295 results on '"Walker MP"'
Search Results
2. Old Brains Come Uncoupled in Sleep: Slow Wave-Spindle Synchrony, Brain Atrophy, and Forgetting
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Helfrich, RF, Mander, BA, Jagust, WJ, Knight, RT, and Walker, MP
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Male ,Aging ,overnight forgetting ,1.1 Normal biological development and functioning ,Neurodegenerative ,Basic Behavioral and Social Science ,Young Adult ,atrophy ,hippocampus-dependent memory consolidation ,Clinical Research ,Underpinning research ,Behavioral and Social Science ,directional cross-frequency coupling ,Acquired Cognitive Impairment ,Humans ,2.1 Biological and endogenous factors ,Psychology ,Aetiology ,hierarchical nesting ,Aged ,Memory Consolidation ,prefrontal cortex ,Neurology & Neurosurgery ,Neurosciences ,Brain ,sleep spindles ,Brain Disorders ,age-related memory decline ,Neurological ,Female ,Mental health ,Cognitive Sciences ,Sleep ,Sleep Research ,slow oscillation - Abstract
© 2017 Elsevier Inc. The coupled interaction between slow-wave oscillations and sleep spindles during non-rapid-eye-movement (NREM) sleep has been proposed to support memory consolidation. However, little evidence in humans supports this theory. Moreover, whether such dynamic coupling is impaired as a consequence of brain aging in later life, contributing to cognitive and memory decline, is unknown. Combining electroencephalography (EEG), structural MRI, and sleep-dependent memory assessment, we addressed these questions in cognitively normal young and older adults. Directional cross-frequency coupling analyses demonstrated that the slow wave governs a precise temporal coordination of sleep spindles, the quality of which predicts overnight memory retention. Moreover, selective atrophy within the medial frontal cortex in older adults predicted a temporal dispersion of this slow wave-spindle coupling, impairing overnight memory consolidation and leading to forgetting. Prefrontal-dependent deficits in the spatiotemporal coordination of NREM sleep oscillations therefore represent one pathway explaining age-related memory decline. Helfrich et al. demonstrate that the precise coupling between sleeping brainwaves, called slow waves and spindles, supports memory retention. However, this brainwave coupling during sleep is impaired in older adults due to loss of tissue in the medial frontal lobe, resulting in next-day forgetting.
- Published
- 2018
3. Implant cast accuracy as a function of impression techniques and impression material viscosity.
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Walker MP, Ries D, and Borello B
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Purpose: The aim of this study was to compare implant cast accuracy as a function of impression technique, closed tray impressions using indirect, metal impression copings at the implant level or direct, plastic impression caps at the abutment level, and impression material viscosity combinations. Materials and Methods: A stainless steel master model with three implant replicas was utilized to produce Type IV stone casts. Master model impressions were made using closed trays at the implant level with screw-on metal impression copings (indirect/implant level) or at the abutment level with snap-on plastic impression caps (direct/abutment level). With both techniques, either medium-body or heavy-body polyether impression material was syringed around the implant impression coping or abutment impression cap with medium body material in a custom tray. Twenty casts were produced with 5 casts in each test group. A measuring microscope (0.001 mm accuracy) was used to measure cast inter-implant or inter-abutment distances. Cast accuracy was calculated based on the percent difference of the measurements as compared to the master model. Results: A repeated measures 2-factor ANOVA (alpha = .05) indicated no significant difference in cast accuracy as a function of impression viscosity. However, cast accuracy was significantly different between casts made with indirect/implant level versus direct/abutment level impressions. With the plastic impression caps, the cast inter-abutment distances were larger than the master model, with mean percent differences of 0.19% to 0.24% across the 3 measurement sites. In contrast, with the metal impression coping impressions, the cast inter-implant distances were almost equal to or slightly smaller than the master model, with mean percent differences -- 0.06% to 0.02%. Conclusions: Impression material viscosity does not appear to be a critical factor for implant cast accuracy. However, casts made with indirect, metal impression copings might be more accurate than casts made with direct, plastic impression caps. This could be an especially important factor with casts used to fabricate multiple-implant restorations. [ABSTRACT FROM AUTHOR]
- Published
- 2008
4. β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation
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Mander, BA, Marks, SM, Vogel, JW, Rao, V, Lu, B, Saletin, JM, Ancoli-Israel, S, Jagust, WJ, and Walker, MP
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musculoskeletal, neural, and ocular physiology ,mental disorders ,psychological phenomena and processes - Abstract
© 2015 Nature America, Inc. Independent evidence associates β-amyloid pathology with both non-rapid eye movement (NREM) sleep disruption and memory impairment in older adults. However, whether the influence of β-amyloid pathology on hippocampus-dependent memory is, in part, driven by impairments of NREM slow wave activity (SWA) and associated overnight memory consolidation is unknown. Here we show that β-amyloid burden in medial prefrontal cortex (mPFC) correlates significantly with the severity of impairment in NREM SWA generation. Moreover, reduced NREM SWA generation was further associated with impaired overnight memory consolidation and impoverished hippocampal-neocortical memory transformation. Furthermore, structural equation models revealed that the association between mPFC β-amyloid pathology and impaired hippocampus-dependent memory consolidation was not direct, but instead statistically depended on the intermediary factor of diminished NREM SWA. By linking β-amyloid pathology with impaired NREM SWA, these data implicate sleep disruption as a mechanistic pathway through which β-amyloid pathology may contribute to hippocampus-dependent cognitive decline in the elderly.
- Published
- 2015
5. Issues surrounding sleep-dependent memory consolidation and plasticity
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Walker Mp
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Pharmacology ,Cognitive science ,Sleep Stages ,Neuronal Plasticity ,Time Factors ,Consolidation (soil) ,Brain ,Cell Biology ,Plasticity ,Sleep in non-human animals ,Memory processing ,Cellular and Molecular Neuroscience ,Memory development ,Memory ,Neuroplasticity ,Animals ,Humans ,Molecular Medicine ,Memory consolidation ,Sleep ,Psychology ,Molecular Biology - Abstract
There is a growing body of evidence in support of sleep-dependent memory consolidation and plasticity. However, there are also examples of memory development and plasticity in the absence of sleep, casting doubt on an exclusive sleep-dependent memory hypothesis. As a result, polarized stances have arisen within the field. Here we reflect on these findings, and explore how they maybe reconcilable in a unified approach to understanding the roles of wake, sleep and specific sleep stages in successful memory processing and brain plasticity.
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- 2004
6. Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging
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Mander, BA, Rao, V, Lu, B, Saletin, JM, Lindquist, JR, Ancoli-Israel, S, Jagust, W, and Walker, MP
- Abstract
Aging has independently been associated with regional brain atrophy, reduced slow wave activity (SWA) during non-rapid eye movement (NREM) sleep and impaired long-term retention of episodic memories. However, whether the interaction of these factors represents a neuropatholgical pathway associated with cognitive decline in later life remains unknown. We found that age-related medial prefrontal cortex (mPFC) gray-matter atrophy was associated with reduced NREM SWA in older adults, the extent to which statistically mediated the impairment of overnight sleep-dependent memory retention. Moreover, this memory impairment was further associated with persistent hippocampal activation and reduced task-related hippocampal-prefrontal cortex functional connectivity, potentially representing impoverished hippocampal-neocortical memory transformation. Together, these data support a model in which age-related mPFC atrophy diminishes SWA, the functional consequence of which is impaired long-term memory. Such findings suggest that sleep disruption in the elderly, mediated by structural brain changes, represents a contributing factor to age-related cognitive decline in later life. © 2013 Nature America, Inc.
- Published
- 2013
7. Flowable Fill Backfill for Use in Sequential Excavations in Contaminated Soil
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Walker, MP, primary and Ash, JR, additional
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8. Vertical dimensional stability and rigidity of occlusal registration materials.
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Walker MP, Wu E, Heckman ME, and Alderman N
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Dimensionally accurate occlusal registration records are essential for restorative dentistry; moreover, since records are not used immediately or may be used more than once, the registration material should exhibit accuracy over time (a concept known as dimensional stability). It has been speculated that materials with increased hardness or rigidity should produce more accurate registration records due to an increased resistance to distortion.This study compared the rigidity and associated dimensional accuracy of a recently marketed bisacrylic occlusal registration material and a vinyl polysiloxane (VPS). Maxillary and mandibular typodont arches were mounted on a plasterless articulator from which teeth No. 3, 13, and 15 had been removed to simulate edentulous spaces. After preparing teeth No. 2, 4, 12, and 14 as bridge abutments, the remaining teeth were equilibrated selectively to produce even anterior contact. Four digital photographs were taken to make vertical interarch measurements at four locations (teeth No. 3, 7, 10, and 14). Following initial photos (controls), 10 interocclusal records were made using each registration material, with material placed only in the segments in which teeth were prepared. The records were used for mounting the maxillary arch against the mandibular arch after 48, 72, and 120 hours.There were significant effects on vertical dimensional change related to arch location, material, and mounting time. Both materials demonstrated significantly larger posterior vertical openings than anterior vertical openings, while the bisacrylate produced a larger posterior opening than VPS at 48 and 72 hours and a larger anterior opening at all mounting times. There also was a significant difference in hardness/rigidity due to material and measurement time; at all measurement times, bisacrylate exhibited a significantly higher hardness number. [ABSTRACT FROM AUTHOR]
