Publications by authors named "M Carrington Reid"

2,830 Publications

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Gender Differences in the Association of Insomnia Symptoms and Coronary Artery Calcification in the Multi-Ethnic Study of Atherosclerosis.

Sleep 2021 May 14. Epub 2021 May 14.

Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA.

Study Objectives: To quantify the gender-specific associations between insomnia symptoms and subclinical atherosclerosis, measured by coronary artery calcium (CAC) scores, which has strong predictive value for incident cardiovascular disease.

Methods: We analyzed data from 1,429 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants completed standardized questionnaires and underwent polysomnography (PSG) and 7-day actigraphy. Insomnia symptoms was defined as: self-reported trouble falling, staying or returning to sleep, early-morning awakenings, or hypnotic use, for ≥5 nights/week. MESA assessed CAC using computed tomography. We employed multivariable linear regression to model the probability of CAC>0 overall and to model the linear continuous effect among those with non-zero CAC.

Results: Our sample was a mean age of 68.1 ± 9.1yrs, 53.9% female, and 36.2% white, 28.0% Black, 24.2% Hispanic, and 11.5% Chinese-American. Insomnia symptoms was present in 49.7% of men and 47.2% of women. In multivariable-adjusted analyses, insomnia symptoms was associated with an 18% higher prevalence of CAC (PR 1.18, 95% CI 1.04, 1.33) among females, but no association was observed among males (PR 1.00, 95% CI 0.91, 1.08). There was no evidence that the association between insomnia symptoms and prevalence of CAC>0 differed by objective sleep duration status (by single-night PSG or multi-night actigraphy) in females or males.

Conclusions: We found that among women, insomnia symptoms was associated with an 18% higher prevalence of CAC compared to no insomnia. Insomnia symptoms was not associated with CAC prevalence in men. Additionally, there was no evidence that the association between insomnia symptoms and CAC score >0 differed by objective short sleep duration status.
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http://dx.doi.org/10.1093/sleep/zsab116DOI Listing
May 2021

Sleep apnea, coronary artery calcium density and cardiovascular events: results from the Multi-Ethnic Study of Atherosclerosis (MESA).

J Clin Sleep Med 2021 May 14. Epub 2021 May 14.

Icahn School of Medicine at Mount Sinai, New York, NY.

Study Objectives: Evaluate the association between obstructive sleep apnea (OSA), coronary artery calcium (CAC) density, and cardiovascular events in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: We analyzed 1041 participants with non-zero CAC scores who had polysomnography and CAC density data from the fifth examination of MESA. OSA was defined as apnea-hypopnea index [AHI] ≥ 15 events/hour. Multivariable linear regression models were used to evaluate the independent association between OSA and CAC density. Additionally, we evaluated the impact of OSA on associations of CAC measures with incident CVD events by testing for interaction in Cox proportional hazard regression models.

Results: Our analytical sample was 45% female with a mean age of 70.6 +/- 9 years. Of this sample, 36.7% (n=383/1041) had OSA (AHI≥15). OSA was inversely and weakly associated with CAC density (β= -0.09, 95% CI -0.17 to -0.02, p=0.014) and remained significantly associated after controlling for traditional cardiovascular risk factors (β= -0.08, 95% CI -0.16 to 0, p=0.043). However, this inverse association was attenuated after controlling for BMI (β=-0.05, 95% CI -0.13 to 0.02, p=0.174). The mean follow-up period for CVD events was 13.3 +/- 2.8 years. Additionally, exploratory analysis demonstrated that CAC density was independently and inversely associated with CVD events only in the non-OSA subgroup (AHI≤15) (HR 0.509 [CI 0.323 - 0.801], p=0.0035).

Conclusions: OSA was associated with lower CAC density, but this association was attenuated by BMI. Further, increased CAC density was associated with a reduced risk of CVD events only in individuals within the non-OSA group in exploratory analysis.
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http://dx.doi.org/10.5664/jcsm.9356DOI Listing
May 2021

Sleep duration and vascular inflammation using hybrid positron emission tomography/magnetic resonance imaging: results from the Multi-Ethnic Study of Atherosclerosis (MESA).

