26 results on '"Amanda Lam"'
Search Results
2. Cephalosporin Induced Toxic Epidermal Necrolysis and Subsequent Penicillin Drug Exanthem
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Amanda Lam, Inderpal Randhawa, and William Klaustermeyer
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beta-lactams ,cephalosporin ,penicillin ,toxic epidernal necrolysis ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Background: Drug hypersensitivity is classically divided into IgE mediated and non-IgE mediated disease. We report a rare case of consequent IgE mediated and non-IgE mediated reactions within the beta lactam class of antibiotics. Case Summary: An 84-year-old man developed toxic epidermal necrolysis (TEN) due to ceftriaxone, a third generation cephalosporin, involving 72% of the body surface area. The patient recovered but within weeks subsequently developed an acute IgE mediated allergic reaction to piperacillin/tazobactam, an extended spectrum penicillin. Further IgE RAST revealed positive results to penicillin major determinant. Discussion: This case demonstrates the complexity of drug hypersensitivity reactions. While it is accepted that IgE mediated penicillin allergy is a predisposition to cephalosporin allergy, this case displays an unusual correlation between drug hypersensitivity and drug class. There have been few studies that evaluate the cross reactivity with penicillin or other beta-lactams in subjects with primary hypersensitivity to cephalosporins. This clinical scenario emphasizes the need of more studies on cephalosporin allergy in particular as shown by this case of sequential non-IgE mediated cephalosporin induced TEN reaction pursuant by an IgE mediated penicillin allergy.
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- 2008
- Full Text
- View/download PDF
3. Bi-allelic LETM1 variants perturb mitochondrial ion homeostasis leading to a clinical spectrum with predominant nervous system involvement
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Rauan Kaiyrzhanov, Sami E.M. Mohammed, Reza Maroofian, Ralf A. Husain, Alessia Catania, Alessandra Torraco, Ahmad Alahmad, Marina Dutra-Clarke, Sabine Grønborg, Annapurna Sudarsanam, Julie Vogt, Filippo Arrigoni, Julia Baptista, Shahzad Haider, René G. Feichtinger, Paolo Bernardi, Alessandra Zulian, Mirjana Gusic, Stephanie Efthymiou, Renkui Bai, Farah Bibi, Alejandro Horga, Julian A. Martinez-Agosto, Amanda Lam, Andreea Manole, Diego-Perez Rodriguez, Romina Durigon, Angela Pyle, Buthaina Albash, Carlo Dionisi-Vici, David Murphy, Diego Martinelli, Enrico Bugiardini, Katrina Allis, Costanza Lamperti, Siegfried Reipert, Lotte Risom, Lucia Laugwitz, Michela Di Nottia, Robert McFarland, Laura Vilarinho, Michael Hanna, Holger Prokisch, Johannes A. Mayr, Enrico Silvio Bertini, Daniele Ghezzi, Elsebet Østergaard, Saskia B. Wortmann, Rosalba Carrozzo, Tobias B. Haack, Robert W. Taylor, Antonella Spinazzola, Karin Nowikovsky, and Henry Houlden
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Mitochondrial Diseases ,oxidative phosphorylation ,LETM1 ,Wolf-Hirschhorn syndrome ,genetics ,mitochondria ,mitochondrial diseases ,neurodegeneration ,neurology ,potassium transport ,volume homeostasis ,Homeostasis ,Humans ,Membrane Proteins ,Mitochondria ,Mitochondrial Proteins ,Nervous System ,Saccharomyces cerevisiae ,Calcium-Binding Proteins ,Genetics (clinical) ,Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] ,Doenças Genéticas ,Settore MED/03 - Genetica Medica ,Settore MED/26 - Neurologia ,Genetics ,Letm1 ,Neurodegeneration ,Neurology ,Oxidative Phosphorylation ,Potassium Transport ,Volume Homeostasis ,Wolf-hirschhorn Syndrome - Abstract
Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) encodes an inner mitochondrial membrane protein with an osmoregulatory function controlling mitochondrial volume and ion homeostasis. The putative association of LETM1 with a human disease was initially suggested in Wolf-Hirschhorn syndrome, a disorder that results from de novo monoallelic deletion of chromosome 4p16.3, a region encompassing LETM1. Utilizing exome sequencing and international gene-matching efforts, we have identified 18 affected individuals from 11 unrelated families harboring ultra-rare bi-allelic missense and loss-of-function LETM1 variants and clinical presentations highly suggestive of mitochondrial disease. These manifested as a spectrum of predominantly infantile-onset (14/18, 78%) and variably progressive neurological, metabolic, and dysmorphic symptoms, plus multiple organ dysfunction associated with neurodegeneration. The common features included respiratory chain complex deficiencies (100%), global developmental delay (94%), optic atrophy (83%), sensorineural hearing loss (78%), and cerebellar ataxia (78%) followed by epilepsy (67%), spasticity (53%), and myopathy (50%). Other features included bilateral cataracts (42%), cardiomyopathy (36%), and diabetes (27%). To better understand the pathogenic mechanism of the identified LETM1 variants, we performed biochemical and morphological studies on mitochondrial K+/H+ exchange activity, proteins, and shape in proband-derived fibroblasts and muscles and in Saccharomyces cerevisiae, which is an important model organism for mitochondrial osmotic regulation. Our results demonstrate that bi-allelic LETM1 variants are associated with defective mitochondrial K+ efflux, swollen mitochondrial matrix structures, and loss of important mitochondrial oxidative phosphorylation protein components, thus highlighting the implication of perturbed mitochondrial osmoregulation caused by LETM1 variants in neurological and mitochondrial pathologies. This research was supported using resources of the Core Facility Cell Imaging and Ultrastructure Research, University of Vienna, a member of the Vienna Life-Science Instruments (VLSI) and the VetCore Facility (Imaging) of the University of Veterinary Medicine Vienna. We acknowledge International Centre for Genomic Medicine in Neuromuscular Diseases. This research was funded in part, by the Wellcome Trust (WT093205MA, WT104033AIA, and the Synaptopathies Strategic Award, 165908). This study was funded by the Medical Research Council (MR/S01165X/1, MR/S005021/1, G0601943), The National Institute for Health Research University College London Hospitals Biomedical Research Centre, Rosetrees Trust, Ataxia UK, Multiple System Atrophy Trust, Brain Research United Kingdom, Sparks Great Ormond Street Hospital Charity, Muscular Dystrophy United Kingdom (MDUK), Muscular Dystrophy Association (MDA USA) and Senior Non-Clinical Fellow ship to A. Spinazzola, (MC_PC_13029). K.N. and S.E.M.M. were supported by the Austrian Science Funds FWF-P29077 and P31471. A. Spinazzola receives support also from The Lily Foun dation and Brain Research UK. R.K. was supported by European Academy of Neurology Research Training Fellowship and Rosetrees Trust PhD Plus award (PhD2022\100042). info:eu-repo/semantics/publishedVersion
