Molecular Epidemiological Investigation of a Nosocomial Cluster of C. auris: Evidence of Recent Emergence in Italy and Ease of Transmission during the COVID-19 Pandemic

Candida auris is an emerging MDR pathogen raising major concerns worldwide. In Italy, it was first and only identified in July 2019 in our hospital (San Martino Hospital, Genoa), where infection or colonization cases have been increasingly recognized during the following months. To gain insights into the introduction, transmission dynamics, and resistance traits of this fungal pathogen, consecutive C. auris isolates collected from July 2019 to May 2020 (n = 10) were subjected to whole-genome sequencing (WGS) and antifungal susceptibility testing (AST); patients' clinical and trace data were also collected. WGS resolved all isolates within the genetic clade I (South Asian) and showed that all but one were part of a cluster likely stemming from the index case. Phylogenetic molecular clock analyses predicted a recent introduction (May 2019) in the hospital setting and suggested that most transmissions were associated with a ward converted to a COVID-19-dedicated ICU during the pandemic. All isolates were resistant to amphotericin B, voriconazole, and fluconazole at high-level, owing to mutations in ERG11(K143R) and TACB1(A640V). Present data demonstrated that the introduction of MDR C. auris in Italy was a recent event and suggested that its spread could have been facilitated by the COVID-19 pandemic. Continued efforts to implement stringent infection prevention and control strategies are warranted to limit the spread of this emerging pathogen within the healthcare system

Neuronal Expression of GalNAc Transferase Is Sufficient to Prevent the Age-Related Neurodegenerative Phenotype of Complex Ganglioside-Deficient Mice

Gangliosides are widely expressed sialylated glycosphingolipids with multifunctional properties in different cell types and organs. In the nervous system, they are highly enriched in both glial and neuronal membranes. Mice lacking complex gangliosides attributable to targeted ablation of the B4galnt1 gene that encodes β-1,4-N-acetylegalactosaminyltransferase 1 (GalNAc–transferase; GalNAcT−/−) develop normally before exhibiting an age-dependent neurodegenerative phenotype characterized by marked behavioral abnormalities, central and peripheral axonal degeneration, reduced myelin volume, and loss of axo-glial junction integrity. The cell biological substrates underlying this neurodegeneration and the relative contribution of either glial or neuronal gangliosides to the process are unknown. To address this, we generated neuron-specific and glial-specific GalNAcT rescue mice crossed on the global GalNAcT−/− background [GalNAcT−/−-Tg(neuronal) and GalNAcT−/−-Tg(glial)] and analyzed their behavioral, morphological, and electrophysiological phenotype. Complex gangliosides, as assessed by thin-layer chromatography, mass spectrometry, GalNAcT enzyme activity, and anti-ganglioside antibody (AgAb) immunohistology, were restored in both neuronal and glial GalNAcT rescue mice. Behaviorally, GalNAcT−/−-Tg(neuronal) retained a normal “wild-type” (WT) phenotype throughout life, whereas GalNAcT−/−-Tg(glial) resembled GalNAcT−/− mice, exhibiting progressive tremor, weakness, and ataxia with aging. Quantitative electron microscopy demonstrated that GalNAcT−/− and GalNAcT−/−-Tg(glial) nerves had significantly increased rates of axon degeneration and reduced myelin volume, whereas GalNAcT−/−-Tg(neuronal) and WT appeared normal. The increased invasion of the paranode with juxtaparanodal Kv1.1, characteristically seen in GalNAcT−/− and attributed to a breakdown of the axo-glial junction, was normalized in GalNAcT−/−-Tg(neuronal) but remained present in GalNAcT−/−-Tg(glial) mice. These results indicate that neuronal rather than glial gangliosides are critical to the age-related maintenance of nervous system integrity

Serum anti‐GM2 and anti‐GalNAc‐GD1a ganglioside IgG antibodies are biomarkers for immune‐mediated polyneuropathies in cats

