| 1. |
- Calder, Philip C, et al.
(författare)
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Early nutrition and immunity - progress and perspectives.
- 2006
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Ingår i: The British journal of nutrition. - 0007-1145. ; 96:4, s. 774-90
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Forskningsöversikt (refereegranskat)abstract
- The immune system exists to protect the host against pathogenic organisms and highly complex pathways of recognition, response, elimination and memory have evolved in order to fulfil this role. The immune system also acts to ensure tolerance to 'self', to food and other environmental components, and to commensal bacteria. A breakdown in the tolerogenic pathways can also lead to inflammatory diseases. The prevalence of inflammatory diseases, including atopic disorders, has increased over the last 60 years. The development of tolerance is the result of active immune mechanisms and both development and maintenance of tolerance are lifelong processes which start very early in life, even prenatally. Profound immunologic changes occur during pregnancy, involving a polarization of T helper (Th) cells towards a dominance of Th2 and regulatory T cell effector responses in both mother and fetus. This situation is important to maintain pregnancy through avoidance of the rejection of the immunologically incompatible fetus. During the third trimester of human pregnancy, fetal T cells are able to mount antigen-specific responses to environmental and food-derived antigens and antigen-specific T cells are detectable in cord blood in virtually all newborns indicating in utero sensitization. If the neonatal immune system is not able to down-regulate the pre-existing Th2 dominance effectively then an allergic phenotype may develop. Changes occur at, and soon after, birth in order that the immune system of the neonate becomes competent and functional and that the gut becomes colonized with bacteria. Exposure to bacteria during birth and from the mother's skin and the provision of immunologic factors in breast milk are amongst the key events that promote maturation of the infant's gut and gut-associated and systemic immune systems. The introduction of formula and of solid foods exposes the infant to novel food antigens and also affects the gut flora. Nutrition may be the source of antigens to which the immune system must become tolerant, provide factors, including nutrients, that themselves might modulate immune maturation and responses, and provide factors that influence intestinal flora, which in turn will affect antigen exposure, immune maturation and immune responses. Through these mechanisms it is possible that nutrition early in life might affect later immune competence, the ability to mount an appropriate immune response upon infection, the ability to develop a tolerogenic response to 'self' and to benign environmental antigens, and the development of immunologic disorders. A Workshop held in February 2006 considered recent findings in the areas of oral tolerance, routes of sensitization to allergens and factors affecting the development of atopic disease; factors influencing the maturation of dendritic cells and the development of regulatory T cells; the influence of gut microflora on immunity, allergic sensitization and infectious disease; the role of nutrition in preventing necrotizing enterocolitis in an animal model of preterm birth; and the role of PUFA of different classes in influencing immune responses and in shaping the development of atopic disease. This report summarizes the content of the lectures and the subsequent discussions.
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| 2. |
- Koletzko, Berthold, et al.
(författare)
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Documentation of functional and clinical effects of infant nutrition : setting the scene for comment
- 2012
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Ingår i: Annals of Nutrition and Metabolism. - : S. Karger. - 0250-6807 .- 1421-9697. ; 60:4, s. 222-232
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Tidskriftsartikel (refereegranskat)abstract
- The Early Nutrition Academy and the Child Health Foundation, in collaboration with the Committee on Nutrition, European Society for Paediatric Gastroenterology, Hepatology and Nutrition, held a workshop in March 2011 to explore guidance on acquiring evidence on the effects of nutritional interventions in infants and young children. The four objectives were to (1) provide guidance on the quality and quantity of evidence needed to justify conclusions on functional and clinical effects of nutrition in infants and young children aged <3 years; (2) agree on a range of outcome measures relevant to nutrition trials in this age group for which agreed criteria are needed; (3) agree on an updated 'core data set' that should generally be recorded in nutrition trials in infants and young children, and (4) provide guidance on the use of surrogate markers in paediatric nutrition research. The participants discussed these objectives and agreed to set up six first working groups under the auspices of the Consensus Group on Outcome Measures Made in Paediatric Enteral Nutrition Clinical Trials (COMMENT). Five groups will aim to identify and define criteria for assessing key outcomes, i.e. growth, acute diarrhoea, atopic dermatitis and cows' milk protein allergy, infections and 'gut comfort'. The sixth group will review and update the 'core data set'. The COMMENT Steering Committee will discuss and decide upon a method for reaching consensus which will be used by all working groups and plan to meet again within 2 years and to report and publish their conclusions.
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| 3. |
- Lavazais, S, et al.
(författare)
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IRAK4 inhibition dampens pathogenic processes driving inflammatory skin diseases
- 2023
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Ingår i: Science translational medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 15:683, s. eabj3289-
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Tidskriftsartikel (refereegranskat)abstract
- Innate immunity not only shapes the way epithelial barriers interpret environmental cues but also drives adaptive responses. Therefore, modulators of innate immune responses are expected to have high therapeutic potential across immune-mediated inflammatory diseases. IRAK4 is a kinase that integrates signaling downstream of receptors acting at the interface between innate and adaptive immune responses, such as Toll-like receptors (TLRs), interleukin-1R (IL-1R), and IL-18R. Because effects of IRAK4 inhibition are stimulus, cell type, and species dependent, the evaluation of the therapeutic potential of IRAK4 inhibitors requires a highly translational approach. Here, we profiled a selective IRAK4 inhibitor, GLPG2534, in an extensive panel of models of inflammatory skin diseases, translationally expanding evidence from in vitro to in vivo and from mouse to human. In vitro, IRAK4 inhibition resulted in substantial inhibition of TLR and IL-1 responses in dendritic cells, keratinocytes, granulocytes, and T cells but only weakly affected dermal fibroblast responses. Furthermore, disease activity in murine models of skin inflammation (IL-23–, IL-33–, imiquimod-, and MC903-induced) was markedly dampened by IRAK4 inhibition. Last, inhibiting IRAK4 reversed pathogenic molecular signatures in human lesional psoriasis and atopic dermatitis biopsies. Over the variety of models used, IRAK4 inhibition consistently affected central mediators of psoriasis (IL-17A) and atopic dermatitis (IL-4 and IL-13). Overall, our data highlight IRAK4 as a central player in skin inflammatory processes and demonstrate the potential of IRAK4 inhibition as a therapeutic strategy in chronic inflammatory skin diseases.
