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Article ; Online: Modeling (circadian).

St Hilaire, Melissa A

2022 Volume 273, Issue 1, Page(s) 181–198

Abstract: In this chapter, we will discuss mathematical models of the master circadian rhythm in the suprachiasmatic nucleus of the hypothalamus with a particular emphasis on models that incorporate the effect of light on circadian phase resetting and melatonin ... ...

Abstract	In this chapter, we will discuss mathematical models of the master circadian rhythm in the suprachiasmatic nucleus of the hypothalamus with a particular emphasis on models that incorporate the effect of light on circadian phase resetting and melatonin suppression. We will show that limit cycle oscillators provide a better representation of the salient properties of the human circadian system than a sinusoid. We will then discuss how the phototransduction of light to the SCN has been incorporated in various models. Finally, we will introduce different theoretical and practical applications of these models and highlight areas for future model development.
MeSH term(s)	Circadian Rhythm/physiology ; Humans ; Melatonin ; Models, Theoretical ; Suprachiasmatic Nucleus/physiology
Chemical Substances	Melatonin (JL5DK93RCL)
Language	English
Publishing date	2022-07-15
Publishing country	Netherlands
Document type	Journal Article
ISSN	1875-7855 ; 0079-6123
ISSN (online)	1875-7855
ISSN	0079-6123
DOI	10.1016/bs.pbr.2022.04.007
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Article ; Online: Measuring Dim Light Melatonin Onset in Humans.

St Hilaire, Melissa A / Lockley, Steven W

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2550, Page(s) 13–20

Abstract: The pineal melatonin rhythm provides a robust reference signal for the timing of the endogenous human circadian system. Dim light melatonin onset (DLMO) time is considered a gold-standard marker of the central circadian clock when measured from plasma or ...

Abstract	The pineal melatonin rhythm provides a robust reference signal for the timing of the endogenous human circadian system. Dim light melatonin onset (DLMO) time is considered a gold-standard marker of the central circadian clock when measured from plasma or saliva. In this chapter, we describe the appropriate conditions for collecting plasma and salivary melatonin and the threshold method to calculate the DLMO.
MeSH term(s)	Biomarkers ; Circadian Rhythm ; Humans ; Light ; Melatonin ; Saliva ; Sleep
Chemical Substances	Biomarkers ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2022-09-27
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2593-4_3
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Article ; Online: Measuring Urinary 6-Sulphatoxymelatonin in Humans.

St Hilaire, Melissa A / Lockley, Steven W

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2550, Page(s) 21–28

Abstract: The pineal melatonin rhythm provides a robust reference signal for the timing of the endogenous human circadian system. The rhythm in the major urinary metabolite of melatonin, 6-sulphatoxymelatonin (aMT6s), is highly correlated with plasma melatonin and ...

Abstract	The pineal melatonin rhythm provides a robust reference signal for the timing of the endogenous human circadian system. The rhythm in the major urinary metabolite of melatonin, 6-sulphatoxymelatonin (aMT6s), is highly correlated with plasma melatonin and provides a noninvasive method to measure circadian phase, particularly in field-based studies. In this chapter, we describe the protocol for collecting urinary aMT6s and the method used to calculate the acrophase, or peak, time as a circadian phase marker.
MeSH term(s)	Biomarkers/urine ; Circadian Rhythm ; Humans ; Melatonin/analogs & derivatives ; Melatonin/metabolism ; Urinary Tract/metabolism
Chemical Substances	Biomarkers ; 6-sulfatoxymelatonin (2208-40-4) ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2022-09-27
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2593-4_4
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Article ; Online: What time is it? A tale of three clocks, with implications for personalized medicine.

Klerman, Elizabeth B / Rahman, Shadab A / St Hilaire, Melissa A

Journal of pineal research

2020 Volume 68, Issue 4, Page(s) e12646

MeSH term(s)	Circadian Clocks ; Humans ; Precision Medicine ; Time
Language	English
Publishing date	2020-03-25
Publishing country	England
Document type	Journal Article
ZDB-ID	632697-3
ISSN	1600-079X ; 0742-3098
ISSN (online)	1600-079X
ISSN	0742-3098
DOI	10.1111/jpi.12646
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Zs.A 2114: Show issues

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Article ; Online: Publisher Correction: Circadian lipid and hepatic protein rhythms shift with a phase response curve different than melatonin.

Kent, Brianne A / Rahman, Shadab A / St Hilaire, Melissa A / Grant, Leilah K / Rüger, Melanie / Czeisler, Charles A / Lockley, Steven W

Nature communications

2022 Volume 13, Issue 1, Page(s) 2241

Language	English
Publishing date	2022-04-20
Publishing country	England
Document type	Published Erratum
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-29917-x
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Article ; Online: Supplementation of ambient lighting with a task lamp improves daytime alertness and cognitive performance in sleep-restricted individuals.

Grant, Leilah K / Crosthwaite, Phoebe C / Mayer, Matthew D / Wang, Wei / Stickgold, Robert / St Hilaire, Melissa A / Lockley, Steven W / Rahman, Shadab A

Sleep

2023 Volume 46, Issue 8

Abstract: Study objectives: We examined the impact of adding a single-high-melanopic-illuminance task lamp in an otherwise low-melanopic-illuminance environment on alertness, neurobehavioral performance, learning, and mood during an 8-h simulated workday.: ... ...

Abstract	Study objectives: We examined the impact of adding a single-high-melanopic-illuminance task lamp in an otherwise low-melanopic-illuminance environment on alertness, neurobehavioral performance, learning, and mood during an 8-h simulated workday. Methods: Sixteen healthy young adults [mean(±SD) age = 24.2 ± 2.9, 8F] participated in a 3-day inpatient study with two 8-h simulated workdays and were randomized to either ambient fluorescent room light (~30 melanopic EDI lux, 50 lux), or room light supplemented with a light emitting diode task lamp (~250 melanopic EDI lux, 210 lux) in a cross-over design. Alertness, mood, and cognitive performance were assessed throughout the light exposure and compared between conditions using linear mixed models. Results: The primary outcome measure of percentage correct responses on the addition task was significantly improved relative to baseline in the supplemented condition (3.15% ± 1.18%), compared to the ambient conditions (0.93% ± 1.1%; FDR-adj q = 0.005). Additionally, reaction time and attentional failures on the psychomotor vigilance tasks were significantly improved with exposure to supplemented compared to ambient lighting (all, FDR-adj q ≤ 0.030). Furthermore, subjective measures of sleepiness, alertness, happiness, health, mood, and motivation were also significantly better in the supplemented, compared to ambient conditions (all, FDR-adj q ≤ 0.036). There was no difference in mood disturbance, affect, declarative memory, or motor learning between the conditions (all, FDR-adj q ≥ 0.308). Conclusions: Our results show that supplementing ambient lighting with a high-melanopic-illuminance task lamp can improve daytime alertness and cognition. Therefore, high-melanopic-illuminance task lighting may be effective when incorporated into existing suboptimal lighting environments. Clinical trials: NCT04745312. Effect of Lighting Supplementation on Daytime Cognition. https://clinicaltrials.gov/ct2/show/NCT04745312.
MeSH term(s)	Young Adult ; Humans ; Lighting ; Wakefulness ; Cognition ; Dietary Supplements ; Sleep
Language	English
Publishing date	2023-04-07
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	424441-2
ISSN	1550-9109 ; 0161-8105
ISSN (online)	1550-9109
ISSN	0161-8105
DOI	10.1093/sleep/zsad096
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Zs.A 1475: Show issues

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Article ; Online: An ensemble mixed effects model of sleep loss and performance.

Cochrane, Courtney / Ba, Demba / Klerman, Elizabeth B / St Hilaire, Melissa A

Journal of theoretical biology

2020 Volume 509, Page(s) 110497

Abstract: Sleep loss causes decrements in cognitive performance, which increases risks to those in safety-sensitive fields, including medicine and aviation. Mathematical models can be formulated to predict performance decrement in response to sleep loss, with the ... ...

