Digital Commons Network^™

Vitamin D In The Prevention Of Exacerbations Of Asthma In Preschoolers (Diva): Protocol For A Multicentre Randomised Placebo-Controlled Triple-Blind Trial, Megan E. Jensen, Francine M. Ducharme, Nathalie Alos, Geneviève Mailhot, Benoît Mâsse, John H. White, Mohsen Sadatsafavi, Ali Khamessan, Sze Man Tse, Reza Alizadehfar, Dirk E. Bock, Patrick Daigneault, Chantal Lemire, Connie Yang, Dhenuka Radhakrishnan

Paediatrics Publications

Introduction Preschoolers have the highest rate of emergency visits and hospitalisations for asthma exacerbations of all age groups, with most triggered by upper respiratory tract infections (URTIs) and occurring in the fall or winter. Vitamin D insufficiency is highly prevalent in Canadian preschoolers with recurrent asthma exacerbations, particularly in winter. It is associated with more URTIs and, in patients with asthma, more oral corticosteroid (OCS) use. Although evidence suggests that vitamin D supplements significantly decrease URTIs and asthma exacerbations requiring OCS, there is insufficient data in preschoolers. This study aims to determine the impact of vitamin D 3 supplementation on …

Current State Of Precision Medicine In Primary Systemic Vasculitides, Erkan Demirkaya, Zehra Serap Arici, Micol Romano, Roberta Audrey Berard, Ivona Aksentijevich

Paediatrics Publications

Precision medicine (PM) is an emerging data-driven health care approach that integrates phenotypic, genomic, epigenetic, and environmental factors unique to an individual. The goal of PM is to facilitate diagnosis, predict effective therapy, and avoid adverse reactions specific for each patient. The forefront of PM is in oncology; nonetheless, it is developing in other fields of medicine, including rheumatology. Recent studies on elucidating the genetic architecture of polygenic and monogenic rheumatological diseases have made PM possible by enabling physicians to customize medical treatment through the incorporation of clinical features and genetic data. For complex inflammatory disorders, the prevailing paradigm is …

Teaching Video Neuroimages: Atypical Childhood Epilepsy With Centrotemporal Spikes: Seizures Often Discussed, Rarely Seen, Egidio Spinelli, Khrystyna Moskalyk, Sunita N. Misra

Paediatrics Publications

A 7-year-old right-handed boy with poorly controlled epilepsy presented to the epilepsy monitoring unit for further clarification of his diagnosis. Seizure onset was at 3 years with focal motor seizures of left face and arm followed by confusion and aphasia. Prominent behavioral and school difficulties were also reported. Valproic acid monotherapy (23 mg/kg/d) was weaned by day 2 and a habitual event captured on day 5 (figure, video 1). Brain MRI and an epilepsy gene panel (including GRIN2A) were nonrevealing. The diagnosis was therefore consistent with atypical childhood epilepsy with centrotemporal spikes. This differs from benign rolandic epilepsy because of …

Video Discharge Instructions For Acute Otitis Media In Children: A Randomized Controlled Open-Label Trial, Sheena Belisle, Andrei Dobrin, Sharlene Elsie, Samina Ali, Shaily Brahmbhatt, Kriti Kumar, Hardika Jasani, Michael Miller, Frank Ferlisi, Naveen Poonai

Paediatrics Publications

Background: Thirty percent of children with acute otitis media (AOM) experience symptoms < 7 days after initiating treatment, highlighting the importance of comprehensive discharge instructions. Methods: We randomized caregivers of children 6 months to 17 years presenting to the emergency department (ED) with AOM to discharge instructions using a video on management of pain and fever to a paper handout. The primary outcome was the AOM Severity of Symptom (AOM-SOS) score at 72 hours postdischarge. Secondary outcomes included caregiver knowledge (10-item survey), absenteeism, recidivism, and satisfaction (5-item Likert scale). Results: A total of 219 caregivers were randomized and 149 completed the 72-hour follow-up (72 paper and 77 video). The median (IQR) AOM-SOS score for the video was significantly lower than paper, even after adjusting for preintervention AOM-SOS score and medication at home (8 [7–11] vs. 10 [7–13], respectively; p = 0.004). There were no significant differences between video and paper in mean (±SD) knowledge score (9.2 [±1.3] vs. 8.8 [±1.8], respectively; p = 0.07), mean (±SD) number of children that returned to a health care provider (8/77 vs. 10/72, respectively; p = 0.49), mean (±SD) number of daycare/school days missed by child (1.2 [±1.5] vs. 1.1 [±2.1], respectively; p = 0.62), mean (±SD) number of workdays missed by caregiver (0.5 [±1] vs. 0.8 [±2], respectively; p = 0.05), or median (IQR) satisfaction score (5 [4–5] vs. 5 [4–5], respectively; p = 0.3). Conclusions: Video discharge instructions in the ED are associated with less perceived AOM symptomatology compared to a paper handout.

