27 research outputs found

    Microglia regulate myelin growth and integrity in the central nervous system

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    Myelin is required for the function of neuronal axons in the central nervous system, but the mechanisms that support myelin health are unclear. Although macrophages in the central nervous system have been implicated in myelin health(1), it is unknown which macrophage populations are involved and which aspects they influence. Here we show that resident microglia are crucial for the maintenance of myelin health in adulthood in both mice and humans. We demonstrate that microglia are dispensable for developmental myelin ensheathment. However, they are required for subsequent regulation of myelin growth and associated cognitive function, and for preservation of myelin integrity by preventing its degeneration. We show that loss of myelin health due to the absence of microglia is associated with the appearance of a myelinating oligodendrocyte state with altered lipid metabolism. Moreover, this mechanism is regulated through disruption of the TGFβ1–TGFβR1 axis. Our findings highlight microglia as promising therapeutic targets for conditions in which myelin growth and integrity are dysregulated, such as in ageing and neurodegenerative disease(2,3)

    Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

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    BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

    High-molecular-weight regular alternating diketopyrrolopyrrole-based terpolymers for efficient organic solar cells

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    The work of K.H.H. was supported by the "Europees Fonds voor Regionale Ontwikkeling" (EFRO) in the Intereg IV-A project "Organext". The research leading to these results has received funding from the Ministry of Education, Culture and Science (Gravity program 024.001.035) and is part of the research program of the Dutch Polymer Institute (DPI project 660) and the Solliance Organic Photovoltaics Programme

    Influence of the position of the side chain on crystallization and solar cell performance of DPP-based small molecules

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    Three isomeric p-conjugated molecules based on diketopyrrolopyrrole and bithiophene (DPP2T) substituted with hexyl side chains in different positions are investigated for use in solution-processed organic solar cells. Efficiencies greater than 3% are obtained when a mild annealing step is used. The position of the side chains on the DDP2Ts has a major influence on the optical and electronic properties of these molecules in thin semicrystalline films. By combining optical absorption and fluorescence spectroscopy, with microscopy (AFM and TEM) and scattering techniques (GIWAXS and electron diffraction), we find that the position of the side chains also affects the morphology and crystallization of these DPP2Ts when they are combined with a C70 fullerene derivative in a thin film. The study demonstrates that changing the side chain position is an additional, yet complex, tool to influence behavior of conjugated molecules in organic solar cells

    Influence of the Position of the Side Chain on Crystallization and Solar Cell Performance of DPP-Based Small Molecules

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    Three isomeric π-conjugated molecules basedon diketopyrrolopyrrole and bithiophene (DPP2T) substitutedwith hexyl side chains in different positions areinvestigated for use in solution-processed organic solar cells.Efficiencies greater than 3% are obtained when a mildannealing step is used. The position of the side chains onthe DDP2Ts has a major influence on the optical andelectronic properties of these molecules in thin semicrystallinefilms. By combining optical absorption and fluorescencespectroscopy, with microscopy (AFM and TEM) andscattering techniques (GIWAXS and electron diffraction), we find that the position of the side chains also affects themorphology and crystallization of these DPP2Ts when they are combined with a C70 fullerene derivative in a thin film. The studydemonstrates that changing the side chain position is an additional, yet complex, tool to influence behavior of conjugatedmolecules in organic solar cells.KEYWORDS: small molecules, solar cells, side chain engineering, morphology, crystallinit
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