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PurposeBetalains are indole-derived pigments found in beet root, and recent studies suggest that they may exert ergogenic effects. Herein, we examined if supplementation for 7 days with betalain-rich beetroot concentrate (BLN) improved cycling performance or altered hemodynamic and serum analytes prior to, during and following a cycling time trial (TT).MethodsTwenty-eight trained male cyclists (29 ± 10 years, 77.3 ± 13.3 kg, and 3.03 ± 0.62 W/kg) performed a counterbalanced crossover study whereby BLN (100 mg/day) or placebo (PLA) supplementation occurred over 7 days with a 1-week washout between conditions. On the morning of day seven of each supplementation condition, participants consumed one final serving of BLN or PLA and performed a 30-min cycling TT with concurrent assessment of several physiological variables and blood markers.ResultsBLN supplementation improved average absolute power compared to PLA (231.6 ± 36.2 vs. 225.3 ± 35.8 W, p = 0.050, d = 0.02). Average relative power, distance traveled, blood parameters (e.g., pH, lactate, glucose, NOx) and inflammatory markers (e.g., IL-6, IL-8, IL-10, TNFα) were not significantly different between conditions. BLN supplementation significantly improved exercise efficiency (W/ml/kg/min) in the last 5 min of the TT compared to PLA (p = 0.029, d = 0.45). Brachial artery blood flow in the BLN condition, immediately post-exercise, tended to be greater compared to PLA (p = 0.065, d = 0.32).ConclusionsWe report that 7 days of BLN supplementation modestly improves 30-min TT power output, exercise efficiency as well as post-exercise blood flow without increasing plasma NOx levels or altering blood markers of inflammation, oxidative stress, and/or hematopoiesis.

Purpose This study examined targeted genomic variants of transforming growth factor beta (TGFB) signaling in Appalachian women. Appalachian women with cervical cancer were compared to healthy Appalachian counterparts to determine whether these polymorphic alleles were over-represented within this high-risk cancer population, and whether lifestyle or environmental factors modified the aggregate genetic risk in these Appalachian women. Methods Appalachian women’s survey data and blood samples from the Community Awareness, Resources, and Education (CARE) CARE I and CARE II studies ( n  = 163 invasive cervical cancer cases, 842 controls) were used to assess gene–environment interactions and cancer risk. Polymorphic allele frequencies and socio-behavioral demographic measurements were compared using t tests and χ 2 tests. Multivariable logistic regression was used to evaluate interaction effects between genomic variance and demographic, behavioral, and environmental characteristics. Results Several alleles demonstrated significant interaction with smoking ( TP53 rs1042522, TGFB1 rs1800469 ), alcohol consumption ( NQO1 rs1800566 ), and sexual intercourse before the age of 18 ( TGFBR1 rs11466445, TGFBR1 rs7034462, TGFBR1 rs11568785 ). Interestingly, we noted a significant interaction between “Appalachian self-identity” variables and NQO1 rs1800566 . Multivariable logistic regression of cancer status in an over-dominant TGFB1 rs1800469 / TGFBR1 rs11568785 model demonstrated a 3.03-fold reduction in cervical cancer odds. Similar decreased odds (2.78-fold) were observed in an over-dominant TGFB1 rs1800469 / TGFBR1 rs7034462 model in subjects who had no sexual intercourse before age 18. Conclusions This study reports novel associations between common low-penetrance alleles in the TGFB signaling cascade and modified risk of cervical cancer in Appalachian women. Furthermore, our unexpected findings associating Appalachian identity and NQO1 rs1800566 suggests that the complex environmental exposures that contribute to Appalachian self-identity in Appalachian cervical cancer patients represent an emerging avenue of scientific exploration.

This study investigated long-term speech and language outcomes in 51 prelingually deaf children, adolescents and young adults who received cochlear implants (CIs) prior to 7 years of age and had used their implants for at least 7 years. Average speech perception scores were similar to those found in prior research with other samples of experienced CI users. Mean language test scores were lower than norm-referenced scores from nationally representative normal-hearing, typically developing samples, although a majority of the CI users scored within 1 standard deviation of the normative mean or higher on the Peabody Picture Vocabulary Test, Fourth Edition (63%), and the Clinical Evaluation of Language Fundamentals, Fourth Edition (69%). Speech perception scores were negatively associated with a meningitic etiology of hearing loss, older age at implantation, poorer preimplant unaided pure-tone average thresholds, lower family income and the use of ‘total communication'. Subjects who had used CIs for 15 years or more were more likely to have these characteristics and were more likely to score lower on measures of speech perception compared to those who had used CIs for 14 years or less. The aggregation of these risk factors in the >15 years of CI use subgroup accounts for their lower speech perception scores and may stem from more conservative CI candidacy criteria in use at the beginning of pediatric cochlear implantation.

