Pediatrics Commons^™

Genomic Analysis Of Chimeric Human Cytomegalovirus Vaccine Candidates Derived From Strains Towne And Toledo, Nicolás M. Suárez, Betty Lau, George M. Kemble, Ronzo Lee, Edward S. Mocarski, Gavin W. G. Wilkinson, Stuart P. Adler, Michael A. Mcvoy, Andrew J. Davison

Pediatrics Publications

Human cytomegalovirus (HCMV) is an important opportunistic pathogen in immunocompromised patients and a major cause of congenital birth defects when acquired in utero. In the 1990s, four chimeric viruses were constructed by replacing genome segments of the high passage Towne strain with segments of the low passage Toledo strain, with the goal of obtaining live attenuated vaccine candidates that remained safe but were more immunogenic than the overly attenuated Towne vaccine. The chimeras were found to be safe when administered to HCMV-seronegative human volunteers, but to differ significantly in their ability to induce seroconversion. This suggests that chimera-specific genetic differences …

Childhood Obesity: Physiological And Psychological Implications And Ethical Responsibilities, Connie S. Lewis

Journal of Health Ethics

Childhood obesity continues to be a health concern in the United States with physiological and psychological consequences. Research conducted in schools may address the physiological effects and exacerbate negative psychological effects, including weight bias and stigmatization. In the home, children are dependent on parents/caregivers to provide a healthy diet and exhibit a healthy lifestyle.The ethical theory, ethics of care, emphasizes dependence and interdependence on others, and ethical and moral responsibilities in the parent/child relationship. The assurance of ethical considerations involving children in research and parental provision for healthy dietary provision is of utmost importance. Any action or inaction that results …

Toward A Rapid Production Of Multivirus-Specific T Cells Targeting Bkv, Adenovirus, Cmv, And Ebv From Umbilical Cord Blood, Hema Dave, Min Luo, J.W. Blaney, Shabnum Patel, Cecilia Barese, Conrad Russell Cruz, Elizabeth J. Shpall, Catherine M. Bollard, Patrick J. Hanley

Pediatrics Faculty Publications

Umbilical cord blood (CB) has emerged as an effective alternative donor source for hematopoietic stem cell transplantation. Despite this success, the prolonged duration of immune suppression following CB transplantation and the naiveté of CB T cells leave patients susceptible to viral infections. Adoptive transfer of ex vivo-expanded virus-specific T cells from CB is both feasible and safe. However, the manufacturing process of these cells is complicated, lengthy, and labor-intensive. We have now developed a simplified method to manufacture a single culture of polyclonal multivirus-specific cytotoxic T cells in less than 30 days. It eliminates the need for a live virus …

Management Of Children With Chronic Wet Cough And Protracted Bacterial Bronchitis Chest Guideline And Expert Panel Report, Anne B. Chang, John J. Oppenheimer, Miles M. Weinberger, Bruce K. Rubin, Cameron C. Grant, Kelly Weir, Richard S. Irwin, Chest Expert Cough Panel

Pediatrics Publications

BACKGROUND: Wet or productive cough is common in children with chronic cough. We formulated recommendations based on systematic reviews related to the management of chronic wet cough in children (aged
METHODS: We used the CHEST expert cough panel's protocol for systematic reviews and the American College of Chest Physicians (CHEST) methodologic guidelines and GRADE framework (the Grading of Recommendations Assessment, Development and Evaluation). Data from the systematic reviews in conjunction with patients' values and preferences and the clinical context were used to form recommendations. Delphi methodology was used to obtain consensus for the recommendations/suggestions made.

RESULTS: Combining data from the …

Graduate Medical Education 2016-2017 Annual Report, Children's Mercy Hospital

GME Annual Reports

Annual report of the Children's Mercy Hospital Graduate Medical Education department, including pediatric residency, internal medicine/pediatrics residency, fellowship programs, medical students, continuing medical education, and library services.

Molecular Characterization Of Nrxn1 Deletions From 19,263 Clinical Microarray Cases Identifies Exons Important For Neurodevelopmental Disease Expression, Chelsea Lowther, Marsha Speevak, Christine M Armour, Elaine S Goh, Gail E Graham, Chumei Li, Susan Zeesman, Malgorzata J M Nowaczyk, Lee-Anne Schultz, Antonella Morra, Rob Nicolson, Peter Bikangaga, Dawa Samdup, Mostafa Zaazou, Kerry Boyd, Jack H Jung, Victoria Siu, Manjulata Rajguru, Sharan Goobie, Mark A Tarnopolsky, Chitra Prasad, Paul T Dick, Asmaa S Hussain, Margreet Walinga, Renske G Reijenga, Matthew Gazzellone, Anath C Lionel, Christian R Marshall, Stephen W Scherer, Dimitri J Stavropoulos, Elizabeth Mccready, Anne S Bassett

Paediatrics Publications

PURPOSE: The purpose of the current study was to assess the penetrance of NRXN1 deletions.

METHODS: We compared the prevalence and genomic extent of NRXN1 deletions identified among 19,263 clinically referred cases to that of 15,264 controls. The burden of additional clinically relevant copy-number variations (CNVs) was used as a proxy to estimate the relative penetrance of NRXN1 deletions.

RESULTS: We identified 41 (0.21%) previously unreported exonic NRXN1 deletions ascertained for developmental delay/intellectual disability that were significantly greater than in controls (odds ratio (OR) = 8.14; 95% confidence interval (CI): 2.91-22.72; P < 0.0001). Ten (22.7%) of these had a second clinically relevant CNV. Subjects with a deletion near the 3' end of NRXN1 were significantly more likely to have a second rare CNV than subjects with a 5' NRXN1 deletion (OR = 7.47; 95% CI: 2.36-23.61; P = 0.0006). The prevalence of intronic NRXN1 deletions was not statistically different between cases and controls (P = 0.618). The majority (63.2%) of intronic NRXN1 deletion cases had a second rare CNV at a prevalence twice as high as that for exonic NRXN1 deletion cases (P = 0.0035).

CONCLUSIONS: The results support the importance of exons …

Cytoplasmic Distribution Of Hiv-1 Tat Sensitizes Jurkat T Cells To Sulphamethoxazole-Hydroxylamine Induced Toxicity, Kemi Adeyanju, Gregory A. Dekaban, Michael J. Rieder

Paediatrics Publications

Background: One medication commonly used by HIV-1-infected individuals is the antimicrobial sulphamethoxazole (SMX), which is used in the treatment and prophylaxis of pneumocystis pneumonia. However, SMX is responsible for a very high incidence of hypersensitivity adverse drug reactions (ADRs) in the HIV-1 population. While the pathophysiology of ADRs in general is unknown, sulphamethoxazole-mediated ADRs have been linked to its reactive metabolite sulphamethoxazole-hydroxylamine (SMX-HA). Our previous work has shown that increased expression of the HIV-1 Tat protein in T cells correlated with increased apoptosis after incubation with SMX-HA. In this study we sought to determine the region of the Tat protein …

Brainstem Shape Is Affected By Clinical Course In The Neonatal Intensive Care Unit, Marcus Lo, Leire Zubiaurre-Elorza, Conor Wild, Annika C Linke, David S C Lee, Victor K Han, Rhodri Cusack

Paediatrics Publications

The brainstem, critical for motor function, autonomic regulation, and many neurocognitive functions, undergoes rapid development from the third trimester. Accordingly, we hypothesized it would be vulnerable to insult during this period, and that a difficult clinical course in the neonatal intensive care unit (NICU) would affect development, and be reflected through atypical shape. Our study population consisted of 66 neonates - all inpatients from the NICU at Victoria Hospital, London Health Sciences Centre, ON, Canada, of which 45 entered the final analysis. The cohort varied in gestational age (GA) and ranged from neurologically healthy to severely brain-injured. Structural MRI was …

Different Effects Of Insulin-Like Growth Factor-1 And Insulin-Like Growth Factor-2 On Myogenic Differentiation Of Human Mesenchymal Stem Cells, Doaa Aboalola, Victor K M Han

Paediatrics Publications

Insulin-like growth factors (IGFs) are critical components of the stem cell niche, as they regulate proliferation and differentiation of stem cells into different lineages, including skeletal muscle. We have previously reported that insulin-like growth factor binding protein-6 (IGFBP-6), which has high affinity for IGF-2, alters the differentiation process of placental mesenchymal stem cells (PMSCs) into skeletal muscle. In this study, we determined the roles of IGF-1 and IGF-2 and their interactions with IGFBP-6. We showed that IGF-1 increased IGFBP-6 levels within 24 hours but decreased after 3 days, while IGF-2 maintained higher levels of IGFBP-6 throughout myogenesis. IGF-1 increased IGFBP-6 …

Pediatric Emergency Care Capacity In A Low-Resource Setting: An Assessment Of District Hospitals In Rwanda, Celestin Hategeka, Jean Shoveller, Lisine Tuyisenge, Cynthia Kenyon, David F Cechetto, Larry D Lynd

Paediatrics Publications

BACKGROUND: Health system strengthening is crucial to improving infant and child health outcomes in low-resource countries. While the knowledge related to improving newborn and child survival has advanced remarkably over the past few decades, many healthcare systems in such settings remain unable to effectively deliver pediatric advance life support management. With the introduction of the Emergency Triage, Assessment and Treatment plus Admission care (ETAT+)-a locally adapted pediatric advanced life support management program-in Rwandan district hospitals, we undertook this study to assess the extent to which these hospitals are prepared to provide this pediatric advanced life support management. The results of …

Identification Of Epigenetic Signature Associated With Alpha Thalassemia/Mental Retardation X-Linked Syndrome, Laila C Schenkel, Kristin D Kernohan, Arran Mcbride, Ditta Reina, Amanda Hodge, Peter J Ainsworth, David I Rodenhiser, Guillaume Pare, Nathalie G Bérubé, Cindy Skinner, Kym M Boycott, Charles Schwartz, Bekim Sadikovic

Paediatrics Publications

BACKGROUND: Alpha thalassemia/mental retardation X-linked syndrome (ATR-X) is caused by a mutation at the chromatin regulator gene

RESULTS: We performed genome-wide DNA methylation assessment of the peripheral blood samples from 18 patients with ATR-X and compared it to 210 controls. We demonstrated the evidence of a unique and highly specific DNA methylation "epi-signature" in the peripheral blood of ATRX patients, which was corroborated by targeted bisulfite sequencing experiments. Although genomically represented, differentially methylated regions showed evidence of preferential clustering in pericentromeric and telometric chromosomal regions, areas where ATRX has multiple functions related to maintenance of heterochromatin and genomic integrity.

CONCLUSION: …

Remote Lifestyle Counseling Influences Cardiovascular Health Outcomes In Youth With Overweight Or Obesity And Congenital Heart Disease, Luis Altamirano-Diaz, Meghan Rombeek, Stefanie De Jesus, Eva Welisch, Harry Prapavessis, Adam A Dempsey, Douglas Fraser, Michael R Miller, Kambiz Norozi

Paediatrics Publications

Background: Children with overweight/obesity and congenital heart disease (CHD) are at increased cardiovascular risk. A lifestyle intervention may help reduce these risks. We sought to determine the feasibility of a smartphone-based lifestyle intervention to improve cardiovascular health outcomes in children with overweight/obesity and CHD.

Methods: We examined the effect of bi-weekly nutrition and fitness counseling delivered

Results: Statistically significant decreases in waist circumference (WC), body mass index

Conclusion: The observed changes in anthropometry were positive with significant improvement to some cardiovascular and metabolic risk indicators. However, this was only observed in the operated group suggesting that other factors, such as …

When Crrt On Ecmo Is Not Enough For Potassium Clearance: A Case Report, Janice A. Tijssen, Guido Filler

Paediatrics Publications

Background: Continuous renal replacement therapy (CRRT) is an excellent method used to remove fluid and solutes. It may also reduce the systemic inflammatory response for patients on extracorporeal membrane oxygenation (ECMO) support. Theobjective of this report is to describe a case where CRRT in combination with ECMO was insufficient to control hyperkalemia. Methods: We report the case of an adolescent patient with refractory symptomatic hyperkalemia due to substantial rhabdomyolysis in which CRRT insufficiently cleared the patient's excess potassium. Results: Intermittent hemodialysis (IHD) was added and proved successful. The patient was weaned off ECMO, CRRT, and IHD, and his cardiac and …

How Does The Social “Get Under The Gums”? The Role Of Socio-Economic Position In The Oral-Systemic Health Link, Noha Gomaa, Belinda Nicolau, Arjumand Siddiqi, Howard Tenenbaum, Michael Glogauer, Carlos Quiñonez

Paediatrics Publications

OBJECTIVES: To evaluate the extent of association between systemic inflammation and periodontal disease in American adults, and to assess whether socio-economic position mediated this relationship. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES IV) (2001-2010). Systemic inflammation was defined by individual and aggregate (cumulative inflammatory load) biomarkers (C-reactive protein, white blood cell counts, neutrophil counts, and neutrophil: lymphocyte ratio). Loss of attachment and bleeding on probing were used to define periodontal disease. Poverty:income ratio and education were indicators of socio-economic position. Covariates included age, sex, ethnicity, smoking, alcohol, and attendance for dental treatment. Univariate and …

