A return to the pre-antimicrobial era? Baker, Stephen
Science (American Association for the Advancement of Science),
03/2015, Letnik:
347, Številka:
6226
Journal Article
Recenzirano
After many years out of the limelight, antimicrobial resistance (AMR) in bacteria is firmly back on the international political and scientific agenda (1, 2). The potential impact of AMR on ...hospital-acquired bacterial infections such as Staphylococcus aureus and Acinetobacter baumannii in higher-income countries has created both fear and a surge of motivation aimed at providing new solutions for the problem (3, 4). The political will and momentum to tackle AMR lies in higher-income countries, but the medical, social, and economic effects of AMR are likely to be felt more in lower-income countries, particularly those in South and Southeast Asia and in sub-Saharan Africa. The identification and development of new drugs is a potential solution but is challenging and costly; any novel therapies introduced into low-income settings without a suitable infrastructure to understand and prevent the rapid development of resistance will likely be expensive and futile.
Salmonella enterica serovar Typhi, the cause of typhoid, is host restricted to humans. S. Typhi has a monophyletic population structure, indicating that typhoid in humans is a relatively new disease. ...Antimicrobial usage is reshaping the current S. Typhi global population and may be driving the emergence of a specific haplotype, H58, that is well adapted to transmission in modern settings and is able to resist antimicrobial killing more efficiently than other S. Typhi. Evidence gathered through genomics and functional studies using the mouse and in vitro cell systems, together with clinical investigations, has provided insight into the mechanisms that underpin the pathogenesis of human typhoid and host restriction. Here we review the latest scientific advances in typhoid research and discuss how these novel approaches are changing our understanding of the disease.
Technologies to address antimicrobial resistance Baker, Stephen J.; Payne, David J.; Rappuoli, Rino ...
Proceedings of the National Academy of Sciences - PNAS,
12/2018, Letnik:
115, Številka:
51
Journal Article
Recenzirano
Odprti dostop
Bacterial infections have been traditionally controlled by antibiotics and vaccines, and these approaches have greatly improved health and longevity. However, multiple stakeholders are declaring that ...the lack of new interventions is putting our ability to prevent and treat bacterial infections at risk. Vaccine and antibiotic approaches still have the potential to address this threat. Innovative vaccine technologies, such as reverse vaccinology, novel adjuvants, and rationally designed bacterial outer membrane vesicles, together with progress in polysaccharide conjugation and antigen design, have the potential to boost the development of vaccines targeting several classes of multidrug-resistant bacteria. Furthermore, new approaches to deliver small-molecule antibacterials into bacteria, such as hijacking active uptake pathways and potentiator approaches, along with a focus on alternative modalities, such as targeting host factors, blocking bacterial virulence factors, monoclonal antibodies, and microbiome interventions, all have potential. Both vaccines and antibacterial approaches are needed to tackle the global challenge of antimicrobial resistance (AMR), and both areas have the underpinning science to address this need. However, a concerted research agenda and rethinking of the value society puts on interventions that save lives, by preventing or treating life-threatening bacterial infections, are needed to bring these ideas to fruition.
The Fiction of Postmodernity is a significant and accessible new study of the relation of postmodern fiction to theories of the postmodern. Contemporary works of fiction by novelists such as Don ...DeLillo, Toni Morrison, Salman Rushdie, Thomas Pynchon and Martin Amis are viewed in relation to critiques of the 'culture industry', analyses of the 'postmodern condition' and theories of simulacra. The work of influential theorists of the postmodern - such as Theodor Adorno, Jean-François Lyotard, Fredric Jameson and Jean Baudrillard - is explained and compared.The book offers descriptions of the postmodern from both the Marxist critical tradition and from the perspective of postmarxism. Key features in both these definitions are explained in relation to modernist and postmodern works of fiction. Issues relating to the postmodern representation of history and the development of a postmodern politics are also addressed in relation to works of contemporary fiction.Key Features*Substantial readings of fiction by major contemporary authors (e.g. Thomas Pynchon, Salman Rushdie, Don DeLillo)*Introduces influential theories of the postmodern (Fredric Jameson, Jean-François Lyotard, Jean Baudrillard)*Analysis of the relationships of modernism and the avant-garde to postmodernism*Focuses on the critical potential of postmodernism and postmodern fiction
Background Few studies have evaluated both the overall effect of ICU telemedicine programs and the effect of individual components of the intervention on clinical outcomes. Methods The effects of ...nonrandomized ICU telemedicine interventions on crude and adjusted mortality and length of stay (LOS) were measured. Additionally, individual intervention components related to process and setting of care were evaluated for their association with mortality and LOS. Results Overall, 118,990 adult patients (11,558 control subjects, 107,432 intervention group patients) from 56 ICUs in 32 hospitals from 19 US health-care systems were included. After statistical adjustment, hospital (hazard ratio HR = 0.84; 95% CI, 0.78-0.89; P < .001) and ICU (HR = 0.74; 95% CI, 0.68-0.79; P < .001) mortality in the ICU telemedicine intervention group was significantly better than that of control subjects. Moreover, adjusted hospital LOS was reduced, on average, by 0.5 (95% CI, 0.4-0.5), 1.0 (95% CI, 0.7-1.3), and 3.6 (95% CI, 2.3-4.8) days, and adjusted ICU LOS was reduced by 1.1 (95% CI, 0.8-1.4), 2.5 (95% CI, 1.6-3.4), and 4.5 (95% CI, 1.5-7.2) days among those who stayed in the ICU for ≥ 7, ≥ 14, and ≥ 30 days, respectively. Individual components of the interventions that were associated with lower mortality, reduced LOS, or both included (1) intensivist case review within 1 h of admission, (2) timely use of performance data, (3) adherence to ICU best practices, and (4) quicker alert response times. Conclusions ICU telemedicine interventions, specifically interventions that increase early intensivist case involvement, improve adherence to ICU best practices, reduce response times to alarms, and encourage the use of performance data, were associated with lower mortality and LOS.
