67 research outputs found
Caderninhos da Déborah: a história do livro didático passa por aqui
No full textIn this testimony, the retired teacher of teaching Déborah Pádua Mello Neves, author of textbooks, tells us how she became one of the authors that have sold more books in Brazil. She initiatedher activities in an important period of transition in Brazilian education and textbook: time of educational reforms and expansion of an incipient public school, of the school texts printing consolidation, of ideas and procedures renewal to attend to curriculum and program changes that represented a remarkable increase in the standard textbook that existed until the First World War.Neste Depoimento, a professora aposentada do magistério Déborah Pádua Mello Neves, autora de livros didáticos, relata como se tornou uma das escritoras que mais vendeu livros no Brasil. Iniciou suas atividades no importante período de transição da educação e do livro didático brasileiro. Época de reformas educacionais e da expansão da escola pública, incipiente até então, de consolidação da impressão de textos escolares no Brasil e de renovação de idéias e procedimentos para atender às modificações de currículos e programas que representam o progresso considerável sobre o padrão de livro didático vigenteaté a Primeira Guerra Mundial
Diagnosis of atypical myopathy based on organic acid and acylcarnitine profiles and evolution of biomarkers in surviving horses
No full textBackground: Atypical myopathy (AM), an acquired multiple acyl-CoA dehydrogenase deficiency (MADD) in horses, induce changes in mitochondrial metabolism. Only few veterinary laboratories offer diagnostic testing for this disease. Inborn and acquired MADD exist in humans, therefore determination of organic acids (OA) in urine and acylcarnitines (AC) in blood by assays available in medical laboratories can serve as AM diagnostics. The evolution of OA and AC profiles in surviving horses is unreported.
Methods: AC profiles using electrospray ionization tandem mass spectrometry (ESI-MS/MS) and OA in urine using gas chromatography mass spectrometry (GC–MS) were determined in dried blot spots (DBS, n = 7) and urine samples (n = 5) of horses with AM (n = 7) at disease presentation and in longitudinal samples from 3/4 survivors and compared to DBS (n = 16) and urine samples (n = 7) from control horses using the Wilcoxon test.
Results: All short- (C2-C5) and medium-chain (C6-C12) AC in blood differed significantly (p < 0.008) between horses with AM and controls, except for C5:1 (p = 0.45) and C5OH + C4DC (p = 0.06). In AM survivors the AC concentrations decreased over time but were still partially elevated after 7 days. 14/62 (23%) of OA differed significantly between horses with AM and control horses. Concentrations of ethylmalonic acid, 2-hydroxyglutaric acid and the acylglycines (butyryl-, valeryl-, and hexanoylglycine) were highly elevated in the urine of all horses with AM at the day of disease presentation. In AM survivors, concentrations of those metabolites were initially lower and decreased during remission to approach normalization after 7 days.
Conclusion: OA and AC profiling by specialized human medical laboratories was used to diagnose AM in horses. Elevation of specific metabolites were still evident several days after disease presentation, allowing diagnosis via analysis of samples from convalescent animals
ACADM Frameshift Variant in Cavalier King Charles Spaniels with Medium-Chain Acyl-CoA Dehydrogenase Deficiency
No full textA 3-year-old, male neutered Cavalier King Charles Spaniel (CKCS) presented with complex focal seizures and prolonged lethargy. The aim of the study was to investigate the clinical signs, metabolic changes and underlying genetic defect. Blood and urine organic acid analysis revealed increased medium-chain fatty acids and together with the clinical findings suggested a diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. We sequenced the genome of the affected dog and compared the data to 923 control genomes of different dog breeds. The ACADM gene encoding MCAD was considered the top functional candidate gene. The genetic analysis revealed a single homozygous private protein-changing variant in ACADM in the affected dog. This variant, XM_038541645.1:c.444_445delinsGTTAATTCTCAATATTGTCTAAGAATTATG, introduces a premature stop codon and is predicted to result in truncation of ~63% of the wild type MCAD open reading frame, XP_038397573.1:p.(Thr150Ilefs*6). Targeted genotyping of the variant in 162 additional CKCS revealed a variant allele frequency of 23.5% and twelve additional homozygous mutant dogs. The acylcarnitine C8/C12 ratio was elevated ~43.3 fold in homozygous mutant dogs as compared to homozygous wild type dogs. Based on available clinical and biochemical data together with current knowledge in humans, we propose the ACADM frameshift variant as causative variant for the MCAD deficiency with likely contribution to the neurological phenotype in the index case. Testing the CKCS breeding population for the identified ACADM variant is recommended to prevent the unintentional breeding of dogs with MCAD deficiency. Further prospective studies are warranted to assess the clinical consequences of this enzyme defect
Feasibility of semi-continuous solar disinfection system for developing countries at a household level