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| 4. |
- Manry, Jérémy, et al.
(författare)
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The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:21
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
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| 5. |
- Renard, Jean-Baptiste, et al.
(författare)
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LOAC : a small aerosol optical counter/sizer for ground-based and balloon measurements of the size distribution and nature of atmospheric particles - Part 1
- 2016
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 9:4, s. 1721-1742
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Tidskriftsartikel (refereegranskat)abstract
- The study of aerosols in the troposphere and in the stratosphere is of major importance both for climate and air quality studies. Among the numerous instruments available, optical aerosol particles counters (OPCs) provide the size distribution in diameter range from about 100 nm to a few tens of mu m. Most of them are very sensitive to the nature of aerosols, and this can result in significant biases in the retrieved size distribution. We describe here a new versatile optical particle/sizer counter named LOAC (Light Optical Aerosol Counter), which is light and compact enough to perform measurements not only at the surface but under all kinds of balloons in the troposphere and in the stratosphere. LOAC is an original OPC performing observations at two scattering angles. The first one is around 12 degrees, and is almost insensitive to the refractive index of the particles; the second one is around 60 degrees and is strongly sensitive to the refractive index of the particles. By combining measurement at the two angles, it is possible to retrieve the size distribution between 0.2 and 100 mu m and to estimate the nature of the dominant particles (droplets, carbonaceous, salts and mineral particles) when the aerosol is relatively homogeneous. This typology is based on calibration charts obtained in the laboratory. The uncertainty for total concentrations measurements is +/- 20% when concentrations are higher than 1 particle cm 3 (for a 10 min integration time). For lower concentrations, the uncertainty is up to about +/- 60% for concentrations smaller than 10 2 particle cm(-3). Also, the uncertainties in size calibration are +/- 0.025 mu m for particles smaller than 0.6 mu m, 5% for particles in the 0.7-2 mu m range, and 10% for particles greater than 2 mu m. The measurement accuracy of sub-micronic particles could be reduced in a strongly turbid case when concentration of particles > 3 mu m exceeds a few particles cm(-3). Several campaigns of cross-comparison of LOAC with other particle counting instruments and remote sensing photometers have been conducted to validate both the size distribution derived by LOAC and the retrieved particle number density. The typology of the aerosols has been validated in well-defined conditions including urban pollution, desert dust episodes, sea spray, fog, and cloud. Comparison with reference aerosol mass monitoring instruments also shows that the LOAC measurements can be successfully converted to mass concentrations.
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| 6. |
- Renard, Jean-Baptiste, et al.
(författare)
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LOAC : a small aerosol optical counter/sizer for ground-based and balloon measurements of the size distribution and nature of atmospheric particles - Part 2
- 2016
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 9:8, s. 3673-3686
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Tidskriftsartikel (refereegranskat)abstract
- In the companion (Part I) paper, we have described and evaluated a new versatile optical particle counter/sizer named LOAC (Light Optical Aerosol Counter), based on scattering measurements at angles of 12 and 60A degrees. That allows for some typology identification of particles (droplets, carbonaceous, salts, and mineral dust) in addition to size-segregated counting in a large diameter range from 0.2aEuro-A mu m up to possibly more than 100aEuro-A mu m depending on sampling conditions (Renard et al., 2016). Its capabilities overpass those of preceding optical particle counters (OPCs) allowing the characterization of all kind of aerosols from submicronic-sized absorbing carbonaceous particles in polluted air to very coarse particles (> 10-20aEuro-A mu m in diameter) in desert dust plumes or fog and clouds. LOAC's light and compact design allows measurements under all kinds of balloons, on-board unmanned aerial vehicles (UAVs) and at ground level. We illustrate here the first LOAC airborne results obtained from a UAV and a variety of scientific balloons. The UAV was deployed in a peri-urban environment near Bordeaux in France. Balloon operations include (i) tethered balloons deployed in urban environments in Vienna (Austria) and Paris (France), (ii) pressurized balloons drifting in the lower troposphere over the western Mediterranean (during the Chemistry-Aerosol Mediterranean Experiment - ChArMEx campaigns), (iii) meteorological sounding balloons launched in the western Mediterranean region (ChArMEx) and from Aire-sur-l'Adour in south-western France (VOLTAIRE-LOAC campaign). More focus is put on measurements performed in the Mediterranean during (ChArMEx) and especially during African dust transport events to illustrate the original capability of balloon-borne LOAC to monitor in situ coarse mineral dust particles. In particular, LOAC has detected unexpected large particles in desert sand plumes.
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