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Bronchoalveolar lavage isolates produced the highest amounts of virulence factors biofilm (44.4% ± 2.7%), elastase (58.5% ± 4.3%), alkaline protease (60.1% ± 5.0%); except for pyocyanin production. The ERIC-PCR assay showed 83 genetic patterns (90% clonal diversity) and 13 isolates had 100% genetic similarity, forming 4 real clones, 3 of these clones were obtained from different anatomical site and/or hospital. P505-15 solubility dmso CONCLUSIONS Antibiotic resistance and virulence factors production was heterogeneous among samples analyzed. Genotyping of P. aeruginosa strains showed high genetic diversity in the studied isolates. Copyright (c) 2019 Rebeca Perez Morales, Eliab M Gonzalez Olvera, Alberto Gonzalez Zamora, Graciela Castro Escarpulli, Ingrid Palma Martinez, Jose J Alba Romero.INTRODUCTION The aim of our study was to evaluate the epidemiology, clinical features and risk factors for shock and mortality from Escherichia coli bacteremia among children and adolescents with hematological disorders. METHODOLOGY A retrospective observational study of E. coli bacteremia in the hematology department at Xiangya Hospital from January 2013 to June 2018 was conducted. Clinical characteristics, laboratory results and antimicrobial susceptibility were analysed. Risk factors for shock and mortality were also investigated. RESULTS Of the 45 strains of E. coli, 73.3% were multidrug-resistant (MDR). Septic shock was observed in 51.1% of patients, and the 30-day all-cause mortality was 22.2%. The risk factors associated with shock were an elevated red blood cell distribution (RDW) value when bloodstream infections (BSIs) occurred (> 15%, OR, 6.840; 95% CI, 1.571 - 29.788) and a lower WBC count ( 0.5 mg/L, OR 12.250, 95% CI 1.268 - 118.361) was a risk factor for 30-day mortality. Furthermore, we observed decreases for RDW changes at two time points (neutropenia and BSIs occurred) in the non-shock group and survival group. CONCLUSIONS MDR infections from E. coli bacteremia were common in pediatric hematological patients. In our setting, the laboratory results may serve as a clue for physicians to distinguish patients at higher risk for shock and mortality. Furthermore, RDW could be used as a biomarker to elucidate potential disorders in hematological patients. Copyright (c) 2019 Haichen Wang, Jianling Liu, Ziyan Huang, Xiaoyan Tao, Jun Li, Yongmei Hu, Qingya Dou, Mingxiang Zou, Qun Yan, Wen' en Liu.INTRODUCTION Carbapenem-resistant Klebsiella pneumoniae (KP) serves as a major threat to onco-hematological patients, resulting in great morbidity and mortality. The purpose of our study was to identify the risk factors for KP bloodstream infections (BSIs) and mortality in onco-hematological patients. METHODOLOGY A retrospective observation study was conducted on KP BSIs in the onco-hematology departments at Xiangya hospital from January 2014 to September 2018. Multivariate analysis was employed to identify the independent risk factors for carbapenem-resistant (CR) KP BSIs and related mortality. RESULTS A total of 89 strains of KP were analyzed in our study, in which 20 strains were CRKP. The only risk factor for CRKP BSI was carbapenem exposure within 30 days before the onset of BSIs (HR 25.122). The 30-day mortality was 24.7%. CRKP caused more mortality than carbapenem-susceptible KP (55.0% vs 15.9%, P = 0.001). In the multivariate analysis, unresolved neutropenia (HR 16.900), diarrhea (HR 3.647) and RDW > 14% (HR 6.292) were independent risk factors for mortality, and appropriate empirical therapy (HR 0.164) was protective against mortality. CONCLUSIONS Our findings showed that carbapenem resistance was spreading in our setting, and a precise combination of antibiotics covering the common pathogen is crucial to improving patient survival. Copyright (c) 2019 Jianling Liu, Haichen Wang, Ziyan Huang, Xiaoyan Tao, Jun Li, Yongmei Hu, Qingya Dou, Mingxiang Zou.The leaves of Garcinia epunctata Stapf have furnished two new phenolic glucosides, epunctosides A and B, along with 13 known secondary metabolites