Modulation Of Reck Levels In Xenopus A6 Cells: Effects On Mt1-Mmp, Mmp-2 And Perk Levels, Jessica A. Willson, Bradley S. Bork, Carlie A. Muir, Sashko Damjanovski

Paediatrics Publications

Background: MT1-MMP is a cell-surface enzyme whose regulation of pro-MMP-2 and ERK activation position it as a key facilitator of ECM remodelling and cell migration. These processes are modulated by endogenous MMP inhibitors, such as RECK, a GPI-anchored protein which has been shown to inhibit both MT1-MMP and MMP-2 activity. Our previous studies have revealed a link between MT1-MMP levels, and pro-MMP-2 and ERK activation in mammalian cells, as well as MT1-MMP and RECK co-localization in Xenopus embryos. We here investigated how modulation of RECK would impact MT1-MMP and MMP-2 levels, as well as ERK signalling in Xenopus A6 cells. …

The Transcription Factor Pu.1 Mediates Enhancer-Promoter Looping That Is Required For Il-1 Erna And Mrna Transcription In Mouse Melanoma And Macrophage Cell Lines, Soon-Duck Ha, Woohyun Cho, Rodney P. Dekoter, Sung Ouk Kim

Paediatrics Publications

The DNA-binding protein PU.1 is a myeloid lineage– determining and pioneering transcription factor due to its ability to bind “closed” genomic sites and maintain “open” chromatin state for myeloid lineage–specific genes. The precise mechanism of PU.1 in cell type–specific programming is yet to be elucidated. The melanoma cell line B16BL6, although it is nonmyeloid lineage, expressed Toll-like receptors and activated the transcription factor NF-B upon stimulation by the bacterial cell wall component lipopolysaccharide. However, it did not produce cytokines, such as IL-1 mRNA. Ectopic PU.1 expression induced remodeling of a novel distal enhancer (located 10 kbp upstream of the IL-1 …

Exploring The Feasibility And Effectiveness Of A Childcare Physical Activity (Play) Policy: Rationale And Protocol For A Pilot, Cluster-Randomized Controlled Trial, Patricia Tucker, Molly Driediger, Leigh M. Vanderloo, Shauna M. Burke, Jennifer D. Irwin, Andrew M. Johnson, Jacob Shelley, Brian W. Timmons

Paediatrics Publications

Background: Young children are prone to low levels of physical activity in childcare. This environment, inclusive of equipment, policies, and staff, has been identified as influencing young children’s activity behaviours. To date, no study has examined the feasibility and effectiveness of such policies in Canadian childcare centres, while the provision of physical activity policies in other countries has shown some promise for improving the activity levels of young children. As such, the primary objective of the Childcare PhysicaL ActivitY (PLAY) Policy study is to examine the feasibility of an evidence-based, stakeholder-informed, written physical activity and sedentary time policy for centre-based …

An Evaluation Of Heart Rate Variability In Female Youth Soccer Players Following Soccer Heading: A Pilot Study, Alexandra B. Harriss, Kolten Abbott, Kurt Kimpinski, Jeffrey D. Holmes, Andrew M. Johnson, David M. Walton, James P. Dickey

Paediatrics Publications

Most head impacts in soccer occur from purposeful heading; however, the link between heading and neurological impairment is unknown. Previous work suggests concussion may result in an uncoupling between the autonomic nervous system and cardiovascular system. Accordingly, heart rate variability (HRV) may be a sensitive measure to provide meaningful information regarding repetitive heading in soccer. The purpose of this pilot study assesses the feasibility of measuring HRV to evaluate autonomic function following soccer heading. Sixteen youth female participants underwent heart rate monitoring during a heading and footing condition. Participants completed a five minute resting supine trial at the start and …

