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We showed greater memory improvement after a night of sleep with zolpidem, compared to placebo, replicating a prior nap study. Additionally, zolpidem increased sigma power, decreased theta and delta power, and altered the phase angle of spindle-SO coupling, compared to placebo. Spindle density, theta power, and spindle-SO coupling, were associated with next-day memory performance. These results are consistent with the hypothesis that sleep, specifically the timing and amount of sleep spindles, plays a causal role in long-term formation of episodic memories. Furthermore, our results emphasize the role of NREM theta activity in human memory consolidation. © Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.OBJECTIVE We sometimes encounter unintentional flow of contrast into the facet joints during cervical interlaminar epidural injection, which leads to false-positive epidural injection. The purposes of this study were to evaluate the rate of facet flow of contrast and to investigate various factors associated with injection into the space of Okada during fluoroscopy-guided cervical interlaminar epidural injection. SETTING AND SUBJECTS Images from consecutive cases of fluoroscopy-guided cervical interlaminar epidural injection performed at a single institution between July 2015 and July 2018 were obtained and reviewed. METHODS Cases of epidural injection were classified as either facet flow or no facet flow. Multivariate logistic regression was used to identify the predictive factors of unintended injection into the Okada space. RESULTS A total of 2,006 cases were included. Intra-articular flow was identified in 6.0% of cases (121/2,006). All cases of flow of contrast into the facet joints were recognized, and appropriate epidurograms were obtained during the procedures. The highest rate of unintended facet flow of the contrast (10.1%, 44/436) occurred at C5-6. Cervical interlaminar epidural injection at C5-6 and above (adjusted odds ratio [aOR] = 1.929, P = 0.001) and the paramidline approach for epidural injection (aOR = 2.427, P less then 0.001) were associated with injection into the space of Okada. CONCLUSIONS We detected injection into the space of Okada during fluoroscopy-guided cervical interlaminar epidural injection in 6.0% of procedures. Cervical interlaminar epidural injection at C5-6 and above and the paramidline approach for epidural injection were positive predictors of unintentional facet flow of the contrast. © The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.INTRODUCTION Fetal changes in DNA methylation may underlie associations of maternal smoking during pregnancy with adverse outcomes in children. We examined critical periods and doses of maternal smoking during pregnancy in relation to newborn DNA methylation, and associations of paternal smoking with newborn DNA methylation. METHODS This study was embedded in the Generation R Study, a population-based prospective cohort study from early pregnancy onwards. We assessed parental smoking during pregnancy using questionnaires. We analyzed associations of prenatal smoke exposure with newborn DNA methylation at 5,915 known maternal smoking-related Cytosine-phosphate-Guanine sites (CpGs) in 1,261 newborns using linear regression. Associations with FDR-corrected p-values less then 0.05 were taken forward. RESULTS Sustained maternal smoking was associated with newborn DNA methylation at 1,391 CpGs, compared to never-smoking. Neither quitting smoking early in pregnancy nor former smoking were associated with DNA methylion in the newborns at CpGs associated with sustained smoking. If the relevance of DNA methylation for clinical outcomes is established, these results may help in counselling parents-to-be about quitting smoking. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. https://www.selleckchem.com/products/ziritaxestat.html For permissions, please e-mail journals.permissions@oup.com.Ever since the availability of genomes from Neanderthals, Denisovans and ancient humans, the field of evolutionary genomics has been searching for protein coding variants that may hold clues to how our species evolved over the last ∼ 400,000 years. In this study, we identify such variants in the human-specific NOTCH2NL gene family, which were recently identified as possible contributors to the evolutionary expansion of the human brain. We find evidence for the existence of unique protein-coding NOTCH2NL variants in Neanderthals and Denisovans which could affect their ability to activate Notch signaling. Furthermore, in the Neanderthal and Denisovan genomes, we find unusual NOTCH2NL configurations, not found in any of the modern human genomes analyzed. Finally, genetic analysis of archaic and modern humans reveals ongoing adaptive evolution of modern human NOTCH2NL genes, identifying three structural variants acting complementary to drive our genome to produce a lower dosage of NOTCH2NL protein. Because copy-number variations of the 1q21.1 locus, encompassing NOTCH2NL genes, are associated with severe neurological disorders, this seemingly contradicting drive towards low levels of NOTCH2NL protein indicates that the optimal dosage of NOTCH2NL may have not yet been settled in the human population. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.OBJECTIVE The objective was to perform a systematic review and meta-analysis of the literature on the effects of buprenorphine on chronic pain outcomes (i.e., patient-reported pain intensity) in patients with and without opioid use disorder (OUD). DESIGN Ovid/Medline, PubMed, Embase, and the Cochrane Library were searched for studies that explored the effectiveness (in reducing pain) of buprenorphine treatment for chronic pain patients with and without a history of OUD. Randomized controlled trials and observational studies were included in the review. METHODS Two separate searches were conducted to identify buprenorphine trials that included chronic pain patients either with or without OUD. Five studies used validated pain report measures and included a chronic pain population with OUD. Nine studies used validated report measures and included chronic pain patients without OUD. Meta-analysis was performed using the R, version 3.2.2, Metafor package, version 1.9-7. RESULTS The meta-analysis revealed that buprenorphine has a beneficial effect on pain intensity overall, with a small mean effect size in patients with comorbid chronic pain and OUD and a moderate- to large-sized effect in chronic pain patients without OUD.
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