The role of host genetic variation in the development of complicated Staphylococcus aureus bacteremia (SAB) is poorly understood. We used whole exome sequencing (WES) to examine the cumulative effect of coding variants in each gene on risk of complicated SAB in a discovery sample of 168 SAB cases (84 complicated and 84 uncomplicated, frequency matched by age, sex, and bacterial clonal complex [CC]), and then evaluated the most significantly associated genes in a replication sample of 240 SAB cases (122 complicated and 118 uncomplicated, frequency matched for age, sex, and CC) using targeted sequence capture. In the discovery sample, gene-based analysis using the SKAT-O program identified 334 genes associated with complicated SAB at p<3.5 x 10-3. These, along with eight biologically relevant candidate genes were examined in the replication sample. Gene-based analysis of the 342 genes in the replication sample using SKAT-O identified one gene, GLS2, significantly associated with complicated SAB (p = 1.2 x 10-4) after Bonferroni correction. In Firth-bias corrected logistic regression analysis of individual variants, the strongest association across all 10,931 variants in the replication sample was with rs2657878 in GLS2 (p = 5 x 10-4). This variant is strongly correlated with a missense variant (rs2657879, p = 4.4 x 10-3) in which the minor allele (associated here with complicated SAB) has been previously associated with lower plasma concentration of glutamine. In a microarray-based gene-expression analysis, individuals with SAB exhibited significantly lower expression levels of GLS2 than healthy controls. Similarly, Gls2 expression is lower in response to S. aureus exposure in mouse RAW 264.7 macrophage cells. Compared to wild-type cells, RAW 264.7 cells with Gls2 silenced by CRISPR-Cas9 genome editing have decreased IL1-β transcription and increased nitric oxide production after S. aureus exposure. GLS2 is an interesting candidate gene for complicated SAB due to its role in regulating glutamine metabolism, a key factor in leukocyte activation.

ABSTRACT Background: Nonsteroidal anti-inflammatory drug (NSAID) use may reduce the incidence of post- cardiothoracic surgery (CTS) atrial fibrillation (AF). The cerebrovascular and cardiovascular safety of using NSAIDs for post-CTS AF has not been determined. Objective: To evaluate whether NSAIDs could reduce the incidence of post-CTS atrial fibrillation without in­creasing patients' risk of stroke or myocardial infarction (MI). Methods: Patients (n = 555) undergoing CTS from the Atrial Fibrillation Suppression Trials I, II and III were evalu­ated in this nested cohort study. Demographic, surgical and medication use characteristics were prospectively collected as part of the AFIST trials. Endpoints included post-CTS atrial fibrillation, stroke, MI and the need for red blood cell transfusion. Multivariable logistic regression was used to control for potential confounders and calculate adjusted odds ratios with 95% confidence intervals. Results: The population was 67.8 ± 8.6 years old and 77.1% male with 127 (22.9%) patients receiving an NSAID postoperatively. Overall, 14.6% underwent valve surgery, 6.1% had prior AF, 12.6% had heart failure and 84.0% and 44.1% received postoperative β-blockade and prophylactic amiodarone. NSAID use was associated with reductions in the adjusted odds of post-CTS atrial fibrilla­tion (0.54 (0.32-0.90)) and the need for RBC transfusions (0.63 (0.41-0.97)). No elevation in the odds of developing stroke (1.10 (0.21-5.66)) or MI (1.70 (0.40-7.10)) was observed. Limitations: Patients were not randomized to receive NSAIDs versus a control. We may not have had adequate power to evaluate stoke or MI in this analysis. Conclusions: NSAIDs decreased the odds of developing post-CTS atrial fibrillation, further supporting the hypothesis of inflammation as a trigger for post-CTS atrial fibrillation. The need for RBC transfusions was also re­duced with NSAID use. We may have been underpowered to evaluate stroke or MI incidence, but the qualitative elevations in these variables suggest more safety data is needed before NSAIDs can be routinely recommended.

Pathogen and chemical exposures lead to profound remodeling of the gene-regulatory landscape across human immune cell populations. Here, we present a single-nucleus chromatin accessibility atlas of human immune cells of individuals exposed to HIV-1, COVID-19, Influenza virus, organophosphates as well as healthy controls that provides insights into gene regulation driven by these cell-extrinsic stimuli. This atlas comprises 271,299 cells and 319,420 candidate regulatory elements that exhibit dynamic accessibility associated with gene expression across immune cell states. Our longitudinal HIV cohort reveals epigenetic signatures of T cell exhaustion, manifested in changes in the accessibility of binding sites for the FOXP family transcription factors. We further identified changes in the accessibility of candidate regulatory elements in CD14 monocytes upon SARS-CoV-2 exposure that are associated with a switch in NF-κB to AP-1-based regulation of cytokine networks. By integrating single-cell profiles of DNA methylation from matched samples we created a multimodal epigenome atlas of human immune cells across exposure states using the accessibility-derived candidate regulatory elements. Both modalities exhibit complementary epigenetic signatures at transcription factor binding sites associated with cell state, as exemplified in the process of memory formation in T-cells. Finally, by linking potentially regulatory DNA methylation signatures to changes in chromatin accessibility in monocytes, we identify AP1 motifs exhibiting epigenetic dynamics, indicating selective remodeling in TF networks in severe cases of COVID-19.

