Medicine and Health Sciences Commons^™

Relationships Among Common Illness Symptoms And The Protective Effect Of Breastfeeding In Early Childhood In Mal-Ed: An Eight-Country Cohort Study, Stephanie A. Richard, Benjamin J. J. Mccormick, Jessica C. Seidman, Zeba Rasmussen, Margaret N. Kosek, Elizabeth T. Rogawski, William Petri, Anurahda Bose, Zulfiqar Ahmed Bhutta, Ali Turab

Department of Paediatrics and Child Health

Children in low-income countries experience multiple illness symptoms in early childhood. Breastfeeding is protective against diarrhea and respiratory infections, and these illnesses are thought to be risk factors of one another, but these relationships have not been explored simultaneously. In the eight-site MAL-ED study, 1,731 infants were enrolled near birth and followed for 2 years. We collected symptoms and diet information through twice-weekly household visits. Poisson regression was used to determine if recent illness history was associated with incidence of diarrhea or acute lower respiratory infections (ALRI), accounting for exclusive breastfeeding. Recent diarrhea was associated with higher risk of incident …

Risk Factors For Major Early Adverse Events Related To Cardiac Catheterization In Children And Young Adults With Pulmonary Hypertension: An Analysis Of Data From The Impact (Improving Adult And Congenital Treatment) Registry., Michael L O'Byrne, Kevin F Kennedy, Joshua P Kanter, John T Berger, Andrew C Glatz

Pediatrics Faculty Publications

BACKGROUND: Cardiac catheterization is the gold standard for assessment and follow-up of patients with pulmonary hypertension (PH). To date, there are limited data about the factors that influence the risk of catastrophic adverse events after catheterization in this population.

METHODS AND RESULTS: A retrospective multicenter cohort study was performed to measure risk of catastrophic adverse outcomes after catheterization in children and young adults with PH and identify risk factors for these outcomes. All catheterizations in children and young adults, aged 0 to 21 years, with PH at hospitals submitting data to the IMPACT (Improving Adult and Congenital Treatment) registry between …

Impaired Type I Interferon Regulation In The Blood Transcriptome Of Recurrent Asthma Exacerbations., Jose L Gomez, Maria P Diaz, Gustavo Nino, Clemente J Britto

Pediatrics Faculty Publications

BACKGROUND: Asthma exacerbations are an important cause of morbidity in asthma. Respiratory infections are often involved in asthma exacerbations in both children and adults. Some individuals with asthma have increased susceptibility to viral infections and as a result increased rates of asthma exacerbations. We sought to identify a transcriptomic signature in the blood associated with asthma exacerbations triggered by respiratory infections (AETRI) and determine its association with increased risk for asthma exacerbations.

METHODS: We conducted a two-step study using publicly available, previously generated transcriptomic signatures in peripheral blood mononuclear cells (PBMCs) from asthmatics to identify novel markers of increased risk …

The Epidemic Of Neonatal Abstinence Syndrome, Historical References Of Its Origins, Assessment, And Management, Enrique Gomez-Pomar, Loretta P. Finnegan

Pediatrics Faculty Publications

Neonatal abstinence syndrome (NAS) refers to a constellation of signs that are present in some newborn infants resulting from the abrupt cessation of passive transfer of maternal opioids used during pregnancy. The classic NAS refers to infants born to mothers who used opioids during pregnancy, but the term has broadened to include infants whose mothers have used or abused other psychoactive substances during pregnancy that contribute to the expression of the syndrome. Pregnant women who use opioids do so illicitly, and/or as medically prescribed for pain relief, and/or as medication assisted treatment for opioid dependence. The first case of NAS …

Adolescence And The Next Generation, George C. Patton, Craig A. Olsson, Vegard Skirbekk, Richard Saffery, Mary E. Wlodek, Peter S. Azzopardi, Marcin Stonawski, Bruce Rasmussen, Elizabeth Spry, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Adolescent growth and social development shape the early development of offspring from preconception through to the post-partum period through distinct processes in males and females. At a time of great change in the forces shaping adolescence, including the timing of parenthood, investments in today's adolescents, the largest cohort in human history, will yield great dividends for future generations.

