Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration.

Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases.

Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT).

Quantitative CMR population imaging on 20,000 subjects of the UK Biobank imaging study: LV/RV quantification pipeline and its evaluation.

Population imaging studies generate data for developing and implementing personalised health strategies to prevent, or more effectively treat disease. Large prospective epidemiological studies acquire imaging for pre-symptomatic populations. These studies enable the early discovery of alterations due to impending disease, and enable early identification of individuals at risk.

Identification of Myocardial Disarray in Patients With Hypertrophic Cardiomyopathy and Ventricular Arrhythmias.

Background: Myocardial disarray is a likely focus for fatal arrhythmia in hypertrophic cardiomyopathy (HCM). This microstructural abnormality can be inferred by mapping the preferential diffusion of water along cardiac muscle fibers using diffusion tensor cardiac magnetic resonance (DT-CMR) imaging. Fractional anisotropy (FA) quantifies directionality of diffusion in 3 dimensions.

Left Ventricular Flow Analysis.

Background: Cardiac remodeling, after a myocardial insult, often causes progression to heart failure. The relationship between alterations in left ventricular blood flow, including kinetic energy (KE), and remodeling is uncertain. We hypothesized that increasing derangements in left ventricular blood flow would relate to (1) conventional cardiac remodeling markers, (2) increased levels of biochemical remodeling markers, (3) altered cardiac energetics, and (4) worsening patient symptoms and functional capacity.

Pirfenidone in Heart Failure with Preserved Ejection Fraction-Rationale and Design of the PIROUETTE Trial.

Background: The PIROUETTE (PIRfenidOne in patients with heart failUre and preserved lEfT venTricular Ejection fraction) trial is designed to evaluate the efficacy and safety of the anti-fibrotic pirfenidone in patients with chronic heart failure and preserved ejection fraction (HFpEF) and myocardial fibrosis. HFpEF is a diverse syndrome associated with substantial morbidity and mortality. Myocardial fibrosis is a key pathophysiological mechanism of HFpEF and myocardial fibrotic burden is strongly and independently associated with adverse outcome.

Repeatability and reproducibility of multiparametric magnetic resonance imaging of the liver.

As the burden of liver disease reaches epidemic levels, there is a high unmet medical need to develop robust, accurate and reproducible non-invasive methods to quantify liver tissue characteristics for use in clinical development and ultimately in clinical practice. This prospective cross-sectional study systematically examines the repeatability and reproducibility of iron-corrected T1 (cT1), T2*, and hepatic proton density fat fraction (PDFF) quantification with multiparametric MRI across different field strengths, scanner manufacturers and models. 61 adult participants with mixed liver disease aetiology and those without any history of liver disease underwent multiparametric MRI on combinations of 5 scanner models from two manufacturers (Siemens and Philips) at different field strengths (1.

Localized rest and stress human cardiac creatine kinase reaction kinetics at 3 T.

Changes in the kinetics of the creatine kinase (CK) shuttle are sensitive markers of cardiac energetics but are typically measured at rest and in the prone position. This study aims to measure CK kinetics during pharmacological stress at 3 T, with measurement in the supine position. A shorter "stressed saturation transfer" (StreST) extension to the triple repetition time saturation transfer (TRiST) method is proposed.

Measuring inorganic phosphate and intracellular pH in the healthy and hypertrophic cardiomyopathy hearts by in vivo 7T P-cardiovascular magnetic resonance spectroscopy.

Background: Cardiovascular phosphorus MR spectroscopy (P-CMRS) is a powerful tool for probing energetics in the human heart, through quantification of phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio. In principle, P-CMRS can also measure cardiac intracellular pH (pH) and the free energy of ATP hydrolysis (ΔG). However, these require determination of the inorganic phosphate (Pi) signal frequency and amplitude that are currently not robustly accessible because blood signals often obscure the Pi resonance.

Automated quality control in image segmentation: application to the UK Biobank cardiovascular magnetic resonance imaging study.

Background: The trend towards large-scale studies including population imaging poses new challenges in terms of quality control (QC). This is a particular issue when automatic processing tools such as image segmentation methods are employed to derive quantitative measures or biomarkers for further analyses. Manual inspection and visual QC of each segmentation result is not feasible at large scale.

Neuropeptide-Y causes coronary microvascular constriction and is associated with reduced ejection fraction following ST-elevation myocardial infarction.

Aims: The co-transmitter neuropeptide-Y (NPY) is released during high sympathetic drive, including ST-elevation myocardial infarction (STEMI), and can be a potent vasoconstrictor. We hypothesized that myocardial NPY levels correlate with reperfusion and subsequent recovery following primary percutaneous coronary intervention (PPCI), and sought to determine if and how NPY constricts the coronary microvasculature.

Methods And Results: Peripheral venous NPY levels were significantly higher in patients with STEMI (n = 45) compared to acute coronary syndromes/stable angina ( n = 48) or with normal coronary arteries (NC, n = 16).

Combined T1-mapping and tissue tracking analysis predicts severity of ischemic injury following acute STEMI-an Oxford Acute Myocardial Infarction (OxAMI) study.

Early risk stratification after ST-segment-elevation myocardial infarction (STEMI) is of major clinical importance. Strain quantifies myocardial deformation and can demonstrate abnormal global and segmental myocardial function in acute ischaemia. Native T1-mapping allows assessment of the severity of acute ischemic injury, however its clinical applicability early post MI is limited by the complex dynamic changes happening in the myocardium post MI.