Variations in DNA methylation patterns in human tissues have been linked to various environmental exposures and infections. Here, we identified the DNA methylation signatures associated with multiple exposures in nine major immune cell types derived from peripheral blood mononuclear cells (PBMCs) at single-cell resolution. We performed methylome sequencing on 111,180 immune cells obtained from 112 individuals who were exposed to different viruses, bacteria, or chemicals. Our analysis revealed 790,662 differentially methylated regions (DMRs) associated with these exposures, which are mostly individual CpG sites. Additionally, we integrated methylation and ATAC-seq data from same samples and found strong correlations between the two modalities. However, the epigenomic remodeling in these two modalities are complementary. Finally, we identified the minimum set of DMRs that can predict exposures. Overall, our study provides the first comprehensive dataset of single immune cell methylation profiles, along with unique methylation biomarkers for various biological and chemical exposures.Variations in DNA methylation patterns in human tissues have been linked to various environmental exposures and infections. Here, we identified the DNA methylation signatures associated with multiple exposures in nine major immune cell types derived from peripheral blood mononuclear cells (PBMCs) at single-cell resolution. We performed methylome sequencing on 111,180 immune cells obtained from 112 individuals who were exposed to different viruses, bacteria, or chemicals. Our analysis revealed 790,662 differentially methylated regions (DMRs) associated with these exposures, which are mostly individual CpG sites. Additionally, we integrated methylation and ATAC-seq data from same samples and found strong correlations between the two modalities. However, the epigenomic remodeling in these two modalities are complementary. Finally, we identified the minimum set of DMRs that can predict exposures. Overall, our study provides the first comprehensive dataset of single immune cell methylation profiles, along with unique methylation biomarkers for various biological and chemical exposures.

Writers of the Black Chicago Renaissance comprehensively explores the contours and content of the Black Chicago Renaissance, a creative movement that emerged from the crucible of rigid segregation in Chicago's \"Black Belt\" from the 1930s through the 1960s. Heavily influenced by the Harlem Renaissance and the Chicago Renaissance of white writers, its participants were invested in political activism and social change as much as literature, art, and aesthetics. The revolutionary writing of this era produced some of the first great accolades for African American literature and set up much of the important writing that came to fruition in the Black Arts Movement._x000B__x000B_The volume covers a vast collection of subjects, including many important writers such as Richard Wright, Gwendolyn Brooks, and Lorraine Hansberry as well as cultural products such as black newspapers, music, and theater. The book includes individual entries by experts on each subject; a discography and filmography that highlight important writers, musicians, films, and cultural presentations; and an introduction that relates the Harlem Renaissance, the White Chicago Renaissance, the Black Chicago Renaissance, and the Black Arts Movement._x000B__x000B_Contributors are Robert Butler, Robert H. Cataliotti, Maryemma Graham, James C. Hall, James L. Hill, Michael Hill, Lovalerie King, Lawrence Jackson, Angelene Jamison-Hall, Keith Leonard, Lisbeth Lipari, Bill V. Mullen, Patrick Naick, William R. Nash, Charlene Regester, Kimberly Ruffin, Elizabeth Schultz, Joyce Hope Scott, James Smethurst, Kimberly M. Stanley, Kathryn Waddell Takara, Steven C. Tracy, Zoe Trodd, Alan Wald, Jamal Eric Watson, Donyel Hobbs Williams, Stephen Caldwell Wright, and Richard Yarborough.

The epigenomic landscape of human immune cells is dynamically shaped by both genetic factors and environmental exposures. However, the relative contributions of these elements are still not fully understood. In this study, we employed single-nucleus methylation sequencing and ATAC-seq to systematically explore how pathogen and chemical exposures, along with genetic variation, influence the immune cell epigenome. We identified distinct exposure-associated differentially methylated regions (eDMRs) corresponding to each exposure, revealing how environmental factors remodel the methylome, alter immune cell states, and affect transcription factor binding. Furthermore, we observed a significant correlation between changes in DNA methylation and chromatin accessibility, underscoring the coordinated response of the epigenome. We also uncovered genotype-associated DMRs (gDMRs), demonstrating that while eDMRs are enriched in regulatory regions, gDMRs are preferentially located in gene body marks, suggesting that exposures and genetic factors exert differential regulatory control. Notably, disease-associated SNPs were frequently colocalized with meQTLs, providing new cell-type-specific insights into the genetic basis of disease. Our findings underscore the intricate interplay between genetic and environmental factors in sculpting the immune cell epigenome, offering a deeper understanding of how immune cell function is regulated in health and disease.