- Published
- 2009
9. Post-radiation dental index: development and reliability.
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Walker MP, Williams KB, Wichman B, Walker, Mary P, Williams, Karen B, and Wichman, Brian
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Goals Of the Work: The aim of this paper was to develop, validate, and assess the reliability of a clinical index for assessing post-radiation dentition breakdown.Materials and Methods: An expert panel of four dentists with expertise in post-radiation patient care, oral radiology, and mineralized tissues reviewed a series of clinical photographs (n = 60) depicting a wide range of post-radiation lesions varying in size, severity, and location. Based on panel input related to lesion severity rankings and cut-points along a continuum of destruction, a semiquantitative, ordinal lesion scale was developed. A companion scale was developed to account for existing restorations. The index was then reviewed by a separate panel of dental clinician/researchers for confirmation of face and content validity and was refined based on their input. Following index approval by the expert and confirmatory panels, the index was evaluated for test-retest reliability by two educator/clinicians. After a brief calibration session, examiners reviewed and independently scored a second series of lesion images (n = 60). One week later, the same examiners independently scored the same images displayed in a different order. Inter- and intra-rater reliability and agreement were assessed (Spearman r and Kappa statistic).Main Results: Respective to sessions 1 and 2, inter-rater reliability values were r = 0.97 and r = 0.98, with Kappa values of kappa = 0.93 and kappa = 0.95. Respective intra-rater reliability and agreement values were 0.99 and 0.98 (rater 1), and 0.98 and 0.95 (rater 2).Conclusions: A new index was developed and subsequently demonstrated face validity and excellent inter- and intra-rater reliability for potentially evaluating the severity of post-radiation dentition breakdown. [ABSTRACT FROM AUTHOR]- Published
- 2008
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10. Sleep and memory: the ongoing debate.
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Stickgold R and Walker MP
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- 2005
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11. Rebuttal.
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Stickgold R and Walker MP
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- 2005
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12. Cognitive consequences of sleep and sleep loss.
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Walker MP
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- 2008
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13. Maintenance of the esthetic integrity of dental restorations: authors examine effect of polishing on restorative materials [corrected] [published erratum appears in RDH 2003 May;23(5)].
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Barnes CM, Covey DA, and Walker MP
- Published
- 2003
14. The new science of sleep: From cells to large-scale societies.
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Sharon O, Ben Simon E, Shah VD, Desel T, and Walker MP
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- Animals, Humans, Brain physiology, Sleep physiology
- Abstract
In the past 20 years, more remarkable revelations about sleep and its varied functions have arguably been made than in the previous 200. Building on this swell of recent findings, this essay provides a broad sampling of selected research highlights across genetic, molecular, cellular, and physiological systems within the body, networks within the brain, and large-scale social dynamics. Based on this raft of exciting new discoveries, we have come to realize that sleep, in this moment of its evolution, is very much polyfunctional (rather than monofunctional), yet polyfunctional for reasons we had never previously considered. Moreover, these new polyfunctional insights powerfully reaffirm sleep as a critical biological, and thus health-sustaining, requisite. Indeed, perhaps the only thing more impressive than the unanticipated nature of these newly emerging sleep functions is their striking divergence, from operations of molecular mechanisms inside cells to entire group societal dynamics., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sharon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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15. Effect of Model Body Type and Print Angle on the Accuracy of 3D-Printed Orthodontic Models.
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Lohfeld S, Belnap B, Retrouvey JM, and Walker MP
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The assortment of low-cost 3D printers for "in-practice" use, e.g., for clear aligner therapies, is ever increasing. To address concerns about the accuracy of orthodontic models produced on such printers when cost-efficient modes of 3D printing are employed, this study examined the effect of print model body type and print angulation on accuracy. Six printing-configuration groups were included: two model types (solid or hollow shell) combined with three print angles (0°, 70°, or 90°) with 10 models/group; all models were printed with 100 µm layer thickness using a digital light processing-based three-dimensional printer. Eleven selected structures and distances were measured on the printed models with a digital microscope and compared to the same measures on a digitized master model. The clinically acceptable range was set at ±0.25 mm difference from the master model for single tooth measurements (intra-tooth) and ±0.5 mm for cross-arch measurements (inter-tooth). For individual measurements across all models, 98% fell within clinical acceptability. For mean measurements within each model group, only canine height for the shell-0° model had a mean difference (-0.26 mm ± 0.03) outside the clinically acceptable range for intra-tooth measurements. Standard deviations for all intra-tooth measurements were within 0.07 mm. While none of the mean inter-tooth measurements exceeded the acceptability range, the standard deviations were larger (0.04 to 0.30 mm). The accuracy of the orthodontic models for clear aligner therapies was not impacted beyond the clinically acceptable range when altering model body type and print angulation to improve efficiency of 3D printing. These findings suggest greater flexibility of the practitioner to alter print settings to address time and cost efficiency in various clinical scenarios and still maintain clinically acceptable model accuracy.
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- 2024
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16. The Negative Effects of Travel on Student Athletes Through Sleep and Circadian Disruption.
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Heller HC, Herzog E, Brager A, Poe G, Allada R, Scheer F, Carskadon M, de la Iglesia HO, Jang R, Montero A, Wright K, Mouraine P, Walker MP, Goel N, Hogenesch J, Van Gelder RN, Kriegsfeld L, Mah C, Colwell C, Zeitzer J, Grandner M, Jackson CL, Roxanne Prichard J, Kay SA, and Paul K
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- Humans, Jet Lag Syndrome, Athletes, Students, Travel, Circadian Rhythm, Sleep
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Collegiate athletes must satisfy the academic obligations common to all undergraduates, but they have the additional structural and social stressors of extensive practice time, competition schedules, and frequent travel away from their home campus. Clearly such stressors can have negative impacts on both their academic and athletic performances as well as on their health. These concerns are made more acute by recent proposals and decisions to reorganize major collegiate athletic conferences. These rearrangements will require more multi-day travel that interferes with the academic work and personal schedules of athletes. Of particular concern is additional east-west travel that results in circadian rhythm disruptions commonly called jet lag that contribute to the loss of amount as well as quality of sleep. Circadian misalignment and sleep deprivation and/or sleep disturbances have profound effects on physical and mental health and performance. We, as concerned scientists and physicians with relevant expertise, developed this white paper to raise awareness of these challenges to the wellbeing of our student-athletes and their co-travelers. We also offer practical steps to mitigate the negative consequences of collegiate travel schedules. We discuss the importance of bedtime protocols, the availability of early afternoon naps, and adherence to scheduled lighting exposure protocols before, during, and after travel, with support from wearables and apps. We call upon departments of athletics to engage with sleep and circadian experts to advise and help design tailored implementation of these mitigating practices that could contribute to the current and long-term health and wellbeing of their students and their staff members., Competing Interests: Conflict of interest statementThe authors have no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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17. Correction: Sleep loss leads to the withdrawal of human helping across individuals, groups, and large-scale societies.
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Simon EB, Vallat R, Rossi A, and Walker MP
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[This corrects the article DOI: 10.1371/journal.pbio.3001733.]., (Copyright: © 2023 Simon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2023
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18. Sleep, alcohol, and caffeine in financial traders.
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Song F and Walker MP
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- Humans, Longitudinal Studies, Ethanol pharmacology, Alcohol Drinking, Caffeine adverse effects, Sleep
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Alcohol and caffeine are two of the most commonly used substances for altering human consciousness. While their adverse effects on sleep have been separately examined in the laboratory and epidemiological levels, how they impact real-world night-to-night sleep, in isolation or together, remains unclear. This is especially true in occupations wherein the use of alcohol and caffeine is high (e.g., financial services sector). Using a six-week micro-longitudinal study, here we examined the real-world impact of alcohol, caffeine, and their combined consumption in a cohort of financial traders. We demonstrate that alcohol consumption significantly degrades the subjective quality of sleep (p < 0.001). Caffeine consumption led to a different phenotype of sleep impairment, resulting in a detrimental reduction in sleep quantity (p = 0.019), rather than a marked alteration in sleep quality. Contrary to our hypothesis, when consumed in combination, evening alcohol consumption interacted with ongoing caffeine consumption such that alcohol partially mitigated the impairments in sleep quantity associated with caffeine (p = 0.032). This finding suggests the sedating effects of alcohol and the psychoactive stimulant effects of caffeine obscure each other's impact on sleep quantity and sleep quality, respectively-potentially explaining their interdependent use in this cohort (i.e., "self-medication" of evening sedation with alcohol to combat the prior daytime ingestion of caffeine and vice versa). More generally, these results contribute to a unique understanding of the singular and combinatory impacts of two of the most commonly used substances for augmenting human consciousness under free-living, real-world conditions, the performance-impairing (and thus economic-cost) consequences of which may be important to the business sector and the society., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Song, Walker. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2023
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19. Effect of Different Crosslinkers on Denatured Dentin Collagen's Biostability, MMP Inhibition and Mechanical Properties.