Impact Of Birth Weight And Postnatal Diet On The Gut Microbiota Of Young Adult Guinea Pigs., Kait Al, Ousseynou Sarr, Kristyn Dunlop, Gregory B Gloor, Gregor Reid, Jeremy Burton, Timothy Regnault

Paediatrics Publications

BACKGROUND: The gastrointestinal tract (GIT) microbiota is essential to metabolic health, and the prevalence of the Western diet (WD) high in fat and sugar is increasing, with evidence highlighting a negative interaction between the GIT and WD, resulting in liver dysfunction. Additionally, an adverse

METHODS: The fecal microbiota of normal birth weight (NBW) and LBW young guinea pig offspring, weaned onto either a control diet (CD) or WD was determined with 16S rRNA gene next generation sequencing at young adulthood following the early rapid growth phase after weaning. A liver blood chemistry profile was also performed.

RESULTS: The life-long consumption …

Children's Mercy Hospital Annual Report 2016, Children's Mercy Hospital

Children's Mercy Annual Reports

Annual report for The Children's Mercy Hospital in Kansas City MO, a pediatric medical center.

Medical Genetics And Genomic Medicine In The United States. Part 2: Reproductive Genetics, Newborn Screening, Genetic Counseling, Training, And Registries, Debra S. Regier, Carlos Ferreira, Suzanne Hart, Donald Hadley, Maximilian Muenke

Pediatrics Faculty Publications

eview of genetics in the United States with emphasis on the prenatal, metabolic, genetic counseling, and training aspects of the field.

Nasopharyngeal Microbiome Diversity Changes Over Time In Children With Asthma, Marcos Pérez-Losada, Lamia Alamri, Keith Crandall, Robert J. Freishtat

Pediatrics Faculty Publications

Background

The nasopharynx is a reservoir for pathogens associated with respiratory illnesses such as asthma. Next-generation sequencing (NGS) has been used to characterize the nasopharyngeal microbiome of infants and adults during health and disease; less is known, however, about the composition and temporal dynamics (i.e., longitudinal variation) of microbiotas from children and adolescents. Here we use NGS technology to characterize the nasopharyngeal microbiomes of asthmatic children and adolescents (6 to 18 years) and determine their stability over time.

Methods

Two nasopharyngeal washes collected 5.5 to 6.5 months apart were taken from 40 children and adolescents with asthma living in the …

Prevalence Of Non-Alcoholic Fatty Liver Disease In Overweight And Obese Children Seeking Ambulatory Health Services In Nairobi, Anne Njeri Mburu

Master of Medicine in Paediatrics and Child Health

Introduction: Non-alcoholic fatty liver disease is often an asymptomatic condition one of the leading causes of chronic liver disease and is associated with an increase in cardiovascular morbidity. Being overweight or obese has been positively linked to non-alcoholic fatty liver disease in children. There is evidence to show that when detected early, non-alcoholic fatty liver disease is reversible primarily upon institution of lifestyle changes targeted at weight reduction. Establishing the prevalence of non-alcoholic fatty liver disease in overweight and obese Kenyan children would serve as a benchmark for long term monitoring of associated morbidity and guide in public health policies …

Prevalence And Possible Factors Associated With Anaemia, And Vitamin B 12 And Folate Deficiencies In Women Of Reproductive Age In Pakistan: Analysis Of National-Level Secondary Survey Data, Sajid Bashir Soofi, Gul Nawaz Khan, Kamran Sadiq, Shabina Ariff, Atif Habib, Sumra Kureishy, Imtiaz Hussain, Muhammad Umer, Zamir Suhag, Arjumand Rizvi, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Objective: To determine the prevalence and possible factors associated with anaemia, and vitamin B12 and folate deficiencies in women of reproductive age (WRA) in Pakistan.
Methods: A secondary analysis was conducted on data collected through the large-scale National Nutrition Survey in Pakistan in 2011. Anaemia was defined as haemoglobin levels /dL, vitamin B12 deficiency as serum vitamin B12 levels of /mL (150 pmol/L) and folate deficiency as serum folate levels /mL (10 nmol/L).
Results: A total of 11 751 blood samples were collected and analysed. The prevalence of anaemia, vitamin B12 deficiency and folate deficiency was 50.4%, 52.4% and 50.8%, …