Mindich Child Health and Development Institute

New York City, NY, United States

Mindich Child Health and Development Institute

New York City, NY, United States
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Le poster (Su1838), intitulé « Tolerance with Viaskin requires TGF-b and can be utilized as a Treatment of Intestinal Inflammation in Murine Models » a été primé et présenté par le Dr David Dunkin, Professeur adjoint du Service de gastroentérologie pédiatrique au Mindich Child Health and Development Institute, à l'Icahn School of Medicine du Mount Sinai, New York, NY, le dimanche 7 mai de midi à 14h HNC. Dans un cadre expérimental, l'administration épicutanée de Viaskin contenant 100µg d'ovalbumine a joué un rôle dans l'induction des cellules T spécifiques de l'ova migrant vers le tube digestif et permettant de prévenir l'apparition de colites et d'iléites chez les souris par effet « bystander ». L'EPIT a démontré un effet sur l'augmentation la sécrétion de cellules Foxp3, LAP+ Tregs et de TGF-b chez les modèles animaux. Ces résultats permettent d'envisager l'application clinique de l'EPIT dans le traitement de la maladie de Crohn. En février 2014, DBV Technologies et l'Icahn School of Medicine du Mount Sinai ont entamé un partenariat de recherche en vue d'étudier l'utilisation de la technologie Viaskin dans le traitement de la maladie de Crohn. En décembre 2015, des données précliniques supplémentaires appuyant l'application de Viaskin dans le traitement de la maladie de Crohn ont été présentées lors de la conférence sur les Maladies Inflammatoires Chroniques de l'Intestin (AIBD) organisée par la Crohn & Colitis Foundation of America qui s'est tenue à Orlando, en Floride. À propos de la maladie de Crohn La maladie de Crohn est une inflammation chronique du tube digestif, qui se caractérise par des douleurs abdominales, des diarrhées et différentes complications digestives et non digestives. Il n'existe aucun traitement médicamenteux ou chirurgical guérissant la maladie de Crohn. Un patient sur cinq souffrant de la maladie de Crohn est hospitalisé chaque année et plus de la moitié de ces patients devront subir une intervention chirurgicale dans les dix années. L'incidence de la maladie de Crohn est en augmentation, en particulier chez les jeunes enfants et les nourrissons. La maladie de Crohn affecte aussi bien les hommes que les femmes et son diagnostic est généralement posé entre 15 et 30 ans. À propos de DBV Technologies  DBV Technologies a créé le patch Viaskin®, une plateforme technologique totalement brevetée avec de nombreuses applications potentielles en immunothérapie. L'immunothérapie par voie épicutanée, ou EPIT®, utilise le Viaskin® pour administrer des composés biologiquement actifs au système immunitaire sur une peau intacte. Viaskin est non-invasif, auto-administré et pourrait permettre une prise en charge en toute sécurité des patients souffrant d'allergies alimentaires, pour lesquelles il n'existe pas de traitements approuvés. Le programme de développement comprend des essais cliniques sur Viaskin Peanut et Viaskin Milk, une étude expérimentale sur le Viaskin Egg et un essai clinique preuve de concept dans l'oesophagite à éosinophiles. DBV a également développé sa plateforme technologique dans le domaine des vaccins et de certaines maladies auto-immunes pour lesquelles les besoins médicaux sont insatisfaits. Le siège social de DBV Technologies est à Montrouge, France et la Société a également des bureaux à New York, États-Unis. Les actions sont négociées sur le segment A d'Euronext Paris (mnémonique : DBV, code ISIN : FR0010417345), intégré à l'indice SBF120. DBV est également cotée sur le Nasdaq Global Select Market sous la forme d'American Depositary Shares, chaque ADS représentant la moitié d'une action ordinaire (mnémonique : DBVT). Pour plus d'informations, visitez notre site Web : www.dbv-technologies.com Déclarations prospectives Ce communiqué de presse contient des déclarations prospectives et des estimations, notamment des déclarations le potentiel de Viaskin dans le traitement de la maladie de Crohn. Ces déclarations prospectives et estimations ne constituent ni des promesses ni des garanties et comportent des risques et des aléas substantiels. Les produits de la société n'ont, à ce jour, été autorisés à la vente dans aucun pays. Les aléas liés de manière générale aux activités de recherche et développement, les essais cliniques, ainsi que les examens et autorisations réglementaires y associés et le risque dû au fait que l'historique des résultats précliniques puisse ne pas refléter les résultats des futurs essais cliniques, constituent autant de facteurs qui pourraient donner lieu à des résultats substantiellement différents de ceux décrits ou anticipés dans les présentes. Une liste détaillée et une description de ces risques, aléas et autres risques figurent dans les documents déposés par la société auprès de l'Autorité des Marchés Financiers au titre de ses obligations réglementaires, dans les documents et rapports de la société déposés auprès de la Security and Exchange Commission aux États-Unis, et dans le formulaire 20-F du rapport annuel de la société relatif à l'exercice social clôturé le 31 décembre 2016, ainsi que les enregistrements et rapports qui seront effectués par la Société. Les investisseurs existants et potentiels sont avertis qu'ils ne doivent pas se fier indûment à ces déclarations prospectives qui ne valent qu'à la date des présentes. Sauf si la loi applicable l'exige, DBV Technologies ne prend aucun engagement de mettre à jour ou réviser les informations contenues dans ce communiqué.


