Excessive Daytime Sleepiness Is Associated with Changes in Salivary Inflammatory Genes Transcripts

Excessive daytime sleepiness (EDS) is a ubiquitous problem that affects public health and safety. A test that can reliably identify individuals that suffer from EDS is needed. In contrast to other methods, salivary biomarkers are an objective, inexpensive, and noninvasive method to identify individuals with inadequate sleep. Although we have previously shown that inflammatory genes are elevated in saliva samples taken from sleep deprived individuals, it is unclear if inflammatory genes will be elevated in clinical populations with EDS. In this study, salivary samples from individuals with sleep apnea were evaluated using the Taqman low density inflammation array. Transcript levels for 3 genes, including prostaglandin-endoperoxide synthase 2 (PTGS2), were elevated in patients with sleep apnea. Interestingly, PTGS2 was also elevated in patients with EDS but who did not have sleep apnea. These data demonstrate the feasibility of using salivary transcript levels to identify individuals that self-report excessive daytime sleepiness

Baseline characteristics of the North American Prodromal Synucleinopathy cohort

OBJECTIVE: Rapid eye movement (REM) sleep behavior disorder (RBD) is widely considered a prodromal synucleinopathy, as most with RBD develop overt synucleinopathy within ~10 years. Accordingly, RBD offers an opportunity to test potential treatments at the earliest stages of synucleinopathy. The North American Prodromal Synucleinopathy (NAPS) Consortium has created a multisite RBD participant, primarily clinic-based cohort to better understand characteristics at diagnosis, and in future work, identify predictors of phenoconversion, develop synucleinopathy biomarkers, and enable early stage clinical trial enrollment. METHODS: Participants ≥18 years of age with overnight polysomnogram-confirmed RBD without Parkinson\u27s disease, dementia, multiple system atrophy, or narcolepsy were enrolled from nine sites across North America (8/2018 to 4/2021). Data collection included family/personal history of RBD and standardized assessments of cognitive, motor, sensory, and autonomic function. RESULTS: Outcomes are primarily reported based on sex (361 total: n = 295 male, n = 66 female), and secondarily based on history of antidepressant use (n = 200 with, n = 154 without; with correction for sex differences) and based on extent of synucleinopathy burden (n = 56 defined as isolated RBD, n = 305 defined as RBD+ [i.e., exhibiting ≥1 abnormality]). Overall, these participants commonly demonstrated abnormalities in global cognition (MoCA; 38%), motor function (alternate tap test; 48%), sensory (BSIT; 57%), autonomic function (orthostatic hypotension, 38.8%), and anxiety/depression (BAI and PHQ-9; 39.3% and 31%, respectively). INTERPRETATION: These RBD participants, assessed with extensive history, demographic, cognitive, motor, sensory, and autonomic function demonstrated a lack of sex differences and high frequency of concomitant neurological abnormalities. These participants will be valuable for future longitudinal study and neuroprotective clinical trials

Comparison of single-channel EEG, actigraphy, and sleep diary in cognitively normal and mildly impaired older adults

STUDY OBJECTIVES: Multiple methods for monitoring sleep-wake activity have identified sleep disturbances as risk factors for Alzheimer disease (AD). In order to identify the level of agreement between different methods, we compared sleep parameters derived from single-channel EEG (scEEG), actigraphy, and sleep diaries in cognitively normal and mildly impaired older adults. METHODS: Two hundred ninety-three participants were monitored at home for up to six nights with scEEG, actigraphy, and sleep diaries. Total sleep time (TST), sleep efficiency (SE), sleep onset latency (SOL), and wake after sleep onset (WASO) were calculated using each of these methods. In 109 of the 293 participants, the ratio of cerebrospinal fluid concentrations of phosphorylated tau (p-tau) and amyloid-β-42 (Aβ42) was used as a biomarker for AD pathology. RESULTS: Agreement was highest for TST across instruments, especially in cognitively normal older adults. Overall, scEEG and actigraphy appeared to have greater agreement for multiple sleep parameters than for scEEG and diary or actigraphy and diary. Levels of agreement between scEEG and actigraphy overall decreased in mildly impaired participants and those with biomarker evidence of AD pathology, especially for measurements of TST. CONCLUSIONS: Caution should be exercised when comparing scEEG and actigraphy in individuals with mild cognitive impairment or with AD pathology. Sleep diaries may capture different aspects of sleep compared to scEEG and actigraphy. Additional studies comparing different methods of measuring sleep-wake activity in older adults are necessary to allow for comparison between studies using different methods

