Citations

Aim: To compare the efficacy of two popular weight loss approaches on weight loss, body composition, and markers of health in sedentary obese women. Methods: In total, 51 sedentary women (age 34.5 ± 7.7 yrs.; weight 90.0 ± 14.5 kg; BMI 34.0 ± 5.1 kg/m2; 46.5 ± 7.0% fat) were matched and randomized to participate in the Weight Watchers® Momentum™ (WW) or Curves® (CV) Fitness and Weight Management program for 16 weeks. Participants in the WW group (n = 27) were provided a point-based diet program, received weekly progress checks and counseling, and were encouraged to exercise. Participants in the CV group (n = 24) followed a menu-based higher protein/low-fat diet (1200 kcal/d) for 1 week; 1500 kcal/d diet for 3 weeks; and 2000–2500 kcals/d for 2 weeks that was repeated three times (except the last segment) while participating in a supervised circuit-style resistance training program (3 d/wk). A general linear model (GLM) with repeated measures was used to analyze data and are presented as mean changes from baseline (mean [UL, LL]). Results: Supervised CV training resulted in greater amounts of vigorous and total physical activity. After 16 weeks, both groups lost weight (WW −6.1 [−7.8, −4.6], CV −4.9 [−6.2, −3.2] kg, p = 0.264). Participants in the CV group observed greater reductions in fat mass (WW −2.9 [−6.7, −0.2], CV −6.4 [−9.2, −3.6] kg, p = 0.081) and increases in lean mass (WW −2.5 [−4.3, −0.7], CV 1.3 [−0.6, 3.2] kg, p = 0.005) resulting in more favorable changes in percent body fat (WW −1.4 [−4.1, 1.2], CV −4.7 [−7.5, −1.8]%, p = 0.098). Both groups observed improvements in peak aerobic capacity and muscular endurance, although bench press lifting volume was greater in the CV group. Those in the CV group experienced a greater increase in HDLc and reduction in the CHL–HDLc ratio and triglycerides. Conclusion: Both interventions promoted weight loss and improvements in fitness and markers of health. The CV program, which included supervised resistance training and higher protein diet menus, promoted greater fat loss, increases in lean mass, and improvements in percent body fat and blood lipids. Trial Registration: clinicaltrials.gov, #NCT04372771, registered retrospectively 1 May 2020.

Introduction There is emerging evidence supporting the use of the radial artery (RA) as a preferred secondary conduit for coronary artery bypass grafting (CABG) as it is associated with higher rates of graft patency at 5 years when compared with saphenous vein grafts (SVG). The modified Allen’s test (MAT) is traditionally regarded as the standard of care in the assessment of ulnar artery (UA) patency prior to RA harvesting. Unfortunately, due to high false-positive rates, a substantial number of pre-CABG patients are found to have an abnormal MAT despite normal UA patency, resulting in inappropriate exclusion from RA harvesting. The SVG is generally used in its place when this occurs, resulting in potentially lower rates of long-term graft patency. Methods and analysis The CAPITAL iRADIAL-CABG trial is currently enrolling participants 18 years of age or older undergoing CABG for whom the treating physician is considering the use of an RA conduit. Eligible patients will be randomised in a 1:1 fashion to MAT or smartphone-based photoplethysmography application assessment to assess collateral palmar circulation prior to RA harvesting. The primary outcome of the trial is the use of the RA as a conduit during CABG. The primary safety outcome is postoperative palmar ischaemia as determined by clinical assessment or requirement of vascular intervention. Secondary outcomes include vascular complications, early graft failure, need for rescue percutaneous coronary intervention during the index hospitalisation and a composite cardiovascular outcome of myocardial infarction, stroke and cardiovascular death prior to discharge from hospital. A total of 236 participants are planned to be recruited. Ethics and dissemination The study was approved by the Ottawa Heart Science Network Research Ethics Board (approval number 20180865-01H). The study results will be disseminated via conference presentations and peer-reviewed publications. Trial registration number NCT03810729.

Background: A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data. Methods: We assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low–glucose and low-glucose hypoglycemia; very high–glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation. Results: The analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals. Conclusion: The GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.

Genome-wide association studies (GWAS) have identified more than 200 susceptibility loci for breast cancer, but these variants explain less than a fifth of the disease risk. Although gene–environment interactions have been proposed to account for some of the remaining heritability, few studies have empirically assessed this. We obtained genotype and risk factor data from 46,060 cases and 47,929 controls of European ancestry from population-based studies within the Breast Cancer Association Consortium (BCAC). We built gene expression prediction models for 4,864 genes with a significant (P < 0.01) heritable component using the transcriptome and genotype data from the Genotype-Tissue Expression (GTEx) project. We leveraged predicted gene expression information to investigate the interactions between gene-centric genetic variation and 14 established risk factors in association with breast cancer risk, using a mixed-effects score test. After adjusting for number of tests using Bonferroni correction, no interaction remained statistically significant. The strongest interaction observed was between the predicted expression of the C13orf45 gene and age at first full-term pregnancy (PGXE = 4.44 × 10−6). In this transcriptome-informed genome-wide gene–environment interaction study of breast cancer, we found no strong support for the role of gene expression in modifying the associations between established risk factors and breast cancer risk. Our study suggests a limited role of gene–environment interactions in breast cancer risk.

