Linezolid and Rifampicin Combination to Combat cfr-Positive Multidrug-Resistant MRSA in Murine Models of Bacteremia and Skin and Skin Structure Infection.

Linezolid resistance mediated by the cfr gene in MRSA represents a global concern. We investigated relevant phenotype differences between cfr-positive and -negative MRSA that contribute to pathogenesis, and the efficacy of linezolid-based combination therapies in murine models of bacteremia and skin and skin structure infection (SSSI). As a group, cfr-positive MRSA exhibited significantly reduced susceptibilities to the host defense peptides tPMPs, human neutrophil peptide-1 (hNP-1), and cathelicidin LL-37 (P < 0.01). In addition, increased binding to fibronectin (FN) and endothelial cells paralleled robust biofilm formation in cfr-positive vs. -negative MRSA. In vitro phenotypes of cfr-positive MRSA translated into poor outcomes of linezolid monotherapy in vivo in murine bacteremia and SSSI models. Importantly, rifampicin showed synergistic activity as a combinatorial partner with linezolid, and the EC50 of linezolid decreased 6-fold in the presence of rifampicin. Furthermore, this combination therapy displayed efficacy against cfr-positive MRSA at clinically relevant doses. Altogether, these data suggest that the use of linezolid in combination with rifampicin poses a viable therapeutic alternative for bacteremia and SSSI caused by cfr-positive multidrug resistant MRSA

Radioprotective effect of lidocaine on neurotransmitter agonist-induced secretion in irradiated salivary glands.

Previously we verified the radioprotective effect of lidocaine on the function and ultrastructure of salivary glands in rabbits. However, the underlying mechanism of lidocaine's radioprotective effect is unknown. We hypothesized that lidocaine, as a membrane stabilization agent, has a protective effect on intracellular neuroreceptor-mediated signaling and hence can help preserve the secretory function of salivary glands during radiotherapy. Rabbits were irradiated with or without pretreatment with lidocaine before receiving fractionated radiation to a total dose of 35 Gy. Sialoscintigraphy and saliva total protein assay were performed before radiation and 1 week after the last radiation fraction. Isolated salivary gland acini were stimulated with either carbachol or adrenaline. Ca(2+) influx in response to the stimulation with these agonists was measured using laser scanning confocal microscopy. The uptake of activity and the excretion fraction of the parotid glands were significantly reduced after radiation, but lidocaine had a protective effect. Saliva total protein concentration was not altered after radiation. For isolated acini, Ca(2+) influx in response to stimulation with carbachol, but not adrenaline, was impaired after irradiation; lidocaine pretreatment attenuated this effect. Lidocaine has a radioprotective effect on the capacity of muscarinic agonist-induced water secretion in irradiated salivary glands

NF-Atlas: Multi-Volume Neural Feature Fields for Large Scale LiDAR Mapping

LiDAR Mapping has been a long-standing problem in robotics. Recent progress in neural implicit representation has brought new opportunities to robotic mapping. In this paper, we propose the multi-volume neural feature fields, called NF-Atlas, which bridge the neural feature volumes with pose graph optimization. By regarding the neural feature volume as pose graph nodes and the relative pose between volumes as pose graph edges, the entire neural feature field becomes both locally rigid and globally elastic. Locally, the neural feature volume employs a sparse feature Octree and a small MLP to encode the submap SDF with an option of semantics. Learning the map using this structure allows for end-to-end solving of maximum a posteriori (MAP) based probabilistic mapping. Globally, the map is built volume by volume independently, avoiding catastrophic forgetting when mapping incrementally. Furthermore, when a loop closure occurs, with the elastic pose graph based representation, only updating the origin of neural volumes is required without remapping. Finally, these functionalities of NF-Atlas are validated. Thanks to the sparsity and the optimization based formulation, NF-Atlas shows competitive performance in terms of accuracy, efficiency and memory usage on both simulation and real-world datasets

The exposure-response relationship between temperature and childhood hand, foot and mouth disease: A multicity study from mainland China.

BACKGROUND: Hand, foot and mouth disease (HFMD) is a rising public health issue in the Asia-Pacific region. Numerous studies have tried to quantify the relationship between meteorological variables and HFMD but with inconsistent results, in particular for temperature. We aimed to characterize the relationship between temperature and HFMD in various locations and to investigate the potential heterogeneity. METHODS: We retrieved the daily series of childhood HFMD counts (aged 0-12 years) and meteorological variables for each of 143 cities in mainland China in the period 2009-2014. We fitted a common distributed lag nonlinear model allowing for over dispersion to each of the cities to obtain the city-specific estimates of temperature-HFMD relationship. Then we pooled the city-specific estimates through multivariate meta-regression with city-level characteristics as potential effect modifiers. RESULTS: We found that the overall pooled temperature-HFMD relationship was shown as an approximately inverted V shape curve, peaking at the 91th percentile of temperature with a risk ratio of 1.30 (95% CI: 1.23-1.37) compared to its 50th percentile. We found that 68.5% of the variations of city-specific estimates was attributable to heterogeneity. We identified rainfall and altitude as the two main effect modifiers. CONCLUSIONS: We found a nonlinear relationship between temperature and HFMD. The temperature-HFMD relationship varies depending on geographic and climatic conditions. The findings can help us deepen the understanding of weather-HFMD relationship and provide evidences for related public health decisions

