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Article ; Online: Circadian and Diurnal Regulation of Cerebral Blood Flow.

Webb, Alastair J S / Klerman, Elizabeth B / Mandeville, Emiri T

2024 Volume 134, Issue 6, Page(s) 695–710

Abstract: Circadian and diurnal variation in cerebral blood flow directly contributes to the diurnal variation in the risk of stroke, either through factors that trigger stroke or due to impaired compensatory mechanisms. Cerebral blood flow results from the ... ...

Abstract	Circadian and diurnal variation in cerebral blood flow directly contributes to the diurnal variation in the risk of stroke, either through factors that trigger stroke or due to impaired compensatory mechanisms. Cerebral blood flow results from the integration of systemic hemodynamics, including heart rate, cardiac output, and blood pressure, with cerebrovascular regulatory mechanisms, including cerebrovascular reactivity, autoregulation, and neurovascular coupling. We review the evidence for the circadian and diurnal variation in each of these mechanisms and their integration, from the detailed evidence for mechanisms underlying the nocturnal nadir and morning surge in blood pressure to identifying limited available evidence for circadian and diurnal variation in cerebrovascular compensatory mechanisms. We, thus, identify key systemic hemodynamic factors related to the diurnal variation in the risk of stroke but particularly identify the need for further research focused on cerebrovascular regulatory mechanisms.
MeSH term(s)	Humans ; Stroke ; Blood Pressure/physiology ; Hemodynamics ; Circadian Rhythm ; Cerebrovascular Circulation/physiology
Language	English
Publishing date	2024-03-14
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.123.323049
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Article ; Online: Altered sleep architecture in children and adolescents with Down syndrome.

Gardner, Kelly J / Wang, Wei / Klerman, Elizabeth B

American journal of medical genetics. Part C, Seminars in medical genetics

2023 Volume 193, Issue 4, Page(s) e32073

Abstract: Objective: Children with Down syndrome (DS) may experience changes in sleep architecture (i.e., different sleep stages) that then affect waketime functioning, including learning, mood, and disruptive behavior. For designing and testing interventions, it ...

Abstract	Objective: Children with Down syndrome (DS) may experience changes in sleep architecture (i.e., different sleep stages) that then affect waketime functioning, including learning, mood, and disruptive behavior. For designing and testing interventions, it is important to document any differences in sleep architecture in children with DS with and without co-occurring diagnoses, including neuropsychiatric diagnoses and obstructive sleep apnea (OSA). Methods: A retrospective cohort study was performed at Massachusetts General Hospital for children and adolescents with DS who underwent polysomnography (PSG) between August 2016 and July 2022. Patient data collected from the electronic medical record included diagnoses, age at PSG, and PSG report. Statistical analysis included unpaired T tests to test hypotheses about differences in sleep architecture within age groups, and differences between children with DS and a co-occurring diagnosis. One way ANOVA was used to determine statistical significance of OSA severity within patients with DS. Results: When compared by age group, those with DS had negative changes in sleep architecture (e.g., less sleep and more wake) when compared to normative data. Within this cohort, having a co-occurring diagnosis of autism resulted in further, negative effects on sleep architecture. 89% of those with DS had diagnosed OSA but only those with severe OSA experienced negative effects on sleep architecture. Conclusion: Age is an important covariate when studying the sleep of children with DS and neurotypical children. Studies are needed to test whether minimizing the observed differences in sleep architecture will translate to improved learning, mood, and behavioral outcomes, and how treating OSA affects sleep architecture.
MeSH term(s)	Child ; Humans ; Adolescent ; Retrospective Studies ; Down Syndrome/complications ; Down Syndrome/diagnosis ; Sleep Apnea, Obstructive/etiology ; Sleep Apnea, Obstructive/diagnosis ; Polysomnography ; Sleep
Language	English
Publishing date	2023-10-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2108622-9
ISSN	1552-4876 ; 0148-7299 ; 1552-4868
ISSN (online)	1552-4876
ISSN	0148-7299 ; 1552-4868
DOI	10.1002/ajmg.c.32073
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Article ; Online: Daylight saving time and mortality-proceed with caution.

Klerman, Elizabeth B / Weaver, Matthew D / Roenneberg, Till / Malow, Beth A / Johnson, Karin G

Nature communications

2024 Volume 15, Issue 1, Page(s) 1576

MeSH term(s)	Seasons ; Circadian Rhythm
Language	English
Publishing date	2024-02-21
Publishing country	England
Document type	Letter
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45837-4
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Article ; Online: Characterizing Alterations in Cortisol Secretion During Cardiac Surgery.

Raju, Vidya / Gibbison, Ben / Klerman, Elizabeth B / Faghih, Rose T

Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference

2023 Volume 2023, Page(s) 1–6

Abstract: Cortisol is a neuroendocrine hormone of the hypothalamus-pituitary-adrenal (HPA) axis secreted from adrenal glands in response to stimulation by adrenocorticotropic hormone (ACTH) from the anterior pituitary and corticotropin releasing hormone (CRH) from ...