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Nisar S, Hass V, Wang R, Walker MP, and Wang Y
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Objective: Sound, natural dentin collagen can be stabilized against enzymatic degradation through exogenous crosslinking treatment for durable bonding; however, the effect on denatured dentin (DD) collagen is unknown. Hence, the ability of different crosslinkers to enhance/restore the properties of DD collagen was assessed., Methods: Demineralized natural and DD collagen films (7 mm × 7 mm × 7 µm) and beams (0.8 mm × 0.8 mm × 7 mm) were prepared. DD collagen was experimentally produced by heat or acid exposure, which was then assessed by various techniques. All specimens were then treated with 1 wt% of chemical crosslinker 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/n-hydroxysuccinimide (EDC/NHS) and two structurally different flavonoids-theaflavins (TF) from black tea and type-A proanthocyanidins from cranberry juice (CR) for either 30 s or 1 h. The controls were untreated. Dentin films were assessed for chemical interaction and cross-linking effect by FTIR, biostability against exogenous collagenase by weight loss (WL) and hydroxyproline release (HYP), and endogenous matrix metalloproteinases (MMPs) activity by confocal laser microscopy. Dentin beams were evaluated for tensile properties. Data were analyzed using ANOVA and Tukey's test (α = 0.05)., Results: Compared with natural collagen, DD collagen showed pronounced structural changes, altered biostability and decreased mechanical properties, which were then improved to various degrees that were dependent on the crosslinkers used, with EDC/NHS being the least effective. Surprisingly, the well-known MMP inhibitor EDC/NHS showed negligible effect on or even increased MMP activity in DD collagen. As compared with control, cross-linking induced by TF and CR significantly increased collagen biostability (reduced WL and HYP release, p < 0.05), MMP inhibition ( p < 0.001) and mechanical properties ( p < 0.05), regardless of denaturation., Conclusions: DD collagen cannot or can only minimally be stabilized via EDC/NHS crosslinking; however, the challenging substrate of DD collagen can be enhanced or restored using the promising flavonoids TF and CR.
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- 2023
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20. Human REM sleep recalibrates neural activity in support of memory formation.
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Lendner JD, Niethard N, Mander BA, van Schalkwijk FJ, Schuh-Hofer S, Schmidt H, Knight RT, Born J, Walker MP, Lin JJ, and Helfrich RF
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- Humans, Mental Recall, Calcium, Cardiac Electrophysiology, Sleep, REM, Sleep
- Abstract
The proposed mechanisms of sleep-dependent memory consolidation involve the overnight regulation of neural activity at both synaptic and whole-network levels. Now, there is a lack of in vivo data in humans elucidating if, and how, sleep and its varied stages balance neural activity, and if such recalibration benefits memory. We combined electrophysiology with in vivo two-photon calcium imaging in rodents as well as intracranial and scalp electroencephalography (EEG) in humans to reveal a key role for non-oscillatory brain activity during rapid eye movement (REM) sleep to mediate sleep-dependent recalibration of neural population dynamics. The extent of this REM sleep recalibration predicted the success of overnight memory consolidation, expressly the modulation of hippocampal-neocortical activity, favoring remembering rather than forgetting. The findings describe a non-oscillatory mechanism how human REM sleep modulates neural population activity to enhance long-term memory.
- Published
- 2023
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21. Coordinated human sleeping brainwaves map peripheral body glucose homeostasis.
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Vallat R, Shah VD, and Walker MP
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- Adult, Humans, Electroencephalography, Glucose, Homeostasis, Sleep physiology, Brain Waves
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Insufficient sleep impairs glucose regulation, increasing the risk of diabetes. However, what it is about the human sleeping brain that regulates blood sugar remains unknown. In an examination of over 600 humans, we demonstrate that the coupling of non-rapid eye movement (NREM) sleep spindles and slow oscillations the night before is associated with improved next-day peripheral glucose control. We further show that this sleep-associated glucose pathway may influence glycemic status through altered insulin sensitivity, rather than through altered pancreatic beta cell function. Moreover, we replicate these associations in an independent dataset of over 1,900 adults. Of therapeutic significance, the coupling between slow oscillations and spindles was the most significant sleep predictor of next-day fasting glucose, even more so than traditional sleep markers, relevant to the possibility of an electroencephalogram (EEG) index of hyperglycemia. Taken together, these findings describe a sleeping-brain-body framework of optimal human glucose homeostasis, offering a potential prognostic sleep signature of glycemic control., Competing Interests: Declaration of interests M.P.W. serves as a consultant for and has equity interest in Bryte, The Sleepfoundation.org, Oura, and StimScience., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2023
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22. NREM sleep as a novel protective cognitive reserve factor in the face of Alzheimer's disease pathology.
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Zavecz Z, Shah VD, Murillo OG, Vallat R, Mander BA, Winer JR, Jagust WJ, and Walker MP
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- Humans, Aged, Magnetic Resonance Imaging, Amyloid beta-Peptides, Sleep, Positron-Emission Tomography, Alzheimer Disease pathology, Sleep, Slow-Wave, Cognitive Reserve, Cognitive Dysfunction
- Abstract
Background: Alzheimer's disease (AD) pathology impairs cognitive function. Yet some individuals with high amounts of AD pathology suffer marked memory impairment, while others with the same degree of pathology burden show little impairment. Why is this? One proposed explanation is cognitive reserve i.e., factors that confer resilience against, or compensation for the effects of AD pathology. Deep NREM slow wave sleep (SWS) is recognized to enhance functions of learning and memory in healthy older adults. However, that the quality of NREM SWS (NREM slow wave activity, SWA) represents a novel cognitive reserve factor in older adults with AD pathology, thereby providing compensation against memory dysfunction otherwise caused by high AD pathology burden, remains unknown., Methods: Here, we tested this hypothesis in cognitively normal older adults (N = 62) by combining
11 C-PiB (Pittsburgh compound B) positron emission tomography (PET) scanning for the quantification of β-amyloid (Aβ) with sleep electroencephalography (EEG) recordings to quantify NREM SWA and a hippocampal-dependent face-name learning task., Results: We demonstrated that NREM SWA significantly moderates the effect of Aβ status on memory function. Specifically, NREM SWA selectively supported superior memory function in individuals suffering high Aβ burden, i.e., those most in need of cognitive reserve (B = 2.694, p = 0.019). In contrast, those without significant Aβ pathological burden, and thus without the same need for cognitive reserve, did not similarly benefit from the presence of NREM SWA (B = -0.115, p = 0.876). This interaction between NREM SWA and Aβ status predicting memory function was significant after correcting for age, sex, Body Mass Index, gray matter atrophy, and previously identified cognitive reserve factors, such as education and physical activity (p = 0.042)., Conclusions: These findings indicate that NREM SWA is a novel cognitive reserve factor providing resilience against the memory impairment otherwise caused by high AD pathology burden. Furthermore, this cognitive reserve function of NREM SWA remained significant when accounting both for covariates, and factors previously linked to resilience, suggesting that sleep might be an independent cognitive reserve resource. Beyond such mechanistic insights are potential therapeutic implications. Unlike many other cognitive reserve factors (e.g., years of education, prior job complexity), sleep is a modifiable factor. As such, it represents an intervention possibility that may aid the preservation of cognitive function in the face of AD pathology, both present moment and longitudinally., (© 2023. The Author(s).)- Published
- 2023
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23. Personalized transcranial alternating current stimulation improves sleep quality: Initial findings.
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Ayanampudi V, Kumar V, Krishnan A, Walker MP, Ivry RB, Knight RT, and Gurumoorthy R
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Insufficient sleep is a major health issue. Inadequate sleep is associated with an array of poor health outcomes, including cardiovascular disease, diabetes, obesity, certain forms of cancer, Alzheimer's disease, depression, anxiety, and suicidality. Given concerns with typical sedative hypnotic drugs for treating sleep difficulties, there is a compelling need for alternative interventions. Here, we report results of a non-invasive electrical brain stimulation approach to optimizing sleep involving transcranial alternating current stimulation (tACS). A total of 25 participants (mean age: 46.3, S.D. ± 12.4, 15 females) were recruited for a null-stimulation controlled (Control condition), within subjects, randomized crossed design, that included two variants of an active condition involving 15 min pre-sleep tACS stimulation. To evaluate the impact on sleep quality, the two active tACS stimulation conditions were designed to modulate sleep-dependent neural activity in the theta/alpha frequency bands, with both stimulation types applied to all subjects in separate sessions. The first tACS condition used a fixed stimulation pattern across all participants, a pattern composed of stimulation at 5 and 10 Hz. The second tACS condition used a personalized stimulation approach with the stimulation frequencies determined by each individual's peak EEG frequencies in the 4-6 Hz and 9-11 Hz bands. Personalized tACS stimulation increased sleep quantity (duration) by 22 min compared to a Control condition ( p = 0.04), and 19 min compared to Fixed tACS stimulation ( p = 0.03). Fixed stimulation did not significantly increase sleep duration compared to Control (mean: 3 min; p = 0.75). For sleep onset, the Personalized tACS stimulation resulted in reducing the onset by 28% compared to the Fixed tACS stimulation (6 min faster, p = 0.02). For a Poor Sleep sub-group ( n = 13) categorized with Clinical Insomnia and a high insomnia severity, Personalized tACS stimulation improved sleep duration by 33 min compared to Fixed stimulation ( p = 0.02), and 30 min compared to Control condition ( p < 0.1). Together, these results suggest that Personalized stimulation improves sleep quantity and time taken to fall asleep relative to Control and Fixed stimulation providing motivation for larger-scale trials for Personalized tACS as a sleep therapeutic, including for those with insomnia., Competing Interests: RK and MW were founding members of StimScience Inc. RI was a member of the Scientific Advisory Board. RK, MW, and RI were not compensated. All authors have equity positions in StimScience. VA, VK, AK, and RG were employed by StimScience Inc., (Copyright © 2023 Ayanampudi, Kumar, Krishnan, Walker, Ivry, Knight and Gurumoorthy.)
