The probiotic Escherichia coli strain Nissle 1917 (EcN) stops acute diarrhoea in infants and toddlers

In most cases, acute diarrhoea will become self-limiting during the first few days after onset. For young children, however, health risks may develop when the disease lasts longer than 3 days. The purpose of the present trial was to determine whether the stool frequency of infants and toddlers suffering from acute diarrhoea could be normalised more quickly by administering the probiotic Escherichia coli Nissle 1917 (EcN) solution than by administering a placebo. The safety of EcN were also assessed. A total of 113 children (aged 2–47 months) with acute diarrhoea (> three watery or loose stools in 24 h) were randomised to either a group receiving the probiotic EcN suspension (n = 55) or a group receiving the placebo suspension (n = 58) in a confirmative, double-blind clinical trial. Depending on the age of patients, 1–3 ml per day of verum suspension (10(8) viable EcN cells per millilitre) or placebo were administered orally. The causes of the diarrhoea were viral rather than bacterial, but they were mainly unspecific infections. The median onset of treatment response (reduction of daily stool frequency to ≤ three watery or loose stools over at least 2 consecutive days) occurred more rapidly in the children receiving the EcN solution (2.5 days) than in those receiving the placebo (4.8 days), a significant difference (2.3 days; p = 0.0007). The number of patients showing a response was clearly higher (p < 0.0001) in the EcN group (52/55; 94.5%) than in the placebo group (39/58; 67.2%). EcN was found to be safe and well-tolerated, and it showed a significant superiority compared to the placebo in the treatment of acute diarrhoea in infants and toddlers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:http://dx.doi.org/10.1007/s00431-007-0419-x) contains supplementary material, which is available to authorized users

Factors promoting larch dominance in central Siberia: fire versus growth performance and implications for carbon dynamics at the boundary of evergreen and deciduous conifers

The relative roles of fire and climate in determining canopy species composition and aboveground carbon stocks were investigated. Measurements were made along a transect extending from the dark taiga zone of Central Siberia, where Picea and Abies dominate the 5 canopy, into the Larix zone of Eastern Siberia. We test the hypotheses that the change in canopy species composition is based (1) on climate-driven performance only, (2) on fire only, or (3) on fire-performance interactions. We show that the evergreen conifers Picea obovata and Abies sibirica are the natural late-successional species both in Central and Eastern Siberia, provided there has been no fire for an 10 extended period of time. There are no changes in the climate-driven performance of the observed species. Fire appears to be the main factor explaining the dominance of Larix. Of lesser influence were longitude, hydrology and active-layer thickness. Stand-replacing fires decreased from 300 to 50 yr between the Yenisei Ridge and the upper Tunguska. Repeated non-stand-replacing surface fires eliminated the regenera15 tion of Abies and Picea. With every 100 yr since the last fire, the percentage of Larix decreased by 20 %. Biomass of stems of single trees did not show signs of age-related decline. Relative diameter increment was 0.41±0.20% at breast height and stem volume increased linearly over time with a rate of about 0.36 tCha−1 yr−1 independent of age class and 20 species. Stand volumes reached about 130 tCha−1 (equivalent to about 520m3 ha−1). Individual trees of Larix were older than 600 yr. The maximum age and biomass seemed to be limited by fungal rot of heart wood. 60% of old Larix and Picea and 30% of Pinus sibirica trees were affected by stem rot. Implications for the future role of fire and of plant diseases are discussed.JRC.H.3-Forest Resources and Climat

Electroluminescence of copper-nitride nanocrystals

Nanocrystals can behave as quantum boxes with confined electronic states governing their optoelectronic properties. The formation of nanometer-size crystals of copper nitride (Cu3N) grown by nitrogen sputtering of a Cu(110) surface is reported. Scanning tunneling spectroscopy shows that the nanocrystals exhibit a series of well-defined sharp electronic resonances, which correspond to confined free-electron-like states. We observe that electrons from a scanning tunneling microscope tip induce the emission of light with a larger efficiency than on the bare metal surface. The spectral analysis of the emitted photons reveals various radiative inelastic pathways enabled by the confined states, which explain the enhanced light emission. Thus, the Cu3N nanocrystals can be employed as nanometer-size light sources

Dissecting the Prognostic Significance and Functional Role of Progranulin in Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is known for its strong dependency on the tumor microenvironment. We found progranulin (GRN), a protein that has been linked to inflammation and cancer, to be upregulated in the serum of CLL patients compared to healthy controls, and increased GRN levels to be associated with an increased hazard for disease progression and death. This raised the question of whether GRN is a functional driver of CLL. We observed that recombinant GRN did not directly affect viability, activation, or proliferation of primary CLL cells in vitro. However, GRN secretion was induced in co-cultures of CLL cells with stromal cells that enhanced CLL cell survival. Gene expression profiling and protein analyses revealed that primary mesenchymal stromal cells (MSCs) in co-culture with CLL cells acquire a cancer-associated fibroblast-like phenotype. Despite its upregulation in the co-cultures, GRN treatment of MSCs did not mimic this effect. To test the relevance of GRN for CLL in vivo, we made use of the Eμ-TCL1 CLL mouse model. As we detected strong GRN expression in myeloid cells, we performed adoptive transfer of Eμ-TCL1 leukemia cells to bone marrow chimeric Grn−/− mice that lack GRN in hematopoietic cells. Thereby, we observed that CLL-like disease developed comparable in Grn−/− chimeras and respective control mice. In conclusion, serum GRN is found to be strongly upregulated in CLL, which indicates potential use as a prognostic marker, but there is no evidence that elevated GRN functionally drives the disease

