51 research outputs found
A DEAD box protein facilitates HIV-1 replication as a cellular co-factor of Rev
AbstractHIV-1 Rev escorts unspliced viral mRNAs out of the nucleus of infected cells, which allows formation of infectious HIV-1 virions. We have identified a putative DEAD box (AspâGluâAlaâAsp) RNA helicase, DDX1, as a cellular co-factor of Rev, through yeast and mammalian two-hybrid systems using the N-terminal motif of Rev as âbaitâ. DDX1 is not a functional homolog of HIV-1 Rev, but down-regulation of DDX1 resulted in an alternative splicing pattern of Rev-responsive element (RRE)-containing mRNA, and attenuation of Gag p24 antigen production from HLfb rev(â) cells rescued by exogenous Rev. Co-transfection of a DDX1 expression vector with HIV-1 significantly increased viral production. DDX1 binding to Rev, as well as to the RRE, strongly suggest that DDX1 affects Rev function through the RevâRRE axis. Moreover, down-regulation of DDX1 altered the steady state subcellular distribution of Rev, from nuclear/nucleolar to cytoplasmic dominance. These findings indicate that DDX1 is a critical cellular co-factor for Rev function, which maintains the proper subcellular distribution of this lentiviral regulatory protein. Therefore, alterations in DDX1âRev interactions could induce HIV-1 persistence and targeting DDX1 may lead to rationally designed and novel anti-HIV-1 strategies and therapeutics
Evaluation of an internet-based behavioral intervention to improve psychosocial health outcomes in children with insomnia (Better Nights, Better Days): Protocol for a randomized controlled trial
Background: Up to 25% of 1- to 10-year-old children experience insomnia (ie, resisting bedtime, trouble falling asleep, night awakenings, and waking too early in the morning). Insomnia can be associated with excessive daytime sleepiness and negative effects on daytime functioning across multiple domains (eg, behavior, mood, attention, and learning). Despite robust evidence supporting the effectiveness of behavioral treatments for insomnia in children, very few children with insomnia receive these treatments, primarily due to a shortage of available treatment resources. Objective: The Better Nights, Better Days (BNBD) internet-based program provides a readily accessible electronic health (eHealth) intervention to support parents in providing evidence-based care for insomnia in typically developing children. The purpose of the randomized controlled trial (RCT) is to evaluate the effectiveness of BNBD in treating insomnia in children aged between 1 and 10 years. Methods: BNBD is a fully automated program, developed based on evidence-based interventions previously tested by the investigators, as well as on the extant literature on this topic. We describe the 2-arm RCT in which participants (500 primary caregivers of children with insomnia residing in Canada) are assigned to intervention or usual care. Results: The effects of this behavioral sleep eHealth intervention will be assessed at 4 and 8 months postrandomization. Assessment includes both sleep (actigraphy, sleep diary) and daytime functioning of the children and daytime functioning of their parents. Results will be reported using the standards set out in the Consolidated Standards of Reporting Trials statement. Conclusions: If the intervention is supported by the results of the RCT, we plan to commercialize this program so that it is sustainable and available at a low cost to all families with internet access
Children\u27s Sleep during COVID-19: How Sleep Influences Surviving and Thriving in Families
Objective The COVID-19 pandemic has the potential to disrupt the lives of families and may have implications for children with existing sleep problems. As such, we aimed to: (1) characterize sleep changes during the COVID-19 pandemic in children who had previously been identified as having sleep problems, (2) identify factors contributing to sleep changes due to COVID-19 safety measures, and (3) understand parents and children s needs to support sleep during the pandemic. Methods Eighty-five Canadian parents with children aged 4 14 years participated in this explanatory sequential, mixed-methods study using an online survey of children s and parents sleep, with a subset of 16 parents, selected based on changes in their children s sleep, participating in semi-structured interviews. Families had previously participated in the Better Nights, Better Days (BNBD) randomized controlled trial. Results While some parents perceived their child s sleep quality improved during the COVID-19 pandemic (14.1%, n 12), many parents perceived their child s sleep had worsened (40.0%, n 34). Parents attributed children s worsened sleep to increased screen time, anxiety, and decreased exercise. Findings from semi-structured interviews highlighted the effect of disrupted routines on sleep and stress, and that stress reciprocally influenced children s and parents sleep. Conclusions The sleep of many Canadian children was affected by the first wave of the COVID-19 pandemic, with the disruption of routines influencing children s sleep. eHealth interventions, such as BNBD with modifications that address the COVID-19 context, could help families address these challenges
Synthetic Plasmodium-Like Hemozoin Activates the Immune Response: A Morphology - Function Study
Increasing evidence points to an important role for hemozoin (HZ), the malaria pigment, in the immunopathology related to this infection. However, there is no consensus as to whether HZ exerts its immunostimulatory activity in absence of other parasite or host components. Contamination of native HZ preparations and the lack of a unified protocol to produce crystals that mimic those of Plasmodium HZ (PHZ) are major technical limitants when performing functional studies with HZ. In fact, the most commonly used methods generate a heterogeneous nanocrystalline material. Thus, it is likely that such aggregates do not resemble to PHZ and differ in their inflammatory properties. To address this issue, the present study was designed to establish whether synthetic HZ (sHZ) crystals produced by different methods vary in their morphology and in their ability to activate immune responses. We report a new method of HZ synthesis (the precise aqueous acid-catalyzed method) that yields homogeneous sHZ crystals (Plasmodium-like HZ) which are very similar to PHZ in their size and physicochemical properties. Importantly, these crystals are devoid of protein and DNA contamination. Of interest, structure-function studies revealed that the size and shape of the synthetic crystals influences their ability to activate inflammatory responses (e.g. nitric oxide, chemokine and cytokine mRNA) in vitro and in vivo. In summary, our data confirm that sHZ possesses immunostimulatory properties and underline the importance of verifying by electron microscopy both the morphology and homogeneity of the synthetic crystals to ensure that they closely resemble those of the parasite. Periodic quality control experiments and unification of the method of HZ synthesis are key steps to unravel the role of HZ in malaria immunopathology
Le dĂ©veloppement dâune approche clinique pour les troubles du sommeil en pĂ©dopsychiatrie
Les sciences de la santĂ© souffrent dâinsomnie : ses experts ne veillent trop souvent que sur les phĂ©nomĂšnes associĂ©s Ă lâĂ©tat dâĂ©veil. Heureusement, quelques-uns dĂ©fient lâhorloge et se consacrent au « tiers obscur de la vie » : le sommeil. Cet article porte sur lâinterface entre le sommeil et la pĂ©dopsychiatrie. La premiĂšre partie dĂ©crit dâabord lâhistoire du dĂ©veloppement du laboratoire de recherche sur le sommeil et les troubles de la santĂ© mentale, les premiĂšres recherches qui y ont Ă©tĂ© faites sur le sommeil dans la schizophrĂ©nie et lâautisme, puis le dĂ©veloppement de la Clinique des troubles du sommeil pour enfants et adolescents de lâHĂŽpital RiviĂšre-des-Prairies. La deuxiĂšme partie dĂ©crit dâabord lâimpact dâun mauvais sommeil sur le fonctionnement diurne des enfants et adolescents en gĂ©nĂ©ral puis rapporte des donnĂ©es statistiques sur la frĂ©quence des troubles du sommeil et leurs consĂ©quences cliniques chez les enfants et adolescents avec un diagnostic psychiatrique. On prĂ©sente ensuite la Clinique des troubles du sommeil de lâHĂŽpital RiviĂšre-des-Prairies, qui sâadresse spĂ©cifiquement et sĂ©lectivement aux enfants aux prises avec un diagnostic psychiatrique, puis on en rĂ©sume le mode de fonctionnement et la dĂ©marche clinique.Objectives Health sciences suffer from insomnia: experts too often concentrate their efforts on the wake state. Fortunately enough, some of them have taken the road towards the âDark Third of Lifeâ: sleep. This article gives an historical account of the development of the first Canadian sleep disorders laboratory and clinic specifically and selectively designed for children and adolescents with a psychiatric diagnosis. It then stresses the importance of sleep in children bearing a psychiatric diagnosis and summarizes therapeutic strategies.Methods Data-on-file and selective review of literature.Results An innovative scheme matching sleep psychologists and psychiatrists with expertise in neurodevelopmental disorders led to the creation of a sleep research laboratory on mental health disorders. The initial research projects on the sleep and dreams of patients with schizophrenia and persons with autism are summarized. The Sleep Disorders Clinic for Children and Adolescents was then created at the HĂŽpital RiviĂšre-des-Prairies, leading to much needed activities focused on youth. Indeed, sleep disorders show a high prevalence in children with a psychiatric diagnosis and the literature shows that these children have an increased sensitivity for diurnal effects of poor sleep. The main sleep-relevant issues at stake are reviewed, including the high frequency of sleep disorders in pedopsychiatric patients. Clinical challenges are described and the operating mode of the Sleep Disorders Clinic is illustrated.Conclusion Sleep disorders and their effects on daytime functioning need to be assessed in children with a psychiatric diagnosis in order to generate a full clinical picture. Appropriate tools and know-how are readily available in order to achieve this goal
Le diagnostic et le traitement des troubles du sommeil: nécessité d'une interaction médico-psychologique.