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- 2023
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24. Sleep Loss Influences the Interconnected Brain-Body Regulation of Cardiovascular Function in Humans.
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Krause AJ, Vallat R, Simon EB, and Walker MP
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- Adult, Humans, Sleep Deprivation complications, Magnetic Resonance Imaging, Brain diagnostic imaging, Sleep physiology, Cardiovascular Diseases etiology, Hypertension
- Abstract
Objective: Poor sleep is associated with hypertension, a major risk factor for cardiovascular disease. However, the mechanism(s) through which sleep loss affects cardiovascular health remains largely unknown, including the brain and body systems that regulate vascular function., Methods: Sixty-six healthy adults participated in a repeated-measures, crossover, experimental study involving assessments of cardiovascular function and brain connectivity after a night of sleep and a night of sleep deprivation., Results: First, sleep deprivation significantly increased blood pressure-both systolic and diastolic. Interestingly, this change was independent of any increase in heart rate, inferring a vasculature-specific rather than direct cardiac pathway. Second, sleep loss compromised functional brain connectivity within the vascular control network, specifically the insula, anterior cingulate, amygdala, and ventral and medial prefrontal cortices. Third, sleep loss-related changes in brain connectivity and vascular tone were not independent, but significantly interdependent, with changes within the vascular control brain network predicting the sleep-loss shift toward hypertension., Conclusions: These findings establish an embodied framework in which sleep loss confers increased risk of cardiovascular disease through an impact upon central brain control of vascular tone, rather than a direct impact on accelerated heart rate itself., (Copyright © 2022 by the American Psychosomatic Society.)
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- 2023
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25. Effect of fluoride varnish in combination with simulated oral environment on enamel-bracket shear bond strength.
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Lohfeld S, Kawamoto B, Wang Y, and Walker MP
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- Fluorides chemistry, Fluorides, Topical, Dental Enamel, Shear Strength, Materials Testing, Dental Stress Analysis, Resin Cements chemistry, Surface Properties, Dental Bonding methods, Orthodontic Brackets
- Abstract
To determine the effect of fluoride varnish application combined with a simulated oral environment prior to bracket bonding on the shear bond strength (SBS) between brackets and tooth enamel. Sixty de-identified, extracted teeth were grouped to either receive or not receive fluoride varnish and then stored for 7 days at 37 °C in phosphate-buffered saline (PBS) solution or PBS combined with three 15-min cycles/day in a demineralizing solution to simulate pH variation following meals. Subsequently, brackets were bonded and after 24-h dark cure at 37 °C, debonded using shear forces in a simulated oral environment. The maximum shear force was used to calculate SBS, and the adhesive remnant index (ARI) was determined by image analysis of photos of the bracket mesh pad after debonding. A statistically higher SBS (10.16 MPa) was observed when fluoride varnish was applied prior to storage in PBS + demineralizing solution compared to SBS (6.38 MPa) following storage in the same solution without varnish application. Based on 37% effect size, this difference is also clinically relevant. In contrast, no significant differences in SBS were observed with varnish application combined with PBS with no demineralizing solution or between storage solution alone. Moreover, there was no significant difference in ARI due to varnish combined with either storage method or storage solution only. Results suggest varnish application prior to bracket bonding in combination with simulated oral environment that included acid exposure is beneficial in maintaining higher SBS between bracket and enamel. Despite higher SBS, adhesive remaining on enamel did not increase., (© 2022. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)
- Published
- 2023
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26. Case presentation of 8-year follow up of recurrent malignant duodenal Insulinoma and lymph node metastases and literature review of malignant Insulinoma management.
- Author
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Walker MP, Shenoy V, Metz DC, Stanley CA, Fraker D, Chandrasekhara V, and Amaro A
- Subjects
- Humans, Female, Adult, Lymphatic Metastasis, Positron Emission Tomography Computed Tomography, Blood Glucose Self-Monitoring, Blood Glucose, Neoplasm Recurrence, Local, Pancreatic Neoplasms surgery, Insulinoma surgery, Insulinoma diagnosis, Hypoglycemia etiology, Hypoglycemia diagnosis
- Abstract
Background: Insulinoma is an uncommon insulin-secreting neuroendocrine tumor that presents with severe recurrent hypoglycemia. Although cases of extrapancreatic insulinomas have been reported, the majority of insulinomas occur in the pancreas. The number of reported cases of ectopic insulinomas with follow-up assessments is limited and they do not report disease recurrence. The current report presents the first documented case of recurrent extrapancreatic insulinoma with 8 years of follow-up, provides relevant literature review, and proposes surveillance and treatment strategies., Case Presentation: We describe an insulinoma localized in the duodenal wall of a 36-year-old female who presented in 2013 with weight gain and Whipple's triad and was successfully managed with duodenotomy and enucleation. She presented again in 2017 with recurrent Whipple's triad and was found to have metastatic disease localized exclusively to peripancreatic lymph nodes. Primary pancreatic insulinoma was not evident and her hypoglycemia resolved following lymph node dissection. Eight years after initial presentation continuous glucose monitoring (CGM) showed a trend for euglycemia, and PET-CT Gallium 68 DOTATATE scan evaluation indicated absence of recurrent disease., Conclusion: Insulinomas are rare clinical entities and extrapancreatic insulinomas are particularly uncommon. Follow-up evaluation and treatment strategies for ectopic insulinoma recurrence presents a significant clinical challenge as the condition has hitherto remained undescribed in the literature. Available evidence in the literature indicates that lymph node metastases of intrapancreatic insulinomas likely do not change prognosis. Given the absence of long-term data informing the management and monitoring of patients with extrapancreatic insulinoma, we suggest patient education for hypoglycemic symptoms, monitoring for hypoglycemia with CGM, annual imaging, and a discussion with patients regarding treatment with octreotide or alternative somatostatin receptor analog therapies., (© 2022. The Author(s).)
- Published
- 2022
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27. How people wake up is associated with previous night's sleep together with physical activity and food intake.
- Author
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Vallat R, Berry SE, Tsereteli N, Capdevila J, Khatib HA, Valdes AM, Delahanty LM, Drew DA, Chan AT, Wolf J, Franks PW, Spector TD, and Walker MP
- Subjects
- Humans, Adult, Prospective Studies, Longitudinal Studies, Eating physiology, Sleep, Exercise
- Abstract
How people wake up and regain alertness in the hours after sleep is related to how they are sleeping, eating, and exercising. Here, in a prospective longitudinal study of 833 twins and genetically unrelated adults, we demonstrate that how effectively an individual awakens in the hours following sleep is not associated with their genetics, but instead, four independent factors: sleep quantity/quality the night before, physical activity the day prior, a breakfast rich in carbohydrate, and a lower blood glucose response following breakfast. Furthermore, an individual's set-point of daily alertness is related to the quality of their sleep, their positive emotional state, and their age. Together, these findings reveal a set of non-genetic (i.e., not fixed) factors associated with daily alertness that are modifiable., (© 2022. The Author(s).)
- Published
- 2022
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28. Sleep loss leads to the withdrawal of human helping across individuals, groups, and large-scale societies.
- Author
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Ben Simon E, Vallat R, Rossi A, and Walker MP
- Subjects
- Altruism, Humans, Magnetic Resonance Imaging, Sleep Deprivation, Brain diagnostic imaging, Brain physiology, Sleep
- Abstract
Humans help each other. This fundamental feature of homo sapiens has been one of the most powerful forces sculpting the advent of modern civilizations. But what determines whether humans choose to help one another? Across 3 replicating studies, here, we demonstrate that sleep loss represents one previously unrecognized factor dictating whether humans choose to help each other, observed at 3 different scales (within individuals, across individuals, and across societies). First, at an individual level, 1 night of sleep loss triggers the withdrawal of help from one individual to another. Moreover, fMRI findings revealed that the withdrawal of human helping is associated with deactivation of key nodes within the social cognition brain network that facilitates prosociality. Second, at a group level, ecological night-to-night reductions in sleep across several nights predict corresponding next-day reductions in the choice to help others during day-to-day interactions. Third, at a large-scale national level, we demonstrate that 1 h of lost sleep opportunity, inflicted by the transition to Daylight Saving Time, reduces real-world altruistic helping through the act of donation giving, established through the analysis of over 3 million charitable donations. Therefore, inadequate sleep represents a significant influential force determining whether humans choose to help one another, observable across micro- and macroscopic levels of civilized interaction. The implications of this effect may be non-trivial when considering the essentiality of human helping in the maintenance of cooperative, civil society, combined with the reported decline in sufficient sleep in many first-world nations., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2022
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29. Effectiveness of digital impressions in a predoctoral clinical curriculum.