No full textThesis (M.Eng.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, 2003.Includes bibliographical references (leaves 98-101).A study to assess the feasibility of a novel solar water disinfection system developed by the author, Semi-Continuous Solar Disinfection (SC-SODIS), was conducted. Three aspects of SC-SODIS feasibility were considered: technical, social and economic feasibility. This study focused on developing countries and specifically, Nepal. To address the technical feasibility, field data included measuring the performance of the prototype system under climatologic conditions found in Lumbini, Nepal during the month of January 2003. The social and economic feasibilities were determined from preliminary feedback from local people and calculation of construction costs from locally available materials respectively. Results suggest SC-SODIS is a feasible technology for developing countries and specifically Lumbini, Nepal. SC-SODIS can be considered a sustainable technology as it is technically simple, effective at microbial inactivation as measured by the E.coli indicator organism, can be made from locally available materials and is economical. Preliminary feedback from locals show SC-SODIS is socio-culturally acceptable. Limited time did not allow study of the operation and maintenance problems that the system might present over the long term.by Déborah Xanat Flores Cervantes.M.Eng
The solute carrier SLC16A12 is critical for creatine and guanidinoacetate handling in the kidney
No full textA heterozygous mutation (c.643C.A; p.Q215X) in the creatine transporter SLC16A12 was proposed to cause a syndrome with juvenile cataracts, microcornea and glucosuria in humans. To further explore the role of SLC16A12 in renal physiology and decipher the mechanism underlying the phenotype of humans with the SLC16A12 mutation, we studied Slc16a12 knock-out (KO) rats. Slc16a12 KO rats had lower plasma levels and increased absolute and fractional urinary excretion of creatine and its precursor guanidinoacetate (GAA). Slc16a12 KO rats displayed lower plasma and urinary creatinine levels, but GFR was normal. The phenotype of heterozygous rats was indistinguishable from wild-type (WT) rats. Renal artery to vein (RAV) concentration differences in WT rats were negative for GAA and positive for creatinine. However, RAV differences for GAA were similar in Slc16a12 KO rats, indicating incomplete compensation of urinary GAA losses by renal GAA synthesis. Together, our results reveal that Slc16a12 in the basolateral membrane of the proximal tubule is critical for reabsorption of creatine and GAA. Our data suggest a dominant-negative mechanism underlying the phenotype of humans affected by the heterozygous SLC16A12 mutation. Furthermore, in the absence of Slc16a12, urinary losses of GAA are not adequately compensated by increased tubular synthesis, caused by feedback inhibition of the rate limiting enzyme L-arginine:glycine amidinotransferase by creatine in proximal tubular cells
Specific GAG ratios in the diagnosis of mucopolysaccharidoses.
No full textMucopolysaccharidoses (MPS) screening is tedious and still performed by analysis of total glycosaminoglycans (GAG) using 1,9-dimethylmethylene blue (DMB) photometric assay, although false positive and negative tests have been reported. Analysis of differentiated GAGs have been pursued classically by gel electrophoresis or more recently by quantitative LC-MS assays. Secondary elevations of GAGs have been reported in urinary tract infections (UTI). In this manuscript, we describe the diagnostic accuracy of urinary GAG measurements by LC-MS for MPS typing in 68 untreated MPS and mucolipidosis (ML) patients, 183 controls and 153 UTI samples. We report age-dependent reference values and cut-offs for chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS) and keratan sulfate (KS) and specific GAG ratios. The use of HS/DS ratio in combination to GAG concentrations normalized to creatinine improves the diagnostic accuracy in MPS type I, II, VI and VII. In total 15 samples classified to the wrong MPS type could be correctly assigned using HS/DS ratio. Increased KS/HS ratio in addition to increased KS improves discrimination of MPS type IV by excluding false positives. Some samples of UTI patients showed elevation of specific GAGs, mainly CS, KS and KS/HS ratio and could be misclassified as MPS type IV. Finally, DMB photometric assay performed in MPS and ML samples reveal four false negative tests (sensitivity of 94%). In conclusion, specific GAG ratios in complement to quantitative GAG values obtained by LC-MS enhance discrimination of MPS types. Exclusion of patients with UTI improve diagnostic accuracy in MPS IV but not in other types
Levels of Circulating Ketone Bodies in Patients Undergoing Cardiac Surgery on Cardiopulmonary Bypass
No full textKetone bodies (KBs) are energy-efficient substrates utilized by the heart depending on its metabolic demand and substrate availability. Levels of circulating KBs have been shown to be elevated in acute and chronic cardiovascular disease and are associated with severity of disease in patients with heart failure and functional outcome after myocardial infarction. To investigate whether this pattern similarly applies to patients undergoing cardiac surgery involving cardiopulmonary bypass (CPB), we analysed prospectively collected pre- and postoperative blood samples from 192 cardiac surgery patients and compared levels and perioperative changes in total KBs with Troponin T as a marker of myocardial cell injury. We explored the association of patient characteristics and comorbidities for each of the two biomarkers separately and comparatively. Median levels of KBs decreased significantly over the perioperative period and inversely correlated with changes observed for Troponin T. Associations of patient characteristics with ketone body perioperative course showed notable differences compared to Troponin T, possibly highlighting factors acting as a “driver” for the change in the respective biomarker. We found an inverse correlation between perioperative change in ketone body levels and changes in troponin, indicating a marked decrease in ketone body concentrations in patients exhibiting greater myocardial cell injury. Further investigations aimed at better understanding the role of KBs on perioperative changes are warranted
Metabolomics analysis of antiquitin deficiency in cultured human cells and plasma: relevance to pyridoxine-dependent epilepsy.