Abstract The human genome encodes large numbers of non-coding RNAs, including divergent antisense transcripts at transcription start sites (TSSs). However, molecular mechanisms by which divergent antisense transcription is regulated have not been detailed. Here, we report a novel ZWC complex composed of ZC3H4, WDR82 and CK2 that suppresses divergent antisense transcription. The ZWC complex preferentially localizes at TSSs of active genes through direct interactions of ZC3H4 and WDR82 subunits with the S5p RNAPII C-terminal domain. ZC3H4 depletion leads to increased divergent antisense transcription, especially at genes that naturally produce divergent antisense transcripts. We further demonstrate that the ZWC complex phosphorylates the previously uncharacterized N-terminal acidic domain of SPT5, a subunit of the transcription-elongation factor DSIF, and that this phosphorylation is responsible for suppressing divergent antisense transcription. Our study provides evidence that the newly identified ZWC-DSIF axis regulates the direction of transcription during the transition from early to productive elongation.

Background Inhaled corticosteroids (ICSs) are important in asthma management, but there are concerns regarding associated risk of pneumonia. While studies in asthmatic adults have shown inconsistent results, this risk in asthmatic children is unclear. Objective Our aim was to determine the association of ICS use with pneumonia risk in asthmatic children. Methods A nested case-control study was performed in the Mayo Clinic Birth Cohort. Asthmatic children (<18 years) with a physician diagnosis of asthma were identified from electronic medical records of children born at Mayo Clinic from 1997 to 2016 and followed until 31 December 2017. Pneumonia cases defined by Infectious Disease Society of America were 1:1 matched with controls without pneumonia by age, sex and asthma index date. Exposure was defined as ICS prescription at least 90 days prior to pneumonia. Associations of ICS use, type and dose (low, medium and high) with pneumonia risk were analysed using conditional logistic regression. Results Of the 2108 asthmatic children eligible for the study (70% mild intermittent and 30% persistent asthma), 312 children developed pneumonia during the study period. ICS use overall was not associated with risk of pneumonia (adjusted OR: 0.94, 95% CI: 0.62 to 1.41). Poorly controlled asthma was significantly associated with the risk of pneumonia (OR: 2.03, 95% CI: 1.35 to 3.05; p<0.001). No ICS type or dose was associated with risk of pneumonia. Conclusion ICS use in asthmatic children was not associated with risk of pneumonia but poorly controlled asthma was. Future asthma studies may need to include pneumonia as a potential outcome of asthma management.

Abstract Background: The etiology of colorectal cancer is not fully understood. Methods: Using genetic variants and metabolomics data including 217 metabolites from the Framingham Heart Study (n = 1,357), we built genetic prediction models for circulating metabolites. Models with prediction R2 &gt; 0.01 (Nmetabolite = 58) were applied to predict levels of metabolites in two large consortia with a combined sample size of approximately 46,300 cases and 59,200 controls of European and approximately 21,700 cases and 47,400 controls of East Asian (EA) descent. Genetically predicted levels of metabolites were evaluated for their associations with colorectal cancer risk in logistic regressions within each racial group, after which the results were combined by meta-analysis. Results: Of the 58 metabolites tested, 24 metabolites were significantly associated with colorectal cancer risk [Benjamini–Hochberg FDR (BH-FDR) &lt; 0.05] in the European population (ORs ranged from 0.91 to 1.06; P values ranged from 0.02 to 6.4 × 10−8). Twenty one of the 24 associations were replicated in the EA population (ORs ranged from 0.26 to 1.69, BH-FDR &lt; 0.05). In addition, the genetically predicted levels of C16:0 cholesteryl ester was significantly associated with colorectal cancer risk in the EA population only (OREA: 1.94, 95% CI, 1.60−2.36, P = 2.6 × 10−11; OREUR: 1.01, 95% CI, 0.99−1.04, P = 0.3). Nineteen of the 25 metabolites were glycerophospholipids and triacylglycerols (TAG). Eighteen associations exhibited significant heterogeneity between the two racial groups (PEUR-EA-Het &lt; 0.005), which were more strongly associated in the EA population. This integrative study suggested a potential role of lipids, especially certain glycerophospholipids and TAGs, in the etiology of colorectal cancer. Conclusions: This study identified potential novel risk biomarkers for colorectal cancer by integrating genetics and circulating metabolomics data. Impact: The identified metabolites could be developed into new tools for risk assessment of colorectal cancer in both European and EA populations.

Background Recent studies have shown improved outcomes in cardiogenic shock through protocols directed toward early identification and initiation of mechanical circulatory support. However, objective therapeutic targets—based on clinical and/or laboratory data—to guide real‐time clinical decision making are lacking. Lactate clearance has been suggested as a potential treatment target because of its independent association with mortality. Methods and Results In a post hoc analysis of the DOREMI (Dobutamine Compared to Milrinone in the Treatment of Cardiogenic Shock) trial—a randomized, double‐blind, controlled trial comparing milrinone to dobutamine in the treatment of cardiogenic shock—we used prospectively collected lactate data to evaluate lactate clearance as a surrogate marker for in‐hospital mortality. In total, 82 (57.7%) patients survived to hospital discharge (survivors). In multivariate logistic regression analysis, complete lactate clearance, percentage lactate clearance, and percentage lactate clearance per hour were independently associated with survival beginning as early as 8 hours after enrollment. Complete lactate clearance was the strongest predictor of survival at all time points, with odds ratios ranging between 2.46 (95% CI, 1.09–5.55; P =0.03) at 8 hours to 5.44 (95% CI, 2.14–13.8; P <0.01) at 24 hours. Conclusions Complete lactate clearance is a strong and independent predictor of in‐hospital survival in patients with cardiogenic shock. Together with previously published data, these results further support the validity of lactate clearance as an appropriate surrogate for mortality and as a potential therapeutic target in future cardiogenic shock trials. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03207165.