Interpretative Phenomenological Analysis of Soldiers’ Experiences of Being Married and Serving in the British Army

© 2016, Copyright © Taylor & Francis Group, LLC. ABSTRACT: Research suggests certain aspects of military life, especially operational deployments, may negatively impact military marriages. However, much of this research is from the United States and uses deductive quantitative methods. Qualitative research investigating the lived experiences of forming and maintaining marriages was conducted with six male U.K. Army personnel. Semistructured interviews were analyzed, using Interpretative Phenomenological Analysis, identifying five themes, each representing different dilemmas the soldiers’ had to balance to maintain successful marriages and Army careers. These five themes are best understood as practical, emotional, and cultural dilemmas that can be alleviated with practical and emotional methods; such factors could be used to build resilience in soldier’s marriages. These possible resilience factors could shape the content of interventions to increase resiliency in military marriages

Relationship Difficulties Among U.K. Military Personnel: Impact of Sociodemographic, Military, and Deployment-Related Factors

© 2015, Taylor & Francis Group, LLC. Military work, especially operational deployments, may impact the romantic relationships of military personnel. Using a subsample of 7,581 participants from a cohort study of U.K. military personnel (data collected between 2007 and 2009), the prevalence of relationship difficulties and associations with sociodemographic, military-, and deployment-related characteristics was examined. Most participants did not report experiencing relationship difficulties. Adjusted regression analyses indicate that childhood adversity, limited support for and from partners, being in unmarried relationships, financial problems, deploying for more than 13 months in 3 years, and work being above trade, ability, and experience were key factors associated with relationship difficulties. The likelihood of U.K. military personnel experiencing relationship difficulties is increased because of personal vulnerabilities that may be exacerbated in the military context

Cross-translational studies in human and Drosophila identify markers of sleep loss

Inadequate sleep has become endemic, which imposes a substantial burden for public health and safety. At present, there are no objective tests to determine if an individual has gone without sleep for an extended period of time. Here we describe a novel approach that takes advantage of the evolutionary conservation of sleep to identify markers of sleep loss. To begin, we demonstrate that IL-6 is increased in rats following chronic total sleep deprivation and in humans following 30 h of waking. Discovery experiments were then conducted on saliva taken from sleep-deprived human subjects to identify candidate markers. Given the relationship between sleep and immunity, we used Human Inflammation Low Density Arrays to screen saliva for novel markers of sleep deprivation. Integrin αM (ITGAM) and Anaxin A3 (AnxA3) were significantly elevated following 30 h of sleep loss. To confirm these results, we used QPCR to evaluate ITGAM and AnxA3 in independent samples collected after 24 h of waking; both transcripts were increased. The behavior of these markers was then evaluated further using the power of Drosophila genetics as a cost-effective means to determine whether the marker is associated with vulnerability to sleep loss or other confounding factors (e.g., stress). Transcript profiling in flies indicated that the Drosophila homologues of ITGAM were not predictive of sleep loss. Thus, we examined transcript levels of additional members of the integrin family in flies. Only transcript levels of scab, the Drosophila homologue of Integrin α5 (ITGA5), were associated with vulnerability to extended waking. Since ITGA5 was not included on the Low Density Array, we returned to human samples and found that ITGA5 transcript levels were increased following sleep deprivation. These cross-translational data indicate that fly and human discovery experiments are mutually reinforcing and can be used interchangeably to identify candidate biomarkers of sleep loss

Induction of Autophagy in Porcine Kidney Cells by Quantum Dots: A Common Cellular Response to Nanomaterials?

