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Translational investigation about individual pancreatic β-cell muscle size enlargement to treat all forms of diabetes.
• The device can be integrated with LAMP for rapid detection of antibiotic resistance genes.• The approach had a high throughput of AR gene analysis in lactic acid bacteria.Multiple interlinked factors are associated with the global resistome, whereas multidrug-resistant (MDR) pathogens have been related to increased mortality rates in humans and animals. CTX-M-type is the most prevalent extended-spectrum β-lactamase (ESBL) among Enterobacteriaceae, which raises concern worldwide. Zoological gardens have a high density of animals that live very close to each other and to humans. Therefore, this study aimed to investigate through the whole-genome sequencing (WGS) MDR Escherichia coli lineages obtained from captivity wild animals in a zoo. Genetic background showed a wide resistome for antimicrobials (e.g., blaCTX-M-65, blaCTX-M-8, blaCMY-2, qnrB19), metals (e.g., pcoABCDERS, silABCEP, merACDEPRT), and antibacterial biocides (e.g., sugE, mdfA) among MDR CTX-M-producing E. coli belonging to CC155 and CC156. Mobilome analysis revealed several plasmids, and eight of them were completely characterized, which showed different backbone-encoding genes. Comparative analysis of plasmids blaCTX-M-65/IncHI2-ST3, blaCTX-M-8/IncI1-ST113, and IncQ1 showed a high identity among plasmids obtained from humans and animals worldwide distributed. Besides, several virulence genes, CRISPR, and prophage-related sequences were also detected. The occurrence of MDR E. coli belonging to CCs closely related to humans and food-producing animals and the high similarity among the plasmids from MDR E. coli carrying clinically significant antimicrobial resistance genes may indicate intercontinental dissemination of these lineages and plasmids. Therefore, these findings contribute to the monitoring of antimicrobial resistance and the human-animal-environment interface worldwide.Key Points• Wide resistome for antimicrobials, metals, and antibacterial biocides.• Multidrug resistance plasmids (blaCTX-M-65/IncHI2-ST3, blaCTX-M-8/IncI1-ST113).• Co-occurrence of plasmid-mediated resistance and virulence genes.The dosimetric effect of artefacts caused by metal hip prostheses in computed tomography imaging is most commonly encountered in the planning of prostate cancer treatment. In this study, a phantom, containing a metal with high atomic number, was prepared for intensity-modulated radiotherapy (IMRT) treatment plans to be used in quality assurance (QA) procedures. Two sets of image files, one without metal artefact correction (ORG) and another with MAR correction (MAR+), were sent to the treatment planning system. In this study, 12 IMRT treatment plans with different fields and segment numbers were calculated. The normal tissue complication probability (NTCP) values of imaginary organs at risk (OARs), such as the rectum and bladder, were investigated, as was the difference in dose maps for ORG and MAR+ derived by calculating gamma passing rates (GPRs). The MatriXX was used for the gamma evaluation of patient-specific IMRT QA measurements. The gamma evaluation was repeated, based on the measurements using an EBT3 gafchromic film, for the plan showing the lowest GPR. The mean relative difference in NTCP values between the two sets of image files was found to be 2.5, 2.1 and 1.4 for the rectum; and 5.33, 6.80 and 9.82 for the bladder, for the investigated 5-, 7- and 9-field beam arrangements, respectively. The relative differences and the standard deviations in GPRs for the standard and metal-containing phantoms were calculated for the MAR+ and ORG sets. The maximum difference found was 7.69% ± 0.88 for the 9-field beam arrangement calculated without metal artefact correction. In the IMRT QA procedures for prostate patients with hip prostheses, the application of a metal-containing phantom that is both easy and inexpensive to prepare, is considered to be a useful method for examining any dose changes involved in introducing a hip prosthesis. Therefore, it is recommended for use in clinics that do not have MAR correction algorithms.Many experimental studies are carried out to compare biological effectiveness of high dose rate (HDR) with that of low dose rate (LDR). The rational for this is the uncertainty regarding the value of the dose rate effectiveness factor (DREF) used in radiological protection. While a LDR is defined as 0.1 mGy/min or lower, anything above that is seen as HDR. In cell and animal experiments, a dose rate around 1 Gy/min is usually used as representative for HDR. However, atomic bomb survivors, the reference cohort for radiological protection, were exposed to tens of Gy/min. The important question is whether gamma radiation delivered at very high dose rate (VHDR-several Gy/min) is more effective in inducing DNA damage than that delivered at HDR. The aim of this investigation was to compare the biological effectiveness of gamma radiation delivered at VHDR (8.25 Gy/min) with that of HDR (0.38 Gy/min or 0.79 Gy/min). Experiments were carried out with human peripheral mononuclear cells (PBMC) and the human osteosarcoma cell line U2OS. Endpoints related to DNA damage response were analysed. The results show that in PBMC, VHDR is more effective than HDR in inducing gene expression and micronuclei. In U2OS cells, the repair of 53BP1 foci was delayed after VHDR indicating a higher level of damage complexity, but no VHDR effect was observed at the level of micronuclei and clonogenic cell survival. We suggest that the DREF value may be underestimated when the biological effectiveness of HDR and LDR is compared.A homemade gold electrode is modified with a carbon nanotubes/gold nanoparticles nanocomposite to perform selective and sensitive electrochemical detection of dengue toxin. This nanostructured composite offers a large specific surface and a reactive