items with closest association to EoE activity

Background and Aims: Eosinophilic Esophagitis (EoE) is reported with increasing frequency over the last two decades. However, it is still unknown whether this reflects a true increase in incidence or just an increased awareness by gastroenterologists. Therefore, we evaluated the incidence and cumulative prevalence of EoE in Olten county over the last 20 years. Methods: Olten county is an area of approximately 91,000 inhabitants without pronounced demographic changes in the last two decades. EoE evaluation is based upon two gastroenterology centers and one pathology center. No public programs for increased EoE awareness were implemented in this region. All EoE patients diagnosed from 1989 to 2009 were entered prospectively into the Olten county database. Results: Fourty-six patients (76% males, mean age 41±16 yrs) were diagnosed with EoE from 1989 to 2009. Ninety-four percent presented with dysphagia. In 70% of the patients concomitant allergies were found. The number of upper endoscopies per year was stable during the entire observation period. An average annual incidence rate of 2/100,000 was found (range 0-8) with a marked increase in the period from 2001 to 2009. A current cumulative EoE prevalence of 43/100,000 inhabitants was calculated. The mean diagnostic delay (time from first symptoms to diagnosis) was 4.3 years from 1989 to 1998 and 4.8 years from 1999 to 2009. Conclusions: Over the last 20 years, a significant increase in EoE incidence was found in a stable indicator region of Switzerland. The constant rate of upper endoscopies, the constant diagnostic delay, as well as the lack of EoE awareness programs in Olten county indicate a true increase in EoE incidence.

Activity of dalbavancin, alone and in combination with rifampicin, against meticillin-resistant Staphylococcus aureus in a foreign-body infection model.

The activity of dalbavancin, a representative of the lipoglycopeptide antibiotics, alone and in combination with rifampicin, was investigated against meticillin-resistant Staphylococcus aureus (MRSA) in a foreign-body infection model in guinea pigs. The MIC, MBC and time-kill profile of dalbavancin were determined for MRSA ATCC 43300 in the logarithmic (MBClog) and stationary (MBCstat) growth phases. The pharmacokinetic profile of dalbavancin was determined in sterile cage fluid in guinea pigs. The activity of intraperitoneal dalbavancin (40, 60 or 80mg/kg as a single dose), rifampicin (12.5mg/kg/12h for 4 days) and their combination was assessed against planktonic and biofilm MRSA. The MIC of dalbavancin was 0.078mg/L; MBClog and MBCstat were both >128Ã- MIC. In time-kill studies, bacterial reduction of 3log10CFU/mL was achieved after 48h at â0/00¥32Ã- MIC (logarithmic growth) and at â0/00¥1Ã- MIC (stationary growth). Dalbavancin was neither synergistic nor antagonistic with rifampicin, and prevented the emergence of rifampicin resistance in vitro. The half-life of dalbavancin in cage fluid was 35.8-45.4h and the concentration remained above the MIC of MRSA during 7 days after a single dose. Dalbavancin reduced planktonic MRSA in cage fluid at high dose (60mg/kg and 80mg/kg) but failed to eradicate biofilm MRSA from cages. In combination with rifampicin, dalbavancin at 80mg/kg cured 36% of infected cages, and emergence of rifampicin resistance was completely prevented. Dalbavancin at 80mg/kg and in combination with rifampicin eradicated approximately one-third of cage-associated MRSA infections and prevented emergence of rifampicin resistance.

A case of acute retinal pigment epithelitis: spectral domain optical coherence tomography time course and physiopathologic hypothesis.

PURPOSE: To report the time course of retinal morphologic changes in a patient with acute retinal pigment epithelitis (ARPE) using spectral domain optical coherence tomography (SD-OCT). METHODS: A 30-year old man was referred for blurred vision of his right eye after five days that appeared suddenly 15 days after recovery from a flu-like syndrome. SD-OCT was performed immediately, followed by fluorescein and infracyanine angiography at eight days and then at three weeks. RESULTS: At presentation, a bubble of sub-macular deposit was observed on the right macula with central golden micronodules in a honeycomb pattern. SD-OCT showed an "anterior dislocation" of all the retinal layers up to the inner/outer segment (IS/OS) line and irregular deposits at the OS level together with thickening of the retinal pigment epithelial (RPE) layer. As visual acuity increased, eight days later, the OCT showed reduction of the sub-retinal deposits and an abnormal hyperflectivity of the sub-retinal and RPE layers was observed. The patient showed a positive serology for picornavirus. DISCUSSION: The acute SD-OCT sections of this patient with ARPE were compared with histological sections of a 35 day old Royal College of Surgeons rat. Similar findings could be observed, with preservation of the IS/OS line and accumulation of debris at the OS level, suggesting that ARPE symptoms could result from a transient phagocytic dysfunction of the RPE at the fovea, inducing reversible accumulation of undigested OS. Picornaviruses comprising enterovirus and coxsachievirus described as being associated with acute chorioretinitis. In this case, it was responsible for ARPE. CONCLUSION: We hypothesize that ARPE syndrome results from a transient dysfunction of RPE, which can occur as a post viral reaction.