No full textAIM
Deficiency of antiquitin (α-aminoadipic semialdehyde dehydrogenase ), an enzyme involved in lysine degradation and encoded by ALDH7A1, is the major cause of vitamin B6 -dependent epilepsy (PDE-ALDH7A1). Despite seizure control with high dose pyridoxine (PN), developmental delay still occurs in approximately 70% of patients. We aimed to investigate metabolic perturbations due to possible previously unidentified roles of antiquitin, which may contribute to developmental delay, as well as metabolic effects of high dose pyridoxine supplementation reflecting the high doses used for seizure control in patients with PDE-ALDH7A1.
METHODS
Untargeted metabolomics by high resolution mass spectrometry (HRMS) was used to analyse plasma of patients with PDE-ALDH7A1 and two independently generated lines of cultured ReNcell CX human neuronal progenitor cells (NPCs) with CRISPR/Cas mediated antiquitin deficiency. Accumulation of lysine pathway metabolites in antiquitin-deficient NPCs and Western-blot analysisconfirmed knockdown of ALDH7A1.
RESULTS
Metabolomics analysis of antiquitin-deficient NPCs in conditions of lysine restriction and PN supplementation identified changes in metabolites related to the transmethylation and transsulfuration pathways and osmolytes, indicating a possible unrecognized role of antiquitin outside the lysine degradation pathway. Analysis of plasma samples of PN treated patients with PDE-ALDH7A1 and antiquitin-deficient NPCs cultured in conditions comparable to the patient plasma samples demonstrated perturbation of metabolites of the gamma-glutamyl cycle, suggesting potential oxidative stress-related effects in PN-treated patients with PDE-ALDH7A1.
CONCLUSIONS
We postulate that a model of human NPCs with CRISPR/Cas mediated antiquitin deficiency is well suited to characterise previously unreported roles of antiquitin, relevant to this most prevalent form of pyridoxine-dependent epilepsy. This article is protected by copyright. All rights reserved
Proceso de aprendizaje de los médicos tradicionales nahuas de Tehuetlán, Huasteca Hidalguense
No full textTesis para obtener el grado de Licenciatura en Etnohistori
Exploratory Inquiring enabled by data visualization to enhance designer's creative process
No full textFord aims to implement a data-enabled design approach, using data to inspire and inform the whole creative process. In this context, in 2020, they took a step to reach this goal by setting up a University Research Project with the Industrial Design Faculty at Technology University of Delft, proposing data visualisation as one of the research lines. In this master thesis project, the role of Data Visualization in Data-Enabled Design projects is investigated, specifically how to use Data Visualization more efficiently to generate insights and inform the creative process of Ford design.The initial stages of the project were focused on understanding how Ford is using data in the design process and reviewing the published literature about creativity, data, data-enabled design, data visualisation, and exploratory data analysis. Then, through a critical reflection about the intersections of the theoretical research, eight possible design directions were identified in which data visualisation can support the creative process, termed “crossing bridges”.Afterwards, in collaboration with the company, the one with higher potential, “Exploratory inquiring”, was selected to investigate further. Hence, three empirical studies were developed: personal explorations, a design students workshop and one workshop with Ford employees.The last steps included the analysis and discussion of these sessions individually and comparatively, considering the limits of this research and the proposal of different aspects to consider in future research. Finally, I present a guide to support Ford in performing Exploratory Inquiring.Design for Interactio
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