Health Care For Mitochondrial Disorders In Canada: A Survey Of Physicians, Karen Paik, Matthew A. Lines, Pranesh Chakraborty, Sara D. Khangura, Maureen Latocki, Walla Al-Hertani, Catherine Brunel-Guitton, Aneal Khan, Blaine Penny, Cheryl Rockman-Greenberg, C. Anthony Rupar, Neal Sondheimer, Mark Tarnopolsky, Kylie Tingley, Doug Coyle, Sarah Dyack, Annette Feigenbaum, Michael T. Geraghty, Jane Gillis, Clara D.M. Van Karnebeek, Jonathan B. Kronick, Julian Little, Murray Potter, Komudi Siriwardena, Rebecca Sparkes, Lesley A. Turner

Paediatrics Publications

Background: An improved understanding of diagnostic and treatment practices for patients with rare primary mitochondrial disorders can support benchmarking against guidelines and establish priorities for evaluative research. We aimed to describe physician care for patients with mitochondrial diseases in Canada, including variation in care. Methods: We conducted a cross-sectional survey of Canadian physicians involved in the diagnosis and/or ongoing care of patients with mitochondrial diseases. We used snowball sampling to identify potentially eligible participants, who were contacted by mail up to five times and invited to complete a questionnaire by mail or internet. The questionnaire addressed: personal experience in providing …

High Diagnostic Yield Of Direct Sanger Sequencing In The Diagnosis Of Neuronal Ceroid Lipofuscinoses, Abdulhakim Jilani, Diana Matviychuk, Susan Blaser, Sarah Dyack, Jean Mathieu, Asuri N. Prasad, Chitra Prasad, Lianna Kyriakopoulou, Saadet Mercimek-Andrews

Paediatrics Publications

Background: Neuronal ceroid lipofuscinoses are neurodegenerative disorders. To investigate the diagnostic yield of direct Sanger sequencing of the CLN genes, we reviewed Molecular Genetics Laboratory Database for molecular genetic test results of the CLN genes from a single clinical molecular diagnostic laboratory. Methods: We reviewed electronic patient charts. We used consent forms and Research Electronic Data Capture questionnaires for the patients from outside of our Institution. We reclassified all variants in the CLN genes. Results: Six hundred and ninety three individuals underwent the direct Sanger sequencing of the CLN genes for the diagnosis of neuronal ceroid lipofuscinoses. There were 343 …

The Impact Of Shorter, More Frequent Outdoor Play Periods On Preschoolers’ Physical Activity During Childcare: A Cluster Randomized Controlled Trial, Molly Driediger, Stephanie Truelove, Andrew M. Johnson, Leigh M. Vanderloo, Brian W. Timmons, Shauna M. Burke, Jennifer D. Irwin, Patricia Tucker

Paediatrics Publications

Children’s physical activity levels are higher at the start of outdoor playtime, which suggests that shorter, more frequent play periods might result in greater amounts of daily physical activity. In this extension of the Supporting Physical Activity in the Childcare Environment (SPACE) cluster randomized controlled trial, we explored the impact of four 30-min daily outdoor unstructured play periods on preschoolers’ moderate-to-vigorous-intensity physical activity (MVPA). Experimental childcare centres (n = 6) implemented four 30-min daily outdoor playtimes for 8 weeks, while control centres (n = 6) maintained their two 60-min outdoor sessions. Actical™ accelerometers were used to measure preschoolers’ physical activity …

Development Of A Teen-Informed Coding Tool To Measure The Power Of Food Advertisements, Drew D. Bowman, Leia M. Minaker, Bonnie J.K. Simpson, Jason A. Gilliland

Paediatrics Publications

The food-related information environment, comprised of food and beverage advertising within one’s surroundings, is a growing concern for adolescent health given that food marketing disproportionately targets adolescents. Despite strong public interest concerning the effects of food marketing on child health, there is limited evidence focused on outdoor food advertising in relation to teenage diets, food purchasing, and perceptions. Further, limited research has considered both the exposure to and influence of such advertisements. This study used a novel multi-method approach to identify and quantify the features of outdoor food and beverage advertisements that are most effective at drawing teenagers into retail …