The use of boron in small-molecule pharmaceuticals is increasing. Boron's ubiquitous occurrence in nature and the recent success of a boronic acid drug (Velcade®) in the clinic have alleviated many ...concerns over its use in pharmaceuticals. In addition, the unique physicochemical properties of boronic acids make them an attractive addition to the medicinal chemists toolbox. This tutorial review will discuss these properties and potential benefits for anyone interested in finding novel enzyme inhibitors. An exceptional class of boronic acids, the oxaboroles, will be highlighted and their properties and uses will be discussed in detail. Finally, the current paradigm for the reaction of boronic acids with enzyme nucleophiles will be summarized.
Background:
Alterations in muscle protein metabolism underlie age-related muscle atrophy. During periods of muscle disuse, muscle protein synthesis is blunted, and muscle atrophy occurs in young and ...old. The impact of a short reduction in physical activity on muscle protein metabolism in older adults is unknown.
Purpose:
The aim of this study was to investigate the impact of 14 days of reduced daily steps on fasted and fed-state rates of myofibrillar protein synthesis (MPS) to provide insight into the mechanisms for changes in muscle mass and markers of metabolic health.
Methods:
Before and after 14 days of reduced daily step-count, 10 healthy older adults (age, 72 ± 1 y) underwent measures of insulin sensitivity, muscle strength, physical function, and body composition. Using a primed constant infusion of L-ring-13C6phenylalanine with serial muscle biopsies, basal, postabsorptive, and postprandial rates of MPS were determined before and after the 14-day intervention.
Results:
Daily step-count was reduced by approximately 76% to 1413 ± 110 steps per day. Leg fat-free mass was reduced by approximately 3.9% (P < .001). Postabsorptive insulin resistance was increased by approximately 12%, and postprandial insulin sensitivity was reduced by approximately 43% after step reduction (P < .005). Concentrations of TNF-α and C-reactive protein were increased by approximately 12 and 25%, respectively, after step reduction (P < .05). Postprandial rates of MPS were reduced by approximately 26% after the intervention (P = .028), with no difference in postabsorptive rates.
Conclusion:
The present study demonstrates that 14 days of reduced steps in older adults induces small but measurable reductions in muscle mass that appear to be underpinned by reductions in postprandial MPS and are accompanied by impairments in insulin sensitivity and systemic inflammatory markers and postprandial MPS.
D.P. Lawr., L.A. Holland & Trouillas has been associated with recent premature peach tree decline in South Carolina, but very little is known about the pathogen or chemical control options. ...Ninety-three
isolates were collected in 2016 and 2017 from 1-year-old peach wood and symptomatic scaffold limbs, respectively, from orchards in six towns in South Carolina. Six unique genotypes were identified based on substantial ITS1-5.8S-ITS2 sequence variability and classified G1 to G6. Three of the genotypes (G2, G3, and G6) were isolated in high frequency in multiple locations of both years. In addition to the genotypic variation, multiple phenotypes were observed between and within genotype groups. Species identity was determined using additional gene loci: ACT, TUB, and EF, and isolates were found to belong to
for all genotype groups. All tested genotypes were sensitive to thiophanate-methyl (FRAC 1) but exhibited slightly lower sensitivity to propiconazole and difenoconazole (both FRAC 3). Boscalid, fluopyram (both FRAC 7s), azoxystrobin, and pyraclostrobin (both FRAC 11s) were ineffective in vitro at inhibiting mycelial growth of
genotypes. Field inoculation of peach and nectarine trees revealed that all genotypes developed twig cankers with differences in virulence. G1 was most virulent, and G6 was least virulent. This study provides a link between the
genetic variability and virulence and provides fungicide sensitivity information that could be used to improve disease management practices.
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