J Clin Sleep Med 2021 May 10. Epub 2021 May 10.

Division of Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.

Study Objectives: Short sleep duration (SD) is associated with cardiovascular disease (CVD). We investigated the relationship between objective SD and subclinical atherosclerosis employing hybrid PET/MRI with F-FDG tracer in the MESA cohort.

Methods: We utilized data from MESA-SLEEP and MESA-PET ancillary studies. SD and sleep fragmentation index (SFI) were assessed using 7-day actigraphy. The primary and secondary outcomes were carotid inflammation, defined using target-to-background ratios (TBR), and measures of carotid wall remodeling (carotid wall thickness [CWT]), summarized by SD category. Multivariate linear regression was performed to assess the association between SD and SFI with the primary/secondary outcomes, adjusting for several covariates including apnea-hypopnea index (AHI), and CVD risk.

Results: Our analytical sample (n=58) was 62% female (mean age 68±8.4 years). Average SD was 5.1±0.9 hours in the short SD group (≤6 hours/night, 31%), and 7.1±0.8 hours in the normal SD group (69%). Prevalence of pathologic vascular inflammation (TBRmax>1.6) was higher in the short SD group (89% vs. 53%, p=0.009). Those with short SD had a higher TBRmax (1.77 vs 1.71), though this was not statistically significant (p=0.39). CWT was positively correlated with SFI even after adjusting for covariates (Beta [SE]=0.073±[0.032], p=0.025).

Conclusions: Prevalence of pathologic vascular inflammation was higher among those who slept ≤6 hours, and vascular inflammation was higher among those with a SD of ≤6 hours. Interestingly, SFI was positively correlated with CWT even after adjustment for covariates. Our results are hypothesis-generating but suggest that both habitual SD and SFI should be investigated in future studies as potential risk factors for subclinical atherosclerosis.
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http://dx.doi.org/10.5664/jcsm.9382DOI Listing
May 2021

Altered Phase Separation and Cellular Impact in -Linked ALS/FTD.

Front Cell Neurosci 2021 21;15:664151. Epub 2021 Apr 21.

UK Dementia Research Institute at King's College London, London, United Kingdom.

Since the discovery of the repeat expansion mutation as causative for chromosome 9-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in 2011, a multitude of cellular pathways have been implicated. However, evidence has also been accumulating for a key mechanism of cellular compartmentalization-phase separation. Liquid-liquid phase separation (LLPS) is fundamental for the formation of membraneless organelles including stress granules, the nucleolus, Cajal bodies, nuclear speckles and the central channel of the nuclear pore. Evidence has now accumulated showing that the formation and function of these membraneless organelles is impaired by both the toxic arginine rich dipeptide repeat proteins (DPRs), translated from the repeat RNA transcript, and the repeat RNA itself. Both the arginine rich DPRs and repeat RNA themselves undergo phase separation and disrupt the physiological phase separation of proteins involved in the formation of these liquid-like organelles. Hence abnormal phase separation may explain a number of pathological cellular phenomena associated with -ALS/FTD. In this review article, we will discuss the principles of phase separation, phase separation of the DPRs and repeat RNA themselves and how they perturb LLPS associated with membraneless organelles and the functional consequences of this. We will then discuss how phase separation may impact the major pathological feature of -ALS/FTD, TDP-43 proteinopathy, and how LLPS may be targeted therapeutically in disease.
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http://dx.doi.org/10.3389/fncel.2021.664151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096919PMC
April 2021

Recommended reading from the Loyola University Medical Center Pulmonary and Critical Care Medicine Fellows.

Am J Respir Crit Care Med 2021 May 5. Epub 2021 May 5.

Loyola University Chicago Stritch School of Medicine, 12248, Division of Pulmonary and Critical Care, Maywood, Illinois, United States.

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http://dx.doi.org/10.1164/rccm.202012-4356RRDOI Listing
May 2021