identified as lanceoloside A, betulinic acid, lupeol, stigmasterol, β-sitosterol, β-sitosterol-3-O-β-d-glucopyranoside, stigmasterol-3-O-β-d-glucopyranoside, luteolin-7-O-glucoside, quercitin-7-O-glucoside, amentoflavone, robustaflavone, 4'-O-methyl-amentoflavone and 4'-O-methyl-robustaflavone. All structures were established from chemical and spectroscopic evidence including 1D and 2D NMR data as well as by comparing the obtained spectroscopic data with literature. This is the first report of the presence of phenolic glucosides in the genus Garcinia.Background The aim of the study was to evaluate the inter- and intrareader variability of the safety margin assessment after microwave ablation of liver tumors using post-procedure computed tomography (CT) images as well as to determine the sensitivity and specificity of identification remnant tumor tissue. Patients and methods A retrospective analysis of 58 patients who underwent microwave ablation (MWA) of primary or secondary liver malignancies (46 hepatocellular carcinoma, 9 metastases of a colorectal cancer and 3 metastases of pancreatic cancer) between September 2017 and June 2019 was conducted. Three readers estimated the minimal safety margin in millimeters using side-by-side comparison of the 1-day pre-ablation CT and 1-day post-ablation CT and judged whether ablation was complete or incomplete. One reader estimated the safety margin again after 6 weeks. Magnetic resonance imaging (MRI) after 6 weeks was the gold standard. Results The intraclass correlation coefficient (ICC) for estimation of the minimal safety margin of all three readers was 0.357 (95%-confidence interval 0.194-0.522). The ICC for repeated assessment (reader 1) was 0.774 (95%-confidence interval 0.645-0.860). Sensitivity and specificity of the detection of complete tumor ablation, defined as no remnant tumor tissue in 6 weeks follow-up MRI, were 93%/82%/82% and 33%/17%/83%, respectively. Conclusions In clinical practice, the safety margin after liver tumor ablation is often assessed using side-by-side comparison of CT images. In the study, we were able to show, that this technique has a poor reliability (ICC 0.357). From our point of view, this proves the necessity of new technical procedures for the assessment of the safety distance.Previous research demonstrated that acute treatment with GnRH-antagonist, Acyline, allowed follicle growth until ⁓8.5 mm and no dominant follicle was selected. This study evaluated whether deficient LH was the underlying mechanism for Acyline effects by replacing LH action, using human chorionic gonadotropin (hCG), during Acyline treatment. Holstein heifers (n=24) during first follicular wave were evaluated by ultrasound and randomized into one of three treatments Control (Saline treatments), Acyline (5 µg/kg Acyline), or Acyline+hCG (Acyline plus 50 IU of hCG at start then 100 IU every 12h). Pulses of LH were present in Control heifers (9 Pulses/10h) but not during Acyline treatment. Data were normalized to the transition to diameter deviation (day 0; F1⁓7.5 mm). Diameter deviation of the largest (F1) and the second largest (F2) follicle was not observed in Acyline-treated heifers, whereas control heifers had decreased growth of F2 at F1 ~7.5mm, indicating deviation. Selection of a single dominant follicle was restored by providing LH activity in Acyline+hCG heifers, as evidenced by F1 and F2 deviation, continued growth of F1, and elevated circulating estradiol. Separation of F1 and F2 occurred 12h (~7.0mm) earlier in Acyline+hCG heifers than Controls. Circulating FSH was greater in Acyline than Controls, but lower in Acyline+hCG than Controls after day 1.5. In conclusion, dominant follicle selection and growth after follicle deviation is due to LH action as shown by inhibition of this process during ablation of GnRH-stimulated LH pulses with Acyline and restoration of it after replacement of LH action by hCG treatment.Loss of ovarian hormones leads to increased adiposity and insulin resistance (IR), increasing the risk for cardiovascular and metabolic diseases. The purpose of this study was