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- 2022
4. Pathogenic SLC25A26 variants impair SAH transport activity causing mitochondrial disease
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Florian A Rosenberger, Jia Xin Tang, Kate Sergeant, Marco F Moedas, Charlotte M Zierz, David Moore, Conrad Smith, David Lewis, Nishan Guha, Sila Hopton, Gavin Falkous, Amanda Lam, Angela Pyle, Joanna Poulton, Gráinne S Gorman, Robert W Taylor, Christoph Freyer, and Anna Wredenberg
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Mice ,S-Adenosylmethionine ,Mitochondrial Diseases ,Genetics ,Animals ,General Medicine ,Molecular Biology ,Methylation ,S-Adenosylhomocysteine ,Genetics (clinical) ,Mitochondria - Abstract
The SLC25A26 gene encodes a mitochondrial inner membrane carrier that transports S-adenosylmethionine (SAM) into the mitochondrial matrix in exchange for S-adenosylhomocysteine (SAH). SAM is the predominant methyl-group donor for most cellular methylation processes, of which SAH is produced as a by-product. Pathogenic, biallelic SLC25A26 variants are a recognized cause of mitochondrial disease in children, with a severe neonatal onset caused by decreased SAM transport activity. Here, we describe two, unrelated adult cases, one of whom presented with recurrent episodes of severe abdominal pain and metabolic decompensation with lactic acidosis. Both patients had exercise intolerance and mitochondrial myopathy associated with biallelic variants in SLC25A26, which led to marked respiratory chain deficiencies and mitochondrial histopathological abnormalities in skeletal muscle that are comparable to those previously described in early-onset cases. We demonstrate using both mouse and fruit fly models that impairment of SAH, rather than SAM, transport across the mitochondrial membrane is likely the cause of this milder, late-onset phenotype. Our findings associate a novel pathomechanism with a known disease-causing protein and highlight the quests of precision medicine in optimizing diagnosis, therapeutic intervention and prognosis.
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- 2021
5. Adult-onset Leigh syndrome linked to the novel stop codon mutation m.6579G>A in MT-CO1
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Enrico Bugiardini, Cathy E. Woodward, Amanda Lam, Robert D S Pitceathly, Michael G. Hanna, Sonia Gandhi, Olivia V. Poole, Ros Quinlivan, Chris M. Everett, and Silvia Marino
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Adult ,0301 basic medicine ,Muscle tissue ,Pathology ,medicine.medical_specialty ,Mitochondrial DNA ,Mitochondrial disease ,Encephalopathy ,Biology ,Electron Transport Complex IV ,03 medical and health sciences ,0302 clinical medicine ,Optic Atrophies, Hereditary ,Basal ganglia ,medicine ,Humans ,Cytochrome c oxidase ,Molecular Biology ,Cell Biology ,medicine.disease ,Hyperintensity ,030104 developmental biology ,medicine.anatomical_structure ,Codon, Terminator ,biology.protein ,Molecular Medicine ,Female ,Brainstem ,Leigh Disease ,030217 neurology & neurosurgery - Abstract
Adult-onset Leigh syndrome is a rare but important manifestation of mitochondrial disease. We report a 17 year old female who presented with subacute encephalopathy, brainstem and extrapyramidal signs, raised CSF lactate, and symmetrical hyperintensities in the basal ganglia on T2-weighted cerebral MRI. The presence of cytochrome c oxidase deficient fibres in muscle tissue prompted sequencing of the entire mitochondrial genome which revealed the novel stop codon mutation m.6579G>A; p.Gly226X in MT-CO1. Here we present the case and review the clinicopathological and molecular spectrum of previously reported MT-CO1 truncating mutations.
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- 2019
6. Diagnosing Mitochondrial Disorders Remains Challenging in the Omics Era
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Cathy E. Woodward, Thomas S. Jacques, Paul Gissen, Simon Heales, Jane A. Hurst, Richard H Scott, Emma Footitt, Sanjay Bhate, Shamima Rahman, James Davison, Stephanie Grunewald, Patrick Forny, Thomas Cullup, Spyros Batzios, Maureen Cleary, Anupam Chakrapani, and Amanda Lam
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Mitochondrial DNA ,Muscle biopsy ,medicine.diagnostic_test ,business.industry ,Mitochondrial disease ,medicine.disease ,Omics ,Bioinformatics ,Article ,Neuroimaging ,Cohort ,Medicine ,Biochemical testing ,Neurology (clinical) ,business ,Genetics (clinical) ,Exome sequencing - Abstract
ObjectiveWe hypothesized that novel investigative pathways are needed to decrease diagnostic odysseys in pediatric mitochondrial disease and sought to determine the utility of clinical exome sequencing in a large cohort with suspected mitochondrial disease and to explore whether any of the traditional indicators of mitochondrial disease predict a confirmed genetic diagnosis.MethodsWe investigated a cohort of 85 pediatric patients using clinical exome sequencing and compared the results with the outcome of traditional diagnostic tests, including biochemical testing of routine parameters (lactate, alanine, and proline), neuroimaging, and muscle biopsy with histology and respiratory chain enzyme activity studies.ResultsWe established a genetic diagnosis in 36.5% of the cohort and report 20 novel disease-causing variants (1 mitochondrial DNA). Counterintuitively, routine biochemical markers were more predictive of mitochondrial disease than more invasive and elaborate muscle studies.ConclusionsWe propose using biochemical markers to support the clinical suspicion of mitochondrial disease and then apply first-line clinical exome sequencing to identify a definite diagnosis. Muscle biopsy studies should only be used in clinically urgent situations or to confirm an inconclusive genetic result.Classification of EvidenceThis is a Class II diagnostic accuracy study showing that the combination of CSF and plasma biochemical tests plus neuroimaging could predict the presence or absence of exome sequencing confirmed mitochondrial disorders.
