New insights on the interplay between psychopharmacology and neuroplasticity in psychiatric disorders

Tese de Doutoramento em Ciências da SaúdeIt is now clear that various forms of structural plasticity, including the generation of new neurons and glial cells, may modify pathophysiological processes in neuropsychiatric disorders, namely in depression. In fact, several studies have shown decreased hippocampal neurogenesis in depressed patients, while treatment with different antidepressant drugs in animal models increases neurogenesis in this region, allowing the recovery from emotional and cognitive changes. However, these effects have not been described for all the available classes of antidepressant drugs. Furthermore, the neuroplastic effects of antidepressants in other neurogenic regions such as the hypothalamus have yet to be determined. Despite the importance of these drugs in the recovery from depression, a significant proportion of depressed patients reveal incomplete remission and develop treatment-resistant forms of the disorder. The use of atypical antipsychotics in these cases has been widely used in the clinical setting. However, the neuroplastic effects of these drugs in depression and schizophrenia are still largely unknown. Taking this into consideration we aimed to explore new perspectives on the interplay between psychopharmacology and neuroplasticity in these psychiatric disorders. To explore the neuroplastic effects of the antidepressant Pirlindole, a MAO-A (monoamine oxidase, type A) inhibitor, we used the unpredictable chronic mild stress (uCMS) animal model of depression. Our results indicate that Pirlindole is able to reverse the behavioural effects of stress exposure, potentiating hippocampal adult neurogenesis and rescuing the stress-induced dendritic atrophy of granule neurons in the dentate gyrus of the hippocampus. These results further reinforce the notion that the modulation of monoaminergic neurotransmission is involved in the neuroplastic effects of currently available antidepressant drugs. To dissect the potential actions of antidepressants in adult neurogenesis in the hypothalamus we treated animals exposed to uCMS with two different classes of antidepressants: fluoxetine (a selective serotonin reuptake inhibitor) and imipramine (a tricyclic antidepressant). Our results demonstrate that chronic stress and antidepressant treatment can modulate hypothalamic neurogenesis. Moreover, we proved that different classes of antidepressants, with an opposite action on appetite and body weight gain, differentially modulate hypothalamic neurogenesis. This data indicates that in addition to the neuroplastic effects on the hippocampus, stress and antidepressant drugs also modulate hypothalamic adult neurogenesis.Furthermore, we explored the role of neuroplasticity in the therapeutic actions of atypical antipsychotics in depression. To achieve this, we treated animals exposed to uCMS with a classical (haloperidol) and an atypical (clozapine) antipsychotic. Our data demonstrates that the atypical antipsychotic clozapine improved measures of depressive-like behavior while haloperidol had no beneficial effect, aggravating learned helplessness in the forced swimming test and behavior flexibility in a cognitive task. Importantly, an upregulation of adult neurogenesis and neuronal survival was observed in animals treated with clozapine while haloperidol promoted a downregulation of these processes. These results demonstrate that the atypical antipsychotic is able to reverse the behavioral effects of chronic stress by improving adult neurogenesis, cell survival and neuronal reorganization. Finally, to understand the impact of different classes of antipsychotics in the negative and cognitive symptoms of schizophrenia, we used a neurodevelopmental model of schizophrenia. Animals expose prenatally to the cytostatic agent methylazoxymethanol (MAM) presented specific cognitive deficits and social impairments. The classical antipsychotic haloperidol presented no beneficial effects in these behavioral dimensions. The atypical antipsychotic clozapine and risperidone revealed a positive effect on both dimensions while aripiprazole presented a significant effect in the social measure. Adult gliogenesis is affected in animals exposed to MAM, being modulated by