Endotoxin-induced monocytic microparticles have contrasting effects on endothelial inflammatory responses

Septic shock is a severe disease state characterised by the body's life threatening response to infection. Complex interactions between endothelial cells and circulating monocytes are responsible for microvasculature dysfunction contributing to the pathogenesis of this syndrome. Here, we intended to determine whether microparticles derived from activated monocytes contribute towards inflammatory processes and notably vascular permeability. We found that endotoxin stimulation of human monocytes enhances the release of microparticles of varying phenotypes and mRNA contents. Elevated numbers of LPS-induced monocytic microparticles (mMP) expressed CD54 and contained higher levels of transcripts for pro-inflammatory cytokines such as TNF, IL-6 and IL-8. Using a prothrombin time assay, a greater reduction in plasma coagulation time was observed with LPS-induced mMP than with non-stimulated mMP. Co-incubation of mMP with the human brain endothelial cell line hCMEC/D3 triggered their time-dependent uptake and significantly enhanced endothelial microparticle release. Unexpectedly, mMP also modified signalling pathways by diminishing pSrc (tyr416) expression and promoted endothelial monolayer tightness, as demonstrated by endothelial impedance and permeability assays. Altogether, these data strongly suggest that LPS-induced mMP have contrasting effects on the intercellular communication network and display a dual potential: enhanced pro-inflammatory and procoagulant properties, together with protective function of the endothelium. © 2014 Wen et al

Intergenerational correlations in size at birth and the contribution of environmental factors: The Uppsala Birth Cohort Multigenerational Study, Sweden, 1915-2002.

Sizes at birth of parents and their children are known to be correlated, reflecting in part the influence of fetal and maternal genes. Sociodemographic factors, regarded as aspects of the shared environment across generations, would also be expected to contribute, but evidence is limited. In the present study, the authors aimed to quantify the role of the shared environment in explaining intergenerational correlations in birth weight and length by using data across 3 consecutive generations from the Uppsala Birth Cohort Multigenerational Study in Uppsala, Sweden. That study included birth and sociodemographic data on 7,657 singletons born in Uppsala in 1915-1929 (generation 1) and their grandchildren (generation 3). Standard regression and biometric models were used to study the correlations in size at birth of generation 1-generation 3 pairs. The data showed stronger correlations in maternal pairs than in paternal pairs for birth weight (0.125 vs. 0.096, P = 0.02) but not for birth length (0.097 vs. 0.093, P = 0.77). These correlations were not reduced by adjustment for sociodemographic factors in regression models. In contrast, significant shared-environment contributions to the intergenerational correlations were identified in biometric models, averaging 14% for both birth measures. These models assumed a common latent factor for the sociodemographic variables. The present results show that the shared environment moderately but significantly contributes to intergenerational correlations

Effective and Efficient Stand Magnifier Use in Visually Impaired Children

Contains fulltext : 167758.pdf (publisher's version ) (Open Access)PURPOSE: The main objective of this study was to analyze the effectiveness and efficiency of magnifier use in children with visual impairment who did not use a low vision aid earlier, in an ecologically valid goal-directed perceptuomotor task. METHODS: Participants were twenty-nine 4- to 8-year-old children with visual impairment and 47 age-matched children with normal vision. After seeing a first symbol (an Lea Hyvarinen [LH] symbol), children were instructed to (1) move the stand magnifier as quickly as possible toward a small target symbol (another LH symbol that could only be seen by using the magnifier), (2) compare the two symbols, and (3) move the magnifier to one of two response areas to indicate whether the two symbols were identical. Performance was measured in terms of accuracy, response time, identification time, and movement time. Viewing distance, as well as hand and eye dominance while using the magnifier was assessed. RESULTS: There were no significant differences between the two groups in accuracy, reaction time, and movement time. Contrary to the prediction, children with visual impairment required less time to identify small symbols than children with normal vision. Both within-subject and between-subject variability in viewing distance were smaller in the visually impaired group than in the normally sighted group. In the visually impaired group, a larger viewing distance was associated with shorter identification time, which in turn was associated with higher accuracy. In the normally sighted group, a faster movement with the magnifier and a faster identification were associated with increasing age. CONCLUSION: The findings indicate that children with visual impairment can use the stand magnifier adequately and efficiently. The normally sighted children show an age-related development in movement time and identification time and show more variability in viewing distance, which is not found in visually impaired children. Visually impaired children seem to choose a standard but less adaptive strategy in which they primarily used their preferred hand to manipulate the magnifier and their preferred eye to identify the symbol. TRIAL REGISTRATION: Registered at http://www.trialregister.nl; NTR2380.11 p

