Digital Commons Network^™

Improving Learning And Confidence Through Small Group, Structured Otoscopy Teaching: A Prospective Interventional Study, Peng You, Saad Chahine, Murad Husein

Paediatrics Publications

Background: Otologic diseases are common and associated with significant health care costs. While accurate diagnosis relies on physical exam, existing studies have highlighted a lack of comfort among trainees with regards to otoscopy. As such, dedicated otoscopy teaching time was incorporated into the undergraduate medical curriculum in the form of a small group teaching session. In this study, we aimed to examine the effect of a small-group, structured teaching session on medical students' confidence with and learning of otoscopic examination. Methods: Using a prospective study design, an otolaryngologist delivered an one-hour, small group workshop to medical learners. The workshop included …

Pharmacogenomics Guided-Personalization Of Warfarin And Tamoxifen, Theodore J. Wigle, Laura E. Jansen, Wendy A. Teft, Richard B. Kim

Paediatrics Publications

The use of pharmacogenomics to personalize drug therapy has been a long-sought goal for warfarin and tamoxifen. However, conflicting evidence has created reason for hesitation in recommending pharmacogenomics-guided care for both drugs. This review will provide a summary of the evidence to date on the association between cytochrome P450 enzymes and the clinical end points of warfarin and tamoxifen therapy. Further, highlighting the clinical experiences that we have gained over the past ten years of running a personalized medicine program, we will offer our perspectives on the utility and the limitations of pharmacogenomics-guided care for warfarin and tamoxifen therapy.

Snapshot: Lysine Methylation Beyond Histones, Kyle K. Biggar, Zhentian Wang, Shawn S.C. Li

Paediatrics Publications

Lysine methylation is a prevalent post-translational modification (PTM) used by the cell to reversibly regulate protein function. Although it has been extensively studied in the context of histones and the associated chromatin, the remaining methyllysine proteome remains largely unexplored. This SnapShot provides an overview of the current state of lysine methylation research and its emergence as a dynamic PTM occurring on histone and non-histone proteins. Lysine methylation is a prevalent post-translational modification (PTM) used by the cell to reversibly regulate protein function. Although it has been extensively studied in the context of histones and the associated chromatin, the remaining methyllysine …

Bone Marrow Myeloid Cells Regulate Myeloid-Biased Hematopoietic Stem Cells Via A Histamine-Dependent Feedback Loop, Xiaowei Chen, Huan Deng, Michael J. Churchill, Larry L. Luchsinger, Xing Du, Timothy H. Chu, Richard A. Friedman, Moritz Middelhoff, Hongxu Ding, Yagnesh H. Tailor, Alexander L.E. Wang, Haibo Liu, Zhengchuan Niu, Hongshan Wang, Zhenyu Jiang, Simon Renders, Siu Hong Ho, Spandan V. Shah, Pavel Tishchenko, Wenju Chang, Theresa C. Swayne, Laura Munteanu, Andrea Califano, Ryota Takahashi, Karan K. Nagar, Bernhard W. Renz, Daniel L. Worthley, C. Benedikt Westphalen, Yoku Hayakawa

Paediatrics Publications

Myeloid-biased hematopoietic stem cells (MB-HSCs) play critical roles in recovery from injury, but little is known about how they are regulated within the bone marrow niche. Here we describe an auto-/paracrine physiologic circuit that controls quiescence of MB-HSCs and hematopoietic progenitors marked by histidine decarboxylase (Hdc). Committed Hdc+ myeloid cells lie in close anatomical proximity to MB-HSCs and produce histamine, which activates the H2 receptor on MB-HSCs to promote their quiescence and self-renewal. Depleting histamine-producing cells enforces cell cycle entry, induces loss of serial transplant capacity, and sensitizes animals to chemotherapeutic injury. Increasing demand for myeloid cells via lipopolysaccharide (LPS) …

Correlates Of Poor Mental Health In Early Pregnancy In Obese European Women, Matteo C. Sattler, Judith G.M. Jelsma, Annick Bogaerts, David Simmons, Gernot Desoye, Rosa Corcoy, Juan M. Adelantado, Alexandra Kautzky-Willer

Paediatrics Publications

Background: Depression during pregnancy is associated with higher maternal morbidity and mortality, and subsequent possible adverse effects on the cognitive, emotional and behavioral development of the child. The aim of the study was to identify maternal characteristics associated with poor mental health, in a group of overweight/obese pregnant women in nine European countries, and thus, to contribute to better recognition and intervention for maternal depression. Methods: In this cross-sectional observational study, baseline data from early pregnancy (< 20 weeks) of the DALI (Vitamin D and Lifestyle Intervention for gestational diabetes mellitus prevention) study were analyzed. Maternal mental health was assessed with the World Health Organization Well-Being Index (WHO-5). Women were classified as having a low (WHO-5 ≤ 50) or high wellbeing. Results.: A total of 735 pregnant women were included. The prevalence of having a low wellbeing was 27.2%, 95% CI [24.0, 30.4]. Multivariate analysis showed independent associations between low wellbeing and European ethnicity, OR = .44, 95% CI [.25,.77], shift work, OR = 1.81, 95% CI [1.11, 2.93], insufficient sleep, OR = 3.30, 95% CI [1.96, 5.55], self-efficacy, OR = .95, 95% CI [.92,.98], social support, OR = .94, 95% CI [.90,.99], and pregnancy-related worries (socioeconomic: OR = 1.08, 95% CI [1.02, 1.15]; health: OR = 1.06, 95% CI [1.01, 1.11]; relationship: OR = 1.17, 95% CI [1.05, 1.31]). Conclusions: Mental health problems are common in European overweight/obese pregnant women. The identified correlates might help in early recognition and subsequent treatment of poor mental health problems during pregnancy. This is important to reduce the unfavorable effects of poor mental health on pregnancy outcomes. Trial registration:ISRCTN70595832 , 02.12.2011.

Oxytocin Receptor Polymorphisms Are Differentially Associated With Social Abilities Across Neurodevelopmental Disorders, Danielle A. Baribeau, Annie Dupuis, Tara A. Paton, Stephen W. Scherer, Russell J. Schachar, Paul D. Arnold, Peter Szatmari, Rob Nicolson, Stelios Emsley, Tim Lynch, Ahmed Mater, Suzanne Schuh, Maggie Rumantir, Stephen B. Freedman

Paediatrics Publications

Oxytocin is a pituitary neuropeptide that affects social behaviour. Single nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR) have been shown to explain some variability in social abilities in control populations. Whether these variants similarly contribute to the severity of social deficits experienced by children with neurodevelopmental disorders is unclear. Social abilities were assessed in a group of children with autism spectrum disorder (ASD, n = 341) or attention deficit hyperactivity disorder (ADHD, n = 276) using two established social measures. Scores were compared by OXTR genotype (rs53576, rs237887, rs13316193, rs2254298). Unexpectedly, the two most frequently studied OXTR SNPs …

Variable Phenotype Expression In A Family Segregating Microdeletions Of The Nrxn1 And Mbd5 Autism Spectrum Disorder Susceptibility Genes, Marc Woodbury-Smith, Rob Nicolson, Mehdi Zarrei, Ryan K.C. Yuen, Susan Walker, Jennifer Howe, Mohammed Uddin, Ny Hoang

Paediatrics Publications

Autism spectrum disorder is a developmental condition of early childhood onset, which impacts socio-communicative functioning and is principally genetic in etiology. Currently, more than 50 genomic loci are deemed to be associated with susceptibility to autism spectrum disorder, showing de novo and inherited unbalanced copy number variants and smaller insertions and deletions (indels), more complex structural variants, as well as single-nucleotide variants deemed of pathological significance. However, the phenotypes associated with many of these genes are variable, and penetrance is largely unelaborated in clinical descriptions. This case report describes a family harboring two copy number variant microdeletions, which affect regions …

Non-Pathological Bilious Vomiting Complicating Therapeutic Hypothermia For Hypoxic Ischaemic Encephalopathy In Neonates: A Retrospective Cohort Study, Julie Hukui, Sarah Jones, Kevin Coughlin, Simon Levin, Jennifer Ruth Foster

Paediatrics Publications

Objective Therapeutic hypothermia (TH) for moderate-to-severe neonatal hypoxic ischaemic encephalopathy (HIE) is generally described as safe. We performed this study to determine the incidence of bilious vomiting or bilious drainage (BVD) attributable to TH in this population. Design A single-centre, retrospective cohort study. Setting Neonatal and paediatric intensive care units (NICU and PICU) of a single tertiary care centre. Patients All newborns with HIE who met criteria for TH between 2009 and 2014. Interventions Cases were matched 1:1 for unit of care (NICU vs PICU), gestational age, gender, and Sarnat score with historic controls who did not receive TH. Groups …

Fatigue In Residency Education: Understanding The Influence Of Work Hours Regulations In Europe, Taryn S. Taylor, Pim W. Teunissen, Tim Dornan, Lorelei Lingard

Paediatrics Publications

Purpose Although one proposed solution to the problem of fatigued medical trainees is the implementation of work hours regulations, concerns about the effectiveness of these regulations are growing. Canada remains one of the few Western jurisdictions without legislated regulation. Recent research suggests that fatigue is a complex social construct, rather than simply a lack of sleep; thus, the authors explored how regulations and fatigue are understood in countries with established work hours frameworks to better inform other jurisdictions looking to address trainee fatigue. Method Using constructivist grounded theory methodology, the authors conducted individual, semistructured interviews in 2015-2016 with 13 postgraduate …

Ifpa Meeting 2016 Workshop Report I: Genomic Communication, Bioinformatics, Trophoblast Biology And Transport Systems, Christiane Albrecht, Julie C. Baker, Cassidy Blundell, Shawn L. Chavez, Lucia Carbone, Larry Chamley, Roberta L. Hannibal, Nick Illsley

Paediatrics Publications

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2016 there were twelve themed workshops, four of which are summarized in this report. These workshops covered innovative technologies applied to new and traditional areas of placental research: 1) genomic communication; 2) bioinformatics; 3) trophoblast biology and pathology; 4) placental transport systems.

Patient Characteristics, Length Of Stay, And Functional Improvement For Schizophrenia Spectrum Disorders: A Population Study Of Inpatient Care In Ontario 2005 To 2015, Sheng Chen, April Collins, Kelly Anderson, Kwame Mckenzie, Sean Kidd

Paediatrics Publications

Objectives: Schizophrenia and associated illnesses account for a large proportion of mental illness burden and health care expenditures, with the majority of expense involving inpatient care. To date, the literature exploring factors associated with length of stay (LOS) and functional improvement during inpatient care is underdeveloped. In response, this study examined the association between patient characteristics, LOS, and functional improvement using Ontario Mental Health Reporting System (OMHRS) data from 2005 to 2015. Methods: The associations of patient characteristics (including key demographics, psychosocial variables, reasons for admission, and service use history) and 2 outcome measures (LOS and Global Assessment of Functioning …

Treatment With Aicar Inhibits Blastocyst Development, Trophectodermdifferentiation And Tight Junction Formation And Function In Mice, Michele D. Calder, Nicole A. Edwards, Dean H. Betts, Andrew J. Watson

Paediatrics Publications

STUDY QUESTION: What is the impact of adenosine monophosphate-activated protein kinase (AMPK) activation on blastocyst formation, gene expression, and tight junction formation and function? SUMMARY ANSWER: AMPK activity must be tightly controlled for normal preimplantation development and blastocyst formation to occur. WHAT IS KNOWN ALREADY: AMPK isoforms are detectable in oocytes, cumulus cells and preimplantation embryos. Cultured embryos are subject to many stresses that can activate AMPK. STUDY DESIGN, SIZE, DURATION: Two primary experiments were carried out to determine the effect of AICAR treatment on embryo development and maintenance of the blastocoel cavity. Embryos were recovered from superovulated mice. First, …

Appendectomy Versus Non-Operative Treatment For Acute Uncomplicated Appendicitis In Children: Study Protocol For A Multicentre, Open-Label, Non-Inferiority, Randomised Controlled Trial, Nigel J. Hall, Simon Eaton, Olivier Abbo, Alexis P. Arnaud, Marianne Beaudin, Mary Brindle, Andreana Bütter, Dafydd Davies, Tim Jancelewicz, Kathy Johnson, Richard Keijzer, Eveline Lapidus-Krol, Martin Offringa, Nelson Piché, Risto Rintala, Erik Skarsgard, Jan F. Svensson, Wendy J. Ungar, Tomas Wester, Andrew R. Willan, Augusto Zani, Shawn D. St Peter, Agostino Pierro

Paediatrics Publications

Background Appendectomy is considered the gold standard treatment for acute appendicitis. Recently the need for surgery has been challenged in both adults and children. In children there is growing clinician, patient and parental interest in non-operative treatment of acute appendicitis with antibiotics as opposed to surgery. To date no multicentre randomised controlled trials that are appropriately powered to determine efficacy of nonoperative treatment (antibiotics) for acute appendicitis in children compared with surgery (appendectomy) have been performed. Methods Multicentre, international, randomised controlled trial with a non-inferiority design. Children (age 5–16 years) with a clinical and/or radiological diagnosis of acute uncomplicated appendicitis …