Abstract	Sleep loss causes decrements in cognitive performance, which increases risks to those in safety-sensitive fields, including medicine and aviation. Mathematical models can be formulated to predict performance decrement in response to sleep loss, with the goal of identifying when an individual may be at highest risk for an accident. This work produces an Ensemble Mixed Effects Model that combines a traditional Linear Mixed Effects (LME) model with a semi-parametric, nonlinear model called Mixed Effects Random Forest (MERF). Using this model, we predict performance on the Psychomotor Vigilance Task (PVT), a test of sustained attention, using biologically motivated features extracted from a dataset containing demographic, sleep, and cognitive test data from 44 healthy participants studied during inpatient sleep loss laboratory experiments. Our Ensemble Mixed Effects Model accurately predicts an individual's trend in PVT performance, and fits the data better than prior published models. The ensemble successfully combines MERF's high rate of peak identification with LME's conservative predictions. We investigate two questions relevant to this model's potential use in operational settings: the tradeoff between additional model features versus ease of collecting these features in real-world settings, and how recent a cognitive task must have been administered to produce strong predictions. This work addresses limitations of previous approaches by developing a predictive model that accounts for interindividual differences and utilizes a nonlinear, semi-parametric method called MERF. We methodologically address the modeling decisions required for this prediction problem, including the choice of cross-validation method. This work is novel in its use of data from a highly-controlled inpatient study protocol that uncouples the influence of the sleep-wake cycle from the endogenous circadian rhythm on the cognitive task being modeled. This uncoupling provides a clearer picture of the model's real-world predictive ability for situations in which people work at different circadian times (e.g., night- or shift-work).
MeSH term(s)	Attention ; Circadian Rhythm ; Humans ; Psychomotor Performance ; Sleep ; Sleep Deprivation ; Wakefulness
Language	English
Publishing date	2020-09-20
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2972-5
ISSN	1095-8541 ; 0022-5193
ISSN (online)	1095-8541
ISSN	0022-5193
DOI	10.1016/j.jtbi.2020.110497
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Zs.A 923: Show issues

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Article ; Online: Circadian lipid and hepatic protein rhythms shift with a phase response curve different than melatonin.

Kent, Brianne A / Rahman, Shadab A / St Hilaire, Melissa A / Grant, Leilah K / Rüger, Melanie / Czeisler, Charles A / Lockley, Steven W

Nature communications

2022 Volume 13, Issue 1, Page(s) 681

Abstract: While studies suggest that light and feeding patterns can reset circadian rhythms in various metabolites, whether these shifts follow a predictable pattern is unknown. We describe the first phase response curves (PRC) for lipids and hepatic proteins in ... ...

Abstract	While studies suggest that light and feeding patterns can reset circadian rhythms in various metabolites, whether these shifts follow a predictable pattern is unknown. We describe the first phase response curves (PRC) for lipids and hepatic proteins in response to combined light and food stimuli. The timing of plasma rhythms was assessed by constant routine before and after exposure to a combined 6.5-hour blue light exposure and standard meal schedule, which was systematically varied by ~20° between in0000dividuals. We find that the rhythms shift according to a PRC, with generally greater shifts for lipids and liver proteins than for melatonin. PRC timing varies relative to the stimulus, with albumin and triglyceride PRCs peaking at a time similar to melatonin whereas the cholesterol and high-density lipoprotein PRCs are offset by ~12 h. These data have important implications for treating circadian misalignment in shiftworkers who consume meals and are exposed to light around the clock.
MeSH term(s)	Adult ; Albumins/metabolism ; Algorithms ; Cholesterol/blood ; Cholesterol, HDL/blood ; Cholesterol, LDL/blood ; Circadian Rhythm/physiology ; Female ; Globulins/metabolism ; Humans ; Lipids/blood ; Liver/metabolism ; Male ; Melatonin/blood ; Melatonin/metabolism ; Models, Theoretical ; Proteome/metabolism ; Time Factors ; Triglycerides/blood ; Young Adult
Chemical Substances	Albumins ; Cholesterol, HDL ; Cholesterol, LDL ; Globulins ; Lipids ; Proteome ; Triglycerides ; Cholesterol (97C5T2UQ7J) ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2022-02-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-28308-6
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Article ; Online: Impact of Upgraded Lighting on Falls in Care Home Residents.

Grant, Leilah K / St Hilaire, Melissa A / Heller, Jenna P / Heller, Rodney A / Lockley, Steven W / Rahman, Shadab A

Journal of the American Medical Directors Association

2022 Volume 23, Issue 10, Page(s) 1698–1704.e2

Abstract: Objectives: Falls in care home residents have major health and economic implications. Given the impact of lighting on visual acuity, alertness, and sleep and their potential influence on falls, we aimed to assess the impact of upgraded lighting on the ... ...

