Different expression of [béta] subunits of the KCa1.1 channel by invasive and non-invasive human fibroblast-like synoviocytes

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'If You Desire to Enjoy Life, Avoid Unpunctual People': Women, Timetabling and Domestic Advice, 1850–1910

In the second half of the nineteenth century domestic advice manuals applied the language of modern, public time management to the private sphere. This article uses domestic advice and cookery books, including Isabella Beeton's Book of Household Management, to argue that women in the home operated within multiple, overlapping temporalities that incorporated daily, annual, linear and cyclical scales. I examine how seasonal and annual timescales coexisted with the ticking clock of daily time as a framework within which women were instructed to organize their lives in order to conclude that the increasing concern of advice writers with matters of timekeeping and punctuality towards the end of the nineteenth century indicates not the triumph of 'clock time' but rather its failure to overturn other ways of thinking about and using time

The Paradoxical Effects of Chronic Intra-Amniotic Ureaplasma parvum Exposure on Ovine Fetal Brain Development

Chorioamnionitis is associated with adverse neurodevelopmental outcomes in preterm infants. Ureaplasma spp. are the microorganisms most frequently isolated from the amniotic fluid of women diagnosed with chorioamnionitis. However, controversy remains concerning the role of Ureaplasma spp. in the pathogenesis of neonatal brain injury. We hypothesize that re-exposure to an inflammatory trigger during the perinatal period might be responsible for the variation in brain outcome of preterms following Ureaplasma driven chorioamnionitis. To investigate these clinical scenarios, we performed a detailed multi-modal study in which ovine neurodevelopmental outcomes were assessed following chronic intra-amniotic Ureaplasma parvum (UP) infection, either alone or combined with subsequent lipopolysaccharide (LPS) exposure. We show that chronic intra-amniotic UP exposure during the second trimester provoked a decrease of astrocytes, increased oligodendrocyte numbers and elevated 5-methylcytosine levels. In contrast, short-term LPS exposure before preterm birth induced increased microglial activation, myelin loss, elevation of 5-hydroxymethylcytosine levels and lipid profile changes. These LPS-induced changes were prevented by chronic pre-exposure to UP (preconditioning). These data indicate that chronic UP exposure provokes dual effects on preterm brain development in utero. On one hand, prolonged UP exposure causes detrimental cerebral changes which may predispose to adverse postnatal clinical outcomes. On the other, chronic intra-amniotic UP exposure preconditions the brain against a second inflammatory hit. This study demonstrates that microbial interactions, timing and duration of inflammatory insults will determine the effects on the fetal brain. Therefore, this study helps to understand the complex and diverse postnatal neurological outcomes following UP driven chorioamnionitis

A comprehensive database of quality-rated fossil ages for Sahul’s Quaternary vertebrates

Published: 19 July 2016The study of palaeo-chronologies using fossil data provides evidence for past ecological and evolutionary processes, and is therefore useful for predicting patterns and impacts of future environmental change. However, the robustness of inferences made from fossil ages relies heavily on both the quantity and quality of available data. We compiled Quaternary non-human vertebrate fossil ages from Sahul published up to 2013. This, the FosSahul database, includes 9,302 fossil records from 363 deposits, for a total of 478 species within 215 genera, of which 27 are from extinct and extant megafaunal species (2,559 records). We also provide a rating of reliability of individual absolute age based on the dating protocols and association between the dated materials and the fossil remains. Our proposed rating system identified 2,422 records with high-quality ages (i.e., a reduction of 74%). There are many applications of the database, including disentangling the confounding influences of hypothetical extinction drivers, better spatial distribution estimates of species relative to palaeo-climates, and potentially identifying new areas for fossil discovery.Marta Rodríguez-Rey, y, Salvador Herrando-Pérez, Barry W. Brook, Frédérik Saltré, John Alroy, Nicholas Beeton, Michael I. Bird, Alan Cooper, Richard Gillespie, Zenobia Jacobs, Christopher N. Johnson, Gifford H. Miller, Gavin J. Prideaux, Richard G. Roberts, Chris S.M. Turney and Corey J.A. Bradsha

Exclusively cephalic venous access for cardiac resynchronisation: A prospective multi-centre evaluation.

BACKGROUND: Small series has shown that cardiac resynchronisation therapy (CRT) can be achieved in a majority of patients using exclusively cephalic venous access. We sought to determine whether this method is suitable for widespread use. METHODS: A group of 19 operators including 11 trainees in three pacing centres attempted to use cephalic access alone for all CRT device implants over a period of 8 years. The access route for each lead, the procedure outcome, duration, and complications were collected prospectively. Data were also collected for 105 consecutive CRT device implants performed by experienced operators not using the exclusively cephalic method. RESULTS: A new implantation of a CRT device using exclusively cephalic venous access was attempted in 1091 patients (73.6% male, aged 73 ± 12 years). Implantation was achieved using cephalic venous access alone in 801 cases (73.4%) and using a combination of cephalic and other access in a further 180 (16.5%). Cephalic access was used for 2468 of 3132 leads implanted (78.8%). Compared to a non-cephalic reference group, complications occurred less frequently (69/1091 vs 12/105; P = .0468), and there were no pneumothoraces with cephalic implants. Procedure and fluoroscopy duration were shorter (procedure duration 118 ± 45 vs 144 ± 39 minutes, P < .0001; fluoroscopy duration 15.7 ± 12.9 vs 22.8 ± 12.2 minutes, P < .0001). CONCLUSIONS: CRT devices can be implanted using cephalic access alone in a substantial majority of cases. This approach is safe and efficient

Phenotypic and genotypic antimicrobial susceptibility patterns of the emerging human respiratory pathogen Mycoplasma amphoriforme isolated from the UK and Denmark

Methods Seven isolates of M. amphoriforme were examined for antimicrobial susceptibility to seven antibiotics using the microbroth dilution assay in line with the CLSI guidelines for mycoplasmas. Each isolate was additionally subjected to WGS to identify resistance-associated mutations. Based on the consensus sequences from the genomic data, PCR primers were designed, and tested, for the amplification of the QRDR within the parC gene. Results Of the seven isolates investigated, four (57%) were resistant to moxifloxacin (0.5–1 mg/L) and levofloxacin (1–2 mg/L), compared with those that were susceptible (0.03–0.06 and 0.006 mg/L, respectively). Isolate H29 was resistant to five of the seven antibiotics tested: moxifloxacin, 0.5 mg/L; levofloxacin, 2 mg/L; azithromycin, 64 mg/L; erythromycin, 128 mg/L; and clindamycin, 64 mg/L. All isolates were susceptible to tetracycline (0.06 mg/L) and lefamulin (0.001–0.004 mg/L). Mutations from genomic data confirmed the presence of an S89F mutation within the ParC protein among all fluoroquinolone-resistant isolates and an A2059G mutation in the 23S rRNA gene in the macrolide- and lincosamide-resistant isolate H29. Conclusions To the best of our knowledge, this is the first time where phenotypic and genotypic resistance data have been paired for M. amphoriforme confirming a correlation between the two. These data suggest the need for focused testing and resistance determination of isolates from high-risk patients given the backdrop of a high prevalence of antimicrobial resistance

Protection of the Ovine Fetal Gut against Ureaplasma-Induced Chorioamnionitis: A Potential Role for Plant Sterols

Chorioamnionitis, clinically most frequently associated with Ureaplasma, is linked to intestinal inflammation and subsequent gut injury. No treatment is available to prevent chorioamnionitis-driven adverse intestinal outcomes. Evidence is increasing that plant sterols possess immune-modulatory properties. Therefore, we investigated the potential therapeutic effects of plant sterols in lambs intra-amniotically (IA) exposed to Ureaplasma. Fetal lambs were IA exposed to Ureaplasma parvum (U. parvum, UP) for six days from 127 d–133 d of gestational age (GA). The plant sterols β-sitosterol and campesterol, dissolved with β-cyclodextrin (carrier), were given IA every two days from 122 d–131 d GA. Fetal circulatory cytokine levels, gut inflammation, intestinal injury, enterocyte maturation, and mucosal phospholipid and bile acid profiles were measured at 133 d GA (term 150 d). IA plant sterol administration blocked a fetal inflammatory response syndrome. Plant sterols reduced intestinal accumulation of proinflammatory phospholipids and tended to prevent mucosal myeloperoxidase-positive (MPO) cell influx, indicating an inhibition of gut inflammation. IA administration of plant sterols and carrier diminished intestinal mucosal damage, stimulated maturation of the immature epithelium, and partially prevented U. parvum-driven reduction of mucosal bile acids. In conclusion, we show that β-sitosterol and campesterol administration protected the fetus against adverse gut outcomes following UP-driven chorioamnionitis by preventing intestinal and systemic inflammation