Molecular basis or arginine and lysine DNA sequence-dependent thermo-stability modulation

We have used a variety of theoretical and experimental techniques to study the role of four basic amino acids-Arginine, Lysine, Ornithine and L-2,4-Diaminobutyric acid-on the structure, flexibility and sequence-dependent stability of DNA. We found that the presence of organic ions stabilizes the duplexes and significantly reduces the difference in stability between AT- and GC-rich duplexes with respect to the control conditions. This suggests that these amino acids, ingredients of the primordial soup during abiogenesis, could have helped to equalize the stability of AT- and GC-rich DNA oligomers, facilitating a general noncatalysed self-replication of DNA. Experiments and simulations demonstrate that organic ions have an effect that goes beyond the general electrostatic screening, involving specific interactions along the grooves of the double helix. We conclude that organic ions, largely ignored in the DNA world, should be reconsidered as crucial structural elements far from mimics of small inorganic cations

Exact prefactors in static and dynamic correlation functions of 1D quantum integrable models: applications to the Calogero-Sutherland, Lieb-Liniger and XXZ models

In this article we demonstrate a recently developed technique which addresses the problem of obtaining non-universal prefactors of the correlation functions of 1D systems at zero temperature. Our approach combines the effective field theory description of generic 1D quantum liquids with the finite size scaling of form factors (matrix elements) which are obtained using microscopic techniques developed in the context of integrable models. We thus establish exact analytic forms for the prefactors of the long-distance behavior of equal time correlation functions as well as prefactors of singularities of dynamic response functions. In this article our focus is on three specific integrable models: the Calogero-Sutherland, Lieb-Liniger, and XXZ models.Comment: 95 pages and 8 figure

Temporal changes in the pattern of invasive angiography use and its outcome in suspected coronary artery disease : implications for patient management and healthcare resource utilization

Introduction: Invasive coronary angiography (CAG), the ‘gold standard’ in coronary artery disease (CAD) diagnosis, requires hospitalization, is not risk-free, and engages considerable healthcare resources. Aim: To assess recent (throught out 10 years) evolution of ‘significant’ (≥ 50% stenosis(es)) CAD prevalence in subjects undergoing CAG for CAD diagnosis in a high-volume tertiary referral center. Material and methods: Anonymized medical records were compared from the last vs. the first 2-years of the decade (June 2007 to May 2018). Referrals for suspected CAD were 2067 of 4522 hospitalizations (45.7%) and 1755 of 5196 (33.8%) respectively (p < 0.001). Results: The median patient age (64 vs. 68 years) and the prevalence of heart failure (24.1% vs. 42.2%) increased significantly (p < 0.001). The CAG atherosclerotic lesions, for all stenosis categories (< 50%; ≥ 50%; ≥ 70%; occlusion(s)), were significantly more prevalent in men. The proportion of subjects with any atherosclerosis on CAG increased (80.7% vs. 77.6%, p = 0.015). However, in the absence of any gross change in, for instance, the fraction of women (40.4% vs. 41.8%), the proportion of CAGs with significant CAD (lesion(s) ≥ 50%) decreased from 55.2% in 2007/2008 to below 1 in every 2 angiograms (48.9%) in 2017/2018 (p < 0.001). This unexpected finding occurred consistently across nearly all CAG referral categories. Conclusions: Despite more advanced age and a higher proportion of subjects with ‘any’ coronary atherosclerosis on CAG, the likelihood of a ‘negative’ angiogram (lesion(s) < 50%; no further evaluation/intervention) has increased significantly over the last decade. The exact nature of this phenomenon requires further investigation, particularly as a reverse trend would be expected with the growing role (and current high penetration) of contemporary non-invasive diagnostic tools to rule out significant CAD

Quench Dynamics in Two-Dimensional Integrable SUSY Models

We analyse quench processes in two dimensional quantum field theories with infinite number of conservation laws which also include fermionic charges that close a N=1 supersymmetric algebra. While in general the quench protocol induces a breaking of supersymmetry, we show that there are particular initial states which ensure the persistence of supersymmetry also for the dynamics out of equilibrium. We discuss the conditions that identify such states and, as application, we present the significant cases of the Tricritical Ising Model and the Sine-Gordon model at its supersymmetric point. We also address the issue of the Generalized Gibbs Ensemble in the presence of fermionic conserved charges

Does Diabetes Accelerate the Progression of Aortic Stenosis through Enhanced Inflammatory Response within Aortic valves?

Diabetes predisposes to aortic stenosis (AS). We aimed to investigate if diabetes affects the expression of selected coagulation proteins and inflammatory markers in AS valves. Twenty patients with severe AS and concomitant type 2 diabetes mellitus (DM) and 40 well-matched patients without DM scheduled for valve replacement were recruited. Valvular tissue factor (TF), TF pathway inhibitor (TFPI), prothrombin, C-reactive protein (CRP) expression were evaluated by immunostaining and TF, prothrombin, and CRP transcripts were analyzed by real-time PCR. DM patients had elevated plasma CRP (9.2 [0.74–51.9] mg/l vs. 4.7 [0.59–23.14] mg/l, p = 0.009) and TF (293.06 [192.32–386.12] pg/ml vs. 140 [104.17–177.76] pg/ml, p = 0.003) compared to non-DM patients. In DM group, TF−, TFPI−, and prothrombin expression within valves was not related to demographics, body mass index, and concomitant diseases, whereas increased expression related to DM was found for CRP on both protein (2.87 [0.5–9]% vs. 0.94 [0–4]%, p = 0.01) and transcript levels (1.3 ± 0.61 vs. 0.22 ± 0.43, p = 0.009). CRP-positive areas were positively correlated with mRNA TF (r = 0.84, p = 0.036). Diabetes mellitus is associated with enhanced inflammation within AS valves, measured by CRP expression, which may contribute to faster AS progression