Background and Aims: Recent work identified anti-GM2 and anti-GalNAc-GD1a IgG ganglioside antibodies as biomarkers in dogs clinically diagnosed with acute canine polyradiculoneuritis, in turn considered a canine equivalent of Guillain-Barré syndrome. This study aims to investigate the serum prevalence of similar antibodies in cats clinically diagnosed with immune-mediated polyneuropathies. Methods: The sera from 41 cats clinically diagnosed with immune-mediated polyneuropathies (IPN), 9 cats with other neurological or neuromuscular disorders (ONM) and 46 neurologically normal cats (CTRL) were examined for the presence of IgG antibodies against glycolipids GM1, GM2, GD1a, GD1b, GalNAc-GD1a, GA1, SGPG, LM1, galactocerebroside and sulphatide. Results: A total of 29/41 IPN-cats had either anti-GM2 or anti-GalNAc-GD1a IgG antibodies, with 24/29 cats having both. Direct comparison of anti-GM2 (sensitivity: 70.7%; specificity: 78.2%) and anti-GalNAc-GD1a (sensitivity: 70.7%; specificity: 70.9%) antibodies narrowly showed anti-GM2 IgG antibodies to be the better marker for identifying IPN-cats when compared to the combined ONM and CTRL groups (p=0.049). Anti-GA1 and/or anti-sulphatide IgG antibodies were ubiquitously present across all sample groups, whereas antibodies against GM1, GD1a, GD1b, SGPG, LM1 and galactocerebroside were overall only rarely observed. Interpretation: Anti-GM2 and anti-GalNAc-GD1a IgG antibodies may serve as serum biomarkers for immune-mediated polyneuropathies in cats, as previously observed in dogs and humans

The microbiology and pathogenesis of nonfermenting Gram-negative infections

Purpose of reviewThis review provides an overview of most recent evidence about pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant nonfermenting Gram-negative bacteria (NFGNB).The growing clinical importance of NFGNB as important opportunistic pathogens causing difficult-to-treat infections in a fragile patients' population in stressed by numerous studies. Identification of novel virulence factors and deciphering of their mechanisms of action have greatly furthered our understanding of NFGNB pathogenesis, revealing that each pathogen-specific armamentarium of virulence factors (adhesins, motility, capsule, biofilm, lipopolysaccharide, exotoxins, exoenzymes, secretion systems, siderophores) can be likely responsible for the difference in the pathophysiology even in the context of a similar infection site. Emerging evidence of the immunomodulatory effect of some virulence factors is also acknowledged.NFGNB continue to be a serious global problem as cause of life-threatening opportunistic infections, owing to a highly heterogeneous content of virulence factors and their extensive number of intrinsic resistance mechanisms. Further efforts in development of novel effective antimicrobials and of alternative strategies targeting key virulence factors are warranted.Papers of particular interest, published within the annual period of review, have been highlighted as:Nonfermenting Gram-negative bacilli (NFGNB) are a group of taxonomically heterogeneous aerobic, nonspore-forming bacilli that are unable to ferment carbohydrates and derive energy by using simple carbohydrates in an oxidative fashion [1]. These organisms are ubiquitously distributed in the environment as saprophytes, typically inhabiting moist ecosystems (e.g. water, soil, plants), and some are recognized as member of the healthy human gut microbiota [2-4].Over past decades, however, NFGNB have emerged as important nosocomial pathogens, owing to their ability to persist in the hospital environment (e.g. sinks, respirators, nebulizers, dialysate, saline, catheters and other devices surfaces) and intrinsic antimicrobial resistance phenotypes (Table 1). As such, this group of microorganisms is increasingly recognized as cause of difficult-to-treat, life-threatening infections in fragile patients [e.g. neutropenic and intensive care unit patients, cystic fibrosis (CF)] [5], being a prevalent cause of nosocomial pneumonia and secondary bacteraemia (which can also develop from contaminated health-care equipment and surgical site infections) [6]. no caption availableOverview of virulence factors and intrinsic antimicrobial resistance profiles of P. aeruginosa, S. maltophilia, A. baumannii, B. cepacia complexAMP, ampicillin; AMX, amoxicillin; AMC, ampicillin/clavulanic acid; AMS, ampicillin/sulbactam; TIC, ticarcillin; TIM, ticarcillin/clavulanic