Steps towards understanding variation for water and nitrogen uptake and use in Brassica napus

Non-Peer Reviewe

An excess of emission in the dark cloud LDN 1111 with the Arcminute Microkelvin Imager

We present observations of the Lynds' dark nebula LDN 1111 made at microwave frequencies between 14.6 and 17.2 GHz with the Arcminute Microkelvin Imager (AMI). We find emission in this frequency band in excess of a thermal free--free spectrum extrapolated from data at 1.4 GHz with matched uv-coverage. This excess is > 15 sigma above the predicted emission. We fit the measured spectrum using the spinning dust model of Drain & Lazarian (1998a) and find the best fitting model parameters agree well with those derived from Scuba data for this object by Visser et al. (2001).Comment: accepted MNRA

Non-Water-Suppressed 1H MR Spectroscopy with Orientational Prior Knowledge Shows Potential for Separating Intra- and Extramyocellular Lipid Signals in Human Myocardium

Conditions such as type II diabetes are linked with elevated lipid levels in the heart, and significantly increased risk of heart failure; however, metabolic processes underlying the development of cardiac disease in type II diabetes are not fully understood. Here we present a non-invasive method for in vivo investigation of cardiac lipid metabolism: namely, IVS-McPRESS. This technique uses metabolite-cycled, non-water suppressed 1H cardiac magnetic resonance spectroscopy with prospective and retrospective motion correction. High-quality IVS-McPRESS data acquired from healthy volunteers allowed us to investigate the frequency shift of extramyocellular lipid signals, which depends on the myocardial fibre orientation. Assuming consistent voxel positioning relative to myofibres, the myofibre angle with the magnetic field was derived from the voxel orientation. For separation and individual analysis of intra- and extramyocellular lipid signals, the angle myocardial fibres in the spectroscopy voxel take with the magnetic field should be within ±24.5°. Metabolite and lipid concentrations were analysed with respect to BMI. Significant correlations between BMI and unsaturated fatty acids in intramyocellular lipids, and methylene groups in extramyocellular lipids were found. The proposed IVS-McPRESS technique enables non-invasive investigation of cardiac lipid metabolism and may thus be a useful tool to study healthy and pathological conditions

Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance

Background & Aims: Serum microRNA (miRNA) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages. Methods: We profiled 2,083 serum miRNAs in a discovery cohort (183 cases with NAFLD representing the complete NAFLD spectrum and 10 population controls). miRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional cases with NAFLD and 15 population controls by quantitative reverse transcriptase PCR. Results: Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages, but miR-193a-5p consistently showed increased levels in all comparisons. Relative to NAFL/non-alcoholic steatohepatitis (NASH) with mild fibrosis (stage 0/1), 3 miRNAs (miR-193a-5p, miR-378d, and miR378d) were increased in cases with NASH and clinically significant fibrosis (stages 2–4), 7 (miR193a-5p, miR-378d, miR-378e, miR-320b, miR-320c, miR-320d, and miR-320e) increased in cases with NAFLD activity score (NAS) 5–8 compared with lower NAS, and 3 (miR-193a-5p, miR-378d, and miR-378e) increased but 1 (miR-19b-3p) decreased in steatosis, activity, and fibrosis (SAF) activity score 2–4 compared with lower SAF activity. The significant findings for miR-193a-5p were replicated in the additional cohort with NAFLD. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n = 80); liver GPX8 levels correlated positively with serum miR-193a-5p. Conclusions: Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD. Lay summary: MicroRNAs (miRNAs) are small pieces of nucleic acid that may turn expression of genes on or off. These molecules can be detected in the blood circulation, and their levels in blood may change in liver disease including non-alcoholic fatty liver disease (NAFLD). To see if we could detect specific miRNA associated with advanced stages of NAFLD, we carried out miRNA sequencing in a group of 183 patients with NAFLD of varying severity together with 10 population controls. We found that a number of miRNAs showed changes, mainly increases, in serum levels but that 1 particular miRNA miR-193a-5p consistently increased. We confirmed this increase in a second group of cases with NAFLD. Measuring this miRNA in a blood sample may be a useful way to determine whether a patient has advanced NAFLD without an invasive liver biopsy

