• Taylor Vedel posted an update 6 months, 1 week ago

    Recent emergence of high-level tigecycline resistance mediated by Tet(X3/X4) in Enterobacteriaceae undoubtably constitutes a serious threat for public health worldwide. Antibiotic adjuvant strategy makes antibiotic more effective against these resistant pathogens through interfering intrinsic resistance mechanisms or enhancing antibiotic actions. Herein, we screened a collection of drugs to identify compounds that are able to restore tigecycline activity against resistant pathogens. Encouragingly, we discovered that anti-HIV agent azidothymidine dramatically potentiates tigecycline activity against clinically resistant bacteria. Meanwhile, addition of azidothymidine prevents the evolution of tigecycline resistance in E. coli and the naturally occurring horizontal transfer of tet(X4). Evidence demonstrated that azidothymidine specifically inhibits DNA synthesis and suppresses resistance enzyme activity. Moreover, in in vivo infection models by Tet(X4)-expression E. coli, the combination of azidothymidine and tigecycline achieved remarkable treatment benefits including increased survival and decreased bacterial burden. These findings provide an effective regimen to treat infections caused by tigecycline-resistant Escherichia coli.Anthracycline chemotherapy is commonly used to treat breast cancer yet may increase the level of matrix metalloproteinases (MMP) -2 and -9, which increase the risk of atherosclerosis. While exercise has been shown to reduce the level of MMP in patients with diabetes, high intensity interval training (HIIT) has not been utilized to improve level of MMP in women with breast cancer receiving anthracycline chemotherapy. Thirty women were randomized to either 8-week HIIT or control (CON) group. The CON group was offered the HIIT intervention after 8 weeks. MMP-1, -2 -7, -9, tissue inhibitor of MMP (TIMP) -1, and-2 were measured at baseline and post-intervention. Repeated measures ANCOVA and paired t-test were performed to assess changes in MMP and TIMP. Post-intervention, no significant between-group differences were observed for MMP and TIMP. However, within-group decrease in MMP-9 was observed in the HIIT group . MMP-9 in the CON group was not significantly changed . MMP-2 significantly increased in both the HIIT group [76.6(11.2) to 83.2(13.1); P = 0.007) and the CON group [69.0(8.9) to 77.6(11.1) P = 0.003). It is unclear whether an 8-week HIIT intervention influences MMP-9 in breast cancer patients undergoing anthracycline chemotherapy. Additional investigations are required to understand the exercise-induced changes in MMP-2 and -9 in women undergoing anthracycline chemotherapy.Generative Adversarial Network (GAN) requires extensive computing resources making its implementation in edge devices with conventional microprocessor hardware a slow and difficult, if not impossible task. In this paper, we propose to accelerate these intensive neural computations using memristive neural networks in analog domain. The implementation of Analog Memristive Deep Convolutional GAN (AM-DCGAN) using Generator as deconvolutional and Discriminator as convolutional memristive neural network is presented. learn more The system is simulated at circuit level with 1.7 million memristor devices taking into account memristor non-idealities, device and circuit parameters. The design is modular with crossbar arrays having a minimum average power consumption per neural computation of 47nW. The design exclusively uses the principles of neural network dropouts resulting in regularization and lowering the power consumption. The SPICE level simulation of GAN is performed with 0.18 μm CMOS technology and WOx memristive devices with RON = 40 kΩ and ROFF = 250 kΩ, threshold voltage 0.8 V and write voltage at 1.0 V.We sought to analyse plasma levels of peripheral blood microRNAs (miRs) as biomarkers of ST-segment-elevation myocardial infarction (STEMI) due to type-1 myocardial infarction as a model situation of vulnerable plaque (VP) rupture. Samples of 20 patients with STEMI were compared both with a group of patients without angina pectoris in whom coronary angiogram did not reveal coronary atherosclerotic disease (no coronary atherosclerosis-NCA) and a group of patients with stable angina pectoris and at least one significant coronary artery stenosis (stable coronary artery disease-SCAD). This study design allowed us to identify miRs deregulated in the setting of acute coronary artery occlusion due to VP rupture. Based on an initial large scale miR assay screening, we selected a total of 12 miRs (three study miRs and nine controls) that were tested in the study. Two of the study miRs (miR-331 and miR-151-3p) significantly distinguished STEMI patients from the control groups, while ROC analysis confirmed their suitability as biomarkers. Importantly, this was observed in patients presenting early with STEMI, even before the markers of myocardial necrosis (cardiac troponin I, miR-208 and miR-499) were elevated, which suggests that the origin of miR-331 and miR-151-3p might be in the VP. In conclusion, the study provides two novel biomarkers observed in STEMI, which may be associated with plaque rupture.African swine fever (ASF) is a severe viral disease that is currently spreading among domestic pigs and wild boar (Sus scrofa) in large areas of Eurasia. Wild boar play a key role in the spread of ASF, yet despite their significance, little is known about the key mechanisms that drive infection transmission and disease persistence. A mathematical model of the wild boar ASF system is developed that captures the observed drop in population density, the peak in infected density and the persistence of the virus observed in ASF outbreaks. The model results provide insight into the key processes that drive the ASF dynamics and show that environmental transmission is a key mechanism determining the severity of an infectious outbreak and that direct frequency dependent transmission and transmission from individuals that survive initial ASF infection but eventually succumb to the disease are key for the long-term persistence of the virus. By considering scenarios representative of Estonia and Spain we show that faster degradation of carcasses in Spain, due to elevated temperature and abundant obligate scavengers, may reduce the severity of the infectious outbreak.

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