the atypical antipsychotics used. Neurogenesis is not altered in MAM animals, with haloperidol negatively affecting this phenomenon. In this work, we proved that classical and atypical antipsychotics differentially modulate hippocampal cell genesis possibly contributing to different behavioural actions in hippocampal dependent functions. Together, these findings contribute to expand our knowledge on the role of psychopharmacological agents (including antidepressants and antipsychotics) on the modulation of different neuroplastic events, including cell genesis and neuronal remodelling. In the future, this knowledge may help to pave the way for new therapeutic interventions both in depression and schizophrenia.É actualmente sabido que várias formas de plasticidade estrutural, incluindo a formação de novos neurónios e células da glia, podem modificar o processo patofisiológico em algumas doenças neuropsiquiátricas, nomeadamente a depressão. De facto, vários estudos têm demonstrado uma redução da neurogénese hipocampal em pacientes com depressão. Para além disso, o tratamento com diferentes fármacos, nomeadamente os antidepressivos, revelou em modelos animais, aumentar a neurogénese nesta região cerebral, permitindo uma recuperação na componente emocional e cognitiva. Contudo, estes efeitos não estão descritos para todas as classes de antidepressivos disponíveis. Além disso, os efeitos dos antidepressivos na neuroplasticidade em outras regiões neurogénicas como o hipotálamo ainda não foram determinados. Apesar da importância destes fármacos na recuperação da depressão, uma proporção significativa de pacientes revela remissão incompleta bem como formas resistentes ao tratamento da doença. Nestes casos, o uso de antipsicóticos atípicos tem sido amplamente utilizado no contexto clínico. No entanto, os efeitos destes fármacos na neuroplasticidade na depressão e esquizofrenia são ainda amplamente desconhecidos. Tendo isto em consideração, propusemos explorar novas perspectivas na inter-relação entre a psicofarmacologia e a neuroplasticidade nestas doenças psiquiátricas. Para determinar os efeitos do antidepressivo inibidor da MAO-A (monoamina oxidase, tipo A) Pirlindol na neuroplasticidade, utilizamos o modelo animal de exposição a stress crónico moderado e imprevisível (uCMS). Os nossos resultados indicam que o Pirlindol é capaz de reverter os efeitos comportamentais de exposição ao stress, potenciando o aumento na neurogénese no hipocampo adulto e recuperando igualmente a atrofia dendrítica induzida pelo stress em neurónios granulares no giro dentado do hipocampo. Estes resultados reforçam a ideia de que a modulação da neurotransmissão monoaminérgica está envolvida nos efeitos neuroplasticos promovida pelos antidepressivos. Para dissecar, as acções dos antidepressivos na neurogénese hipotalâmica, utilizamos o modelo animal de depressão uCMS e tratamento com diferentes classes de antidepressivos: fluoxetina (um inibidor selectivo da reabsorção de serotonina) e imipramina (um antidepressivo tricíclico). Os nossos resultados demonstram que o stress crónico e o tratamento com antidepressivos modulam a neurogénese no hipotálamo. Além disso, provou-se que diferentes classes de antidepressivos, com uma acção contrária no apetite e no ganho de peso corporal, modulam a neurogénese no hipotálamo de uma forma diferencial. Estes resultados, indicam que, para além do hipocampo, o stress e os antidepressivos também modulam a neurogénese no hipotálamo adulto. Em seguida, exploramos o papel da neuroplasticidade nas acções terapêuticas dos antipsicóticos atípicos na depressão. Para isso, utilizou-se o modelo animal de depressão uCMS e tratamento com o antipsicótico clássico (haloperidol) e o atípico (clozapina). Os nossos dados demonstram que, o antipsicótico atípico clozapina melhorou o comportamento depressivo. Por outro lado, o haloperidol não teve qualquer efeito benéfico, agravando o desalento aprendido no teste de natação forçada e a flexibilidade comportamental numa tarefa cognitiva. Simultaneamente observou-se um aumento da neurogénese adulta e da sobrevivência neuronal em animais tratados com clozapina, enquanto que o haloperidol promoveu uma redução nestes processos. Estes resultados, demonstram que o antipsicótico atípico é capaz de reverter os efeitos comportamentais do stress