Abstract	Cortisol is a neuroendocrine hormone of the hypothalamus-pituitary-adrenal (HPA) axis secreted from adrenal glands in response to stimulation by adrenocorticotropic hormone (ACTH) from the anterior pituitary and corticotropin releasing hormone (CRH) from the hypothalamus. Cortisol has multiple functionalities in maintaining bodily homeostasis - including anti-inflammatory influences - through its diurnal secretion pattern (which has been studied extensively); its secretion is also increased in response to major traumatic events such as surgery. Due to the adverse health consequences of an abnormal immune response, it is crucial to understand the effect of cortisol in modulating inflammation. To address this physiological issue, we characterize the secretion of cortisol using a high temporal resolution dataset of ten patients undergoing coronary arterial bypass grafting (CABG) surgery, in comparison with a control group not undergoing surgery. We find that cortisol exhibits different pulsatile dynamics in those undergoing cardiac surgery compared to the control subjects. We also summarize the causality of cortisol's relationship with different cytokines (which are one type of inflammatory markers) by performing Granger causality analysis.Clinical relevance- This work documents time-varying patterns of the HPA axis hormone cortisol in the inflammatory response to cardiac surgery and may eventually help improve patients' prognosis post-surgery (or in other conditions) by enabling early detection of an abnormal cortisol or inflammatory response and enabling patient specific remedial interventions.
MeSH term(s)	Humans ; Hydrocortisone/pharmacology ; Hypothalamo-Hypophyseal System/metabolism ; Pituitary-Adrenal System/metabolism ; Adrenocorticotropic Hormone/metabolism ; Adrenocorticotropic Hormone/pharmacology ; Cardiac Surgical Procedures/adverse effects
Chemical Substances	Hydrocortisone (WI4X0X7BPJ) ; Adrenocorticotropic Hormone (9002-60-2)
Language	English
Publishing date	2023-12-11
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2694-0604
ISSN (online)	2694-0604
DOI	10.1109/EMBC40787.2023.10340220
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Article ; Online: From Bench to Bedside and Back Again: Translating Circadian Science to Medicine.

Klerman, Elizabeth B / Kramer, Achim / Zee, Phyllis C

Journal of biological rhythms

2022 Volume 38, Issue 2, Page(s) 125–130

MeSH term(s)	Circadian Rhythm ; Medicine
Language	English
Publishing date	2022-12-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	896387-3
ISSN	1552-4531 ; 0748-7304
ISSN (online)	1552-4531
ISSN	0748-7304
DOI	10.1177/07487304221142743
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Article ; Online: The circadian system, sleep, and the health/disease balance: a conceptual review.

Roenneberg, Till / Foster, Russell G / Klerman, Elizabeth B

Journal of sleep research

2022 Volume 31, Issue 4, Page(s) e13621

Abstract: The field of "circadian medicine" is a recent addition to chronobiology and sleep research efforts. It represents a logical step arising from the increasing insights into the circadian system and its interactions with life in urbanised societies; ... ...

Abstract	The field of "circadian medicine" is a recent addition to chronobiology and sleep research efforts. It represents a logical step arising from the increasing insights into the circadian system and its interactions with life in urbanised societies; applying these insights to the health/disease balance at home and in the medical practice (outpatient) and clinic (inpatient). Despite its fast expansion and proliferating research efforts, circadian medicine lacks a formal framework to categorise the many observations describing interactions among the circadian system, sleep, and the health/disease balance. A good framework allows us to categorise observations and then assign them to one or more components with hypothesised interactions. Such assignments can lead to experiments that document causal (rather than correlational) relationships and move from describing observations to discovering mechanisms. This review details such a proposed formal framework for circadian medicine and will hopefully trigger discussion among our colleagues, so that the framework can be improved and expanded. As the basis of the framework for circadian medicine, we define "circadian health" and how it links to general health. We then define interactions among the circadian system, sleep, and the health/disease balance and put the framework into the context of the literature with examples from six domains of health/disease balance: fertility, cancer, immune system, mental health, cardiovascular, and metabolism.
MeSH term(s)	Circadian Rhythm ; Humans ; Mental Health ; Sleep ; Sleep Wake Disorders
Language	English
Publishing date	2022-06-07
Publishing country	England
Document type	Journal Article ; Review ; 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	1122722-9
ISSN	1365-2869 ; 0962-1105
ISSN (online)	1365-2869
ISSN	0962-1105
DOI	10.1111/jsr.13621
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Article ; Online: Chronic Circadian Disruption and Sleep Restriction Influence Subjective Hunger, Appetite, and Food Preference.

McHill, Andrew W / Hull, Joseph T / Klerman, Elizabeth B

Nutrients

2022 Volume 14, Issue 9

Abstract: Chronic circadian disruption (CCD), such as occurs during rotating shiftwork, and insufficient sleep are each independently associated with poor health outcomes, including obesity and glucose intolerance. A potential mechanism for poor health is ... ...