Gene therapy with tumor-specific promoter mediated suicide gene plus IL-12 gene enhanced tumor inhibition and prolonged host survival in a murine model of Lewis lung carcinoma

<p>Abstract</p> <p>Background</p> <p>Gene therapy is a promising therapeutic approach for cancer. Targeted expression of desired therapeutic proteins within the tumor is the best approach to reduce toxicity and improve survival. This study is to establish a more effective and less toxic gene therapy of cancer.</p> <p>Methods</p> <p>Combined gene therapy strategy with recombinant adenovirus expressing horseradish peroxidase (HRP) mediated by human telomerase reverse transcriptase (hTERT) promoter (AdhTERTHRP) and murine interleukin-12 (mIL-12) under the control of Cytomegalovirus (CMV) promoter (AdCMVmIL-12) was developed and evaluated against Lewis lung carcinoma (LLC) both <it>in vivo </it>and <it>in vitro</it>. The mechanism of action and systemic toxicities were also investigated.</p> <p>Results</p> <p>The combination of AdhTERTHRP/indole-3-acetic acid (IAA) treatment and AdCMVmIL-12 resulted in significant tumor growth inhibition and survival improvement compared with AdhTERTHRP/IAA alone (tumor volume, 427.4 ± 48.7 mm³<it>vs </it>581.9 ± 46.9 mm³, <it>p </it>= 0.005 on day 15; median overall survival (OS), 51 d <it>vs </it>33 d) or AdCMVmIL-12 alone (tumor volume, 362.2 ± 33.8 mm³<it>vs </it>494.4 ± 70.2 mm³, <it>p </it>= 0.046 on day 12; median OS, 51 d <it>vs </it>36 d). The combination treatment stimulated more CD4⁺and CD8⁺T lymphocyte infiltration in tumors, compared with either AdCMVmIL-12 alone (1.3-fold increase for CD4⁺T cells and 1.2-fold increase for CD8⁺T cells, <it>P </it>< 0.01) or AdhTERTHRP alone (2.1-fold increase for CD4⁺T cells and 2.2-fold increase for CD8⁺T cells, <it>P </it>< 0.01). The apoptotic cells in combination group were significantly increased in comparison with AdCMVmIL-12 alone group (2.8-fold increase, <it>P </it>< 0.01) or AdhTERTHRP alone group (1.6-fold increase, <it>P </it>< 0.01). No significant systematic toxicities were observed.</p> <p>Conclusions</p> <p>Combination gene therapy with AdhTERTHRP/IAA and AdCMVmIL-12 could significantly inhibit tumor growth and improve host survival in LLC model, without significant systemic adverse effects.</p

Automatic liver vessel segmentation using 3D region growing and hybrid active contour model

This paper proposes a new automatic method for liver vessel segmentation by exploiting intensity and shape constraints of 3D vessels. The core of the proposed method is to apply two different strategies: 3D region growing facilitated by bi-Gaussian filter for thin vessel segmentation, and hybrid active contour model combined with K-means clustering for thick vessel segmentation. They are then integrated to generate final segmentation results. The proposed method is validated on abdominal computed tomography angiography (CTA) images, and obtains an average accuracy, sensitivity, specificity, Dice, Jaccard, and RMSD of 98.2%, 68.3%, 99.2%, 73.0%, 66.1%, and 2.56 mm, respectively. Experimental results show that our method is capable of segmenting complex liver vessels with more continuous and complete thin vessel details, and outperforms several existing 3D vessel segmentation algorithms

Temperature Dependence of Photoelectrical Properties of Single Selenium Nanowires

Influence of temperature on photoconductivity of single Se nanowires has been studied. Time response of photocurrent at both room temperature and low temperature suggests that the trap states play an important role in the photoelectrical process. Further investigations about light intensity dependence on photocurrent at different temperatures reveal that the trap states significantly affect the carrier generation and recombination. This work may be valuable for improving the device optoelectronic performances by understanding the photoelectrical properties

Tumor subtypes and signature model construction based on chromatin regulators for better prediction of prognosis in uveal melanoma

Background: Uveal Melanoma (UM) is the most prevalent primary intraocular malignancy in adults. This study assessed the importance of chromatin regulators (CRs) in UM and developed a model to predict UM prognosis.Methods: Gene expression data and clinical information for UM were obtained from public databases. Samples were typed according to the gene expression of CRs associated with UM prognosis. The prognostic key genes were further screened by the protein interaction network, and the risk model was to predict UM prognosis using the least absolute shrinkage and selection operator (LASSO) regression analysis and performed a test of the risk mode. In addition, we performed gene set variation analysis, tumor microenvironment, and tumor immune analysis between subtypes and risk groups to explore the mechanisms influencing the development of UM.Results: We constructed a signature model consisting of three CRs (RUVBL1, SIRT3, and SMARCD3), which was shown to be accurate, and valid for predicting prognostic outcomes in UM. Higher immune cell infiltration in poor prognostic subtypes and risk groups. The Tumor immune analysis and Tumor Immune Dysfunction and Exclusion (TIDE) score provided a basis for clinical immunotherapy in UM.Conclusion: The risk model has prognostic value for UM survival and provides new insights into the treatment of UM