Epigenetic Etiology Of Intellectual Disability., Shigeki Iwase, Nathalie G Bérubé, Zhaolan Zhou, Nael Nadif Kasri, Elena Battaglioli, Marilyn Scandaglia, Angel Barco

Paediatrics Publications

Intellectual disability (ID) is a prevailing neurodevelopmental condition associated with impaired cognitive and adaptive behaviors. Many chromatin-modifying enzymes and other epigenetic regulators have been genetically associated with ID disorders (IDDs). Here we review how alterations in the function of histone modifiers, chromatin remodelers, and methyl-DNA binding proteins contribute to neurodevelopmental defects and altered brain plasticity. We also discuss how progress in human genetics has led to the generation of mouse models that unveil the molecular etiology of ID, and outline the direction in which this field is moving to identify therapeutic strategies for IDDs. Importantly, because the chromatin regulators linked …

Parent Cardiac Response In The Context Of Their Child’S Completion Of The Cold Pressor Task: A Pilot Study, Kaytlin Constantin, Rachel L. Moline, C. Meghan Mcmurtry, Heidi N. Bailey

Paediatrics Publications

Parents’ ability to regulate their emotions is essential to providing supportive caregiving behaviours when their child is in pain. Extant research focuses on parent self-reported experience or observable behavioural responses. Physiological responding, such as heart rate (HR) and heart rate variability (HRV), is critical to the experience and regulation of emotions and provides a complementary perspective on parent experience; yet, it is scarcely assessed. This pilot study examined parent (n = 25) cardiac response (HR, HRV) at rest (neutral film clip), immediately before the cold pressor task (pre-CPT), and following the CPT (post-CPT). Further, variables that may influence changes in …

Correction: Sequence Homology At The Breakpoint And Clinical Phenotype Of Mitochondrial Dna Deletion Syndromes (Plos One (2010) 5:12 (E15687) Doi: 10.1371/Journal.Pone.0015687), Bekim Sadikovic, Jing Wang, Ayman W. El-Hattab, Megan Landsverk, Ganka Douglas, Ellen K. Brundage, William J. Craigen, Eric S. Schmitt, Lee Jun C. Wong

Paediatrics Publications

The middle initial of the third author is missing. The third author’s complete name is: Ayman W. El-Hattab. The correct citation is: Sadikovic B, Wang J, El-Hattab AW, Landsverk M, Douglas G, Brundage EK, et al. (2010) Sequence Homology at the Breakpoint and Clinical Phenotype of Mitochondrial DNA Deletion Syndromes. PLoS ONE 5(12): e15687. https://doi.org/10.1371/journal.pone.0015687.

Exercise And Pregnancy In Recreational And Elite Athletes: 2016/17 Evidence Summary From The Ioc Expert Group Meeting, Lausanne. Part 3 - Exercise In The Postpartum Period, Kari Bø, Raul Artal, Ruben Barakat, Wendy J. Brown, Gregory A.L. Davies, Michael Dooley, Kelly R. Evenson, Lene A.H. Haakstad, Bengt Pusic, Don Mcconnell, Cheri Nijssen-Jordan, Norm Silver, Brett Taylor, Ian G. Stiell

Paediatrics Publications

This is Part 3 in the series of reviews from the IOC expert committee on exercise and pregnancy in recreational and elite athletes. Part 1 focused on the effects of training during pregnancy and on the management of common pregnancy-related complaints experienced by athletes1; Part 2 addressed maternal and fetal perinatal outcomes.2 In this part, we review the implications of pregnancy and childbirth on return to exercise and on common illnesses and complaints in the postpartum period. The postpartum period can be divided into hospital-based (during hospital stay), immediate postpartum (hospital discharge to 6 weeks postpartum) and later postpartum (6 …

Canadian Guidelines For Controlled Pediatric Donation After Circulatory Determination Of Death-Summary Report, Matthew J Weiss, Laura Hornby, Bram Rochwerg, Michael Van Manen, Sonny Dhanani, V Ben Sivarajan, Amber Appleby, Mary Bennett, Daniel Buchman, Catherine Farrell, Aviva Goldberg, Rebecca Greenberg, Ram Singh, Thomas A Nakagawa, William Witteman, Jill Barter, Allon Beck, Kevin Coughlin, Alf Conradi, Cynthia Cupido, Rosanne Dawson, Anne Dipchand, Darren Freed, Karen Hornby, Valerie Langlois, Cheryl Mack, Meagan Mahoney, Deepak Manhas, Christopher Tomlinson, Samara Zavalkoff, Sam D Shemie

Paediatrics Publications

OBJECTIVES: Create trustworthy, rigorous, national clinical practice guidelines for the practice of pediatric donation after circulatory determination of death in Canada.

