Reactivation of the mitosis-promoting factor in postmitotic cardiomyocytes

Cardiomyocytes cease to divide shortly after birth and an irreversible cell cycle arrest is evident accompanied by the downregulation of cyclin-dependent kinase activities. To get a better understanding of the cardiac cell cycle and its regulation, the effect of functional recovery of the mitosis-promoting factor (MPF) consisting of cyclin B1 and the cyclin-dependent kinase Cdc2 was assessed in primary cultures of postmitotic ventricular adult rat cardiomyocytes ( ARC). Gene transfer into ARC was achieved using the adenovirus-enhanced transferrinfection system that was characterized by the absence of cytotoxic events. Simultaneous ectopic expression of wild-type versions of cyclin B1 and Cdc2 was sufficient to induce MPF activity. Reestablished MPF resulted in a mitotic phenotype, marked by an abnormal condensation of the nuclei, histone H3 phosphorylation and variable degree of decay of the contractile apparatus. Although a complete cell division was not observed, the results provided conclusive evidence that cell cycle-related events in postmitotic cardiomyocytes could be triggered by genetic intervention downstream of the G1/S checkpoint. This will be of importance to design novel strategies to overcome the proliferation arrest in adult cardiomyocytes

Circulating omentin as a novel biomarker for colorectal cancer risk: Data from the EPIC - Potsdam cohort study

Omentin is a novel biomarker shown to exert metabolic, inflammatory and immune-related properties, and thereby could be implicated in the risk of colorectal cancer (CRC). So far, the association between omentin and CRC risk has not been evaluated in prospective cohort studies. We investigated the association between pre-diagnostic plasma omentin concentrations and risk of CRC in a case-cohort comprising 251 incident CRC cases diagnosed over a mean follow-up time of 10.4 years and 2,295 persons who remained free of cancer in the European Prospective Investigation into Cancer and Nutrition-Potsdam study. Hazard ratios as a measure of relative risk (RR) and 95% confidence intervals (CI-s) were computed using a Prentice modified Cox regression. In a model adjusted for established CRC risk factors, age, sex, education, dietary and lifestyle factors, body mass index (BMI) and waist circumference, higher omentin concentrations were associated with a higher CRC risk (RRcontinuously per doubling of omentin concentrations=1.98, 95%CI: 1.45-2.73). Additional adjustment for metabolic biomarkers, including glycated hemoglobin, high-density lipoprotein cholesterol and C-reactive protein, did not alter the results. In stratified analyses, the positive association between omentin and CRC risk was retained in participants with BMI< 30 (RRcontinuously per doubling of omentin concentrations=2.26; 95%CI: 1.57-3.27), whereas among participants with BMI{greater than or equal to} 30 no association was revealed (RRcontinuously per doubling of omentin concentrations =1.07; 95%CI: 0.63-1.83; Pinteraction= 0.005). These novel findings provide the first lines of evidence for an independent association between pre-diagnostic omentin concentrations and CRC risk and suggest a potential interaction with the adiposity state of the individual

Holographic surface measurement system for the Fred Young Submillimeter Telescope

We describe a system being developed for measuring the shapes of the mirrors of the Fred Young Submillimeter Telescope (FYST), now under construction for the CCAT Observatory. "Holographic" antenna-measuring techniques are an efficient and accurate way of measuring the surfaces of large millimeter-wave telescopes and they have the advantage of measuring the wave-front errors of the whole system under operational conditions, e.g. at night on an exposed site. Applying this to FYST, however, presents significant challenges because of the high accuracy needed, the fact that the telescope consists of two large off-axis mirrors, and a requirement that measurements can be made without personnel present. We use a high-frequency (~300GHz) source which is relatively close to the telescope aperture (<1/100th of the Fresnel distance) to minimize atmospheric effects. The main receiver is in the receiver cabin and can be moved under remote control to different positions, so that the wave-front errors in different parts of the focal plane can be measured. A second receiver placed on the yoke provides a phase reference. The signals are combined in a digital cross-correlation spectrometer. Scanning the telescope provides a map of the complex beam pattern. The surface errors are found by inference, i.e. we make models of the reflectors with errors and calculate the patterns expected, and then iterate to find the best match to the data. To do this we have developed a fast and accurate method for calculating the patterns using the Kirchhoff-Fresnel formulation. This paper presents details of the design and outlines the results from simulations of the measurement and inference process. These indicate that a measurement accuracy of ~3 microns rms is achievable.Comment: Proceedings Volume 11445, Ground-based and Airborne Telescopes VIII SPIE Astronomical Telescopes + Instrumentation, 2020, Online Only Conferenc

State-of-the-art CT and MR imaging and assessment of atherosclerotic carotid artery disease: the reporting-a consensus document by the European Society of Cardiovascular Radiology (ESCR).

