Plos One
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Antibacterial compounds that affect bacterial viability have traditionally been identified, confirmed, and characterized in standard laboratory media. The historical success of identifying new antibiotics via this route has justifiably established a traditional means of screening for new antimicrobials. The emergence of multi-drug-resistant (MDR) bacterial pathogens has expedited the need for new antibiotics, though many in the industry have questioned the source(s) of these new compounds. ⋯ We also show that these compounds have potent activity on both enzymes that comprise the glyoxylate shunt, a feature that was supported by computational homology modeling. By dual-targeting both enzymes in this pathway, we would expect to see a reduced propensity for resistance development to these compounds. Taken together, these data suggest that understanding the in vivo environment that bacterial pathogens must tolerate, and adjusting the antibacterial screening paradigm to reflect those conditions, could identify novel antibiotics for the treatment of serious MDR pathogens.
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Recent studies suggest that anhedonia, an inability to experience pleasure, can be measured as an enduring trait in non-clinical samples. In order to examine trait anhedonia in a non-clinical sample, we examined the properties of a range of widely used questionnaires capturing anhedonia. ⋯ Concerning the comparison on each item of physical and social anhedonia, the results indicated that individuals with SPD feature exhibited higher than individuals without SPD features on more items of social anhedonia than physical anhedonia scale. These preliminary findings suggested that trait anhedonia can be identified a non-clinical sample. Exploring the demographic and clinical correlates of trait anhedonia in the general population may provide clues to the pathogenesis of psychotic disorder.
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Neutrophils (PMNs) and cytokines have a critical role to play in host defense and systemic inflammatory response syndrome (SIRS). Neutrophil extracellular traps (NETs) have been shown to extracellularly kill pathogens, and inflammatory potential of NETs has been shown. Microbial killing inside the phagosomes or by NETs is mediated by reactive oxygen and nitrogen species (ROS/RNS). ⋯ Treatment of neutrophils from healthy subjects with TNFα, IL-1β, or IL-8 enhanced free radicals generation and NETs formation, which was mediated through the activation of NADPH oxidase and MPO. Pre-incubation of plasma from SIRS with TNFα, IL-1β, or IL-8 antibodies reduced the NETs release. Role of IL-1β, TNFα and IL-8 thus seems to be involved in the enhanced release of NETs in SIRS subjects.
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Although increasing numbers of very elderly patients are requiring intensive care, few large sample studies have investigated ICU admission of very elderly patients. Data on pre triage by physicians from other specialities is limited. This observational cohort study aims at examining inter-hospital variability of ICU admission rates and its association with patients' outcomes. All patients over 80 years possibly qualifying for ICU admission who presented to the emergency departments (ED) of 15 hospitals in the Paris (France) area during a one-year period were prospectively included in the study. Main outcome measures were ICU eligibility, as assessed by the ED and ICU physicians; in-hospital mortality; and vital and functional status 6 months after the ED visit. 2646 patients (median age 86; interquartile range 83-91) were included in the study. 94% of participants completed follow-up (n = 2495). 12.4% (n = 329) of participants were deemed eligible for ICU admission by ED physicians and intensivists. The overall in-hospital and 6-month mortality rates were respectively 27.2% (n = 717) and 50.7% (n = 1264). At six months, 57.5% (n = 1433) of patients had died or had a functional deterioration. Rates of patients deemed eligible for ICU admission ranged from 5.6% to 38.8% across the participating centers, and this variability persisted after adjustment for patients' characteristics. Despite this variability, we found no association between level of ICU eligibility and either in-hospital death or six-month death or functional deterioration. In France, the likelihood that a very elderly person will be admitted to an ICU varies widely from one hospital to another. Influence of intensive care admission on patients' outcome remains unclear.
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Early HIV testing and diagnosis are paramount for increasing treatment initiation among children, necessary for their survival and improved health. However, uptake of pediatric HIV testing is low in high-prevalence areas. We present data on attitudes towards pediatric testing from a nationally representative survey in Zimbabwe. ⋯ Pediatric HIV testing is the essential gateway to prevention and care services. Our data indicate positive attitudes to testing children, suggesting a conducive environment for increasing uptake of pediatric testing in Zimbabwe. However, there is a need to better understand the barriers to pediatric testing, such as stigma and discrimination, and address the gaps in knowledge regarding HIV/AIDS in children.