- Published
- 2021
7. Trends in cardiovascular risk factors and treatment goals in patients with diabetes in Singapore-analysis of the SingHealth Diabetes Registry
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Tazeen H. Jafar, David Carmody, Yong Mong Bee, Gilbert Choon Seng Tan, Liang Feng, Amanda Lam, Ching Wee Lim, and Su-Yen Goh
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Male ,Epidemiology ,Cardiovascular Medicine ,Biochemistry ,Geographical Locations ,chemistry.chemical_compound ,Endocrinology ,Medical Conditions ,Medicine and Health Sciences ,Diabetes diagnosis and management ,Registries ,Generalized estimating equation ,Singapore ,Multidisciplinary ,Disease Management ,Regression analysis ,Middle Aged ,Type 2 Diabetes ,Cardiovascular Diseases ,Hypertension ,Medicine ,Female ,Type 2 Diabetes Risk ,Research Article ,Adult ,medicine.medical_specialty ,HbA1c ,Asia ,Adolescent ,Endocrine Disorders ,Science ,Cardiology ,Diastole ,Ethnic Epidemiology ,Young Adult ,Asian People ,Diabetes mellitus ,Internal medicine ,Diabetes Mellitus ,medicine ,Humans ,In patient ,Hemoglobin ,Risk factor ,Aged ,Retrospective Studies ,Glycated Hemoglobin ,Biology and life sciences ,business.industry ,Proteins ,Cholesterol, LDL ,Cardiovascular Disease Risk ,medicine.disease ,Diagnostic medicine ,Blood pressure ,Diabetes Mellitus, Type 2 ,chemistry ,Heart Disease Risk Factors ,Metabolic Disorders ,Medical Risk Factors ,People and Places ,Glycated hemoglobin ,business - Abstract
BackgroundAsian populations are at high risk of diabetes and related vascular complications. We examined risk factor control, preventive care, and disparities in these trends among adults with diabetes in Singapore.MethodsThe sample included 209,930 adults with diabetes aged≥18 years from a multi-institutional SingHealth Diabetes Registry between 2013 and 2019 in Singapore. We performed logistic generalized estimating equations (GEEs) regression analysis and used linear mixed effect modeling to evaluate the temporal trends.ResultsBetween 2013 and 2019, the unadjusted control rates of glycated hemoglobin (4.8%, 95%CI (4.4 to 5.1) and low-density lipoprotein cholesterol (LDL-C) (11.5%, 95%CI (11.1 to 11.8)) improved, but blood pressure (BP) control worsened (systolic BP (SBP)/diastolic BP (DBP) ConclusionsTrends in risk factor control improved for glycated hemoglobin and LDL-C, but worsened for BP among diabetic adults in Singapore from 2013 to 2019. Control rates for all risk factors remain inadequate.
- Published
- 2021
8. Expanding the molecular and phenotypic spectrum of truncating MT-ATP6 mutations
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Alejandro Horga, Amanda Lam, Rosaline Quinlivan, Kerrie Venner, Enrico Bugiardini, Eleonora Lamantea, Massimo Zeviani, Janice L. Holton, Cathy E. Woodward, Alessandra Valerio, Iain P. Hargreaves, Annapurna Chalasani, Silvia Marchet, Robert D S Pitceathly, Costanza Lamperti, Cristiane Benincá, Emanuela Bottani, Olivia V. Poole, Michael G. Hanna, and Henry Houlden
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Mitochondrial encephalomyopathy ,RM ,Ataxia ,Mitochondrial disease ,Biology ,Article ,RS ,Electron Transport Complex IV ,03 medical and health sciences ,QH301 ,0302 clinical medicine ,medicine ,Genetics (clinical) ,030304 developmental biology ,0303 health sciences ,Cerebellar ataxia ,Leukodystrophy ,medicine.disease ,Molecular biology ,3. Good health ,QR ,Mitochondria ,Transplantation ,MT-ATP6 ,Mutation ,biology.protein ,Electron Transport Complex IV, Mitochondria, Mutation ,Myoclonic epilepsy ,Neurology (clinical) ,medicine.symptom ,030217 neurology & neurosurgery - Abstract
ObjectiveTo describe the clinical and functional consequences of 1 novel and 1 previously reported truncating MT-ATP6 mutation.MethodsThree unrelated probands with mitochondrial encephalomyopathy harboring truncating MT-ATP6 mutations are reported. Transmitochondrial cybrid cell studies were used to confirm pathogenicity of 1 novel variant, and the effects of all 3 mutations on ATPase 6 and complex V structure and function were investigated.ResultsPatient 1 presented with adult-onset cerebellar ataxia, chronic kidney disease, and diabetes, whereas patient 2 had myoclonic epilepsy and cerebellar ataxia; both harbored the novel m.8782G>A; p.(Gly86*) mutation. Patient 3 exhibited cognitive decline, with posterior white matter abnormalities on brain MRI, and severely impaired renal function requiring transplantation. The m.8618dup; p.(Thr33Hisfs*32) mutation, previously associated with neurogenic muscle weakness, ataxia, and retinitis pigmentosa, was identified. All 3 probands demonstrated a broad range of heteroplasmy across different tissue types. Blue-native gel electrophoresis of cultured fibroblasts and skeletal muscle tissue confirmed multiple bands, suggestive of impaired complex V assembly. Microscale oxygraphy showed reduced basal respiration and adenosine triphosphate synthesis, while reactive oxygen species generation was increased. Transmitochondrial cybrid cell lines studies confirmed the deleterious effects of the novel m.8782 G>A; p.(Gly86*) mutation.ConclusionsWe expand the clinical and molecular spectrum of MT-ATP6-related mitochondrial disorders to include leukodystrophy, renal disease, and myoclonic epilepsy with cerebellar ataxia. Truncating MT-ATP6 mutations may exhibit highly variable mutant levels across different tissue types, an important consideration during genetic counseling.
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- 2020
9. Attaching protein-adsorbing silica particles to the surface of cotton substrates for bioaerosol capture including SARS-CoV-2
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Kieran Collings, Cedric Boisdon, Tung-Ting Sham, Kevin Skinley, Hyun-Kyung Oh, Tessa Prince, Adham Ahmed, Shaun H. Pennington, Philip J. Brownridge, Thomas Edwards, Giancarlo A. Biagini, Claire E. Eyers, Amanda Lamb, Peter Myers, and Simon Maher
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Science - Abstract
Abstract The novel coronavirus pandemic (COVID-19) has necessitated a global increase in the use of face masks to limit the airborne spread of the virus. The global demand for personal protective equipment has at times led to shortages of face masks for the public, therefore makeshift masks have become commonplace. The severe acute respiratory syndrome caused by coronavirus-2 (SARS-CoV-2) has a spherical particle size of ~97 nm. However, the airborne transmission of this virus requires the expulsion of droplets, typically ~0.6–500 µm in diameter (by coughing, sneezing, breathing, and talking). In this paper, we propose a face covering that has been designed to effectively capture SARS-CoV-2 whilst providing uncompromised comfort and breathability for the wearer. Herein, we describe a material approach that uses amorphous silica microspheres attached to cotton fibres to capture bioaerosols, including SARS CoV-2. This has been demonstrated for the capture of aerosolised proteins (cytochrome c, myoglobin, ubiquitin, bovine serum albumin) and aerosolised inactivated SARS CoV-2, showing average filtration efficiencies of ~93% with minimal impact on breathability.
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- 2023
- Full Text
- View/download PDF
10. 7. Teenage Motherhood, Responsibility, and Docile Female
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Amanda Lam
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This research paper critiques the harmful dominant discourse in America which posits that teenage mothers are “unfit” parents because they bore a child outside the confines of heterosexuality, monogamy, marriage, and middle-class status. Based on secondary research, the paper uses a Foucauldian feminist perspective to argue that the negative discourse around teenage pregnancy and motherhood reified by America’s abstinence-only sex education curriculum and advice from sexual health experts seeks to produce docile female bodies. America’s abstinence-only sex education curriculum promotes gender differences in bodily movements whereby female sexual activity is demonized while male sexual activity is normalized. Sexual health experts also morally judge the teenage mother’s actions under the guise of professional knowledge, and fail to recognize the structural factors that may have contributed to teenage pregnancy as a means to produce docile female bodies. Additionally, both America’s abstinence-only sex education curriculum and sexual health experts absolve the teenage father of any responsibility. By challenging the sex education curriculum and sexual health experts, the power of language and discourse of authorities in framing what they consider to be a social problem will be brought to light.
- Published
- 2018
11. Social Media in the Middle East: The Story of 2017
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Amanda Lam and Damian Radcliffe
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History ,Middle East ,Polymers and Plastics ,business.industry ,Media studies ,North africa ,Popularity ,Industrial and Manufacturing Engineering ,Variety (cybernetics) ,Digital media ,White paper ,Political science ,Key (cryptography) ,Social media ,Business and International Management ,business - Abstract
This report is the sixth in a series of annual reports designed to highlight key developments and data related to usage of social media in the Middle East and North Africa. As in previous reports, this White Paper captures insights from a wide variety of academic, industry and media sources, distilling the key lessons from the past year. Social Media adoption, and usage, around the world continues to rapidly evolve; and the Middle East is no exception. This 2017 research and industry round-up highlights the increasing prominence of visually led social media in the region, and the ongoing popularity of Facebook’s different products.
- Published
- 2018
12. Urine analysis of glucose tetrasaccharide by HPLC; a useful marker for the investigation of patients with Pompe and other glycogen storage diseases
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Niamh Finnegan, Simon Heales, Ashok Vellodi, Victoria Manwaring, Amanda Lam, Katie Bainbridge, Rebecca Franses, Derek Burke, and Helen Prunty
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Male ,medicine.medical_specialty ,Urinary system ,Oligosaccharides ,Urine ,Glucose tetrasaccharide ,High-performance liquid chromatography ,chemistry.chemical_compound ,Internal medicine ,Genetics ,medicine ,Humans ,Glycogen storage disease ,Enzyme Replacement Therapy ,Child ,Chromatography, High Pressure Liquid ,Genetics (clinical) ,chemistry.chemical_classification ,Glycogen ,Glycogen Storage Disease Type II ,Chemistry ,Infant ,Enzyme replacement therapy ,Middle Aged ,Glycogen Storage Disease ,medicine.disease ,Endocrinology ,Enzyme ,Child, Preschool ,Female ,Biomarkers - Abstract
A high performance liquid chromatography method, adapted from an established urinary sugars method, has been developed for the analysis of a tetraglucose oligomer (Glc4) in urine. Pompe disease results from defects in the activity of lysosomal acid α-glucosidase (GAA) with patients typically excreting increased amounts of Glc4. Rapid determination of GAA in dried blood spots is now possible. However, enzymatic analysis is unable to discriminate between patients with Pompe disease and those individuals harbouring pseudo deficiency mutations. This method was able to quantify Glc4 levels in all patients analysed with an established diagnosis of Pompe disease, and all controls analysed had Glc4 levels below the limit of detection for this method. Importantly the method was able to discriminate between an individual known to harbour a pseudo Pompe mutation and patients with Pompe disease, providing a useful supporting test to enzymatic analysis. Sequential measurement of urinary Glc4 has been proposed to monitor the effects of enzyme replacement therapy (ERT). We observed a clear decrease in Glc4 levels following commencement of treatment in three patients studied. Additionally, raised levels of Glc4 were observed in patients with glycogen storage disease (GSD) type Ia and type III suggesting that this method may have applications in other GSDs. Abbreviations C5 Cellopentaose
- Published
- 2011
13. Corticospinal tract dysfunction and development of amyotrophic lateral sclerosis following electrical injury
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Matthew C. Kiernan, Steve Vucic, Amanda Lam, Benjamin C. Cheah, William Huynh, and Paul Clouston
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Adult ,Male ,Physiology ,medicine.medical_treatment ,Pyramidal Tracts ,Electromyography ,Lower motor neuron ,Cellular and Molecular Neuroscience ,Physiology (medical) ,medicine ,Humans ,Amyotrophic lateral sclerosis ,Motor Neurons ,Denervation ,medicine.diagnostic_test ,business.industry ,Amyotrophic Lateral Sclerosis ,Brain ,medicine.disease ,Magnetic Resonance Imaging ,people.cause_of_death ,Electric Injuries ,Transcranial magnetic stimulation ,Electrocution ,medicine.anatomical_structure ,Corticospinal tract ,Neurology (clinical) ,business ,people ,Neuroscience ,Motor cortex - Abstract
The causal relationship between electrical injury and development of amyotrophic lateral sclerosis (ALS) remains controversial. We describe the case of a 25-year-old man who developed ALS after a severe electrical injury. Cerebral magnetic resonance imaging (MRI) demonstrated hyperintensities involving the corticospinal tract. Functional testing with transcranial magnetic stimulation established that the motor cortex was relatively inexcitable. In addition, there were features of denervation on electromyography and muscle biopsy that supported concomitant lower motor neuron findings and the diagnosis of ALS.
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- 2010
14. Galactokinase deficiency in a patient with congenital hyperinsulinism
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Khalid Hussain, Derek Burk, Dunia Ismail, Wolfgang Högler, Sarah E. Flanagan, Amanda Lam, Mashbat Bayarchimeg, Sian Ellard, and Jeremy Kirk
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Pediatrics ,medicine.medical_specialty ,business.industry ,Galactose Metabolism ,medicine.disease ,Galactokinase ,Galactokinase deficiency ,Article ,Hyperinsulinaemic hypoglycaemia ,Cataracts ,medicine ,Congenital hyperinsulinism ,business ,Complication ,ABCC8 gene - Abstract
Galactokinase catalyses the first committed step in galactose metabolism, the conversion of galactose to galactose-1-phosphate. Galactokinase deficiency is an extremely rare form of galactosaemia, and the most frequent complication reported is cataracts. Congenital hyperinsulinism (CHI) is a cause of severe hypoglycaemia in the newborn period. Galactosaemia has not previously been reported in a neonate with concomitant CHI.To report the first case of a patient with CHI and galactokinase deficiency, and to describe the diagnostic pitfalls with bedside blood glucose testing in a neonate with combined galactokinase deficiency and CHI.A 3-day-old baby girl from consanguineous parents presented with poor feeding, irritability and seizures. Capillary blood glucose testing using bedside test strips and glucometer showed a glucose level of 18 mmol/L, but the actual laboratory blood glucose level was only 1.8 mmol/L. After discontinuation of oral feeding (stopping provision of dietary galactose), the bedside capillary blood glucose correlated with laboratory glucose concentrations.Biochemically the patient had CHI (blood glucose level 2.3 mmol/L with simultaneous serum insulin level of 30 mU/L) and galactokinase deficiency (elevated serum galactose level 0.62 μmol/L). Homozygous loss of function mutations in ABCC8 and GALK1 were found, which explained the patient's CHI and galactokinase deficiency, respectively.This is the first reported case of CHI and galactokinase deficiency occurring in the same patient. Severe hypoglycaemia in neonates with CHI may go undetected with bedside blood glucose meters in patients with galactokinase deficiency.
- Published
- 2011
15. MELAS mitochondrial DNA mutation A3243G reduces glutamate transport in cybrids cell lines
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Jacopo C. DiFrancesco, J. Mark Cooper, Carlo Ferrarese, Lucio Tremolizzo, Paul E. Hart, Antony H. Schapira, Amanda Lam, DI FRANCESCO, J, Cooper, J, Lam, A, Hart, P, Tremolizzo, L, Ferrarese, C, and Schapira, A
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Excitotoxicity ,Down-Regulation ,Glutamic Acid ,Mitochondrion ,Biology ,Glutamate Plasma Membrane Transport Proteins ,MELAS syndrome ,medicine.disease_cause ,Tritium ,DNA, Mitochondrial ,Radioligand Assay ,Adenosine Triphosphate ,Developmental Neuroscience ,Glutamate homeostasis ,Mitochondrial myopathy ,Cell Line, Tumor ,medicine ,MELAS Syndrome ,Humans ,Glutamate Plasma Membrane Transport Protein ,Hybridomas ,Glutamate receptor ,Biological Transport ,Glutamic acid ,medicine.disease ,Cell biology ,Mitochondria ,Neurology ,Biochemistry ,Mutation ,Hybridoma ,Energy Metabolism ,Human - Abstract
MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) is commonly associated with the A3243G mitochondrial DNA (mtDNA) mutation encoding the transfer RNA of leucine (UUR) (tRNA (Le(UUR))). The pathogenetic mechanisms of this mutation are not completely understood. Neuronal functions are particularly vulnerable to alterations in oxidative phosphorylation, which may affect the function of the neurotransmitter glutamate, leading to excitotoxicity. In order to investigate the possible effects of A3243G upon glutamate homeostasis, we assessed glutamate uptake in osteosarcoma-derived cytoplasmic hybrids (cybrids) expressing high levels of this mutation. High-affinity Na+-dependent glutamate uptake was assessed as radioactive [H-3]-glutamate influx mediated by specific excitatory amino acid transporters (EAATs). The maximal rate (V-max) of Na+-dependent glutamate uptake was significantly reduced in all the mutant clones. Although the defect did not relate to either the mutant load or magnitude of oxidative phosphorylation defect, we found an inverse relationship between A3243G mutation load and mitochondrial ATP synthesis, without any evidence of increased cellular or mitochondrial free radical production in these A3243G clones. These data suggest that a defect of glutamate transport in MELAS neurons may be due to decreased energy production and might be involved in mediating the pathogenic effects of the A3243G mtDNA mutation. (C) 2008 Elsevier Inc. All rights reserved.
- Published
- 2008
16. Sickle Cell Hemoglobin Genotypes Affect Malaria Parasite Growth and Correlate with Exosomal miR-451a and let-7i-5p Levels
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Keri Oxendine Harp, Alaijah Bashi, Felix Botchway, Daniel Addo-Gyan, Mark Tetteh-Tsifoanya, Amanda Lamptey, Georgina Djameh, Shareen A. Iqbal, Cecilia Lekpor, Saswati Banerjee, Michael D. Wilson, Yvonne Dei-Adomakoh, Andrew A. Adjei, Jonathan K. Stiles, and Adel Driss
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malaria ,sickle cell disease ,parasitemia ,red blood cells ,microRNA ,exosomes ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Malaria affects a significant portion of the global population, with 247 million cases in 2021, primarily in Africa. However, certain hemoglobinopathies, such as sickle cell trait (SCT), have been linked to lower mortality rates in malaria patients. Hemoglobin (Hb) mutations, including HbS and HbC, can cause sickle cell disease (SCD) when both alleles are inherited (HbSS and HbSC). In SCT, one allele is inherited and paired with a normal allele (HbAS, HbAC). The high prevalence of these alleles in Africa may be attributed to their protective effect against malaria. Biomarkers are crucial for SCD and malaria diagnosis and prognosis. Studies indicate that miRNAs, specifically miR-451a and let-7i-5p, are differentially expressed in HbSS and HbAS compared to controls. Our research examined the levels of exosomal miR-451a and let-7i-5p in red blood cells (RBCs) and infected red blood cells (iRBCs) from multiple sickle Hb genotypes and their impact on parasite growth. We assessed exosomal miR-451a and let-7i-5p levels in vitro in RBC and iRBC supernatants. Exosomal miRNAs exhibited distinct expression patterns in iRBCs from individuals with different sickle Hb genotypes. Additionally, we discovered a correlation between let-7i-5p levels and trophozoite count. Exosomal miR-451a and let-7i-5p could modulate SCD and malaria severity and serve as potential biomarkers for malaria vaccines and therapies.
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- 2023
- Full Text
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17. Identification of an androgen-dependent enhancer within the prostate stem cell antigen gene
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Robert E. Reiter, Anjali Jain, Michael Carey, Igor Vivanco, and Amanda Lam
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Male ,Green Fluorescent Proteins ,Molecular Sequence Data ,Enhancer RNAs ,Biology ,GPI-Linked Proteins ,Response Elements ,Prostate cancer ,Endocrinology ,Antigens, Neoplasm ,Genes, Reporter ,medicine ,Tumor Cells, Cultured ,Humans ,Binding site ,Enhancer ,Promoter Regions, Genetic ,Molecular Biology ,Binding Sites ,Membrane Glycoproteins ,Base Sequence ,Prostatic Neoplasms ,General Medicine ,medicine.disease ,Molecular biology ,Prostate Stem Cell Antigen ,Neoplasm Proteins ,Androgen receptor ,Luminescent Proteins ,Enhancer Elements, Genetic ,Mutation ,Androgens ,DNA, Intergenic ,Transcription Initiation Site ,Androgen Response Element ,Deoxyribonuclease I - Abstract
Prostate stem cell antigen (PSCA) is emerging as an important diagnostic marker and therapeutic target in prostate cancer. Previous studies indicated that PSCA was directly regulated by androgens, but the mechanism has not been elucidated. Here we describe the identification of a compact cell-specific and androgen-responsive enhancer between 2.7 and 3 kb upstream of the transcription start site. The enhancer functions autonomously when positioned immediately adjacent to a minimal promoter. Deoxyribonuclease I footprinting analysis with recombinant androgen receptor (AR) reveals that the enhancer contains two AR binding sites at one end. Mutational analysis of the AR binding sites revealed the importance of the higher affinity one. The dissociation constant of the high affinity binding site (androgen response element I) was determined to be approximately 87 nm. The remainder of the enhancer contains elements that function synergistically with the AR. We discuss the structural organization of the PSCA enhancer and compare it with that found in other AR-regulated genes.
- Published
- 2002
18. Erratum to: Urine analysis of glucose tetrasaccharide by HPLC; a useful marker for the investigation of patients with Pompe and other glycogen storage diseases
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Victoria Manwaring, Helen Prunty, Katie Bainbridge, Derek Burke, Niamh Finnegan, Rebecca Franses, Amanda Lam, Ashok Vellodi, and Simon Heales
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Genetics ,Genetics (clinical) - Published
- 2011
19. Informing Antibiotic Guardianship to Combat Antimicrobial Resistance: The Liverpool Citizens’ Jury on AMR
- Author
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William Hope, James Amos, Sarah Atwood, Kyle Bozentko, Amanda Lamb, Gary Leeming, Matthew Smith, Rachel Thompson, and Andrew Townsend
- Subjects
citizen jury ,public engagement ,deliberative democracy ,AMR ,antimicrobial resistance ,data ,Medicine - Abstract
The Liverpool Citizens’ Jury was a public consultation on the use of health data to tackle the significant problem of Antimicrobial Resistance (AMR) and is the first step in creating a local AMR network with national and international relevance. The 18 jurors were tasked with learning about AMR as it relates to research and considered how organisations might collect, share and utilise pseudo-anonymised patient data. The overarching aim is to produce a new model supporting societal change focused on Antibiotic Guardianship and to combat the public health challenge of AMR. The model will be implemented in the UK and provided to an international network enabling global knowledge transfer.