acid; PIP, piperacillin; TZP, piperacillin/tazobactam; IMI, imipenem; MEM, meropenem; AZT, aztreonam; CTX, cefotaxime; CRO, ceftriaxone; ETP, ertapenem; CM, chloramphenicol; TET, tetracycline; TIG, tigecycline; TMP, trimethoprim; KAN, kanamycin; AGs: all aminoglycosides; FOS, Fosfomycin; CIP, ciprofloxacin; COL, colistin; OMVs: outer-membrane vescicles; LPS, lipopolysaccharide.A. baumannnii, A. pittii, A. nosocomialis.Here, we provide an overview of the pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B.cepacia complex, among the most clinically relevant NFGNB.Purpose of reviewThis review provides an overview of most recent evidence about pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant nonfermenting Gram-negative bacteria (NFGNB).The growing clinical importance of NFGNB as important opportunistic pathogens causing difficult-to-treat infections in a fragile patients' population in stressed by numerous studies. Identification of novel virulence factors and deciphering of their mechanisms of action have greatly furthered our understanding of NFGNB pathogenesis, revealing that each pathogen-specific armamentarium of virulence factors (adhesins, motility, capsule, biofilm, lipopolysaccharide, exotoxins, exoenzymes, secretion systems, siderophores) can be likely responsible for the difference in the pathophysiology even in the context of a similar infection site. Emerging evidence of the immunomodulatory effect of some virulence factors is also acknowledged.NFGNB continue to be a serious global problem as cause of life-threatening opportunistic infections, owing to a highly heterogeneous content of virulence factors and their extensive number of intrinsic resistance mechanisms. Further efforts in development of novel effective antimicrobials and of alternative strategies targeting key virulence factors are warranted.Papers of particular interest, published within the annual period of review, have been highlighted as:Nonfermenting Gram-negative bacilli (NFGNB) are a group of taxonomically heterogeneous aerobic, nonspore-forming bacilli that are unable to ferment carbohydrates and derive energy by using simple carbohydrates in an oxidative fashion [1]. These organisms are ubiquitously distributed in the environment as saprophytes, typically inhabiting moist ecosystems (e.g. water, soil, plants), and some are recognized as member of the healthy human gut microbiota [2-4].Over past decades, however, NFGNB have emerged as important nosocomial pathogens, owing to their ability to persist in the hospital environment (e.g. sinks, respirators, nebulizers, dialysate, saline, catheters and other devices surfaces) and intrinsic antimicrobial resistance phenotypes (Table 1). As such, this group of microorganisms is increasingly recognized as cause of difficult-to-treat, life-threatening infections in fragile patients [e.g. neutropenic and intensive care unit patients, cystic fibrosis (CF)] [5], being a prevalent cause of nosocomial pneumonia and secondary bacteraemia (which can also develop from contaminated health-care equipment and surgical site infections) [6]. no caption availableOverview of virulence factors and intrinsic antimicrobial resistance profiles of P. aeruginosa, S. maltophilia, A. baumannii, B. cepacia complexAMP, ampicillin; AMX, amoxicillin; AMC, ampicillin/clavulanic acid; AMS, ampicillin/sulbactam; TIC, ticarcillin; TIM, ticarcillin/clavulanic acid; PIP, piperacillin; TZP, piperacillin/tazobactam; IMI, imipenem; MEM, meropenem; AZT, aztreonam; CTX, cefotaxime; CRO, ceftriaxone; ETP, ertapenem; CM, chloramphenicol; TET, tetracycline; TIG, tigecycline; TMP, trimethoprim; KAN, kanamycin; AGs: all aminoglycosides; FOS, Fosfomycin; CIP, ciprofloxacin; COL, colistin; OMVs: outer-membrane vescicles; LPS, lipopolysaccharide.A. baumannnii, A. pittii, A. nosocomialis.Here, we provide an overview of the pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant NFGNB.Purpose of reviewThis review provides an overview of most recent evidence about pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant nonfermenting Gram-negative bacteria (NFGNB).The growing clinical importance of NFGNB as important opportunistic pathogens causing difficult-to-treat infections in a fragile patients' population in stressed by numerous studies. Identification of novel virulence factors and deciphering of their mechanisms of action have greatly furthered our understanding of NFGNB