crónico através da melhoria na neurogénese adulta, da sobrevivência celular e da reorganização neuronal. Por último, para compreender o impacto das diferentes classes de antipsicóticos nos sintomas negativos e cognitivos da esquizofrenia, utilizamos um modelo de neurodesenvolvimento desta mesma patologia. Os animais expostos no período pré-natal ao agente acetato de metilazoximetanol (MAM) apresentaram défices cognitivos e sociais. O antipsicótico clássico haloperidol não apresentou efeitos benéficos nestas dimensões de comportamento. Por outro lado, os antipsicóticos atípicos, clozapina e risperidona, apresentaram um efeito positivo em ambas as dimensões com o aripiprazol apresentando apenas um efeito estatístico na dimensão social. A gliogénese adulta esta afectada nos animais MAM, sendo esta modulada pelos antipsicóticos atípicos usados. A neurogénese não se encontra alterada neste modelo, sendo, no entanto, negativamente afectada pelo haloperidol. Neste trabalho, provamos que os antipsicóticos clássicos e atípicos modulam diferencialmente a formação de novas células no hipocampo, contribuindo possivelmente para diferentes acções comportamentais, em funções dependentes do hipocampo. Em suma, estes resultados contribuem para expandir o nosso conhecimento sobre o papel de agentes psicofarmacológicos (incluindo antidepressivos e antipsicóticos) na modulação de diferentes eventos neuroplásticos, incluindo a formação de novas células e a remodelação neuronal. No futuro, este conhecimento poderá ajudar na implementação de novas intervenções terapêuticas tanto na depressão como na esquizofrenia.The work presented in this thesis was performed in the Life and Health Sciences Research Institute (ICVS), University of Minho. Financial support was provided by a PhD grant (SFRH/BD/88825/2012) from the FCT - Foundation for Science and Technology -, by FEDER funds through the Operational Programme Competitiveness Factors - COMPETE and National Funds through FCT under the project POCI-01-0145-FEDER-007038; and by the project NORTE-01-0145-FEDER-000013, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)

Unraveling the genetic background of individuals with a clinical familial hypercholesterolemia phenotype

Familial hypercholesterolemia (FH) is a common genetic disorder of lipid metabolism caused by pathogenic/likely pathogenic variants in LDLR, APOB, and PCSK9 genes. Variants in FH-phenocopy genes (LDLRAP1, APOE, LIPA, ABCG5, and ABCG8), polygenic hypercholesterolemia, and hyperlipoprotein (a) [Lp(a)] can also mimic a clinical FH phenotype. We aim to present a new diagnostic tool to unravel the genetic background of clinical FH phenotype. Biochemical and genetic study was performed in 1,005 individuals with clinical diagnosis of FH, referred to the Portuguese FH Study. A next-generation sequencing panel, covering eight genes and eight SNPs to determine LDL-C polygenic risk score and LPA genetic score, was validated, and used in this study. FH was genetically confirmed in 417 index cases: 408 heterozygotes and 9 homozygotes. Cascade screening increased the identification to 1,000 FH individuals, including 11 homozygotes. FH-negative individuals (phenotype positive and genotype negative) have Lp(a) >50 mg/dl (30%), high polygenic risk score (16%), other monogenic lipid metabolism disorders (1%), and heterozygous pathogenic variants in FH-phenocopy genes (2%). Heterozygous variants of uncertain significance were identified in primary genes (12%) and phenocopy genes (7%). Overall, 42% of our cohort was genetically confirmed with FH. In the remaining individuals, other causes for high LDL-C were identified in 68%. Hyper-Lp(a) or polygenic hypercholesterolemia may be the cause of the clinical FH phenotype in almost half of FH-negative individuals. A small part has pathogenic variants in ABCG5/ABCG8 in heterozygosity that can cause hypercholesterolemia and should be further investigated. This extended next-generation sequencing panel identifies individuals with FH and FH-phenocopies, allowing to personalize each person’s treatment according to the affected pathway

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved

4Th Pediatric Allergy And Asthma Meeting (Paam)

