Waltersecher6093

Infections caused by metallo-β-lactamase (MBL)-producing bacteria are emerging and carry a significant impact on patients' outcome. MBL producers are spread worldwide, both in community and hospital setting, with increasingly reported epidemic clusters and the search for MBL inhibitors is an important topic for public health. MBLs are zinc-dependent enzymes whose functioning can be hampered by zinc chelators. We evaluated the potential of six zinc chelators (disulfiram, nitroxoline, 5-amino-8-hydroxyquinoline, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid [DOTA], cyclam, and N,N,N',N'-tetrakis (2-pyridymethyl) ethylenediamine [TPEN]) in restoring carbapenem activity against MBL producers. Zinc chelators alone or in combination with meropenem against MBL-producing Klebsiella pneumoniae, Chryseobacterium indologenes, Elizabethkingia meningoseptica, and Stenotrophomonas maltophilia isolates were tested in vitro and in vivo (Galleria mellonella). In vitro experiments showed a synergistic activity between TPEN and meropenem toward all the strains. Nitroxoline alone retained activity against S. maltophilia, C. indologenes, and E. meningoseptica. In vivo experiments showed that TPEN or nitroxoline in combination with meropenem increased survival in larvae infected with E. meningoseptica, S. maltophilia, and K. pneumoniae. Based on our data, zinc chelators are potential carbapenem adjuvants molecules (restoring carbapenem activity) against MBL-sustained infections and could represent an interesting option for infections induced by these microorganisms.Knowledge about bone morphology and bone quality of the scapula throughout the population is fundamental in the design of shoulder implants. In particular, regions with the best bone stock (cortical bone) are taken into account when planning the supporting screws, aiming for an optimal fixation. As an alternative to manual measurements, statistical shape models (SSMs) have been commonly used to describe shape variability within a population. However, explicitly including cortical thickness information in an SSM of the scapula still remains a challenge. Therefore, the goal of this study is to combine scapular bone shape and cortex morphology in an SSM. First, a method to estimate cortical thickness, based on HU (Hounsfield Unit) profile analysis, was developed and validated. Then, based on the manual segmentations of 32 healthy scapulae, a statistical shape model including cortical information was created and evaluated. Generalization, specificity and compactness were calculated in order to assess the quality of the SSM. The average cortical thickness of the SSM was 2.0 ± 0.63 mm. Generalization, specificity and compactness performances confirmed that the combined SSM was able to capture the bone quality changes in the population. In this work we integrated information on the cortical thickness in an SSM for the scapula. From the results we conclude that this methodology is a valuable tool for automatically generating a large population of scapulae and deducing statistics on the cortex. Hence, this SSM can be useful to automate implant design and screw placement in shoulder arthroplasty.Interferon-λ (IFN-λ) plays an important role in mucosal immunity, but reliable information regarding the expression of the IFN-λ receptor in individual cells is still missing. One reason for this knowledge gap is the lack of antibodies that specifically recognize the unique IFNLR1 subunit of the dimeric IFN-λ receptor complex. In this study, we investigated whether a reporter mouse carrying a bacterial β-galactosidase gene inserted into the Ifnlr1 locus could be used to visualize IFN-λ receptor-expressing cells in whole organs. First we confirmed that insertion of the reporter cassette inactivated the Ifnlr1 gene, and that gene function could be restored by removing the β-galactosidase insert by site-specific recombination. When whole tissues were analyzed, prominent β-galactosidase activity was confined to the intestinal tract of reporter mice. However, only the snout expressed β-galactosidase at levels high enough for reliable detection in whole tissue extracts. Interestingly, individual epithelial cells in the upper airways expressed β-galactosidase activity to variable degrees as determined by flow cytometry and histology, suggesting a remarkable heterogeneity in IFNLR1 expression levels. Taken together, our results demonstrate a surprisingly strong within- and cross-tissue heterogeneity of IFNLR1 expression that may have physiological implications.The present study aimed to evaluate the psychometric properties of the Brazilian adaptation of the Trait Emotional Intelligence Questionnaire-Short Form (TEIQue-SF). In a sample of 512 participants, we tested model fit by bifactor Exploratory Structural Equation Modeling (ESEM), followed by measurement invariance testing against UK and Chilean datasets of the measure. The Big Five Mini-Markers, Satisfaction with Life Scale and Subjective Happiness Scale were also administered as external validation measures. We obtained the following results (a) final adequate bifactor ESEM model fit; (b) a significantly higher global trait EI mean for men (d = .27); (c) high internal consistency for global trait EI (α = .88), in spite of lower Cronbach's α values at the factor level (.60-.85); (d) high correlation (r = .89) in the test-retest; (e) significant correlation between global trait EI and most of the Big Five dimensions (r = -.66-.46), life satisfaction (.59) and happiness (.68); (f) evidence of incremental validity of trait EI for life satisfaction and happiness over and above the Big Five; (g) equivalent measurement across the Brazilian, UK and Chilean versions of the TEIQue-SF. We conclude that the Brazilian TEIQue-SF is psychometrically sound and can be recommended for research and practical use.Background Childhood abuse has been associated with poor health outcomes in adulthood. However, the physiologic pathways by which abuse is linked to health are not fully elucidated. Inflammation plays a significant role in the pathophysiology of multiple chronic diseases. We tested whether childhood trauma exposure was related to increased systemic inflammation in midlife women. Barasertib-HQPA Materials and Methods Participants were 304 nonsmoking perimenopausal and postmenopausal women aged 40 to 60 years and free of cardiovascular disease. They completed questionnaires assessing psychosocial and behavioral factors, including childhood trauma, anthropometric measures, wrist actigraphy sleep measurements, and a fasting blood draw for inflammatory markers high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). Associations between childhood trauma and inflammatory markers were tested in linear regression models controlling for age, race/ethnicity, education, body mass index, anti-inflammatory medication use, and alcohol consumption.