Neonatal screening for cystic fibrosis in São Paulo State, Brazil : a pilot study

Cystic fibrosis is one of the most common autosomal recessive hereditary diseases in the Caucasian population, with an incidence of 1:2000 to 1:3500 liveborns. More than 1000 mutations have been described with the most common being F508del. It has a prevalence of 23-55% within the Brazilian population. The lack of population-based studies evaluating the incidence of cystic fibrosis in São Paulo State, Brazil, and an analysis concerning the costs of implantation of a screening program motivated the present study. A total of 60,000 dried blood samples from Guthrie cards obtained from April 2005 to January 2006 for neonatal screening at 4 reference centers in São Paulo State were analyzed. The immunoreactive trypsinogen (IRT)/IRT protocol was used with the cut-off value being 70 ng/mL. A total of 532 children (0.9%) showed IRT >70 ng/mL and a 2nd sample was collected from 418 (80.3%) of these patients. Four affected children were detected at two centers, corresponding to an incidence of 1:8403. The average age at diagnosis was 69 days, and 3 of the children already showed severe symptoms of the disease. The rate of false-positive results was 95.2% and the positive predictive value for the test was 8%. The cost of detecting an affected subject was approximately US$8,000.00 when this cystic fibrosis program was added to an existing neonatal screening program. The present study clearly shows the difficulties involved in cystic fibrosis screening using the IRT/IRT protocol, particularly in a population with no long-term tradition of neonatal screening421

hERG, Plasmodium life cycle, and cross resistance profiling of new azabenzimidazole analogues of astemizole

SUPPLEMENTARY INFORMATION : Experimental procedures and characterization data of synthetic intermediates (5a–5f, 6a–6f, 13, and 15) and target compounds (7–12 and 15); biochemical assay protocols, including solubility and cross-resistance studies; H NMR spectra of representative target compounds.Please read abstract in the article.The University of Cape Town (UCT), South African Medical Research Council, the South African Research Chairs Initiative (SARChI) of the Department of Science and Innovation (DSI) administered through the South African National Research Foundation (NRF), the Brazilian National Council for Scientific and Technological Development, Proep-Fiocruz Program (Brazil), the Neville Isdell Chair in African-centric Drug Discovery and Development, and Neville Isdell for generously funding the Chair.http://pubs.acs.org/journal/amclcthj2024BiochemistryGeneticsMicrobiology and Plant PathologyUP Centre for Sustainable Malaria Control (UP CSMC)SDG-03:Good heatlh and well-bein

Trends In Metal-binding And Metalloprotein Analysis

This review describes recent tendencies for metal-binding and metalloprotein analysis, emphasizing metal quantification in proteins through X-ray, atomic absorption, mass spectrometric techniques, and others. Hyphenated techniques such as capillary electrophoresis-synchrotron radiation X-ray fluorescence (CE-SRXRF), laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), matrix-assisted laser desorption/ionisation-time-of- flight mass spectrometry (MALDI-TOF-MS), etc. are also presented. As protein separation techniques electrophoresis (mainly sodium dodecyl sulphate-polyacrylamide gel electrophoresis, SDS-PAGE), capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC) are indicated, due to their inherent sensitivity, resolution and/or easy implementation. Latest challenges in metallomics are also commented. © 2005 Elsevier B.V. All rights reserved.691115Jakubowski, N., Lobinski, R., Moens, L., (2004) J. Anal. At. 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Efeito da peletização na germinação e desenvolvimento de cultivares de sorgo.

O sorgo quando cultivado apos a soja requer agilidade na semeadura para aproveitamento do periodo chuvoso. A semeadura aerea permite que o sorgo seja semeado antes da colheita da soja, favorecendo um melhor uso do periodo chuvoso com consequente aumento da produtividade. O aumento no peso das sementes em decorrencia da peletizacao e a presenca de nutrientes proximos as plantulas, devera aumentar a eficiencia da semeadura aerea e favorecer o desenvolvimento das plantulas de sorgo. Visando avaliar o efeito da peletizacao de sementes de sorgo com diferentes adubos, foram instalados tres ensaios, com quatro repeticoes, compostos dos seguintes tratamentos: tres cultivares de sorgo, Savana 5, BR 601 e BR 304; quatro revestimentos (peletes); FTE, KCI + SS, calcario,Yoorin e uma testemunha sem peletizacao. Apos a peletizacao, as sementes de sorgo foram colocadas para germinar em laboratorio em placas de Petri, na casa de vegetacao em caixas de madeira e no campo. Os parametros avaliados foram: porcentagem de germinacao, indice de velocidade de emergencia e peso seco das plantulas. No laboratorio, o Yoorin destacou-se como o melhor revestimento. Na casa de vegetacao, apenas a germinacao das sementes foi alterada pelos revestimentos, tendo sobressaido os tratamentos KCl+SS, FTE e calcario. No campo nao foram obtidas diferencas significativas entre os tratamentos. Pode-se concluir que a peletizacao em geral aumentou a qualidade e o vigor das sementes de sorgo.199

In Vitro Microleakage Of Glass-ionomer Composite Resin Hybrid Materials.

The purpose of this study was to evaluate the microleakage of six glass-ionomer composite resin hybrid materials compared with a glass-ionomer cement and a composite resin. Standardized class 5 dentin cavities were prepared on root surfaces of 240 extracted human teeth that were randomly assigned to eight groups and restored using the following restorative systems: (I) Vitremer, (II) Compoglass, (III) Photac-Fil Aplicap, (IV) Variglass, (V) Dyract, (VI) Fuji II LC, (VII) Ketac-Fil Aplicap, and (VIII) Z100. The teeth were thermocycled, placed in a 2% methylene blue solution, and sectioned with diamond disks. Dye penetration was scored on a scale of 0-3. Results showed no significant differences among groups VIII, IV, I, V, VI, III, and II. There were also no significant differences among groups VI, III, II, and VII.242899

Neonatal screening for cystic fibrosis in São Paulo State, Brazil: a pilot study

Cystic fibrosis is one of the most common autosomal recessive hereditary diseases in the Caucasian population, with an incidence of 1:2000 to 1:3500 liveborns. More than 1000 mutations have been described with the most common being F508del. It has a prevalence of 23-55% within the Brazilian population. The lack of population-based studies evaluating the incidence of cystic fibrosis in São Paulo State, Brazil, and an analysis concerning the costs of implantation of a screening program motivated the present study. A total of 60,000 dried blood samples from Guthrie cards obtained from April 2005 to January 2006 for neonatal screening at 4 reference centers in São Paulo State were analyzed. The immunoreactive trypsinogen (IRT)/IRT protocol was used with the cut-off value being 70 ng/mL. A total of 532 children (0.9%) showed IRT >70 ng/mL and a 2nd sample was collected from 418 (80.3%) of these patients. Four affected children were detected at two centers, corresponding to an incidence of 1:8403. The average age at diagnosis was 69 days, and 3 of the children already showed severe symptoms of the disease. The rate of false-positive results was 95.2% and the positive predictive value for the test was 8%. The cost of detecting an affected subject was approximately US$8,000.00 when this cystic fibrosis program was added to an existing neonatal screening program. The present study clearly shows the difficulties involved in cystic fibrosis screening using the IRT/IRT protocol, particularly in a population with no long-term tradition of neonatal screening

CYBB, an NADPH-oxidase gene: restricted diversity in humans and evidence for differential long-term purifying selection on transmembrane and cytosolic domains

CYBB encodes the gp91-phox protein of the phagocytic NADPH oxidase; the innate immunity-related enzymatic complex responsible for the respiratory burst. Mutations in CYBB can cause chronic granulomatous disease (CGD), a primary immunodeficiency characterized by ineffective microbicidal activity, for which over 150 family-specific mutations have been described. It is also plausible that common SNPs in CYBB alter the expression or function of gp91-phox, determining differences in susceptibility to complex disorders such as autoimmune or infectious diseases. We have resequenced the exons, UTRs, and intronic regions of CYBB in 102 ethnically diverse individuals and genotyped nine tag-SNPs in 942 individuals from 52 worldwide populations. The 28 observed SNPs (none of which nonsynonymous) reside on 28 haplotypes that can be collapsed into five clades. CYBB shows lower diversity than other X-chromosome genes and most of the between-population genetic variance was observed among Africans and non-Africans. The African population shows the highest diversity and the lowest linkage disequilibrium (LD). Because there is extensive shared LD among non,Africans, tag-SNPs can be effectively employed in gene,centric association studies and are portable across Eurasian and Native American populations. Comparison of CYBB coding sequences among mammals evidences the action of long-term purifying selection, which is stronger on the C-terminal cytosolic domain than on the N-terminal transmembrane domain of gp91-phox