Experiences Regarding Nutrition And Exercise Among Women During Early Postpartum: A Qualitative Grounded Theory Study, Beth Murray-Davis, Lindsay Grenier, Stephanie A. Atkinson, Michelle F. Mottola, Olive Wahoush, Lehana Thabane, Feng Xie, Jennifer Vickers-Manzin, Caroline Rosenblatt, David Watkins, Avraham Shaag, Stanley H. Korman, Samuel N. Heyman, Aya Gal, J. P. Newman, Bettina Steiner-Birmanns, Oded Abramsky, Yoav Kohn

Paediatrics Publications

Background: Excess gestational weight gain has long- and short-term implications for women and children, and postpartum weight retention is associated with an increased risk of long-term obesity. Despite the existence of dietary and exercise guidelines, many women struggle to return to pre-pregnancy weight. Experiences of women in tackling postpartum weight loss are poorly understood. We undertook this study to explore experiences related to nutrition, exercise and weight in the postpartum in women in Ontario, Canada. Methods: This was a nested qualitative study within The Be Healthy in Pregnancy Study, a randomized controlled trial. Women randomized to the control group were …

Consensus-Based Care Recommendations For Congenital And Childhood-Onset Myotonic Dystrophy Type 1, Nicholas E. Johnson, Eugenio Zapata Aldana, Nathalie Angeard, Tetsuo Ashizawa, Kiera N. Berggren, Chiara Marini-Bettolo, Tina Duong, Anne Berit Ekström

Paediatrics Publications

Purpose of reviewMyotonic dystrophy type 1 is a multisystemic disorder caused by a noncoding triplet repeat. The age of onset is variable across the lifespan, but in its most severe form, the symptoms appear at birth (congenital myotonic dystrophy) or in the pediatric age range (childhood-onset myotonic dystrophy). These children have a range of disabilities that reduce the lifespan and cause significant morbidity. Currently, there are no agreed upon recommendations for caring for these children.Recent findingsThe Myotonic Dystrophy Foundation recruited 11 international clinicians who are experienced with congenital and childhood-onset myotonic dystrophy to create consensus-based care recommendations. The experts used …

Say No To Ros: Their Roles In Embryonic Heart Development And Pathogenesis Of Congenital Heart Defects In Maternal Diabetes, Anish Engineer, Tana Saiyin, Elizabeth R. Greco, Qingping Feng

Paediatrics Publications

Congenital heart defects (CHDs) are the most prevalent and serious birth defect, occurring in 1% of all live births. Pregestational maternal diabetes is a known risk factor for the development of CHDs, elevating the risk in the child by more than four-fold. As the prevalence of diabetes rapidly rises among women of childbearing age, there is a need to investigate the mechanisms and potential preventative strategies for these defects. In experimental animal models of pregestational diabetes induced-CHDs, upwards of 50% of offspring display congenital malformations of the heart, including septal, valvular, and outflow tract defects. Specifically, the imbalance of nitric …

Prevalence And Impact Of Bumps, Bruises, And Other Painful Incidents Among Children While Handling And Riding Horses, Lara M. Genik, C. Meghan Mcmurtry

Paediatrics Publications

Horseback riding and related activities bring risks for serious injury. Extant literature focuses largely on moderate to severe horse-related injuries resulting in a need for medical care. Yet incidents deemed as less severe are also important, with potential to impact subsequent safety precautions and behaviors of parents and children. The study objectives were to gather preliminary information about: (1) the prevalence of a range of horse-related painful incidents experienced by children, (2) children's helmet use and supervision, and (3) the subsequent impact of horse-related painful incidents. The methodological approach was based on a questionnaire. One hundred and twenty four child …

Apixaban Concentrations With Lower Than Recommended Dosing In Older Adults With Atrial Fibrillation, Smrithi Sukumar, Markus Gulilat, Bradley Linton, Steven E. Gryn, George K. Dresser, Jeffrey E. Alfonsi, Ute I. Schwarz, Richard B. Kim

Paediatrics Publications

OBJECTIVES: Lower than recommended doses of direct-acting oral anticoagulants are often prescribed to older adults with nonvalvular atrial fibrillation (NVAF). Our goal was to determine the consequences of lower than recommended dosing on plasma apixaban concentrations during the clinical care of older adults with NVAF. DESIGN: Convenience sample of patients receiving anticoagulation during 2017. SETTING: Academic medical center. PARTICIPANTS: Stable adults older than 65 years with NVAF receiving apixaban on a chronic basis. MEASUREMENTS: Patient age, weight, creatinine, co-medications, and apixaban concentrations. RESULTS: A total of 110 older adults with NVAF (mean age = 80.4 y; range = 66-100 y …

