The rabbit in atherosclerosis research

The rabbit was the first animal model in atherosclerosis research and it has been the most popular species during the last nine decades despite some critique concerning the nature ofthe experimental atherosclerosis The rabbit fulfils a number ofpractical and biological criteria for being an ideal animal model tor human atherosclerosis. The shortcomings of the Classical rabbit model, the Cholesterol-fed rabbit, concerning the morphology of the lesions have been overcome. and new  genetic variants which offer expanded possibilities of exploring the relationship between lipid metabolism and development of atherosclerosis have been developed. At present the mostly used rabbit models are: the eholesterol-l‘ed rabbit. the Watanabe heritable hyperlipidemic rabbit, and St. Thomas’ Hospital rabbit Different study designs can be applied to the eholesterol-fed rabbit. Atherosclerosis in rabbit models can be evaluated by macroscopic, biochemical and microseopie methods

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

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

IPCC, 2023: Climate Change 2023: Synthesis Report, Summary for Policymakers. Contribution of Working Groups I, II and III to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change [Core Writing Team, H. Lee and J. Romero (eds.)]. IPCC, Geneva, Switzerland.

This Synthesis Report (SYR) of the IPCC Sixth Assessment Report (AR6) summarises the state of knowledge of climate change, its widespread impacts and risks, and climate change mitigation and adaptation. It integrates the main findings of the Sixth Assessment Report (AR6) based on contributions from the three Working Groups1 , and the three Special Reports. The summary for Policymakers (SPM) is structured in three parts: SPM.A Current Status and Trends, SPM.B Future Climate Change, Risks, and Long-Term Responses, and SPM.C Responses in the Near Term.This report recognizes the interdependence of climate, ecosystems and biodiversity, and human societies; the value of diverse forms of knowledge; and the close linkages between climate change adaptation, mitigation, ecosystem health, human well-being and sustainable development, and reflects the increasing diversity of actors involved in climate action. Based on scientific understanding, key findings can be formulated as statements of fact or associated with an assessed level of confidence using the IPCC calibrated language

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570