Nusinersen Versus Sham Control In Later-Onset Spinal Muscular Atrophy., Eugenio Mercuri, Basil T Darras, Claudia A Chiriboga, John W Day, Craig Campbell, Anne M Connolly, Susan T Iannaccone, Janbernd Kirschner, Nancy L Kuntz, Kayoko Saito, Perry B Shieh, Már Tulinius, Elena S Mazzone, Jacqueline Montes, Kathie M Bishop, Qingqing Yang, Richard Foster, Sarah Gheuens, C Frank Bennett, Wildon Farwell, Eugene Schneider, Darryl C De Vivo, Richard S Finkel

Paediatrics Publications

BACKGROUND: Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA).

METHODS: We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was …

Nusinersen Versus Sham Control In Later-Onset Spinal Muscular Atrophy, Eugenio Mercuri, Basil T Darras, Claudia A Chiriboga, John W Day, Craig Campbell, Anne M Connolly, Susan T Iannaccone, Janbernd Kirschner, Nancy L Kuntz, Kayoko Saito, Perry B Shieh, Már Tulinius, Elena S Mazzone, Jacqueline Montes, Kathie M Bishop, Qingqing Yang, Richard Foster, Sarah Gheuens, C Frank Bennett, Wildon Farwell, Eugene Schneider, Darryl C De Vivo, Richard S Finkel

Paediatrics Publications

Background

Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA).

Methods

We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was …

Peripheral Blood Epi-Signature Of Claes-Jensen Syndrome Enables Sensitive And Specific Identification Of Patients And Healthy Carriers With Pathogenic Mutations In Kdm5c, Laila C Schenkel, Erfan Aref-Eshghi, Cindy Skinner, Peter Ainsworth, Hanxin Lin, Guillaume Paré, David I Rodenhiser, Charles Schwartz, Bekim Sadikovic

Paediatrics Publications

Background

Claes-Jensen syndrome is an X-linked inherited intellectual disability caused by mutations in the

Results

Genome-wide DNA methylation analysis of 7 male patients affected with Claes-Jensen syndrome and 56 age- and sex-matched controls identified a specific DNA methylation defect (epi-signature) in the peripheral blood of these patients, including 1769 individual CpGs and 9 genomic regions. Six healthy female carriers showed less pronounced but distinctive changes in the same regions enabling their differentiation from both patients and controls. Highly specific computational model using the most significant methylation changes demonstrated 100% accuracy in differentiating patients, carriers, and controls in the training cohort, …

Promising Biomarkers Of Environmental Enteric Dysfunction: A Prospective Cohort Study In Pakistani Children., Najeeha Talat Iqbal, Kamran Sadiq, Sana Syed, Tauseefullah Akhund, Fayyaz Umrani, Sheraz Ahmed, Mohammad Yawar Yakoob, Najeeb Rehman, Shahida Qureshi, Syed Asad Ali

Department of Paediatrics and Child Health

Environmental Enteric Dysfunction (EED), a syndrome characterized by chronic gut inflammation, contributes towards stunting and poor response to enteric vaccines in children in developing countries. In this study, we evaluated major putative biomarkers of EED using growth faltering as its clinical proxy. Newborns (n = 380) were enrolled and followed till 18 months with monthly anthropometry. Biomarkersassociated with gut and systemic inflammation were assessed at 6 and 9 months. Linear mixed effects model was used to determine the associations of these biomarkers with growth faltering between birth and 18 months. Fecal myeloperoxidase (neutrophil activation marker) at 6 months [β = …

Machine Learning From Fetal Flow Waveforms To Predict Adverse Perinatal Outcomes: A Study Protocol, Zahra Hoodbhoy, Babar Hasan, Fyezah Jehan, Bart Bijnens, Devyani Chowdhury

Department of Paediatrics and Child Health

Background: In Pakistan, stillbirth rates and early neonatal mortality rates are amongst the highest in the world. The aim of this study is to provide proof of concept for using a computational model of fetal haemodynamics, combined with machine learning. This model will be based on Doppler patterns of the fetal cardiovascular, cerebral and placental flows with the goal to identify those fetuses at increased risk of adverse perinatal outcomes such as stillbirth, perinatal mortality and other neonatal morbidities.
Methods: This will be prospective one group cohort study which will be conducted in Ibrahim Hyderi, a peri-urban settlement in south …

Eculizumab Dosing In Infants, M Kobrzynski, B Wile, S S Huang, G Filler

Paediatrics Publications

Eculizumab is the therapy of choice for patients with atypical hemolytic uremic syndrome (aHUS). Dosing recommendations stem from two trials: one retrospective trial (19 children and 5 infants) and one prospective trial (22 patients and 5 infants). This case report highlights the need for more precise dosing recommendations in children, particularly in infants, and for smaller vials of the medication to facilitate more precise dosing. Such changes would ensure that adverse events are minimized and that the children with aHUS who are treated with eculizumab experience an optimal clinical response.

