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Study Objectives: The current study aimed to examine clinically relevant psychiatric and sociodemographic predictors of insomnia treatment outcomes in pediatric patients clinically referred for insomnia. Methods: Pediatric patients (n = 1,428; ages 1.5–18 years) presenting for insomnia evaluation in a medical/sleep center–based behavioral sleep clinic were followed for treatment as clinically indicated. According to patient age, parents/patients completed validated measures of insomnia severity, psychiatric symptoms, and sociodemographic measures. Patients were also categorized by treatment outcome status (ie, not recommended to follow-up after initial evaluation and treatment session, successful treatment completion, lost to follow-up after initial evaluation and treatment session, and early termination) according to the clinically indicated treatment recommended and dose of treatment received. Results: Youth had elevated scores on psychiatric screening indexes and affective problems were highest for all age groups. Other comorbid sleep disorders were present in nearly 25% of patients with insomnia and use of sleep aids (melatonin or hypnotics) was commonplace. Baseline insomnia severity significantly predicted sleep treatment trajectories and posttreatment insomnia severity with large effects for all age groups. Other clinically relevant predictors of insomnia treatment outcomes included medication use and externalizing mental health concerns in younger patients and internalizing mental health concerns and chronological age in older patients. Lack of treatment follow-up and premature treatment termination was observed for patients with the worst insomnia symptoms at time of initial evaluation. Conclusions: Pediatric health providers delivering insomnia treatment should take a developmentally sensitive approach that is proactive with regards to managing treatment barriers that are likely influenced by severity of insomnia and comorbid mental health concerns. Citation: Van Dyk TR, Simmons DM, Durracio K, Becker SP, Byars KC. The role of psychiatric symptoms, sociodemographic factors, and baseline sleep variables on pediatric insomnia treatment outcomes in a clinically referred population. J Clin Sleep Med. 2024;20(11):1727–1738.

Study Objectives: Children with overweight or obesity are more likely to experience sleep disorders, although the role of weight in pediatric insomnia treatment has not been examined. The current study examined the relationships of high body mass with pretreatment insomnia severity and global sleep problems and the potential moderating impact of weight on changes in insomnia severity following insomnia treatment. Methods: Participants included 1,133 youth ages 2–18 years clinically referred for insomnia treatment. The Pediatric Insomnia Severity Index was collected at the initial assessment and throughout treatment as part of routine clinical care. Treatment status was coded as no treatment, early termination, and completed treatment. Secondary measures of global sleep problems at the initial assessment included the Adolescent Sleep Wake Scale, Adolescent Sleep Hygiene Scale, and Children’s Sleep Habits Questionnaire. Medical chart review of visits within ± 3 months of baseline was used to obtain age-adjusted and sex-adjusted body mass index Z-score. Results: Among adolescents, regression analyses found that higher body mass index Z-score modestly predicted baseline insomnia severity ( P = .021) and worse sleep hygiene ( P < .001). For children, higher body mass index Z-score was modestly associated with baseline total sleep problems ( P = .006) but not insomnia severity ( P = .792). Across ages, body mass index Z-score predicted neither treatment status nor insomnia improvement ( P > .05). Findings were similar in categorical analyses comparing patients with overweight/obesity to healthy weight. Conclusions: Although there is evidence that children of higher body mass present for insomnia treatment with greater sleep concerns, body mass does not predict treatment completion or insomnia improvement. Data suggest insomnia treatment is effective irrespective of weight status. Citation: Duraccio KM, Simmons DM, Beebe DW, Byars KC. Relationship of overweight and obesity to insomnia severity, sleep quality, and insomnia improvement in a clinically referred pediatric sample. J Clin Sleep Med . 2022;18(4):1083–1091.

One approach to reducing the costs of advanced biofuel production from cellulosic biomass is to engineer a single microorganism to both digest plant biomass and produce hydrocarbons that have the properties of petrochemical fuels. Such an organism would require pathways for hydrocarbon production and the capacity to secrete sufficient enzymes to efficiently hydrolyze cellulose and hemicellulose. To demonstrate how one might engineer and coordinate all of the necessary components for a biomass-degrading, hydrocarbon-producing microorganism, we engineered a microorganism naïve to both processes, Escherichia coli, to grow using both the cellulose and hemicellulose fractions of several types of plant biomass pretreated with ionic liquids. Our engineered strains express cellulase, xylanase, beta-glucosidase, and xylobiosidase enzymes under control of native E. coli promoters selected to optimize growth on model cellulosic and hemicellulosic substrates. Furthermore, our strains grow using either the cellulose or hemicellulose components of ionic liquid-pretreated biomass or on both components when combined as a coculture. Both cellulolytic and hemicellulolytic strains were further engineered with three biofuel synthesis pathways to demonstrate the production of fuel substitutes or precursors suitable for gasoline, diesel, and jet engines directly from ionic liquid-treated switchgrass without externally supplied hydrolase enzymes. This demonstration represents a major advance toward realizing a consolidated bioprocess. With improvements in both biofuel synthesis pathways and biomass digestion capabilities, our approach could provide an economical route to production of advanced biofuels.