pathogenesis, revealing that each pathogen-specific armamentarium of virulence factors (adhesins, motility, capsule, biofilm, lipopolysaccharide, exotoxins, exoenzymes, secretion systems, siderophores) can be likely responsible for the difference in the pathophysiology even in the context of a similar infection site. Emerging evidence of the immunomodulatory effect of some virulence factors is also acknowledged.NFGNB continue to be a serious global problem as cause of life-threatening opportunistic infections, owing to a highly heterogeneous content of virulence factors and their extensive number of intrinsic resistance mechanisms. Further efforts in development of novel effective antimicrobials and of alternative strategies targeting key virulence factors are warranted.Papers of particular interest, published within the annual period of review, have been highlighted as:Nonfermenting Gram-negative bacilli (NFGNB) are a group of taxonomically heterogeneous aerobic, nonspore-forming bacilli that are unable to ferment carbohydrates and derive energy by using simple carbohydrates in an oxidative fashion [1]. These organisms are ubiquitously distributed in the environment as saprophytes, typically inhabiting moist ecosystems (e.g. water, soil, plants), and some are recognized as member of the healthy human gut microbiota [2-4].Over past decades, however, NFGNB have emerged as important nosocomial pathogens, owing to their ability to persist in the hospital environment (e.g. sinks, respirators, nebulizers, dialysate, saline, catheters and other devices surfaces) and intrinsic antimicrobial resistance phenotypes (Table 1). As such, this group of microorganisms is increasingly recognized as cause of difficult-to-treat, life-threatening infections in fragile patients [e.g. neutropenic and intensive care unit patients, cystic fibrosis (CF)] [5], being a prevalent cause of nosocomial pneumonia and secondary bacteraemia (which can also develop from contaminated health-care equipment and surgical site infections) [6]. no caption availableOverview of virulence factors and intrinsic antimicrobial resistance profiles of P. aeruginosa, S. maltophilia, A. baumannii, B.cepacia complexAMP, ampicillin; AMX, amoxicillin; AMC, ampicillin/clavulanic acid; AMS, ampicillin/sulbactam; TIC, ticarcillin; TIM, ticarcillin/clavulanic acid; PIP, piperacillin; TZP, piperacillin/tazobactam; IMI, imipenem; MEM, meropenem; AZT, aztreonam; CTX, cefotaxime; CRO, ceftriaxone; ETP, ertapenem; CM, chloramphenicol; TET, tetracycline; TIG, tigecycline; TMP, trimethoprim; KAN, kanamycin; AGs: all aminoglycosides; FOS, Fosfomycin; CIP, ciprofloxacin; COL, colistin; OMVs: outer-membrane vescicles; LPS, lipopolysaccharide.A. baumannnii, A. pittii, A. nosocomialis.Here, we provide an overview of the pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant NFGNB.Purpose of reviewThis review provides an overview of most recent evidence about pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant nonfermenting Gram-negative bacteria (NFGNB).The growing clinical importance of NFGNB as important opportunistic pathogens causing difficult-to-treat infections in a fragile patients' population in stressed by numerous studies. Identification of novel virulence factors and deciphering of their mechanisms of action have greatly furthered our understanding of NFGNB pathogenesis, revealing that each pathogen-specific armamentarium of virulence factors (adhesins, motility, capsule, biofilm, lipopolysaccharide, exotoxins, exoenzymes, secretion systems, siderophores) can be likely responsible for the difference in the pathophysiology even in the context of a similar infection site. Emerging evidence of the immunomodulatory effect of some virulence factors is also acknowledged.NFGNB continue to be a serious global problem as cause of life-threatening opportunistic infections, owing to a highly heterogeneous content of virulence factors and their extensive number of intrinsic resistance mechanisms. Further efforts in development of novel effective antimicrobials and of alternative strategies targeting key virulence factors are warranted.Papers of particular interest, published within the annual period of review, have been highlighted as:Nonfermenting Gram-negative bacilli (NFGNB) are a group of taxonomically heterogeneous