METHODS: We followed a process of clinical practice guideline development based on World Health Organization and Canadian Medical Association methods. This included application of Grading of Recommendations Assessment, Development, and Evaluation methodology. Questions requiring recommendations were generated based on 1) 2006 Canadian donation after circulatory determination of death guidelines (not pediatric specific), 2) a multidisciplinary symposium of national and international pediatric donation after circulatory determination of death leaders, and 3) a scoping review of the pediatric donation after circulatory …

Identification Of A Novel Synaptic Protein, Tmtc3, Involved In Periventricular Nodular Heterotopia With Intellectual Disability And Epilepsy, Sali M K Farhan, Kevin C J Nixon, Michelle Everest, Tara N Edwards, Shirley Long, Dmitri Segal, Maria J Knip, Heleen H Arts, Rana Chakrabarti, Jian Wang, John F Robinson, Donald Lee, Seyed M Mirsattari, C Anthony Rupar, Victoria M Siu, Forge Canada Consortium, Michael O Poulter, Robert A Hegele, Jamie M Kramer

Paediatrics Publications

Defects in neuronal migration cause brain malformations, which are associated with intellectual disability (ID) and epilepsy. Using exome sequencing, we identified compound heterozygous variants (p.Arg71His and p. Leu729ThrfsTer6) in TMTC3, encoding transmembrane and tetratricopeptide repeat containing 3, in four siblings with nocturnal seizures and ID. Three of the four siblings have periventricular nodular heterotopia (PVNH), a common brain malformation caused by failure of neurons to migrate from the ventricular zone to the cortex. Expression analysis using patient-derived cells confirmed reduced TMTC3 transcript levels and loss of the TMTC3 protein compared to parental and control cells. As TMTC3 function is currently …

Disparities In Rate, Triggers, And Management In Pediatric And Adult Cases Of Suspected Drug-Induced Anaphylaxis In Canada, Sofianne Gabrielli, Ann E Clarke, Harley Eisman, Judy Morris, Lawrence Joseph, Sebastien La Vieille, Peter Small, Rodrick Lim, Paul Enarson, Michal Zelcer, Edmond S Chan, Chris Mill, Moshe Ben-Shoshan

Paediatrics Publications

Introduction

Data is sparse on drug-induced anaphylaxis (DIA) and there have not been studies assessing the differences in clinical characteristics and management of DIA between adults and children.

Objective

We assessed the percentage, diagnosis, and management of DIA among all anaphylaxis visits in three pediatric and one adult emergency departments (ED) across Canada.

Methods

Children presenting to the Montreal Children's Hospital (MCH), British Columbia Children's Hospital (BCCH), and Children's Hospital at London Health Sciences Center and adults presenting to Hôpital du Sacré-Coeur with anaphylaxis were recruited as part of the Cross-Canada Anaphylaxis Registry. A standardized data form documenting the reaction …

Emotional Well-Being In Children With Epilepsy: Family Factors As Mediators And Moderators, Shane W. Goodwin, Piotr Wilk, M. Karen Campbell, Kathy N. Speechley

Paediatrics Publications

Objective: Our objective was to examine the relationships of factors associated with children's emotional well-being 2 years after diagnosis, and to examine if these relationships are mediated or moderated by family factors. Methods: Data came from a multicenter prospective cohort study of children with newly diagnosed epilepsy from across Canada (Health-Related Quality of Life in Children with Epilepsy Study; HERQULES, n = 373). Emotional well-being was assessed using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55). The relationships between clinical factors, family factors, and emotional well-being were assessed using multiple regression analyses. Results: Family functioning, family stress, and repertoire …

Legionellosis Following Water Birth In A Hot Tub In A Canadian Neonate, Michelle Barton, Brianna Mckelvie, Aaron Campigotto, Tara Mullowney

Paediatrics Publications

No abstract provided.

Oral Morphine Versus Ibuprofen Administered At Home For Postoperative Orthopedic Pain In Children: A Randomized Controlled Trial, Naveen Poonai, Natasha Datoo, Samina Ali, Megan Cashin, Amy L Drendel, Rongbo Zhu, Natasha Lepore, Michael Greff, Michael Rieder, Debra Bartley

Paediatrics Publications

BACKGROUND: Oral morphine for postoperative pain after minor pediatric surgery, while increasingly popular, is not supported by evidence. We evaluated whether oral morphine was superior to ibuprofen for at-home management of children's postoperative pain.

METHODS: We conducted a randomized superiority trial comparing oral morphine (0.5 mg/kg) with ibuprofen (10 mg/kg) in children 5 to 17 years of age who had undergone minor outpatient orthopedic surgery (June 2013 to September 2016). Participants took up to 8 doses of the intervention drug every 6 hours as needed for pain at home. The primary outcome was pain, according to the Faces Pain Scale …

Papillary Thyroid Cancer Recurrence 43 Years Following Total Thyroidectomy And Radioactive Iodine Ablation: A Case Report, Yaw Amoako-Tuffour, M. Elise Graham, Martin Bullock, Matthew H. Rigby, Jonathan Trites, S. Mark Taylor, Robert D. Hart

Paediatrics Publications

Background: Recurrent papillary thyroid carcinoma (PTC) beyond the first two decades of definitive treatment (i.e. total thyroidectomy and radioactive iodine ablation) is a rare occurrence. Case presentation: We present a case of a 71-year old Caucasian female with a distant history of PTC treated with total thyroidectomy and radioactive iodine ablation who experienced recurrence of her disease 43 years following initial diagnosis and definitive treatment. She presented with palpable left-sided neck mass and subsequently underwent a level II, III, neck dissection and adjuvant iodine ablation. This case presents the latest recurrence in papillary thyroid cancer documented to date in the …

Targeting Cysteine Thiols For In Vitro Site-Specific Glycosylation Of Recombinant Proteins, Yoo Jung Choi, Jinhui Zhu, Steve Chung, Naveed Siddiqui, Qingping Feng, Peter B. Stathopulos

Paediatrics Publications

Stromal interaction molecule-1 (STIM1) is a type-I transmembrane protein located on the endoplasmic reticulum (ER) and plasma membranes (PM). ER-resident STIM1 regulates the activity of PM Orai1 channels in a process known as store operated calcium (Ca2+) entry which is the principal Ca2+ signaling process that drives the immune response. STIM1 undergoes post-translational N-glycosylation at two luminal Asn sites within the Ca2+ sensing domain of the molecule. However, the biochemical, biophysical, and structure biological effects of N-glycosylated STIM1 were poorly understood until recently due to an inability to readily obtain high levels of homogeneous N-glycosylated protein. Here, we describe the …

Scaffolding Proteins In The Development And Maintenance Of The Epidermal Permeability Barrier, Melissa Crawford, Lina Dagnino

Paediatrics Publications

The skin of mammals and other terrestrial vertebrates protects the organism against the external environment, preventing heat, water and electrolyte loss, as well as entry of chemicals and pathogens. Impairments in the epidermal permeability barrier function are associated with the genesis and/or progression of a variety of pathological conditions, including genetic inflammatory diseases, microbial and viral infections, and photodamage induced by UV radiation. In mammals, the outside-in epidermal permeability barrier is provided by the joint action of the outermost cornified layer, together with assembled tight junctions in granular keratinocytes found in the layers underneath. Tight junctions serve as both outside-in …

Proteomic Characterisation Reveals Active Wnt-Signalling By Human Multipotent Stromal Cells As A Key Regulator Of Beta Cell Survival And Proliferation, Miljan Kuljanin, Gillian I. Bell, Stephen E. Sherman, Gilles A. Lajoie, David A. Hess

Paediatrics Publications

Aims/hypothesis: Novel strategies to stimulate the expansion of beta cell mass in situ are warranted for diabetes therapy. The aim of this study was to elucidate the secretome of human bone marrow (BM)-derived multipotent stromal cells (MSCs) with documented islet regenerative paracrine function. We hypothesised that regenerative MSCs will secrete a unique combination of protein factors that augment islet regeneration. Methods: Human BM-derived MSCs were examined for glucose-lowering capacity after transplantation into streptozotocin-treated NOD/severe combined immunodeficiency (SCID) mice and segregated into samples with regenerative (MSCR) vs nonregenerative (MSCNR) capacity. Secreted proteins associated with islet regenerative function were identified using stable …

Burst Suppression On Eeg: Not Always An Ominous Sign, Egidio Spinelli, Sandra Penney, Sharon Carline, Adam Romanovsky, Syed Nizamuddin Ahmed

Paediatrics Publications

No abstract provided.

Epidemiology Of Gestational Diabetes Mellitus According To Iadpsg/Who 2013 Criteria Among Obese Pregnant Women In Europe, Aoife M. Egan, Akke Vellinga, Jürgen Harreiter, David Simmons, Gernot Desoye, Rosa Corcoy, Juan M. Adelantado, Roland Devlieger, Andre Dahlben, Karl G. Helmer, Andrew M. Johnson, Jeffrey D. Holmes, Lorie A. Forwell, Elaine N. Skopelja, Martha E. Shenton, Paul S. Echlin, Inga K. Koerte

Paediatrics Publications

Aims/hypothesis: Accurate prevalence estimates for gestational diabetes mellitus (GDM) among pregnant women in Europe are lacking owing to the use of a multitude of diagnostic criteria and screening strategies in both high-risk women and the general pregnant population. Our aims were to report important risk factors for GDM development and calculate the prevalence of GDM in a cohort of women with BMI ≥29 kg/m2 across 11 centres in Europe using the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)/WHO 2013 diagnostic criteria. Methods: Pregnant women (n = 1023, 86.3% European ethnicity) with a BMI ≥29.0 kg/m2 enrolled into …

Mutations In Keops-Complex Genes Cause Nephrotic Syndrome With Primary Microcephaly, Daniela A Braun, Jia Rao, Geraldine Mollet, David Schapiro, Marie-Claire Daugeron, Weizhen Tan, Olivier Gribouval, Olivia Boyer, Patrick Revy, Tilman Jobst-Schwan, Johanna Magdalena Schmidt, Jennifer A Lawson, Denny Schanze, Shazia Ashraf, Jeremy F P Ullmann, Charlotte A Hoogstraten, Nathalie Boddaert, Bruno Collinet, Gaëlle Martin, Dominique Liger, Svjetlana Lovric, Monica Furlano, I Chiara Guerrera, Oraly Sanchez-Ferras, Jennifer F Hu, Anne-Claire Boschat, Sylvia Sanquer, Björn Menten, Sarah Vergult, Nina De Rocker, Merlin Airik, Tobias Hermle, Shirlee Shril, Eugen Widmeier, Heon Yung Gee, Won-Il Choi, Carolin E Sadowski, Werner L Pabst, Jillian K Warejko, Ankana Daga, Tamara Basta, Verena Matejas, Karin Scharmann, Sandra D Kienast, Babak Behnam, Brendan Beeson, Amber Begtrup, Malcolm Bruce, Gaik-Siew Ch'ng, Shuan-Pei Lin, Jui-Hsing Chang, Chao-Huei Chen, Megan T Cho, Patrick M Gaffney, Patrick E Gipson, Chyong-Hsin Hsu, Jameela A Kari, Yu-Yuan Ke, Cathy Kiraly-Borri, Wai-Ming Lai, Emmanuelle Lemyre, Rebecca Okashah Littlejohn, Amira Masri, Mastaneh Moghtaderi, Kazuyuki Nakamura, Fatih Ozaltin, Marleen Praet, Chitra Prasad, Agnieszka Prytula, Elizabeth R Roeder, Patrick Rump, Rhonda E Schnur, Takashi Shiihara, Manish D Sinha, Neveen A Soliman, Kenza Soulami, David A Sweetser, Wen-Hui Tsai, Jeng-Daw Tsai, Rezan Topaloglu, Udo Vester, David H Viskochil, Nithiwat Vatanavicharn, Jessica L Waxler, Klaas J Wierenga, Matthias T F Wolf, Sik-Nin Wong, Sebastian A Leidel, Gessica Truglio, Peter C Dedon, Annapurna Poduri, Shrikant Mane, Richard P Lifton, Maxime Bouchard, Peter Kannu, David Chitayat, Daniella Magen, Bert Callewaert, Herman Van Tilbeurgh, Martin Zenker, Corinne Antignac, Friedhelm Hildebrandt

Paediatrics Publications

Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced …