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Jesse L Parker,1 Andrew Vakulin,1,2 Yohannes Adama Melaku,1 Gary A Wittert,3,4 Sean A Martin,3,4 Angela L D’Rozario,2,5 Peter G Catcheside,1 Bastien Lechat,1 Barbara Toson,6 Alison J Teare,1 Sarah L Appleton,1,4,* Robert J Adams1,4,7,* 1Flinders Health and Medical Research Institute, Adelaide Institute for Sleep Health, Flinders University, Adelaide, SA, Australia; 2CIRUS, Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW, Australia; 3Freemasons Centre for Male Health and Wellbeing, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia; 4South Australian Health and Medical Research Institute, Adelaide, SA, Australia; 5The University of Sydney, Faculty of Science, School of Psychology, Sydney, NSW, Australia; 6College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia; 7Respiratory and Sleep Services, Southern Adelaide Local Health Network, Adelaide, SA, Australia*These authors contributed equally to this workCorrespondence: Jesse L Parker, Flinders Health and Medical Research Institute, Adelaide Institute for Sleep Health, Mark Oliphant Building, Flinders University, 5 Laffer Drive, Bedford Park, Adelaide, SA, 5042, Australia, Tel +61 0420431392, Email park0769@flinders.edu.auPurpose: Prospective studies examining associations between baseline sleep microarchitecture and future cognitive function recruited from small samples with predominantly short follow-up. This study examined sleep microarchitecture predictors of cognitive function (visual attention, processing speed, and executive function) after 8 years in community-dwelling men.Patients and Methods: Florey Adelaide Male Ageing Study participants (n=477) underwent home-based polysomnography (2010– 2011), with 157 completing baseline (2007– 2010) and follow-up (2018– 2019) cognitive assessments (trail-making tests A [TMT-A] and B [TMT-B] and the standardized mini-mental state examination [SMMSE]). Whole-night F4-M1 sleep EEG recordings were processed following artifact exclusion, and quantitative EEG characteristics were obtained using validated algorithms. Associations between baseline sleep microarchitecture and future cognitive function (visual attention, processing speed, and executive function) were examined using linear regression models adjusted for baseline obstructive sleep apnoea, other risk factors, and cognition.Results: The final sample included men aged (mean [SD]) 58.9 (8.9) years at baseline, overweight (BMI 28.5 [4.2] kg/m2), and well educated (75.2% ≥Bachelor, Certificate, or Trade), with majorly normal baseline cognition. Median (IQR) follow-up was 8.3 (7.9, 8.6) years. In adjusted analyses, NREM and REM sleep EEG spectral power was not associated with TMT-A, TMT-B, or SMMSE performance (all p> 0.05). A significant association of higher N3 sleep fast spindle density with worse TMT-B performance (B=1.06, 95% CI [0.13, 2.00], p=0.026) did not persist following adjustment for baseline TMT-B performance.Conclusion: In this sample of community-dwelling men, sleep microarchitecture was not independently associated with visual attention, processing speed, or executive function after 8 years.Keywords: quantitative EEG, spindles, attention, processing speed, executive function

Bastien Lechat,1 Kelly A Loffler,1 Douglas M Wallace,2,3 Amy Reynolds,1 Sarah L Appleton,1 Hannah Scott,1 Andrew Vakulin,1,4 Nicole Lovato,1,4 Robert Adams,1,4 Danny J Eckert,1 Peter G Catcheside,1 Alexander Sweetman1,4 1Adelaide Institute for Sleep Health and FHMRI Sleep Health, Flinders University, Adelaide, South Australia, Australia; 2Department of Neurology, Sleep Medicine Division, University of Miami Miller School of Medicine, Miami, FL, USA; 3Neurology Service, Bruce W. Carter Department of Veterans Affairs Medical Centre, Miami, FL, USA; 4National Centre for Sleep Health Services Research: A NHMRC Centre of Research Excellence, Flinders University, Adelaide, South Australia, AustraliaCorrespondence: Bastien Lechat, Adelaide Institute for Sleep Health and Flinders Health and Medical Research Institute: Sleep Health, Level 2A, Mark Oliphant Building, 5 Laffer Drive, Flinders University, Bedford Park, South Australia, 5042, Australia, Email bastien.lechat@flinders.edu.auPurpose: Insomnia symptoms and sleep apnea frequently co-occur and are associated with worse sleep, daytime function, mental health and quality of life, compared to either insomnia or obstructive sleep apnea (OSA) alone. This study aimed to investigate the association of symptoms of co-morbid insomnia and sleep apnea (COMISA) with all-cause mortality.Patients and Methods: Wisconsin Sleep Cohort data were analysed to assess potential associations between COMISA symptoms and all-cause mortality. Nocturnal insomnia symptoms were defined as difficulties initiating sleep, maintaining sleep, and/or early morning awakenings “often” or “almost always”, and/or regular sedative-hypnotic medicine use. OSA was defined as an apnea-hypopnea index ≥ 5/hr sleep. Participants were classified as having neither insomnia symptoms nor OSA, insomnia symptoms alone, OSA alone, or COMISA symptoms. Associations between the four groups and all-cause mortality over 20 years of follow-up were examined via multivariable adjusted Cox regression models.Results: Among 1115 adult participants (mean ± SD age 55 ± 8 years, 53% males), 19.1% had COMISA symptoms. After controlling for sociodemographic and behavioral factors, COMISA symptoms were associated with an increased risk of all-cause mortality compared to no insomnia symptoms or OSA (HR [95% CI]; 1.71 [1.00– 2.93]). OSA alone (0.91 [0.53, 1.57]) and insomnia symptoms alone (1.04 [0.55, 1.97]) were not associated with increased mortality risk.Conclusion: Co-morbid insomnia symptoms and sleep apnea is associated with increased all-cause mortality risk. Future research should investigate mechanisms underpinning COMISA and the effectiveness of different treatment approaches to reduce mortality risk for this common condition.Keywords: sleep disordered breathing, Wisconsin Sleep Cohort, COMISA, obstructive, sleep apnea, insomnia, respiratory

