Metabolic profiling of Arabidopsis thaliana epidermal cells

Metabolic phenotyping at cellular resolution may be considered one of the challenges in current plant physiology. A method is described which enables the cell type-specific metabolic analysis of epidermal cell types in Arabidopsis thaliana pavement, basal, and trichome cells. To achieve the required high spatial resolution, single cell sampling using microcapillaries was combined with routine gas chromatography-time of flight-mass spectrometry (GC-TOF-MS) based metabolite profiling. The identification and relative quantification of 117 mostly primary metabolites has been demonstrated. The majority, namely 90 compounds, were accessible without analytical background correction. Analyses were performed using cell type-specific pools of 200 microsampled individual cells. Moreover, among these identified metabolites, 38 exhibited differential pool sizes in trichomes, basal or pavement cells. The application of an independent component analysis confirmed the cell type-specific metabolic phenotypes. Significant pool size changes between individual cells were detectable within several classes of metabolites, namely amino acids, fatty acids and alcohols, alkanes, lipids, N-compounds, organic acids and polyhydroxy acids, polyols, sugars, sugar conjugates and phenylpropanoids. It is demonstrated here that the combination of microsampling and GC-MS based metabolite profiling provides a method to investigate the cellular metabolism of fully differentiated plant cell types in vivo

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Be Free? The European Union's post-Arab Spring Women's Empowerment as Neoliberal Governmentality

This article analyses post-Arab Spring EU initiatives to promote women's empowerment in the Southern Mediterranean region. Inspired by Foucauldian concepts of governmentality, it investigates empowerment as a technology of biopolitics that is central to the European neoliberal model of governance. In contrast to dominant images such as normative power Europe that present the EU as a norm-guided actor promoting political liberation, the article argues that the EU deploys a concept of functional freedom meant to facilitate its vision of economic development. As a consequence, the alleged empowerment of women based on the self-optimisation of individuals and the statistical control of the female population is a form of bio-power. In this regard, empowerment works as a governmental technology of power instead of offering a measure to foster fundamental structural change in Middle Eastern and North African (MENA) societies. The EU therefore fails in presenting and promoting an alternative normative political vision distinct from the incorporation of women into the hierarchy of the existing market society

Mechanisms and consequences of atrial fibrillation: insights into the electrical mechanisms sustaining atrial fibrillation, the drivers of underlying atrial remodeling, and the factors governing symptom severity and quality of life

