Medical Specialties Commons^™

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 …

Mobilising Expertise And Resources To Close The Radiotherapy Gap In Cancer Care., D Rodin, J Longo, T Sherertz, M M Shah, O Balagun, N Wendling, Jacob Van Dyk, C N Coleman, M J Xu, S Grover

Oncology Publications

Closing the gap in cancer care within low- and middle-income countries and in indigenous and geographically isolated populations in high-income countries requires investment and innovation. This is particularly true for radiotherapy, for which the global disparity is one of the largest in healthcare today. New models and paradigms and non-traditional collaborations have been proposed to improve global equity in cancer control. We describe recent initiatives from within the radiation oncology community to increase access to treatment, build the low- and middle-income countries' radiation oncology workforce, mobilise more professionals from within high-income countries and raise awareness of the global need for …

Analysis Of Global Radiotherapy Needs And Costs By Geographic Region And Income Level., E Zubizarreta, Jacob Van Dyk, Y Lievens

Oncology Publications

Recent years have seen various reviews on the lack of access to radiotherapy often based on geographic regions of the world such as Africa, Asia Pacific, Europe, Latin America and North America. Countries are often defined by their national income per capita levels based on World Bank definitions of high income, upper middle income, lower middle income and low income. Within the world regions, there are significant variations in gross national income (GNI) per capita among the different countries, and even within similar income levels, large variations exist. This report presents the actual status of radiotherapy and analyses the current …

Detection Of Α-Thalassemia By Using Multiplex Ligation-Dependent Probe Amplification As An Additional Method For Rare Mutations In Southern Turkey, Ozge Ozalp Yuregir, Akif Ayaz, Sinem Yalcintepe, Sezin Canbek, Didar Yanardag Acik, Basak Taburoglu Yilmaz, Tugce B. Balci

Paediatrics Publications

α-thalassemia is the most common single gene disorder in the Cukurova Region in Turkey. It is therefore routinely screened, including premaritally, in our region. The heterogeneous molecular basis of the disease makes α-thalassemia mutation detection difficult and complex. Besides well established methods, multiplex ligation dependent probe amplification (MLPA) is known as an effective, simple and specific method for the detection and characterization of deletions and duplications. We employed MLPA testing to 30 patients with hematological parameters suggestive of α-thalassemia carrier status but was negative for α-thalassemia with conventional reverse dot blot hybridization (RDB). We found α-globin gene deletions in 3 …

Accuracy Requirements And Uncertainties In Radiotherapy: A Report Of The International Atomic Energy Agency., Debbie Van Der Merwe, Jacob Van Dyk, Brendan Healy, Eduardo Zubizarreta, Joanna Izewska, Ben Mijnheer, Ahmed Meghzifene

Oncology Publications

BACKGROUND: Radiotherapy technology continues to advance and the expectation of improved outcomes requires greater accuracy in various radiotherapy steps. Different factors affect the overall accuracy of dose delivery. Institutional comprehensive quality assurance (QA) programs should ensure that uncertainties are maintained at acceptable levels. The International Atomic Energy Agency has recently developed a report summarizing the accuracy achievable and the suggested action levels, for each step in the radiotherapy process. Overview of the report: The report seeks to promote awareness and encourage quantification of uncertainties in order to promote safer and more effective patient treatments. The radiotherapy process and the radiobiological …

Radiation Oncology Quality And Safety Considerations In Low Resource Settings: A Medical Physics Perspective, Jacob Van Dyk, Ahmed Meghzifene

Oncology Publications

The last few years have seen a significant growth of interest in the global radiation therapy crisis. Various organizations have quantified the need and are providing aid in support of addressing the shortfalls existing in many low-to-middle income countries (LMICs). With the tremendous demand for new facilities, equipment and personnel, it is very important to recognize the quality and safety challenges and to address them directly. An examination of publications on quality and safety in radiation therapy indicates a consistency in a number of the recommendations; however, these authoritative reports were generally based on input from high-resourced contexts. Here we …

Structural Conservation And E2f Binding Specificity Within The Retinoblastoma Pocket Protein Family, Tyler J. Liban, Michael J. Thwaites, Frederick A. Dick, Seth M. Rubin

Paediatrics Publications

The human pocket proteins retinoblastoma (Rb), p107, and p130 are critical negative regulators of the cell cycle and contribute to tumor suppression. While strong structural conservation within the pocket protein family provides for some functional redundancy, important differences have been observed and may underlie the reason that Rb is a uniquely potent tumor suppressor. It has been proposed that distinct pocket protein activities are mediated by their different E2F transcription factor binding partners. In humans, Rb binds E2F1–E2F5, whereas p107 and p130 almost exclusively associate with E2F4 and E2F5. To identify the molecular determinants of this specificity, we compared the …

Global Access To Radiation Therapy For Cervical Cancer: The Cost Of Inaction, Jacob Van Dyk, D Rodin, Timothy Paul Hanna, E Burger, Eduardo Zubizarreta, Mei Ling Yap, Michael Barton, Rifat Atun, Felicia Marie Knaul, Y Lievens, Mary K. Gospodarowicz, D A. Jaffray, M Milosevic

Oncology Publications

No abstract provided.

Biallelic Hypomorphic Mutations In A Linear Deubiquitinase Define Otulipenia, An Early-Onset Autoinflammatory Disease, Qing Zhou, Xiaomin Yu, Erkan Demirkaya, Natalie Deuitch, Deborah Stone, Wanxia Li Tsai, Hye Sun Kuehn, Hongying Wang, Dan Yang, Yong Hwan Park, Amanda K. Ombrello, Mary Blake, Tina Romeo, Elaine F. Remmers, Jae Jin Chae, James C. Mullikin, Ferhat Güzel, Joshua D. Milner, Manfred Boehm, Sergio D. Rosenzweig, Massimo Gadina, Steven B. Welch, Seza Özen, Rezan Topaloglu, Mario Abinun, Daniel L. Kastner, Ivona Aksentijevich

Paediatrics Publications

Systemic autoinflammatory diseases are caused by mutations in genes that function in innate immunity. Here, we report an autoinflammatory disease caused by loss-of-function mutations in OTULIN (FAM105B), encoding a deubiquitinase with linear linkage specificity. We identified two missense and one frameshift mutations in one Pakistani and two Turkish families with four affected patients. Patients presented with neonatal-onset fever, neutrophilic dermatitis/panniculitis, and failure to thrive, but without obvious primary immunodeficiency. HEK293 cells transfected with mutated OTULIN had decreased enzyme activity relative to cells transfected with WT OTULIN, and showed a substantial defect in the linear deubiquitination of target molecules. Stimulated patients' …

Effects Of American Ginseng On Preimplantation Development And Pregnancy In Mice., Danyka Belanger, Michele D Calder, Alessandra Gianetto-Berruti, Edmund M Lui, Andrew J Watson, Valter Feyles

Obstetrics & Gynaecology Publications

In North America, a high proportion of pregnant women use herbal medications including North American ginseng. This medicinal plant contains high amounts of triterpene saponins (ginsenosides), which are the main bioactive compounds. It is important to assess ginseng's impact on all reproductive functions to ensure the safety of pregnant women and fetuses. In this study, we defined the concentration-responsive effects of North American alcoholic and aqueous ginseng extracts on preimplantation development in vitro and on pregnancy and post-partum development in the mouse. Two-cell mouse embryos were cultured with 5 different concentrations of whole ginseng root extracts, or ginsenosides Rb1, Rg1 …

P66shc, A Key Regulator Of Metabolism And Mitochondrial Ros Production, Is Dysregulated By Mouse Embryo Culture., Nicole A Edwards, Andrew J Watson, Dean H Betts

Obstetrics & Gynaecology Publications

STUDY QUESTION: Do high oxygen tension and high glucose concentrations dysregulate p66Shc (Src homologous-collagen homologue adaptor protein) expression during mouse preimplantation embryo culture?

SUMMARY ANSWER: Compared with mouse blastocysts in vivo, P66Shc mRNA and protein levels in blastocysts maintained in vitro increased under high oxygen tension (21%), but not high glucose concentration.

WHAT IS KNOWN ALREADY: Growth in culture adversely impacts preimplantation embryo development and alters the expression levels of the oxidative stress adaptor protein p66Shc, but it is not known if p66Shc expression is linked to metabolic changes observed in cultured embryos.

STUDY DESIGN, SAMPLES/MATERIALS, METHODS: We used a …

Total Versus Partial Splenectomy In Pediatric Hereditary Spherocytosis: A Systematic Review And Meta-Analysis, Leonardo Guizzetti

Epidemiology and Biostatistics Publications

To compare the clinical effectiveness of total (TS) or partial (PS) splenectomy in pediatric hereditary spherocytosis, a systematic review and meta-analysis was performed (PROSPERO registration CRD42015030056). There were 14 observational studies comparing pre- and post- operative hematologic parameters. Secondary outcomes include in-hospital infections, surgical complications, symptomatic recurrence and biliary disease. TS is more effective than PS to increase hemoglobin (3.6 g/dL vs 2.2 g/dL) and reduce reticulocytes (12.5% vs 6.5%) after one year; outcomes following PS are stable for at least 6 years. There were no cases of overwhelming post-splenectomy sepsis. A population-based patient registry is needed for long-term follow-up.

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 …

Continuous Eeg For Diagnosis Of Electrographic Seizures In The Pediatric Cardiac Critical Care Unit: Using A Precious Resource Wisely, Saptharishi Lalgudi Ganesan

Data and Test Instruments

No abstract provided.

Principles Of Fatigue In Residency Education: A Qualitative Study, Taryn S Taylor, Christopher J Watling, Pim W Teunissen, Tim Dornan, Lorelei Lingard

Obstetrics & Gynaecology Publications

BACKGROUND: Proposals to implement fatigue-management strategies in residency education assume that medicine shares the view of other risk-adverse industries that fatigue is hazardous. This view is an essential underpinning of fatigue-management strategies that other industries have embedded as part of their workplace occupational health and safety programs. We sought to explore how residents understand fatigue in the context of their training environment.

METHODS: We interviewed 21 residents in 7 surgical and nonsurgical programs at Western University in 2014. All participants met the inclusion criteria of routinely working 24-hour call shifts while enrolled in their training program. Data collection and analysis …

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.

An Intra-Bone Axial Load Transducer: Development And Validation In An In-Vitro Radius Model, Nikolas K. Knowles, Michael Gladwell, Louis M. Ferreira

Surgery Publications

Background

Accurate measurement of forces through the proximal radius can assess the effects of some surgical procedures on radioulnar load sharing, but is difficult to achieve given the redundant loading nature of the musculoskeletal system. Previously reported devices have relied on indirect measurements that may alter articular joint location and function. An axial load transducer interposed in the diaphysis of the radius may accurately quantify unknown axial loads of the proximal radius, and maintain articular location.

Methods

An in-vitro radius model was developed by interposing an axial load transducer in the diaphysis of the proximal radius. Static loads of 20, …

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 …

Renal Oncocytosis In A Pediatric Patient: Case Report And Review Of The Literature, Stacey Speer, Daniele Wiseman, Madeleine Moussa, Andreana Bütter

Surgery Publications

Renal oncocytosis is a rare condition in which the kidney develops numerous oncocytomas. We present a case of a 12-year-old female who presented with right-sided flank pain of one-year duration. Imaging revealed several masses in the right kidney. Tissue biopsy confirmed multiple benign oncocytomas. Due to the presence of multiple oncocytomas throughout the kidney, a radical nephrectomy was performed. Given the rarity of this condition, as well as its known association with von Hippel-Lindau disease and Birt-Hogg-Dube syndrome, genetic investigations were pursued but failed to identify any abnormalities. This patient remains well and disease free six years after surgery. A …

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 …