- Author
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Petrie CS, Hayes K, Scott JM, and Walker MP
- Subjects
- Curriculum, Dental Impression Technique, Dental Marginal Adaptation, Dental Materials, Humans, Retrospective Studies, Computer-Aided Design, Dental Prosthesis Design methods
- Abstract
Aim: The purpose of the present study was to investigate the effectiveness of digital impressions made by 3rd and 4th year dental students using a retrospective record review at one USA dental school during a 1-year period., Materials and Methods: After reviewing patient records related to quality assurance, 125 digital impressions and the produced restorations were evaluated. Effectiveness and acceptability of digital impressions and restorations were associated with students' educational level, number of prepared teeth scanned, type of produced restoration, and restorative material used. Fisher's exact and chi-square tests were used for the statistical analysis. All dental students had previous experience of the digital curriculum in their preclinical education., Results: A total of 91% of the digital impressions were acceptable, and 80% of the produced restorations had clinically acceptable margins. Impression approval and restoration acceptance were not affected by students' educational level, number of preparations or restoration type. Restoration acceptance was significantly affected by restorative material (P = 0.039), with higher rates of acceptable marginal integrity found with glass-ceramic and zirconia materials., Conclusions: Within the parameters of the present study, 3rd and 4th year dental students, after having extensive education in the preclinical curriculum, can utilize digital impressions effectively for clinical practice. The results show that with adequate educational experiences, dental students can use digital impressions effectively for clinically acceptable restorations. Dental schools can and should educate students in digital dentistry.
- Published
- 2022
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30. Direct type I interferon signaling in hepatocytes controls malaria.
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Marques-da-Silva C, Peissig K, Walker MP, Shiau J, Bowers C, Kyle DE, Vijay R, Lindner SE, and Kurup SP
- Subjects
- Animals, Hepatocytes, Humans, Immunity, Innate, Liver, Sporozoites, Antimalarials, Interferon Type I, Malaria, Plasmodium
- Abstract
Malaria is a devastating disease impacting over half of the world's population. Plasmodium parasites that cause malaria undergo obligatory development and replication in hepatocytes before infecting red blood cells and initiating clinical disease. While type I interferons (IFNs) are known to facilitate innate immune control to Plasmodium in the liver, how they do so has remained unresolved, precluding the manipulation of such responses to combat malaria. Utilizing transcriptomics, infection studies, and a transgenic Plasmodium strain that exports and traffics Cre recombinase, we show that direct type I IFN signaling in Plasmodium-infected hepatocytes is necessary to control malaria. We also show that the majority of infected hepatocytes naturally eliminate Plasmodium infection, revealing the potential existence of anti-malarial cell-autonomous immune responses in such hepatocytes. These discoveries challenge the existing paradigms in Plasmodium immunobiology and are expected to inspire anti-malarial drugs and vaccine strategies., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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31. Impact of insufficient sleep on dysregulated blood glucose control under standardised meal conditions.
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Tsereteli N, Vallat R, Fernandez-Tajes J, Delahanty LM, Ordovas JM, Drew DA, Valdes AM, Segata N, Chan AT, Wolf J, Berry SE, Walker MP, Spector TD, and Franks PW
- Subjects
- Adolescent, Adult, Aged, Female, Glycemic Control, Glycemic Index, Humans, Male, Middle Aged, Postprandial Period physiology, Young Adult, Blood Glucose metabolism, Breakfast, Diet, Sleep Deprivation blood
- Abstract
Aims/hypothesis: Sleep, diet and exercise are fundamental to metabolic homeostasis. In this secondary analysis of a repeated measures, nutritional intervention study, we tested whether an individual's sleep quality, duration and timing impact glycaemic response to a breakfast meal the following morning., Methods: Healthy adults' data (N = 953 [41% twins]) were analysed from the PREDICT dietary intervention trial. Participants consumed isoenergetic standardised meals over 2 weeks in the clinic and at home. Actigraphy was used to assess sleep variables (duration, efficiency, timing) and continuous glucose monitors were used to measure glycaemic variation (>8000 meals)., Results: Sleep variables were significantly associated with postprandial glycaemic control (2 h incremental AUC), at both between- and within-person levels. Sleep period time interacted with meal type, with a smaller effect of poor sleep on postprandial blood glucose levels when high-carbohydrate (low fat/protein) (p
interaction = 0.02) and high-fat (pinteraction = 0.03) breakfasts were consumed compared with a reference 75 g OGTT. Within-person sleep period time had a similar interaction (high carbohydrate: pinteraction = 0.001, high fat: pinteraction = 0.02). Within- and between-person sleep efficiency were significantly associated with lower postprandial blood glucose levels irrespective of meal type (both p < 0.03). Later sleep midpoint (time deviation from midnight) was found to be significantly associated with higher postprandial glucose, in both between-person and within-person comparisons (p = 0.035 and p = 0.051, respectively)., Conclusions/interpretation: Poor sleep efficiency and later bedtime routines are associated with more pronounced postprandial glycaemic responses to breakfast the following morning. A person's deviation from their usual sleep pattern was also associated with poorer postprandial glycaemic control. These findings underscore sleep as a modifiable, non-pharmacological therapeutic target for the optimal regulation of human metabolic health. Trial registration ClinicalTrials.gov NCT03479866., (© 2021. The Author(s).)- Published
- 2022
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32. Addendum: Transcriptomics and proteomics reveal two waves of translational repression during the maturation of malaria parasite sporozoites.
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Lindner SE, Swearingen KE, Shears MJ, Sebastian A, Walker MP, Vrana EN, Hart KJ, Minns AM, Albert I, Sinnis P, Moritz RL, and Kappe SHI
- Subjects
- Animals, Humans, Parasites, Plasmodium falciparum, Plasmodium yoelii, RNA-Seq, Malaria parasitology, Protein Processing, Post-Translational, Proteomics, Sporozoites genetics, Sporozoites metabolism, Transcriptome
- Published
- 2022
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33. A Nationally Representative Survey Assessing Restorative Sleep in US Adults.
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Robbins R, Quan SF, Buysse D, Weaver MD, Walker MP, Drake CL, Monten K, Barger LK, Rajaratnam SMW, Roth T, and Czeisler CA
- Abstract
Restorative sleep is a commonly used term but a poorly defined construct. Few studies have assessed restorative sleep in nationally representative samples. We convened a panel of 7 expert physicians and researchers to evaluate and enhance available measures of restorative sleep. We then developed the revised Restorative Sleep Questionnaire (REST-Q), which comprises 9 items assessing feelings resulting from the prior sleep episode, each with 5-point Likert response scales. Finally, we assessed the prevalence of high, somewhat, and low REST-Q scores in a nationally representative sample of US adults (n= 1,055) and examined the relationship of REST-Q scores with other sleep and demographic characteristics. Pairwise correlations were performed between the REST-Q scores and other self-reported sleep measures. Weighted logistic regression analyses were conducted to compare scores on the REST-Q with demographic variables. The prevalence of higher REST-Q scores (4 or 5 on the Likert scale) was 28.1% in the nationally representative sample. REST-Q scores positively correlated with sleep quality (r=0.61) and sleep duration (r=0.32), and negatively correlated with both difficulty falling asleep (r=-0.40) and falling back asleep after waking (r=-0.41). Higher restorative sleep scores (indicating more feelings of restoration upon waking) were more common among those who were: ≥60 years of age (OR=4.20, 95%CI: 1.92-9.17); widowed (OR=2.35, 95%CI:1.01-5.42), and retired (OR=2.02, 95%CI:1.30-3.14). Higher restorative sleep scores were less frequent among those who were not working (OR=0.36, 95%CI: 0.10-1.00) and living in a household with two or more persons (OR=0.51,95%CI:0.29-0.87). Our findings suggest that the REST-Q may be useful for assessing restorative sleep., Competing Interests: Competing interests Dr. Rebecca Robbins has received consulting fees from Rituals Cosmetics BV, Savoir Beds Ltd, With Deep Inc, Sleep Cycle AB, Oura Ring Ltd, Denihan Hospitality Group, and the Skimm. This work was supported by a grant from the Bryte Foundation. Dr. Walker serves as a consultant for and has equity interest in the companies, Bryte, Shuni, Oura Ring, and StimScience. Dr. Quan reports receiving consulting fees from Whispersom, Bryte Foundation, Best Doctors, DR Capital. Dr. Rajaratnam has unpaid appointments at CRC for Alertness, Safety and Productivity, Australia and the Sleep Health Foundation. Dr. Rajaratnam also is supported on grants from Vanda Pharmaceuticals, Philips Respironics, Cephalon, Rio Tinto, BHP Billiton and Shell. Dr. Rajaratnam also has received other support from Optalert, Compumedics, Teva Pharmaceuticals and Circadian Therapeutics. Dr. Czeisler reports grants and contracts to BWH from Dayzz Live Well, Delta Airlines, Jazz Pharma, Puget Sound Pilots, Regeneron Pharmaceuticals/Sanofi; is/was paid consultant/speaker for Inselspital Bern, Institute of Digital Media and Child Development, Klarman Family Foundation, M. Davis and Co, National Council for Mental Wellbeing, National Sleep Foundation, Physician’s Seal, SRS Foundation, State of Washington Board of Pilotage Commissioners, Tencent, Teva Pharma Australia, With Deep, and Vanda Pharmaceuticals, in which Dr. Czeisler holds an equity interest; received travel support from Aspen Brain Institute, Bloomage International Investment Group, Inc., Dr. Stanley Ho Medical Development Foundation, German National Academy of Sciences, Ludwig-Maximilians-Universität München, National Highway Transportation Safety Administration, National Safety Council, National Sleep Foundation, Salk Institute for Biological Studies/Fondation Ipsen, Society for Research on Biological Rhythms, Stanford Medical School Alumni Association, Tencent Holdings, Ltd, and Vanda Pharmaceuticals; receives research/education gifts through BWH from Arbor Pharmaceuticals, Avadel Pharmaceuticals, Bryte, Alexandra Drane, Cephalon, DR Capital Ltd, Eisai, Harmony Biosciences, Jazz Pharmaceuticals, Johnson & Johnson, Mary Ann & Stanley Snider via Combined Jewish Philanthropies, NeuroCare, Inc., Optum, Philips Respironics, Regeneron, Regional Home Care, ResMed, San Francisco Bar Pilots, Sanofi SA, Schneider, Simmons, Sleep Cycle. Sleep Number, Sysco, Teva Pharmaceuticals, Vanda Pharmaceuticals; is/was an expert witness in legal cases, including those involving Advanced Power Technologies, Aegis Chemical Solutions, Amtrak; Casper Sleep Inc, C&J Energy Services, Catapult Energy Services Group, Covenant Testing Technologies, Dallas Police Association, Enterprise Rent-A-Car, Espinal Trucking/Eagle Transport Group/Steel Warehouse Inc, FedEx, Greyhound, Pomerado Hospital/Palomar Health District, PAR Electrical Contractors, Product & Logistics Services LLC/Schlumberger Technology, Puckett EMS, Puget Sound Pilots, Union Pacific Railroad, UPS, and Vanda Pharmaceuticals; serves as the incumbent of an endowed professorship given to Harvard by Cephalon; and receives royalties from McGraw Hill and Philips Respironics for the Actiwatch-2 and Actiwatch Spectrum devices. Dr. Czeisler’s interests were reviewed and are managed by the Brigham and Women’s Hospital and Mass General Brigham in accordance with their conflict-of-interest policies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
- Published
- 2022
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34. Distinct effects of polyphenols and solvents on dentin collagen crosslinking interactions and biostability.
- Author
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Hass V, Liu H, Cook W, Walker MP, and Wang Y
- Subjects
- Collagen, Dentin, Polyphenols, Solvents, Tensile Strength, Dental Bonding, Dentin-Bonding Agents
- Abstract
Objective: To evaluate the effects of different polyphenols and solvents on dentin collagen's crosslinking interactions and biostabilization against MMPs and collagenase degradation., Methods: Two polyphenols [proanthocyanidin (PA) and quercetin (QC)] with different water solubility were prepared as treatment solutions using ethanol (EtOH) or dimethyl sulfoxide (DMSO) as solvents. 6-um-thick dentin films were microtomed from dentin slabs of third molars. Following demineralization, films or slabs were subject to 60-s treatment (PA or QC) or no treatment (control) with subsequent extended-rinse with original solvent (EtOH or DMSO) or distilled water (DW). Collagen crosslinking interactions were assessed by FTIR. Biostability was assessed through endogenous MMPs activity via confocal laser scanning microscopy, and exogenous collagenase degradation via weight loss, hydroxyproline release and SEM. Finally, direct collagenase inactivation was also evaluated. Data were analyzed by three-way ANOVA and post-hoc tests (α=0.05%)., Results: Distinct effects of two polyphenols and solvents on collagen crosslinking and biostabilization were observed. Higher crosslinking and biostability efficacy occurred with PA than QC (p<0.001) that demonstrated negligible collagen interactions. With DMSO solvent, efficacy results were significantly reduced with both polyphenols (p<0.05). DMSO-rinse further weakened interactions of PA with collagen, diminishing biostability (p<0.05). Low biostability was detected with QC and DW-rinse, suggesting direct enzymatic inhibition due to physical presence in collagen., Significance: Collagen crosslinking interactions and biostability depend on polyphenol chemical characteristics. Treatment-solution solvents may affect interactions between polyphenols and collagen, specifically, DMSO showed detrimental effects on collagen crosslinking and biostability and should be used with caution., (Copyright © 2021 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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35. An open-source, high-performance tool for automated sleep staging.
- Author
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Vallat R and Walker MP
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Automation, Case-Control Studies, Child, Electroencephalography, Electromyography, Electrooculography, Female, Humans, Male, Middle Aged, Observer Variation, Predictive Value of Tests, Randomized Controlled Trials as Topic, Reproducibility of Results, Sleep Apnea, Obstructive physiopathology, Young Adult, Algorithms, Brain physiopathology, Polysomnography, Signal Processing, Computer-Assisted, Sleep Apnea, Obstructive diagnosis, Sleep Stages, Software Design
- Abstract
The clinical and societal measurement of human sleep has increased exponentially in recent years. However, unlike other fields of medical analysis that have become highly automated, basic and clinical sleep research still relies on human visual scoring. Such human-based evaluations are time-consuming, tedious, and can be prone to subjective bias. Here, we describe a novel algorithm trained and validated on +30,000 hr of polysomnographic sleep recordings across heterogeneous populations around the world. This tool offers high sleep-staging accuracy that matches human scoring accuracy and interscorer agreement no matter the population kind. The software is designed to be especially easy to use, computationally low-demanding, open source, and free. Our hope is that this software facilitates the broad adoption of an industry-standard automated sleep staging software package., Competing Interests: RV, MW No competing interests declared, (© 2021, Vallat and Walker.)
- Published
- 2021
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36. Tau and β-Amyloid Burden Predict Actigraphy-Measured and Self-Reported Impairment and Misperception of Human Sleep.
- Author
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Winer JR, Morehouse A, Fenton L, Harrison TM, Ayangma L, Reed M, Kumar S, Baker SL, Jagust WJ, and Walker MP
- Subjects
- Actigraphy, Aged, Aged, 80 and over, Aging metabolism, Brain diagnostic imaging, Female, Humans, Male, Neuropsychological Tests, Positron-Emission Tomography, Self Report, Surveys and Questionnaires, Amyloid beta-Peptides metabolism, Brain metabolism, Sleep physiology, tau Proteins metabolism
- Abstract
Alzheimer's disease is associated with poor sleep, but the impact of tau and β-amyloid (Aβ) pathology on sleep remains largely unknown. Here, we test the hypothesis that tau and Aβ predict unique impairments in objective and self-perceived human sleep under real-life, free-living conditions. Eighty-nine male and female cognitively healthy older adults received
18 F-FTP-tau and11 C-PIB-Aβ PET imaging, 7 nights of sleep actigraphy and questionnaire measures, and neurocognitive assessment. Tau burden, but not Aβ, was associated with markedly worse objective sleep. In contrast, Aβ and tau were associated with worse self-reported sleep quality. Of clinical relevance, Aβ burden predicted a unique perceptual mismatch between objective and subject sleep evaluation, with individuals underestimating their sleep. The magnitude of this mismatch was further predicted by worse executive function. Thus, early-stage tau and Aβ deposition are linked with distinct phenotypes of real-world sleep impairment, one that includes a cognitive misperception of their own sleep health. SIGNIFICANCE STATEMENT Alzheimer's disease is associated with sleep disruption, often before significant memory decline. Thus, real-life patterns of sleep behavior have the potential to serve as a window into early disease progression. In 89 cognitive healthy older adults, we found that tau burden was associated with worse wristwatch actigraphy-measured sleep quality, and that both tau and β-amyloid were independently predictive of self-reported sleep quality. Furthermore, individuals with greater β-amyloid deposition were more likely to underestimate their sleep quality, and sleep quality underestimation was associated with worse executive function. These data support the role of sleep impairment as a key marker of early Alzheimer's disease, and offer the possibility that actigraphy may be an affordable and scalable tool in quantifying Alzheimer's disease-related behavioral changes., (Copyright © 2021 the authors.)- Published
- 2021
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37. Sleep essentialism.
- Author
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Walker MP
- Subjects
- Animals, Humans, Sleep physiology
- Published
- 2021
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38. A survey of US dental schools on predoctoral implant curricula with emphasis on diagnosing and treating implant complications.