Troubles psychotiques et troubles du sommeil : revue de la littérature
Contexte La disparition de la nomenclature des troubles du sommeil dits primaires ou secondaires, rendue obsolĂšte par le Manuel diagnostique et statistique des troubles mentaux (DSM-5), reprĂ©sente bien lâengouement acadĂ©mique actuel pour ce domaine de recherche. Il est de plus en plus reconnu que les troubles du sommeil sont plus que de simples consĂ©quences dâun trouble psychiatrique et quâils peuvent persister malgrĂ© un traitement adĂ©quat de la condition comorbide et mĂȘme prĂ©cĂ©der ou exacerber cette derniĂšre. Les troubles du sommeil dans les troubles psychotiques, trĂšs frĂ©quents, sont donc devenus un sujet dâactualitĂ©, reprĂ©sentant une cible dâintervention jusquâici sous-estimĂ©e.Objectif Cet article vise Ă prĂ©senter lâĂ©tat des connaissances actuelles sur la relation entre les troubles du sommeil et les troubles psychotiques ainsi que sur lâutilisation de la thĂ©rapie cognitivo-comportementale (TCC) pour traiter les troubles du sommeil dans ce contexte.MĂ©thode Lâarticle fait une recension narrative de la littĂ©rature pour dĂ©crire la relation bidirectionnelle entre la psychose et les troubles du sommeil, les corrĂ©lations cliniques et les traitements ciblant lâinsomnie chez les patients psychotiques.RĂ©sultats MalgrĂ© la prĂ©sence dâune relation entre les troubles du sommeil et les troubles psychotiques, les mĂ©canismes neuronaux, hormonaux et socioculturels rĂ©gissant cette relation demeurent encore incertains. Bien que lâassociation reliant les troubles du sommeil et les troubles psychotiques demeure Ă clarifier, les Ă©tudes dĂ©montrent quâelle serait bidirectionnelle et peut engendrer un cercle vicieux oĂč ces deux composantes sâaggravent mutuellement. Dans ce contexte de comorbiditĂ©s, les modĂšles unifiĂ©s en TCC deviennent un traitement de choix, Ă condition dâadapter les protocoles de TCC pour insomnie (TCC-i) Ă une population avec trouble psychotique (TCC-ip).Conclusion MalgrĂ© la complexitĂ© de la relation entre les troubles psychotiques et ceux du sommeil, la TCC-i a Ă©tĂ© dĂ©montrĂ©e efficace pour traiter les troubles du sommeil dans une population psychotique et pourrait, dans certains cas, permettre dâallĂ©ger la symptomatologie psychotique. De futures Ă©tudes sur ce domaine pourraient permettre le dĂ©veloppement de protocoles de thĂ©rapie cognitivo-comportementale pour les troubles du sommeil mieux adaptĂ©s Ă la population avec troubles psychotiques.Context Psychotic disorders are severe mental disorders that can cause a loss of contact with reality. Along with positive symptoms (delusions and hallucinations), they also encompass many other dysfunctions, such as sleep problems, which themselves can cause great distress and impairment in patients.Objective To review current literature on the relationship between sleep disorders and psychosis, on the clinical impact of such a relationship, and the psychological treatment of sleep disorders in the context of psychosis.Method Narrative overview of the literature synthesizing the findings about the relationship between psychosis and sleep disorders, and the psychological treatment of the latter, retrieved from searches of computerized databases, hand searches, and authoritative texts.Results Evidence shows a bidirectional relationship between psychosis and sleep disorders. Despite many hypotheses involving genetics, hormones, or neuronal functions regarding the nature of this association, the exact mechanism remains elusive. However, sleep-related problems are an interesting therapeutic target to improve quality of life and psychotic symptoms and respond well to psychological interventions.Conclusion Patients with psychotic disorders can benefit from CBT for insomnia, given a few adaptations to existing protocols. Additional studies are necessary to determine which patients are most likely to benefit from such interventions and to clarify the relationship between psychosis and sleep disorders, and the clinical implications of them co-existing
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