Madison Nation, MD1, Megyn Beyer, DO2, Margaret Ellis, DO, MSPH3, Nicholas M. Potisek, MD4*

1Pediatric Residency

4*Department of Pediatrics, Wake Forest Baptist Medical Center Winston-Salem, NC

DOI: 10.29245/2578-2940/2018/3.1125 View / Download Pdf

Kyle N. Kaneko1*, Miki Wong1,3, Michael J. Corley1,2, Ryan W.Y. Lee1,2,3

1Shriners Hospitals for Children®—Honolulu, Department of Research, Honolulu, HI, USA

2John A. Burns School of Medicine, University of Hawaii School of Medicine, Honolulu, HI, USA

3Milestones Center for Pediatric Neurodevelopment, Honolulu, HI, USA

Down syndrome is a common genetic intellectual disability seen in humans. Currently, therapeutic interventions are inadequate in improving the quality of life for individuals with Down syndrome that have cognitive and behavioral impairments. Nutrition therapies for Down syndrome have focused on addressing obesity but not intellectual disability and cognitive decline. The ketogenic diet is a very low carbohydrate, moderate protein, and high fat diet used to treat childhood and adult epilepsy, however, there is growing interest in its potential to improve cognition and behavior. There is evidence suggesting that the ketogenic diet may be effective in treating comorbidities associated with Down syndrome such as early onset of Alzheimer’s disease and dementia. This review aims to discuss the ketogenic diet and the potential benefits that the diet may provide in neurodevelopmental and neurodegenerative diseases. We propose that the ketogenic diet may be a therapeutic option for cognitive decline in Down syndrome and warrants investigation.

DOI: 10.29245/2578-2940/2018/2.1121 View / Download Pdf

Danielle E. Arnold1 and Jennifer Heimall1*

1Division of Allergy & Immunology, Children’s Hospital of Philadelphia, United States

Severe combined immunodeficiency (SCID) is a group of the most severe of primary immunodeficiencies and is typically fatal in the first year of life without hematopoietic cell transplantation (HCT). Improved transplantation techniques and supportive care measures have resulted in improved survival following HCT. Furthermore, patients are being diagnosed earlier since the widespread implementation of SCID newborn screening in the United States and moving on to transplantation before 3.5 months of age. As such, most SCID patients are now expected to live well into adulthood following successful HCT. Many centers are using conditioning with alkylating agents, including busulfan and melphalan, pre-transplantation to achieve full T and B cell immune reconstitution; however, significant concerns remain regarding the attendant risks of using chemotherapeutic agents in early infancy. Several long-term follow-up studies have demonstrated high rates of non-immunologic late effects depending on the conditioning regimen employed and SCID genotype. The full risk of conditioning in this patient population remains incompletely characterized, and further research on post-HCT outcomes is needed. It is imperative that all providers caring for SCID survivors both in childhood and adulthood be aware of the risk of late effects. Guidelines for long-term follow-up were recently published, and the recommendations are briefly summarized here.

DOI: 10.29245/2578-2940/2018/2.1119 View / Download Pdf

Pinting Chen MS1*, Anthony Khong MS2, Gary Ledley MD3, Vicki Mahan MD4

1,2Drexel University College of Medicine

3Hahnemann University Hospital, Drexel University College of Medicine

4St. Christopher’s Hospital for Children and Drexel University College of Medicine

Anomalous left coronary artery to pulmonary artery (ALCAPA) is a congenital heart defect in which the left coronary artery (LCA) originates from the pulmonary trunk instead of from the aorta. This disease occurs in 1 in 300,000 births and, if untreated, 90% of these neonates die within the first year. Individuals who live beyond this tend to be asymptomatic and either experience sudden death at an average age of 35 or present with cardiac abnormalities, including myocardial ischemia, arrhythmia, or mitral regurgitation. There are various surgical interventions used to treat ALCAPA, and the establishment of a two coronary artery system is the preferred treatment of choice. We report a case of a five-year-old presenting with supraventricular tachycardia since birth who, upon diagnosis of ALCAPA by angiography, was treated by surgical ligation. Thirty years later, he returned to a cardiologist with symptoms of congestive heart failure. The initial presentation of this patient is unusual because the manifestation of ALCAPA usually occurs within the first few months of birth and because ligation is no longer the preferred method of intervention. We discuss this unique case, suggest possible associations between ALCAPA and arrhythmias, review the various surgical methods used to treat ALCAPA, and evaluate the long-term outcome of ligation.

DOI: 10.29245/2578-2940/2018/2.1118 View / Download Pdf

Xian Wu1,2, Raymond Swetenburg2, Forrest Goodfellow1,2, Steven L. Stice1,2 *

1Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602, United States

2Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, United States

Developmental neurotoxicity is any toxic effect on the developing nervous system interfering with normal nervous system structure or function before or after birth and can be associated with neurodevelopmental disorders such as autism, attention deficit disorder, mental retardation and cerebral palsy. Currently, developmental neurotoxicity testing relies heavily on neurobehavioral and neuropathological studies in rodent models; however, an existing backlog of chemicals lack appropriate neurotoxicity information due to the low throughput nature and subsequent high cost of in vivo animal testing. Alternative models have been developed to replace rodent models (including non-mammalian models, brain slice culture, and primary and transformed cell models) though limitations to increasing throughput and reproducibility remain. In this review, we focus on the use of human pluripotent stem cells as a cell source for in vitro chemical screening. Pluripotent stem cell-based assays are derived from a virtually unlimited and uniform cell source making studies highly reproducible and relatively low cost compared to rodent models. Moreover, directed differentiation to distinct neural lineages, including neurons and astrocytes, provides isogenic, precise and tunable cell mixtures to mimic in vivo brain composition for high throughput screening. Thus, human pluripotent stem cell-derived neural models are poised to vastly increase throughput and decrease costs for developmental neurotoxicity screening.

DOI: 10.29245/2578-2940/2018/1.1114 View / Download Pdf

Roberto Crepaz

Pediatric Cardiology and Congenital Heart Disease in the Adult Dept. of Cardiology Regional Hospital S. Maurizio Bolzano, Italy

DOI: 10.29245/2578-2940/2018/1.1112 View / Download Pdf

Issaka Yougbaré1-3, Darko Zdravic1-4, Heyu Ni1-6*

1*Toronto Platelet Immunobiology Group

2Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON Canada

3Canadian Blood Services Centre for Innovation, Toronto, ON K1G 4J5, Canada

4Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada

5Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada

6Department of Medicine, University of Toronto, Toronto, ON M5S 1A8

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening disease. Maternal alloimmune responses against fetal platelet antigens in FNAIT may lead to clinical complications including bleeding disorders, intrauterine growth restriction (IUGR) and in severe cases fetal death (miscarriage). It has been long suspected that thrombocytopenia may be the reason for bleeding disorders in FNAIT, recent studies from us and other groups, however, suggested that the anti-angiogenic effects of anti-platelet antibodies may play a key role in bleeding, particularly in intracranial hemorrhages. Our earlier studies using murine models also suggested that some anti-platelet antibodies can activate platelets and initiate thrombotic events in the placenta, which may contribute to miscarriage. Most recently, we found that maternal anti-β3 integrin antibodies can target fetal allogenic trophoblasts, form immune complexes, and generate binding sites for natural killer (NK) cell Fcγ receptors. Uterine NK cell activation through NKp46 and perforin release caused trophoblast apoptosis, impaired spiral artery remodeling, and ultimately lead to IUGR and/or fetal death. We found that NK cell-mediated placental pathologies are preventable by anti-NK antibody treatments, which may have translational importance. This mini-review mainly discussed the latest discoveries regarding activated uterine NK cells-mediated miscarriage. Future research on placental inflammation and remodeling should open new avenues for interventions in FNAIT-mediated pregnancy failures.

DOI: 10.29245/2578-2940/2018/1.1113 View / Download Pdf

1*Megan E. Gray, 2Sheela V Shenoi, 3Rebecca Dillingham

1*Division of Infectious Diseases and International Health. University of Virginia, Charlottesville, VA

2Assistant Professor of Medicine. Yale University, New Haven, CT

3Director of the Center for Global Health, Associate Professor of Medicine. Division of Infectious Diseases and International Health. University of Virginia, Charlottesville, VA

DOI: 10.29245/2578-2940/2018/1.1108 View / Download Pdf

Ana Rita Soares1*, Gonçalo Inocêncio2, Céu Rodrigues2, Elisa Proença3, Gabriela Soares1, Ana Maria Fortuna1, Céu Mota3

1Medical Genetics Department, Centro de Genética Médica Doutor Jacinto Magalhães, Porto, Portugal

2Obstetrics/Gynecology Department, Centro Materno-Infantil do Norte, Porto, Portugal

3Neonatology Department, Centro Materno-Infantil do Norte, Porto, Portugal

Cornelia de Lange Syndrome is a rare disease characterized by prenatal and postnatal growth restriction, mild to severe intellectual disability, characteristic facial dysmorphisms, and other anomalies. The diagnosis is based on clinical criteria or on detection of a pathological variant in one of the five disease causing genes - NIPBL, RAD21, SMC3, HDAC8 or SMC1A. The prognosis may depend on the precocity of malformations’ treatment, early institution of therapies and careful follow-up of possible complications. We present a case of Cornelia de Lange Syndrome whose clinical diagnosis was made during perinatal period due to a suspicious prenatal history followed by characteristic dysmorphisms and anomalies. The molecular confirmation was only possible after two years, revealing a pathogenic variant in SMC1A gene, located at X chromosome, which occurred as de novo event. The clinical suspicion during perinatal period made it possible to start an earlier multidisciplinary follow-up and to offer a better management for the child and a proper genetic counseling for the parents.

DOI: 10.29245/2578-2940/2018/1.1115 View / Download Pdf

Victoria Bell1, Jorge Ferrao2 and Tito Fernandes3*

1Faculty of Pharmacy, Coimbra University, Pólo das Ciências da Saúde, 3000-548 Coimbra, Portugal

2The Vice-Chancellor’s Office, Universidade Pedagógica, Rua João Carlos Raposo Beirão 135, Maputo, Moçambique

3Associação para o Desenvolvimento das Ciências Veterinárias (ACIVET), Faculty of Veterinary Medicine, Lisbon University, 1300-477 Lisboa, Portugal

The authors try to synthesise their communication elsewhere on general fermented foods giving an emphasis to its use in children. Most nutritional guidelines in the world, including in Asian countries where fermented foods are widely used, do not mention fermented foods and beverages besides yoghurt as a dairy product. Children get their gut microbioma from the stage of birth and milking and the intestinal flora remains most the same throughout their life. Fermented foods and mushroom biomass may modulate the probiotic profile of gut flora.

DOI: 10.29245/2578-2940/2018/1.1111 View / Download Pdf

Tatsuo Tomita1*

1Departments of Integrative Bioscience and Pathology, Oregon Health and Science University 611 SW Campus Drive, Portland, Oregon 97239-3097, USA

Type 1 diabetes (T1D) results from autoimmune destruction of pancreatic β-cells after asymptomatic period over years. Insulitis activates antigen presenting cells, which trigger activating DC4+ helper-T cells, releasing cytokines. Cytokines activate CD8+ cytotoxic –T cells and lead to β-cell destruction. Apoptosis pathway consists of extrinsic and intrinsic pathway. Extrinsic pathway includes Fas pathway to CD4+-CD8+ interaction whereas intrinsic pathway includes mitochondria-driven pathway at balance between anti-apoptotic Bcl-2 and Bcl-xL and pro-apoptotic proteins. Activated cleaved caspase-3 (ACC) is the converging point between extrinsic and intrinsic pathway. ACC may be used as a marker for β-cell apoptosis: inT1DM islets weakly insulin-positive β-cells are present with increased ACC positive β-cells whereas β-cell absent islets, which exclusively consist of α-cells and PP-cells with decreased ACC-cells, represent the end-stage of regenerating β-cells. Weakly insulin-positive β-cells could be rejuvenated to supply endogenous insulin. Apoptosis takes place only when pro-apoptotic protein exceeds anti-apoptotic proteins. Since concordance rate of T1D in the identical twins is about 50%, environmental factors are involved in development of T1D, opening a door to means to prevent autoimmune β-cell destruction for therapeutic application by transfecting β-cells with Casp3-/- genes or pan-caspase inhibitor therapy. Prudent glucose control prevents ongoing hyperglycemia-induced β-cell apoptosis.

DOI: 10.29245/2578-2940/2018/1.1107 View / Download Pdf

Chaowapong Jarasvaraparn1, David A. Gremse2*

1Department of Pediatrics, University of South Alabama, Mobile, Alabama 36604, USA

2Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of South Alabama, Mobile, Alabama 36604, USA

Autoimmune hepatitis (AIH) is a chronic liver disease that may be associated with extrahepatic autoimmune disorders. Evans syndrome (ES) is an autoimmune disorder that is characterized by a combination of immune thrombocytopenia and autoimmune hemolytic anemia. Association of autoimmune hepatitis with Evans syndrome is rare, especially in children. We reported a 3-year-old-female with pre-existing Evans syndrome who developed AIH type 11This commentary reviews this case along with other reported cases of AIH and ES.

DOI: 10.29245/2578-2940/2018/1.1109 View / Download Pdf

Ulrich Desselberger

Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge, U.K.

Compared to classical ‘forward’ genetics in which the changed phenotype of an organism is correlated with mutations in the genome, the availability of complete nucleotide sequences of many microbes and animals now allows the rational engineering of mutations in individual genes and identification of the correlated change in phenotype of the reconstituted organism (‘reverse genetics’). Reverse genetics enables precise assignment of phenotypic changes to genomic mutations. The goal to ‘rescue’ infectious rotavirus from a mutated genome has eluded success for a long time, and only recently a plasmid only-based, helper virus-free reverse genetics system for species A rotaviruses has been developed. Based on background information on rotavirus structure, classification, replication and genetic research, the new procedure is reviewed in detail, and its versatility and significance for future basic and translational research are discussed.

DOI: 10.29245/2578-2940/2018/1.1110 View / Download Pdf

Consuelo Romero- Sánchez1,2*

1Pediatric Rheumatology Program, School of Medicine, Unit of Oral Basic Investigation, School of Dentistry, Universidad El Bosque, Bogota, Colombia
2Group of Applied Clinical Immunology, Rheumatology and Immunology Department Hospital Militar Central, School of Medicine, Universidad Militar Nueva Granada, Bogota, Colombia.

DOI: 10.29245/2578-2940/2018/1.1106 View / Download Pdf

Elsia A. Obus1, Natalie H. Brito2, Lauren Sanlorenzo2, Corinna Rea2, Laura Engelhardt2, Kimberly G. Noble1*

1Teachers College, Columbia University, USA
2Columbia University Medical Center, USA

This study examines how the addition of a modest addendum to the well-established pediatric primary care program, Reach Out and Read (ROR), is associated with increased clinician adherence to ROR and caregiver home literacy behavior. This study took place in four ambulatory care clinics at a large urban medical center. All clinics received standard ROR training. Two of the four clinics received additional ROR training and bookmarks with age-specific advice about reading aloud with children. Following the intervention, medical providers reported no behavioral differences, however caregivers in the intervention group reported: more frequent trips to the library, receiving more books from their pediatrician, and receiving more advice on how to read with their child than caregivers in from the comparison clinics. Thus the addition of a modest training and bookmark intervention to the ROR program was associated with caregiver report of both increased clinician adherence to ROR and increased caregiver literacy behavior. The bookmark intervention may be an inexpensive way to improve the effects of the ROR program.

DOI: 10.29245/2578-2940/2018/1.1103 View / Download Pdf

Deena L. Gibbons1* and Paul Fleming2

1Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, Kings College London
2Department of Neonatology, Homerton University Hospital NHS Foundation Trust, London

DOI: 10.29245/2578-2940/2018/1.1102 View / Download Pdf