77 research outputs found

    Outpatient decolonization after recurrent skin infection with Panton-Valentine leukocidin (PVL)-producing S. aureus - The importance of treatment repetition

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    Background: Recurrent skin abscesses are often associated with Panton-Valentine leukocidin-producing strains of S. aureus (PVL-SA). Decolonization measures are required along with treatment of active infections to prevent re-infection and spreading. Even though most PVL-SA patients are treated as outpatients, there are few studies that assess the effectiveness of outpatient topical decolonization in PVL-SA patients. Methods: We assessed the results of topical decolonization of PVL-SA in a retrospective review of patient files and personal interviews. Successful decolonization was defined as the absence of any skin abscesses for at least 6 months after completion of the final decolonization treatment. Clinical and demographic data was assessed. An intention-to-treat protocol was used. Results: Our cohort consisted of 115 symptomatic patients, 66% from PVL-positive MSSA and 19% from PVL-positive MRSA. The remaining 16% consisted of symptomatic patients with close contact to PVL-SA positive index patients but without detection of PVL-SA. The majority of patients were female (66%). The median age was 29.87% of the patients lived in multiple person households. Our results showed a 48% reduction in symptomatic PVL-SA cases after the first decolonization treatment. The results also showed that the decrease continued with each repeated decolonization treatment and reached 89% following the 5th treatment. A built multivariable Cox proportional-hazards model showed that the absence of PVL-SA detection (OR 2.0) and living in single person households (OR 2.4) were associated with an independently increased chance of successful decolonization. Conclusion: In our cohort, topical decolonization was a successful preventive measure for reducing the risk of PVL-SA skin abscesses in the outpatient setting. Special attention should be given to patients living in multiple person households because these settings could confer a risk that decolonization will not be successful

    Retrospective rigid motion correction of undersampled MRI data

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    The present study combines retrospective motion correction and GRAPPA reconstruction. We propose a technique that performs several alternations of GRAPPA interpolation and motion correction steps, suppressing the artifacts caused by motion over the course of the optimization. Motion parameters are estimated directly from the data with the aid of free induction decay navigators. The proposed algorithm does not require a priori knowledge of coil sensitivity profiles and can be applied retrospectively to data acquired with generic sequences such as MP-RAGE. The algorithm was tested on motion corrupted brain images of healthy volunteers, performing controlled head movement during the scan. Results demonstrate a significant improvement in image quality

    Severe infections of Panton-Valentine leukocidin positive Staphylococcus aureus in children

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    Infections caused by Panton-Valentine leukocidin-positive Staphylococcus aureus (PVL-SA) mostly present as recurrent skin abscesses and furunculosis. However, life-threatening infections (eg, necrotizing pneumonia, necrotizing fasciitis, and osteomyelitis) caused by PVL-SA have also been reported.We assessed the clinical phenotype, frequency, clinical implications (surgery, length of treatment in hospitals/intensive care units, and antibiotic treatments), and potential preventability of severe PVL-SA infections in children.Total, 75 children treated for PVL-SA infections in our in- and outpatient units from 2012 to 2017 were included in this retrospective study.Ten out of 75 children contracted severe infections (PVL-methicillin resistant S aureus n = 4) including necrotizing pneumonia (n = 4), necrotizing fasciitis (n = 2), pyomyositis (n = 2; including 1 patient who also had pneumonia), mastoiditis with cerebellitis (n = 1), preorbital cellulitis (n = 1), and recurrent deep furunculosis in an immunosuppressed patient (n = 1). Specific complications of PVL-SA infections were venous thrombosis (n = 2), sepsis (n = 5), respiratory failure (n = 5), and acute respiratory distress syndrome (n = 3). The median duration of hospital stay was 14 days (range 5-52 days). In 6 out of 10 patients a history suggestive for PVL-SA colonization in the patient or close family members before hospital admission was identified.PVL-SA causes severe to life-threatening infections requiring lengthy treatments in hospital in a substantial percentage of symptomatic PVL-SA colonized children. More than 50% of severe infections might be prevented by prompt testing for PVL-SA in individuals with a history of abscesses or furunculosis, followed by decolonization measures

    MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration

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    Background: MicroRNA (miRNA) expression in the brain is altered in neurodegenerative diseases. Recent studies demonstrated that selected miRNAs conventionally regulating gene expression at the post-transcriptional level can act extracellularly as signaling molecules. The identity of miRNA species serving as membrane receptor ligands involved in neuronal apoptosis in the central nervous system (CNS), as well as the miRNAs' sequence and structure required for this mode of action remained largely unresolved. Methods. Using a microarray-based screening approach we analyzed apoptotic cortical neurons of C56BL/6 mice and their supernatant with respect to alterations in miRNA expression/presence. HEK-Blue Toll-like receptor (TLR) 7/8 reporter cells, primary microglia and macrophages derived from human and mouse were employed to test the potential of the identified miRNAs released from apoptotic neurons to serve as signaling molecules for the RNA-sensing receptors. Biophysical and bioinformatical approaches, as well as immunoassays and sequential microscopy were used to analyze the interaction between candidate miRNA and TLR. Immunocytochemical and -histochemical analyses of murine CNS cultures and adult mice intrathecally injected with miRNAs, respectively, were performed to evaluate the impact of miRNA-induced TLR activation on neuronal survival and microglial activation. Results: We identified a specific pattern of miRNAs released from apoptotic cortical neurons that activate TLR7 and/or TLR8, depending on sequence and species. Exposure of microglia and macrophages to certain miRNA classes released from apoptotic neurons resulted in the sequence-specific production of distinct cytokines/chemokines and increased phagocytic activity. Out of those miRNAs miR-100-5p and miR-298-5p, which have consistently been linked to neurodegenerative diseases, entered microglia, located to their endosomes, and directly bound to human TLR8. The miRNA-TLR interaction required novel sequence features, but no specific structure formation of mature miRNA. As a consequence of miR-100-5p- and miR-298-5p-induced TLR activation, cortical neurons underwent cell-autonomous apoptosis. Presence of miR-100-5p and miR-298-5p in cerebrospinal fluid led to neurodegeneration and microglial accumulation in the murine cerebral cortex through TLR7 signaling. Conclusion: Our data demonstrate that specific miRNAs are released from apoptotic cortical neurons, serve as endogenous TLR7/8 ligands, and thereby trigger further neuronal apoptosis in the CNS. Our findings underline the recently discovered role of miRNAs as extracellular signaling molecules, particularly in the context of neurodegeneration

    Xenoandrogenic Activity in Serum Differs across European and Inuit Populations

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    Background: Animal and in vitro studies have indicated that human male reproductive disorders can arise as a result of disrupted androgen receptor (AR) signalling by persistent organic pollutants (POPs) . Our aim in the present study was to compare serum xenoandrogenic activity between study groups with different POP exposures and to evaluate correlations to the POP proxy markers 2,2\ub4,4,4\ub4,5,5\ub4-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl) -ethylene (p,p\ub4-DDE) .Methods: We determined xenoandrogenic activity in the serum fraction containing the lipophilic POPs but free of endogenous hormones. Adult male serum (n = 261) from Greenland, Sweden, Warsaw (Poland) , and Kharkiv (Ukraine) was analyzed. Xenoandrogenic activity was determined as the effect of serum extract alone (XAR) and in the presence of the synthetic AR agonist R1881 (XARcomp) on AR transactivated luciferase activity.Results: The study groups differed significantly with respect to XARcomp activity, which was increased in the Inuits and decreased in the European study groups ; we observed no difference for XAR activity. We found the highest level of the AR antagonist p,p\ub4-DDE in Kharkiv, and accordingly, this study group showed the highest percent of serum samples with decreased XARcomp activities. Furthermore, the percentage of serum samples with decreased XARcomp activities followed the p,p\ub4-DDE serum level for the European study groups. No correlations between serum XAR or XARcomp activities and the two POP markers were revealed.Conclusions: The differences in XARcomp serum activity between the study groups suggest differences in chemical exposure profiles, genetics, and/or lifestyle factors
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