Novel loci and biomedical consequences of iron homoeostasis variation.

Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported.

Long-term physical and psychological symptoms in Syrian men subjected to detention, conflict-related sexual violence and torture: cohort study of self-reported symptom evolution.

Background: Since March 2011, more than 1 million people, mostly men, have been arrested, detained, and tortured by the Assad regime. Published literature does not reflect the evolution of symptoms after male sexual and physical violence in detention. This cohort study examines the constellation and evolution of self-reported symptoms after male conflict-related sexual violence (CRSV) in Syrian state detention.

Turning the tide on inequity through systematic equity action-analysis.

Background: Collective agreement about the importance of centering equity in health research, practice, and policy is growing. Yet, responsibility for advancing equity is often situated as belonging to a vague group of 'others', or delegated to the leadership of 'equity-seeking' or 'equity-deserving' groups who are tasked to lead systems transformation while simultaneously navigating the violence and harms of oppression within those same systems. Equity efforts also often overlook the breadth of equity scholarship.

Dispersion of repolarization increases with cardiac resynchronization therapy and is associated with left ventricular reverse remodeling.

Purpose: Cardiac resynchronization therapy (CRT) reduces ventricular activation times and electrical dyssynchrony, however the effect on repolarization is unclear. In this study, we sought to investigate the effect of CRT and left ventricular (LV) remodeling on dispersion of repolarization using electrocardiographic imaging (ECGi).

Methods: 11 patients with heart failure and electrical dyssynchrony underwent ECGi 1-day and 6-months post CRT.

Cueing emotional memories during slow wave sleep modulates next-day activity in the orbitofrontal cortex and the amygdala.

Emotional memories are preferentially consolidated during sleep, through the process of memory reactivation. Targeted memory reactivation (TMR) has been shown to boost memory consolidation during sleep, but its neural correlates remain unclear, particularly for emotional memories. Here, we aimed to examine how TMR of emotional material during slow wave sleep (SWS) impacts upon neural processing during a subsequent arousal rating task.

Noninvasive electrocardiographic assessment of ventricular activation and remodeling response to cardiac resynchronization therapy.

Background: Cardiac resynchronization therapy (CRT) produces acute changes in electric resynchronization that can be measured noninvasively with electrocardiographic body surface mapping (ECGi). The relation between baseline acute electrophysiology metrics and their manipulation with CRT and reverse remodeling is unclear.

Objective: To test (ECGi) derived parameters of electrical activation as predictors of volumetric response to CRT.

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present, and drives mortality, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units.

Associations of appetite sensations and metabolic characteristics with weight retention in postpartum women.

Postpartum weight retention (PPWR) is an important risk factor for long-term obesity. Appetite may be a key factor regulating PPWR. The objectives of this study were to determine the associations between () PPWR and appetite; and () appetite, lactation, and metabolic characteristics.

Olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): a multicentre, open-label, randomised, phase 2 trial.

Background: Metastatic castration-resistant prostate cancer is enriched in DNA damage response (DDR) gene aberrations. The TOPARP-B trial aims to prospectively validate the association between DDR gene aberrations and response to olaparib in metastatic castration-resistant prostate cancer.

Methods: In this open-label, investigator-initiated, randomised phase 2 trial following a selection (or pick-the-winner) design, we recruited participants from 17 UK hospitals.

The Consortium of Metabolomics Studies (COMETS): Metabolomics in 47 Prospective Cohort Studies.

The Consortium of Metabolomics Studies (COMETS) was established in 2014 to facilitate large-scale collaborative research on the human metabolome and its relationship with disease etiology, diagnosis, and prognosis. COMETS comprises 47 cohorts from Asia, Europe, North America, and South America that together include more than 136,000 participants with blood metabolomics data on samples collected from 1985 to 2017. Metabolomics data were provided by 17 different platforms, with the most frequently used labs being Metabolon, Inc.

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure.

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2.

The influence of energy metabolism on postpartum weight retention.

Background: Profiling postpartum energy metabolism may assist in optimizing weight management following childbirth.

Objectives: The aims of this study were to profile total energy expenditure (TEE), resting energy expenditure (REE), exercise energy expenditure, sleep energy expenditure, and respiratory quotient in women at 3 and 9 mo postpartum (3M-PP, 9M-PP, respectively), and to examine the association between energy metabolism and postpartum weight retention (PPWR).

Methods: In this cohort study, 1-h REE (measured in a whole body calorimetry unit, WBCU) and body composition (BC, measured by dual-energy X-ray absorptiometry) were measured at 3M-PP and 9M-PP (n = 49).

The use of whole body calorimetry to compare measured versus predicted energy expenditure in postpartum women.

Background: Accurate assessment of energy expenditure may support weight-management recommendations. Measuring energy expenditure for each postpartum woman is unfeasible; therefore, accurate predictive equations are needed.

Objectives: This study compared measured with predicted resting energy expenditure (REE) and total energy expenditure (TEE) in postpartum women.

Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups.

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus.

Trajectory and determinants of change in lean soft tissue over the postpartum period.

The aim of this study was to characterise changes in lean soft tissue (LST) and examine the contributions of energy intake, physical activity and breast-feeding practices to LST changes at 3 and 9 months postpartum. We examined current weight, LST (via dual-energy X-ray absorptiometry), dietary intake (3-d food diary), physical activity (Baecke questionnaire) and breast-feeding practices (3-d breast-feeding diary) in forty-nine women aged 32·9 (sd 3·8) years. Changes in LST varied from -2·51 to +2·50 kg with twenty-nine women gaining LST (1·1 (sd 0·7) kg, P<0·001) and twenty women losing LST (-0·9 (sd 0·8) kg, P<0·001).

Changes in Energy Metabolism from Prepregnancy to Postpartum: A Case Report.

Purpose: Energy metabolism is at the core of maintaining healthy body weights. Likewise, the assessment of energy needs is essential for providing adequate dietary advice. We explored differences in energy metabolism of a primigravid woman (age: 30 years) at 1 month prepregnancy ("baseline"), during pregnancy (33 weeks), and at 3 and 9 months postpartum.

Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions.

A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure.

Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals.