Medical Specialties Commons^™

Myocardial Infarction In Neonatal Mice, A Model Of Cardiac Regeneration, Jessica N. Blom, Xiangru Lu, Paul Arnold, Qingping Feng

Paediatrics Publications

Myocardial infarction induced by coronary artery ligation has been used in many animal models as a tool to study the mechanisms of cardiac repair and regeneration, and to define new targets for therapeutics. For decades, models of complete heart regeneration existed in amphibians and fish, but a mammalian counterpart was not available. The recent discovery of a postnatal window during which mice possess regenerative capabilities has led to the establishment of a mammalian model of cardiac regeneration. A surgical model of mammalian cardiac regeneration in the neonatal mouse is presented herein. Briefly, postnatal day 1 (P1) mice are anesthetized by …

Recovery Of Sleep Or Recovery Of Self? A Grounded Theory Study Of Residents' Decision Making Regarding How To Spend Their Nonclinical Postcall Time, Taryn S. Taylor, Jeff Nisker, Pim W. Teunissen, Tim Dornan, Lorelei Lingard

Paediatrics Publications

Purpose As resident work hours policies evolve, residents' off-duty time remains poorly understood. Despite assumptions about how residents should be using their postcall, off-duty time, there is little research on how residents actually use this time and the reasoning underpinning their activities. This study sought to understand residents' nonclinical postcall activities when they leave the hospital, their decision-making processes, and their perspectives on the relationship between these activities and their well-being or recovery. Method The study took place at a Liaison Committee on Medical Education-accredited Canadian medical school from 2012 to 2014. The authors recruited a purposive and convenience sample …

Cardiac Acetylcholine Inhibits Ventricular Remodeling And Dysfunction Under Pathologic Conditions, Ashbeel Roy, Mouhamed Dakroub, Geisa C.S.V. Tezini, Yin Liu, Silvia Guatimosim, Qingping Feng, Helio C. Salgado, Vania F. Prado, Marco A.M. Prado, Robert Gros

Paediatrics Publications

Autonomic dysfunction is a characteristic of cardiac disease and decreased vagal activity is observed in heart failure. Rodent cardiomyocytes produce de novo ACh, which is critical in maintaining cardiac homeostasis. We report that this nonneuronal cholinergic system is also found in human cardiomyocytes, which expressed choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter (VAChT). Furthermore, VAChT expression was increased 3- and 1.5-fold at the mRNA and protein level, respectively, in ventricular tissue from patients with heart failure, suggesting increased ACh secretion in disease. Weusedmicewith geneticdeletionof cardiomyocytespecificVAChTor ChATandmice overexpressingVAChT to test the functional significance of cholinergic signaling. Mice deficient for VAChT …

Rac1 Signaling Is Required For Anterior Second Heart Field Cellular Organization And Cardiac Outflow Tract Development, Carmen Leung, Yin Liu, Xiangru Lu, Mella Kim, Thomas A. Drysdale, Qingping Feng

Paediatrics Publications

Background-The small GTPase Rac1 regulates diverse cellular functions, including both apicobasal and planar cell polarity pathways; however, its role in cardiac outflow tract (OFT) development remains unknown. In the present study, we aimed to examine the role of Rac1 in the anterior second heart field (SHF) splanchnic mesoderm and subsequent OFT development during heart morphogenesis. Methods and Results-Using the Cre/loxP system, mice with an anterior SHF-specific deletion of Rac1 (Rac1SHF) were generated. Embryos were collected at various developmental time points for immunostaining and histological analysis. Intrauterine echocardiography was also performed to assess aortic valve blood flow in embryos at embryonic …

Is Testosterone Detrimental To Renal Function?, Guido Filler, Amanda Ramsaroop, Robert Stein, Claire Grant, Raanan Marants, Aaron So, Christopher Mcintyre

Paediatrics Publications

No abstract provided.

