Extravascular lipid deposition and morphology of atherosclerosis in heterozygous WHHL rabbits fed vegetable (n-6) and marine (11-3) oils

The aim of this experiment was to test the cholesterol-fed heterozugous WHHL rabbit as a model for investigation of atherogenicity of different fats. Twentytwo rabbits of both sexes, 8—9.5 months old were randomized in 3 groups, and fed 100 g diet daily: cholesterol enriched standard diet (group I, n=8), cholesterol enriched diet with added vegetable (group II, n=7). or marine (group III, n=7) oils during 14 weeks. The vegetable oil (n-6 = 33 %, n—3 less than 1 %) and a marine oil(n-6 = 18 %, n-3 = 17 %) were adjusted to contain equal amounts of saturated and monounsaturated fatty acids. One percent cholesterol in the diet caused a pronounced hypercholesterolemia which was significantly enhanced by addition of oils.The increase in total cholesterol was especially reflected in the increase in the VLDL concentration. The blood cholesterol and triglyceride levels were comparable between the two of fed groups apart from a transitory lowering in the marine oilfed rabbits. The atherosclerotie lesions caused by 1 % cholesterol in the diet were fibrous plaques and plaques with foam cells. The added oils aggravated the atherosclerosis caused by cholesterol. Based on morphological appearance of the aorticand coronary atherosclerosis the marine oil was more atherogcnic than the vegetable oil. In pulmonary arteries, however, the less severe atherosclerotic changes were found in the marine oil group. In this group no lipid infiltrations were seen in the myocardium but very severe infiltrations were seen in the liver. In the vegetable oil group these infiltrations were severe in the myocardium and less pronounced in the liver. The massive hypereholesterolemia and extravascular lipid deposition in different parenchymatous organs suggest that lower doses of dietary cholesterol should be used when the cholesterol-fed heterozygous WHHL rabbit is chosen to study the ellect ot'van'ous fats on blood lipids and developmentof atherosclerosis

Ischemic Heart Disease in Chronic Hepatitis B: A Danish Nationwide Cohort Study

OBJECTIVE: Data on the risk of ischemic heart disease (IHD) in patients with chronic hepatitis B virus (CHB) are conflicting. Our objective was to address the rate of IHD in patients with CHB compared with individuals without CHB (control-persons) from the general population. STUDY DESIGN AND SETTING: We conducted a cohort study of prospectively obtained data from Danish nationwide registries. We produced cumulative incidence curves and calculated the unadjusted incidence rate ratio (IRR) of IHD in persons with and without CHB. The adjusted association between having CHB and developing IHD was examined using a cause-specific Cox regression model. RESULTS: In total, 6472 persons with CHB and 62,251 age- and sex-matched individuals from the general population were followed for 48,840 and 567,456 person-years, respectively, during which 103 (1,59%) with CHB and 1058 (1,70%) control-persons developed IHD. The crude IRR was 1.13 (95% CI: 0.91–1.39). CHB did not have a statistically significant effect on the rate of IHD after adjusting for several confounding factors (adjusted hazard ratio: 0.96, 95% CI: 0.76–1.21). CONCLUSION: In this nationwide cohort study, we did not find any difference between rate of IHD in persons with CHB in comparison with the general population

Diffusion-Weighted MRI for Verification of Electroporation-Based Treatments

Clinical electroporation (EP) is a rapidly advancing treatment modality that uses electric pulses to introduce drugs or genes into, e.g., cancer cells. The indication of successful EP is an instant plasma membrane permeabilization in the treated tissue. A noninvasive means of monitoring such a tissue reaction represents a great clinical benefit since, in case of target miss, retreatment can be performed immediately. We propose diffusion-weighted magnetic resonance imaging (DW-MRI) as a method to monitor EP tissue, using the concept of the apparent diffusion coefficient (ADC). We hypothesize that the plasma membrane permeabilization induced by EP changes the ADC, suggesting that DW-MRI constitutes a noninvasive and quick means of EP verification. In this study we performed in vivo EP in rat brains, followed by DW-MRI using a clinical MRI scanner. We found a pulse amplitude–dependent increase in the ADC following EP, indicating that (1) DW-MRI is sensitive to the EP-induced changes and (2) the observed changes in ADC are indeed due to the applied electric field

Co‐developing guidance for conservation: An example for seabirds in the North‐East Atlantic in the face of climate change impacts

Conservation guidance—an authoritative source of information and recommendations explicitly supporting decision-making and action regarding nature conservation—represents an important tool to communicate evidence-based advice to conservation actors. Given the rapidly increasing pressure that climate change poses to biodiversity, producing accessible, well-informed guidance on how to best manage the impacts and risks of changing climatic conditions is particularly urgent. Guidance documents should ideally be produced with multistage input from stakeholders who are likely to use and implement such advice; however, this step can be complicated and costly, and remains largely unformalized. Moreover, there is currently little direct evidence synthesized for actions that specifically target climate change and guidance remains largely absent. Here, we introduce a process for co-developing guidance for species conservation in the face of climate change, using seabirds in the North-East Atlantic as a case study. Specifically, we collated evidence on climate change vulnerability and possible conservation actions using literature synthesis, stakeholder surveys, and ecological modeling. This evidence base was then discussed, refined, and expanded using structured stakeholder workshops. We summarize the knowledge gained through stakeholder engagement and provide recommendations for future international efforts to co-produce conservation guidance for managing wildlife, in the context of a rapidly changing climate.info:eu-repo/semantics/publishedVersio

SecM-Stalled Ribosomes Adopt an Altered Geometry at the Peptidyl Transferase Center

A structure of a ribosome stalled during translation of the SecM peptide provides insight into the mechanism by which the large subunit active site is inactivated

Human model of primary carnitine deficiency cardiomyopathy reveals ferroptosis as a novel mechanism

Primary carnitine deficiency (PCD) is an autosomal recessive monogenic disorder caused by mutations in SLC22A5. This gene encodes for OCTN2, which transports the essential metabolite carnitine into the cell. PCD patients suffer from muscular weakness and dilated cardiomyopathy. Two OCTN2-defective human induced pluripotent stem cell lines were generated, carrying a full OCTN2 knockout and a homozygous OCTN2 (N32S) loss-of-function mutation. OCTN2-defective genotypes showed lower force development and resting length in engineered heart tissue format compared with isogenic control. Force was sensitive to fatty acid-based media and associated with lipid accumulation, mitochondrial alteration, higher glucose uptake, and metabolic remodeling, replicating findings in animal models. The concordant results of OCTN2 (N32S) and -knockout emphasizes the relevance of OCTN2 for these findings. Importantly, genome-wide analysis and pharmacological inhibitor experiments identified ferroptosis, an iron- and lipid-dependent cell death pathway associated with fibroblast activation as a novel PCD cardiomyopathy disease mechanism