Comprehensive 4D velocity mapping of the heart and great vessels by cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>Phase contrast cardiovascular magnetic resonance (CMR) is able to measure all three directional components of the velocities of blood flow relative to the three spatial dimensions and the time course of the heart cycle. In this article, methods used for the acquisition, visualization, and quantification of such datasets are reviewed and illustrated.</p> <p>Methods</p> <p>Currently, the acquisition of 3D cine (4D) phase contrast velocity data, synchronized relative to both cardiac and respiratory movements takes about ten minutes or more, even when using parallel imaging and optimized pulse sequence design. The large resulting datasets need appropriate post processing for the visualization of multidirectional flow, for example as vector fields, pathlines or streamlines, or for retrospective volumetric quantification.</p> <p>Applications</p> <p>Multidirectional velocity acquisitions have provided 3D visualization of large scale flow features of the healthy heart and great vessels, and have shown altered patterns of flow in abnormal chambers and vessels. Clinically relevant examples include retrograde streams in atheromatous descending aortas as potential thrombo-embolic pathways in patients with cryptogenic stroke and marked variations of flow visualized in common aortic pathologies. Compared to standard clinical tools, 4D velocity mapping offers the potential for retrospective quantification of flow and other hemodynamic parameters.</p> <p>Conclusions</p> <p>Multidirectional, 3D cine velocity acquisitions are contributing to the understanding of normal and pathologically altered blood flow features. Although more rapid and user-friendly strategies for acquisition and analysis may be needed before 4D velocity acquisitions come to be adopted in routine clinical CMR, their capacity to measure multidirectional flows throughout a study volume has contributed novel insights into cardiovascular fluid dynamics in health and disease.</p

Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: An individual patient data meta-analysis

Objective Liver biopsy is still needed for fibrosis staging in many patients with non-alcoholic fatty liver disease. The aims of this study were to evaluate the individual diagnostic performance of liver stiffness measurement by vibration controlled transient elastography (LSM-VCTE), Fibrosis-4 Index (FIB-4) and NAFLD (non-alcoholic fatty liver disease) Fibrosis Score (NFS) and to derive diagnostic strategies that could reduce the need for liver biopsies. Design Individual patient data meta-analysis of studies evaluating LSM-VCTE against liver histology was conducted. FIB-4 and NFS were computed where possible. Sensitivity, specificity and area under the receiver operating curve (AUROC) were calculated. Biomarkers were assessed individually and in sequential combinations. Results Data were included from 37 primary studies (n=5735; 45% women; median age: 54 years; median body mass index: 30 kg/m2; 33% had type 2 diabetes; 30% had advanced fibrosis). AUROCs of individual LSM-VCTE, FIB-4 and NFS for advanced fibrosis were 0.85, 0.76 and 0.73. Sequential combination of FIB-4 cut-offs (&lt;1.3; ≥2.67) followed by LSM-VCTE cut-offs (&lt;8.0; ≥10.0 kPa) to rule-in or rule-out advanced fibrosis had sensitivity and specificity (95% CI) of 66% (63-68) and 86% (84-87) with 33% needing a biopsy to establish a final diagnosis. FIB-4 cut-offs (&lt;1.3; ≥3.48) followed by LSM cut-offs (&lt;8.0; ≥20.0 kPa) to rule out advanced fibrosis or rule in cirrhosis had a sensitivity of 38% (37-39) and specificity of 90% (89-91) with 19% needing biopsy. Conclusion Sequential combinations of markers with a lower cut-off to rule-out advanced fibrosis and a higher cut-off to rule-in cirrhosis can reduce the need for liver biopsies

An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD)

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, encompasses steatosis and metabolic dysfunction-associated steatohepatitis (MASH), leading to cirrhosis and hepatocellular carcinoma. Preclinical MASLD research is mainly performed in rodents; however, the model that best recapitulates human disease is yet to be defined. We conducted a wide-ranging retrospective review (metabolic phenotype, liver histopathology, transcriptome benchmarked against humans) of murine models (mostly male) and ranked them using an unbiased MASLD ‘human proximity score’ to define their metabolic relevance and ability to induce MASH-fibrosis. Here, we show that Western diets align closely with human MASH; high cholesterol content, extended study duration and/or genetic manipulation of disease-promoting pathways are required to intensify liver damage and accelerate significant (F2+) fibrosis development. Choline-deficient models rapidly induce MASH-fibrosis while showing relatively poor translatability. Our ranking of commonly used MASLD models, based on their proximity to human MASLD, helps with the selection of appropriate in vivo models to accelerate preclinical research

Ensuring competency in end-of-life care: controlling symptoms

BACKGROUND: Palliative medicine is assuming an increasingly important role in patient care. The Education for Physicians in End-of-life Care (EPEC) Project is an ambitious program to increase core palliative care skills for all physicians. It is not intended to transmit specialty level competencies in palliative care. METHOD: The EPEC Curriculum was developed to be a comprehensive syllabus including trainer notes, multiple approaches to teaching the material, slides, and videos of clinical encounters to trigger discussion are provided. The content was developed through a combination of expert opinion, participant feedback and selected literature review. Content development was guided by the goal of teaching core competencies not included in the training of generalist and non-palliative medicine specialist physicians. RESULTS: Whole patient assessment forms the basis for good symptom control. Approaches to the medical management of pain, depression, anxiety, breathlessness (dyspnea), nausea/vomiting, constipation, fatigue/weakness and the symptoms common during the last hours of life are described. CONCLUSION: While some physicians will have specialist palliative care services upon which to call, most in the world will need to provide the initial approaches to symptom control at the end-of-life