Abstract	Chronic circadian disruption (CCD), such as occurs during rotating shiftwork, and insufficient sleep are each independently associated with poor health outcomes, including obesity and glucose intolerance. A potential mechanism for poor health is increased energy intake (i.e., eating), particularly during the circadian night, when the physiological response to energy intake is altered. However, the contributions of CCD and insufficient sleep to subjective hunger, appetite, food preference, and appetitive hormones are not clear. To disentangle the influences of these factors, we studied seventeen healthy young adults in a 32-day in-laboratory study designed to distribute sleep, wakefulness, and energy intake equally across all phases of the circadian cycle, thereby imposing CCD. Participants were randomized to the Control (1:2 sleep:wake ratio,
MeSH term(s)	Appetite/physiology ; Food Preferences ; Ghrelin ; Humans ; Hunger/physiology ; Sleep/physiology ; Sleep Deprivation ; Young Adult
Chemical Substances	Ghrelin
Language	English
Publishing date	2022-04-26
Publishing country	Switzerland
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu14091800
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Article: An Anticipatory Scheme for the Model Predictive Control of Circadian Phase for Expected Environmental Light Changes.

Brown, Lindsey S / Klerman, Elizabeth B / Doyle, Francis J

IEEE control systems letters

2021 Volume 6, Page(s) 1616–1621

Abstract: The circadian system is critical to timing biological functions in anticipation of daily environmental light changes, but much previous work on the development of molecular control inputs to shift the phase of the circadian system has applied model ... ...

Abstract	The circadian system is critical to timing biological functions in anticipation of daily environmental light changes, but much previous work on the development of molecular control inputs to shift the phase of the circadian system has applied model predictive control (MPC) without considering expected environmental light changes. We augment the MPC algorithm to develop an anticipatory control algorithm, which has advantages over MPC in achieving scheduled phase shifts (as occurs with jet lag and shiftwork). We further extend the algorithm in a model switching control scheme to account for changes in the light environment. Taken together, these two enhancements to the standard MPC framework allow for better control of the circadian oscillator in more realistic environments by anticipating environmental light changes.
Language	English
Publishing date	2021-11-22
Publishing country	United States
Document type	Journal Article
ISSN	2475-1456
ISSN	2475-1456
DOI	10.1109/LCSYS.2021.3129475
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Article ; Online: Estimating Community Disruption from Nighttime Gunshots in 6 U.S. Cities, 2015 to 2021.

Robbins, Rebecca / Affouf, Mahmoud / Masiakos, Peter T / Iyer, Jay M / Griggs, Cornelia / Klerman, Elizabeth B / Sacks, Chana A

Journal of general internal medicine

2024

Abstract: Background: Gunshots affect those directly involved in an incident and those in the surrounding community. The community-level impact of nighttime gunshots, which may be particularly disruptive to the sleep of nearby community members, is unknown.: ... ...

Abstract	Background: Gunshots affect those directly involved in an incident and those in the surrounding community. The community-level impact of nighttime gunshots, which may be particularly disruptive to the sleep of nearby community members, is unknown. Objective: Our aim is to estimate the number of people potentially affected by nighttime gunshots and the relationship between nighttime gunshots and median household income in the USA. Design: We collected publicly available data on the timing and location of gunshots in six U.S. cities (Baltimore, MD; Boston, MA; Washington, D.C.; New York, NY; Philadelphia, PA; and Portland, OR) from 2015 to 2021. We then analyzed the data by computing rate ratios (RRs) to compare the frequency of gunshots during nighttime hours (6:00 pm to 5:59 am) versus daytime hours (6:00 am to 5:59 pm). Additionally, we used geospatial mapping to create choropleth maps to visualize the variation in nighttime gunshot density across cities. We estimated, using city-wide population, person-nights potentially impacted by the sound of gunshots within areas of 0.2- (low) and 0.5-mile (high) radius. Finally, for five of six cities where data on median household income were available by census tract, we built nonlinear regression models to estimate the relationship between the number of nighttime gunshots and median household income. Key results: We analyzed 72,236 gunshots. Gunshots were more common during the nighttime than daytime (overall RR = 2.5). Analyses demonstrated that the low estimates for the mean annual number of person-nights impacted by nighttime gunshots were 0.4 million in Baltimore and Portland, 1.3 million in Philadelphia, 1.6 million in Boston, 2.9 million in New York City, and 5.9 million in Washington. The number of nighttime gunshots was inversely related to median household income. Conclusions: Nighttime gunshots are prevalent, particularly in low-income neighborhoods, and may have under-recognized effects on the surrounding community.
Language	English
Publishing date	2024-04-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	639008-0
ISSN	1525-1497 ; 0884-8734
ISSN (online)	1525-1497
ISSN	0884-8734
DOI	10.1007/s11606-024-08707-9
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Article: Timing of diuretic administration effects on urine volume in hospitalized patients.

McCullar, Katie S / Abbaspour, Sara / Wang, Wei / Aguirre, Aaron D / Westover, M Brandon / Klerman, Elizabeth B

Frontiers in physiology

2024 Volume 14, Page(s) 1208324

Abstract: Importance: ...

Abstract	Importance:
Language	English
Publishing date	2024-01-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2023.1208324
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