© 2015 Dr. Tomos Evan Rhys WaltersAtrial fibrillation (AF) exists on a clinical spectrum from paroxysmal to persistent and eventually permanent AF. Progression through this spectrum is well described, but is not universal. Mechanistically, paroxysmal AF is driven by fast electrical triggers most commonly located in the myocardial sleeves of the pulmonary veins, whilst persistent AF is dependent on perpetuating electrical mechanisms rooted in an abnormal atrial substrate. The nature of these mechanisms remains a subject of debate, with recent evidence pointing towards rotors, a form of functional reentry, providing a driving source for human persistent AF. Various studies have ascribed quite different properties to these rotors. More severe abnormalities in the electroanatomic properties of the left atrium (LA) have been demonstrated in persistent than in paroxysmal AF, and improvement in such properties has been described after catheter ablation of AF, but there is little data describing the rate of deterioration in LA properties with ongoing AF, or the key drivers of change. Finally, it is recognized that AF is frequently associated with significant quality of life impairment, but there is a wide spectrum of clinical severity and the factors governing this variation are incompletely understood. Chapters 2 and 3 of this thesis examine the atrial substrate. The extent of remodeling of the LA is a key determinant of the success of catheter ablation, and so non-invasive techniques with which to assess remodeling are keenly sought. In chapter 2, the association between the extent of LA electroanatomic remodeling and the fibrillatory cycle length derived from lead V1 of the surface electrocardiogram during AF is characterized. It is demonstrated that a longer AF cycle length in lead V1 is associated with more advanced LA remodeling, specifically slower atrial conduction and more extensive electrogram fractionation. Given that gender-based differences in clinical behaviour of multiple cardiac arrhythmias are well described, the presence of systematic gender-based differences in the pulmonary vein and atrial substrate is examined in chapter 3. No such between-gender differences were observed, either in those with or without a history of AF, and with a similar prevalence of AF-related comorbidities seen in both male and female groups. Chapters 4, 5 and 6 move to an exploration of the electrical mechanisms underlying AF, through detailed epicardial mapping studies of the LA and its junction with the pulmonary vein (PV-LA junction). Chronic stretch is fundamental to atrial remodeling in human AF, and conditions associated with acute stretch are recognized triggers for episodes of AF. In chapter 4 the response of the PV-LA junction to acute stretch was characterized, with the observation that acute stretch results in conduction slowing across the PV-LA junction and a greater degree of signal complexity, providing conditions suitable for reentry. Chapters 5 and 6 involved epicardial mapping in patients with longstanding persistent AF, with the aim of determining the spatiotemporal stability of the AF cycle length and of atrial activation patterns, including the stability of any demonstrated rotors, over a 10 minute period. This is a time period much in excess of that over which detailed mapping has previously ben performed. It was observed that atrial activation patterns are spatiotemporally stable over this time scale, with clear anatomic determinism, and that in the great majority of patients transient rotors can be demonstrated. These appear to last only a median of 3 cycles, usually develop due to perpendicular wavefront-wavetail interaction, and are commonly anchored on a region of short cycle electrical activity. Such activity, however, is highly non-specific for rotor localization, more often being the result of passive wavefront collision. The frequency of atrial activation appears much more variable over 10 minutes, but there was clear inter-dependence between left and right atrial cycle lengths during mapping of anatomically disparate regions, and within each region the relative distribution of locations with faster and slower activation frequencies was highly conserved. These observations, indicating significant underlying spatiotemporal organization, are consistent with the presence of focal drivers such as rotors governing global atrial activation. Chapter 7 returns to the issue of atrial remodeling, with the aim of defining the magnitude and the predictors of change in the extent of LA electroanatomic remodeling over 12 months of high burden AF. Using measures of atrial myocardial deformation characteristics derived from strain imaging to of the atrial wall and P-wave characteristics as non-invasive biomarkers of remodeling, ongoing high burden AF was found to be associated with measurable progression in the extent of LA remodeling even over a 12 month period, whilst after AF ablation in a similar cohort results there was significant reversal of existing remodeling. These data may have implications for timing of ablative intervention. Finally, chapter 8 addresses the key determinants of AF symptom severity and quality of life. It is demonstrated that a high proportion of patients with AF experience significant psychological distress and even thoughts of self-harm. Clinical variables including age, body mass index and the burden of AF influence the perceived severity of the AF syndrome, with key differences between patients with intermittent and continuous forms of AF. The influence of organic cardiac variables, however, is subsumed by the dominant influence of personality style, with a predisposition to perceive life events as stressful and a chronic tendency to anxiety and negativity particularly powerful. Effective rhythm control through AF ablation was found to lead to marked improvements in AF symptom severity, quality of life and levels of psychological distress, suggesting that psychological distress is a consequence of the arrhythmia itself interacting with a vulnerable personality style

New Insights into Reentry Circuits from Mapping and Ablation of Atrioventricular Nodal Reentrant Tachycardia

Atrioventricular nodal reentrant tachycardia (AVNRT) is a very common cardiac arrhythmia and is due to reentry within the region of the atrioventricular junction. The anatomy of the atrioventricular (AV) node, including inferior extensions within the triangle of Koch and a transitional zone of cells interposed between the compact node and atrial myocardial cells, has been extensively investigated. The functional inputs to the AV node have been revealed to be multiple, from both sides of the interatrial septum. Despite this knowledge the precise nature of the reentry circuit and its variants remains elusive, with a variety of proposed models. Regardless, catheter ablation of the slowly conducting pathway inferior to the compact node, within the triangle of Koch or anterior to the ostium of the coronary sinus, is a highly effective method by which the circuit can be disrupted and AVNRT eliminated. This edition first published 201

Radiofrequency ablation for atrial tachycardia and atrial flutter

Atrial tachycardia is a generic term for a range of tachyarrhythmias with their origin in the atria. These can be broadly divided by mechanism into macro-reentrant, focal and small circuit re-entry. "Atrial flutter" is a term which, today, should be restricted to those classical circuits around the tricuspid annulus dependent on the cavo-tricuspid isthmus. The advent of sophisticated mapping solutions has rendered the vast majority of these atrial circuits curable with catheter ablation, with high success rates and very low incidence of complications. (Heart, Lung and Circulation 2012;21:386-394) (C) 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved