Perioperative provider safety in the pandemic : Development, implementation and evaluation of an adjunct COVID-19 Surgical Patient Checklist

We would like to acknowledge Eliana Lillevik, Luciano Barbosa, Daniela Farchi, Dr Laila Woc-Colburn, Dr Gustavo Moraes, Suko Dwi Nugroho, Nguyen Tri Dung, Dr Rong Hu, Priya Desai and Senait Bitew for their contributions to language translations, survey distribution and data collection. Funding The authors disclosed receipt of the following financial support for the research, authorship, and publication of this article: NS received salary support during the conduct of this study from NIH Fogarty International Center (Global Health Equity Scholars NIH FIC D43TW010540).Peer reviewedPublisher PD

Perioperative oxygen fraction – effect on surgical site infection and pulmonary complications after abdominal surgery: a randomized clinical trial. Rationale and design of the PROXI-Trial

<p>Abstract</p> <p>Background</p> <p>A high perioperative inspiratory oxygen fraction may reduce the risk of surgical site infections, as bacterial eradication by neutrophils depends on wound oxygen tension. Two trials have shown that a high perioperative inspiratory oxygen fraction (Fi<smcaps>O</smcaps>₂= 0.80) significantly reduced risk of surgical site infections after elective colorectal surgery, but a third trial was stopped early because the frequency of surgical site infections was more than doubled in the group receiving Fi<smcaps>O</smcaps>₂= 0.80. It has not been settled if a high inspiratory oxygen fraction increases the risk of pulmonary complications, such as atelectasis, pneumonia and respiratory failure. The aim of our trial is to assess the potential benefits and harms of a high perioperative oxygen fraction in patients undergoing abdominal surgery.</p> <p>Methods and design</p> <p>The PROXI-Trial is a randomized, patient- and assessor blinded trial of perioperative supplemental oxygen in 1400 patients undergoing acute or elective laparotomy in 14 Danish hospitals. Patients are randomized to receive either 80% oxygen (Fi<smcaps>O</smcaps>₂= 0.80) or 30% oxygen (Fi<smcaps>O</smcaps>₂= 0.30) during surgery and for the first 2 postoperative hours. The primary outcome is surgical site infection within 14 days. The secondary outcomes are: atelectasis, pneumonia, respiratory failure, re-operation, mortality, duration of postoperative hospitalization, and admission to intensive care unit. The sample size allows detection of a 33% relative risk reduction in the primary outcome with 80% power.</p> <p>Discussion</p> <p>This trial assesses benefits and harms of a high inspiratory oxygen fraction, and the trial may be generalizable to a general surgical population undergoing laparotomy.</p> <p>Trial registration</p> <p>ClinicalTrials.gov identifier: NCT00364741.</p

Comparative Genomic and Transcriptomic Characterization of the Toxigenic Marine Dinoflagellate Alexandrium ostenfeldii

Many dinoflagellate species are notorious for the toxins they produce and ecological and human health consequences associated with harmful algal blooms (HABs). Dinoflagellates are particularly refractory to genomic analysis due to the enormous genome size, lack of knowledge about their DNA composition and structure, and peculiarities of gene regulation, such as spliced leader (SL) trans-splicing and mRNA transposition mechanisms. Alexandrium ostenfeldii is known to produce macrocyclic imine toxins, described as spirolides. We characterized the genome of A. ostenfeldii using a combination of transcriptomic data and random genomic clones for comparison with other dinoflagellates, particularly Alexandrium species. Examination of SL sequences revealed similar features as in other dinoflagellates, including Alexandrium species. SL sequences in decay indicate frequent retro-transposition of mRNA species. This probably contributes to overall genome complexity by generating additional gene copies. Sequencing of several thousand fosmid and bacterial artificial chromosome (BAC) ends yielded a wealth of simple repeats and tandemly repeated longer sequence stretches which we estimated to comprise more than half of the whole genome. Surprisingly, the repeats comprise a very limited set of 79–97 bp sequences; in part the genome is thus a relatively uniform sequence space interrupted by coding sequences. Our genomic sequence survey (GSS) represents the largest genomic data set of a dinoflagellate to date. Alexandrium ostenfeldii is a typical dinoflagellate with respect to its transcriptome and mRNA transposition but demonstrates Alexandrium-like stop codon usage. The large portion of repetitive sequences and the organization within the genome is in agreement with several other studies on dinoflagellates using different approaches. It remains to be determined whether this unusual composition is directly correlated to the exceptionally genome organization of dinoflagellates with a low amount of histones and histone-like proteins

