The dreaming sleep stage: A new neurobiological model of schizophrenia?

The rapid eye movement dreaming sleep stage and schizophrenia are both characterized by common intracerebral disconnections, disturbed responsiveness and sensory deafferentation processes. Moreover, in both states, there is dorsolateral prefrontal deactivation as shown by the decrease of blood flow. Finally, identical pharmacological and neurochemical variations are observed for acetylcholine, dopamine, noradrenaline, serotonin and glutamate concentrations. Consequently, rapid eye movement sleep could become a useful new neurobiological model of this mental disease since more functional than current rat models using stimulation, lesion or drugs.     

Tiagabine is associated with sustained attention during sleep restriction: evidence for the value of slow-wave sleep enhancement?

STUDY OBJECTIVES: To evaluate the impact of enhanced slow-wave sleep (SWS) on behavioral, psychological, and physiologic changes resulting from sleep restriction DESIGN: A double-blind, parallel-group, placebo-controlled design was used to compare tiagabine, 8 mg, (a SWS-enhancing drug) to placebo during 4 nights of sleep restriction (time in bed = 5 hours per night). Behavioral, psychological, and physiologic measures of the impact of sleep restriction were compared between groups at baseline, during sleep restriction, and following recovery sleep. SETTING: Two sleep research laboratories. PARTICIPANTS: Thirty-eight healthy adults; 9 men and 10 women (mean age: 26.0 +/- 6.1 years) in the placebo group and 8 men and 11 women (mean age: 26.7 +/- 8.1 years) in the tiagabine 8 mg group INTERVENTIONS: Both experimental groups underwent 4 nights of sleep restriction. Each group received either tiagabine 8 mg or placebo on all sleep-restriction nights, and both groups received placebo on baseline and recovery nights. MEASUREMENTS AND RESULTS: Polysomnography documented a SWS-enhancing effect of tiagabine. The placebo group displayed the predicted deficits due to sleep restriction on the Psychomotor Vigilance Task and the Multiple Sleep Latency Test. Compared with placebo, the tiagabine group did not demonstrate impairment in sustained attention on the Psychomotor Vigilance Test, performed better on the Wisconsin Card Sorting Task, reported more restorative sleep, and had less of an increase in afternoon-evening salivary free cortisol. Multiple Sleep Latency Test, ratings of sleepiness, recovery sleep, and other measures did not differ between groups. CONCLUSIONS: To our knowledge these findings are the first to be consistent with the hypothesis that pharmacologic SWS enhancement reduces selective aspects of the behavioral, psychological, and physiologic impact of sleep restriction.     

Finding cancer stem cells: are aldehyde dehydrogenases fit for purpose?

Despite many years of intensive effort, there is surprisingly little consensus on the most suitable markers with which to locate and isolate stem cells from adult tissues. By comparison, the study of cancer stem cells is still in its infancy; so, unsurprisingly, there is great uncertainty as to the identity of these cells. Stem cell markers can be broadly categorized into molecular determinants of self‐renewal, clonogenicity, multipotentiality, adherence to the niche, and longevity. This review assesses the utility of recognizing cancer stem cells by virtue of high expression of aldehyde dehydrogenases (ALDHs), probably significant determinants of cell survival through their ability to detoxify many potentially cytotoxic molecules, and contributing to drug resistance. Antibodies are available against the ALDH enzyme family, but the vast majority of studies have used cell sorting techniques to enrich for cells expressing these enzymes. Live cells expressing high ALDH activity are usually identified by the ALDEFLUOR kit and sorted by fluorescence activated cell sorting (FACS). For many human tumours, but notably breast cancer, cell selection based upon ALDH activity appears to be a useful marker for enriching for cells with tumour‐initiating activity (presumed cancer stem cells) in immunodeficient mice, and indeed the frequency of so‐called ALDH^bri cells in many tumours can be an independent prognostic indicator. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Fetal sleep organization: A biological precursor of self-regulation in childhood and adolescence?

Fetal sleep states emerge during the third trimester of pregnancy and involve multiple interconnected neuronal networks. We examined whether fetal sleep characteristics predict child and adolescent self-regulation in a non-clinical sample (study group, n=25; reference group, n=48). Combined recordings of three sleep variables (fetal heart rate, body movements and rapid eye movements) were made for 2 h at 36-38 weeks' gestation. Fetuses showing synchronous change of sleep variables (i.e. within 3 min) at transition from quiet into active sleep reached a higher level of effortful control, both at 8-9 and 14-15 years, than fetuses not making synchronous transitions and compared with the reference group. Results are discussed from a Developmental Origins of Behavior, Health and Disease (DOBHaD) point of view. It is concluded that studying sleep ontogeny offers the possibility to gain insight into brain maturational processes and/or environmental adaptive processes that may have long term behavioral developmental consequences.     

Antenatal depression: an artefact of sleep disturbance?

Research indicates that poor sleep quality is linked to and may precede depressive symptomatology in pregnancy, complicating screening for either condition. Pregnancy onset may also contribute to the development of sleep-disordered breathing (SDB). For the first time, the link between SDB and depression was examined in pregnancy. A total of 189 pregnant women completed the Edinburgh Postnatal Depression Scale (EPDS), Pittsburgh Sleep Quality Index (PSQI) for sleep quality and the Berlin Questionnaire for SDB. Women were also asked what they felt was the cause of their symptoms. PSQI-assessed poor sleep quality and self-perceived depression were strongly associated with EPDS scores of probable depression (X ² 13.39; p?<?0.001). Berlin-assessed risk of SDB was also associated with probable depression (X ² 9.20 p?<?0.01), though this was attenuated following multivariate analysis. There was a significant relationship between total PSQI score and the tendency for participants to attribute ‘sleep-related causes’ to their low mood (X ² 20.78; p?<?0.001). This study confirms the link between PSQI-assessed poor sleep quality and depressive symptoms in pregnancy, suggesting the two questionnaires assess the same or overlapping conditions. Although there was a relationship between probable depression and high risk SDB, the effect was attenuated after accounting for other depression risk factors, including body mass index (BMI).     

The biographical component of schizophrenia: a two-faced definition of relationship?

The schizophrenic's disturbed relationship with reality is generally ascribed to a mental illness of endogenous origin. Following the author's paper on a fixation disorder (1) provable in these patients, she expounds that their disturbed relationship with reality does not primarily concern their consciousness of objective reality but of their own self. As a result of contradictory definitions of relationship within his group (2,3) the schizophrenic is unable to integrate the awareness of his potentialities with the awareness of his social role. He cannot protect himself against a joker role imposed on him since his fixation disorder acts like a one-way valve impeding him from taking an active part in the definition of relationship. A hypothesis is presented as to how the schizophrenic's described fixation disorder may cause this one-way functioning of the definition of relationship.     

Laterality of the sleep onset process: Which hemisphere goes to sleep first?

This study aims to assess whether the hemispheric asymmetry inversion observed in the wake-sleep transition can also be revealed by the latency of inter tapping intervals >or= 2.5s for each hand and the latency of theta burst >or= 2.5s in symmetrical loci of the two hemispheres during the sleep onset process. Data collected from 16 right-handed subjects showed a hemispheric asymmetry in the sleep onset latency with both behavioural and EEG indices. For the first time, a hemispheric asymmetry in the sleep onset latency was found considering a visual analysis of EEG. Results suggest that the hemispheric pattern found during sleep onset can be considered a steady characteristic of the transition from wake to sleep, relatively independent of homeostatic and time of night effects. These results are interpreted as being consistent with the hypothesis concerning an advantage of the right hemisphere in sustaining vigilance.     

Auto-CPAP therapy for obstructive sleep apnea: induction of microarousals by automatic variations of CPAP pressure?

STUDY OBJECTIVES: To investigate the frequency of microarousals (MA) associated with pressure changes during auto-CPAP therapy (APAP) for obstructive sleep apnea (OSA). DESIGN: Patients with OSA were studied by polysomnography during APAP therapy (Somnosmart). The MA were classified on the basis of concomitant changes in APAP pressure. SETTING: Sleep laboratory of a university hospital PARTICIPANTS: 30 patients with moderate to severe OSA. MEASUREMENTS AND RESULTS: The mean AHI during APAP was 4.7+/-4.7, the mean arousal index was 14.5+/-6.6 per hour. During epochs with a pressure variation greater than 0.5 mbar, significantly more MA occurred (0.30+/-0.17 MA per epoch) than in epochs with constant treatment pressure (0.10+/-0.054 MA per epoch; p<0.001). There were more MA during pressure-increase epochs than during pressure-decrease epochs (0.42+/-0.24 vs. 0.16+/-0.12 MA per epoch; p<0.001). 82.5 percent of the MA were not preceded by a significant change in pressure (at least 0.5 mbar within 30 sec.), 10.6% were associated with a significant prior increase and 6.9% with a significant prior decrease in pressure. The percentage of MA preceded by a significant pressure variation varied between 2.3% and 61%, with a mean of 18.9%. CONCLUSIONS: The overall frequency of MA was low, and in most individuals the relative amount of "pressure-associated MA" was not significant. However in some individuals it cannot be excluded that some additional MA may have been induced by pressure variations. Should it prove possible to prevent such "pressure-associated MA" by optimizing the regulation of APAP pressure, the overall clinical effect of APAP treatment may be improved.     

Analysis of antigen-specific T-cell responses with synthetic peptides--what kind of peptide for which purpose?

The analysis of T-cell responses to peptides has recently become a busy area of immunologic research. Peptides may be used as single stimulants, pools or libraries, or as part of peptide/major histocompatibility complexes (MHC) for direct T-cell receptor staining. For stimulating T cells, peptides must be bound to MHC molecules. In this study we have used 9- or 10-amino acid peptides, 15-amino acid peptides containing stimulating shorter sequences, and peptides with modified C-terminal function. On average 67% of the T cells from healthy cytomegalovirus-positive donors that bound a frequently used cytomegalovirus pp65/HLA-A*0201 tetramer were able to produce interferon-gamma on stimulation with the respective 9-amino acid peptide. Peptides of 15 amino acids length used at the same concentration (in microg/ml) stimulated CD8 T cells somewhat less efficiently (on average 77% of the frequencies induced with the respective shorter peptides). Modifications of 9-amino acid peptides such as addition of amino acids or functional groups often resulted in a decreased ability to stimulate. However, based on our own results, published data, and theoretic considerations, we conclude that sets of peptides of 15 amino acids length with 11 amino acids overlap represent a good compromise for stimulating both CD8 and CD4 T cells in a number of applications. These parameters may be modified subject to the purpose of a study.     

Sarcopenia definition: Does it really matter? Implications for resistance training

The loss of muscle mass, strength and function, known as sarcopenia, is common in older adults, and is associated with falls, fractures, cardiometabolic diseases, and lower quality of life. Sarcopenia can also occur secondarily to chronic diseases. Recently, sarcopenia was recognized as a disease with an International Classification of Disease (ICD) code, yet, at least five definitions for its clinical identification exist. Most definitions include three themes: low muscle mass, strength and physical performance. However, the definitions vary by the number of themes needed to diagnose sarcopenia and, within each theme various parameters and cut-off levels exist. The lack of consensus on what constitutes a diagnosis can create confusion and hesitation in sarcopenia diagnosis. Currently, no pharmacological treatment exists for sarcopenia. Resistance training (RT) is safe and effective to improve muscle mass, strength and physical performance in older adults and clinical populations. Based on current guidelines, whether an individual is defined as “sarcopenic”, or not, does not change the way RT is prescribed. Here, we present evidence and the inconsistencies in sarcopenia definitions and recommend that focus should be on optimizing ways to prescribe RT and increase long-term adherence, rather than on slight modifications to sarcopenia definitions.     

Collective Cell Migration: “All for One and One for All”

Cell migration is a key mechanism during neural development, as it allows cells to reach their final destination from their birthplace. In some cases, cells migrate in isolation, whereas in others they migrate in collectives, as chains, streams, clusters, or sheets. The coordinated and timely process of collective migration eventually ensures the proper organization of the nervous system and its misregulation leads to severe diseases, including neurological disorders. This review impinges upon the cellular and molecular interactions underlying collective cell migration in animal models, and highlights the recent advances made through in vivo analyses of the Drosophila wing glia.     

Obstructive sleep apnea and insulin resistance: a role for microcirculation?

Obstructive sleep apnea is an increasingly recognized medical problem. The recent attention to its frequency in the general population and its important role in metabolic, vascular, and behavioral aspects have sharply increased the number and nature of investigations, thereby revealing new aspects that open new approaches in research. Whereas obstructive sleep apnea is a well-known phenomenon accompanying obesity and diabetes, new findings strongly suggest that this close relationship may also operate in the opposite direction. Indeed obstructive sleep apnea may be a primary feature inducing or aggravating a series of vascular and metabolic disturbances closely resembling the metabolic syndrome. This review will discuss established and potential mechanisms responsible for these changes. Obstructive sleep apnea indeed appears to gather all the elements necessary to induce insulin resistance, hypertension, and possibly heart failure. After careful analysis of these modifications and considering how they are intertwined, we propose that microcirculation could represent the common denominator mediating the progression of this pathology, as it is eventually the case in the metabolic syndrome and diabetes domain. This plausible hypothesis is discussed in detail and should be verified by appropriate preclinical and clinical protocols, which are now achievable by using noninvasive techniques in humans.     

K-complexes: are they signs of arousal or sleep protective?

SUMMARY  The number of K-complexes recorded at the central-temporal EEG derivation (C3-T3) during 5 min periods for both the ascending and descending phase of Stage 2 of NREM sleep for cycles 1,2… etc. were counted in 10 subjects for each of the following five groups: normal persons, patients with a primary generalized form of epilepsy, narcolepsy, insomnia and obstructive sleep apnoea. The differences in time spent in different stages of sleep were as expected for these types of patients. A 2-within, 1-between factors, repeated measure ANOVA was applied to the data on K-complexes. Overall, there was no significant difference between the number of K-complexes observed during the ascending and descending phases of the different sleep cycles. Patients with a sleep disorder had significantly less well-defined K-complexes than the normals and the patients with a primary form of generalized epilepsy: for insomnia ( P = 0.035), for apnoea ( P = 0.011) and for narcolepsy ( P = 0.001). There was a significant, but very low correlation coefficient between the number of K-complexes observed during Stage 2 of NREM sleep and the time spent during that stage for all groups combined (Rho 0.27, P = 0.002) and for the narcoleptic patients (Rho 0.44, P = 0.017). In all, the findings lend support to the hypothesis that a K-complex can be seen as a 'defensive response', or has a sleep protective function.