Sorting of chromosomes by magnetic separation

Chromosomes were isolated from Chinese hamster x human hybrid cell lines containing four and nine human chromosomes. Human genomic DNA was biotinylated by nick translation and used to label the human chromosomes by in situ hybridization in suspension. Streptavidin was covalently coupled to the surface of magnetic beads and these were incubated with the hybridized chromosomes. The human chromosomes were bound to the magnetic beads through the strong biotin-streptavidin complex and then rapidly separated from nonlabeled Chinese hamster chromosomes by a simple permanent magnet. The hybridization was visualized by additional binding of avidin-FITC (fluorescein) to the unoccupied biotinylated human DNA bound to the human chromosomes. After magnetic separation, up to 98% of the individual chromosomes attached to magnetic beads were classified as human chromosomes by fluorescence microscopy

Episodic Star Formation Coupled to Reignition of Radio Activity in 3C 236

We present Hubble Space Telescope UV and optical imaging of the radio galaxy 3C 236, whose relic 4 Mpc radio jet lobes and inner 2 kpc CSS radio source are evidence of multiple epochs of AGN activity. Our data confirm the presence of four bright knots of FUV emission in an arc along the edge of the inner circumnuclear dust disk in the galaxy's nucleus, as well as FUV emission cospatial with the nucleus itself. We interpret these to be sites of recent or ongoing star formation. We present photometry of these knots, as well as an estimate for the internal extinction in the source using the Balmer decrement from SDSS spectroscopy. We estimate the ages of the knots by comparing our extinction-corrected photometry with stellar population synthesis models. We find the four knots cospatial with the dusty disk to be young, of order 10^7 yr old. The FUV emission in the nucleus is likely due to an episode of star formation triggered ~10^9 yr ago. We argue that the young 10^7 yr old knots stem from an episode of star formation that was roughly coeval with the event resulting in reignition of radio activity, creating the CSS source. The 10^9 yr old stars in the nucleus may be associated with the previous epoch of activity that generated the 4 Mpc relic source, before it was cut off by exhaustion or interruption. The ages of the knots, considered in context with the disturbed morphology of the nuclear dust and the double-double morphology of the "old" and "young" radio sources, present evidence for an episodic AGN/starburst connection. We suggest that the AGN fuel supply was interrupted for ~10^7 yr due to a minor merger event and has now been restored, and the resultant non-steady flow of gas toward the nucleus is likely responsible for both the new episode of infall-induced star formation and also the multiple epochs of radio activity.Comment: 15 pages, 7 figures. Accepted for publication in ApJ

Features of Muon Arrival Time Distributions of High Energy EAS at Large Distances From the Shower Axis

In view of the current efforts to extend the KASCADE experiment (KASCADE-Grande) for observations of Extensive Air Showers (EAS) of primary energies up to 1 EeV, the features of muon arrival time distributions and their correlations with other observable EAS quantities have been scrutinised on basis of high-energy EAS, simulated with the Monte Carlo code CORSIKA and using in general the QGSJET model as generator. Methodically various correlations of adequately defined arrival time parameters with other EAS parameters have been investigated by invoking non-parametric methods for the analysis of multivariate distributions, studying the classification and misclassification probabilities of various observable sets. It turns out that adding the arrival time information and the multiplicity of muons spanning the observed time distributions has distinct effects improving the mass discrimination. A further outcome of the studies is the feature that for the considered ranges of primary energies and of distances from the shower axis the discrimination power of global arrival time distributions referring to the arrival time of the shower core is only marginally enhanced as compared to local distributions referring to the arrival of the locally first muon.Comment: 24 pages, Journal Physics G accepte

Wyniki leczenia topiramatem padaczki u osób w podeszłym wieku

Cele. Ocena skuteczności, tolerancji i jakości życia u starszych pacjentów z padaczką, leczonych topiramatem. Metody. Otwarte, trwające rok badanie kliniczne z elastycznym dawkowaniem. Wyniki. Przebadano 107 pacjentów (średni wiek 69 lat; 53% mężczyzn) przez okres 273 &#177; 141 dni. Średnia dawka, którą osiąga- no ostatecznie w monoterapii, wynosiła 98 mg/dobę - w porównaniu z 153 mg/dobę w ramach leczenia wspomagającego. Średnia skumulowana miesięczna częstość napadów padaczkowych zmniejszyła się z 3,7 &#177; 15 do 1,6 &#177; 7,7 (n = 101; p < 0,0001). U 78% pacjentów z napadami padaczkowymi w momencie rozpoczęcia badania (n = 102) osiągnięto przynajmniej 50-procentową redukcję częstości napadów, 44% nie miało napadów w okresie badania. Całkowita punktacja w skali jakości &#348;ycia osób z padaczką (QOLIE-31) poprawiła się z 57 &#177; 17 na 68 &#177; 18 (n = 64; p < 0,0001). Najczęściej zgłaszanymi zdarzeniami niepożądanymi były drgawki, zawroty głowy i zmęczenie. Wnioski. Pacjenci w starszym wieku leczeni topiramatem osiągali wyraźne zmniejszenie liczby napadów padaczkowych i istotną poprawę w zakresie licznych aspektów jakości życia przy dobrej tolerancji leku