APBSmem: A Graphical Interface for Electrostatic Calculations at the Membrane

Electrostatic forces are one of the primary determinants of molecular interactions. They help guide the folding of proteins, increase the binding of one protein to another and facilitate protein-DNA and protein-ligand binding. A popular method for computing the electrostatic properties of biological systems is to numerically solve the Poisson-Boltzmann (PB) equation, and there are several easy-to-use software packages available that solve the PB equation for soluble proteins. Here we present a freely available program, called APBSmem, for carrying out these calculations in the presence of a membrane. The Adaptive Poisson-Boltzmann Solver (APBS) is used as a back-end for solving the PB equation, and a Java-based graphical user interface (GUI) coordinates a set of routines that introduce the influence of the membrane, determine its placement relative to the protein, and set the membrane potential. The software Jmol is embedded in the GUI to visualize the protein inserted in the membrane before the calculation and the electrostatic potential after completing the computation. We expect that the ease with which the GUI allows one to carry out these calculations will make this software a useful resource for experimenters and computational researchers alike. Three examples of membrane protein electrostatic calculations are carried out to illustrate how to use APBSmem and to highlight the different quantities of interest that can be calculated

Characterization of the clinical and immunologic phenotype and management of 157 individuals with 56 distinct heterozygous NFKB1 mutations

Background: An increasing number of NFKB1 variants are being identified in patients with heterogeneous immunologic phenotypes. Objective: To characterize the clinical and cellular phenotype as well as the management of patients with heterozygous NFKB1 mutations. Methods: In a worldwide collaborative effort, we evaluated 231 individuals harboring 105 distinct heterozygous NFKB1 variants. To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-kappa B) signaling. Results: We classified 56 of the 105 distinct NFKB1 variants in 157 individuals from 68 unrelated families as pathogenic. Incomplete clinical penetrance (70%) and age-dependent severity of NFKB1-related phenotypes were observed. The phenotype included hypogammaglobulinemia (88.9%), reduced switched memory B cells (60.3%), and respiratory (83%) and gastrointestinal (28.6%) infections, thus characterizing the disorder as primary immunodeficiency. However, the high frequency of autoimmunity (57.4%), lymphoproliferation (52.4%), noninfectious enteropathy (23.1%), opportunistic infections (15.7%), autoinflammation (29.6%), and malignancy (16.8%) identified NF-kappa B1-related disease as an inborn error of immunity with immune dysregulation, rather than a mere primary immunodeficiency. Current treatment includes immunoglobulin replacement and immunosuppressive agents. Conclusions: We present a comprehensive clinical overview of the NF-kappa B1-related phenotype, which includes immunodeficiency, autoimmunity, autoinflammation, and cancer. Because of its multisystem involvement, clinicians from each and every medical discipline need to be made aware of this autosomal-dominant disease. Hematopoietic stem cell transplantation and NF-kappa B1 pathway-targeted therapeutic strategies should be considered in the future.Peer reviewe

First year of energetic particle measurements in the inner heliosphere with Solar Orbiter's Energetic Particle Detector

Context. Solar Orbiter strives to unveil how the Sun controls and shapes the heliosphere and fills it with energetic particle radiation. To this end, its Energetic Particle Detector (EPD) has now been in operation, providing excellent data, for just over a year.Aims. EPD measures suprathermal and energetic particles in the energy range from a few keV up to (near-) relativistic energies (few MeV for electrons and about 500 MeV nuc(-1) for ions). We present an overview of the initial results from the first year of operations and we provide a first assessment of issues and limitations. In addition, we present areas where EPD excels and provides opportunities for significant scientific progress in understanding how our Sun shapes the heliosphere.Methods. We used the solar particle events observed by Solar Orbiter on 21 July and between 10 and 11 December 2020 to discuss the capabilities, along with updates and open issues related to EPD on Solar Orbiter. We also give some words of caution and caveats related to the use of EPD-derived data.Results. During this first year of operations of the Solar Orbiter mission, EPD has recorded several particle events at distances between 0.5 and 1 au from the Sun. We present dynamic and time-averaged energy spectra for ions that were measured with a combination of all four EPD sensors, namely: the SupraThermal Electron and Proton sensor (STEP), the Electron Proton Telescope (EPT), the Suprathermal Ion Spectrograph (SIS), and the High-Energy Telescope (HET) as well as the associated energy spectra for electrons measured with STEP and EPT. We illustrate the capabilities of the EPD suite using the 10 and 11 December 2020 solar particle event. This event showed an enrichment of heavy ions as well as He-3, for which we also present dynamic spectra measured with SIS. The high anisotropy of electrons at the onset of the event and its temporal evolution is also shown using data from these sensors. We discuss the ongoing in-flight calibration and a few open instrumental issues using data from the 21 July and the 10 and 11 December 2020 events and give guidelines and examples for the usage of the EPD data. We explain how spacecraft operations may affect EPD data and we present a list of such time periods in the appendix. A list of the most significant particle enhancements as observed by EPT during this first year is also provided.</p