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Abstract DNA methylation comprises a cumulative record of lifetime exposures superimposed on genetically determined markers. Little is known about methylation dynamics in humans following an acute perturbation, such as infection. We characterized the temporal trajectory of blood epigenetic remodeling in 133 participants in a prospective study of young adults before, during, and after asymptomatic and mildly symptomatic SARS‐CoV‐2 infection. The differential methylation caused by asymptomatic or mildly symptomatic infections was indistinguishable. While differential gene expression largely returned to baseline levels after the virus became undetectable, some differentially methylated sites persisted for months of follow‐up, with a pattern resembling autoimmune or inflammatory disease. We leveraged these responses to construct methylation‐based machine learning models that distinguished samples from pre‐, during‐, and postinfection time periods, and quantitatively predicted the time since infection. The clinical trajectory in the young adults and in a diverse cohort with more severe outcomes was predicted by the similarity of methylation before or early after SARS‐CoV‐2 infection to the model‐defined postinfection state. Unlike the phenomenon of trained immunity, the postacute SARS‐CoV‐2 epigenetic landscape we identify is antiprotective.

Abstract Background Implementation of the World Health Organization's DOTS strategy (Directly Observed Treatment Short-course therapy) can result in significant reduction in tuberculosis incidence. We estimated potential costs and benefits of DOTS expansion in Haiti from the government, and societal perspectives. Methods Using decision analysis incorporating multiple Markov processes (Markov modelling), we compared expected tuberculosis morbidity, mortality and costs in Haiti with DOTS expansion to reach all of the country, and achieve WHO benchmarks, or if the current situation did not change. Probabilities of tuberculosis related outcomes were derived from the published literature. Government health expenditures, patient and family costs were measured in direct surveys in Haiti and expressed in 2003 US$. Results Starting in 2003, DOTS expansion in Haiti is anticipated to cost $4.2 million and result in 63,080 fewer tuberculosis cases, 53,120 fewer tuberculosis deaths, and net societal savings of $131 million, over 20 years. Current government spending for tuberculosis is high, relative to the per capita income, and would be only slightly lower with DOTS. Societal savings would begin within 4 years, and would be substantial in all scenarios considered, including higher HIV seroprevalence or drug resistance, unchanged incidence following DOTS expansion, or doubling of initial and ongoing costs for DOTS expansion. Conclusion A modest investment for DOTS expansion in Haiti would provide considerable humanitarian benefit by reducing tuberculosis-related morbidity, mortality and costs for patients and their families. These benefits, together with projected minimal Haitian government savings, argue strongly for donor support for DOTS expansion.

Aims: Anecdotal reports have suggested increased soft tissue calcification in individuals with long-term exposures to high blood glucose. The association of costal cartilage calcification (CCC), a reliably quantifiable marker obtainable from non-contrast cardiac computed tomography (CT) with cumulative fasting blood glucose (FBG) exposure, is unknown. In this study, we aimed to determine the association between quantified CCC and cumulative glucose exposure using non-contrast coronary artery calcium (CAC) scoring computed tomography (CT) images in the Multi-Ethnic Study of Atherosclerosis (MESA)., Methods: The volume of bilateral CCC was quantified in high-density pixels (threshold of Hounsfield Unit>180) using the CAC scoring CT images acquired in the 5 th MESA exam. Prior long-term cumulative exposure to FBG was calculated by area under the FBG-time curve over ten years before the time of the CT exam., Results: A total of 2,305 participants (mean age: 69, female/male: 1.3) were included in this study. The median CCC volume was lower in females than males (1158 mm 3 [IQR: 1751] vs. 3054 mm 3 [3851], p<0.001). In cross-sectional analysis, quantified CCC was associated with FBG (9% increase per SD) and HbA1c (7% increase per SD) at the CT exam only in female participants after adjustment for age, race, BMI, and glomerular filtration rate. Only in female participants, quantified CCC was also associated with prior cumulative FBG (3% increase per decile change). In the subgroup of females with zero CAC scores, the adjusted CCC was still associated with FBG (13% increase per SD) at the time of CT exam and with prior cumulative FBG exposure (4% increase per decile change) before the CT exam., Conclusions: The CCC, a reliably quantified marker in non-contrast cardiac CT, is associated with 10-year cumulative FBG exposure only in female participants, even those with zero CAC., Competing Interests: The 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. The reviewer AS declared a shared affiliation with one of the authors, CW, to the handling editor at time of review., (Copyright © 2021 Shabani, Pishgar, Akhtarkhavari, Quinaglia, Budoff, Bluemke, Barr, Post, Wu, Arbab-Zadeh, Sidhaye, Lima and Demehri.)

Background and Aims: Modern tobacco regulatory science requires an understanding of which biomarkers of cardiovascular injury are most sensitive to cigarette smoking exposure., Methods: We studied self-reported current smokers from the Multi-Ethnic Study of Atherosclerosis. Smoking intensity was defined by number of cigarettes/day and urinary cotinine levels. Subclinical cardiovascular injury was assessed using markers of inflammation [high-sensitivity C-reactive protein (hsCRP), interleukin 6 & 2 (IL-2 & IL-6), tumor necrosis factor alpha (TNF-α)], thrombosis (fibrinogen, D-dimer, homocysteine), myocardial injury (troponin T; TnT), endothelial damage (albumin: creatinine ratio), and vascular function [aortic & carotid distensibility, flow-mediated dilation (FMD)]. Biomarkers were modeled as absolute and percent change using multivariable-adjusted linear regression models adjusted for cardiovascular risk factors and smoking duration., Results: Among 843 current smokers, mean age was 58 (9) years, 53% were men, 39% were African American, mean number of cigarettes per day was 13 (10), and median smoking duration was 39 (15) years. Cigarette count was significantly associated with higher hsCRP, IL-6 and fibrinogen (β coefficients: 0.013, 0.011, 0.60 respectively), while ln-transformed cotinine was associated with the same biomarkers (β coefficients: 0.12, 0.04, 5.3 respectively) and inversely associated with aortic distensibility (β coefficient: -0.13). There was a limited association between smoking intensity and homocysteine, D-dimer, and albumin:creatinine ratio in partially adjusted models only, while there was no association with IL-2, TNF-α, carotid distensibility, FMD, or TnT in any model. In percent change analyses, relationships were strongest with hsCRP., Conclusions: Smoking intensity was associated with early biomarkers of CVD, particularly, markers of systemic inflammation. Of these, hsCRP may be the most sensitive., (Copyright © 2017 Elsevier B.V. All rights reserved.)

It is often difficult to make a correct diagnosis of a uveal melanoma in an eye with opaque media. A patient with a blind, painful eye and opaque media was evaluated clinically and with computed axial tomography and ultrasonography. We were unable to establish the definitive diagnosis of a uveal melanoma until the eye was examined histologically. Necrotic melanomas usually present with inflammatory signs, may produce opaque media and can be difficult to diagnose with clinical and imaging studies.