- Author
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Petrie CS, Nakatani B, Scott JM, Moniz J, and Walker MP
- Subjects
- Curriculum, Dental Implantation, Education, Dental, Esthetics, Dental, Humans, Prosthodontics, Surveys and Questionnaires, Dental Implants adverse effects, Schools, Dental
- Abstract
Statement of Problem: Implant complications have been reported to occur at high rates and frequencies. Whether these high rates are observed in predoctoral implant programs and whether future dentists are educated to diagnose and treat implant complications is unknown., Purpose: The purpose of this study was to analyze and report the results of a survey on US predoctoral curricula related to implant treatment and with an emphasis on diagnosing and treating implant complications., Material and Methods: A 26-question survey was distributed to all (66) US dental schools. In addition to 3 questions regarding descriptive information about each school, 13 questions were used to calculate a curriculum composite score that was used to assess the quality of the school's implant curriculum. The remaining survey topics and number of questions included frequency of complications (2), tracking and types of complications (6), and school-reported student preparedness to identify or treat implant complications (2). A Kruskal-Wallis test was used to evaluate the relationship between the curriculum composite scores and student preparedness to diagnose and treat implant complications., Results: Twenty-eight schools responded to the survey for a response rate of 42.4%, and 23 schools completed the entire survey (completion rate 34.8%). Fifteen schools (65.2%) reported methods of recording implant complications, and 8 of 23 schools (34.8%) reported methods of assessing student knowledge in recognizing implant complications. Only 2 schools reported methods of assessing student preparedness to treat implant complications. Most implant complications were mechanical (64.3%), followed by biological (28.6%) and esthetic (7.1%). The prostheses associated with the most complications were implant overdentures (39.1%), followed by single crowns (34.8%) and fixed partial dentures (4.3%). A positive relational trend was observed between reported student preparedness to recognize and treat implant complications and curriculum composite scores., Conclusions: Within the limitation of this survey-based study, implant curricula in US dental schools should consider improving the scope of teaching the diagnosis and treatment of implant complications. The implant complications observed at US dental schools showed similar trends to those reported in the literature., (Copyright © 2020 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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39. Author Correction: Overanxious and underslept.
- Author
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Ben Simon E, Rossi A, Harvey AG, and Walker MP
- Published
- 2020
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40. Sleep Disturbance Forecasts β-Amyloid Accumulation across Subsequent Years.
- Author
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Winer JR, Mander BA, Kumar S, Reed M, Baker SL, Jagust WJ, and Walker MP
- Subjects
- Aged, Alzheimer Disease diagnosis, Alzheimer Disease etiology, Alzheimer Disease pathology, Brain diagnostic imaging, Cross-Sectional Studies, Disease Progression, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Polysomnography statistics & numerical data, Positron-Emission Tomography, Protein Aggregates physiology, Risk Assessment methods, Risk Factors, Sleep Wake Disorders diagnosis, Sleep Wake Disorders epidemiology, Sleep Wake Disorders physiopathology, Sleep, Slow-Wave physiology, Alzheimer Disease epidemiology, Amyloid beta-Peptides metabolism, Brain pathology, Sleep Wake Disorders complications
- Abstract
Experimental sleep-wake disruption in rodents and humans causally modulates β-amyloid (Aβ) dynamics (e.g., [1-3]). This leads to the hypothesis that, beyond cross-sectional associations, impaired sleep structure and physiology could represent prospective biomarkers of the speed with which Aβ accumulates over time. Here, we test the hypothesis that initial baseline measures of non-rapid eye movement (NREM) sleep slow-wave activity (SWA) and sleep quality (efficiency) provide future forecasting sensitivity to the rate of Aβ accumulation over subsequent years. A cohort of clinically normal older adults was assessed using objective sleep polysomnography in combination with longitudinal tracking of Aβ accumulation with [
11 C]PiB positron emission tomography (PET) imaging. Both the proportion of NREM SWA below 1 Hz and the measure of sleep efficiency predicted the speed (slope) of subsequent Aβ deposition over time, and these associations remained robust when taking into account additional cofactors of interest (e.g., age, sex, sleep apnea). Moreover, these measures were specific, such that no other macro- and microphysiological architecture metrics of sleep demonstrated such sensitivity. Our data support the proposal that objective sleep markers could be part of a set of biomarkers that statistically forecast the longitudinal trajectory of cortical Aβ deposition in the human brain. Sleep may therefore represent a potentially affordable, scalable, repeatable, and non-invasive tool for quantifying of Aβ pathological progression, prior to cognitive symptoms of Alzheimer's disease (AD)., Competing Interests: Declaration of Interests M.P.W. serves as a consultant for and has equity interest in Bryte, Oura Health Oy, Shuni, and StimScience. W.W.J. serves as a consultant to Genentech, Biogen, Bioclinica, CuraSen, and Grifols. B.A.M. has served as a consultant to Eisai., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
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41. An electrophysiological marker of arousal level in humans.
- Author
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Lendner JD, Helfrich RF, Mander BA, Romundstad L, Lin JJ, Walker MP, Larsson PG, and Knight RT
- Subjects
- Adult, Aged, Aged, 80 and over, Electroencephalography, Female, Humans, Male, Middle Aged, Anesthesia, Arousal physiology, Propofol, Sleep Stages physiology, Sleep, REM physiology
- Abstract
Deep non-rapid eye movement sleep (NREM) and general anesthesia with propofol are prominent states of reduced arousal linked to the occurrence of synchronized oscillations in the electroencephalogram (EEG). Although rapid eye movement (REM) sleep is also associated with diminished arousal levels, it is characterized by a desynchronized, 'wake-like' EEG. This observation implies that reduced arousal states are not necessarily only defined by synchronous oscillatory activity. Using intracranial and surface EEG recordings in four independent data sets, we demonstrate that the 1/f spectral slope of the electrophysiological power spectrum, which reflects the non-oscillatory, scale-free component of neural activity, delineates wakefulness from propofol anesthesia, NREM and REM sleep. Critically, the spectral slope discriminates wakefulness from REM sleep solely based on the neurophysiological brain state. Taken together, our findings describe a common electrophysiological marker that tracks states of reduced arousal, including different sleep stages as well as anesthesia in humans., Competing Interests: JL, RH, BM, LR, JL, MW, PL, RK No competing interests declared, (© 2020, Lendner et al.)
- Published
- 2020
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42. Retraction Notice to: A Societal Sleep Prescription.
- Author
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Walker MP
- Published
- 2020
- Full Text
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43. Broken sleep predicts hardened blood vessels.
- Author
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Vallat R, Shah VD, Redline S, Attia P, and Walker MP
- Subjects
- Actigraphy, Aged, Atherosclerosis pathology, Female, Humans, Male, Middle Aged, Polysomnography, Severity of Illness Index, Blood Vessels pathology, Sleep Deprivation complications
- Abstract
Why does poor-quality sleep lead to atherosclerosis? In a diverse sample of over 1,600 individuals, we describe a pathway wherein sleep fragmentation raises inflammatory-related white blood cell counts (neutrophils and monocytes), thereby increasing atherosclerosis severity, even when other common risk factors have been accounted for. Improving sleep quality may thus represent one preventive strategy for lowering inflammatory status and thus atherosclerosis risk, reinforcing public health policies focused on sleep health., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
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44. Sleep Loss and the Socio-Emotional Brain.
- Author
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Ben Simon E, Vallat R, Barnes CM, and Walker MP
- Subjects
- Anxiety, Humans, Loneliness, Sleep, Brain, Emotions, Sleep Deprivation
- Abstract
Are you feeling emotionally fragile, moody, unpredictable, even ungenerous to those around you? Here, we review how and why these phenomena can occur as a result of insufficient sleep. Sleep loss disrupts a broad spectrum of affective processes, from basic emotional operations (e.g., recognition, responsivity, expression), through to high-order, complex socio-emotional functioning (e.g., loneliness, helping behavior, abusive behavior, and charisma). Translational insights further emerge regarding the pervasive link between sleep disturbance and psychiatric conditions, including anxiety, depression, and suicidality. More generally, such findings raise concerns regarding society's mental (ill)health and the prevalence of insufficient and disrupted sleep., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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45. Overanxious and underslept.
- Author
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Ben Simon E, Rossi A, Harvey AG, and Walker MP
- Subjects
- Adult, Amygdala diagnostic imaging, Amygdala physiopathology, Anxiety diagnostic imaging, Anxiety prevention & control, Anxiety Disorders prevention & control, Electroencephalography, Female, Humans, Limbic System diagnostic imaging, Magnetic Resonance Imaging, Male, Nerve Net diagnostic imaging, Prefrontal Cortex diagnostic imaging, Sleep Deprivation diagnostic imaging, Young Adult, Anxiety etiology, Anxiety physiopathology, Functional Neuroimaging, Limbic System physiopathology, Nerve Net physiopathology, Prefrontal Cortex physiopathology, Sleep Deprivation complications, Sleep Deprivation physiopathology, Sleep Stages physiology
- Abstract
Are you feeling anxious? Did you sleep poorly last night? Sleep disruption is a recognized feature of all anxiety disorders. Here, we investigate the basic brain mechanisms underlying the anxiogenic impact of sleep loss. Additionally, we explore whether subtle, societally common reductions in sleep trigger elevated next-day anxiety. Finally, we examine what it is about sleep, physiologically, that provides such an overnight anxiety-reduction benefit. We demonstrate that the anxiogenic impact of sleep loss is linked to impaired medial prefrontal cortex activity and associated connectivity with extended limbic regions. In contrast, non-rapid eye movement (NREM) slow-wave oscillations offer an ameliorating, anxiolytic benefit on these brain networks following sleep. Of societal relevance, we establish that even modest night-to-night reductions in sleep across the population predict consequential day-to-day increases in anxiety. These findings help contribute to an emerging framework explaining the intimate link between sleep and anxiety and further highlight the prospect of non-rapid eye movement sleep as a therapeutic target for meaningfully reducing anxiety.
- Published
- 2020
- Full Text
- View/download PDF
46. Transcriptomics and proteomics reveal two waves of translational repression during the maturation of malaria parasite sporozoites.