aerobic, nonspore-forming bacilli that are unable to ferment carbohydrates and derive energy by using simple carbohydrates in an oxidative fashion [1]. These organisms are ubiquitously distributed in the environment as saprophytes, typically inhabiting moist ecosystems (e.g. water, soil, plants), and some are recognized as member of the healthy human gut microbiota [2-4].Over past decades, however, NFGNB have emerged as important nosocomial pathogens, owing to their ability to persist in the hospital environment (e.g. sinks, respirators, nebulizers, dialysate, saline, catheters and other devices surfaces) and intrinsic antimicrobial resistance phenotypes (Table 1). As such, this group of microorganisms is increasingly recognized as cause of difficult-to-treat, life-threatening infections in fragile patients [e.g. neutropenic and intensive care unit patients, cystic fibrosis (CF)] [5], being a prevalent cause of nosocomial pneumonia and secondary bacteraemia (which can also develop from contaminated health-care equipment and surgical site infections) [6].no caption availableOverview of virulence factors and intrinsic antimicrobial resistance profiles of P. aeruginosa, S. maltophilia, A. baumannii, B. cepacia complexAMP, ampicillin; AMX, amoxicillin; AMC, ampicillin/clavulanic acid; AMS, ampicillin/sulbactam; TIC, ticarcillin; TIM, ticarcillin/clavulanic acid; PIP, piperacillin; TZP, piperacillin/tazobactam; IMI, imipenem; MEM, meropenem; AZT, aztreonam; CTX, cefotaxime; CRO, ceftriaxone; ETP, ertapenem; CM, chloramphenicol; TET, tetracycline; TIG, tigecycline; TMP, trimethoprim; KAN, kanamycin; AGs: all aminoglycosides; FOS, Fosfomycin; CIP, ciprofloxacin; COL, colistin; OMVs: outer-membrane vescicles; LPS, lipopolysaccharide.A. baumannnii, A. pittii, A. nosocomialis.Here, we provide an overview of the pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant NFGNB.Purpose of reviewThis review provides an overview of most recent evidence about pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant nonfermenting Gram-negative bacteria (NFGNB).The growing clinical importance of NFGNB as important opportunistic pathogens causing difficult-to-treat infections in a fragile patients' population in stressed by numerous studies. Identification of novel virulence factors and deciphering of their mechanisms of action have greatly furthered our understanding of NFGNB pathogenesis, revealing that each pathogen-specific armamentarium of virulence factors (adhesins, motility, capsule, biofilm, lipopolysaccharide, exotoxins, exoenzymes, secretion systems, siderophores) can be likely responsible for the difference in the pathophysiology even in the context of a similar infection site. Emerging evidence of the immunomodulatory effect of some virulence factors is also acknowledged.NFGNB continue to be a serious global problem as cause of life-threatening opportunistic infections, owing to a highly heterogeneous content of virulence factors and their extensive number of intrinsic resistance mechanisms. Further efforts in development of novel effective antimicrobials and of alternative strategies targeting key virulence factors are warranted.Papers of particular interest, published within the annual period of review, have been highlighted as:Nonfermenting Gram-negative bacilli (NFGNB) are a group of taxonomically heterogeneous aerobic, nonspore-forming bacilli that are unable to ferment carbohydrates and derive energy by using simple carbohydrates in an oxidative fashion [1]. These organisms are ubiquitously distributed in the environment as saprophytes, typically inhabiting moist ecosystems (e.g. water, soil, plants), and some are recognized as member of the healthy human gut microbiota [2-4].Over past decades, however, NFGNB have emerged as important nosocomial pathogens, owing to their ability to persist in the hospital environment (e.g. sinks, respirators, nebulizers, dialysate, saline, catheters and other devices surfaces) and intrinsic antimicrobial resistance phenotypes (Table 1). As such, this group of microorganisms is increasingly recognized as cause of difficult-to-treat, life-threatening infections in fragile patients [e.g.neutropenic and intensive care unit patients, cystic fibrosis (CF)] [5], being a prevalent cause of nosocomial pneumonia and secondary