Abstract	Objectives: Falls in care home residents have major health and economic implications. Given the impact of lighting on visual acuity, alertness, and sleep and their potential influence on falls, we aimed to assess the impact of upgraded lighting on the rate of falls in long-term care home residents. Design: An observational study of 2 pairs of care homes (4 sites total). One site from each pair was selected for solid-state lighting upgrade, and the other site served as a control. Setting and participants: Two pairs of care homes with 758 residents (126,479 resident-days; mean age (±SD) 81.0 ± 11.7 years; 57% female; 31% with dementia). Methods: One "experimental" site from each pair had solid-state lighting installed throughout the facility that changed in intensity and spectrum to increase short-wavelength (blue light) exposure during the day (6 am-6 pm) and decrease it overnight (6 pm-6 am). The control sites retained standard lighting with no change in intensity or spectrum throughout the day. The number of falls aggregated from medical records were assessed over an approximately 24-month interval. The primary comparison between the sites was the rate of falls per 1000 resident-days. Results: Before the lighting upgrade, the rate of falls was similar between experimental and control sites [6.94 vs 6.62 falls per 1000 resident-days, respectively; rate ratio (RR) 1.05; 95% CI 0.70-1.58; P = .82]. Following the upgrade, falls were reduced by 43% at experimental sites compared with control sites (4.82 vs 8.44 falls per 1000 resident-days, respectively; RR 0.57; 95% CI 0.39-0.84; P = .004). Conclusions and implications: Upgrading ambient lighting to incorporate higher intensity blue-enriched white light during the daytime and lower intensity overnight represents an effective, passive, low-cost, low-burden addition to current preventive strategies to reduce fall risk in long-term care settings.
MeSH term(s)	Aged ; Aged, 80 and over ; Attention ; Female ; Humans ; Lighting ; Long-Term Care ; Luminescent Agents ; Male ; Sleep
Chemical Substances	Luminescent Agents
Language	English
Publishing date	2022-07-16
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2171030-2
ISSN	1538-9375 ; 1525-8610
ISSN (online)	1538-9375
ISSN	1525-8610
DOI	10.1016/j.jamda.2022.06.013
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Zs.A 5971: Show issues

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Article ; Online: Age-related changes in circadian regulation of the human plasma lipidome.

Rahman, Shadab A / Gathungu, Rose M / Marur, Vasant R / St Hilaire, Melissa A / Scheuermaier, Karine / Belenky, Marina / Struble, Jackson S / Czeisler, Charles A / Lockley, Steven W / Klerman, Elizabeth B / Duffy, Jeanne F / Kristal, Bruce S

Communications biology

2023 Volume 6, Issue 1, Page(s) 756

Abstract: Aging alters the amplitude and phase of centrally regulated circadian rhythms. Here we evaluate whether peripheral circadian rhythmicity in the plasma lipidome is altered by aging through retrospective lipidomics analysis on plasma samples collected in ... ...

Abstract	Aging alters the amplitude and phase of centrally regulated circadian rhythms. Here we evaluate whether peripheral circadian rhythmicity in the plasma lipidome is altered by aging through retrospective lipidomics analysis on plasma samples collected in 24 healthy individuals (9 females; mean ± SD age: 40.9 ± 18.2 years) including 12 younger (4 females, 23.5 ± 3.9 years) and 12 middle-aged older, (5 females, 58.3 ± 4.2 years) individuals every 3 h throughout a 27-h constant routine (CR) protocol, which allows separating evoked changes from endogenously generated oscillations in physiology. Cosinor regression shows circadian rhythmicity in 25% of lipids in both groups. On average, the older group has a ~14% lower amplitude and a ~2.1 h earlier acrophase of the lipid circadian rhythms (both, p ≤ 0.001). Additionally, more rhythmic circadian lipids have a significant linear component in addition to the sinusoidal across the 27-h CR in the older group (44/56) compared to the younger group (18/58, p < 0.0001). Results from individual-level data are consistent with group-average results. Results indicate that prevalence of endogenous circadian rhythms of the human plasma lipidome is preserved with healthy aging into middle-age, but significant changes in rhythmicity include a reduction in amplitude, earlier acrophase, and an altered temporal relationship between central and lipid rhythms.
MeSH term(s)	Middle Aged ; Female ; Humans ; Young Adult ; Adult ; Lipidomics ; Retrospective Studies ; Circadian Rhythm/physiology ; Aging ; Lipids
Chemical Substances	Lipids
Language	English
Publishing date	2023-07-20
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-023-05102-8
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