Corrigendum: Pain Management Practices Surrounding Lumbar Punctures In Children: A Survey Of Canadian Emergency Physicians (Canadian Journal Of Emergency Medicine (2018) Doi: 10.1017/Cem.2018.382), Naveen Poonai, Victoria Brzozowski, Antonia S. Stang, Amy L. Drendel, Philippe Boisclair, Michael Miller, Stuart Harman, Samina Ali

Paediatrics Publications

In the original publication of this article, Pediatric Emergency Research Canada (PERC) was not listed as an author. The authors regret this error. The original version has been updated.

Utility Of Clinical Features With Fine Needle Aspiration Biopsy For Diagnosis Of Warthin Tumor., Thomas So, Axel Sahovaler, Anthony Nichols, Kevin Fung, John Yoo, Michele M Weir, S Danielle Macneil

Paediatrics Publications

BACKGROUND:
Conservative management of Warthin tumor (WT) may be a viable alternative to surgery, but there are concerns of missed malignancies on fine needle aspiration biopsy (FNAB). The purpose of this study is to measure the sensitivity and positive predictive value of FNAB for WT, and to identify clinical features associated with WT that can aid in this diagnosis.

METHODS:
Retrospective analysis of patients from January 1, 2006 to April 30, 2017 at a tertiary care center in London, Ontario, Canada. All patients with a diagnosis of WT on FNAB or resection were included. Electronic medical records were identified for …

Correction To: Eight Years After An International Workshop On Myotonic Dystrophy Patient Registries: Case Study Of A Global Collaboration For A Rare Disease (Orphanet Journal Of Rare Diseases (2018) 13 (155) Doi: 10.1186/S13023-018-0889-0), Libby Wood, Guillaume Bassez, Corinne Bleyenheuft, Craig Campbell, Louise Cossette, Aura Cecilia Jimenez-Moreno, Yi Dai, Hugh Dawkins, Jordi Harreiter, Alexandra Kautzky-Willer, Peter Damm, Elisabeth R. Mathiesen, Dorte M. Jensen, Lise Lotte T. Andersen, Mette Tanvig, Annunziata Lapolla, Maria G. Dalfra, Alessandra Bertolotto, Urszula Manta, Ewa Wender-Ozegowska, Agnieszka Zawiejska, David J. Hill, Frank J. Snoek, Judith G.M. Jelsma, Mireille Van Poppel

Paediatrics Publications

The original version of this article [1] unfortunately included an error to an author's name. Author Jordi Díaz-Manera was erroneously presented as Jorge Alberto Diaz Manera. The correct author name has been included in the author list of this Correction article. For citation purposes the author's given name is Jordi and family name Diaz-Manera. Therefore, the correct citation of the author's details is: Diaz-Manera J.

Gld2 Activity Is Regulated By Phosphorylation In The N-Terminal Domain, Christina Z. Chung, Nileeka Balasuriya, Emad Manni, Xuguang Liu, Shawn Shun Cheng Li, Patrick O’Donoghue, Ilka U. Heinemann

Paediatrics Publications

The de-regulation of microRNAs (miRNAs) is associated with multiple human diseases, yet cellular mechanisms governing miRNA abundance remain largely elusive. Human miR-122 is required for Hepatitis C proliferation, and low miR-122 abundance is associated with hepatic cancer. The adenylyltransferase Gld2 catalyses the post-transcriptional addition of a single adenine residue (A + 1) to the 3ʹ-end of miR-122, enhancing its stability. Gld2 activity is inhibited by binding to the Hepatitis C virus core protein during HepC infection, but no other mechanisms of Gld2 regulation are known. We found that Gld2 activity is regulated by site-specific phosphorylation in its disordered N-terminal domain. …

Review Of Recent Physical Activity Guidelines During Pregnancy To Facilitate Advice By Health Care Providers, Kelly R. Evenson, Michelle F. Mottola, Raul Artal

