Imaging algorithm for COVID-19: A practical approach

© 2020 Elsevier Inc. The global pandemic of COVID-19 pneumonia caused by the novel coronavirus (SARS-CoV-2) has strained healthcare resources across the world with emerging challenges of mass testing, resource allocation and management. While reverse transcriptase-polymerase chain reaction (RT-PCR) test is the most commonly utilized test and considered the current gold standard for diagnosis, the role of chest imaging has been highlighted by several studies demonstrating high sensitivity of computed tomography (CT). Many have suggested using CT chest as a first-line screening tool for the diagnosis of COVID-19. However, with advancement of laboratory testing and challenges in obtaining a CT scan without significant risk to healthcare providers, the role of imaging in diagnosis has been questioned. Several imaging societies have released consensus statements and guidelines on utilizing imaging resources and optimal reporting. In this review, we highlight the current evidence on various modalities in thoracic imaging for the diagnosis of COVID-19 and describe an algorithm on how to use these resources in an optimal fashion in accordance with the guidelines and statements released by major imaging societies

Selective mitochondrial superoxide generation in vivo is cardioprotective through hormesis

Reactive oxygen species (ROS) have an equivocal role in myocardial ischaemia reperfusion injury. Within the cardiomyocyte, mitochondria are both a major source and target of ROS. We evaluate the effects of a selective, dose-dependent increase in mitochondrial ROS levels on cardiac physiology using the mitochondria-targeted redox cycler MitoParaquat (MitoPQ). Low levels of ROS decrease the susceptibility of neonatal rat ventricular myocytes (NRVMs) to anoxia/reoxygenation injury and also cause profound protection in an in vivo mouse model of ischaemia/reperfusion. However higher doses of MitoPQ resulted in a progressive alteration of intracellular [Ca2+] homeostasis and mitochondrial function in vitro, leading to dysfunction and death at high doses. Our data show that a primary increase in mitochondrial ROS can alter cellular function, and support a hormetic model in which low levels of ROS are cardioprotective while higher levels of ROS are cardiotoxic.The work is supported by an MRC Studentship to JFM and a Wellcome Trust Investigator award to RCH (110158/Z/15/Z), the Leducq Transatlantic Network of Excellence, and the University of Padova Strategico grant (FDL). Part of the study was funded by an MRC Project Grant to TK (MR/P000320/1). Michele Cariello is thanked for help with cyclic voltammetry

GAUCHE: A Library for Gaussian Processes in Chemistry

We introduce GAUCHE, an open-source library for GAUssian processes in CHEmistry. Gaussian processes have long been a cornerstone of probabilistic machine learning, affording particular advantages for uncertainty quantification and Bayesian optimisation. Extending Gaussian processes to molecular representations, however, necessitates kernels defined over structured inputs such as graphs, strings and bit vectors. By providing such kernels in a modular, robust and easy-to-use framework, we seek to enable expert chemists and materials scientists to make use of state-of-the-art black-box optimization techniques. Motivated by scenarios frequently encountered in practice, we showcase applications for GAUCHE in molecular discovery, chemical reaction optimisation and protein design. The codebase is made available at https://github.com/leojklarner/gauche

Monoamine oxidase-dependent endoplasmic reticulum-mitochondria dysfunction and mast cell degranulation lead to adverse cardiac remodeling in diabetes.

Monoamine oxidase (MAO) inhibitors ameliorate contractile function in diabetic animals, but the mechanisms remain unknown. Equally elusive is the interplay between the cardiomyocyte alterations induced by hyperglycemia and the accompanying inflammation. Here we show that exposure of primary cardiomyocytes to high glucose and pro-inflammatory stimuli leads to MAO-dependent increase in reactive oxygen species that causes permeability transition pore opening and mitochondrial dysfunction. These events occur upstream of endoplasmic reticulum (ER) stress and are abolished by the MAO inhibitor pargyline, highlighting the role of these flavoenzymes in the ER/mitochondria cross-talk. In vivo, streptozotocin administration to mice induced oxidative changes and ER stress in the heart, events that were abolished by pargyline. Moreover, MAO inhibition prevented both mast cell degranulation and altered collagen deposition, thereby normalizing diastolic function. Taken together, these results elucidate the mechanisms underlying MAO-induced damage in diabetic cardiomyopathy and provide novel evidence for the role of MAOs in inflammation and inter-organelle communication. MAO inhibitors may be considered as a therapeutic option for diabetic complications as well as for other disorders in which mast cell degranulation is a dominant phenomenon

