35 research outputs found

    Anatomical Correlates of Age-Related Working Memory Declines

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    Aging studies consistently show a relationship between decreased gray matter volume and decreased performance on working memory tasks. Few aging studies have investigated white matter changes in relation to functional brain changes during working memory tasks. Twenty-five younger and 25 older adults underwent anatomical magnetic resonance imaging (MRI) scans to measure gray matter volume, diffusion tensor imaging (DTI) to measure fractional anisotropy (FA) as a measure of white matter integrity, and functional magnetic resonance imaging (fMRI) while performing a working memory task. Significant increases in activation (fMRI) were seen in the left dorsal and ventral lateral prefrontal cortex with increased working memory load and with increased age (older showing greater bilateral activation). Partial correlational analyses revealed that even after controlling for age, frontal FA correlated significantly with fMRI activation during performance on the working memory task. These findings highlight the importance of white matter integrity in working memory performance associated with normal aging

    Spatially aggregated clusters and scattered smaller loci of elevated malaria vector density and human infection prevalence in urban Dar es Salaam, Tanzania

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    Background Malaria transmission, primarily mediated by Anopheles gambiae, persists in Dar es Salaam (DSM) despite high coverage with bed nets, mosquito-proofed housing and larviciding. New or improved vector control strategies are required to eliminate malaria from DSM, but these will only succeed if they are delivered to the minority of locations where residual transmission actually persists. Hotspots of spatially clustered locations with elevated malaria infection prevalence or vector densities were, therefore, mapped across the city in an attempt to provide a basis for targeting supplementary interventions. Methods Two phases of a city-wide population-weighted random sample of cross-sectional household surveys of malaria infections were complemented by two matching phases of geographically overlapping, high-resolution, longitudinal vector density surveys; spanning 2010–2013. Spatial autocorrelations were explored using Moran’s I and hotspots were detected using flexible spatial scan statistics. Results Seven hotspots of spatially clustered elevated vector density and eight of malaria infection prevalence were detected over both phases. Only a third of vectors were collected in hotspots in phase 1 (30 %) and phase 2 (33 %). Malaria prevalence hotspots accounted for only half of malaria infections detected in phase 1 (55 %) and phase 2 (47 %). Three quarters (76 % in phase 1 and 74 % in phase 2) of survey locations with detectable vector populations were outside of hotspots. Similarly, more than half of locations with higher infection prevalence (>10 %) occurred outside of hotspots (51 % in phase 1 and 54 % in phase 2). Vector proliferation hazard (exposure to An. gambiae) and malaria infection risk were only very loosely associated with each other (Odds ratio (OR) [95 % Confidence Interval (CI)] = 1.56 [0.89, 1.78], P = 0.52)). Conclusion Many small, scattered loci of local malaria transmission were haphazardly scattered across the city, so interventions targeting only currently identifiable spatially aggregated hotspots will have limited impact. Routine, spatially comprehensive, longitudinal entomological and parasitological surveillance systems, with sufficient sensitivity and spatial resolution to detect these scattered loci, are required to eliminate transmission from this typical African city. Intervention packages targeted to both loci and hotspots of transmission will need to suppress local vector proliferation, treat infected residents and provide vulnerable residents with supplementary protective measures against exposure

    SheddomeDB: the ectodomain shedding database for membrane-bound shed markers

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    Entstehung und Vermeidung von Betonabplatzungen bei extremer Brandeinwirkung

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    Available from TIB Hannover: RA 1125(172) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

    What the evolution of the amyloid protein precursor supergene family tells us about its function

