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 (Asp–Glu–Ala–Asp) 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 “bait”. 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(−) 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 Rev–RRE 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 DDX1–Rev 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 développement d’une approche clinique pour les troubles du sommeil en pédopsychiatrie

Les sciences de la santé souffrent d’insomnie : ses experts ne veillent trop souvent que sur les phénomènes associés à l’état d’éveil. Heureusement, quelques-uns défient l’horloge et se consacrent au « tiers obscur de la vie » : le sommeil. Cet article porte sur l’interface entre le sommeil et la pédopsychiatrie. La première partie décrit d’abord l’histoire du développement du laboratoire de recherche sur le sommeil et les troubles de la santé mentale, les premières recherches qui y ont été faites sur le sommeil dans la schizophrénie et l’autisme, puis le développement de la Clinique des troubles du sommeil pour enfants et adolescents de l’Hôpital Rivière-des-Prairies. La deuxième partie décrit d’abord l’impact d’un mauvais sommeil sur le fonctionnement diurne des enfants et adolescents en général puis rapporte des données statistiques sur la fréquence des troubles du sommeil et leurs conséquences cliniques chez les enfants et adolescents avec un diagnostic psychiatrique. On présente ensuite la Clinique des troubles du sommeil de l’Hôpital Rivière-des-Prairies, qui s’adresse spécifiquement et sélectivement aux enfants aux prises avec un diagnostic psychiatrique, puis on en résume le mode de fonctionnement et la démarche 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 “Dark Third of Life”: 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 Hôpital Rivière-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

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 obsolète par le Manuel diagnostique et statistique des troubles mentaux (DSM-5), représente bien l’engouement académique actuel pour ce domaine de recherche. Il est de plus en plus reconnu que les troubles du sommeil sont plus que de simples conséquences d’un trouble psychiatrique et qu’ils peuvent persister malgré un traitement adéquat de la condition comorbide et même précéder ou exacerber cette dernière. Les troubles du sommeil dans les troubles psychotiques, très fréquents, sont donc devenus un sujet d’actualité, représentant une cible d’intervention jusqu’ici sous-estimée.Objectif Cet article vise à présenter l’état des connaissances actuelles sur la relation entre les troubles du sommeil et les troubles psychotiques ainsi que sur l’utilisation de la thérapie cognitivo-comportementale (TCC) pour traiter les troubles du sommeil dans ce contexte.Méthode L’article fait une recension narrative de la littérature pour décrire la relation bidirectionnelle entre la psychose et les troubles du sommeil, les corrélations cliniques et les traitements ciblant l’insomnie chez les patients psychotiques.Résultats Malgré la présence d’une relation entre les troubles du sommeil et les troubles psychotiques, les mécanismes neuronaux, hormonaux et socioculturels régissant cette relation demeurent encore incertains. Bien que l’association reliant les troubles du sommeil et les troubles psychotiques demeure à clarifier, les études démontrent qu’elle serait bidirectionnelle et peut engendrer un cercle vicieux où ces deux composantes s’aggravent mutuellement. Dans ce contexte de comorbidités, les modèles unifiés en TCC deviennent un traitement de choix, à condition d’adapter les protocoles de TCC pour insomnie (TCC-i) à une population avec trouble psychotique (TCC-ip).Conclusion Malgré la complexité de la relation entre les troubles psychotiques et ceux du sommeil, la TCC-i a été démontrée efficace pour traiter les troubles du sommeil dans une population psychotique et pourrait, dans certains cas, permettre d’alléger la symptomatologie psychotique. De futures études sur ce domaine pourraient permettre le développement de protocoles de thérapie cognitivo-comportementale pour les troubles du sommeil mieux adaptés à 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