Quantum dots (QDs) are being investigated as novel in vivo imaging agents. The leaching of toxic metals from these QDs in biological systems is of great concern. This study compared the cytotoxic mechanisms of two QD species made of different core materials (cadmium selenide [CdSe] vs. indium gallium phosphide [InGaP]) but similar core sizes (5.1 vs. 3.7 nm) and surface compositions (both ZnS capped, lipid-coated and pegylated). The CdSe QD was found to be 10-fold more toxic to porcine renal proximal tubule cells (LLC-PK1) than the InGaP QD on a molar basis, as determined by MTT assay (48 h IC50 10nM for CdSe vs. 100nM for InGaP). Neither of the QD species induced appreciable oxidative stress, as determined by lipid peroxide and reduced glutathione content, suggesting that toxicity was not metal associated. In agreement, treatment of cells with CdSe QDs was not associated with changes in metallothionein-IA (MT-IA) gene expression or Cd-associated caspase 3 enzyme activation. By contrast, incubation of the LLC-PK1 cells with the InGaP QD resulted in a dramatic increase in MT-IA expression by 21- and 43-fold, at 8 and 24 h, respectively. The most remarkable finding was evidence of extensive autophagy in QD-treated cells, as determined by Lysotracker Red dye uptake, TEM, and LC3 immunobloting. Autophagy induction has also been described for other nanomaterials and may represent a common cellular response. These data suggest that QD cytotoxicity is dependent upon properties of the particle as a whole, and not exclusively the metal core materials

Cross-Translational Studies in Human and <i>Drosophila</i> Identify Markers of Sleep Loss

Inadequate sleep has become endemic, which imposes a substantial burden for public health and safety. At present, there are no objective tests to determine if an individual has gone without sleep for an extended period of time. Here we describe a novel approach that takes advantage of the evolutionary conservation of sleep to identify markers of sleep loss. To begin, we demonstrate that IL-6 is increased in rats following chronic total sleep deprivation and in humans following 30 h of waking. Discovery experiments were then conducted on saliva taken from sleep-deprived human subjects to identify candidate markers. Given the relationship between sleep and immunity, we used Human Inflammation Low Density Arrays to screen saliva for novel markers of sleep deprivation. Integrin αM (ITGAM) and Anaxin A3 (AnxA3) were significantly elevated following 30 h of sleep loss. To confirm these results, we used QPCR to evaluate ITGAM and AnxA3 in independent samples collected after 24 h of waking; both transcripts were increased. The behavior of these markers was then evaluated further using the power of Drosophila genetics as a cost-effective means to determine whether the marker is associated with vulnerability to sleep loss or other confounding factors (e.g., stress). Transcript profiling in flies indicated that the Drosophila homologues of ITGAM were not predictive of sleep loss. Thus, we examined transcript levels of additional members of the integrin family in flies. Only transcript levels of scab, the Drosophila homologue of Integrin α5 (ITGA5), were associated with vulnerability to extended waking. Since ITGA5 was not included on the Low Density Array, we returned to human samples and found that ITGA5 transcript levels were increased following sleep deprivation. These cross-translational data indicate that fly and human discovery experiments are mutually reinforcing and can be used interchangeably to identify candidate biomarkers of sleep loss.</p

Immune-related transcripts are associated with increased sleep drive in <i>Drosophila</i> clock mutants.

<p>(<b>A</b>) Immune related transcripts are substantially increased in <i>cyc⁰¹</i> mutants following 7 h of sleep deprivation but are not consistently activated when 7 h of waking is induced by starvation; data are expressed as % change from untreated siblings. Experiments were conducted in constant darkness (DD). (<b>B</b>–<b>E</b>) Transcript levels for <i>AttB</i>, <i>Dro</i>, <i>Mtk</i> and <i>Drs</i> in <i>tim⁰¹</i> mutants following 3, 6, 9 and 12 h of sleep deprivation. Immune related transcripts are consistently elevated following 9 and 12 hour sleep deprivation (Light Green) but not after 3 or 6 h of sleep deprivation when no sleep rebound is observed (dark Green).</p