Early, low-level auditory-somatosensory multisensory interactions impact reaction time speed.

Several lines of research have documented early-latency non-linear response interactions between audition and touch in humans and non-human primates. That these effects have been obtained under anesthesia, passive stimulation, as well as speeded reaction time tasks would suggest that some multisensory effects are not directly influencing behavioral outcome. We investigated whether the initial non-linear neural response interactions have a direct bearing on the speed of reaction times. Electrical neuroimaging analyses were applied to event-related potentials in response to auditory, somatosensory, or simultaneous auditory-somatosensory multisensory stimulation that were in turn averaged according to trials leading to fast and slow reaction times (using a median split of individual subject data for each experimental condition). Responses to multisensory stimulus pairs were contrasted with each unisensory response as well as summed responses from the constituent unisensory conditions. Behavioral analyses indicated that neural response interactions were only implicated in the case of trials producing fast reaction times, as evidenced by facilitation in excess of probability summation. In agreement, supra-additive non-linear neural response interactions between multisensory and the sum of the constituent unisensory stimuli were evident over the 40-84 ms post-stimulus period only when reaction times were fast, whereas subsequent effects (86-128 ms) were observed independently of reaction time speed. Distributed source estimations further revealed that these earlier effects followed from supra-additive modulation of activity within posterior superior temporal cortices. These results indicate the behavioral relevance of early multisensory phenomena.

Neuroligin-1 links neuronal activity to sleep-wake regulation.

Maintaining wakefulness is associated with a progressive increase in the need for sleep. This phenomenon has been linked to changes in synaptic function. The synaptic adhesion molecule Neuroligin-1 (NLG1) controls the activity and synaptic localization of N-methyl-d-aspartate receptors, which activity is impaired by prolonged wakefulness. We here highlight that this pathway may underlie both the adverse effects of sleep loss on cognition and the subsequent changes in cortical synchrony. We found that the expression of specific Nlg1 transcript variants is changed by sleep deprivation in three mouse strains. These observations were associated with strain-specific changes in synaptic NLG1 protein content. Importantly, we showed that Nlg1 knockout mice are not able to sustain wakefulness and spend more time in nonrapid eye movement sleep than wild-type mice. These changes occurred with modifications in waking quality as exemplified by low theta/alpha activity during wakefulness and poor preference for social novelty, as well as altered delta synchrony during sleep. Finally, we identified a transcriptional pathway that could underlie the sleep/wake-dependent changes in Nlg1 expression and that involves clock transcription factors. We thus suggest that NLG1 is an element that contributes to the coupling of neuronal activity to sleep/wake regulation.

Effect of temperature and moisture on the dormancy and activation pattern of Oxalis latifolia bulbs

Con objeto de buscar información para un mejor control de Oxalis latifolia Kunth, se ha estudiado el efecto que presentan la temperatura y la humedad sobre la activación de sus bulbos, tanto en la forma común como en la forma Cornwall de la misma. Los bulbos de la mala hierba se mantuvieron en un refrigerador a +4°C durante 13, 20, 27, 41, 48 y 55 días. Se sacaron tres grupos de 30 bulbos de cada forma en cada fecha de muestreo y se colocaron a 21°C; 15 de ellos se mantuvieron en condiciones de sequía —no se regaron— y otros 15 en condiciones de humedad —añadiendo el agua necesaria—. Los resultados muestran que la activación ocurre durante un período prolongado de tiempo en ambas formas, tanto en seco como en húmedo. También se observó que los bulbos secos se activaron antes que los húmedos y los de la forma común antes que los Cornwall. Se observaron dos patrones de activación: los bulbos secos de la forma común generalmente presentaron una activación que sigue un patrón logarítmico, mientras que sus bulbos humedecidos mostraron una tendencia linear; los bulbos Cornwall se activaron con una tendencia exponencial en la mayoría de los casos. El tiempo medio requerido para la activación después del almacenamiento en frío fue constante en la forma común, sin embargo la activación de Cornwall fue más rápida cuanto más tiempo permanecieron almacenados en frío.