Assessing circadian rhythms in propofol PK and PD during prolonged infusion in ICU patients

This study evaluates possible circadian rhythms during prolonged propofol infusion in patients in the intensive care unit. Eleven patients were sedated with a constant propofol infusion. The blood samples for the propofol assay were collected every hour during the second day, the third day, and after the termination of the propofol infusion. Values of electroencephalographic bispectral index (BIS), arterial blood pressure, heart rate, blood oxygen saturation and body temperature were recorded every hour at the blood collection time points. A two-compartment model was used to describe propofol pharmacokinetics. Typical values of the central and peripheral volume of distribution and inter-compartmental clearance were VC = 27.7 l, VT = 801 l, and CLD = 2.73 l/min. The systolic blood pressure (SBP) was found to influence the propofol metabolic clearance according to Cl (l/min) = 2.65·(1 − 0.00714·(SBP − 135)). There was no significant circadian rhythm detected with respect to propofol pharmacokinetics. The BIS score was assessed as a direct effect model with EC50 equal 1.98 mg/l. There was no significant circadian rhythm detected within the BIS scores. We concluded that the light–dark cycle did not influence propofol pharmacokinetics and pharmacodynamics in intensive care units patients. The lack of night–day differences was also noted for systolic blood pressure, diastolic blood pressure and blood oxygenation. Circadian rhythms were detected for heart rate and body temperature, however they were severely disturbed from the pattern of healthy patients

Clinical correlates and prognostic impact of neurologic disorders in Takotsubo syndrome

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Cardiac alterations are frequently observed after acute neurological disorders. Takotsubo syndrome (TTS) represents an acute heart failure syndrome and is increasingly recognized as part of the spectrum of cardiac complications observed after neurological disorders. A systematic investigation of TTS patients with neurological disorders has not been conducted yet. The aim of the study was to expand insights regarding neurological disease entities triggering TTS and to investigate the clinical profile and outcomes of TTS patients after primary neurological disorders. The International Takotsubo Registry is an observational multicenter collaborative effort of 45 centers in 14 countries (ClinicalTrials.gov, identifier NCT01947621). All patients in the registry fulfilled International Takotsubo Diagnostic Criteria. For the present study, patients were included if complete information on acute neurological disorders were available. 2402 patients in whom complete information on acute neurological status were available were analyzed. In 161 patients (6.7%) an acute neurological disorder was identified as the preceding triggering factor. The most common neurological disorders were seizures, intracranial hemorrhage, and ischemic stroke. Time from neurological symptoms to TTS diagnosis was ≤ 2 days in 87.3% of cases. TTS patients with neurological disorders were younger, had a lower female predominance, fewer cardiac symptoms, lower left ventricular ejection fraction, and higher levels of cardiac biomarkers. TTS patients with neurological disorders had a 3.2-fold increased odds of in-hospital mortality compared to TTS patients without neurological disorders. In this large-scale study, 1 out of 15 TTS patients had an acute neurological condition as the underlying triggering factor. Our data emphasize that a wide spectrum of neurological diseases ranging from benign to life-threatening encompass TTS. The high rates of adverse events highlight the need for clinical awareness.The International Takotsubo Registry was supported by the Biss Davies Charitable Trust. Dr. Scheitz has been supported by the Corona Foundation. Dr. Templin has been supported by the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme and the Swiss Heart Foundation.info:eu-repo/semantics/publishedVersio

On the search for the right definition of heart failure with preserved ejection fraction

The definition of heart failure with preserved ejection fraction (HFpEF) has evolved from a clinically based “diagnosis of exclusion” to definitions focused on objective evidence of diastolic dysfunction and/or elevated left ventricular filling pressures. Despite advances in our understanding of HFpEF pathophysiology and the development of more sophisticated imaging modalities, the diagnosis of HFpEF remains challenging, especially in the chronic setting, given that symptoms are provoked by exertion and diagnostic evaluation is largely conducted at rest. Invasive hemodynamic study, and in particular — invasive exercise testing, is considered the reference method for HFpEF diagnosis. However, its use is limited as opposed to the high number of patients with suspected HFpEF. Thus, diagnostic criteria for HFpEF should be principally based on non-invasive measurements. As no single non-invasive variable can adequately corroborate or refute the diagnosis, different combinations of clinical, echocardiographic, and/or biochemical parameters have been introduced. Recent years have brought an abundance of HFpEF definitions. Here, we present and compare four of them: 1) the 2016 European Society of Cardiology criteria for HFpEF; 2) the 2016 echocardiographic algorithm for diagnosing diastolic dysfunction; 3) the 2018 evidence-based H2FPEF score; and 4) the most recent, 2019 Heart Failure Association HFA-PEFF algorithm. These definitions vary in their approach to diagnosis, as well as sensitivity and specificity. Further studies to validate and compare the diagnostic accuracy of HFpEF definitions are warranted. Nevertheless, it seems that the best HFpEF definition would originate from a randomized clinical trial showing a favorable effect of an intervention on prognosis in HFpEF