Digital health for migrants, ethnic and cultural minorities and the role of participatory development : a scoping review

Digital health interventions (DHIs) are increasingly used to address the health of migrants and ethnic minorities, some of whom have reduced access to health services and worse health outcomes than majority populations. This study aims to give an overview of digital health interventions developed for ethnic or cultural minority and migrant populations, the health problems they address, their effectiveness at the individual level and the degree of participation of target populations during development. We used the methodological approach of the scoping review outlined by Tricco. We found a total of 2248 studies, of which 57 were included, mostly using mobile health technologies, followed by websites, informational videos, text messages and telehealth. Most interventions focused on illness self-management, mental health and wellbeing, followed by pregnancy and overall lifestyle habits. About half did not involve the target population in development and only a minority involved them consistently. The studies we found indicate that the increased involvement of the target population in the development of digital health tools leads to a greater acceptance of their use

PI(18:1/18:1) is a SCD1-derived lipokine that limits stress signaling

Cytotoxic stress activates stress-activated kinases, initiates adaptive mechanisms, including the unfolded protein response (UPR) and autophagy, and induces programmed cell death. Fatty acid unsaturation, controlled by stearoyl-CoA desaturase (SCD)1, prevents cytotoxic stress but the mechanisms are diffuse. Here, we show that 1,2-dioleoyl-sn-glycero-3-phospho-(1’-myo-inositol) [PI(18:1/18:1)] is a SCD1-derived signaling lipid, which inhibits p38 mitogen-activated protein kinase activation, counteracts UPR, endoplasmic reticulum-associated protein degradation, and apoptosis, regulates autophagy, and maintains cell morphology and proliferation. SCD1 expression and the cellular PI(18:1/18:1) proportion decrease during the onset of cell death, thereby repressing protein phosphatase 2 A and enhancing stress signaling. This counter-regulation applies to mechanistically diverse death-inducing conditions and is found in multiple human and mouse cell lines and tissues of Scd1-defective mice. PI(18:1/18:1) ratios reflect stress tolerance in tumorigenesis, chemoresistance, infection, high-fat diet, and immune aging. Together, PI(18:1/18:1) is a lipokine that links fatty acid unsaturation with stress responses, and its depletion evokes stress signaling

Postwachstum und Raumentwicklung : Denkanstöße für Wissenschaft und Praxis

Dieses von Mitgliedern des Arbeitskreises "Postwachstumsökonomien" (2016 - 2020) der ARL verfasste Positionspapier ordnet die internationale Postwachstumsdebatte ein und diskutiert ihre Relevanz für die Raumentwicklung und die raumwissenschaftliche Forschung. Neben sektoralen Zugängen und Befunden werden konkrete Vorschläge zur Postwachstumsorientierung in Planung, Forschung und Lehre gemacht. Dabei wird zwischen kurzfristig erreichbaren Veränderungen und mittel- bis langfristig auszulegenden Maßnahmen unterschieden

A Novel Tandem Mass Spectrometry Method for Rapid Confirmation of Medium- and Very Long-Chain acyl-CoA Dehydrogenase Deficiency in Newborns

BACKGROUND:Newborn screening for medium- and very long-chain acyl-CoA dehydrogenase (MCAD and VLCAD, respectively) deficiency, using acylcarnitine profiling with tandem mass spectrometry, has increased the number of patients with fatty acid oxidation disorders due to the identification of additional milder, and so far silent, phenotypes. However, especially for VLCADD, the acylcarnitine profile can not constitute the sole parameter in order to reliably confirm disease. Therefore, we developed a new liquid chromatography tandem mass spectrometry (LC-MS/MS) method to rapidly determine both MCAD- and/or VLCAD-activity in human lymphocytes in order to confirm diagnosis. METHODOLOGY:LC-MS/MS was used to measure MCAD- or VLCAD-catalyzed production of enoyl-CoA and hydroxyacyl-CoA, in human lymphocytes. PRINCIPAL FINDINGS:VLCAD activity in controls was 6.95+/-0.42 mU/mg (range 1.95 to 11.91 mU/mg). Residual VLCAD activity of 4 patients with confirmed VLCAD-deficiency was between 0.3 and 1.1%. Heterozygous ACADVL mutation carriers showed residual VLCAD activities of 23.7 to 54.2%. MCAD activity in controls was 2.38+/-0.18 mU/mg. In total, 28 patients with suspected MCAD-deficiency were assayed. Nearly all patients with residual MCAD activities below 2.5% were homozygous 985A>G carriers. MCAD-deficient patients with one other than the 985A>G mutation had higher MCAD residual activities, ranging from 5.7 to 13.9%. All patients with the 199T>C mutation had residual activities above 10%. CONCLUSIONS:Our newly developed LC-MS/MS method is able to provide ample sensitivity to correctly and rapidly determine MCAD and VLCAD residual activity in human lymphocytes. Importantly, based on measured MCAD residual activities in correlation with genotype, new insights were obtained on the expected clinical phenotype