Rapid Intravenous Rehydration Of Children With Acute Gastroenteritis And Dehydration: A Systematic Review And Meta-Analysis, M. A. Iro, T. Sell, N. Brown, K. Maitland

Department of Paediatrics and Child Health

Background: The World Health Organization (WHO) recommends rapid intravenous rehydration, using fluid volumes of 70-100mls/kg over 3–6 h, with some of the initial volume given rapidly as initial fluid boluses to treat hypovolaemic shock for children with acute gastroenteritis (AGE) and severe dehydration. The evidence supporting the safety and efficacy of rapid versus slower rehydration remains uncertain.
Methods: We conducted a systematic review of randomised controlled trials (RCTs) on 11th of May 2017 comparing different rates of intravenous fluid therapy in children with AGE and moderate or severe dehydration, using standard search terms. Two authors independently assessed trial quality and …

Predicting Cyp3a-Mediated Midazolam Metabolism In Critically Ill Neonates, Infants, Children And Adults With Inflammation And Organ Failure., Janneke M Brussee, Nienke J Vet, Elke H J Krekels, Abraham J Valkenburg, Evelyne Jacqz-Aigrain, Joop M A Van Gerven, Eleonora L Swart, Johannes N Van Den Anker, Dick Tibboel, Matthijs De Hoog, Saskia N De Wildt, Catherijne A J Knibbe

Pediatrics Faculty Publications

No abstract provided.

Cardiovascular Effects Of Metabolic Syndrome After Transplantation: Convergence Of Obesity And Transplant-Related Factors., Kristen Sgambat, Sarah Clauss, Asha Moudgil

Pediatrics Faculty Publications

Children are at increased risk of developing metabolic syndrome (MS) after kidney transplantation, which contributes to long-term cardiovascular (CV) morbidities and decline in allograft function. While MS in the general population occurs due to excess caloric intake and physical inactivity, additional chronic kidney disease and transplant-related factors contribute to the development of MS in transplant recipients. Despite its significant health consequences, the interplay of the individual components in CV morbidity in pediatric transplant recipients is not well understood. Additionally, the optimal methods to detect early CV dysfunction are not well defined in this unique population. The quest to establish clear …

Pura Syndrome: Clinical Delineation And Genotype-Phenotype Study In 32 Individuals With Review Of Published Literature, Margot R F Reijnders, Robert Janowski, Mohsan Alvi, Jay E Self, Ton J Van Essen, Maaike Vreeburg, Rob P W Rouhl, Servi J C Stevens, Alexander P A Stegmann, Jolanda Schieving, Rolph Pfundt, Katinke Van Dijk, Eric Smeets, Connie T R M Stumpel, Levinus A Bok, Jan Maarten Cobben, Marc Engelen, Sahar Mansour, Margo Whiteford, Kate E Chandler, Sofia Douzgou, Nicola S Cooper, Ene-Choo Tan, Roger Foo, Angeline H M Lai, Julia Rankin, Andrew Green, Tuula Lönnqvist, Pirjo Isohanni, Shelley Williams, Ilene Ruhoy, Karen S Carvalho, James J Dowling, Dorit L Lev, Katalin Sterbova, Petra Lassuthova, Jana Neupauerová, Jeff L Waugh, Sotirios Keros, Jill Clayton-Smith, Sarah F Smithson, Han G Brunner, Ceciel Van Hoeckel, Mel Anderson, Virginia E Clowes, Victoria Mok Siu, The Ddd Study, Paulo Selber, Richard J Leventer, Christoffer Nellaker, Dierk Niessing, David Hunt, Diana Baralle

Paediatrics Publications

BACKGROUND: De novo mutations in

OBJECTIVES: To delineate the clinical spectrum of PURA syndrome and study genotype-phenotype correlations.

METHODS: Diagnostic or research-based exome or Sanger sequencing was performed in individuals with ID. We systematically collected clinical and mutation data on newly ascertained PURA syndrome individuals, evaluated data of previously reported individuals and performed a computational analysis of photographs. We classified mutations based on predicted effect using 3D in silico models of crystal structures of

RESULTS: We report mutations in

CONCLUSION: We delineate the clinical spectrum of PURA syndrome with the identification of 32 additional individuals. The identification of one individual …

De Novo And Rare Inherited Copy-Number Variations In The Hemiplegic Form Of Cerebral Palsy, Mehdi Zarrei, Darcy L Fehlings, Karizma Mawjee, Lauren Switzer, Bhooma Thiruvahindrapuram, Susan Walker, Daniele Merico, Guillermo Casallo, Mohammed Uddin, Jeffrey R Macdonald, Matthew J Gazzellone, Edward J Higginbotham, Craig Campbell, Gabrielle Deveber, Pam Frid, Jan Willem Gorter, Carolyn Hunt, Anne Kawamura, Marie Kim, Anna Mccormick, Ronit Mesterman, Dawa Samdup, Christian R Marshall, Dimitri J Stavropoulos, Richard F Wintle, Stephen W Scherer

Paediatrics Publications

PurposeHemiplegia is a subtype of cerebral palsy (CP) in which one side of the body is affected. Our earlier study of unselected children with CP demonstrated de novo and clinically relevant rare inherited genomic copy-number variations (CNVs) in 9.6% of participants. Here, we examined the prevalence and types of CNVs specifically in hemiplegic CP.MethodsWe genotyped 97 unrelated probands with hemiplegic CP and their parents. We compared their CNVs to those of 10,851 population controls, in order to identify rare CNVs (

The Canadian Neuromuscular Disease Registry: Connecting Patients To National And International Research Opportunities, Yi Wei, Anna Mccormick, Alex Mackenzie, Erin O'Ferrall, Shannon Venance, Jean K. Mah, Kathryn Selby, Hugh J. Mcmillan, Garth Smith, Maryam Oskoui, Gillian Hogan, Laura Mcadam, Gracia Mabaya, Victoria Hodgkinson, Josh Lounsberry, Lawrence Korngut, Craig Campbell

Paediatrics Publications

Introduction

Patient registries serve an important role in rare disease research, particularly for the recruitment and planning of clinical trials. The Canadian Neuromuscular Disease Registry was established with the primary objective of improving the future for neuromuscular (NM) patients through the enablement and support of research into potential treatments.

Methods

In this report, we discuss design and utilization of the Canadian Neuromuscular Disease Registry with special reference to the paediatric cohort currently enrolled in the registry.

Results

As of July 25, 2017, there are 658 paediatric participants enrolled in the registry, 249 are dystrophinopathies (229 are Duchenne muscular dystrophy), 57 …

Cua Guideline On The Care Of The Normal Foreskin And Neonatal Circumcision In Canadian Infants, Sumit Dave, Kourosh Afshar, Luis H. Braga, Peter Anderson

Paediatrics Publications

No abstract provided.

Association Between Environmental Tobacco Smoke And Dental Caries Amongst 5-14 Years Old Children In Karachi, Pakistan., Anna Ali Nayani, Romaina Iqbal, Syed Iqbal Azam, Farhan Raza Khan, Aysha Habib Khan, Naveed Janjua, Azmina Hussain

Community Health Sciences

Objective:To determine the association between environmental tobacco smoke and dental caries.
Methods:This cross-sectional study was conducted in peri-urban and urban areas of Karachi, from February to August 2014, and comprised children aged 5-14 years. A pre-coded questionnaire for environmental tobacco smoke and food frequency questionnaire for dietary habits were used. Dental examination of children was done to detect caries. Cox-proportional hazard algorithm was used to measure the association of environmental tobacco smoke with dental caries at multivariable level. STATA version 12.0 was used for statistical analysis.
Result:Of the 500 children, 250(50%) each were from peri-urban and urban …

The World Database For Pediatric And Congenital Heart Surgery: Use Of An International Congenital Database In South Korea., James D. St Louis, Cheul Lee, Hiromi Kurosawa, Richard A. Jonas, Sakamoto Kisaburo, Christo I. Tchervenkov, Jeffery P. Jacobs, James K. Kirklin

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Quality Of Care Of Treatment For Uncomplicated Severe Acute Malnutrition Provided By Lady Health Workers In Pakistan, Eleanor Rogers, Muhammad Ali, Shahid Fazal, Deepak Kumar, Saul Guerrero, Imtiaz Hussain, Sajid Bashir Soofi, Jose Luis Alvarez Morán

Department of Paediatrics and Child Health

Objective: To assess the quality of care provided by lady health workers (LHW) managing cases of uncomplicated severe acute malnutrition (SAM) in the community.
Design: Cross-sectional quality-of-care study.
Setting: The feasibility of the implementation of screening and treatment for uncomplicated SAM in the community by LHW was tested in Sindh Province, Pakistan. An observational, clinical prospective multicentre cohort study compared the LHW-delivered care with the existing outpatient health facility model.
Subjects: LHW implementing treatment for uncomplicated SAM in the community.
Results: Oedema was diagnosed conducted correctly for 87·5 % of children; weight and mid upper-arm circumference were measured correctly for …

High Smad7 And P-Smad2,3 Expression Is Associated With Environmental Enteropathy In Children, Sana Syed, Vincenzo Dinallo, Najeeha Talat Iqbal, Laura Di Iorio, Davide Di Fusco, Shan Guleria, Beatrice C. Amadi, Kamran Sadiq, Christopher Moskaluk, Syed Asad Ali

Department of Paediatrics and Child Health

Enteropathies such as Crohn's disease are associated with enteric inflammation characterized by impaired TGF-β signaling, decreased expression of phosphorylated (p)-SMAD2,3 and increased expression of SMAD7 (an inhibitor of SMAD3 phosphorylation). Environmental enteropathy (EE) is an acquired inflammatory disease of the small intestine (SI), which is associated with linear growth disruption, cognitive deficits, and reduced oral vaccine responsiveness in childrenp-SMAD2,3 levels (using Western blotting) in EE duodenal biopsies (N = 19 children, 7 from Pakistan, 12 from Zambia) and comparing these with healthy controls (Ctl) and celiac disease (CD) patients from Italy. Densitometric analysis of immunoblots showed that EE SI biopsies …

Consensus Guidelines For Newborn Screening, Diagnosis And Treatment Of Infantile Krabbe Disease., Jennifer M. Kwon, Dietrich Matern, Joanne Kurtzberg, Lawrence Wrabetz, Michael H. Gelb, David A. Wenger, Can Ficicioglu, Amy T. Waldman, Barbara K. Burton, Patrick V. Hopkins, Joseph J. Orsini

Department of Neurology Faculty Papers

BACKGROUND: Krabbe disease is a rare neurodegenerative genetic disorder caused by deficiency of galactocerebrosidase. Patients with the infantile form of Krabbe disease can be treated at a presymptomatic stage with human stem cell transplantation which improves survival and clinical outcomes. However, without a family history, most cases of infantile Krabbe disease present after onset of symptoms and are ineligible for transplantation. In 2006, New York began screening newborns for Krabbe disease to identify presymptomatic cases. To ensure that those identified with infantile disease received timely treatment, New York public health and medical systems took steps to accurately diagnose and rapidly …

The Prevalence Of Human Papillomavirus In Pediatric Tonsils: A Systematic Review Of The Literature, Monika Wojtera, Josee Paradis, Murad Husein, Anthony C Nichols, John W Barrett, Marina I Salvadori, Julie E Strychowsky

Paediatrics Publications

Background

HPV-related head and neck cancer rates have been increasing in recent years, with the tonsils being the most commonly affected site. However, the current rate of HPV infection in the pediatric population remains poorly defined. The objective of this study was to systematically review and evaluate the prevalence and distribution of HPV in the tonsils of pediatric patients undergoing routine tonsillectomy.

Methods and Results

The literature was searched using PubMed, EMBASE, Scopus, CINAHL, Cochrane Library, and ProQuest Dissertations & Theses Global databases (inception to December 2017) by two independent review authors. Inclusion criteria included articles which evaluated the prevalence …

Teenage Exercise Is Associated With Earlier Symptom Onset In Dysferlinopathy: A Retrospective Cohort Study., Ursula R Moore, Marni Jacobs, Roberto Fernandez-Torron, Jiji Jang, Meredith K James, Diana X Bharucha-Goebel, +Several Additional Authors

Pediatrics Faculty Publications

No abstract provided.

Birth Weight And Body Mass Index Z-Score In Childhood Brain Tumors: A Cross-Sectional Study, Kuan-Wen Wang, Russell J De Souza, Adam Fleming, Donna L Johnston, Shayna M Zelcer, Shahrad Rod Rassekh, Sarah Burrow, Lehana Thabane, M Constantine Samaan

Paediatrics Publications

Children with brain tumors (CBT) are at higher risk of cardiovascular disease and type 2 diabetes compared to the general population, in which birth weight is a risk factor for these diseases. However, this is not known in CBT. The primary aim of this study was to explore the association between birth weight and body mass measures in CBT, compared to non-cancer controls. This is a secondary data analysis using cross-sectional data from the CanDECIDE study (n = 78 CBT and n = 133 non-cancer controls). Age, sex, and birth weight (grams) were self-reported, and confirmed through examination of the …

Direct Detection Of Shigella In Stool Specimens By Use Of A Metagenomic Approach, Jie Liu, Mathieu Almeida, Furqan Kabir, Sadia Shakoor, Shahida Qureshi, Anita K. M. Zaidi, Shan Li, Boubou Tamboura, Samba O. Sow, Inacio Mandomando

Department of Paediatrics and Child Health

The underestimation of Shigella species as a cause of childhood diarrhea disease has become increasingly apparent with quantitative PCR (qPCR)-based diagnostic methods versus culture. We sought to confirm qPCR-based detection of Shigella via a metagenomics approach. Three groups of samples were selected from diarrheal cases from the Global Enteric Multicenter Study: nine Shigella culture-positive and qPCR-positive (culture⁺ qPCR⁺) samples, nine culture-negative but qPCR-positive (culture^- qPCR⁺) samples, and nine culture-negative and qPCR-negative (culture^- qPCR^-) samples. Fecal DNA was sequenced using paired-end Illumina HiSeq, whereby 3.26 × 10⁸ ± 5.6 × 10 …

Partnerships For Child Health: Capitalising On Links Between The Sustainable Development Goals, Yulia Blomstedt, Zulfiqar Ahmed Bhutta, Johan Dahlstrand, Peter Friberg, Lawrence O. Gostin, Måns Nilsson, Nelson K. Sewankambo, Göran Tomson, Tobias Alfvén

Department of Paediatrics and Child Health

No abstract provided.

Emotion Regulation And Positive Affect In The Context Of Salivary Alpha-Amylase Response To Pain In Children With Cancer, Brooke N. Jenkins, Douglas A. Granger, Ryan J. Roemer, Ariana Martinez, Tara K. Torres, Michelle A. Fortier

Psychology Faculty Articles and Research

Background

Children with cancer routinely undergo painful medical procedures invoking strong physiological stress responses. Resilience to this pain may be conferred through resources such as emotion regulation strategies and positive affect.

Procedure

This study measured dispositional positive affect in children with cancer (N = 73) and randomly assigned participants to one of three emotion regulation strategy conditions (distraction, reappraisal, or reassurance). Children applied their assigned strategy during an experimental pain procedure (the cold pressor task [CPT]) and provided saliva samples before, immediately after, and 15 min after the CPT. Saliva samples were later assayed for salivary alpha amylase (sAA)—a surrogate …

Fasoracetam In Adolescents With Adhd And Glutamatergic Gene Network Variants Disrupting Mglur Neurotransmitter Signaling., Josephine Elia, Grace Ungal, Charlly Kao, Alexander Ambrosini, Nilsa De Jesus-Rosario, Lene Larsen, Rosetta Chiavacci, Tiancheng Wang, Christine Kurian, Kanani Titchen, Brian Sykes, Sharon Hwang, Bhumi Kumar, Jacqueline Potts, Joshua Davis, Jeffrey Malatack, Emma Slattery, Ganesh Moorthy, Athena Zuppa, Andrew Weller, Enda Byrne, Yun R. Li, Walter K. Kraft, Hakon Hakonarson

Department of Pediatrics Faculty Papers

The glutamatergic neurotransmitter system may play an important role in attention-deficit hyperactivity disorder (ADHD). This 5-week, open-label, single-blind, placebo-controlled study reports the safety, pharmacokinetics and responsiveness of the metabotropic glutamate receptor (mGluR) activator fasoracetam (NFC-1), in 30 adolescents, age 12-17 years with ADHD, harboring mutations in mGluR network genes. Mutation status was double-blinded. A single-dose pharmacokinetic profiling from 50-800 mg was followed by a single-blind placebo at week 1 and subsequent symptom-driven dose advancement up to 400 mg BID for 4 weeks. NFC-1 treatment resulted in significant improvement. Mean Clinical Global Impressions-Improvement (CGI-I) and Severity (CGI-S) scores were, respectively, 3.79 …