Aging is associated with cognitive impairment and degenerative processes in the brain. Here, Tony Wyss-Coray and colleagues report that exposure of aged mice to young blood improves learning and memory in aged mice. This effect is associated with structural improvements in dendritic spine density in the hippocampus and functionally with increased synaptic plasticity. These findings suggest that circulating factors in young blood can reverse impairments in learning, memory and synaptic plasticity in aged mice. As human lifespan increases, a greater fraction of the population is suffering from age-related cognitive impairments, making it important to elucidate a means to combat the effects of aging 1 , 2 . Here we report that exposure of an aged animal to young blood can counteract and reverse pre-existing effects of brain aging at the molecular, structural, functional and cognitive level. Genome-wide microarray analysis of heterochronic parabionts—in which circulatory systems of young and aged animals are connected—identified synaptic plasticity–related transcriptional changes in the hippocampus of aged mice. Dendritic spine density of mature neurons increased and synaptic plasticity improved in the hippocampus of aged heterochronic parabionts. At the cognitive level, systemic administration of young blood plasma into aged mice improved age-related cognitive impairments in both contextual fear conditioning and spatial learning and memory. Structural and cognitive enhancements elicited by exposure to young blood are mediated, in part, by activation of the cyclic AMP response element binding protein (Creb) in the aged hippocampus. Our data indicate that exposure of aged mice to young blood late in life is capable of rejuvenating synaptic plasticity and improving cognitive function.

The mammalian brain is complex, with multiple cell types performing a variety of diverse functions, but exactly how each cell type is affected in aging remains largely unknown. Here we performed a single-cell transcriptomic analysis of young and old mouse brains. We provide comprehensive datasets of aging-related genes, pathways and ligand–receptor interactions in nearly all brain cell types. Our analysis identified gene signatures that vary in a coordinated manner across cell types and gene sets that are regulated in a cell-type specific manner, even at times in opposite directions. These data reveal that aging, rather than inducing a universal program, drives a distinct transcriptional course in each cell population, and they highlight key molecular processes, including ribosome biogenesis, underlying brain aging. Overall, these large-scale datasets (accessible online at https://portals.broadinstitute.org/single_cell/study/aging-mouse-brain) provide a resource for the neuroscience community that will facilitate additional discoveries directed towards understanding and modifying the aging process.

Digital infrared thermal imaging (DITI) has resurfaced in this era of modernized computer technology. Its role in the detection of breast cancer is evaluated. In this prospective clinical trial, 92 patients for whom a breast biopsy was recommended based on prior mammogram or ultrasound underwent DITI. Three scores were generated: an overall risk score in the screening mode, a clinical score based on patient information, and a third assessment by artificial neural network. Sixty of 94 biopsies were malignant and 34 were benign. DITI identified 58 of 60 malignancies, with 97% sensitivity, 44% specificity, and 82% negative predictive value depending on the mode used. Compared to an overall risk score of 0, a score of 3 or greater was significantly more likely to be associated with malignancy (30% vs 90%, P < .03). DITI is a valuable adjunct to mammography and ultrasound, especially in women with dense breast parenchyma.

Until now, no tools existed to selectively manipulate the small number of sparsely distributed neurons activated during a drug-related learned behavior. Here the authors describe a new method for selectively inactivating only those neurons activated by cocaine in an environment repeatedly paired with drug injections. Learned associations between effects of abused drugs and the drug administration environment are important in drug addiction. Histochemical and electrophysiological studies suggest that these associations are encoded in sparsely distributed nucleus accumbens neurons that are selectively activated by drugs and drug-associated cues. Although correlations have been observed between nucleus accumbens neuronal activity and responsivity to drugs and drug cues, no technique exists for selectively manipulating these activated neurons and establishing their causal role in behavioral effects of drugs and drug cues. Here we describe a new approach, which we term the 'Daun02 inactivation method', that selectively inactivates a minority of neurons previously activated by cocaine in an environment repeatedly paired with cocaine to demonstrate a causal role for these activated neurons in context-specific cocaine-induced psychomotor sensitization in rats. This method provides a new tool for studying the causal roles of selectively activated neurons in behavioral effects of drugs and drug cues and in other learned behaviors.

Cognitive problems occur in asymptomatic gene carriers of Huntington's disease (HD), and mouse models of the disease exhibit impaired learning and substantial deficits in the cytoskeletal changes that stabilize long-term potentiation (LTP). The latter effects may be related to the decreased production of brain-derived neurotrophic factor (BDNF) associated with the HD mutation. This study asked whether up-regulating endogenous BDNF levels with an ampakine, a positive modulator of AMPA-type glutamate receptors, rescues plasticity and reduces learning problems in HD (CAG140) mice. Twice-daily injections of a short half-life ampakine normalized BDNF levels, activity-driven actin polymerization in dendritic spines, and LTP stabilization in 8-week-old mutants. Comparable results were obtained in 16-week-old HD mice with more severe LTP deficits. Ampakine treatments had no measurable effect on the decreased locomotor activity observed in the mutants but offset their impairments in long-term memory. Given that ampakines are well tolerated in clinical trials and were effective in this study after brief exposures, these results suggest a novel strategy for chronic treatment of the cognitive difficulties that occur in the early stages of HD.