Stephen Harris

Bio: Stephen Harris is an academic researcher from Waltham Centre for Pet Nutrition. The author has contributed to research in topics: Gingivitis & Periodontitis. The author has an hindex of 21, co-authored 43 publications receiving 1456 citations. Previous affiliations of Stephen Harris include Boston Children's Hospital & University of Leeds.

Global patient outcomes after elective surgery: Prospective cohort study in 27 low-, middle- and high-income countries

Abstract: Background As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. Methods We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. Results A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2–7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. Conclusions Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care.

The hexA gene of Erwinia carotovora encodes a LysR homologue and regulates motility and the expression of multiple virulence determinants.

Abstract: Summary We have identified a gene important for the regulation of exoenzyme virulence factor synthesis in the plant pathogen Erwinia carotovora ssp carotovora (Ecc) and virulence and motility in Erwinia carotovora ssp atroseptica (Eca) This gene, hexA (hyperproduction of exoenzymes), is a close relative of the Erwinia chrysanthemi (Echr ) gene pecT and encodes a member of the LysR family of transcriptional regulators hexA mutants in both Ecc and Eca produce abnormally high levels of the exoenzyme virulence factors pectate lyase, cellulase and protease In addition, Eca hexA mutants show increased expression of the fliA and fliC genes and hypermotility Consistent with a role as a global regulator, expression of hexA from even a low-copy plasmid can suppress exoenzyme production in Ecc and Eca and motility in Eca Production of the quorum-sensing pheromone OHHL in Ecc hexA is higher throughout the growth curve compared with the wild-type strain Overexpression of Ecc hexA also caused widespread effects in several strains of the opportunistic human pathogen, Serratia Low-copy hexA expression resulted in repression of exoenzyme, pigment and antibiotic production and repression of the spreading phenotype Finally, mutations in hexA were shown to increase Ecc or Eca virulence in planta

Effect of exercise on cerebral perfusion in humans at high altitude

Abstract: The effects of submaximal and maximal exercise on cerebral perfusion were assessed using a portable, recumbent cycle ergometer in nine unacclimatized subjects ascending to 5,260 m. At 150 m, mean (SD) cerebral oxygenation (rSO2%) increased during submaximal exercise from 68.4 (SD 2.1) to 70.9 (SD 3.8) (P < 0.0001) and at maximal oxygen uptake (.VO2(max)) to 69.8 (SD 3.1) (P < 0.02). In contrast, at each of the high altitudes studied, rSO2 was reduced during submaximal exercise from 66.2 (SD 2.5) to 62.6 (SD 2.1) at 3,610 m (P < 0.0001), 63.0 (SD 2.1) to 58.9 (SD 2.1) at 4,750 m (P < 0.0001), and 62.4 (SD 3.6) to 61.2 (SD 3.9) at 5,260 m (P < 0.01), and at .VO2(max) to 61.2 (SD 3.3) at 3,610 m (P < 0.0001), to 59.4 (SD 2.6) at 4,750 m (P < 0.0001), and to 58.0 (SD 3.0) at 5,260 m (P < 0.0001). Cerebrovascular resistance tended to fall during submaximal exercise (P = not significant) and rise at .VO2(max), following the changes in arterial oxygen saturation and end-tidal CO(2). Cerebral oxygen delivery was maintained during submaximal exercise at 150 m with a nonsignificant fall at .VO2(max), but at high altitude peaked at 30% of .VO2(max) and then fell progressively at higher levels of exercise. The fall in rSO2 and oxygen delivery during exercise may limit exercise at altitude and is likely to contribute to the problems of acute mountain sickness and high-altitude cerebral edema.

A conserved RNA structure within the HCV IRES eIF3-binding site.

Abstract: The hepatitis C virus (HCV) internal ribosome entry site (IRES) is recognized specifically by the small ribosomal subunit and eukaryotic initiation factor 3 (eIF3) before viral translation initiation. Using extensive mutagenesis and structure probing analysis, we show that the eIF3-binding domain of the HCV IRES contains an internal loop structure (loop IIIb) and an adjacent mismatched helix that are important for IRES-dependent initiation of translation. NMR studies reveal a unique three-dimensional structure for this internal loop that is conserved between viral isolates of varying primary sequence in this region. These data indicate that internal loop IIIb may be an attractive target for structure-based design of new antiviral agents.

Novel quorum-sensing-controlled genes in Erwinia carotovora subsp. carotovora: identification of a fungal elicitor homologue in a soft-rotting bacterium.

Abstract: Seven new genes controlled by the quorum-sensing signal molecule N-(3-oxohexanoyl)-L-homoserine lactone (OHHL) have been identified in Erwinia carotovora subsp. carotovora. Using TnphoA as a mutagen, we enriched for mutants defective in proteins that could play a role in the interaction between E. carotovora subsp. carotovora and its plant hosts, and identified NipEcc and its counterpart in E. carotovora subsp. atroseptica. These are members of a growing family of proteins related to Nep1 from Fusarium oxysporum which can induce necrotic responses in a variety of dicotyledonous plants. NipEcc produced necrosis in tobacco, NipEca affected potato stem rot, and both affected virulence in potato tubers. In E. carotovora subsp. carotovora, nip was shown to be subject to weak repression by the LuxR family regulator, EccR, and may be regulated by the negative global regulator RsmA.

GTDB-Tk: a toolkit to classify genomes with the Genome Taxonomy Database

Abstract: A Summary: The Genome Taxonomy Database Toolkit (GTDB-Tk) provides objective taxonomic assignments for bacterial and archaeal genomes based on the GTDB. GTDB-Tk is computationally efficient and able to classify thousands of draft genomes in parallel. Here we demonstrate the accuracy of the GTDB-Tk taxonomic assignments by evaluating its performance on a phylogenetically diverse set of 10 156 bacterial and archaeal metagenome-assembled genomes.

Flaviviridae :T he Viruses and Their Replication

Abstract: FLAVIVIRUSES 1103 Background and Classification 1103 Structure and Physical Properties of the Virion 1104 Binding and Entry 1105 Genome Structure 1106 Translation and Proteolytic Processing 1107 Features of the Structural Proteins 1108 Features of the Nonstructural Proteins 1109 RNA Replication 1112 Membrane Reorganization and the Compartmentalization of Flavivirus Replication 1112 Assembly and Release of Particles from Flavivirus-infected Cells 1112 Host Resistance to Flavivirus Infection 1113

Quorum‐sensing in Gram‐negative bacteria

Abstract: It has become increasingly and widely recognised that bacteria do not exist as solitary cells, but are colonial organisms that exploit elaborate systems of intercellular communication to facilitate their adaptation to changing environmental conditions. The languages by which bacteria communicate take the form of chemical signals, excreted from the cells, which can elicit profound physiological changes. Many types of signalling molecules, which regulate diverse phenotypes across distant genera, have been described. The most common signalling molecules found in Gram-negative bacteria are N-acyl derivatives of homoserine lactone (acyl HSLs). Modulation of the physiological processes controlled by acyl HSLs (and, indeed, many of the non-acyl HSL-mediated systems) occurs in a cell density- and growth phase-dependent manner. Therefore, the term ‘quorum-sensing’ has been coined to describe this ability of bacteria to monitor cell density before expressing a phenotype. In this paper, we review the current state of research concerning acyl HSL-mediated quorum-sensing. We also describe two non-acyl HSL-based systems utilised by the phytopathogens Ralstonia solanacearum and Xanthomonas campestris.