interface allowing the immobilization of biological material. Dengue antibodies are immobilized on gold nanoparticles via covalent bonding for dengue toxin detection. The porous tridimensional network of carbon nanotubes and gold nanoparticles enhances the electrochemical signal and the overall performance of the sensor. After optimization, the system exhibits a high sensitivity of - 0.44 ± 0.01 μA per decade with wide linear range between 1 × 10-12 and 1 × 10-6 g/mL at a working potential of 0.22 V vs Ag/AgCl. The extremely low detection limit (3 × 10-13 g/mL) ranks this immunosensor as one of the most efficient reported in the literature for the detection of recombinant viral dengue virus 2 NS1. This biosensor also offers good selectivity, characterized by a low response to various non-specific targets and assays in human serum. The outstanding performances and the reproducibility of the system place the biosensor developed among the best candidates for future medical applications and for early diagnosis of dengue fever. Graphical abstract.IL6 is an inflammatory cytokine with pleiotropic functions in both immune and nonimmune cells, and its expression level is inversely correlated with disease prognosis in patients with cancer. However, blocking IL6 alone has only yielded minimal efficacy in human cancer patients. We aimed at defining IL6 expression profiles under inflammatory conditions and cancer, and elucidating the mechanism underlying IL6 intrinsic signaling in colon carcinoma. We report here that colonic inflammation induces IL6 expression primarily in the CD11b+Ly6G+Ly6Clo polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) in colon. Although both tumor cells, T cells and myeloid cells all express IL6, PMN-MDSCs are the primary cell type that express IL6 in colon carcinoma, suggesting that IL6 up-regulation is a response to inflammation in colon epithelium and tumor microenvironment. Furthermore, we determined that IL6 activates STAT3 to up-regulate DNMT1 and DNMT3b expression in colon tumor cells, thereby revealing an epigenetic mechanism that mediates the IL6-STAT3 signaling pathway in colon carcinoma. Surprisingly, knocking out IL6 in colon tumor cells did not significantly alter tumor growth in WT mice. Conversely, IL6-sufficient colon and pancreatic tumor grow at similar rate in WT and IL6-deficient mice. However, overexpression of IL6 in colon tumor cells significantly increases tumor growth in vivo. Our findings determine that a high tumor local IL6 threshold is essential for IL6 function in colon tumor promotion and targeting the IL6-expressing PMN-MDSCs is potentially an effective approach to suppress colon tumor growth in vivo.Purpose One out of three migraine patients might have accompanying restless legs syndrome (RLS). In our study, we aimed to compare the volumes of the brain structures of migraineurs with and without RLS. Methods We had 37 female patients with migraine and 17 females as the control group. https://www.selleckchem.com/products/Trichostatin-A.html Nineteen migraineurs had no RLS (RLS0) and 18 migraineurs had comorbidity of RLS (RLS1). The volumes of the brain structures were obtained by manual measurements, volBrain, and voxel-based morphometry (VBM). Manually, we measured caudate and putamen volumes. We used age, years of education, depression, anxiety scores, and total intracranial volume as covariates. Results According to VBM analyses, the volumes of the left superior occipital gyrus and precuneus were increased, and the substantia nigra and cuneus were decreased in the RLS1 group compared with the RLS0 group. RLS1 patients had larger superior temporal gyrus, Brodmann area 38, and left insula, and RLS0 patients had larger Brodmann area 22, right superior temporal gyrus, and Heschl gyrus compared with controls. Migraine and RLS0 patients had a smaller corpus callosum anteriorly, whereas RLS1 patients had a smaller splenium. Caudate volumes were larger in migraine patients via the three techniques. There was a positive relation between the caudate and putamen volumes and attack frequency. Conclusions Comorbidity of RLS might be a confounding factor in structural neuroimaging studies in migraine. Deficits in the visual network seem to be related to accompanying RLS; deficits in the auditory network are particularly related to migraine.Purpose Endovascular therapy to the spinal dural arteriovenous fistula (SDAVF) with a common origin of the radiculomedullary artery and the feeder of the shunt has the risk of spinal cord infarction. This study aimed to retrospectively assess the detection rate of normal spinal arteries from the feeder of SDAVF. Methods We retrospectively collected the angiographic and clinical data of SDAVFs. This study included 19 patients with 20 SDAVF lesions admitted to our department between January 2007 and December 2018. We assessed the detection rate of normal radiculomedullary artery branched from the feeder of SDAVF between the period using the image intensifier (II) and flat panel detector (FPD) and evaluated the treatment results. Results The detection rates of the radiculomedullary artery branched from the feeder of SDAVF were 10% (1/10 lesions) during the II period and 30% (3/10 lesions) during the FPD period. During the FPD period, all normal radiculomedullary arteries branched from the feeder were only detected on slab maximum intensity projection (MIP) images of rotational angiography, and we could not detect them in 2D or 3D digital subtraction angiography. All lesions that had a common origin of a normal radiculomedullary artery and the feeder were completely obliterated without complications. There was no recurrence during the follow-up period. Conclusions The flat panel detector and slab MIP images seem to show the common origin of the normal radiculomedullary arteries from the feeder more accurately. With detailed analyses, SDAVF can be safety treated.
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