To assess the outcome of Staphylococcus aureus bacteraemia (SAB) according to factors associated with necessity for longer treatment in conjunction with the duration of treatment.
We prospectively ...collected the data of patients with SAB consecutively during 12 to 39 months from 11 hospitals. If multiple episodes of SAB occurred in one patient, only the first episode was enrolled. Factors associated with necessity for longer treatment were defined as follows: persistent bacteraemia, metastatic infection, prosthesis and endocarditis. If any of the factors were present, then the case was defined as longer antibiotic treatment warranted (LW) group; those without any factors were defined as shorter antibiotic treatment sufficient (SS) group. Poor outcome was defined as a composite of 90-day mortality or 30-day recurrence. Duration of antibiotic administration was classified as <14 or ≥14 days in the SS group and <28 or ≥28 days in the LW group.
Among 2098 cases, the outcome was analysed in 1866 cases, of which 591 showed poor outcome. The SS group accounted for 964 cases and the LW group for 852. On multivariate analysis, age over 65 years, pneumonia, higher Sequential Organ Failure Assessment (SOFA) score and chronic liver diseases were risk factors for poor outcome. Administration of antibiotics less than the recommendation was associated with poor outcome, but this significance was observed only in the LW group (adjusted odds ratio = 1.68; 95% confidence interval, 1.00–2.83; p 0.05).
Inappropriately short antibiotic treatment was associated with poor outcome in the LW group. Vigilant evaluation for risk factors to determine the duration of treatment may improve the outcome among patients with SAB.
Mammalian sirtuin 1 (SIRT1) has connected to an ever widening circle of activities that encompass cellular stress resistance, energy metabolism and tumorigenesis. However, underlying mechanisms ...leading to oncogenic SIRT1 overexpression are less understood. In this study, we identified SIRT1 regulatory microRNA (miRNA) and its function in hepatocellular carcinoma (HCC). Aberrant SIRT1 overexpression was demonstrated in a subset of human HCCs. SIRT1 knockdown suppressed HCC cell growth by transcriptional deregulation of cell cycle proteins. This led to hypophosphorylation of pRb, which inactivated E2F/DP1 target gene transcription, and thereby caused significant increase of HCC cells to remain in the G1/S phase. A comprehensive miRNA profiling analysis indentified five putative endogenous miRNAs that are significantly downregulated in HCC. Ectopic expression of miRNA mimics evidenced miR-29c to suppress SIRT1 in HCC cells. Notably, ectopic miR-29c expression repressed cancer cell growth and proliferation, and it recapitulated SIRT1 knockdown effects in HCC cells. In addition, miR-29c expression was downregulated in a large cohort of HCC patients, and low expression of miR-29c was significantly associated with poor prognosis of HCC patients. Taken together, we demonstrated that miR-29c suppresses oncogenic SIRT1 by way of binding to 3'-untranslated region of SIRT1 mRNA causing translational inhibition in liver cancer cells. The loss or suppression of miR-29c may cause aberrant SIRT1 overexpression and promotes liver tumorigenesis. Overall, we suggest that miR-29c functions as a tumor suppressor by regulating abnormal SIRT1 activity in liver.
Current microlensing surveys are sensitive to free-floating planets down to Earth-mass objects. All published microlensing events attributed to unbound planets were identified based on their short ...timescale (below two days), but lacked an angular Einstein radius measurement (and hence lacked a significant constraint on the lens mass). Here, we present the discovery of a Neptune-mass free-floating planet candidate in the ultrashort (tE = 0.320 0.003 days) microlensing event OGLE-2016-BLG-1540. The event exhibited strong finite-source effects, which allowed us to measure its angular Einstein radius of θE = 9.2 0.5 as. There remains, however, a degeneracy between the lens mass and distance. The combination of the source proper motion and source-lens relative proper motion measurements favors a Neptune-mass lens located in the Galactic disk. However, we cannot rule out that the lens is a Saturn-mass object belonging to the bulge population. We exclude stellar companions up to ∼15 au.
To investigate the anti-obesity effect of Rubi Fructus (RF) extract using brown adipose tissue (BAT) and primary brown preadipocytes in vivo and in vitro.
Male C57BL/6 J mice (n=5 per group) were fed ...a high-fat diet (HFD) for 10 weeks with or without RF. Brown preadipocytes from the interscapular BAT of mice (age, post-natal days 1-3) were cultured with differentiation media (DM) including isobutylmethylxanthine, dexamethasone, T3, indomethacin and insulin with or without RF.
In HFD-induced obese C57BL/6 J mice, long-term RF treatment significantly reduced weight gain as well as the weights of the white adipose tissue, liver and spleen. Serum levels of total cholesterol and low-density lipoprotein cholesterol were also reduced in the HFD group which received RF treatment. Furthermore, RF induced thermogenic-, adipogenic- and mitochondria-related gene expressions in BAT. In primary brown adipocytes, RF effectively stimulated the expressions of thermogenic- and mitochondria-related genes. In addition, to examine whether LIPIN1, a regulator of adipocyte differentiation, is regulated by RF, Lipin1 small interfering RNA (siRNA) and RF were pretreated in primary brown adipocytes. Pretreatment with Lipin1 siRNA and RF downregulated the DM-induced expression levels of thermogenic- and mitochondria-related genes. Moreover, RF markedly upregulated AMP-activated protein kinase. Our study shows that RF is capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes.
This study demonstrates that RF prevents the development of obesity in mice fed with a HFD and that it is also capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes, which suggests that RF has potential as a therapeutic application for the treatment or prevention of obesity.
Background: The aim of this study was to determine whether expressions of the excision repair cross-complementing (ERCC1), thymidylate synthase (TS), and glutathione S-transferase P1 (GSTP1) predict ...clinical outcome in patients with advanced gastric cancer treated with fluorouracil (5-fluorouracil)/oxaliplatin chemotherapy. Patients and methods: The study population consisted of 64 advanced gastric cancer patients (median age 51 years). Patients were treated with oxaliplatin 85 mg/m2 as a 2-h infusion at day 1 plus leucovorin 20 mg/m2 over 10 min, followed by 5-FU bolus 400 mg/m2 and 22-h continuous infusion of 600 mg/m2 at days 1–2. Treatment was repeated in 2-week intervals. The expressions of ERCC1, TS, and GSTP1 of primary tumors were examined by immunohistochemistry. Results: The positive rates of ERCC1, TS, and GSTP1 were 70.3%, 29.7%, and 50.0%, respectively. The patients without ERCC1 expression were more likely to respond to chemotherapy (P = 0.045). There were no significant differences between response and TS or GSTP1 expression pattern (P = 0.813, P = 0.305, respectively). Median overall survival (OS) was significantly longer in patients without ERCC1 expression (P = 0.0396). TS or GSTP1 expression were not related to survival (P = 0.4578, P = 0.8121, respectively). Multivariate analysis revealed that ERCC1 expression significantly impacted on OS (hazard ratio 1.92, P = 0.037). Conclusion: Immunohistochemical studies for ERCC1 may be useful in prediction of the clinical outcome in advanced gastric cancer patients treated with 5-FU and oxaliplatin.
Status of LAMPS at RAON Hong, B.; Ahn, D.S.; Ahn, J.K. ...
Nuclear instruments & methods in physics research. Section B, Beam interactions with materials and atoms,
August 2023, 2023-08-00, Letnik:
541
Journal Article
Recenzirano
A new radioactive ion-beam accelerator facility, RAON, is under construction in Korea. Among the seven experimental systems being built, the Large Acceptance Multi-Purpose Spectrometer (LAMPS) in the ...high-energy experimental hall is the versatile detector system for nuclear physics. Its primary goal is to study the nuclear equation of state (EoS) and the symmetry energy of the compressed nuclear matter, which should be essential to understand the effective nuclear interactions and structure of the astrophysical objects like neutron stars. The basic LAMPS system consists of the beam diagnostic elements such as the starting counters and beam drift chambers, the time-projection chamber, the barrel and forward time-of-flight systems, the forward neutron detector array, and the superconducting solenoid magnet. In this paper the overview of the present status of each detector component for LAMPS will be given with some prospects.
We report the discovery of a giant planet in the OGLE-2017-BLG-1522 microlensing event. The planetary perturbations were clearly identified by high-cadence survey experiments despite the relatively ...short event timescale of tE ∼ 7.5 days. The Einstein radius is unusually small, θE = 0.065 mas, implying that the lens system either has very low mass or lies much closer to the microlensed source than the Sun, or both. A Bayesian analysis yields component masses and source-lens distance , implying that this is a brown-dwarf/Jupiter system that probably lies in the Galactic bulge, a location that is also consistent with the relatively low lens-source relative proper motion = 3.2 0.5 mas yr−1. The projected companion-host separation is , indicating that the planet is placed beyond the snow line of the host, i.e., asl ∼ 0.12 au. Planet formation scenarios combined with the small companion-host mass ratio q ∼ 0.016 and separation suggest that the companion could be the first discovery of a giant planet that formed in a protoplanetary disk around a brown-dwarf host.
Abstract
Pronounced changes in the Arctic environment add a new potential driver of anomalous weather patterns in midlatitudes that affect billions of people. Recent studies of these ...Arctic/midlatitude weather linkages, however, state inconsistent conclusions. A source of uncertainty arises from the chaotic nature of the atmosphere. Thermodynamic forcing by a rapidly warming Arctic contributes to weather events through changing surface heat fluxes and large-scale temperature and pressure gradients. But internal shifts in atmospheric dynamics—the variability of the location, strength, and character of the jet stream, blocking, and stratospheric polar vortex (SPV)—obscure the direct causes and effects. It is important to understand these associated processes to differentiate Arctic-forced variability from natural variability. For example in early winter, reduced Barents/Kara Seas sea-ice coverage may reinforce existing atmospheric teleconnections between the North Atlantic/Arctic and central Asia, and affect downstream weather in East Asia. Reduced sea ice in the Chukchi Sea can amplify atmospheric ridging of high pressure near Alaska, influencing downstream weather across North America. In late winter southward displacement of the SPV, coupled to the troposphere, leads to weather extremes in Eurasia and North America. Combined tropical and sea ice conditions can modulate the variability of the SPV. Observational evidence for Arctic/midlatitude weather linkages continues to accumulate, along with understanding of connections with pre-existing climate states. Relative to natural atmospheric variability, sea-ice loss alone has played a secondary role in Arctic/midlatitude weather linkages; the full influence of Arctic amplification remains uncertain.
Intercalation of magnetic iron atoms through graphene formed on the SiC(0001) surface is found to induce significant changes in the electronic properties of graphene due mainly to the Fe-induced ...asymmetries in charge as well as spin distribution. From our synchrotron-based photoelectron spectroscopy data together with ab initio calculations, we observe that the Fe-induced charge asymmetry results in the formation of a quasi-free-standing bilayer graphene while the spin asymmetry drives multiple spin-split bands. We find that Fe adatoms are best intercalated upon annealing at 600 °C, exhibiting split linear π-bands, characteristic of a bilayer graphene, but much diffused. Subsequent changes in the C 1s, Si 2p, and Fe 3p core levels are consistently described in terms of Fe-intercalation. Our calculations together with a spin-dependent tight binding model ascribe the diffuse nature of the π-bands to the multiple spin-split bands originated from the spin-injected carbon atoms residing only in the lower graphene layer.
The hypothesis of cancer stem cells has been proposed to explain the therapeutic failure in a variety of cancers including lung cancers. Previously, we demonstrated acquisition of ...epithelial-mesenchymal transition, a feature highly reminiscent of cancer stem-like cells, in gefitinib-resistant A549 cells (A549/GR). Here, we show that A549/GR cells contain a high proportion of CXCR4+ cells that are responsible for having high potential of self-renewal activity in vitro and tumorigenicity in vivo. A549/GR cells exhibited strong sphere-forming activity and high CXCR4 expression and SDF-1α secretion compared with parent cells. Pharmacological inhibition (AMD3100) and/or siRNA transfection targeting CXCR4 significantly suppressed sphere-forming activity in A549 and A549/GR cells, and in various non-small cell lung cancer (NSCLC) cell lines. A549/GR cells showed enhanced Akt, mTOR and STAT3 (Y705) phosphorylation. Pharmacological inhibition of phosphatidyl inositol 3-kinase or transfection with wild-type PTEN suppressed phosphorylation of Akt, mTOR and STAT3 (Y705), sphere formation, and CXCR4 expression in A549/GR cells, whereas mutant PTEN enhanced these events. Inhibition of STAT3 by WP1066 or siSTAT3 significantly suppressed the sphere formation, but not CXCR4 expression, indicating that STAT3 is a downstream effector of CXCR4-mediated signaling. FACS-sorted CXCR4+ A549/GR cells formed many large spheres, had self-renewal capacity, demonstrated radiation resistance in vitro and exhibited stronger tumorigenic potential in vivo than CXCR4- cells. Lentiviral-transduction of CXCR4 enhanced sphere formation and tumorigenicity in H460 and A549 cells, whereas introduction of siCXCR4 suppressed these activities in A549/GR cells. Our data indicate that CXCR4+ NSCLC cells are strong candidates for tumorigenic stem-like cancer cells that maintain stemness through a CXCR4-medated STAT3 pathway and provide a potential therapeutic target for eliminating these malignant cells in NSCLC.
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