bacteraemia (which can also develop from contaminated health-care equipment and surgical site infections) [6]. no caption availableOverview of virulence factors and intrinsic antimicrobial resistance profiles of P. aeruginosa, S. maltophilia, A. baumannii, B. cepacia complexAMP, ampicillin; AMX, amoxicillin; AMC, ampicillin/clavulanic acid; AMS, ampicillin/sulbactam; TIC, ticarcillin; TIM, ticarcillin/clavulanic acid; PIP, piperacillin; TZP, piperacillin/tazobactam; IMI, imipenem; MEM, meropenem; AZT, aztreonam; CTX, cefotaxime; CRO, ceftriaxone; ETP, ertapenem; CM, chloramphenicol; TET, tetracycline; TIG, tigecycline; TMP, trimethoprim; KAN, kanamycin; AGs: all aminoglycosides; FOS, Fosfomycin; CIP, ciprofloxacin; COL, colistin; OMVs: outer-membrane vescicles; LPS, lipopolysaccharide.A. baumannnii, A. pittii, A. nosocomialis.Here, we provide an overview of the pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant NFGNB.Purpose of reviewThis review provides an overview of most recent evidence about pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant nonfermenting Gram-negative bacteria (NFGNB).The growing clinical importance of NFGNB as important opportunistic pathogens causing difficult-to-treat infections in a fragile patients' population in stressed by numerous studies. Identification of novel virulence factors and deciphering of their mechanisms of action have greatly furthered our understanding of NFGNB pathogenesis, revealing that each pathogen-specific armamentarium of virulence factors (adhesins, motility, capsule, biofilm, lipopolysaccharide, exotoxins, exoenzymes, secretion systems, siderophores) can be likely responsible for the difference in the pathophysiology even in the context of a similar infection site. Emerging evidence of the immunomodulatory effect of some virulence factors is also acknowledged.NFGNB continue to be a serious global problem as cause of life-threatening opportunistic infections, owing to a highly heterogeneous content of virulence factors and their extensive number of intrinsic resistance mechanisms. Further efforts in development of novel effective antimicrobials and of alternative strategies targeting key virulence factors are warranted.Papers of particular interest, published within the annual period of review, have been highlighted as:Nonfermenting Gram-negative bacilli (NFGNB) are a group of taxonomically heterogeneous aerobic, nonspore-forming bacilli that are unable to ferment carbohydrates and derive energy by using simple carbohydrates in an oxidative fashion [1]. These organisms are ubiquitously distributed in the environment as saprophytes, typically inhabiting moist ecosystems (e.g. water, soil, plants), and some are recognized as member of the healthy human gut microbiota [2-4].Over past decades, however, NFGNB have emerged as important nosocomial pathogens, owing to their ability to persist in the hospital environment (e.g. sinks, respirators, nebulizers, dialysate, saline, catheters and other devices surfaces) and intrinsic antimicrobial resistance phenotypes (Table 1).As such, this group of microorganisms is increasingly recognized as cause of difficult-to-treat, life-threatening infections in fragile patients [e.g. neutropenic and intensive care unit patients, cystic fibrosis (CF)] [5], being a prevalent cause of nosocomial pneumonia and secondary bacteraemia (which can also develop from contaminated health-care equipment and surgical site infections) [6]. no caption availableOverview of virulence factors and intrinsic antimicrobial resistance profiles of P. aeruginosa, S. maltophilia, A. baumannii, B. cepacia complexAMP, ampicillin; AMX, amoxicillin; AMC, ampicillin/clavulanic acid; AMS, ampicillin/sulbactam; TIC, ticarcillin; TIM, ticarcillin/clavulanic acid; PIP, piperacillin; TZP, piperacillin/tazobactam; IMI, imipenem; MEM, meropenem; AZT, aztreonam; CTX, cefotaxime; CRO, ceftriaxone; ETP, ertapenem; CM, chloramphenicol; TET, tetracycline; TIG, tigecycline; TMP, trimethoprim; KAN, kanamycin; AGs: all aminoglycosides; FOS, Fosfomycin; CIP, ciprofloxacin; COL, colistin; OMVs: outer-membrane vescicles; LPS, lipopolysaccharide.A. baumannnii, A. pittii, A. nosocomialis.Here, we provide an overview of the pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aerugi