Control of stem cell response and bone growth on biomaterials by fully non-peptidic integrin selective ligands.

In this communication we report that anchoring αvβ3 or α5β1 integrin-selective RGD peptidomimetics to titanium efficiently tunes mesenchymal stem cell response in vitro and bone growth in rat calvarial defects. Our results demonstrate that this molecular chemistry-derived approach could be successful to engineer instructive coatings for orthopedic applications.

Independent Left Ventricular Morphometric Atlases Show Consistent Relationships with Cardiovascular Risk Factors: A UK Biobank Study.

Left ventricular (LV) mass and volume are important indicators of clinical and pre-clinical disease processes. However, much of the shape information present in modern imaging examinations is currently ignored. Morphometric atlases enable precise quantification of shape and function, but there has been no objective comparison of different atlases in the same cohort.

The importance of sexuality, changes in erectile functioning and its association with self-esteem in men with localized prostate cancer: data from an observational study.

Background: Treatment for localized prostate cancer (PCa) can cause long-term changes in erectile functioning. However, data on the importance of sexuality and possible consequences of altered erectile functioning on self-esteem in men with localized PCa are lacking.

Methods: Self-report questionnaires were completed by 292 men with PCa, initially managed with active surveillance (AS) or radical prostatectomy (RP).

Acute Microvascular Impairment Post-Reperfused STEMI Is Reversible and Has Additional Clinical Predictive Value: A CMR OxAMI Study.

Objectives: This study sought to investigate the clinical utility and the predictive relevance of absolute rest myocardial blood flow (MBF) by cardiac magnetic resonance (CMR) in acute myocardial infarction.

Background: Microvascular obstruction (MVO) remains one of the worst prognostic factors in patients with reperfused ST-segment elevation myocardial infarction (STEMI). Clinical trials have focused on cardioprotective strategies to maintain microvascular functionality, but there is a need for a noninvasive test to determine their efficacy.

[Guideline-Orientated Prescription of Disease-Modifying Drugs in Patients with Rheumatoid Arthritis - an Analysis Based on Social Health Insurance Claims Data].

Background: With the market entry of biologics, the treatment of rheumatoid arthritis (RA) has changed fundamentally in terms of efficacy and costs.

The Aim: of this study is to analyse the treatment according the guideline of the German society of rheumatology for RA patients with disease-modifying anti-rheumatic drugs (DMARDs) using claims data from the statutory health insurance.

Materials And Methods: The claims data of the Techniker Krankenkasse were analysed retrospectively for the years 2011 - 2014.

Differential Modulation of Platelet Adhesion and Spreading by Adhesive Ligand Density.

Platelets play a major role in hemostasis and thrombosis, by binding to the underlying extracellular matrix around injured blood vessels, via integrin receptors. In this study, we investigated the effects of adhesive ligand spacing on the stability of platelets' adhesion and the mode of their spreading on extracellular surfaces. Toward this end, we have examined the differential adhesion and spreading of human platelets onto nanogold-patterned surfaces, functionalized with the αIIbβ3 integrin ligand, SN528.

Medical diagnoses showed low relatedness in an explorative mutual information analysis of 190,837 inpatient cases.

Objectives: We aimed to quantify the shared information between medical diagnoses of an adult inpatient population to explore both multimorbidity patterns and vice versa the unrelatedness of medical diagnoses.

Study Design And Setting: This was a cross-sectional study, performed at a tertiary care center in Switzerland. Diagnoses were routinely coded using the International Classification of Diseases, 10th revision.

The interplay between metabolic alterations, diastolic strain rate and exercise capacity in mild heart failure with preserved ejection fraction: a cardiovascular magnetic resonance study.

Background: Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. However its role in mild HF with preserved ejection fraction (HFpEF) is uncertain. We measured myocardial triglyceride content (MTG) in HFpEF and assessed its relationships with diastolic function and exercise capacity.

Measurement of liver iron by magnetic resonance imaging in the UK Biobank population.

The burden of liver disease continues to increase in the UK, with liver cirrhosis reported to be the third most common cause of premature death. Iron overload, a condition that impacts liver health, was traditionally associated with genetic disorders such as hereditary haemochromatosis, however, it is now increasingly associated with obesity, type-2 diabetes and non-alcoholic fatty liver disease. The aim of this study was to assess the prevalence of elevated levels of liver iron within the UK Biobank imaging study in a cohort of 9108 individuals.

Covariation of the endocranium and splanchnocranium during great ape ontogeny.

That great ape endocranial shape development persists into adolescence indicates that the splanchnocranium succeeds brain growth in driving endocranial development. However, the extent of this splanchnocranial influence is unknown. We applied two-block partial least squares analyses of Procrustes shape variables on an ontogenetic series of great ape crania to explore the covariation of the endocranium (the internal braincase) and splanchnocranium (face, or viscerocranium).

Neandertal Introgression Sheds Light on Modern Human Endocranial Globularity.

One of the features that distinguishes modern humans from our extinct relatives and ancestors is a globular shape of the braincase [1-4]. As the endocranium closely mirrors the outer shape of the brain, these differences might reflect altered neural architecture [4, 5]. However, in the absence of fossil brain tissue, the underlying neuroanatomical changes as well as their genetic bases remain elusive.