Intracranial Aneurysm Rupture Is Predicted by Measures of Solar Activity.

OBJECTIVE: The cause precipitating intracranial aneurysm rupture remains unknown in many cases. It has been observed that aneurysm ruptures are clustered in time, but the trigger mechanism remains obscure. Because solar activity has been associated with cardiovascular mortality and morbidity, we decided to study its association to aneurysm rupture in the Swiss population. METHODS: Patient data were extracted from the Swiss SOS database, at time of analysis covering 918 consecutive patients with angiography-proven aneurysmal subarachnoid hemorrhage treated at 7 Swiss neurovascular centers between January 1, 2009, and December 31, 2011. The daily rupture frequency (RF) was correlated to the absolute amount and the change in various parameters of interest representing continuous measurements of solar activity (radioflux [F10.7 index], solar proton flux, solar flare occurrence, planetary K-index/planetary A-index, Space Environment Services Center [SESC] sunspot number and sunspot area) using Poisson regression analysis. RESULTS: During the period of interest, there were 517 days without recorded aneurysm rupture. There were 398, 139, 27, 12, 1, and 1 days with 1, 2, 3, 4, 5, and 6 ruptures per day. Poisson regression analysis demonstrated a significant correlation of F10.7 index and RF (incidence rate ratio [IRR] = 1.006303; standard error (SE) 0.0013201; 95% confidence interval (CI) 1.003719-1.008894; P < 0.001), according to which every 1-unit increase of the F10.7 index increased the count for an aneurysm to rupture by 0.63%. A likewise statistically significant relationship of both the SESC sunspot number (IRR 1.003413; SE 0.0007913; 95% CI 1.001864-1.004965; P < 0.001) and the sunspot area (IRR 1.000419; SE 0.0000866; 95% CI 1.000249-1.000589; P < 0.001) emerged. All other variables analyzed showed no significant correlation with RF. CONCLUSIONS: We found greater radioflux, SESC sunspot number, and sunspot area to be associated with an increased count of aneurysm rupture. The clinical meaningfulness of this statistical association must be interpreted carefully and future studies are warranted to rule out a type-1 error.

Improvement of the antibacterial activity of daptomycin-loaded polymeric microparticles by Eudragit RL 100: An assessment by isothermal microcalorimetry.

The aim of the present study was to develop novel daptomycin-loaded acrylic microparticles with improved release profiles and antibacterial activity against two clinically relevant methicillin-susceptible and methicillin-resistant Staphylococcus aureus strains (MSSA and MRSA, respectively). Daptomycin was encapsulated into poly(methyl methacrylate) (PMMA) and PMMA-Eudragit RL 100 (EUD) microparticles by a double emulsion-solvent evaporation method. For comparison purposes similar formulations were prepared with vancomycin. Particle morphology, size distribution, encapsulation efficiency, surface charge, physicochemical properties, in vitro release and biocompatibility were assessed. Particles exhibited a micrometer size and a spherical morphology. The addition of EUD to the formulation caused a shift in the surface charge of the particles from negative zeta potential values (100% PMMA formulations) to strongly positive. It also improved daptomycin encapsulation efficiency and release, whereas vancomycin encapsulation and release were strongly hindered. Plain and antibiotic-loaded particles presented comparable biocompatibility profiles. The antibacterial activity of the particles was assessed by isothermal microcalorimetry against both MSSA and MRSA. Daptomycin-loaded PMMA-EUD particles presented the highest antibacterial activity against both strains. The addition of 30% EUD to the daptomycin-loaded PMMA particles caused a 40- and 20-fold decrease in the minimum inhibitory (MIC) and bactericidal concentration (MBC) values, respectively, when compared to the 100% PMMA formulations. On the other hand, vancomycin-loaded microparticles presented the highest antibacterial activity in PMMA particles. Unlike conventional methods, isothermal microcalorimetry proved to be a real-time, sensitive and accurate method for assessment of antibacterial activity of antibiotic-loaded polymeric microparticles. Finally, the addition of EUD to formulations proved to be a powerful strategy to improve daptomycin encapsulation efficiency and release, and consequently improving the microparticles activity against two relevant S. aureus strains.

Dose and time-dependent selective neurotoxicity induced by mephedrone in mice.

Mephedrone is a drug of abuse marketed as 'bath salts'. There are discrepancies concerning its long-term effects. We have investigated the neurotoxicity of mephedrone in mice following different exposition schedules. Schedule 1: four doses of 50 mg/kg. Schedule 2: four doses of 25 mg/kg. Schedule 3: three daily doses of 25 mg/kg, for two consecutive days. All schedules induced, in some animals, an aggressive behavior and hyperthermia as well as a decrease in weight gain. Mephedrone (schedule 1) induced dopaminergic and serotoninergic neurotoxicity that persisted 7 days after exposition. At a lower dose (schedule 2) only a transient dopaminergic injury was found. In the weekend consumption pattern (schedule 3), mephedrone induced dopamine and serotonin transporter loss that was accompanied by a decrease in tyrosine hydroxylase and tryptophan hydroxylase 2 expression one week after exposition. Also, mephedrone induced a depressive-like behavior, as well as a reduction in striatal D2 density, suggesting higher susceptibility to addictive drugs. In cultured cortical neurons, mephedrone induced a concentration-dependent cytotoxic effect. Using repeated doses for 2 days in an elevated ambient temperature we evidenced a loss of frontal cortex dopaminergic and hippocampal serotoninergic neuronal markers that suggest injuries at nerve endings.

Time patterns and perceptions of online learning success factors

Online learning provides the opportunity to work on academic tasks at any time at the same time as doing other activities, such as using in web 2.0 tools. This study identifies factors that contribute to success in online learning from the students¿ perspective and their relationship with time patterns. A survey of learning outputs was used to find relationships between students¿ satisfaction, knowledge acquisition and knowledge transfer with time for working on academic tasks. In this study, 199 students from a university in Mexico completed the survey. Findings suggest that knowledge transfer has a significant association with the number of hours online per day, hours spent on social networks and the use made of e-learning during working hours. Learner satisfaction has a strong relationship with the time in years a learner has been using the Internet and the number of hours devoted to the course per week. The findings of this research will be helpful for faculty and instructional designers for implementing learning strategies.

Dose and time-dependent selective neurotoxicity induced by mephedrone in mice.

Mephedrone is a drug of abuse marketed as 'bath salts'. There are discrepancies concerning its long-term effects. We have investigated the neurotoxicity of mephedrone in mice following different exposition schedules. Schedule 1: four doses of 50 mg/kg. Schedule 2: four doses of 25 mg/kg. Schedule 3: three daily doses of 25 mg/kg, for two consecutive days. All schedules induced, in some animals, an aggressive behavior and hyperthermia as well as a decrease in weight gain. Mephedrone (schedule 1) induced dopaminergic and serotoninergic neurotoxicity that persisted 7 days after exposition. At a lower dose (schedule 2) only a transient dopaminergic injury was found. In the weekend consumption pattern (schedule 3), mephedrone induced dopamine and serotonin transporter loss that was accompanied by a decrease in tyrosine hydroxylase and tryptophan hydroxylase 2 expression one week after exposition. Also, mephedrone induced a depressive-like behavior, as well as a reduction in striatal D2 density, suggesting higher susceptibility to addictive drugs. In cultured cortical neurons, mephedrone induced a concentration-dependent cytotoxic effect. Using repeated doses for 2 days in an elevated ambient temperature we evidenced a loss of frontal cortex dopaminergic and hippocampal serotoninergic neuronal markers that suggest injuries at nerve endings.

Quantifying the time for accurate EEG decoding of single value-based decisions.

BACKGROUND: Recent neuroimaging studies suggest that value-based decision-making may rely on mechanisms of evidence accumulation. However no studies have explicitly investigated the time when single decisions are taken based on such an accumulation process. NEW METHOD: Here, we outline a novel electroencephalography (EEG) decoding technique which is based on accumulating the probability of appearance of prototypical voltage topographies and can be used for predicting subjects' decisions. We use this approach for studying the time-course of single decisions, during a task where subjects were asked to compare reward vs. loss points for accepting or rejecting offers. RESULTS: We show that based on this new method, we can accurately decode decisions for the majority of the subjects. The typical time-period for accurate decoding was modulated by task difficulty on a trial-by-trial basis. Typical latencies of when decisions are made were detected at ∼500ms for 'easy' vs. ∼700ms for 'hard' decisions, well before subjects' response (∼340ms). Importantly, this decision time correlated with the drift rates of a diffusion model, evaluated independently at the behavioral level. COMPARISON WITH EXISTING METHOD(S): We compare the performance of our algorithm with logistic regression and support vector machine and show that we obtain significant results for a higher number of subjects than with these two approaches. We also carry out analyses at the average event-related potential level, for comparison with previous studies on decision-making. CONCLUSIONS: We present a novel approach for studying the timing of value-based decision-making, by accumulating patterns of topographic EEG activity at single-trial level.

