The Role of Formylpeptide Receptors, C5a Receptors, and Cytosolic-Free Calcium in Neutrophil Priming

Polymorphonuclear leukocytes (PMNL) exposed to chemoattractants or cytokines change their functional capacity. The effect of endotoxin-activated serum as a priming agent on humanPMNL was tested. PretreatmentofPMNL with endotoxin-activated serum increased their oxidative burst in response to formylpeptide (FMLP) (P<.02)and CSa (P<.05). Priming for membrane depolarization was observed in PMNL preincubated with either endotoxin-activated serum, low concentrations of purified C5a, or endotoxin but not with decomplemented plasma. Primed PMNL had an increased number of FMLP but not C5a receptors as compared with control PMNL. The "resting” cytosolic freecalcium was increased in primed PMNL (P<.02). Intracellular calcium buffering abolished the priming effect of endotoxin-activated serum. Thus, endotoxin-activated serum can prime cellular responsiveness for membrane depolarization and superoxide production in response to FMLP and to C5a. Priming may be due to an increased resting cytosolic-free calciu

Function of Soluble CD14 in Serum from Patients with Septic Shock

Soluble CD14 (sCD14) mediates lipopolysaccharide (LPS) activation of epithelial cells in vitro and may thereby be harmful in sepsis.sCD14 function was analyzed in sera from 62 patients with septic shock and compared with data from appropriate controls. sCD14 function was measured as sCD14-dependentLPS-induced interleukin (IL)-8 release in the SW620 epithelial cell line. In these cells, IL-8 production correlated with LPS concentration and the amount of sCD14. The effect of natural or recombinant sCD14 was maximal at 100 ng/mL and blocked by anti-CD14 antibodies. Patient and control sera (0.5% final concentration) promoted induction of IL-8 by 100 ng/mL LPS in SW620 cells. In sepsis patients (highest serum sCD14), values were significantly higher than in the other groups. The LPS-induced IL-8 response was blocked by anti-CD14 and correlated with the serum CD14 level in sepsis patients. Thus, sCD14 could playa pathogenetic role in sepsi

A Crosslinguistic Study of Child Code-Switching within the Noun Phrase: A Usage-Based Perspective

This paper aims to investigate whether language use can account for the differences in code-switching within the article-noun phrase in children exposed to English and German, French and Russian, and English and Polish. It investigates two aspects of language use: equivalence and segmentation. Four children’s speech is derived from corpora of naturalistic interactions recorded between the ages of two and three and used as a source of the children’s article-noun phrases. We demonstrate that children’s CS cannot be fully explained by structural equivalence in each two languages: there is CS in French-Russian although French does, and Russian does not, use articles. We also demonstrate that language pairs which use higher numbers of articles types, and therefore have more segmented article-noun phrases, are also more open to switching. Lastly, we show that longitudinal use of monolingual articles-noun phrases corresponds with the trends in the use of bilingual article-noun phrases. The German-English child only starts to mix English articles once they become more established in monolingual combinations while the French-Russian child ceases to mix French proto-articles with Russian nouns once target articles enter frequent use. These findings are discussed in the context of other studies which report code-switching across different language pairs

Climate variability in the subarctic area for the last 2 millennia

To put recent climate change in perspective, it is necessary to extend the instrumental climate records with proxy data from paleoclimate archives. Arctic climate variability for the last 2 millennia has been investigated using statistical and signal analyses from three regionally averaged records from the North Atlantic, Siberia and Alaska based on many types of proxy data archived in the Arctic 2k database v1.1.1. In the North Atlantic and Alaska, the major climatic trend is characterized by long-term cooling interrupted by recent warming that started at the beginning of the 19th century. This cooling is visible in the Siberian region at two sites, warming at the others. The cooling of the Little Ice Age (LIA) was identified from the individual series, but it is characterized by wide-range spatial and temporal expression of climate variability, in contrary to the Medieval Climate Anomaly. The LIA started at the earliest by around AD 1200 and ended at the latest in the middle of the 20th century. The widespread temporal coverage of the LIA did not show regional consistency or particular spatial distribution and did not show a relationship with archive or proxy type either. A focus on the last 2 centuries shows a recent warming characterized by a well-marked warming trend parallel with increasing greenhouse gas emissions. It also shows a multidecadal variability likely due to natural processes acting on the internal climate system on a regional scale. A similar to 16-30-year cycle is found in Alaska and seems to be linked to the Pacific Decadal Oscillation, whereas similar to 20-30- and similar to 50-90-year periodicities characterize the North Atlantic climate variability, likely in relation with the Atlantic Multidecadal Oscillation. These regional features are probably linked to the sea ice cover fluctuations through ice-temperature positive feedback.Peer reviewe

a pilot study

Background Utilising fluorescence optical imaging (FOI), the distribution of an intravenously applied colouring agent indocyanine green (ICG) can be analysed with the potential to identify malperfusion by little to no tissue enhancement. Systemic sclerosis (SSc) is characterised by the presence of digital ulcers reflecting progressive vasculopathy. The objective was to investigate the potential of FOI in the detection of disturbed microcirculation in the hands and fingers of patients with SSc and to link FOI findings to clinical signs of ischemia such as digital ulcers and pitting scars. Methods In this cross-sectional study, 63 patients with SSc and 26 healthy subjects were examined. FOI was performed in all 89 individuals and compared to clinical data and capillaroscopic findings assembled for the SSc cohort. Results Healthy subjects showed initial ICG signals in their fingertips in 93.6%, SSc patients in 78.5% (limited SSc) and 43.2% (diffuse SSc). Moreover, in SSc patients, FOI findings were significantly associated with a late capillaroscopic pattern, disseminated SSc features, a diffuse SSc subtype, and the presence of digital ulcers or pitting scars. Intra- and inter-reader reliability for FOI amounted to κ = 0.786 and κ = 0.834, respectively. Conclusions FOI is able to detect areas of reduced microcirculation in patients with SSc with high association to capillaroscopic findings. The results pave the way for future FOI investigations into its role in the prediction of complications due to an impaired acral perfusion

a comparative study with ultrasonography

Background Valid detection of arthritis is essential in differential diagnosis of joint pain. Indocyanin green (ICG)-enhanced fluorescence optical imaging (FOI) is a new imaging method that visualizes inflammation in wrist and finger joints. Objectives of this study were to compare FOI with ultrasonography (US, by gray-scale (GS) and power Doppler (PD)) and clinical examination (CE) and to estimate the predictive power of FOI for discrimination between inflammatory and non-inflammatory juvenile joint diseases. Methods FOI and GSUS/PDUS were performed in both hands of 76 patients with joint pain (53 with juvenile idiopathic arthritis (JIA), 23 with non-inflammatory joint diseases). Inflammation was graded by a semiquantitative score (grades 0–3) for each imaging method. Joints were defined clinically active if swollen or tender with limited range of motion. Sensitivity and specificity of FOI in three phases dependent on ICG enhancement (P1–P3) were analyzed with CE and GSUS/PDUS as reference. Results For JIA patients, FOI had an overall sensitivity of 67.3%/72.0% and a specificity of 65.0%/58.8% with GSUS/PDUS as reference; specificity was highest in P3 (GSUS 94.3%/PDUS 91.7%). FOI was more sensitive for detecting clinically active joints than GSUS/PDUS (75.2% vs 57.3%/32.5%). In patients with non-inflammatory joint diseases both FOI and US showed positive (i.e., pathological) findings (25% and 14% of joints). The predictive value for discrimination between inflammatory and non-inflammatory joint diseases was 0.79 for FOI and 0.80/0.85 for GSUS/PDUS. Conclusions Dependent on the phase evaluated, FOI had moderate to good agreement with CE and US. Both imaging methods revealed limitations and should be interpreted cautiously. FOI may provide an additional diagnostic method in pediatric rheumatology. Trial registration Deutsches Register Klinischer Studien DRKS00012572. Registered 31 July 2017

Centre de recherches historiques

Marie-Anne Polo de Beaulieu et Jacques Berlioz, directeurs de recherche au CNRS Les exempla médiévaux. Discours et pratiques Le séminaire s’est ouvert par la présentation de Gian Paolo Maggioni (Florence) sur « Hagiographie et prédication, légendes et exempla. L’assemblage de récits exemplaires et d’hagiographies dans les légen-diers abrégés du XIIIe siècle ». Nous avons profité de l’invitation par l’EHESS de ce spécialiste de l’hagiographie (le nouvel éditeur de la Legenda aurea de Jacques d..

Subjective Cognitive Complaints in Participants of the Healthy Brain Ageing Study (HeBA)

Subjective cognitive complaints (SCC) have the potential for earlier detection of Alzheimer’s disease and Parkinson’s disease. Currently, the results of the completed online survey in the frame of the HeBA study reveal that 23% of the Luxembourgish participants have SCC with the SCC group having a higher prevalence rate of depression

Association between physical activity and risk of hepatobiliary cancers : A multinational cohort study

Background & Aims: To date, evidence on the association between physical activity and risk of hepatobiliary cancers has been inconclusive. Weexamined this association in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC). Methods: We identified 275 hepatocellular carcinoma (HCC) cases, 93 intrahepatic bile duct cancers (IHBCs), and 164 non-gallbladder extrahepatic bile duct cancers (NGBCs) among 467,336 EPIC participants (median follow-up 14.9 years). We estimated cause-specific hazard ratios (HRs) for total physical activity and vigorous physical activity and performed mediation analysis and secondary analyses to assess robustness to confounding (e.g. due to hepatitis virus infection). Results: In the EPIC cohort, the multivariable-adjusted HR of HCC was 0.55 (95% CI 0.38-0.80) comparing active and inactive individuals. Regarding vigorous physical activity, for those reporting >2 hours/week compared to those with no vigorous activity, the HR for HCC was 0.50 (95% CI 0.33-0.76). Estimates were similar in sensitivity analyses for confounding. Total and vigorous physical activity were unrelated to IHBC and NGBC. In mediation analysis, waist circumference explained about 40% and body mass index 30% of the overall association of total physical activity and HCC. Conclusions: These findings suggest an inverse association between physical activity and risk of HCC, which is potentially mediated by obesity. Lay summary: In a pan-European study of 467,336 men and women, we found that physical activity is associated with a reduced risk of developing liver cancers over the next decade. This risk was independent of other liver cancer risk factors, and did not vary by age, gender, smoking status, body weight, and alcohol consumption. (C) 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.Peer reviewe