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    The Alzheimer's disease amyloid protein precursor (APP) gene is part of a multi-gene super-family from which sixteen homologous amyloid precursor-like proteins (APLP) and APP species homologues have been isolated and characterised. Comparison of exon structure (including the uncharacterised APL-1 gene), construction of phylogenetic trees, and analysis of the protein sequence alignment of known homologues of the APP super-family were performed to reconstruct the evolution of the family and to assess the functional significance of conserved protein sequences between homologues. This analysis supports an adhesion function for all members of the APP super family, with specificity determined by those sequences which are not conserved between APLP lineages, and provides evidence for an increasingly complex APP superfamily during evolution. The analysis also suggests that Drosophila APPL and Caenorhabdotids elegans APL-1 may be a fourth APLP lineage indicating that these proteins, while not functional homologues of human APP, are similarly likely to regulate cell adhesion. Furthermore, the beta A4 sequence is highly conserved only in APP orthologues, strongly suggesting this sequence is of significant functional importance in this lineage. (C) 2000 Elsevier Science Ltd. All rights reserved

    Prevalence of healthcare-associated cervicitis and antimicrobial resistance of the responsible pathogens in Ukraine: results of a multicenter study (2019-2021)

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    The aim: To obtain the first estimates of the current prevalence of healthcare-associated cervicitis (HACs) and antimicrobial resistance of responsible pathogens in Ukraine. Materials and methods: We conducted a retrospective multicentre cohort study was based on surveillance data from January 1st, 2019 to December 31st, 2021 in Ukraine. Antibiotic susceptibility testing was determined by Kirby–Bauer disc diffusion test according to the protocol of the European Committee on Antimicrobial Susceptibility Testing. Results: Of the 6,885 participants in this study, 1746 women (25.5%) met the clinical definition of cervicitis. Prevalence of HACs and cervcits caused sexually transmitted pathogens were 12.7% and 8.3%, respectively. The incidence of HACs among women with a history of gynecological procedures was 25.4%. The main causes of HACs were legal induced abortions (28.8%), vaginal hysterectomy (23.9%), and postpartum instrumental examination (12.8%). The predominant pathogens of HACs were: Escherichia coli, Enterobacter spp., Klebsiella spp., Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecalis. Methicillin-resistance was observed in 20.8% of S. aureus (MRSA). Vancomycin resistance was observed in 7.4% of isolated enterococci (VRE). Resistance to third-generation cephalosporins was observed in 13.1% Klebsiella spp. and E.coli 17.5% isolates. Carbapenem resistance was identified in 11.6% of P.aeruginosa isolates. The prevalence of ESBL production among E. coli isolates was significantly higher than in K. pneumoniae (33.5%, vs 8.7%). The overall proportion of extended spectrum beta-lactamases (ESBL) production among Enterobacteriaceae was 34.6%. Conclusions: This study showed that the prevalence of healthcare-associated cervicitis in Ukraine is high, and many cases were caused by antibiotic-resistant pathogens

    Apoptosis is a natural stimulus of IL6R shedding and contributes to the proinflammatory trans-signaling function of neutrophils

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    Interleukin 6 (IL6) trans-signaling has emerged as a prominent regulator of immune responses during both innate and acquired immunity. Regulation of IL6 trans-signaling is reliant upon the release of soluble IL6 receptor (sIL6R), which binds IL6 to create an agonistic IL6/sIL6R complex capable of activating cell types that would not normally respond to IL6 itself. Here we show that intrinsic and extrinsic apoptotic stimulation by DNA damage, cytokine deprivation, and Fas stimulation promotes shedding of sIL6R. Apoptosis-induced shedding of the IL6R was caspase dependent but PKC independent, with inhibition of ADAM17 preventing IL6R shedding. Such insight is relevant to the control of acute inflammation, where transition from the initial neutrophil infiltration to a more sustained population of mononuclear cells is essential for the resolution of the inflammatory process. This transitional event is governed by IL6 trans-signaling. This study demonstrates that IL6R is shed from apoptotic human neutrophils. In vivo studies in a murine inflammation model showed that neutrophil depletion resulted in reduced local sIL6R levels and a concomitant decrease in mononuclear cells, suggesting that apoptosis-induced IL6R shedding from neutrophils promotes IL6 trans-signaling and regulates the attraction of monocytic cells involved in the clearance of apoptotic neutrophils
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