WORKSHOP 4: Challenging clinical scenarios (CS01–CS06), CS01 Bullous lesions in two children: solitary mastocytoma, S. Tolga Yavuz, Ozan Koc, Ali Gungor, Faysal Gok, CS02 Multi-System Allergy (MSA) of cystic fibrosis: our institutional experience, Jessica Hawley, Christopher O’Brien, Matthew Thomas, Malcolm Brodlie, Louise Michaelis, CS03 Cold urticaria in pediatric age: an invisible cause for severe reactions, Inês Mota, Ângela Gaspar, Susana Piedade, Graça Sampaio, José Geraldo Dias, Miguel Paiva, Mário Morais-Almeida, CS04 Angioedema with C1 inhibitor deficiency in a girl: a challenge diagnosis, Cristina Madureira, Tânia Lopes, Susana Lopes, Filipa Almeida, Alexandra Sequeira, Fernanda Carvalho, José Oliveira, CS05 A child with unusual multiple organ allergy disease: what is the primer?, Fabienne Gay-Crosier, CS06 A case of uncontrolled asthma in a 6-year-old patient, Ioana-Valentina Nenciu, Andreia Florina Nita, Alexandru Ulmeanu, Dumitru Oraseanu, Carmen Zapucioiu, ORAL ABSTRACT SESSION 1: Food allergy (OP01–OP06), OP01 Food protein-induced enterocolitis syndrome: oral food challenge outcomes for tolerance evaluation in a Pediatric Hospital, Adrianna Machinena, Olga Domínguez Sánchez, Montserrat Alvaro Lozano, Rosa Jimenez Feijoo, Jaime Lozano Blasco, Mònica Piquer Gibert, Mª Teresa Giner Muñoz, Marcia Dias da Costa, Ana Maria Plaza Martín, OP02 Characteristics of infants with food protein-induced enterocolitis syndrome and allergic proctocolitis, Ebru Arik Yilmaz, Özlem Cavkaytar, Betul Buyuktiryaki, Ozge Soyer, Cansin Sackesen, OP03 The clinical and immunological outcomes after consumption of baked egg by 1–5 year old egg allergic children: results of a randomised controlled trial, MerrynNetting, Adaweyah El-Merhibi, Michael Gold, PatrickQuinn, IrmeliPenttila, Maria Makrides, OP04 Oral immunotherapy for treatment of egg allergy using low allergenic, hydrolysed egg, Stavroula Giavi, Antonella Muraro, Roger Lauener, Annick Mercenier, Eugen Bersuch, Isabella M. Montagner, Maria Passioti, Nicolò Celegato, Selina Summermatter, Sophie Nutten, Tristan Bourdeau, Yvonne M. Vissers, Nikolaos G. Papadopoulos, OP05 Chemical modification of a peanut extract results in an increased safety profile while maintaining efficacy, Hanneke van der Kleij, Hans Warmenhoven, Ronald van Ree, Raymond Pieters, Dirk Jan Opstelten, Hans van Schijndel, Joost Smit, OP06 Administration of the yellow fever vaccine in egg allergic children, Roisin Fitzsimons, Victoria Timms, George Du Toit, ORAL ABSTRACT SESSION 2: Asthma (OP07–OP12), OP07 Previous exacerbation is the most important risk factor for future exacerbations in school-age children with asthma, S. Tolga Yavuz, Guven Kaya, Mustafa Gulec, Mehmet Saldir, Osman Sener, Faysal Gok, OP08 Comparative study of degree of severity and laboratory changes between asthmatic children using different acupuncture modalities, Nagwa Hassan, Hala Shaaban, Hazem El-Hariri, Ahmed Kamel Inas E. Mahfouz, OP09 The concentration of exhaled carbon monoxide in asthmatic children with different controlled stadium, Papp Gabor, Biro Gabor, Kovacs Csaba, OP10 Effect of vitamin D3 supplementation during pregnancy on risk of persistent wheeze in the offspring: a randomised clinical trial, Bo Chawes, Klaus Bønnelykke, Jakob Stokholm, Lene Heickendorff, Susanne Brix, Morten Rasmussen, Hans Bisgaard, OP11 Lung function development in childhood, Henrik Wegener Hallas, Bo Chawes, Lambang Arianto, Hans Bisgaard, OP12 Is the effect of maternal and paternal asthma different in female and male children before puberty?, Maike Pincus, Thomas Keil, Andreas Reich, Ulrich Wahn, Susanne Lau, Linus Grabenhenrich, ORAL ABSTRACT SESSION 3: Epidemiology—genetics (OP13–OP18), OP13 Lifestyle is associated with incidence and category of allergen sensitisation: the ALADDIN birth cohort, Sara Fagerstedt, Helena Marell Hesla, Emelie Johansson, Helen Rosenlund, Axel Mie, Annika Scheynius, Johan Alm, OP15 Maternal filaggrin mutations increase the risk of atopic dermatitis in children: an effect independent of mutation inheritance, Jorge Esparza-Gordillo, Anja Matanovic, Ingo Marenholz, Anja Bauerfeind, Klaus Rohde, Katja Nemat, Min-Ae Lee-Kirsch, Magnus Nordenskjöld, Marten C. G. Winge, Thomas Keil, Renate Krüger, Susanne Lau, Kirsten Beyer, Birgit Kalb, Bodo Niggemann, Norbert Hübner, Heather J. Cordell, Maria Bradley, Young-Ae Lee, OP16 Allergic multimorbidity of asthma, rhinitis and eczema in the first 2 decades of the German MAS birth cohort, Thomas Keil, Hannah Gough, Linus Grabenhenrich, Dirk Schramm, Andreas Reich, John Beschorner, Antje Schuster, Carl-Peter Bauer, Johannes Forster, Fred Zepp, Young-Ae Lee, Renate Bergmann, Karl Bergmann, Ulrich Wahn, Susanne Lau, OP17 Childhood anaphylaxis: a growing concern, Filipe Benito Garcia, Inês Mota, Susana Piedade, Ângela Gaspar, Natacha Santos, Helena Pité, Mário Morais-Almeida, OP18 Indoor exposure to molds and dampness in infancy and its association to persistent atopic dermatitis in school age. Results from the Greek ISAAC II study, Athina Papadopoulou, Despina Mermiri, Elpida Xatziagorou, Ioannis Tsanakas, Stavroula Lampidi, Kostas Priftis, ORAL ABSTRACT SESSION 4: Pediatric rhinitis—immunotherapy (OP19–OP24), OP19 Associations between residential greenness and childhood allergic rhinitis and aeroallergen sensitisation in seven birth cohorts, Elaine Fuertes, Iana Markevych, Gayan Bowatte, Olena Gruzieva, Ulrike Gehring, Allan Becker, Dietrich Berdel, Michael Brauer, Chris Carlsten, Barbara Hoffmann, Anita Kozyrskyj, Caroline Lodge, Göran Pershagen, Alet Wijga, Heinrich Joachim, OP20 Full symptom control in pediatric patients with allergic rhinitis and asthma: results of a 2-year sublingual allergen immunotherapy study, Zorica Zivkovic, Ivana Djuric-Filipovic, Jasmina Jocić-Stevanovic, Snežana Zivanovic, OP21 Nasal epithelium of different ages of atopic subjects present increased levels of oxidative stress and increased cell cytotoxicity upon rhinovirus infection, Styliani Taka, Dimitra Kokkinou, Aliki Papakonstantinou, Panagiota Stefanopoulou, Anastasia Georgountzou, Paraskevi Maggina, Sofia Stamataki, Vassiliki Papaevanggelou, Evangelos Andreakos, Nikolaos G. Papadopoulos, OP22 Cluster subcutaneous immunotherapy schedule: tolerability profile in children, Monica Piquer Gibert, Montserrat Alvaro Lozano, Jaime Lozano Blasco, Olga Domínguez Sánchez, Rosa Jiménez Feijoo, Marcia Dias da Costa, Mª Teresa Giner Muñoz, Adriana Machinena Spera, Ana Maria Plaza Martín, OP23 Rhinitis as a risk factor for asthma severity in 11-year old children: population-based cohort study, Matea Deliu, Danielle Belgrave, Angela Simpson, Adnan Custovic, OP24 The Global Lung Function Initiative equations in airway obstruction evaluation of asthmatic children, João Gaspar Marques, Pedro Carreiro-Martins, Joana Belo, Sara Serranho, Isabel Peralta, Nuno Neuparth, Paula Leiria-Pinto, POSTER DISCUSSION SESSION 1: Food allergy (PD01–PD05), PD01 Allergen-specific humoral and cellular responses in children who fail egg oral immunotherapy due to allergic reactions, Marta Vazquez-Ortiz, Mariona Pascal, Ana Maria Plaza, Manel Juan, PD02 FoxP3 epigenetic features in children with cow milk allergy, Lorella Paparo, Rita Nocerino, Rosita Aitoro, Ilaria Langella, Antonio Amoroso, Alessia Amoroso, Carmen Di Scala, Roberto Berni Canani, PD04 Combined milk and egg allergy in early childhood: let them eat cake?, Santanu Maity, Giuseppina Rotiroti, Minal Gandhi, PD05 Introduction of complementary foods in relation to allergy and gut microbiota in farm and non-farm children, Karin Jonsson, Annika Ljung, Bill Hesselmar, Ingegerd Adlerbert, Hilde Brekke, Susanne Johansen, Agnes Wold, Ann-Sofie Sandberg, POSTER DISCUSSION SESSION 2: Asthma and wheeze (PD06–PD16), PD06 The association between asthma and exhaled nitric oxide is influenced by genetics and sensitisation, Björn Nordlund, Cecilia Lundholm, Villhelmina Ullemar, Marianne van Hage, Anne Örtqvist, Catarina Almqvist, PD09 Prevalence patterns of infant wheeze across Europe, Anna Selby, Kate Grimshaw, Thomas Keil, Linus Grabenhenrich, Michael Clausen, Ruta Dubakiene, Alessandro Fiocchi, Marek Kowalski, Nikos Papadopoulos, Marta Reche, Sigurveig Sigurdardottir, Aline Sprikkleman, Paraskevi Xepapadaki, Clare Mills, Kirsten Beyer, Graham Roberts, PD10 Epidemiologic changes in recurrent wheezing infants, Herberto Jose Chong Neto, Gustavo Falbo Wandalsen, Ana Carolina Dela Bianca, Carolina Aranda, Nelson Augusto Rosário, Dirceu Solé, Javier Mallol, Luis García Marcos, PD13 A single nucleotide polymorphism in the GLCCI1 gene is associated with response to asthma treatment in children, IvanaBanic, Matija Rijavec, Davor Plavec, Peter Korosec, Mirjana Turkalj, PD14 Pollen induced asthma: Could small molecules in pollen exacerbate the protein-mediated allergic response?, Alen Bozicevic, Maria De Mieri, Matthias Hamburger, PD15 A qualitative study to understand how we can empower teenagers to better self-manage their asthma, Simone Holley, Ruth Morris, Frances Mitchell, Rebecca Knibb, Susan Latter, Christina Liossi, Graham Roberts, PD16 Polymorphism of endothelial nitric oxide synthase (eNOS) gene among Egyptian children with bronchial asthma, Mostafa M. M. Hassan, POSTER DISCUSSION SESSION 3: Mechanisms—Epidemiology (PD17–PD21), PD17 Pregnancy outcomes in relation to development of allergy in a Swedish birth cohort, Malin Barman, Anna Sandin, Agnes Wold, Ann-Sofie Sandberg, PD18 Evolution of the IgE response to house dust mite molecules in childhood, Daniela Posa, Serena Perna, Carl-Peter Bauer, Ute Hoffmann, Johannes Forster, Fred Zepp, Antje Schuster, Ulrich Wahn, Thomas Keil, Susanne Lau, Kuan-Wei Chen, Yvonne Resch, Susanne Vrtala, Rudolf Valenta, Paolo Maria Matricardi, PD19 Antibody recognition of nsLTP-molecules as antigens but not as allergens in the German-MAS birth cohort, Olympia Tsilochristou, Alexander Rohrbach, Antonio Cappella, Stephanie Hofmaier, Laura Hatzler, Carl-Peter Bauer, Ute Hoffmann, Johannes Forster, Fred Zepp, Antje Schuster, RaffaeleD’Amelio, Ulrich Wahn, Thomas Keil, Susanne Lau, Paolo Maria Matricardi, PD20 Early life colonization with Lactobacilli and Staphylococcus aureus oppositely associates with the maturation and activation of FOXP3+ CD4 T-cells, Sophia Björkander, Maria A. Johansson, Gintare Lasaviciute, Eva Sverremark-Ekström, PD21 Genome-wide meta-analysis identifies 7 susceptibility loci involved in the atopic march, Ingo Marenholz, Jorge Esparza-Gordillo, Franz Rüschendorf, Anja Bauerfeind, David P. Strachan, Ben D. Spycher, Hansjörg Baurecht, Patricia Margaritte-Jeannin, Annika Sääf, Marjan Kerkhof, Markus Ege, Svetlana Baltic, Melanie C Matheson, Jin Li, Sven Michel, Wei Q. Ang, Wendy McArdle, Andreas Arnold, Georg Homuth, Florence Demenais, Emmanuelle Bouzigon, Cilla Söderhäll, Göran Pershagen, Johan C. de Jongste, Dirkje S Postma, Charlotte Braun-Fahrländer, Elisabeth Horak, Ludmila M. Ogorodova, Valery P. Puzyrev, Elena Yu Bragina, Thomas J Hudson, Charles Morin, David L Duffy, Guy B Marks, Colin F Robertson, Grant W Montgomery, Bill Musk, Philip J Thompson, Nicholas G. Martin, Alan James, Patrick Sleiman, Elina Toskala, Elke Rodriguez, Regina Fölster-Holst, Andre Franke, Wolfgang Lieb, Christian Gieger, Andrea Heinzmann, Ernst Rietschel, Thomas Keil, Sven Cichon, Markus M Nöthen, Craig E Pennell, Peter D Sly, Carsten O Schmidt, Anja Matanovic, Valentin Schneider, Matthias Heinig, Norbert Hübner, Patrick G. Holt, Susanne Lau, Michael Kabesch, Stefan Weidinger, Hakon Hakonarson, Manuel AR Ferreira, Catherine Laprise, Maxim B. Freidin, Jon Genuneit, Gerard H Koppelman, Erik Melén, Marie-Hélène Dizier, A. John Henderson, Young Ae Lee, POSTER DISCUSSION SESSION 4: Food allergy—Anaphylaxis (PD22–PD26), PD22 Atopy patch test in food protein induced enterocolitis caused by solid food, Purificacion González-Delgado, Esther Caparrós, Fernando Clemente, Begoña Cueva, Victoria M. Moreno, Jose Luis Carretero, Javier Fernández, PD23 Watermelon allergy: a novel presentation, Kate Swan, George Du Toit, PD24 A pilot study evaluating the usefulness of a guideline template for managing milk allergy in primary care, Mudiyur Gopi, Tim Smith, Edara Ramesh, Arun Sadasivam, PD26 Efficacy and safety of cow’s milk oral immunotherapy protocol, Inês Mota, Filipe Benito Garcia, Susana Piedade, Angela Gaspar, Graça Sampaio, Cristina Arêde, Luís Miguel Borrego, Graça Pires, Cristina Santa-Marta, Mário Morais-Almeida, POSTER DISCUSSION SESSION 5: Prevention and treatment—Allergy (PD27–PD36), PD27 Allergy-protection by the lactic acid bacterium Lactococcus lactis G121: mode-of-action as revealed in a murine model of experimental allergy, Stephanie Brand, Karina Stein, Holger Heine, Marion Kauth, PD29 The relationship between quality of life and morning salivary cortisol after acute bronchiolitis in infancy, Leif Bjarte Rolfsjord, Egil Bakkeheim, Johan Alm, Håvard Ove Skjerven, Kai-Håkon Carlsen, Jon Olav Hunderi, Teresa Løvold Berents, Petter Mowinckel, Karin C. Lødrup Carlsen, PD30 Randomised trial of the efficacy of MP29-02* compared with fluticasone propionate nasal spray in children aged ≥6 years to <12 years with allergic rhinitis, Ulrich Wahn, Ullrich Munzel, William Berger, PD31 10 mg of oral bilastine in 2 to 11 years old children has similar exposure to the adult therapeutic dose (20 mg), Ulrich Wahn, Román Valiente, Valvanera Vozmediano, John C. Lukas, Mónica Rodríguez, PD33 Daily symptoms, nocturnal symptoms, activity limitations and reliever therapies during the three steps of IOEASMA programme: a comparison, Sebastiano Guarnaccia, Luigi Vitale, Ada Pluda, Emanuele D’Agata, Denise Colombo, Stefano Felici, Valeria Gretter, Susanna Facchetti, Gaia Pecorelli, Cristina Quecchia, PD34 Sensitisation to an inert aeroallergen in weaning rats and longstanding disease, in a sensitisation-tolerant and easily tolerisable rodent strain, George Guibas, Evangelia Spandou, Spyridon Megremis, Peter West, Nikolaos Papadopoulos, PD35 Bacterial and fungi exposure in school and allergic sensitisation in children, João Cavaleiro Rufo, Joana Madureira, Inês Paciência, Lívia Aguiar, Patrícia Padrão, Mariana Pinto, Luís Delgado, Pedro Moreira, João Paulo Teixeira, Eduardo Oliveira Fernandes, André Moreira, PD36 Comparative study of allergy rhinitis between two populations: children vs. adults, Adriana Izquierdo Dominguez, Antonio Valero, Joaquim Mullol, Alfonso Del Cuvillo, Javier Montoro, Ignacio Jauregui, Joan Bartra, Ignacio Davila, Marta Ferrer, Joaquin Sastre, POSTER VIEWING SESSION 1: Inflammation—Genetics—Immunology—Dermatology (PP01–PP09), PP01 Immune profile in late pregnancy: immunological markers in atopic asthmaticwomen as risk factors for atopy in the progeny, Catarina Martins, Jorge Lima, Maria José Leandro, Glória Nunes, Jorge Cunha Branco, Hélder Trindade, Luis Miguel Borrego, PP02 The impact of neonatal sepsis on development of allergic diseases, Secil Conkar, Mehtap Kilic, Canan Aygun, Recep Sancak, PP03 Clinical overview of selective IgE deficiency in childhood, Athina Papadopoulou, Eleni Tagalaki, Lambros Banos, Anna Vlachou, Fotini Giannoula, Despina Mermiri, PP04 Inverse relationship between serum 25(ΟΗ) vitamin D3 and total IgE in children and adolescence, Athina Papadopoulou, Stavroula Lampidi, Marina Pavlakou, Maria Kryoni, Kostas Makris, PP05, PP06, PP07 Asthma control questionnaire and specific IgE in children, Snezhina Lazova, Guergana Petrova, Dimitrinka Miteva, Penka Perenovska, PP08 Features of chronic urticaria of adolescents, Aliya Klyucharova, Olesya Skorohodkina, PP09 Cutaneous mastocytosis in children: a clinical analysis of 8 cases in Greece, Dimitra Koumaki, Alkisti Manousaki, Maria Agrapidi, Lida Iatridou, Omima Eruk, Konstantinos Myridakis, Emmanouil Manousakis, Vasiliki Koumaki, POSTER VIEWING SESSION 2: Food allergy—Anaphylaxis (PP10–PP47), PP10 Prognostic factors in egg allergy, Maria Dimou, Maria Ingemansson, Gunilla Hedlin, PP11 Evaluation of the efficacy of an amino acid-based formula in infants who are intolerant to extensively hydrolysed protein formula, Nitida Pastor, Delphine de Boissieu, Jon Vanderhoof, Nancy Moore, Kaitlin Maditz, PP12 Anaphylaxis and epinephrine auto-injector use: a survey of pediatric trainees, Adeli Mehdi, Shaza Elhassan, Carolin Beck, Ahmed Al-Hammadi, PP13 Anaphylaxis in children: acute management in the Emergency Department, Ioana Maris, Ronan O’Sullivan, Jonathan Hourihane,, PP14 Understanding Cumbrian schools preparedness in managing children at risk of anaphylaxis in order to provide training and support which will create healthy and safe environments for children with allergies, George Raptis, Louise Michaelis, PP15 A new valid and reliable parent and child questionnaire to measure the impact of food protein enterocolitis syndrome on children: the FPIES Quality of Life Questionnaire (FPIESQL), Parent and Child Short Form, Audrey DunnGalvin, Matthew Greenhawt, Carina Venter, Jonathan Hourihane, PP16 An in-depth case study investigation of the experiences of teenagers and young adults in growing up and living with food allergy with emphasis on coping, management and risk, support, and social and self-identity, Evelyn O’Regan, Duncan Cronin, Jonathan Hourihane, Anna O’Reilly, Audrey DunnGalvin, PP17 Cow’s milk protein allergy in Constantine. A retrospective study of 62 cases between 1996 and 2013, Foued Abdelaziz, Dounia Khelifi-Touhami, Nihad