- Author
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Lindner SE, Swearingen KE, Shears MJ, Walker MP, Vrana EN, Hart KJ, Minns AM, Sinnis P, Moritz RL, and Kappe SHI
- Subjects
- Animals, Anopheles parasitology, Chromatography, Liquid, Epigenetic Repression genetics, Gene Expression Profiling, Humans, Malaria, Malaria, Falciparum, Mosquito Vectors parasitology, Oocysts metabolism, Plasmodium falciparum metabolism, Plasmodium yoelii metabolism, Proteomics, Rodentia, Salivary Glands parasitology, Sporozoites metabolism, Tandem Mass Spectrometry, Up-Regulation, Gene Expression Regulation, Developmental genetics, Oocysts genetics, Plasmodium falciparum genetics, Plasmodium yoelii genetics, Proteome metabolism, RNA, Messenger metabolism, Sporozoites genetics, Transcriptome genetics
- Abstract
Plasmodium sporozoites are transmitted from infected mosquitoes to mammals, and must navigate the host skin and vasculature to infect the liver. This journey requires distinct proteomes. Here, we report the dynamic transcriptomes and proteomes of both oocyst sporozoites and salivary gland sporozoites in both rodent-infectious Plasmodium yoelii parasites and human-infectious Plasmodium falciparum parasites. The data robustly define mRNAs and proteins that are upregulated in oocyst sporozoites (UOS) or upregulated in infectious sporozoites (UIS) within the salivary glands, including many that are essential for sporozoite functions in the vector and host. Moreover, we find that malaria parasites use two overlapping, extensive, and independent programs of translational repression across sporozoite maturation to temporally regulate protein expression. Together with gene-specific validation experiments, these data indicate that two waves of translational repression are implemented and relieved at different times during sporozoite maturation, migration and infection, thus promoting their successful development and vector-to-host transition.
- Published
- 2019
- Full Text
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47. A Societal Sleep Prescription.
- Author
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Walker MP
- Subjects
- Accidents, Traffic statistics & numerical data, Adolescent, Adult, Appointments and Schedules, Child, Health Personnel psychology, Health Promotion, Hospital Design and Construction, Humans, Hyperalgesia etiology, Inpatients psychology, Intensive Care Units, Learning Disabilities etiology, Lighting adverse effects, Physician Impairment, Professional Impairment, Sleep Deprivation economics, Sleep Deprivation psychology, Sleep Disorders, Circadian Rhythm epidemiology, Sleep Disorders, Circadian Rhythm etiology, Work Performance, Work Schedule Tolerance, Sleep Deprivation epidemiology, Social Change
- Abstract
We are suffering a global sleep-loss epidemic. The health consequences within an individual are well characterized. But does society suffer just as much? Here, I discuss how insufficient sleep erodes our societal fabric as much as it does our biological fabric, and offer some prescriptive remedies., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
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48. Bidirectional prefrontal-hippocampal dynamics organize information transfer during sleep in humans.
- Author
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Helfrich RF, Lendner JD, Mander BA, Guillen H, Paff M, Mnatsakanyan L, Vadera S, Walker MP, Lin JJ, and Knight RT
- Subjects
- Adult, Drug Resistant Epilepsy diagnosis, Drug Resistant Epilepsy therapy, Electrodes, Implanted, Electroencephalography, Female, Humans, Male, Middle Aged, Polysomnography, Young Adult, Hippocampus physiology, Memory Consolidation physiology, Models, Psychological, Prefrontal Cortex physiology, Sleep, Slow-Wave physiology
- Abstract
How are memories transferred from short-term to long-term storage? Systems-level memory consolidation is thought to be dependent on the coordinated interplay of cortical slow waves, thalamo-cortical sleep spindles and hippocampal ripple oscillations. However, it is currently unclear how the selective interaction of these cardinal sleep oscillations is organized to support information reactivation and transfer. Here, using human intracranial recordings, we demonstrate that the prefrontal cortex plays a key role in organizing the ripple-mediated information transfer during non-rapid eye movement (NREM) sleep. We reveal a temporally precise form of coupling between prefrontal slow-wave and spindle oscillations, which actively dictates the hippocampal-neocortical dialogue and information transfer. Our results suggest a model of the human sleeping brain in which rapid bidirectional interactions, triggered by the prefrontal cortex, mediate hippocampal activation to optimally time subsequent information transfer to the neocortex during NREM sleep.
- Published
- 2019
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49. Sleep as a Potential Biomarker of Tau and β-Amyloid Burden in the Human Brain.
- Author
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Winer JR, Mander BA, Helfrich RF, Maass A, Harrison TM, Baker SL, Knight RT, Jagust WJ, and Walker MP
- Subjects
- Aged, Alzheimer Disease diagnostic imaging, Alzheimer Disease pathology, Aniline Compounds, Biomarkers, Carbolines, Carbon Radioisotopes, Electroencephalography, Female, Fluorine Radioisotopes, Humans, Magnetic Resonance Imaging, Male, Models, Neurological, Polysomnography, Positron-Emission Tomography, Predictive Value of Tests, Prognosis, Radiopharmaceuticals, Sleep Disorders, Intrinsic diagnostic imaging, Sleep Disorders, Intrinsic pathology, Thiazoles, Alzheimer Disease metabolism, Amyloid beta-Peptides analysis, Nerve Tissue Proteins analysis, Sleep Disorders, Intrinsic metabolism, Sleep Stages physiology, Temporal Lobe chemistry, tau Proteins analysis
- Abstract
Recent proposals suggest that sleep may be a factor associated with accumulation of two core pathological features of Alzheimer's disease (AD): tau and β-amyloid (Aβ). Here we combined PET measures of Aβ and tau, electroencephalogram sleep recordings, and retrospective sleep evaluations to investigate the potential utility of sleep measures in predicting in vivo AD pathology in male and female older adults. Regression analyses revealed that the severity of impaired slow oscillation-sleep spindle coupling predicted greater medial temporal lobe tau burden. Aβ burden was not associated with coupling impairment but instead predicted the diminished amplitude of <1 Hz slow-wave-activity, results that were statistically dissociable from each other. Additionally, comparisons of AD pathology and retrospective, self-reported changes in sleep duration demonstrated that changes in sleep across the lifespan can predict late-life Aβ and tau burden. Thus, quantitative and qualitative features of human sleep represent potential noninvasive, cost-effective, and scalable biomarkers (current and future forecasting) of AD pathology, and carry both therapeutic and public health implications. SIGNIFICANCE STATEMENT Several studies have linked sleep disruption to the progression of Alzheimer's disease (AD). Tau and β-amyloid (Aβ), the primary pathological features of AD, are associated with both objective and subjective changes in sleep. However, it remains unknown whether late life tau and Aβ burden are associated with distinct impairments in sleep physiology or changes in sleep across the lifespan. Using polysomnography, retrospective questionnaires, and tau- and Aβ-specific PET, the present study reveals human sleep signatures that dissociably predict levels of brain tau and Aβ in older adults. These results suggest that a night of polysomnography may aid in evaluating tau and Aβ burden, and that treating sleep deficiencies within decade-specific time windows may serve in delaying AD progression., (Copyright © 2019 the authors.)
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- 2019
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50. Effects of Alpha-tocopherol Antioxidant on Dentin-composite Microtensile Bond Strength after Sodium Perborate Bleaching.
- Author
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Harrison MS, Wang Y, Frick KJ, Moniz J, and Walker MP
- Subjects
- Borates, Composite Resins, Resin Cements, Tensile Strength, Antioxidants pharmacology, Dental Bonding, Dentin drug effects, Tooth Bleaching, alpha-Tocopherol pharmacology
- Abstract
It has been reported that bond strength can be reversed to prebleached levels with the application of 10% alpha-tocopherol in a 2-hour time frame or by delaying bonding for 2 weeks. This study evaluated the effectiveness of a 5-minute application of 20% alpha-tocopherol to reverse the deleterious effects of nonvital bleaching on consequent bond strength. Thirty third molars were assigned to the following 3 groups: unbleached, bleached, and bleached followed by treatment with alpha-tocopherol. The bleached groups were exposed to sodium perborate (2 g/mL) for 7 days. The postbleach treatment group was subsequently treated with 20% alpha-tocopherol for 5 minutes, and then all groups were restored with composite resin. After 24 hours of storage at 37°C and 100% humidity, restored tooth specimens were sectioned into 1-mm
2 dentin-composite beams. Six beams from each tooth were subjected to microtensile bond strength testing. Representative beams were further evaluated with Raman microspectroscopy and scanning electron microscopy. The mean bond strength values (MPa) for each group were as follows: unbleached control group = 26.2, bleached control group = 20.3, and post-bleach treatment group = 18.5. A 1-factor analysis of variance and Tukey post hoc test (α = 0.05) indicated that bleaching had a detrimental effect on bond strength and that short-term alpha-tocopherol treatments did not improve postbleach bond strength. Raman microspectroscopy and scanning electron microscopy revealed no noted improvement for the post-bleach treatment group.The application of 20% alpha-tocopherol in a clinically relevant time frame was not effective in counteracting the deleterious effect of bleaching on bond strength. Bonding procedures should be delayed after tooth bleaching., (Copyright © 2019. Published by Elsevier Inc.)- Published
- 2019
- Full Text
- View/download PDF
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