Tordesillas L.,Mount Sinai School of Medicine | Goswami R.,Mount Sinai School of Medicine | Benede S.,Institute of Food Science Research CIAL | Jarvinen K.M.,Albany Medical College | And 5 more authors.
Journal of Clinical Investigation | Year: 2014

Sensitization to foods often occurs in infancy, without a known prior oral exposure, suggesting that alternative exposure routes contribute to food allergy. Here, we tested the hypothesis that peanut proteins activate innate immune pathways in the skin that promote sensitization. We exposed mice to peanut protein extract on undamaged areas of skin and observed that repeated topical exposure to peanut allergens led to sensitization and anaphylaxis upon rechallenge. In mice, this epicutaneous peanut exposure induced sensitization to the peanut components Ara h 1 and Ara h 2, which is also observed in human peanut allergy. Both crude peanut extract and Ara h 2 alone served as adjuvants, as both induced a bystander sensitization that was similar to that induced by the atopic dermatitisassociated staphylococcal enterotoxin B. In cultured human keratinocytes and in murine skin, peanut extract directly induced cytokine expression. Moreover, topical peanut extract application induced an alteration dependent on the IL-33 receptor ST2 in skin-draining DCs, resulting in Th2 cytokine production from T cells. Together, our data support the hypothesis that peanuts are allergenic due to inherent adjuvant activity and suggest that skin exposure to food allergens contributes to sensitization to foods in early life.


Burris H.H.,Beth Israel Deaconess Medical Center | Burris H.H.,Harvard University | Baccarelli A.A.,Harvard University | Wright R.O.,Mindich Child Health and Development Institute | And 2 more authors.
Pediatric Research | Year: 2016

Preterm birth remains a leading cause of infant mortality and morbidity. Despite decades of research, marked racial and socioeconomic disparities in preterm birth persist. In the Unites States, more than 16% of African-American infants are born before 37 wk of gestation compared with less than 11% of white infants. While income and education differences predict a portion of these racial disparities, income and education are proxies of the underlying causes rather than the true cause. How these differences lead to the pathophysiology remains unknown. Beyond tobacco smoke exposure, most preterm birth investigators overlook environment exposures that often correlate with poverty. Environmental exposures to industrial contaminants track along both socioeconomic and racial/ethnic lines due to cultural variation in personal product use, diet, and residential geographical separation. Emerging evidence suggests that environmental exposure to metals and plasticizers contribute to preterm birth and epigenetic modifications. The extent to which disparities in preterm birth result from interactions between the social and physical environments that produce epigenetic modifications remains unclear. In this review, we highlight studies that report associations between environmental exposures and preterm birth as well as perinatal epigenetic sensitivity to environmental contaminants and socioeconomic stressors. © 2016 International Pediatric Research Foundation, Inc.


Glessner J.T.,Applied Genomics | Glessner J.T.,University of Pennsylvania | Bick A.G.,Harvard University | Ito K.,Harvard University | And 26 more authors.
Circulation Research | Year: 2014

Rationale: Congenital heart disease (CHD) is among the most common birth defects. Most cases are of unknown pathogenesis. Objective: To determine the contribution of de novo copy number variants (CNVs) in the pathogenesis of sporadic CHD. Methods and Results: We studied 538 CHD trios using genome-wide dense single nucleotide polymorphism arrays and whole exome sequencing. Results were experimentally validated using digital droplet polymerase chain reaction. We compared validated CNVs in CHD cases with CNVs in 1301 healthy control trios. The 2 complementary high-resolution technologies identified 63 validated de novo CNVs in 51 CHD cases. A significant increase in CNV burden was observed when comparing CHD trios with healthy trios, using either single nucleotide polymorphism array (P=7×10-5; odds ratio, 4.6) or whole exome sequencing data (P=6×10-4; odds ratio, 3.5) and remained after removing 16% of de novo CNV loci previously reported as pathogenic (P=0.02; odds ratio, 2.7). We observed recurrent de novo CNVs on 15q11.2 encompassing CYFIP1, NIPA1, and NIPA2 and single de novo CNVs encompassing DUSP1, JUN, JUP, MED15, MED9, PTPRE SREBF1, TOP2A, and ZEB2, genes that interact with established CHD proteins NKX2-5 and GATA4. Integrating de novo variants in whole exome sequencing and CNV data suggests that ETS1 is the pathogenic gene altered by 11q24.2-q25 deletions in Jacobsen syndrome and that CTBP2 is the pathogenic gene in 10q subtelomeric deletions. Conclusions: We demonstrate a significantly increased frequency of rare de novo CNVs in CHD patients compared with healthy controls and suggest several novel genetic loci for CHD. © 2014 American Heart Association, Inc.


Den Hoed M.,University of Cambridge | Den Hoed M.,Uppsala University | Brage S.,University of Cambridge | Zhao J.H.,University of Cambridge | And 9 more authors.
American Journal of Clinical Nutrition | Year: 2013

Background: Twin and family studies that estimated the heritability of daily physical activity have been limited by poor measurement quality and a small sample size. Objective: We examined the heritability of daily physical activity and sedentary behavior assessed objectively by using combined heart rate and movement sensing in a large twin study. Design: Physical activity traits were assessed in daily life for a mean (6SD) 6.7 ± 1.1 d in 1654 twins from 420 monozygotic and 352 dizygotic same-sex twin pairs aged 56.3 ± 10.4 y with body mass index (in kg/m2) of 26.1 ± 4.8. We estimated the average daily movement, physical activity energy expenditure, and time spent in moderate-to-vigorous intensity physical activity and sedentary behavior from heart rate and acceleration data. We used structural equation modeling to examine the contribution of additive genetic, shared environmental, and unique environmental factors to betweenindividual variation in traits. Results: Additive genetic factors (ie, heritability) explained 47% of the variance in physical activity energy expenditure (95% CI: 23%, 53%) and time spent in moderate-to-vigorous intensity physical activity (95% CI: 29%, 54%), 35% of the variance in acceleration of the trunk (95% CI: 0%, 44%), and 31% of the variance in the time spent in sedentary behavior (95% CI: 9%, 51%). The remaining variance was predominantly explained by unique environmental factors and random error, whereas shared environmental factors played only a marginal role for all traits with a range of 0-15%. Conclusions: The between-individual variation in daily physical activity and sedentary behavior is mainly a result of environmental influences. Nevertheless, genetic factors explain up to one-half of the variance, suggesting that innate biological processes may be driving some of our daily physical activity. © 2013 American Society for Nutrition.


News Article | February 15, 2017
Site: www.eurekalert.org

A population of cells in early development may give rise to the ventricular chambers of the heart, but not the atria, according to a study led by researchers from the Mindich Child Health and Development Institute at the Icahn School of Medicine at Mount Sinai and published today in Nature Communications. Congenital heart defects are the most common type of birth defect, affecting 35,000 babies in the United States each year, according to the U.S. Department of Health and Human Services. Many of these defects originate as the heart chambers are forming. While much is known about the development of the heart, the formation of the four distinct chambers of the heart has lacked thorough understanding. Using a model that traces cell lineage in mice, investigators studied the protein-coding gene Foxa2, primarily associated with endoderm and ectoderm development during embryogenesis. They discovered a population of progenitor cells expressing Foxa2 during early development that gave rise to cardiovascular cells of both the left and right ventricular chambers, but not the atria. Their research showed that atrial-ventricular segregation may occur long before the morphological establishment of differentiated cardiac structures. "An in-depth understanding of the formation of the heart chambers will enable us to better comprehend the biology behind detrimental heart defects and how best to address them," said lead investigator Nicole Dubois, PhD, Assistant Professor in the Department of Cell, Developmental and Regenerative Biology at the Icahn School of Medicine at Mount Sinai. "In addition to informing our understanding of early heart development, we hope that these findings will also lead to new protocols for the generation of ventricular cardiomyocytes in cell culture that could potentially be used in therapeutic settings." "There is a lot we still don't understand about this population, or the function of Foxa2 during the formation of the heart, but we think these findings provide a powerful new system to answer some of the most relevant open questions about how early heart development occurs," said Evan Bardot, PhD student and first author of the Nature Communications study. The National Institutes of Health (NIH/NHLBI) and the Mindich Child Health and Development Institute supported this research. The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services -- from community-based facilities to tertiary and quaternary care. The System includes approximately 6,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is ranked as one of the nation's top 10 hospitals in Geriatrics, Cardiology/Heart Surgery, and Gastroenterology, and is in the top 25 in five other specialties in the 2014-2015 "Best Hospitals" issue of U.S. News & World Report. Mount Sinai's Kravis Children's Hospital also is ranked in seven out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 11th nationally for Ophthalmology, while Mount Sinai Beth Israel is ranked regionally. For more information, visit http://www. , or find Mount Sinai on Facebook, Twitter and YouTube.


Dhandapany P.S.,Mount Sinai School of Medicine | Dhandapany P.S.,Mindich Child Health and Development Institute | Razzaque M.A.,Cincinnati Childrens Hospital | Razzaque M.A.,University of Wisconsin - Madison | And 30 more authors.
Nature Genetics | Year: 2014

Dilated cardiomyopathy (DCM) is a highly heterogeneous trait with sarcomeric gene mutations predominating. The cause of a substantial percentage of DCMs remains unknown, and no gene-specific therapy is available. On the basis of resequencing of 513 DCM cases and 1,150 matched controls from various cohorts of distinct ancestry, we discovered rare, functional RAF1 mutations in 3 of the cohorts (South Indian, North Indian and Japanese). The prevalence of RAF1 mutations was 1/49% in childhood-onset DCM cases in these three cohorts. Biochemical studies showed that DCM-associated RAF1 mutants had altered kinase activity, resulting in largely unaltered ERK activation but in AKT that was hyperactivated in a BRAF-dependent manner. Constitutive expression of these mutants in zebrafish embryos resulted in a heart failure phenotype with AKT hyperactivation that was rescued by treatment with rapamycin. These findings provide new mechanistic insights and potential therapeutic targets for RAF1-associated DCM and further expand the clinical spectrum of RAF1-related human disorders. © 2014 Nature America, Inc.


Bosquet Enlow M.,Boston Childrens Hospital | Bosquet Enlow M.,Harvard University | King L.,Boston Childrens Hospital | Schreier H.M.C.,Kravis Childrens Hospital | And 7 more authors.
Early Human Development | Year: 2014

Background: Early environmental exposures may help shape the development of the autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis, influencing vulnerability for health problems across the lifespan. Little is known about the role of maternal sensitivity in influencing the development of the ANS in early life. Aims: To examine associations among maternal sensitivity and infant behavioral distress and ANS and HPA axis reactivity to the Repeated Still-Face Paradigm (SFP-R), a dyadic stress task. Study design: Observational repeated measures study. Subjects: Thirty-five urban, sociodemographically diverse mothers and their 6-month-old infants. Outcome measures: Changes in infant affective distress, heart rate, respiratory sinus arrhythmia (RSA), and T-wave amplitude (TWA) across episodes of the SFP-R were assessed. A measure of cortisol output (area under the curve) in the hour following cessation of the SFP-R was also obtained. Results: Greater maternal insensitivity was associated with greater infant sympathetic activation (TWA) during periods of stress and tended to be associated with greater cortisol output following the SFP-R. There was also evidence for greater affective distress and less parasympathetic activation (RSA) during the SFP-R among infants of predominantly insensitive mothers. Conclusions: Caregiving quality in early life may influence the responsiveness of the sympathetic and parasympathetic branches of the ANS as well as the HPA axis. Consideration of the ANS and HPA axis systems together provides a fuller representation of adaptive versus maladaptive stress responses. The findings highlight the importance of supporting high quality caregiving in the early years of life, which is likely to promote later health. © 2014 Elsevier Ltd.


Leventakou V.,University of Crete | Micali N.,University College London | Micali N.,Mindich Child Health and Development Institute | Georgiou V.,University of Crete | And 7 more authors.
Journal of Child Psychology and Psychiatry and Allied Disciplines | Year: 2016

Background There is some evidence that aberrant eating behaviours and obesity co-occur with attention-deficit/hyperactivity disorder (ADHD) symptoms. The present study is the first that aims to investigate the association between eating behaviours and ADHD symptoms in early childhood in a population-based cohort. Methods We included 471 preschool children from the Rhea mother-child cohort in Crete, Greece. Parents completed the Children's Eating Behaviour Questionnaire to assess children's eating behaviour and the 36-item ADHD test (ADHDT) to evaluate ADHD symptoms at 4 years of age. Multivariable linear regression models were used to examine the association of eating behaviours with ADHD symptoms. Results Regarding children's food approach eating behaviours, we observed a positive association between food responsiveness and total ADHD index, as well as impulsivity, inattention and hyperactivity subscale, separately. Similarly, there was a significant positive association between emotional overeating and ADHD symptoms. With regard to children's food avoidant behaviours, food fussiness was found to be significantly associated with the impulsivity subscale. A dose-response association between the food approach behaviours and ADHD symptoms was also observed. Children on the medium and highest tertile of the food responsiveness subscale had increased scores on the ADHD total scale, as compared to those on the lowest tertile. As regards emotional overeating, children in the highest tertile of the scale had higher scores on ADHD total and hyperactivity. Conclusions Our findings provide evidence that food approach eating behaviours such as food responsiveness and emotional overeating are associated with the increased ADHD symptoms in preschool children. Future studies to better understand this overlap will enhance potential interventions. © 2015 Association for Child and Adolescent Mental Health.

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