to investigate whether the molecular mechanism behind the adverse systemic and adipose tissue-specific metabolic effects of ovariectomy requires loss of signaling through estrogen receptor alpha (ERα) or estrogen receptor β (ERβ). We examined ovariectomized (OVX) and ovary-intactwild-type (WT), ERα-null (αKO), and ERβ-null (βKO) female mice (age ~49 weeks; n = 7-12/group). All mice were fed a phytoestrogen-free diet ( less then 15 mg/kg) and either remained ovary-intact (INT) or were OVX and followed for 12 weeks. Body composition, energy expenditure, glucose tolerance, and adipose tissue gene and protein expression were analyzed. INT αKO were ~25% fatter with reduced energy expenditure compared to age-matched INT WT controls and βKO mice (all P less then 0.001). Following OVX, αKO mice did not increase adiposity or experience a further increase in IR, unlike WT and βKO, suggesting that loss of signaling through ERα mediates OVX-induced metabolic dysfunction. In fact, OVX in αKO mice (i.e., signaling through ERβ in the absence of ERα) resulted in reduced adiposity, adipocyte size, and IR (P less then 0.05 for all). βKO mice responded adversely to OVX in terms of increased adiposity and development of IR. Together, these findings challenge the paradigm that ERα mediates metabolic protection over ERβ in all settings. These findings lead us to suggest that, following ovarian hormone loss, ERβ may mediate protective metabolic benefits.Overall survival (OS) is considered the standard measure of outcome in oncology. However, considering that resectable pancreatic neuroendocrine neoplasms (Pan-NENs) usually have a long OS, the feasibility of prospective studies is questionable due to a long follow-up period needed. The primary endpoint was to validate the use of disease-specific survival (DFS) as a surrogate measure of OS. The secondary endpoint was to calculate the gain in sample size using DFS instead of OS in hypothetical prospective studies with two parallel groups. A Systematic review of studies reporting both OS and DFS in resected Pan-NENs was carried out. Multivariate linear regression analysis was used to evaluate if DFS predicts the OS in patients undergoing radical resection. Monte Carlo simulation was performed to estimate the gain in sample size, supposing the use of DFS instead of OS, to evaluate a hypothetical adjuvant treatment after surgery in a randomized trial. Six studies reporting data about seven cohorts of resected Pan-NENs were included, for a total of 1088 patients. The median OS and DFS were 144 (27-134) and 122 (50-267) months, respectively. There was a significant correlation between DFS and OS (R2= 0.988; P= 0.035). Monte Carlo simulations showed that the number of patients needed to demonstrate a significant reduction of probability of a 'target event' in a hypothetical two-arm group exploring the hypothetical role of adjuvant therapy was reduced using DFS instead OS. This finding supports the legitimacy of using DFS as an acceptable surrogate for OS in surgical clinical trials.Microtubules are cytoskeletal polymers whose function depends on their property to switch between states of growth and shrinkage. Growing microtubules are thought to be stabilized by a GTP cap at their ends. The nature of this cap, however, is still poorly understood. End Binding proteins (EBs) recruit a diverse range of regulators of microtubule function to growing microtubule ends. Whether the EB binding region is identical to the GTP cap is unclear. Using mutated human tubulin with blocked GTP hydrolysis, we demonstrate that EBs bind with high affinity to the GTP conformation of microtubules. Slowing-down GTP hydrolysis leads to extended GTP caps. We find that cap length determines microtubule stability and that the microtubule conformation changes gradually in the cap as GTP is hydrolyzed. These results demonstrate the critical importance of the kinetics of GTP hydrolysis for microtubule stability and establish that the GTP cap coincides with the EB-binding region. © 2020, Roostalu et al.

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