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According to the literature, hepatic fibrosis is observed in liver biopsies in about 70% of the pediatric recipients during the ten years following the liver transplantation. lt is associated with inflammation. ln parallel to the histologic changes, a high rate of anti-HLA OSA is measured in patient serum sample. Fibrosis is more severe in OSA positive groups than in OSA negative groups. Inflammation is nine times higher in OSA positive groups than OSA negative groups. Furthermore, the survival rate of the liver graft is weaker when the OSA anti-HLA is detected from class II. Among these OSA class II, the most correlated subtype with fibrosis and inflammation development would be OQ. An anti-HLA OSA threshold, measured with MFI method in the serum of pediatric patient, would predispose fibrosis development. Currently, there is no consensus in pediatry about anti-HLA OSA threshold present in pediatric serum predisposing fibrosis development. This threshold varies from 1000 to 5000 among adult studies. Through our study, we tried to identify anti-HLA antibodies subtypes included in the inflammation and fibrosis development after liver allo-transplantation in a pediatric population. We also wanted to determine an optimal clinical MFI threshold favoring fibrosis development in order to maintain healthy graft in the long term. We analyzed a retrospective cohort including 102 pediatric patients who underwent a liver transplantation between 2004 and 2012 (<18 years old at the time of the liver transplantation) and who performed a protocol biopsy during the years post transplantation (between 2012 and 2015). This study is performed in the pediatric ward of the CUSL. The biopsies performed were analyzed for fibrosis with Metavir score and LASFc. Concerning the inflammation, it was examined in the lobule and portal tract. The results show that portal, centro-lobular and total fibrosis are significantly correlated with anti-HLA OSA class Il de novo presence (OR = 6, 13, p<0, 01 for LAFScT). Furthermore, portal inflammation development is significantly correlated to OSA anti-HLA class Il presence (OR = 8, 02, p<0, 01). Concerning lobular inflammation, we have OR = 5, 73 with p<0, 03. Among all the OSA subtypes, OQ class is significantly linked to fibrosis development (PCC = 0, 50) and to portal inflammation (PCC = 0, 77). Finally, OSA anti-HLA type OQ presence is predictive for inflammation if the MFI threshold is based at 5 000. This threshold gives us a specificity evaluated at 71, 4% and a sensibility at 83,3%. These results are less straightforward when patient are analyzed individually because, even if fibrosis appears or worsen in some patients, it can improve or disappear in others. Fibrosis appearance and hepatic inflammation are linked to OSA anti-HLA class II development, especially the subclass named OQ. OSA anti-HLA OQ type presence is predictive of inflammation if the MFI threshold is based at 5 000. Selon la littérature, la fibrose hépatique est observée aux biopsies hépatiques chez environ 70% des receveurs pédiatriques dans les dix années suivant la transplantation. Elle est associée à la présence d'inflammation. Parallèlement à ces modifications histologiques, un taux élevé de OSA anti-HLA est mesuré dans le sérum de ces patients. La fibrose est plus sévère dans le groupe OSA positif que dans le groupe OSA négatif. L'inflammation portale est, quant à elle, neuf fois plus élevée dans les groupes OSA positifs que dans les OSA négatifs. De plus, le taux de survie du greffon hépatique est plus faible lorsque les anticorps DSA anti-HLA détectés sont de classe Il. Parmi ces OSA de classe Il, le sous type majoritairement corrélé au développement de fibrose et d'inflammation semblerait être DO. Un seuil de OSA anti-HLA mesuré par MFI dans le sérum des patients pédiatriques prédisposerait au développement de fibrose dans le greffon. Actuellement, aucun consensus n'existe en pédiatrie sur le seuil de OSA anti-HLA présent dans le sérum des patients prédisposant au développement de fibrose. Ce seuil varie entre 1000 et 5 000 selon les études adultes. A travers notre étude, nous cherchons à identifier les sous types d'anticorps anti-HLA impliqués dans le développement de l'inflammation et de la fibrose hépatique post allo-transplantation dans une population pédiatrique. Nous cherchons également à déterminer un seuil clinique MFI optimal favorisant le développement de la fibrose dans le but de maintenir un greffon sain au long court. Nous analysons une cohorte rétrospective incluant 102 patients pédiatriques transplantés entre 2004 et 2012 (<18 ans au moment de la transplantation hépatique) et ayant suivi un protocole de biopsie dans le décours de la greffe (entre 2012 et 2015). Cette étude est réalisée au sein du service de pédiatrie des CUSL. Les biopsies réalisées ont été évaluées pour la fibrose avec les scores Métavir et LASFc. L'inflammation a été examinée au niveau portal et lobulaire. Les résultats montrent que les fibroses portales, centro-lobulaires et totales sont significativement corrélées à la présence de OSA anti-HLA de classe Il de novo (OR = 6,13, p<0,01 pour LAFScT). De plus, le développement d'inflammation portale est significativement corrélé à la présence de OSA anti-HLA de classe Il (OR = 8,02, p<0,01). Concernant l'inflammation lobulaire on obtient OR = 5,73 avec p< 0,03. Parmi les sous types de DSA, la classe DO est significativement associée au développement de fibrose (PCC = 0,50) et d'inflammation portale (PCC = 0,77). Enfin, la présence de DSA anti-HLA de type DO est prédictive d'inflammation si le seuil MFI est placé à 5 000. Ce seuil nous donne une spécificité de 71,4% et une sensibilité de 83,3%. Ces résultats s'avèrent moins francs lors de l'analyse individuelle des patients, car si la fibrose apparaît ou s'aggrave chez certains patients, elle s'améliore voir disparaît chez d'autres. L'apparition de fibrose et d'inflammation hépatique est liée au développement de OSA anti-HLA de classe II essentiellement le sous type DO. La présence de OSA anti-HLA de type DO est prédictive d'inflammation si le seuil MFI est placé à 5000.

