Scientific reports
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Pentameric ligand-gated ion channels (pLGICs) are targets of general anesthetics, but molecular mechanisms underlying anesthetic action remain debatable. We found that ELIC, a pLGIC from Erwinia chrysanthemi, can be functionally inhibited by isoflurane and other anesthetics. Structures of ELIC co-crystallized with isoflurane in the absence or presence of an agonist revealed double isoflurane occupancies inside the pore near T237(6') and A244(13'). ⋯ Electrophysiology measurements with a single-point mutation at position 6' or 13' support the notion that binding at these sites renders isoflurane inhibition. Molecular dynamics simulations suggested that isoflurane binding was more stable in the resting than in a desensitized pore conformation. This study presents compelling evidence for a direct pore-binding mechanism of isoflurane inhibition, which has a general implication for inhibitory action of general anesthetics on pLGICs.
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Ebola virus disease (EVD) has erupted many times in some zones since it was first found in 1976. The 2014 EVD outbreak in West Africa is the largest ever, which has caused a large number of deaths and the most serious country is Liberia during the outbreak period. Based on the data released by World Health Organization and the actual transmission situations, we investigate the impact of different transmission routes on the EVD outbreak in Liberia and estimate the basic reproduction number R0 = 2.012 in the absence of effective control measures. ⋯ Furthermore, we study the influence of control measures (isolation and safe burial measures) on EVD outbreak. It is found that if combined control measures are taken, the basic reproduction number will be less than one and thus EVD in Liberia may be well contained. The obtained results may provide new guidance to prevent and control the spread of disease.
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Quorum sensing (QS) is a chemical communication process that Pseudomonas aeruginosa uses to regulate virulence and biofilm formation. Disabling of QS is an emerging approach for combating its pathogenicity. Silver nanoparticles (AgNPs) have been widely applied as antimicrobial agents against human pathogenic bacteria and fungi, but not for the attenuation of bacterial QS. ⋯ LasA protease, LasB elastrase, pyocyanin, pyoverdin, pyochelin, rhamnolipid, and alginate) and reduced AHLs production. Further genes quantification analyses revealed that mfAgNPs significantly down-regulated QS-regulated genes, specifically those encoded to the secretion of virulence factors. The results clearly indicated the anti-virulence property of mfAgNPs by inhibiting P. aeruginosa QS signaling.
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Comparative Study
The comparative cost-effectiveness of colorectal cancer screening using faecal immunochemical test vs. colonoscopy.
Faecal immunochemical tests (FITs) and colonoscopy are two common screening tools for colorectal cancer(CRC). Most cost-effectiveness studies focused on survival as the outcome, and were based on modeling techniques instead of real world observational data. This study evaluated the cost-effectiveness of these two tests to detect colorectal neoplastic lesions based on data from a 5-year community screening service. ⋯ Using FIT as control, the ICER of screening colonoscopy in detecting adenoma, advanced adenoma, CRC and a composite endpoint of either advanced adenoma or stage I CRC was US$3,489, US$27,962, US$922,762 and US$23,981 respectively. The respective ICER was US$3,597, US$439,513, -US$2,765,876 and US$32,297 among lower-risk subjects; whilst the corresponding figure was US$3,153, US$14,852, US$184,162 and US$13,919 among higher-risk subjects. When compared to FIT, colonoscopy is considered cost-effective for screening adenoma, advanced neoplasia, and a composite endpoint of advanced neoplasia or stage I CRC.
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The risk for herpes zoster (HZ) in acute kidney injury (AKI) survivors was never explored. We identified 2,387 adults in the Taiwan National Health Insurance Research Database who recovered from dialysis-requiring AKI and matched them with non-recovery and non-AKI patients by propensity score. During a mean follow-up of 2.7 years, the incidences of HZ were 6.9, 8.2 and 4.8 episodes per 1,000 person-years in AKI-non-recovery, AKI-recovery and non-AKI group, respectively. ⋯ Patients without acute kidney injury were less likely to develop herpes zoster than those AKI, recovered from dialysis or not (hazard ratio HR 0.66, 95% CI 0.46-0.95). Dialysis-requiring acute kidney injury poses a long-term risk of herpes zoster after hospital discharge. Even patients who have recovered from dialysis still carry a significantly higher risk of developing herpes zoster.