Rapid Fecal Calprotectin Testing To Assess For Endoscopic Disease Activity In Inflammatory Bowel Disease: A Diagnostic Cohort Study, Lukasz Kwapisz, Mahmoud Mosli, Nilesh Chande, Brian Yan, Melanie Beaton, Jessica Micsko, Pauline W. Mennill, William Barnett, Kevin Bax, Terry Ponich, John Howard, Anthony Tirolese, Robert Lannigan, James Gregor

Paediatrics Publications

Background and Aim: With increasing numbers of patients diagnosed with inflammatory bowel disease (IBD), it is important to identify noninvasive methods of detecting disease activity. The aim of this study is to examine the diagnostic accuracy of fecal rapid calprotectin (FC) testing in the detection of endoscopically active IBD. Patients and Methods: All consecutive patients presenting to outpatient clinics with lower gastrointestinal symptoms were prospectively recruited. Patients provided FC samples. Sensitivity (Sn), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) for FC were calculated. Receiver-operator characteristics (ROC) curve was used to identify the ideal FC cutoff that …

Quality Of Life In Children With Adverse Drug Reactions: A Narrative And Systematic Review, Blanca R. Del Pozzo-Magaña, Michael J. Rieder, Alejandro Lazo-Langner

Paediatrics Publications

Aims Adverse drug reactions are a common problem affecting adults and children. The economic impact of the adverse drug reactions has been widely evaluated; however, studies of the impact on the quality of life of children with adverse drug reactions are scarce. The aim was to evaluate studies assessing the health-related quality of life of children with adverse drug reactions. Methods We conducted a systematic review that included the following electronic databases: MEDLINE, EMBASE and the Cochrane Library (including the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Controlled Trials Register and the …

Using Simplified Blood Pressure Tables To Avoid Underdiagnosing Childhood Hypertension, Ajay P. Sharma, Javed Mohammed, Benson Thomas, Ram N. Singh, Guido Filler

Paediatrics Publications

Background: Recent studies have revealed that hypertension remains underdiagnosed in a significant number of children despite their recorded office blood pressure (OBP) exceeding the recommended fourth report OBP thresholds. Simplified OBP thresholds have been proposed to reduce this underdiagnosis of hypertension in children. In clinical practice, OBP screened as elevated according to the fourth report OBP thresholds are referred for ambulatory blood pressure (ABP) monitoring to rule out 'white coat' hypertension. Objectives: The present study tested the usefulness of simplified OBP thresholds to screen abnormal OBP for ABP monitoring referral. Methods: A total of 155 subjects were retrospectively analyzed with …

Retinoic Acid And The Development Of The Endoderm, Gregory M. Kelly, Thomas A. Drysdale

Paediatrics Publications

Retinoic acid (RA) is an important signaling molecule in the development of the endoderm and an important molecule in protocols used to generate endodermal cell types from stem cells. In this review, we describe the RA signaling pathway and its role in the patterning and specification of the extra embryonic endoderm and different endodermal organs. The formation of endoderm is an ancient evolutionary feature and RA signaling appears to have coevolved with the vertebrate lineage. Towards that end, we describe how RA participates in many regulatory networks required for the formation of extraembryonic structures as well as the organs of …

Pthrp-Related Hypercalcaemia In Infancy And Congenital Anomalies Of The Kidney And Urinary Tract (Cakut), Nardeen Kodous, Guido Filler, Ajay Parkash Sharma, Tamara Angela Van Hooren

Paediatrics Publications

BACKGROUND: Severe hypercalcaemia is a rare but clinically significant condition in infancy and childhood. Parathyroid hormone-related peptide (PTHrP)-mediated hypercalcaemia resulting from a malignancy is rare and only a handful of case reports have outlined its incidence alongside a benign condition.

OBJECTIVES: To describe the diagnostic workup and management of an infant with hypercalcaemia, renal dysplasia, and elevated PTHrP levels.

DESIGN: Case report.

SETTING: The Victoria Hospital campus of the London Health Sciences Centre in London, Ontario, Canada.