Activity patterns and foraging behaviour of Audouin's gulls at the Ebro Delta, NW Mediterranean.

Twenty Audouin´s gulls, Larus audouinii, breeding in the Ebro Delta (NW Mediterranean) were radio-tracked in 1998 to study their foraging behaviour and activity patterns. Some detrimental effects of tagging on the breeding success of the birds were detected, especially when both members of the pair were tagged. The results were actually constrained by the low number of locations due to natural breeding failure and failure in tag emission, as well as the adverse effect of tagging. However, through a combination of aircraft surveys at sea and a fixed station for automatic tracking of the presence of the birds at the colony, novel individual-based information of home ranges and activity patterns was obtained. Trawler fishing activity seemed to influence both the foraging range and habitat use: while trawlers operated, gulls overlapped their fishing grounds with vessels, probably to scavenge on discards. Very few locations were obtained during a trawling moratorium period, although they were all recorded in coastal bays and terrestrial habitats. During the trawling activity period, gulls ranged over a minimum convex polygon area of 2900 km2. Gulls were tracked up to 40 km from the colony, but some individuals were observed beyond 150 km while still breeding. Arrivals and departures from the colony were in accordance with the trawling timetable. However, most birds also showed some nocturnal foraging activity, probably linked to active fishing of clupeoids (following diel migrations) or to the exploitation of purse-seine fishing activity. Foraging trips lasted on average 15 hours: males performed significantly shorter trips than females, which spent more time outside the colony. The proportion of nocturnal time involved in the foraging trips was the same for males and females, but whilst all males initiated their trips both during the day and at night, some females only initiated their trips during the day. Hatching success was found to be related to foraging effort by males. Gulls spent on average ca. 38% of their time budget outside the nesting territory, representing the time devoted mainly to flying, foraging and other activities.

Activity-Based Costing Model for a Vendor Managed Inventory Service

Uusien paperikoneiden kysyntä on vähentynyt ja jälkimarkkinointipalveluiden, kuten huoltojen ja varaosamyyntien, merkittävyys paperikoneliiketoiminnassa on kasvanut entisestään viime aikoina. Uudentyyppisiä palveluja kilpailuedun lisäämiseksi kehitellään jatkuvasti. Esimerkki tällaisesta palvelusta on sopimusperusteinen varastointipalvelu, jossa osat ovat myyjän varastossa kunnes asiakas ottaa ne käyttöön. Diplomityön tavoite on rakentaa malli varastoinnin kustannuslaskentaan ja laskea sen avulla varastointipalvelun kustannukset. Perinteinen toimitusketju monine varastoineen ei nykykäsityksen mukaan ole enää kustannustehokas. Yhä useammat yritykset kaupan ja teollisuuden aloilla ovat ryhtyneet soveltamaan VMI (Vendor Managed Inventory) teoriaa toimitusketjuissaan. Varastot ovat tällöin keskitettyjä, tiedonkulku toimitusketjun portaiden välillä on nopeaa ja kysyntään pystytään vastaamaan lyhyemmällä viiveellä sen ennakoitavuuden paranemisen takia. Työn tuloksena on toimintolaskentaan pohjautuva kustannuslaskentamalli, jota voidaan hyödyntää myös hinnoittelupäätöksiä tehtäessä. Työssä esitellään mallin soveltaminen eri tapauksiin ja ehdotetaan jatkotoimenpiteitä.

Targeted inactivation of hypocretin receptors in dopaminergic and noradrenergic systems alters brain activity in wakefulness

Since the discovery of hypocretins/orexins (Hcrt/Ox) in 1998, several narcoleptic mouse models, such as Hcrt-KO, Hcrtrl-KO, Hcrtr2-KO and double receptors KO mice, and orexin-ataxin transgenic mice were generated. The available Hcrt mouse models do not allow the dissection of the specific role of Hcrt in each target region. Dr. Anne Vassalli generated loxP-flanked alleles for each Hcrt receptor, which are manipulated by Cre recombinase to generate mouse lines with disrupted Hcrtrl or Hcrtr2 (or both) in cell type-specific manner. The role of noradrenaline (NA) and dopamine (OA) in ttie regulation of vigilance states is well documented. The purpose of this thesis is to explore the role of the Hcrt input into these two monoaminergic systems. Chronic loss of Hcrtrl in NA neurons consolidated paradoxical sleep (PS), and altered wakefulness brain activity in baseline, during the sleep deprivation (SD), and when mice were challenged by a novel environment, or exposed to nest-building material. The analysis of alterations in the sleep EEG delta power showed a consistent correlation with the changes in the preceding waking quality in these mice. Targeted inactivation of Hcrt input into DA neurons showed that Hcrtr2 inactivation present the strongest phenotype. The loss of Hcrtr2 in DA neurons caused modified brain activities in spontaneous wakefulness, during SD, and in novel environmental conditions. In addition to alteration of wakefulness quality and quantity, conditional inactivation of Hcrtr2 in DA neurons caused an increased in time spent in PS in baseline and a delayed and less complete PS recovery after SD. In the first 30 min of sleep recovery, single (i.e. for Hcrtrl or Hcrtr2) conditional knockout receptor mice had opposite changes in delta activity, including an increased power density in the fast delta range with specific inactivation of Hcrtr2, but a decreased power density in the same range with specific inactivation of Hcrtrl in DA cells. These studies demonstrate a complex impact of Hcrt receptors signaling in both NA and DA system, not only on quantity and quality of wakefulness, but also on PS amount regulation as well as on SWS delta power expression. -- Depuis la découverte des hypocrétines/orexines (Hcrt/Ox) en 1998, plusieurs modèles de souris, narcoleptiques telles que Hcrt-KO, Hcrtr2-KO et récepteurs doubles KO et les souris transgéniques orexine-ataxine ont été générés. Les modèles de souris Hcrt disponibles ne permettaient pas la dissection du rôle spécifique de l'Hcrt dans chaque noyau neuronal cible. Notre laboratoire a généré des allèles loxP pour chacun des 2 gènes codant pour les récepteurs Hcrtr, qui sont manipulés par recombinase Cre pour générer des lignées de souris avec Hcrtrl inactivé, ou Hcrtr2 inactivé, (ou les deux), spécifiquement dans un type cellulaire particulier. Le rôle de la noradrénaline (NA) et la dopamine (DA) dans la régulation des états de vigilance est bien documentée. Le but de cette thèse est d'étudier le rôle de l'afférence Hcrt dans ces deux systèmes monoaminergiques au niveau de l'activité cérébrale telle qu'elle apparaît dans l'électroencéphalogramme (EEG). Mon travail montre que la perte chronique de Hcrtrl dans les neurones NA consolide le sommeil paradoxal (PS), et l'activité cérébrale de l'éveil est modifiée en condition spontanée, au cours d'une experience de privation de sommeil (SD), et lorsque les souris sont présentées à un nouvel environnement, ou exposées à des matériaux de construction du nid. Ces modifications de l'éveil sont corrélées à des modifications de puissance de l'activité delta du sommeil lent qui le suit. L'inactivation ciblée des Hcrtrs dans les neurones DA a montré que l'inactivation Hcrtr2 conduit au phénotype le plus marqué. La perte de Hcrtr2 dans les neurones DA mène à des modification d'activité cérébrale en éveil spontané, pendant SD, ainsi que dans des conditions environnementales nouvelles. En plus de l'altération de la qualité de l'éveil et de la quantité, l'inactivation conditionnelle de Hcrtr2 dans les neurones DA a provoqué une augmentation du temps passé en sommeil paradoxal (PS) en condition de base, et une reprise retardée et moins complète du PS après SD. Dans les 30 premières minutes de la récupération de sommeil, les modèles inactivés pour un seul des récepteurs (ie pour Hcrtrl ou Hcrtr2 seulement) montrent des changements opposés en activité delta, en particulier une densité de puissance accrue dans le delta rapide avec l'inactivation spécifique de Hcrtr2, mais une densité de puissance diminuée dans cette même gamme chez les souris inactivées spécifiquement en Hcrtrl dans les neurones DA. Ces études démontrent un impact complexe de l'inactivation de la neurotransmission au niveau des récepteurs d'Hcrt dans les deux compartiments NA et DA, non seulement sur la quantité et la qualité de l'éveil, mais aussi sur la régulation de quantité de sommeil paradoxal, ainsi que sur l'expression de la puissance delta pendant le sommeil lent.