Bacteria-inducing legume nodules involved in the improvement of plant growth, health and nutrition

Bacteria-inducing legume nodules are known as rhizobia and belong to the class Alphaproteobacteria and Betaproteobacteria. They promote the growth and nutrition of their respective legume hosts through atmospheric nitrogen fixation which takes place in the nodules induced in their roots or stems. In addition, rhizobia have other plant growth-promoting mechanisms, mainly solubilization of phosphate and production of indoleacetic acid, ACC deaminase and siderophores. Some of these mechanisms have been reported for strains of rhizobia which are also able to promote the growth of several nonlegumes, such as cereals, oilseeds and vegetables. Less studied are the mechanisms that have the rhizobia to promote the plant health; however, these bacteria are able to exert biocontrol of some phytopathogens and to induce the plant resistance. In this chapter, we revised the available data about the ability of the legume nodule-inducing bacteria for improving the plant growth, health and nutrition of both legumes and nonlegumes. These data showed that rhizobia meet all the requirements of sustainable agriculture to be used as bio-inoculants allowing the total or partial replacement of chemicals used for fertilization or protection of crops

Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

The potential for ischemic preconditioning to reduce infarct size was first recognized more than 30 years ago. Despite extension of the concept to ischemic postconditioning and remote ischemic conditioning and literally thousands of experimental studies in various species and models which identified a multitude of signaling steps, so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients. Many potential reasons for this disappointing lack of clinical translation of cardioprotection have been proposed, including lack of rigor and reproducibility in preclinical studies, and poor design and conduct of clinical trials. There is, however, universal agreement that robust preclinical data are a mandatory prerequisite to initiate a meaningful clinical trial. In this context, it is disconcerting that the CAESAR consortium (Consortium for preclinicAl assESsment of cARdioprotective therapies) in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size. However, ischemic preconditioning—due to its very nature—can only be used in elective interventions, and not in acute myocardial infarction. Therefore, better strategies to identify robust and reproducible strategies of cardioprotection, which can subsequently be tested in clinical trials must be developed. We refer to the recent guidelines for experimental models of myocardial ischemia and infarction, and aim to provide now practical guidelines to ensure rigor and reproducibility in preclinical and clinical studies on cardioprotection. In line with the above guideline, we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment

Enthalpy of mixing of 1:1 electrolytic solutions at varying ionic strength at 298.15 K in water + l,4-dioxane mixed solvent system

467-472Enthalpy of mixing for six possible combinations of solutions of NaCl, KCl, NaBr and KBr have been determined as a function of ionic strength. The experiments have been performed at constant ionic strengths of 1.0 and 2.0 mol kg-1 at 298.15 K using LKB now microcalorimeter in water +1,4-dioxane mixed solvent system. Data differ appreciably from corresponding data in water and even do not support Young's Cross Square Rule. Pitzer ion-interaction model is utilized to obtain binary and triplet interaction parameters i.e. ΘN and ΨNX .The data suggest that deviation from Young Cross Square Rule may arise from preferential solvation of the ions and ion clusters, as organic cosolvent is also incorporated in the solvation shell. </span

Life-Threatening Hemoptysis

AbstractLife-threatening hemoptysis (LTH) is any amount of hemoptysis that causes significant hemodynamic decompensation or respiratory distress which may lead to death if left untreated. While the amount of hemoptysis that qualifies as massive hemoptysis has continued to be debated, any amount between 100 to 1,000 mL/day is considered significant. Up to 15% cases of hemoptysis are LTH and need urgent life-saving intervention. Understanding of pulmonary vascular anatomy is of paramount importance to manage LTH. The goal of treatment lies in airway protection, appropriate oxygenation, and prevention of exsanguination. Once the airway is stabilized, a quick diagnosis and control of bleeding site is targeted. This chapter highlights current practices and approach to LTH including medical management, bronchoscopic approach, and advanced therapies such as bronchial artery embolization and surgical resection. We review situations, such as bronchiectasis, vascular malformation, diffuse alveolar hemorrhage, and tracheostomy bleed and specific approach to management of these conditions in a systematic and evidence-based manner.</jats:p