The European Society of Cardiovascular Radiology (ESCR) is the European specialist society of cardiac and vascular imaging. This society's highest priority is the continuous improvement, development, and standardization of education, training, and best medical practice, based on experience and evidence. The present intra-society consensus is based on the existing scientific evidence and on the individual experience of the members of the ESCR writing group on carotid diseases, the members of the ESCR guidelines committee, and the members of the executive committee of the ESCR. The recommendations published herein reflect the evidence-based society opinion of ESCR. The purpose of this second document is to discuss suggestions for standardized reporting based on the accompanying consensus document part I. KEY POINTS: • CT and MR imaging-based evaluation of carotid artery disease provides essential information for risk stratification and prediction of stroke. • The information in the report must cover vessel morphology, description of stenosis, and plaque imaging features. • A structured approach to reporting ensures that all essential information is delivered in a standardized and consistent way to the referring clinician

State-of-the-art CT and MR imaging and assessment of atherosclerotic carotid artery disease: standardization of scanning protocols and measurements - a consensus document by the European Society of Cardiovascular Radiology (ESCR)

The European Society of Cardiovascular Radiology (ESCR) is the European specialist society of cardiac and vascular imaging. This society's highest priority is the continuous improvement, development, and standardization of education, training, and best medical practice, based on experience and evidence. The present intra-society consensus is based on the existing scientific evidence and on the individual experience of the members of the ESCR writing group on carotid diseases, the members of the ESCR guidelines committee, and the members of the executive committee of the ESCR. The recommendations published herein reflect the evidence-based society opinion of ESCR. We have produced a twin-papers consensus, indicated through the documents as respectively "Part I" and "Part II." The first document (Part I) begins with a discussion of features, role, indications, and evidence for CT and MR imaging-based diagnosis of carotid artery disease for risk stratification and prediction of stroke (Section I). It then provides an extensive overview and insight into imaging-derived biomarkers and their potential use in risk stratification (Section II). Finally, detailed recommendations about optimized imaging technique and imaging strategies are summarized (Section III). The second part of this consensus paper (Part II) is focused on structured reporting of carotid imaging studies with CT/MR

Alcohol Consumption, Genetic Variants in Alcohol Deydrogenases, and Risk of Cardiovascular Diseases: A Prospective Study and Meta-Analysis

OBJECTIVE: First, to investigate and compare associations between alcohol consumption and variants in alcohol dehydrogenase (ADH) genes with incidence of cardiovascular diseases (CVD) in a large German cohort. Second, to quantitatively summarize available evidence of prospective studies on polymorphisms in ADH1B and ADH1C and CVD-risk. METHODS: We conducted a case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort including a randomly drawn subcohort (n = 2175) and incident cases of myocardial infarction (MI; n = 230) or stroke (n = 208). Mean follow-up time was 8.2±2.2 years. The association between alcohol consumption, ADH1B or ADH1C genotypes, and CVD-risk was assessed using Cox proportional hazards regression. Additionally, we report results on associations of variants in ADH1B and ADH1C with ischemic heart disease and stroke in the context of a meta-analysis of previously published prospective studies published up to November 2011. RESULTS: Compared to individuals who drank >0 to 6 g alcohol/d, we observed a reduced risk of MI among females consuming >12 g alcohol/d (HR = 0.31; 95% CI: 0.10-0.97) and among males consuming >24 to 60 g/d (HR = 0.57; 95% CI: 0.33-0.98) or >60 g alcohol/d (HR = 0.30; 95% CI: 0.12-0.78). Stroke risk was not significantly related to alcohol consumption >6 g/d, but we observed an increased risk of stroke in men reporting no alcohol consumption. Individuals with the slow-coding ADH1B*1/1 genotype reported higher median alcohol consumption. Yet, polymorphisms in ADH1B or ADH1C were not significantly associated with risk of CVD in our data and after pooling results of eligible prospective studies [ADH1B*1/1: RR = 1.35 (95% CI: 0.98-1.88; p for heterogeneity: 0.364); ADH1C*2/2: RR = 1.07 (95% CI: 0.90-1.27; p for heterogeneity: 0.098)]. CONCLUSION: The well described association between alcohol consumption and CVD-risk is not reflected by ADH polymorphisms, which modify the rate of ethanol oxidation

State-of-the-art CT and MR imaging and assessment of atherosclerotic carotid artery disease: standardization of scanning protocols and measurements-a consensus document by the European Society of Cardiovascular Radiology (ESCR).

The European Society of Cardiovascular Radiology (ESCR) is the European specialist society of cardiac and vascular imaging. This society's highest priority is the continuous improvement, development, and standardization of education, training, and best medical practice, based on experience and evidence. The present intra-society consensus is based on the existing scientific evidence and on the individual experience of the members of the ESCR writing group on carotid diseases, the members of the ESCR guidelines committee, and the members of the executive committee of the ESCR. The recommendations published herein reflect the evidence-based society opinion of ESCR. We have produced a twin-papers consensus, indicated through the documents as respectively "Part I" and "Part II." The first document (Part I) begins with a discussion of features, role, indications, and evidence for CT and MR imaging-based diagnosis of carotid artery disease for risk stratification and prediction of stroke (Section I). It then provides an extensive overview and insight into imaging-derived biomarkers and their potential use in risk stratification (Section II). Finally, detailed recommendations about optimized imaging technique and imaging strategies are summarized (Section III). The second part of this consensus paper (Part II) is focused on structured reporting of carotid imaging studies with CT/MR. KEY POINTS: • CT and MR imaging-based evaluation of carotid artery disease provides essential information for risk stratification and prediction of stroke. • Imaging-derived biomarkers and their potential use in risk stratification are evolving; their correct interpretation and use in clinical practice must be well-understood. • A correct imaging strategy and scan protocol will produce the best possible results for disease evaluation