Mushroom-forming fungi (Agaricomycetes) have the greatest morphological diversity and complexity of any group of fungi. They have radiated into most niches and fulfil diverse roles in the ecosystem, including wood decomposers, pathogens or mycorrhizal mutualists. Despite the importance of mushroom-forming fungi, large-scale patterns of their evolutionary history are poorly known, in part due to the lack of a comprehensive and dated molecular phylogeny. Here, using multigene and genome-based data, we assemble a 5,284-species phylogenetic tree and infer ages and broad patterns of speciation/extinction and morphological innovation in mushroom-forming fungi. Agaricomycetes started a rapid class-wide radiation in the Jurassic, coinciding with the spread of (sub)tropical coniferous forests and a warming climate. A possible mass extinction, several clade-specific adaptive radiations and morphological diversification of fruiting bodies followed during the Cretaceous and the Paleogene, convergently giving rise to the classic toadstool morphology, with a cap, stalk and gills (pileate-stipitate morphology). This morphology is associated with increased rates of lineage diversification, suggesting it represents a key innovation in the evolution of mushroom-forming fungi. The increase in mushroom diversity started during the Mesozoic-Cenozoic radiation event, an era of humid climate when terrestrial communities dominated by gymnosperms and reptiles were also expanding.

Reduced upper airway muscle activity during sleep is a key contributor to obstructive sleep apnea pathogenesis. Hypoglossal nerve stimulation activates upper airway dilator muscles, including the genioglossus, and has the potential to reduce obstructive sleep apnea severity. The objective of this study was to examine the safety, feasibility and efficacy of a novel hypoglossal nerve stimulation system (HGNS; Apnex Medical, St Paul, MN, USA) in treating obstructive sleep apnea at 12 months following implantation. Thirty-one subjects (35% female, age 52.4 ± 9.4 years) with moderate to severe obstructive sleep apnea and unable to tolerate positive airway pressure underwent surgical implantation and activation of the hypoglossal nerve stimulation system in a prospective single-arm interventional trial. Primary outcomes were changes in obstructive sleep apnea severity (apnea-hypopnea index, from in-laboratory polysomnogram) and sleep-related quality of life [Functional Outcomes of Sleep Questionnaire (FOSQ)]. Hypoglossal nerve stimulation was used on 86 ± 16% of nights for 5.4 ± 1.4 h per night. There was a significant improvement (P < 0.001) from baseline to 12 months in apnea-hypopnea index (45.4 ± 17.5 to 25.3 ± 20.6 events h(-1) ) and Functional Outcomes of Sleep Questionnaire score (14.2 ± 2.0 to 17.0 ± 2.4), as well as other polysomnogram and symptom measures. Outcomes were stable compared with 6 months following implantation. Three serious device-related adverse events occurred: an infection requiring device removal; and two stimulation lead cuff dislodgements requiring replacement. There were no significant adverse events with onset later than 6 months following implantation. Hypoglossal nerve stimulation demonstrated favourable safety, feasibility and efficacy.

Insomnia and obstructive sleep apnoea (OSA) frequently co-occur and may be causally related through sleep fragmentation and/or hyperarousal mechanisms. Previous studies suggest that OSA treatment can improve insomnia severity. However, the effect of insomnia treatment on OSA severity has not been investigated. We performed a randomised controlled trial to investigate the effect of cognitive behavioural therapy for insomnia (CBTi) on OSA severity, controlling for potential sleep-stage and posture effects. 145 patients with comorbid insomnia (International Classification of Sleep Disorders, 3rd Edn) and untreated OSA (apnoea–hypopnoea index (AHI) ≥15 events·h−1 sleep) were randomised to a four-session CBTi programme or to a no-treatment control. Overnight sleep studies were completed pre- and post-treatment to measure AHI, arousal index and sleep architecture, to investigate the effect of intervention group, time, sleep stage (N1–3 or REM) and posture (supine or nonsupine) on OSA severity. The CBTi group showed a 7.5 event·h−1 greater AHI difference (mean (95% CI) decrease 5.5 (1.3–9.7) events·h−1, Cohen's d=0.2, from 36.4 events·h−1 pre-treatment) across sleep-stages and postures, compared to control (mean increase 2.0 (−2.0–6.1) events·h−1, d=0.01, from 37.5 events·h−1 at pre-treatment; interaction p=0.012). Compared to control, the CBTi group also had a greater reduction in total number (mean difference 5.6 (0.6–10.6) greater overall reduction; p=0.029) and duration of nocturnal awakenings (mean difference 21.1 (2.0–40.3) min greater reduction; p=0.031) but showed no difference in the arousal index, or sleep architecture. CBTi consolidates sleep periods and promotes a 15% decrease in OSA severity in patients with comorbid insomnia and OSA. This suggests that insomnia disorder may exacerbate OSA and provides further support for treating insomnia in the presence of comorbid OSA.

We present an analysis of over 1,100 of the approximately 10,000 predicted proteins encoded by the genome sequence of the filamentous fungus Neurospora crassa. Seven major areas of Neurospora genomics and biology are covered. First, the basic features of the genome, including the automated assembly, gene calls, and global gene analyses are summarized. The second section covers components of the centromere and kinetochore complexes, chromatin assembly and modification, and transcription and translation initiation factors. The third area discusses genome defense mechanisms, including repeat induced point mutation, quelling and meiotic silencing, and DNA repair and recombination. In the fourth section, topics relevant to metabolism and transport include extracellular digestion; membrane transporters; aspects of carbon, sulfur, nitrogen, and lipid metabolism; the mitochondrion and energy metabolism; the proteasome; and protein glycosylation, secretion, and endocytosis. Environmental sensing is the focus of the fifth section with a treatment of two-component systems; GTP-binding proteins; mitogen-activated protein, p21-activated, and germinal center kinases; calcium signaling; protein phosphatases; photobiology; circadian rhythms; and heat shock and stress responses. The sixth area of analysis is growth and development; it encompasses cell wall synthesis, proteins important for hyphal polarity, cytoskeletal components, the cyclin/cyclin-dependent kinase machinery, macroconidiation, meiosis, and the sexual cycle. The seventh section covers topics relevant to animal and plant pathogenesis and human disease. The results demonstrate that a large proportion of Neurospora genes do not have homologues in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe. The group of unshared genes includes potential new targets for antifungals as well as loci implicated in human and plant physiology and disease.

Background: Irregularities in sleep duration and sleep timing have emerged as potential risk factors for hypertension. This study examined associations between irregularity in sleep duration and timing with hypertension in a large, global sample over multiple months. Methods: Data from 12 287 adults, who used an under-mattress device to monitor sleep duration and timing and also provided blood pressure recordings on ≥5 separate occasions, were analyzed. Sleep duration irregularity was assessed as the SD in total sleep time across the ≈9-month recording period. Sleep timing irregularity was assessed as SDs in sleep onset time, sleep midpoint, and sleep offset time. Logistic regressions were conducted to investigate associations between sleep irregularity and hypertension, defined as median systolic blood pressure ≥140 mm Hg or median diastolic blood pressure ≥90 mm Hg. Results: Participants were middle-aged (mean±SD, 50±12 years), mostly men (88%) and overweight (body mass index, 28±6 kg/m−2). Sleep duration irregularity was consistently associated with an ≈9% to 17% increase in hypertension independently of the total sleep time. A ≈34-minute increase in sleep onset time irregularity was associated with a 32% increase in hypertension (1.32 [1.20–1.45]). A 32-minute increase in sleep midpoint irregularity was associated with an 18% increase in hypertension (1.18 [1.09–1.29]), while a 43-minute increase in sleep offset time irregularity was associated with an 8.9% increase in hypertension (1.09 [1.001–1.18]). Conclusions: These findings support that sleep irregularity, both in duration and timing, is a risk marker for poor cardiovascular health. Further mechanistic investigations of temporal relationships between day-to-day fluctuations in sleep duration and timing, next-day blood pressure, and other cardiovascular outcomes are warranted. [ABSTRACT FROM AUTHOR]