- Published
- 2022
- Full Text
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20. Emergency Response to Australia’s Black Summer 2019–2020: The Role of a Zoo-Based Conservation Organisation in Wildlife Triage, Rescue, and Resilience for the Future
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Marissa L. Parrott, Leanne V. Wicker, Amanda Lamont, Chris Banks, Michelle Lang, Michael Lynch, Bonnie McMeekin, Kimberly A. Miller, Fiona Ryan, Katherine E. Selwood, Sally L. Sherwen, and Craig Whiteford
- Subjects
wildlife ,bushfires ,emergency response ,conservation ,animal welfare ,threatened species ,Veterinary medicine ,SF600-1100 ,Zoology ,QL1-991 - Abstract
Modern zoos are increasingly taking a leading role in emergency management and wildlife recovery. In the face of climate change and the predicted increase in frequency and magnitude of catastrophic events, zoos provide specialised expertise to assist wildlife welfare and endangered species recovery. In the 2019–2020 Australian bushfire season, now called Australia’s Black Summer, a state government-directed response was developed, assembling specialised individuals and organisations from government, non-government organisations, research institutions, and others. Here, we detail the role of Zoos Victoria staff in wildlife triage and welfare, threatened species evacuation and recovery, media and communications, and fundraising during and after the fires. We share strategies for future resilience, readiness, and the ability to mobilise quickly in catastrophic events. The development of triage protocols, emergency response kits, emergency enclosures, and expanded and new captive breeding programs is underway, as are programs for care of staff mental health and nature-based community healing for people directly affected by the fires. We hope this account of our response to one of the greatest recent threats to Australia’s biodiversity, and steps to prepare for the future will assist other zoos and wildlife organisations around the world in preparations to help wildlife before, during, and after catastrophic events.
- Published
- 2021
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21. Cephalosporin Induced Toxic Epidermal Necrolysis and Subsequent Penicillin Drug Exanthem
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William B. Klaustermeyer, Inderpal Randhawa, and Amanda Lam
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lcsh:Immunologic diseases. Allergy ,Male ,medicine.drug_class ,Cephalosporin ,Antibiotics ,cephalosporin ,Penicillanic Acid ,Immunoglobulin E ,Tazobactam ,Microbiology ,Drug Hypersensitivity ,toxic epidernal necrolysis ,medicine ,polycyclic compounds ,Humans ,Immunology and Allergy ,Aged, 80 and over ,Piperacillin ,biology ,business.industry ,beta-lactams ,General Medicine ,Exanthema ,medicine.disease ,Toxic epidermal necrolysis ,Cephalosporins ,Penicillin ,Piperacillin, Tazobactam Drug Combination ,penicillin ,Stevens-Johnson Syndrome ,Immunology ,biology.protein ,Ceftriaxone ,lcsh:RC581-607 ,business ,medicine.drug - Abstract
Background Drug hypersensitivity is classically divided into IgE mediated and non-IgE mediated disease. We report a rare case of consequent IgE mediated and non-IgE mediated reactions within the beta lactam class of antibiotics. Case Summary An 84-year-old man developed toxic epidermal necrolysis (TEN) due to ceftriaxone, a third generation cephalosporin, involving 72% of the body surface area. The patient recovered but within weeks subsequently developed an acute IgE mediated allergic reaction to piperacillin/tazobactam, an extended spectrum penicillin. Further IgE RAST revealed positive results to penicillin major determinant. Discussion This case demonstrates the complexity of drug hypersensitivity reactions. While it is accepted that IgE mediated penicillin allergy is a predisposition to cephalosporin allergy, this case displays an unusual correlation between drug hypersensitivity and drug class. There have been few studies that evaluate the cross reactivity with penicillin or other beta-lactams in subjects with primary hypersensitivity to cephalosporins. This clinical scenario emphasizes the need of more studies on cephalosporin allergy in particular as shown by this case of sequential non-IgE mediated cephalosporin induced TEN reaction pursuant by an IgE mediated penicillin allergy.
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22. Periodontal status among patients with diabetes in Nuuk, Greenland
- Author
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Amanda Lamer Schjetlein, Marit Eika Jørgensen, Torsten Lauritzen, and Michael Lynge Pedersen
- Subjects
diabetes ,periodontitis ,Greenland ,Inuit ,Arctic medicine. Tropical medicine ,RC955-962 - Abstract
Background: Diabetes is becoming more common in the Greenlandic population. Patients with diabetes are more prone to periodontal disease. Periodontal status may have an effect on metabolic control. Objective: The aim of this study was to estimate the prevalence of periodontitis amongst patients with diabetes in Nuuk, Greenland, and secondly, to observe if dental care was associated with improved periodontal status and metabolic control. Study design: Observational cross-sectional study and a pilot study of a dental care intervention. Methods: Sixty-two Greenlandic patients with diabetes were included in the study. Data were collected from the Electronic Medical Records (EMR), in addition to a telephone interview. Patients were offered 3 dental examinations with a 3-month interval. The dental examinations consisted of a full-mouth assessment of number of remaining teeth and assessment of periodontal status. Patients received scaling and root planing, together with information and instructions on oral hygiene. Information on glycated haemoglobin (HbA1C) values was collected from the EMR at each dental examination. Results: In this study, 21.0% (13/62) of patients with diabetes had periodontitis. About 42% had less than 20 teeth. The association between diabetes and periodontitis was known by 20 out of the 62 patients. Over half of the patients had been to a dental examination within the last year. The prevalence of periodontitis decreased significantly from 21.0 to 0% (p
- Published
- 2014
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23. An analysis of the process and results of manual geocode correction
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Yolanda J. McDonald, Michael Schwind, Daniel W. Goldberg, Amanda Lampley, and Cosette M. Wheeler
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Manual geocode correction ,Geocode inaccuracies ,Match rate improvement ,Geocode ,Geography (General) ,G1-922 - Abstract
Geocoding is the science and process of assigning geographical coordinates (i.e. latitude, longitude) to a postal address. The quality of the geocode can vary dramatically depending on several variables, including incorrect input address data, missing address components, and spelling mistakes. A dataset with a considerable number of geocoding inaccuracies can potentially result in an imprecise analysis and invalid conclusions. There has been little quantitative analysis of the amount of effort (i.e. time) to perform geocoding correction, and how such correction could improve geocode quality type. This study used a low-cost and easy to implement method to improve geocode quality type of an input database (i.e. addresses to be matched) through the processes of manual geocode intervention, and it assessed the amount of effort to manually correct inaccurate geocodes, reported the resulting match rate improvement between the original and the corrected geocodes, and documented the corresponding spatial shift by geocode quality type resulting from the corrections. Findings demonstrated that manual intervention of geocoding resulted in a 90% improvement of geocode quality type, took 42 hours to process, and the spatial shift ranged from 0.02 to 151,368 m. This study provides evidence to inform research teams considering the application of manual geocoding intervention that it is a low-cost and relatively easy process to execute.