Selim, Tahar Khelifi-Touhami, PP18, PP19 Cow’s milk and egg oral immunotherapy in children older than 5 years, Pablo Merida, Ana Mª Plaza, Juan Heber Castellanos, Adrianna Machinena, Montserrat Alvaro Lozano, Jaime Lozano, Olga Dominguez, Monica Piquer, Rosa Jimenez, Mª Teresa Giner, PP20 Professionals’ awareness of management of Cow’s Milk Protein Allergy (CMPA) in North Wales Hospitals, Konstantinos Kakleas, Manohar Joishy, Wendmu Maskele, Huw R. Jenkins, PP21, PP22 Anaphylaxis: the great unknown for teachers. Presentation of a protocol for schools, Mercedes Escarrer, Agustín Madroñero, Maria Teresa Guerra, Juan Carlos Julia, Juan Carlos Cerda, Javier Contreras, Eulalia Tauler, Maria Jesus Vidorreta, Ana Rojo, Silvia Del Valle, PP23 Challenges facing children with food allergies and their parents in out of school activity sectors, Niamh Flynn, PP24 A review of food challenges at a Regional Irish Centre, Gary Foley, Carol Harmon, John Fitzsimons, PP25 The use of epinephrine in infants with anaphylaxis, Krasimira Baynova, Ávila Maria Del Robledo, Labella Marina, PP26, PP27, PP28 Mother’s psychological state predicts the expression of symptoms in food allergic children, Aaron Cortes, Alicia Sciaraffia, Angela Castillo, PP29 The correlation between sIgE towards tree nuts and birch pollen in a Danish Pediatric Allergy Clinic, Nanna Juel-Berg, Kirsten Skamstrup Hansen, Lars Kærgaard Poulsen, PP30 Food allergy in children: evaluation of parents’ use of online social media, Andreia Florina Nita, Ioana Valentina Nenciu, Adina Lazar, Dumitru Oraseanu, PP31 The impact of food allergy on quality of life: FAQLQ questionnaire, Rita Aguiar, Anabela Lopes, Maria J. Paes, Amélia S. Santos, M. A. Pereira-Barbosa, PP32 An unexpected cause of anaphylaxis: potato, Hatice Eke Gungor, Salih Uytun, Umit Murat Sahiner, Yasemin Altuner Torun, PP33 Is it clinical phenotype of allergic diseases determined by sensitisation to food?, Mirjana Zivanovic, Marina Atanasković-Marković, PP34, PP35 Prescribing adrenaline auto-injectors in children in 2014: the data from regional pediatricians, Tina Vesel, Mihaela Nahtigal, Andreja Obermayer-Temlin, Eva Šoster Križnik, Mirjana Maslar, Ruben Bizjak, Marjeta Tomšič-Matic, Sonja Posega-Devetak, Maja Skerbinjek-Kavalar, Mateja Predalič, Tadej Avčin, PP36 Who should have an adrenaline autoinjector? Adherence to the European and French guidelines among 121 allergists from the Allergy Vigilance Network, Guillaume Pouessel, Etienne Beaudouin, Anne M. Moneret-Vautrin, Antoine Deschildre, Allergy Vigilance Network, PP37 Anaphylaxis by Anacardium Occidentale, Marta Viñas, Bartolomé Borja, Nora Hernández, Mª José Castillo, Adriana Izquierdo, Marcel Ibero, PP38 Anaphylaxis with honey in a child, S. Tolga Yavuz, Ali Gungor, Betul Buyuktiryaki, Ozan Koc, Can Naci Kocabas, Faysal Gok, PP39 Evaluation of courses adopted to children on prevention, recognition and management of anaphylaxis, Tina Vesel, Mihaela Nahtigal, PP40 Symptomatic dust mites and shrimp allergy: three pediatric case reports, Filipa Almeida, Susana Lopes, Cristina Madureira, Tânia Lopes, Fernanda Carvalho, PP41 Poor identification rates of nuts by high risk individuals: a call for improved education and support for families, Camille Heming, Emily Garrett, Adam Blackstock, Santanu Maity, Rahul Chodhari, PP42 DAFALL: database of food allergies in the Czech Republic, Simona Belohlavkova, Eliska Kopelentova, Petr Visek, Ivana Setinova, Ivana Svarcova, PP43 Serological cross-reactivity between grass and wheat is not only caused by profilins and CCDs, Sigrid Sjölander, Nora Nilsson, Malin Berthold, Helena Ekoff, Gunilla Hedlin, Magnus Borres, Caroline Nilsson, PP44 Oil body associated proteins in children with nuts allergy. Allergens to consider in IgE-mediated nuts allergy, Loreto González Domínguez, Cristina Muñoz Archidona, Ana Moreira Jorge, Sergio Quevedo Teruel, Teresa Bracamonte Bermejo, Miriam Castillo Fernández, Fernando Pineda de la Losa, Luis Ángel Echeverría Zudaire, PP45, PP46 Protective effect of helicobacter pylori infection against food allergy in children, Olga Vrani, Antigone Mavroudi, Maria Fotoulaki, Maria Emporiadou, Kleomenis Spiroglou, Ioannis Xinias, PP47 Anaphylaxis pathway: A road tryp-tase to success?, Helyeh A. Sadreddini, Mia Warnes, Donna Traves, POSTER VIEWING SESSION 3: Miscell