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Staphylococcus aureus bloodstream infection (SA-BSI) is an infection with increasing morbidity and mortality. Concomitant Staphylococcus aureus bacteriuria (SABU) frequently occurs in patients with SA-BSI. It is considered as either a sign of exacerbation of SA-BSI or a primary source in terms of urosepsis. The clinical implications are still under investigation. In this study, we investigated the role of SABU in patients with SA-BSI and its effect on the patients' mortality. We performed a retrospective cohort study that included all patients in our university hospital (Charité Universitätsmedizin Berlin) between 1 January 2014 and 31 March 2017. We included all patients with positive blood cultures for Staphylococcus aureus who had a urine culture 48 h before or after the first positive blood culture. We identified cases while using the microbiology database and collected additional demographic and clinical parameters, retrospectively, from patient files and charts. We conducted univariate analyses and multivariable Cox regression analysis to evaluate the risk factors for in-hospital mortality. 202 patients met the eligibility criteria. see more Overall, 55 patients (27.5%) died during their hospital stay. Cox regression showed SABU (OR 2.3), Pitt Bacteremia Score (OR 1.2), as well as moderate to severe liver disease (OR 2.1) to be independent risk factors for in-hospital mortality. Our data indicates that SABU in patients with concurrent SA-BSI is a prognostic marker for in-hospital death. Further studies are needed for evaluating implications for therapeutic optimization.The expansion of the habitat of mosquitoes belonging to the Aedes genus puts nearly half of the world's population at risk of contracting dengue fever, and a significant fraction will develop its serious hemorrhagic complication, which can be fatal if not diagnosed properly and treated in a timely fashion. Although several diagnostic methods have been approved for dengue diagnostics, their applicability is limited in rural areas of developing countries by sample preparation costs and methodological requirements, as well as cross-reactivity among the different serotypes of the Dengue virus and other flavivirus, such as the Zika virus. For these reasons, it is necessary to generate more specific antigens to improve serological methods that could be cheaper and used in field operations. Here, we describe a strategy for the inactivation of cross-reacting epitopes on the surface of the Dengue virus envelope protein through the synthetic generation of recombinant peptide sequences, where key amino acid residues from Dengue virus serotype 1 (DENV-1) and 2 (DENV-2) are substituted by alanine residues. The proteins thus generated are recognized by 88% of sera from Dengue NS1+ patients and show improved serotype specificity because they do not react with the antibodies present in seroconverted, PCR-serotyped DEN-4 infected patients.The systematic evaluation of the gas transport properties related to differences in the history of the samples is a useful tool to appropriately design a membrane-based gas separation system. The permeation rate of six pure gases was measured over time in asymmetric hollow-fiber (HF) samples, that were prepared according to the non-solvent-induced phase separation in different operation conditions, in order to identify their response to physical aging. Four types of HFs having a different structure were analyzed, comparing samples spun in a triple-orifice spinneret to HFs prepared using a conventional spinneret. A generalized gas permeance decline, coupled to a maintained permselectivity for the different gas pairs, was observed for all HFs. Instead, H2/N2 permselectivity values were enhanced upon aging. Cross-linked hollow-fiber samples showed a marked size-sieving behavior that favored the separation of small species, e.g., hydrogen, from other larger species and a good stability over time. Some HFs, post-treated using different alcohols, presented a permeance decay independently on the alcohol type and a greater selectivity over time.Breast cancer is the most common cancer in women worldwide and the solid tumor type for which the highest number of drugs have been approved to date. This study examines new drug approvals for breast cancer by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA), based on an analysis of regulatory documents from both agencies for the period from 1995 to 2018. Of the 29 breast cancer drugs approved over this time span, 17 received positive decisions from both the FDA and EMA, including all drugs licensed after 2008. Nineteen of the 25 FDA-approved drugs, but none of the EMA approvals, benefited from special regulatory pathways (such as fast track, breakthrough therapy, or priority review). In the U.S.A., four accelerated approvals were granted (of which one, for bevacizumab, was later revoked), while only two drugs received provisional approvals following EMA review. New breast cancer drugs were approved approximately twelve months earlier in the United States than in Europe. These results suggest that a broader use of special regulatory pathways by EMA could help to accelerate access to novel drugs for European breast cancer patients.The aim of the study was to understand the internal relationship between milk quality and lipid metabolism in cow mammary glands. A serial of studies was conducted to assess the molecular mechanism of PRL/microRNA-183/IRS1 (Insulin receptor substrate) pathway, which regulates milk fat metabolism in dairy cows. microRNA-183 (miR-183) was overexpressed and inhibited in cow mammary epithelial cells (CMECs), and its function was detected. The function of miR-183 in inhibiting milk fat metabolism was clarified by triglycerides (TAG), cholesterol and marker genes. There is a CpG island in the 5'-flanking promoter area of miR-183, which may inhibit the expression of miR-183 after methylation. Our results showed that prolactin (PRL) inhibited the expression of miR-183 by methylating the 5' terminal CpG island of miR-183. The upstream regulation of PRL on miR-183 was demonstrated, and construction of the lipid metabolism regulation network of microRNA-183 and target gene IRS1 was performed. These results reveal the molecular mechanism of PRL/miR-183/IRS1 pathway regulating milk fat metabolism in dairy cows, thus providing an experimental basis for the improvement of milk quality.Hydrophilic interaction liquid chromatography (HILIC) and electrospray ionization (ESI) coupled to either Fourier-transform (FT) orbital-trap or linear ion-trap tandem mass spectrometry (LIT-MS/MS) was used to characterize the phospholipidome of yellow lupin (Lupinus luteus) seeds. Phosphatidylcholines (PC) were the most abundant species (41 ± 6%), which were followed by lyso-forms LPC (30 ± 11%), phosphatidylethanolamines (PE, 13 ± 4%), phosphatidylglycerols (PG, 5.1 ± 1.7%), phosphatidic acids (PA, 4.9 ± 1.8%), phosphatidylinositols (PI, 4.7 ± 1.1%), and LPE (1.2 ± 0.5%). The occurrence of both isomeric forms of several LPC and LPE was inferred by a well-defined fragmentation pattern observed in negative ion mode. An unprecedented characterization of more than 200 polar lipids including 52 PC, 42 PE, 42 PA, 35 PG, 16 LPC, 13 LPE, and 10 PI, is reported. The most abundant fatty acids (FA) as esterified acyl chains in PL were 181 (oleic), 182 (linoleic), 160 (palmitic), and 183 (linolenic) with relatively high contents of long fatty acyl chains such as 220 (behenic), 240 (lignoceric), 201 (gondoic), and 221 (erucic). Their occurrence was confirmed by reversed-phase (RP) LC-ESI-FTMS analysis of a chemically hydrolyzed sample extract in acid conditions at 100 °C for 45 min.The Mar Menor is a hypersaline coastal lagoon with high environmental value and a characteristic example of a highly anthropized hydro-ecosystem located in the southeast of Spain. An unprecedented eutrophication crisis in 2016 and 2019 with abrupt changes in the quality of its waters caused a great social alarm. Understanding and modeling the level of a eutrophication indicator, such as chlorophyll-a (Chl-a), benefits the management of this complex system. In this study, we investigate the potential machine learning (ML) methods to predict the level of Chl-a. Particularly, Multilayer Neural Networks (MLNNs) and Support Vector Regressions (SVRs) are evaluated using as a target dataset information of up to nine different water quality parameters. The most relevant input combinations were extracted using wrapper feature selection methods which simplified the structure of the model, resulting in a more accurate and efficient procedure. Although the performance in the validation phase showed that SVR models obtained better results than MLNNs, experimental results indicated that both ML algorithms provide satisfactory results in the prediction of Chl-a concentration, reaching up to 0.7 R2CV (cross-validated coefficient of determination) for the best-fit models.Quantifying the response of cancer cells to a drug, and understanding the mechanistic basis of the response, are the cornerstones for anti-cancer drug discovery. Classical single target-based IC50 measurements are inadequate at describing cancer cell responses to targeted drugs. In this study, based on an analysis of targeted inhibition of colorectal cancer cell lines, we develop a new biphasic mathematical model that accurately describes the cell-drug response. The model describes the drug response using three kinetic parameters ratio of target-specific inhibition, F1, potency of target-specific inhibition, Kd1, and potency of off-target toxicity, Kd2. Determination of these kinetic parameters also provides a mechanistic basis for predicting effective combination targeted therapy for multi-driver cancer cells. The experiments confirmed that a combination of inhibitors, each blocking a driver pathway and having a distinct target-specific effect, resulted in a potent and synergistic blockade of cell viability, improving potency over mono-agent treatment by one to two orders of magnitude. We further demonstrate that mono-driver cancer cells represent a special scenario in which F1 becomes nearly 100%, and the drug response becomes monophasic. Application of this model to the responses of >400 cell lines to kinase inhibitor dasatinib revealed that the ratio of biphasic versus monophasic responses is about 41. This study develops a new mathematical model of quantifying cancer cell response to targeted therapy, and suggests a new framework for developing rational combination targeted therapy for colorectal and other multi-driver cancers.Obesity is characterized by the excessive deposition of fat that may interfere with the normal metabolic process of the body. It is a chronic condition associated with various metabolic syndromes, whose prevalence is grossly increasing, and affects both children and adults. Accumulation of excessive macronutrients on the adipose tissues promotes the secretion and release of inflammatory mediators, including interleukin-6 (IL-6), interleukin 1β, tumor necrotic factor-α (TNF-α), leptin, and stimulation of monocyte chemoattractant protein-1 (MCP-1), which subsequently reduce the production of adiponectin thereby initiating a proinflammatory state. During obesity, adipose tissue synthesizes and releases a large number of hormones and cytokines that alter the metabolic processes, with a profound influence on endothelial dysfunction, a situation associated with the formation of atherosclerotic plaque. Endothelial cells respond to inflammation and stimulation of MCP-1, which is described as the activation of adhesion molecules leading to proliferation and transmigration of leukocytes, which facilitates their increase in atherogenic and thromboembolic potentials.
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