Associations of a plant-centered diet and lung function across early to mid-adulthood: The CARDIA Lung Study.

BACKGROUND: Lung function throughout adulthood predicts morbidity and mortality even among adults without chronic respiratory disease. Diet quality may represent a modifiable risk factor for lung function impairment later in life. We investigated associations between nutritionally-rich plant-centered diet and lung function across early and middle adulthood from the Coronary Artery Risk Development in Young Adults (CARDIA) Study. METHODS: Diet was assessed at baseline and years 7 and 20 of follow-up using the validated CARDIA diet history questionnaire. Plant-centered diet quality was scored using the validated A Priori Diet Quality Score (APDQS), which weights food groups to measure adherence to a nutritionally-rich plant-centered diet for 20 beneficially rated foods and 13 adversely rated foods. Scores were cumulatively averaged over follow-up and categorized into quintiles. The primary outcome was lung function decline, including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), measured at years 0, 2, 5, 10, 20, and 30. We estimated the association of APDQS with annual pulmonary function changes and cross-sectional differences in a repeated measures regression model, adjusting for clinically relevant covariates. RESULTS: The study included 3,787 Black and White men and women aged 18-30 in 1985-86 and followed for 30 years. In multivariable repeated measures regression models, individuals in the lowest APDQS quintile (poorest diet) had declines in FEV1 that were 1.6 ml/year greater than individuals in the highest quintile (35.0 vs. 33.4 ml/year, ß ± SE per 1 SD change APDQS 0.94 ± 0.36, p = 0.009). Additionally, declines in FVC were 2.4 ml/year greater in the lowest APDQS quintile than those in the highest quintile (37.0 vs 34.6 ml/year, ß ± SE per 1 SD change APDQS 1.71 ± 0.46, p < 0.001). The association was not different between never and ever smokers (pint = 0.07 for FVC and 0.32 for FEV1). In sensitivity analyses where current asthma diagnosis and cardiorespiratory fitness were further adjusted, results remained similar. Cross-sectional analysis at each exam year also showed significant differences in lung function according to diet after covariate adjustment. CONCLUSIONS: In this 30-year longitudinal cohort study, long-term adherence to a nutritionally-rich plant-centered diet was associated with cross-sectional differences in lung function as well as slower decline in lung function, highlighting diet quality as a potential treatable trait supporting long-term lung health.

Increased left and right atrial volume indices are associated with decreased survival times post-cardiac arrest.

BACKGROUND: Left and right atrial volume indices (LAVI and RAVI) are markers of cardiac remodeling. LAVI and RAVI are associated with worse outcomes in other cardiac conditions. This study aimed to determine the associations of these atrial volume indices with survival time post-cardiac arrest. METHODS: This was a single center, retrospective study of patients with a sudden cardiac arrest event during index hospitalization from 2014-2018 based on pre-arrest parameters. The analysis was stratified based on whether a pulseless ventricular tachycardia/ventricular fibrillation (pVT/VF) event or a pulseless electrical activity (PEA)/asystole event occurred. Cox proportional hazards regression and model selection with best subsets approach evaluated the association of atrial volume parameters with survival times in the context of other covariates. RESULTS: Of 305 patients studied (64 ± 14 years, 37% female), the mean LAVI was 34.0 ± 15.8 mL/m2 (based on 162 reliable measurements), and mean RAVI was 25.0 ± 15.6 mL/m2 (based on 163 measurements). Increased atrial volume indices were most strongly associated with survival in patients who had sustained pVT/VF (LAVI HR 0.47, 95% CI 0.25-0.90, p = 0.020; RAVI HR 0.57, 95% CI 0.30-1.05, p = 0.074). In multivariable best subsets Cox regression with LAVI, RAVI, and 13 other scaled covariates, LAVI < 34 ml/m2 was by far the best single predictor of survival (p < 0.0001), and the next best predictor was the absence of pulmonary hypertension. CONCLUSION: Among patients with cardiac arrest from ventricular arrhythmias, those with no more than mild left atrial enlargement pre-arrest by LAVI measurement had the best prognosis. Additional studies are indicated to validate the importance of this finding for clinical management decisions. CONDENSED ABSTRACT: In patients with sudden cardiac arrest associated with ventricular arrhythmias, a left atrial volume index (LAVI) < 34 mL/m2 prior to the arrest had the strongest association with survival among fifteen candidate predictors. Pulmonary hypertension was more common in patients with an elevated right atrial volume index (RAVI), and the absence of pulmonary hypertension was the next best pre-arrest parameter predictive of survival. Larger studies are indicated to validate the use of LAVI for clinical management decisions in this condition.

Rev7 and 53BP1/Crb2 prevent RecQ helicase-dependent hyper-resection of DNA double-strand breaks.

Poly(ADP ribose) polymerase inhibitors (PARPi) target cancer cells deficient in homology-directed repair of DNA double-strand breaks (DSBs). In preclinical models, PARPi resistance is tied to altered nucleolytic processing (resection) at the 5' ends of a DSB. For example, loss of either 53BP1 or Rev7/MAD2L2/FANCV derepresses resection to drive PARPi resistance, although the mechanisms are poorly understood. Long-range resection can be catalyzed by two machineries: the exonuclease Exo1, or the combination of a RecQ helicase and Dna2. Here, we develop a single-cell microscopy assay that allows the distinct phases and machineries of resection to be interrogated simultaneously in living S. pombe cells. Using this assay, we find that the 53BP1 orthologue and Rev7 specifically repress long-range resection through the RecQ helicase-dependent pathway, thereby preventing hyper-resection. These results suggest that 'rewiring' of BRCA1-deficient cells to employ an Exo1-independent hyper-resection pathway is a driver of PARPi resistance.