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Stressful life events contribute to insomnia, psychosocial functioning, and illness. Though individuals with a history of insomnia may be especially vulnerable during stressful life events, risk may be mitigated by prior intervention. This study evaluated the effect of prior digital cognitive-behavioral therapy for insomnia (dCBT-I) versus sleep education on health resilience during the COVID-19 pandemic.

COVID impact, insomnia, general- and COVID-related stress, depression, and global health were assessed in April 2020 in adults with a history of insomnia who completed a randomized controlled trial of dCBT-I (n = 102) versus sleep education control (n = 106) in 2016-2017. Regression analyses were used to evaluate the effect of intervention conditions on subsequent stress and health during the pandemic.

Insomnia symptoms were significantly associated with COVID-19 related disruptions, and those who previously received dCBT-I reported less insomnia symptoms, less general stress and COVID-related cognitive intrusions, less depression, and better global health than those who received sleep education. Moreover, the odds for resurgent insomnia was 51% lower in the dCBT-I versus control condition. Similarly, odds of moderate to severe depression during COVID-19 was 57% lower in the dCBT-I condition.

Those who received dCBT-I had increased health resilience during the COVID-19 pandemic in adults with a history of insomnia and ongoing mild to moderate mental health symptoms. These data provide evidence that dCBT-I is a powerful tool to promote mental and physical health during stressors, including the COVID-19 pandemic.

NCT02988375.

NCT02988375.The origin and deep history of retroviruses remain mysterious and contentious, largely because the diversity of retroviruses is incompletely understood. Here, we report the discovery of lokiretroviruses, a novel major lineage of retroviruses, within the genomes of a wide range of vertebrates (at least 137 species), including lampreys, ray-finned fishes, lobe-finned fishes, amphibians, and reptiles. Lokiretroviruses share a similar genome architecture with known retroviruses, but display some unique features. Interestingly, lokiretrovirus Env proteins share detectable similarity with fusion glycoproteins of viruses within the Mononegavirales order, blurring the boundary between retroviruses and negative sense single-stranded RNA viruses. Phylogenetic analyses based on reverse transcriptase demonstrate that lokiretroviruses are sister to all the retroviruses sampled to date, providing a crucial nexus for studying the deep history of retroviruses. Comparing congruence between host and virus phylogenies suggests lokiretroviruses mainly underwent cross-species transmission. Moreover, we find that retroviruses replaced their ribonuclease H and integrase domains multiple times during their evolutionary course, revealing the importance of domain shuffling in the evolution of retroviruses. Overall, our findings greatly expand our views of the diversity of retroviruses, and provide novel insights into the origin and complex evolutionary history of retroviruses.

Choroid plexus tumors (CPTs) are intraventricular brain tumors predominantly arising in children but also affecting adults. In most cases, driver mutations have not been identified, although there are reports of frequent chromosome-wide copy-number alterations and TP53 mutations, especially in choroid plexus carcinomas (CPCs).

DNA methylation profiling and RNA-sequencing was performed in a series of 47 CPTs. Samples comprised 35 choroid plexus papillomas (CPPs), 6 atypical choroid plexus papillomas (aCPPs) and 6 CPCs plus three recurrences thereof. Targeted TP53 and TERT promotor sequencing was performed in all samples. Whole exome sequencing (WES) and linked-read whole genome sequencing (WGS) was performed in 25 and 4 samples, respectively.

Tumors comprised the molecular subgroups “pediatric A” (N=11), “pediatric B” (N=12) and “adult” (N=27). Copy-number alterations mainly represented whole-chromosomal alterations with subgroup-specific enrichments (gains of Chr1, 2 and 21q in “pediatric B” and gains of Chr5 and 9 and loss of Chr21q in “adult”). RNA sequencing yielded a novel CCDC47-PRKCA fusion transcript in one adult choroid plexus papilloma patient with aggressive clinical course; an underlying Chr17 inversion was demonstrated by linked-read WGS. WES and targeted sequencing showed TP53 mutations in 7/47 CPTs (15%), five of which were children. On the contrary, TERT promoter mutations were encountered in 7/28 adult patients (25%) and associated with shorter progression-free survival (log-rank test, p=0.015).

Pediatric CPTs lack recurrent driver alterations except for TP53, whereas CPTs in adults show TERT promoter mutations or a novel CCDC47-PRKCA gene fusion, being associated with a more unfavorable clinical course.

Pediatric CPTs lack recurrent driver alterations except for TP53, whereas CPTs in adults show TERT promoter mutations or a novel CCDC47-PRKCA gene fusion, being associated with a more unfavorable clinical course.

Smoking and obesity are two modifiable risk factors for disability. We examine the impact of smoking and obesity on disability-free life expectancy (DFLE) at older ages, using two levels of disability.

We used the DYNOPTA dataset, derived by harmonizing and pooling risk factors and disability outcomes from five Australian longitudinal ageing studies. We defined mobility disability as inability to walk one kilometre, and more severe (ADL) disability by the inability to dress or bathe. Mortality data for the analytic sample (N=20,401; 81.2% women) were obtained from Government Records via data linkage. Conteltinib nmr We estimated sex-specific total life expectancy, DFLE, and years spent with disability by Interpolated Markov Chain (IMaCh) software for each combination of smoking (never vs ever), obesity (Body Mass Index ≥30 vs 18.5-<30), and education (left school age 14 or younger vs age 15 or older).

Compared to those without either risk factor, high educated non-obese smokers at age 65 lived shorter lives (men and women 2.