Paediatrics Publications

Importance: Physical activity during pregnancy can offer many maternal and fetal health benefits. Objective: The aim was to summarize American, Canadian, and international recommendations published recently on physical activity during pregnancy to aid health care providers in their delivery of advice on the topic. Evidence Acquisition: A descriptive review of 3 national guidelines and 1 international guideline on physical activity during pregnancy was conducted. The guidelines included the 2019 Canadian recommendations, the 2018 United States' Physical Activity Guidelines for Americans (second edition), the 2015 (reaffirmed in 2017) American College of Obstetrics and Gynecology guideline, and the 2016-2018 International Olympic Committee …

Heating Injection Drug Preparation Equipment Used For Opioid Injection May Reduce Hiv Transmission Associated With Sharing Equipment, Laura J. Ball, Colin Venner, Rommel G. Tirona, Eric Arts, Kaveri Gupta, Joshua C. Wiener, Sharon Koivu, Michael S. Silverman

Paediatrics Publications

London, Canada, experienced an HIV outbreak among persons who inject drugs despite widespread distribution of harm reduction equipment. Hydromorphone controlled-release (HMC) is the local opioid of choice. Injection drug preparation equipment (IDPE; ie, cookers and filters) is often shared and reused because of the perception that there is residual HMC in the IDPE after use. The purpose of this study was to investigate the mechanisms of HIV transmission in this context.Methods:Residual hydromorphone, (controlled-release or immediate-release), remaining in the IDPE, was measured with liquid chromatography-tandem mass spectrometry, in conditions replicating persons who inject drug use. HIV was added to IDPE in …

Impact Of Deferring Critically Ill Children Away From Their Designated Pediatric Critical Care Unit: A Population-Based Retrospective Cohort Study, Janice A. Tijssen, Britney N. Allen, Krista M.Bray Jenkyn, Salimah Z. Shariff

Paediatrics Publications

BACKGROUND: The impact of deferring critically ill children in referral hospitals away from their designated pediatric critical care unit (PCCU) on patients and the healthcare system is unknown. We aimed to identify factors associated with deferrals and patient outcomes and to study the impact of a referral policy implemented to balance PCCU bed capacity with regional needs. METHODS: We conducted a population-based retrospective cohort study of admissions to a PCCU following inter-facility transport from 2004 to 2016 in Ontario, Canada. RESULTS: Of 10,639 inter-facility transfers, 24.8% (95% confidence interval [CI]: 23.5-26.1%) were deferred during pre-implementation and 16.0% (95% CI: 15.1-16.9%) …

Classification Criteria For Autoinflammatory Recurrent Fevers., Marco Gattorno, Michael Hofer, Silvia Federici, Federica Vanoni, Francesca Bovis, Ivona Aksentijevich, Jordi Anton, Juan Ignacio Arostegui, Karyl Barron, Eldad Ben-Cherit, Paul A Brogan, Luca Cantarini, Isabella Ceccherini, Fabrizio De Benedetti, Fatma Dedeoglu, Erkan Demirkaya, Joost Frenkel, Raphaela Goldbach-Mansky, Ahmet Gul, Veronique Hentgen, Hal Hoffman, Tilmann Kallinich, Isabelle Kone-Paut, Jasmin Kuemmerle-Deschner, Helen J Lachmann, Ronald M Laxer, Avi Livneh, Laura Obici, Seza Ozen, Dorota Rowczenio, Ricardo Russo, Yael Shinar, Anna Simon, Nataša Toplak, Isabelle Touitou, Yosef Uziel, Marielle Van Gijn, Dirk Foell, Claudia Garassino, Dan Kastner, Alberto Martini, Maria Pia Sormani, Nicolino Ruperto

Paediatrics Publications

BACKGROUND:
Different diagnostic and classification criteria are available for hereditary recurrent fevers (HRF)-familial Mediterranean fever (FMF), tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS), mevalonate kinase deficiency (MKD) and cryopyrin-associated periodic syndromes (CAPS)-and for the non-hereditary, periodic fever, aphthosis, pharyngitis and adenitis (PFAPA). We aimed to develop and validate new evidence-based classification criteria for HRF/PFAPA.

METHODS:
Step 1: selection of clinical, laboratory and genetic candidate variables; step 2: classification of 360 random patients from the Eurofever Registry by a panel of 25 clinicians and 8 geneticists blinded to patients' diagnosis (consensus ≥80%); step 3: statistical analysis for the selection of …

Offspring From Maternal Nutrient Restriction In Mice Show Variations In Adult Glucose Metabolism Similar To Human Fetal Growth Restriction., B N Radford, V K M Han

Paediatrics Publications

Fetal growth restriction (FGR) is a pregnancy condition in which fetal growth is suboptimal for gestation, and this population is at increased risk for type 2 diabetes as adults. In humans, maternal malnutrition and placental insufficiency are the most common causes of FGR, and both result in fetal undernutrition. We hypothesized that maternal nutrient restriction (MNR) in mice will cause FGR and alter glucose metabolism in adult offspring. Pregnant CD-1 mice were subjected to MNR (70% of average ad libitum) or control (ad libitum) from E6.5 to birth. Following birth, mice were fostered by mothers on ad libitum feeds. Weight, …

Maternal Voluntary Exercise Mitigates Oxidative Stress And Incidence Of Congenital Heart Defects In Pre-Gestational Diabetes, Tana Saiyin, Anish Engineer, Elizabeth R. Greco, Mella Y. Kim, Xiangru Lu, Douglas L. Jones, Qingping Feng

Paediatrics Publications

Women with pre-gestational diabetes have a higher risk of producing children with congenital heart defects (CHDs), caused predominantly by hyperglycemia-induced oxidative stress. In this study, we evaluated if exercise during pregnancy could mitigate oxidative stress and reduce the incidence of CHDs in the offspring of diabetic mice. Female mice were treated with streptozotocin to induce pre-gestational diabetes, then mated with healthy males to produce offspring. They were also given access to running wheels 1 week before mating and allowed to exercise voluntarily until E18.5. Heart morphology, gene expression, and oxidative stress were assessed in foetal hearts. Maternal voluntary exercise results …

Inhibition Of Stat3 Activation Mediated By Toll-Like Receptor 4 Attenuates Angiotensin Ii-Induced Renal Fibrosis And Dysfunction, Zheng Xu, Chunpeng Zou, Weihui Yu, Sujing Xu, Lan Huang, Zia Khan, Jingying Wang, Guang Liang

Paediatrics Publications

Background and Purpose: Hypertension adversely affects the kidney and is the second leading cause of kidney failure. Overproduction of angiotensin II greatly contributes to the progression of hypertensive kidney disease. Angiotensin II has recently been shown to activate STAT3 in cardiovascular cells. However, the underlying mechanisms of STAT3 activation by angiotensin II and downstream functional consequences in the kidneys are not fully understood. Experimental Approach: C57BL/6 mice were treated with angiotensin II by subcutaneous infusion for 1 month to develop nephropathy. Mice were treated with either adeno-associated virus expressing STAT3 shRNA or STAT3 inhibitor, S3I-201. Human archival kidney samples from …

Blockade Of Myeloid Differentiation 2 Attenuates Diabetic Nephropathy By Reducing Activation Of The Renin-Angiotensin System In Mouse Kidneys, Yi Wang, Qilu Fang, Yiyi Jin, Zhoudi Liu, Chunpeng Zou, Weihui Yu, Weixin Li, Xiaoou Shan

Paediatrics Publications

Background and Purpose: Both innate immunity and the renin-angiotensin system (RAS) play important roles in the pathogenesis of diabetic nephropathy (DN). Myeloid differentiation factor 2 (MD2) is a co-receptor of toll-like receptor 4 (TLR4) in innate immunity. While TLR4 is involved in the development of DN, the role of MD2 in DN has not been characterized. It also remains unclear whether the MD2/TLR4 signalling pathway is associated with RAS activation in diabetes. Experimental Approach: MD2 was blocked using siRNA or the low MW inhibitor, L6H9, in renal proximal tubular cells (NRK-52E cells) exposed to high concentrations of glucose (HG). In …

Chromium: Rise And Shine In Peritoneal Dialysis Patients?, Guido Filler, Christopher Mcintyre

Paediatrics Publications

Some trace elements are altered with chronic kidney disease. Selenium, zinc, and manganese tend to be wasted, and there is growing evidence that selenium deficiency is associated with mortality on dialysis. Other trace elements accumulate, such as chromium, cobalt, lead, molybdenum, and vanadium. The highest chromium levels are found in dialysis patients. The dialysis modality may further affect these levels, especially in hemodialysis patients, where even small contaminations in the dialysis feed water may lead to a concentration gradient that increases the concentration of certain trace elements. Chromium levels in peritoneal dialysis (PD) patients have been understudied. A single cross-sectional …