HLA Antigens --- Liver Cirrhosis --- Transplantation Tolerance

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Autism Spectrum Disorder (ASD) is currently diagnosed based on a series of behavioral tests. The challenge for researchers is to try to uncover the biological basis for these typical behaviors in order to improve diagnosis and identify potential targets for treatment. A multidisciplinary approach is necessary in order to move forward. This includes analysis of the current animal models for ASD and their suitability, reviewing immunological, immunogenetic and epigenetic research, reassessing clinical diagnostic tools, and surveying radiological, pathological, and serological records for clues. This volume includes research from some of the leading researchers on ASD. We are hopeful that it will stimulate further dialogue and research in this challenging field.

Intelligence --- Sensory Thresholds --- Autoimmune Diseases --- Autism spectrum disorders (ASD) --- HLA Antigens --- Behavior --- Genetic syndromes

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Autism Spectrum Disorder (ASD) is currently diagnosed based on a series of behavioral tests. The challenge for researchers is to try to uncover the biological basis for these typical behaviors in order to improve diagnosis and identify potential targets for treatment. A multidisciplinary approach is necessary in order to move forward. This includes analysis of the current animal models for ASD and their suitability, reviewing immunological, immunogenetic and epigenetic research, reassessing clinical diagnostic tools, and surveying radiological, pathological, and serological records for clues. This volume includes research from some of the leading researchers on ASD. We are hopeful that it will stimulate further dialogue and research in this challenging field.

Intelligence --- Sensory Thresholds --- Autoimmune Diseases --- Autism spectrum disorders (ASD) --- HLA Antigens --- Behavior --- Genetic syndromes

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Toxicology in the Middle Ages and Renaissance provides an authoritative and fascinating exploration into the use of toxins and poisons in the Middle Ages and Renaissance. Part of the History of Toxicology and Environmental Health series, this volume is a follow-up, chronologically, to the first two volumes which explored toxicology in antiquity.The book approximately covers the 1100s through the 1600s, delving into different aspects of toxicology, such as the contributions of scientific scholars of the time, sensational poisoners and poisoning cases, as well as myths. Historical figures, such as the Borgias and Catherine de Medici are discussed. Toxicologists, students, medical researchers, and those interested in the history of science will find insightful and relevant material in this volume.

Toxicology --- Toxins --- History. --- Natural toxicants --- Toxicants, Natural --- Toxins and antitoxins --- Antigens --- Metabolites --- Poisons --- Antitoxins --- Detoxification (Health) --- Chemicals --- Medicine --- Pharmacology --- Poisoning --- toxins; poisons; Middle ages; Reanaissance; toxicology

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This volume deals mainly with the specialized aspect of toxins and drug discovery. Man has been using natural resources especially plants to treat diseases from very early times in history of mankind. Although many drugs derived from plants and microbes have been discovered and being used in clinical practice, not many drugs have been developed from venoms and toxins although many laboratories worldwide are actively working on it. This volume describe some of the recent developments in this research area, such as snake venoms, conotoxins , bioinformatics in drug discovery from peptide toxins.

Medicine. --- Pharmaceutical technology. --- Biochemistry. --- Animal physiology. --- Biomedicine. --- Pharmaceutical Sciences/Technology. --- Animal Biochemistry. --- Animal Physiology. --- Animal physiology --- Animals --- Biological chemistry --- Chemical composition of organisms --- Organisms --- Physiological chemistry --- Pharmaceutical laboratory techniques --- Pharmaceutical laboratory technology --- Technology, Pharmaceutical --- Clinical sciences --- Medical profession --- Physiology --- Composition --- Biology --- Anatomy --- Chemistry --- Medical sciences --- Technology --- Toxins. --- Natural toxicants --- Toxicants, Natural --- Toxins and antitoxins --- Antigens --- Metabolites --- Poisons --- Antitoxins --- Detoxification (Health)