The design of a digital single-molecule detection platform, with direct application to single cell analysis

We have designed and developed a novel form of biosensor with implications to both the understanding of the mechanistics of the cell function and as a biomedical diagnostic tool. As part of a platform of technologies orientated to single cell proteomics, this project focuses on the development of single molecule microarrays (SMM), which is intended to produce proteome snap shots of individual cells. The single cell proteomics platform includes technologies for microfluidics based live cell analysis, manipulation, lysis and analysis of the proteome of a single cell. Analysis of single cells to high and detailed resolution will provide both quantitative and qualitative information on discrete events and protein dynamics, usually overlooked through ensemble measurements of large populations of inhomogeneous cells. With the aim of developing a quantitative and qualitative tool oriented to single cell proteomics; we present an antibody microarray capable of simultaneous quantification of multiple proteins to the single molecule level. The principle enhancements of design enabling the capabilities described are based around single molecule detection of fluorescently labelled analytes bound to affinity patches of antibodies; the affinity patches are limited to the microscope field of view and incorporated into microfluidic devices, detection is performed with a single resolution through the use of total internal reflection fluorescence (TIRF) microscopy. The cell is handled and lysed in a microfluidic device to minimize dilution of the sample, so that the greater majority of analyte is bound to the sensing surface at equilibrium and so detectable at the surface through TIRF evanescent wave. This technology also bears significance for the detection of many forms of analyte, such as glycan profiling, direct mRNA quantification and the analysis of post translational modification (PTM). The SMM produces rapid snap shots of a proteome; this makes it suitable for rapidly changing and dynamic cell signalling cascades, of which PTM makes a significant contribution to cell fate. We present here the basic principles of design and the initial testing of the design and current setup. Also discussed are intensions and capabilities for the technology, as well inevitable potential pitfalls and intrinsic limitations.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Delayed hospital presentation in patients who have had acute myocardial infarction.

BACKGROUND: In patients who have had acute myocardial infarction, the delay between the onset of symptoms and hospital presentation is a critical factor in determining the initial management strategy and outcomes of treatment. OBJECTIVE: To examine the determinants of delayed hospital presentation in patients who have had acute myocardial infarction. DESIGN: Retrospective chart review. SETTING: 37 hospitals in Minnesota. PATIENTS: 2409 persons hospitalized with acute myocardial infarction between October 1992 and July 1993. MAIN OUTCOME MEASURE: Hospital presentation delayed more than 6 hours after the onset of symptoms of acute myocardial infarction. RESULTS: Information on length of delay was available for 2404 patients. Of these patients, 969 (40%) delayed presentation to the hospital for more than 6 hours after the onset of symptoms. Factors associated with prolonged delay included advanced age and female sex. The presence of chest discomfort and a history of mechanical revascularization significantly reduced the risk for prolonged delay. Risk for delay was greatest during the evening and early morning hours (6:00 p.m. to 6:00 a.m.) Patients with a history of hypertension were more likely to delay presentation. Only 42% of all patients hospitalized with acute myocardial infarction had used emergency medical transport services. CONCLUSIONS: Patients who have had acute myocardial infarction often delay hospital presentation. Educational interventions that encourage the prompt use of emergency medical transport services and target specific patient populations, such as elderly persons, women, and persons with cardiac risk factors, may be most successful in reducing the length of delay and improving the outcomes of patients with acute myocardial infarction