185 research outputs found

    Phospholipase C-β4 Is Essential for the Progression of the Normal Sleep Sequence and Ultradian Body Temperature Rhythms in Mice

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    BACKGROUND: THE SLEEP SEQUENCE: i) non-REM sleep, ii) REM sleep, and iii) wakefulness, is stable and widely preserved in mammals, but the underlying mechanisms are unknown. It has been shown that this sequence is disrupted by sudden REM sleep onset during active wakefulness (i.e., narcolepsy) in orexin-deficient mutant animals. Phospholipase C (PLC) mediates the signaling of numerous metabotropic receptors, including orexin receptors. Among the several PLC subtypes, the beta4 subtype is uniquely localized in the geniculate nucleus of thalamus which is hypothesized to have a critical role in the transition and maintenance of sleep stages. In fact, we have reported irregular theta wave frequency during REM sleep in PLC-beta4-deficient mutant (PLC-beta4-/-) mice. Daily behavioral phenotypes and metabotropic receptors involved have not been analyzed in detail in PLC-beta4-/- mice, however. METHODOLOGY/PRINCIPAL FINDINGS: Therefore, we analyzed 24-h sleep electroencephalogram in PLC-beta4-/- mice. PLC-beta4-/- mice exhibited normal non-REM sleep both during the day and nighttime. PLC-beta4-/- mice, however, exhibited increased REM sleep during the night, their active period. Also, their sleep was fragmented with unusual wake-to-REM sleep transitions, both during the day and nighttime. In addition, PLC-beta4-/- mice reduced ultradian body temperature rhythms and elevated body temperatures during the daytime, but had normal homeothermal response to acute shifts in ambient temperatures (22 degrees C-4 degrees C). Within the most likely brain areas to produce these behavioral phenotypes, we found that, not orexin, but group-1 metabotropic glutamate receptor (mGluR)-mediated Ca(2+) mobilization was significantly reduced in the dorsal lateral geniculate nucleus (LGNd) of PLC-beta4-/- mice. Voltage clamp recordings revealed that group-1 mGluR-mediated currents in LGNd relay neurons (inward in wild-type mice) were outward in PLC-beta4-/- mice. CONCLUSIONS/SIGNIFICANCE: These lines of evidence indicate that impaired LGNd relay, possibly mediated via group-1 mGluR, may underlie irregular sleep sequences and ultradian body temperature rhythms in PLC-beta4-/- mice

    Looking both ways

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    On the occasion of the 25th anniversary of the journal, Psychotherapy Research, three former editors first look back at: (i) the controversial persistence of the Dodo verdict (i.e., the observation that all bona fide therapies seem equally effective); (ii) the connection between process and outcome; (iii) the move toward methodological pluralism; and (iv) the politicization of the field around evidence-based practice and treatment guidelines. We then look forward to the next 25 years, suggesting that it would be promising to focus on three areas: (i) systematic theory-building research; (ii) renewed attention to fine-grained study of therapist techniques; and (iii) politically expedient research on the outcomes of marginalized or emerging therapies

    Expressivity in children's drawings of themselves for adult audiences with varied authority and familiarity

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    This study investigated whether children’s expressive drawings of themselves vary as a function of audience authority and familiarity. One hundred and seventy-five children, 85 boys and 90 girls, aged between 8 years 1 months and 9 years 2 months (M= 8 years 5 months) were allocated into seven groups; a reference group (n=25) where no audience was specified, and six audience groups (n=25 per group) varying by audience type (policeman vs. teacher vs. man) and familiarity (familiar vs. unfamiliar). They drew baseline then happy and sad drawings of themselves, rated affect towards drawings type, and rated perceived audience authority. Audience familiarity and authority impacted expressive drawing strategy use and this varied by gender. There was higher overall expressive strategy use for happy drawings and for girls, and influences of affect type, familiarity and authority were found. The implications of children’s perceptions of audience type on their expressive drawings are discussed

    Role of Homer Proteins in the Maintenance of Sleep-Wake States

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    Sleep is an evolutionarily conserved process that is linked to diurnal cycles and normal daytime wakefulness. Healthy sleep and wakefulness are integral to a healthy lifestyle; this occurs when an organism is able to maintain long bouts of both sleep and wake. Homer proteins, which function as adaptors for group 1 metabotropic glutamate receptors, have been implicated in genetic studies of sleep in both Drosophila and mouse. Drosophila express a single Homer gene product that is upregulated during sleep. By contrast, vertebrates express Homer as both constitutive and immediate early gene (H1a) forms, and H1a is up-regulated during wakefulness. Genetic deletion of Homer in Drosophila results in fragmented sleep and in failure to sustain long bouts of sleep, even under increased sleep drive. However, deletion of Homer1a in mouse results in failure to sustain long bouts of wakefulness. Further evidence for the role of Homer1a in the maintenance of wake comes from the CREB alpha delta mutant mouse, which displays a reduced wake phenotype similar to the Homer1a knockout and fails to up-regulate Homer1a upon sleep loss. Homer1a is a gene whose expression is induced by CREB. Sustained behaviors of the sleep/wake cycle are created by molecular pathways that are distinct from those for arousal or short bouts, and implicate an evolutionarily-conserved role for Homer in sustaining these behaviors

    Understanding the nature and mechanism of foot pain

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    Approximately one-quarter of the population are affected by foot pain at any given time. It is often disabling and can impair mood, behaviour, self-care ability and overall quality of life. Currently, the nature and mechanism underlying many types of foot pain is not clearly understood. Here we comprehensively review the literature on foot pain, with specific reference to its definition, prevalence, aetiology and predictors, classification, measurement and impact. We also discuss the complexities of foot pain as a sensory, emotional and psychosocial experience in the context of clinical practice, therapeutic trials and the placebo effect. A deeper understanding of foot pain is needed to identify causal pathways, classify diagnoses, quantify severity, evaluate long term implications and better target clinical intervention

    Self-directed behavioral family intervention: Do therapists matter?

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    Behavioral family intervention is an effective form of intervention for the prevention and treatment of a wide range of emotional and behavioral problems in children. There is a growing need to address the accessibility of these services. This paper reviews the literature on self-directed interventions designed to help parents manage difficult child behaviors. Evidence regarding the efficacy of interventions is reviewed, and some of the difficulties associated with self-directed programs are discussed. The Self-directed Triple P and Teen Triple P-Positive Parenting Programs are highlighted as examples of efficacious and effective behavioral family interventions fitting into a larger multi-level model of family intervention. The discussion of the efficacy and effectiveness of self-directed Triple P has implications for service delivery of parenting programs

    Instrumentation issues in implementation science

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    Background Like many new fields, implementation science has become vulnerable to instrumentation issues that potentially threaten the strength of the developing knowledge base. For instance, many implementation studies report findings based on instruments that do not have established psychometric properties. This article aims to review six pressing instrumentation issues, discuss the impact of these issues on the field, and provide practical recommendations. Discussion This debate centers on the impact of the following instrumentation issues: use of frameworks, theories, and models; role of psychometric properties; use of ‘home-grown’ and adapted instruments; choosing the most appropriate evaluation method and approach; practicality; and need for decision-making tools. Practical recommendations include: use of consensus definitions for key implementation constructs; reporting standards (e.g., regarding psychometrics, instrument adaptation); when to use multiple forms of observation and mixed methods; and accessing instrument repositories and decision aid tools. Summary This debate provides an overview of six key instrumentation issues and offers several courses of action to limit the impact of these issues on the field. With careful attention to these issues, the field of implementation science can potentially move forward at the rapid pace that is respectfully demanded by community stakeholders
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