PATIENTS: A child with congenital anomalies of the kidneys and urinary tract (CAKUT), stage 2 chronic kidney disease (CKD), and renal dysplasia who …

Evidence-Based Recommendations For Genetic Diagnosis Of Familial Mediterranean Fever, Gabriella Giancane, Nienke M.Ter Haar, Nico Wulffraat, Sebastiaan J. Vastert, Karyl Barron, Veronique Hentgen, Tilmann Kallinich, Huri Ozdogan, Jordi Anton, Paul Brogan, Luca Cantarini, Joost Frenkel, Caroline Galeotti, Marco Gattorno, Gilles Grateau, Michael Hofer, Isabelle Kone-Paut, Jasmin Kuemmerle-Deschner, Helen J. Lachmann, Anna Simon, Erkan Demirkaya, Brian Feldman, Yosef Uziel, Seza Ozen

Paediatrics Publications

Familial Mediterranean fever (FMF) is a disease of early onset which can lead to significant morbidity. In 2012, Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched with the aim of optimising and disseminating diagnostic and management regimens for children and young adults with rheumatic diseases. The objective was to establish recommendations for FMF focusing on provision of diagnostic tools for inexperienced clinicians particularly regarding interpretation of MEFV mutations. Evidencebased recommendations were developed using the European League against Rheumatism standard operating procedure. An expert committee of paediatric rheumatologists defined search terms for the systematic literature review. …

Modulation Of Type Ii Tgf-Β Receptor Degradation By Integrin-Linked Kinase, Linda Vi, Stellar Boo, Samar Sayedyahossein, Randeep K. Singh, Sarah Mclean, Gianni M. Di Guglielmo, Lina Dagnino

Paediatrics Publications

Cutaneous responses to injury, infection, and tumor formation involve the activation of resident dermal fibroblasts and subsequent transition to myofibroblasts. The key for induction of myofibroblast differentiation is the activation of transforming growth factor-β (TGF-β) receptors and stimulation of integrins and their associated proteins, including integrin-linked kinase (ILK). Cross-talk processes between TGF-β and ILK are crucial for myofibroblast formation, as ILK-deficient dermal fibroblasts exhibit impaired responses to TGF-β receptor stimulation. We now show that ILK associates with type II TGF-β receptors (TβRII) in ligand- and receptor kinase activity-independent manners. In cells with targeted Ilk gene inactivation, cellular levels of TβRII …

Understanding Early Organogenesis Using A Simplified In Situ Hybridization Protocol In Xenopus, Steven J. Deimling, Rami R. Halabi, Stephanie A. Grover, Jean H. Wang, Thomas A. Drysdale

Paediatrics Publications

Organogenesis is the study of how organs are specified and then acquire their specific shape and functions during development. The Xenopuslaevis embryo is very useful for studying organogenesis because their large size makes them very suitable for identifying organs at the earliest steps in organogenesis. At this time, the primary method used for identifying a specific organ or primordium is whole mount in situ hybridization with labeled antisense RNA probes specific to a gene that is expressed in the organ of interest. In addition, it is relatively easy to manipulate genes or signaling pathways in Xenopus and in situ hybridization …

Nfkb1 Activation By The E26 Transformation-Specific Transcription Factors Pu.1 And Spi-B Promotes Toll-Like Receptor-Mediated Splenic B Cell Proliferation, Stephen K.H. Li, Ali K. Abbas, Lauren A. Solomon, Gaëlle M.N. Groux, Rodney P. Dekoter

Paediatrics Publications

Generation of antibodies against T-independent and T-dependent antigens requires Toll-like receptor (TLR) engagement on B cells for efficient responses. However, the regulation of TLR expression and responses in B cells is not well understood. PU.1 and Spi-B (encoded by Sfpi1 and Spib, respectively) are transcription factors of the E26 transformation-specific (ETS) family and are important for B cell development and function. It was found that B cells from mice knocked out for Spi-B and heterozygous for PU.1 (Sfpi1^+/- Spib^-/- [PUB] mice) proliferated poorly in response to TLR ligands compared to wild-type (WT) B cells. The NF-κB family member …

Estimation Of Gfr Using Β-Trace Protein In Children, Samantha H. Witzel, Shih Han S. Huang, Branko Braam, Guido Filler

Paediatrics Publications

Background and objectives Sexmay affect the performance of smallmolecularweight proteins as markers of GFR because of differences in fat mass between the two sexes. The hypothesis was that the diagnostic performance of b-trace protein, a novel marker of GFR, would be significantly better in boys than in girls. Design, setting, participants, & measurements GFR, height, weight, serum creatinine, and β-trace protein were measured in 755 children and adolescents (331 girls) undergoing 99technetium diethylenetriamine penta–acetic acid renal scans from July of 1999 to July of 2006. Boys and girls were separated into formula generation cohorts (284 boys and 220 girls) and …

Low Birth Weight Followed By Postnatal Over-Nutrition In The Guinea Pig Exposes A Predominant Player In The Development Of Vascular Dysfunction., Jennifer A Thompson, Ousseynou Sarr, Karolina Piorkowska, Robert Gros, Timothy Regnault

Paediatrics Publications

The association between intrauterine growth restriction (IUGR) and hypertension is well established, yet the interaction between IUGR and other pathogenic contributors remains ill-defined. This study examined the independent and interactive effects of fetal growth reduction resulting in low birth weight (LBW), and postnatal Western diet (WD) on vascular function. Growth reduction was induced in pregnant guinea pigs by uterine artery ablation. LBW and normal birth weight (NBW) offspring were randomly assigned to a control diet (CD) or a WD. In young adulthood, length-tension curves were generated in aortic rings and responses to methacholine (MCh) were evaluated in the carotid and …

The Health Initiative Program For Kids (Hip Kids): Effects Of A 1-Year Multidisciplinary Lifestyle Intervention On Adiposity And Quality Of Life In Obese Children And Adolescents -- A Longitudinal Pilot Intervention Study, Dirk E. Bock, Tracy Robinson, Jamie A Seabrook, Meghan Rombeek, Kambiz Norozi, Guido Filler, Ralf Rauch, Cheril L Clarson

Paediatrics Publications

BACKGROUND: Though recent data suggest that multidisciplinary outpatient interventions can have a positive effect on childhood obesity, it is still unclear which program components are most beneficial and how they affect quality of life (QoL). The aim of this study was to determine if a 1-year multidisciplinary, family-centered outpatient intervention based on social cognitive theory would be effective in (i) preventing further increases in BMI and BMI z-score, and (ii) improving QoL in obese children and adolescents.

METHODS: Obese children and adolescents 8-17 years of age and their families participated in this 1-year longitudinal pilot intervention study. The intervention consisted …

Propranolol Therapy For Infantile Hemangioma Is Less Toxic But Longer In Duration Than Corticosteroid Therapy, Kathryn Sawa, Arjang Yazdani, Michael J. Rieder, Guido Filler

Paediatrics Publications

BACKGROUND: Infantile hemangioma is the most common benign, self-limiting tumour of childhood. Treatment is reserved for hemangiomas that obstruct vital structures or cause significant disfigurement. Traditionally, corticosteroids have been the medical treatment of choice. Since 2008, however, propranolol has been rapidly adopted as an effective pharmacological treatment for infantile hemangioma. Published data regarding the long-term side effects of propranolol are currently lacking. OBJECTIVE: To describe the long-term effects of propranolol and corticosteroids on anthropometric measurements (height, body mass index [BMI]) and blood pressure in children. METHODS: A prospective database analysis of all infantile hemangioma patient visits to the pediatric vascular …

Atrx Is Required For Maintenance Of The Neuroprogenitor Cell Pool In The Embryonic Mouse Brain, Kieran Ritchie, L Ashley Watson, Benjamin Davidson, Yan Jiang, Nathalie G. Bérubé

Paediatrics Publications

Mutations in the alpha-thalassemia mental retardation X-linked (ATRX) gene cause a spectrum of abnormalities including intellectual disability, developmental delay, seizures, and microcephaly. The ATRX protein is highly enriched at heterochromatic repetitive sequences adjacent to the centromere, and ATRX depletion results in chromosome congression, segregation, and cohesion defects. Here, we show that Cre-mediated inactivation of Atrx in the embryonic mouse (Mus musculus) brain results in expansion of cerebral cortical layer VI, and a concurrent thinning of layers II-IV. We observed increased cell cycle exit during early-mid neurogenesis, and a depletion of apical progenitors by late neurogenesis in the Atrx-null neocortex, explaining …

Analysis Of Neonatal Brain Lacking Atrx Or Mecp2 Reveals Changes In Nucleosome Density, Ctcf Binding And Chromatin Looping, Kristin D Kernohan, Douglas Vernimmen, Gregory B Gloor, Nathalie G. Bérubé

Paediatrics Publications

ATRX and MeCP2 belong to an expanding group of chromatin-associated proteins implicated in human neurodevelopmental disorders, although their gene-regulatory activities are not fully resolved. Loss of ATRX prevents full repression of an imprinted gene network in the postnatal brain and in this study we address the mechanistic aspects of this regulation. We show that ATRX binds many imprinted domains individually but that transient co-localization between imprinted domains in the nuclei of neurons does not require ATRX. We demonstrate that MeCP2 is required for ATRX recruitment and that deficiency of either ATRX or MeCP2 causes decreased frequency of long-range chromatin interactions …

Three Dimensional Dual Labelled Dna Fluorescent In Situ Hybridization Analysis In Fixed Tissue Sections, Kristin D Kernohan, Nathalie G. Bérubé

Paediatrics Publications

Emerging studies demonstrate that three-dimensional organization of chromatin in the nucleus plays a vital role in regulating the genome. DNA fluorescent in situ hybridization (FISH) is a common molecular technique used to visualize the location of DNA sequences. The vast majority of DNA FISH studies are conducted on cultured cells due to the technical difficulties encountered using fixed tissue sections. However, the use of cultured cells poses important limitations that could yield misleading results, making in vivo analysis a far superior approach. Here we present a protocol for multiplexed three dimensional DNA FISH in mouse brain sections, which is also …

Choline Kinase Beta Is Required For Normal Endochondral Bone Formation, Zhuo Li, Gengshu Wu, Roger B. Sher, Zohreh Khavandgar, Martin Hermansson, Gregory A. Cox, Michael R. Doschak, Monzur Murshed, Frank Beier, Dennis E. Vance

Paediatrics Publications

Background Choline kinase has three isoforms encoded by the genes Chka and Chkb. Inactivation of Chka in mice results in embryonic lethality, whereas Chkb-/- mice display neonatal forelimb bone deformations. Methods To understand the mechanisms underlying the bone deformations, we compared the biology and biochemistry of bone formation from embryonic to young adult wild-type (WT) and Chkb-/- mice. Results The deformations are specific to the radius and ulna during the late embryonic stage. The radius and ulna of Chkb-/- mice display expanded hypertrophic zones, unorganized proliferative columns in their growth plates, and delayed formation of primary ossification centers. The differentiation …

The Role Of The Insula In Speech And Language Processing, Anna Oh, Emma G. Duerden, Elizabeth W. Pang

Paediatrics Publications

Lesion and neuroimaging studies indicate that the insula mediates motor aspects of speech production, specifically, articulatory control. Although it has direct connections to Broca's area, the canonical speech production region, the insula is also broadly connected with other speech and language centres, and may play a role in coordinating higher-order cognitive aspects of speech and language production. The extent of the insula's involvement in speech and language processing was assessed using the Activation Likelihood Estimation (ALE) method. Meta-analyses of 42 fMRI studies with healthy adults were performed, comparing insula activation during performance of language (expressive and receptive) and speech (production …

Measuring Physicians' Productivity: A Three-Year Study To Evaluate A New Remuneration System, Guido Filler, Vanessa Burkoski, Gary Tithecott

Paediatrics Publications

PURPOSE: To evaluate a new assessment tool measuring physicians' academic productivity and its use in a performance-based remuneration system. METHOD: The authors developed an assessment tool based on existing tools to measure productivity. Yearly, from 2008 to 2011, physicians at the University of Western Ontario received a score of up to three points for each of four components (impact, application, scholarly activity, mentorship) in each of four domains (clinical practice, education, research, administration). Scores were weighted by the percentage of time physicians spent on tasks in each domain. Year 1 scores were a baseline. In Years 2 and 3, scores …

Diagnosis By Peritoneal Scintigraphy Of Peritoneal Dialysis–Associated Hydrothorax In An Infant, M. Chavannes, A. P. Sharma, R. N. Singh, R. H. Reid, G. Filler

Paediatrics Publications

No abstract provided.

Chronic Abdominal Pain & Colonic Non-Fixation Case Report, Brett Howe, Andreana Butter

Paediatrics Publications

Abnormalities of intestinal rotation and fixation occur in one out of 500 live births and usually present within the first month of life. We report a case of a 14-year-old girl with lifelong, chronic abdominal pain. Despite treatment by multiple specialists and psychiatrists, her pain remained severe. A barium enema revealed that her left colon was located along her right paracolic gutter, suggesting a form of malrotation/ non-fixation. Laparoscopy, followed by laparotomy, demonstrated a complete lack of fixation of her entire colon. Due to the mobility of the colon, as well as its redundant mesentery, her entire small bowel was …

Low Birth Weight Male Guinea Pig Offspring Display Increased Visceral Adiposity In Early Adulthood., Ousseynou Sarr, Jennifer A Thompson, Lin Zhao, Ting-Yim Lee, Timothy Regnault

Paediatrics Publications

Uteroplacental insufficiency (UPI)-induced intrauterine growth restriction (IUGR) predisposes individuals to adult visceral obesity. We postulated that low birth weight (LBW) offspring, from UPI-induced IUGR pregnancies, would display a visceral adipose lipogenic molecular signature involving altered gene expression, phosphorylation status of proteins of the lipid synthesis pathway and microRNA (miR) expression profile, occurring in association with increased visceral adiposity. Normal birth weight (NBW) and LBW (obtained by uterine artery ablation) male guinea pig pups were fed a control diet from weaning to 145 days and sacrificed. Despite being lighter at birth, LBW pups displayed body weights similar to NBW offspring at …

Loss Of Atrx Does Not Confer Susceptibility To Osteoarthritis, Lauren A. Solomon, Bailey A. Russell, David Makar, Nathalie G. Bérubé, Frank Beier

Paediatrics Publications

The chromatin remodelling protein ATRX is associated with the rare genetic disorder ATR-X syndrome. This syndrome includes developmental delay, cognitive impairment, and a variety of skeletal deformities. ATRX plays a role in several basic chromatin-mediated cellular events including DNA replication, telomere stability, gene transcription, and chromosome congression and cohesion during cell division. We have used a loss-of-function approach to directly investigate the role of Atrx in the adult skeleton in three different models of selective Atrx loss. We specifically targeted deletion of Atrx to the forelimb mesenchyme, to cartilage and to bone-forming osteoblasts. We previously demonstrated that loss of ATRX …

The Centre Of The Brain: Topographical Model Of Motor, Cognitive, Affective, And Somatosensory Functions Of The Basal Ganglia, Marie Arsalidou, Emma G. Duerden, Margot J. Taylor

Paediatrics Publications

The basal ganglia have traditionally been viewed as motor processing nuclei; however, functional neuroimaging evidence has implicated these structures in more complex cognitive and affective processes that are fundamental for a range of human activities. Using quantitative meta-analysis methods we assessed the functional subdivisions of basal ganglia nuclei in relation to motor (body and eye movements), cognitive (working-memory and executive), affective (emotion and reward) and somatosensory functions in healthy participants. We document affective processes in the anterior parts of the caudate head with the most overlap within the left hemisphere. Cognitive processes showed the most widespread response, whereas motor processes …

Techniques For The Isolation Of High-Quality Rna From Cells Encapsulated In Chitosan Hydrogels, Claire Yu, Stuart Young, Valerio Russo, Brian G. Amsden, Lauren E. Flynn

Paediatrics Publications

Extracting high-quality RNA from hydrogels containing polysaccharide components is challenging, as traditional RNA isolation techniques designed for cells and tissues can have limited yields and purity due to physiochemical interactions between the nucleic acids and the biomaterials. In this study, a comparative analysis of several different RNA isolation methods was performed on human adipose-derived stem cells photo-encapsulated within methacrylated glycol chitosan hydrogels. The results demonstrated that RNA isolation methods with cetyl trimethylammonium bromide (CTAB) buffer followed by purification with an RNeasy® mini kit resulted in low yields of RNA, except when the samples were preminced directly within the buffer. In …