- Published
- 2017
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24. Nonfluent/Agrammatic PPA with In-Vivo Cortical Amyloidosis and Pick’s Disease Pathology
- Author
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Francesca Caso, Benno Gesierich, Maya Henry, Manu Sidhu, Amanda LaMarre, Miranda Babiak, Bruce L. Miller, Gil D. Rabinovici, Eric J. Huang, Giuseppe Magnani, Massimo Filippi, Giancarlo Comi, William W. Seeley, and Maria Luisa Gorno-Tempini
- Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
The role of biomarkers in predicting pathological findings in the frontotemporal dementia (FTD) clinical spectrum disorders is still being explored. We present comprehensive, prospective longitudinal data for a 66 year old, right-handed female who met current criteria for the nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA). She first presented with a 3-year history of progressive speech and language impairment mainly characterized by severe apraxia of speech. Neuropsychological and general motor functions remained relatively spared throughout the clinical course. Voxel-based morphometry (VBM) showed selective cortical atrophy of the left posterior inferior frontal gyrus (IFG) and underlying insula that worsened over time, extending along the left premotor strip. Five years after her first evaluation, she developed mild memory impairment and underwent PET-FDG and PiB scans that showed left frontal hypometabolism and cortical amyloidosis. Three years later (11 years from first symptom), post-mortem histopathological evaluation revealed Pick's disease, with severe degeneration of left IFG, mid-insula, and precentral gyrus. Alzheimer’s disease (AD) (CERAD frequent/Braak Stage V) was also detected. This patient demonstrates that biomarkers indicating brain amyloidosis should not be considered conclusive evidence that AD pathology accounts for a typical FTD clinical/anatomical syndrome.
- Published
- 2013
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25. Utilization of the Nursing Process to Foster Clinical Reasoning During a Simulation Experience
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Amanda Lambie, Kelly Schwend, and Andrea Scholl
- Subjects
History of scholarship and learning. The humanities ,AZ20-999 ,Social Sciences - Abstract
Nursing practice includes complex reasoning and multifaceted decision making with minimal standardized guidance in how to evaluate this phenomenon among nursing students. Learning outcomes related to the clinical reasoning process among novice baccalaureate nursing students during a simulation experience were evaluated. Nursing process records were utilized to evaluate and foster the development of clinical reasoning in a high-fidelity medical-surgical simulation experience. Students were unable to describe and process pertinent patient information appropriately prior to the simulation experience. Students’ ability to identify pertinent patient cues and plan appropriate patient care improved following the simulation. The learning activity afforded a structured opportunity to identify cues, prioritize the proper course of nursing interventions, and engage in collaboration among peers. The simulation experience provides faculty insight into the students’ clinical reasoning processes, while providing students with a clear framework for successfully accomplishing learning outcomes.
- Published
- 2015
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26. The yeast Shu complex utilizes homologous recombination machinery for error-free lesion bypass via physical interaction with a Rad51 paralogue.
- Author
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Xin Xu, Lindsay Ball, Wangyang Chen, Xuelei Tian, Amanda Lambrecht, Michelle Hanna, and Wei Xiao
- Subjects
Medicine ,Science - Abstract
DNA-damage tolerance (DDT) is defined as a mechanism by which eukaryotic cells resume DNA synthesis to fill the single-stranded DNA gaps left by replication-blocking lesions. Eukaryotic cells employ two different means of DDT, namely translesion DNA synthesis (TLS) and template switching, both of which are coordinately regulated through sequential ubiquitination of PCNA at the K164 residue. In the budding yeast Saccharomyces cerevisiae, the same PCNA-K164 residue can also be sumoylated, which recruits the Srs2 helicase to prevent undesired homologous recombination (HR). While the mediation of TLS by PCNA monoubiquitination has been extensively characterized, the method by which K63-linked PCNA polyubiquitination leads to template switching remains unclear. We recently identified a yeast heterotetrameric Shu complex that couples error-free DDT to HR as a critical step of template switching. Here we report that the Csm2 subunit of Shu physically interacts with Rad55, an accessory protein involved in HR. Rad55 and Rad57 are Rad51 paralogues and form a heterodimer to promote Rad51-ssDNA filament formation by antagonizing Srs2 activity. Although Rad55-Rad57 and Shu function in the same pathway and both act to inhibit Srs2 activity, Shu appears to be dedicated to error-free DDT while the Rad55-Rad57 complex is also involved in double-strand break repair. This study reveals the detailed steps of error-free lesion bypass and also brings to light an intrinsic interplay between error-free DDT and Srs2-mediated inhibition of HR.
- Published
- 2013
- Full Text
- View/download PDF
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