Pharmacogenetics of pediatric acute lymphoblastic leukemia in Uruguay: adverse events related to induction phase drugs.

In Uruguay, the pediatric acute lymphoblastic leukemia (ALL) cure rate is 82.2%, similar to those reported in developed countries. However, many patients suffer adverse effects that could be attributed, in part, to genetic variability. This study aims to identify genetic variants related to drugs administered during the induction phase and analyze their contribution to adverse effects, considering individual genetic ancestry. Ten polymorphisms in five genes (ABCB1, CYP3A5, CEP72, ASNS, and GRIA1) related to prednisone, vincristine, and L-asparaginase were genotyped in 200 patients. Ancestry was determined using 45 ancestry informative markers (AIMs). The sample ancestry was 69.2% European, 20.1% Native American, and 10.7% African, but with high heterogeneity. Mucositis, Cushing syndrome, and neurotoxicity were the only adverse effects linked with genetic variants and ancestry. Mucositis was significantly associated with ASNS (rs3832526; 3R/3R vs. 2R carriers; OR: = 6.88 [1.88-25.14], p = 0.004) and CYP3A5 (non-expressors vs. expressors; OR: 4.55 [1.01-20.15], p = 0.049) genes. Regarding Cushing syndrome, patients with the TA genotype (rs1049674, ASNS) had a higher risk of developing Cushing syndrome than those with the TT genotype (OR: 2.60 [1.23-5.51], p = 0.012). Neurotoxicity was significantly associated with ABCB1 (rs9282564; TC vs. TT; OR: 4.25 [1.47-12.29], p = 0.007). Moreover, patients with <20% Native American ancestry had a lower risk of developing neurotoxicity than those with ≥20% (OR: 0.312 [0.120-0.812], p = 0.017). This study shows the importance of knowing individual genetics to improve the efficacy and safety of acute lymphoblastic leukemia.

An updated examination of the perception of barriers for pharmacogenomics implementation and the usefulness of drug/gene pairs in Latin America and the Caribbean.

Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers based on their importance. In addition, a paired list of 54 genes/drugs was analyzed to determine an association between biomarkers and response to genomic medicine. This survey was compared to a previous survey performed in 2014 to assess progress in the region. The search results indicated that Latin American and Caribbean countries have contributed 3.44% of the total publications and 2.45% of the PGx-related clinical trials worldwide thus far. A total of 106 professionals from 17 countries answered the survey. Six major groups of barriers were identified. Despite the region's continuous efforts in the last decade, the primary barrier to PGx implementation in LAC remains the same, the "need for guidelines, processes, and protocols for the clinical application of pharmacogenetics/pharmacogenomics". Cost-effectiveness issues are considered critical factors in the region. Items related to the reluctance of clinicians are currently less relevant. Based on the survey results, the highest ranked (96%-99%) gene/drug pairs perceived as important were CYP2D6/tamoxifen, CYP3A5/tacrolimus, CYP2D6/opioids, DPYD/fluoropyrimidines, TMPT/thiopurines, CYP2D6/tricyclic antidepressants, CYP2C19/tricyclic antidepressants, NUDT15/thiopurines, CYP2B6/efavirenz, and CYP2C19/clopidogrel. In conclusion, although the global contribution of LAC countries remains low in the PGx field, a relevant improvement has been observed in the region. The perception of the usefulness of PGx tests in biomedical community has drastically changed, raising awareness among physicians, which suggests a promising future in the clinical applications of PGx in LAC.

Impact of different complete coverage onlay preparation designs and the intraoral scanner on the accuracy of digital scans.

STATEMENT OF PROBLEM: The trueness and precision of intraoral scanners (IOSs) and the effect of intracoronal restorations have been reported. However, studies addressing the accuracy of IOSs in reproducing different complete coverage onlay preparation designs are lacking. PURPOSE: The purpose of this in vitro study was to evaluate the influence of complete coverage onlay preparation design and intraoral scanning devices on the accuracy of digital scans in terms of trueness and precision. MATERIAL AND METHODS: Three preparation designs on the mandibular first molar were considered: a traditional preparation design with isthmus reduction (IST), a traditional preparation design without isthmus reduction (wIST), and simplified nonretentive preparation (nRET). Digital scans of epoxy resin mandibular arch reference models of the preparations (containing second premolar, first molar, and second molar) were obtained by using 3 IOSs (iTero Element 2 [ELE], Trios 3 [TRI], and Primescan [PRI]) (n=10). Trueness (µm) and precision (µm) were analyzed by superimposing the digital scan on the digital reference models obtained with a high-accuracy industrial scanner (ATOS Core 80) in a tridimensional metrology software program. Accuracy was quantified by the absolute deviation (µm). Local and overall mean positive and negative deviations for trueness were also obtained. Data were analyzed by using the Kruskal-Wallis and Dunn tests with a statistical software program (α=.05). RESULTS: The nonretentive preparation groups obtained higher trueness (3.8 µm) and precision (2.7 µm) than the IST and wIST groups (trueness=7.5 to 6.3 µm, precision=5.5 to 4.6 µm). Trueness values were lower with ELE×IST (16 µm), followed by ELE×wIST (13 µm), and PRI×IST (7.8 µm). In general, no difference was found between PRI and TRI scanners (6.3 to 5.9 µm), with lower performance for ELE (13 µm). Positive deviations were higher on the proximal box of the IST and wIST preparation and on the occlusal box of the IST group. Negative deviation was higher on the ELE×IST occlusal box. CONCLUSIONS: Different intraoral scanners and preparation designs influenced the accuracy of digital scans. A more complex preparation such as IST and wIST showed higher deviation. The iTero Element 2 scanner exhibited higher deviation for both trueness and precision.

Alpha thalassemia and alpha-MRE haplotypes in Uruguayan patients with microcytosis and hypochromia without anemia.

Alpha thalassemia is the most common genetic disorder across the world, being the α-3.7 deletion the most frequent mutation. In order to analyze the spectrum and origin of alpha thalassemia mutations in Uruguay, we obtained a sample of 168 unrelated outpatients with normal hemoglobin levels with microcytosis and hypochromia from two cities: Montevideo and Salto. The presence of α-thalassemia mutations was investigated by gap-PCR, restriction endonucleases analysis and HBA2 and HBA1 genes sequencing, whereas the alpha-MRE haplotypes were investigated by sequencing. We found 55 individuals (32.7%) with α-thalassemia mutations, 51(30.4%) carrying the -α3.7 deletion, one with the -α4.2 deletion and three having the rare punctual mutation HBA2:c.-59C>T. Regarding alpha-MRE analysis, we observed a significant higher frequency of haplotype D, characteristic of African populations, in the sample with the -α3.7 deletion. These results show that α-thalassemia mutations are an important determinant of microcytosis and hypochromia in Uruguayan patients with microcytosis and hypochromia without anemia, mainly due to the -α3.7 deletion. The alpha-MRE haplotypes and the α-thalassemia mutations spectrum suggest a predominant, but not exclusive, African origin of these mutations in Uruguay.

Novel speed sintered zirconia by microwave technology.

OBJECTIVE: Continuous efforts have been made to hasten the zirconia densification process without compromising properties. This study evaluated the long-term structural durability of microwave speed-sintered zirconia (MWZ) relative to a conventionally sintered zirconia (CZ). METHODS: As-machined dental 3Y-TZP discs (Ø12 × 1.2 mm) were speed sintered at 1450 °C for 15 min using an industrial microwave oven, while conventional sintering was conducted in a standard dental furnace at 1530 °C for 2 h. Both were followed by natural cooling. The total sintering time was 105 min for MWZ and 600 min for CZ. Groups were compared regarding density, grain size, phase composition, and fracture resistance. Structural durability was investigated employing two fatigue protocols, step-stress and dynamic fatigue. RESULTS: Compared to CZ, MWZ exhibited a slightly lower density (MWZ = 5.98 g/cm3, CZ = 6.03 g/cm3), but significantly smaller grain sizes (MWZ = 0.53 ± 0.09 µm, CZ = 0.89 ± 0.10 µm), lower cubic-zirconia contents (MWZ = 15.3%, CZ = 22.7%), and poorer translucency properties (TP) (MWZ = 13 ± 1, CZ = 29 ± 0.8). However, the two materials showed similar flexural strength (MWZ = 978 ± 112 MPa, CZ = 1044 ± 161 MPa). Additionally, step-stress testing failed to capture the fatigue effect in 3Y-TZP, whereas dynamic fatigue revealed structural degradation due to moisture-assisted slow-crack-growth (SCG). Finally, MWZ possessed a slightly higher Weibull modulus (MWZ = 7.9, CZ = 6.7) but similar resistance to SCG (MWZ = 27.5, CZ = 24.1) relative to CZ. SIGNIFICANCE: Dental 3Y-TZP with similar structural durability can be fabricated six-times faster by microwave than conventional sintering.

Ancestry and TPMT-VNTR Polymorphism: Relationship with Hematological Toxicity in Uruguayan Patients with Acute Lymphoblastic Leukemia.

6-Mercaptopurine (6-MP) is a thiopurine drug widely used in childhood acute lymphoblastic leukemia (ALL) therapy. Genes such as TPMT and NUDT15 have an outstanding role in 6-MP metabolism. Mutations in both genes explain a significant portion of hematological toxicities suffered by ALL Uruguayan pediatric patients. A variable number tandem repeat in the TPMT promoter (TPMT-VNTR) has been associated with TPMT expression. This VNTR has a conservative architecture (AnBmC). To explore new causes of hematological toxicities related to ALL therapy, we genotyped the TPMT-VNTR of 130 Uruguayan pediatric patients. Additionally, individual genetic ancestry was estimated by 45 ancestry-informative markers (AIMs). Hematological toxicity was measured as the number of leukopenia events and 6-MP dose along the maintenance phase. As previously reported, we found TPMT*2 and TPMT*3C alleles were associated to TPMT-VNTR A2BC and AB2C, respectively. However, contrasting with other reports, TPMT*3A allele was found in a heterogeneous genetic background in linkage equilibrium. Patients carrying more than 5 A repeats present a significant higher number of leukopenia events among patients without TPMT and/or NUDT15 variants. Native American ancestry and the number of A repeats were significantly correlated with the number of leukopenia events. However, the correlation between Native American ancestry and the number of leukopenia events was lost when the number of A repeats was considered as covariate. This suggests that TPMT-VNTR alleles are more relevant than Native American ancestry in the hematological toxicity. Our results emphasize that TPMT-VNTR may be used as a pharmacogenetic biomarker to predict 6-MP-related hematological toxicity in ALL childhood therapy.

Failure Probability, Stress Distribution and Fracture Analysis of Experimental Screw for Micro Conical Abutment.

The aim of this study was to evaluate the failure probability of two types of abutment screws after compressive load and to analyze the stress distribution with finite element method. Sixty (60) single-tooth implant restorations were assembled on titanium implants (e-fix, A.S. Technology - Titanium Fix). The groups were divided into Conventional screw (Screw neck 1.5 ø mm) and Experimental screw (Screw neck constricted with 1.2 ø mm). Specimens were subjected to single load to failure with compressive test according ISO 14801. The fractured specimens were subjected to stereomicroscopy for measurement of remaining screws inside the implant and characterization of fracture origin. Representative specimens were analyzed by scanning electronic microscopy. For finite element method (FEM), an identical 3D model of the two in vitro test groups were used with similar conditions (30º, 100 N load). The stress in the abutment screw was analyzed by von-Mises criteria. The results of strength means were 4132.5 ± 76 MPa and 4528.2 ± 127.2 for conventional and experimental groups, respectively. During microscopy, the mean (mm) of the remaining screw piece inside the implants were 0.97 ± 0.23 and 1.32 ± 0.12 for conventional and experimental groups, respectively. In FEM, the conventional group showed stress concentered in an unfavorable region (peak of 39.23 MPa), while the experimental group showed more stress areas but less concentration than the conventional group (36.6 MPa). In using the tested experimental geometry, the abutment screw can have its strength improved, and the origin of failure can be more favorable to clinical resolution.

Prevalencia de anemia en niñas/os de 6 a 48 meses que concurren a dos CAIF de la ciudad de Salto / Prevalência de anemia em crianças de 6 a 48 meses que concorrem a centros de atenção a primeira infância da cidade de salto / Prevalence of anemia in 6 to 48 month children attending to an infancy primary care center of salto city

Introducción. La anemia en los niños es un problema de salud pública importante en nuestro país, siendo la anemia por deficiencia de hierro la más frecuente. La frecuencia de anemia en el interior del país es mayor a lo observado en Montevideo. Sin embargo, no existen datos específicos del Departamento de Salto. Objetivos. Determinar la prevalencia de anemia en niños y niñas de 6 a 48 meses que concurren a dos Centros de Atención a la Primera Infancia (CAIF) de la ciudad de Salto y analizar los factores de riesgo asociados. Metodología. Se determino los niveles de hemoglobina por punción digital en 240 niños de dos CAIF, se relevaron los antecedentes perinatales del carnet del niño/a y datos de ancestralidad por medio de una encuesta a los responsables de los niños. Resultados. La prevalencia de anemia fue de 22,5% en toda la muestra, siendo levemente mayor en el CAIF2 (27,4%) que en el CAIF1(18,4%). La frecuencia de anemia fue significativamente menor en los niños que tuvieron lactancia materna exclusiva hasta los 6 meses de edad, mientras que las restantes variables analizadas no presentaron asociación con la anemia. Conclusiones. La disminución observada de la frecuencia de anemia comparada con lo reportado en 2011 sugiere que las políticas de fortificación con hierro de los alimentos y de administración de hierro profiláctico a niños entre 6 y 24 meses ha sido positiva. Adicionalmente, la menor frecuencia de anemia observada en el CAIF1 indica la importancia de la acción coordinada entre los servicios de salud y la sociedad.

Introduction. Anemia in children is a public health problem in Uruguay, being iron deficiency anemia the most frequent etiology. The anemia prevalence is higher in regions or cities different to Montevideo. However, there is no specific data from the Salto city. Objectives. Determine and compare the prevalence of anemia in children aged 6 to 48 months from two educational institutions (CAIFs) in the city of Salto and analyze the associated risk factors. Methodology. The hemoglobin levels were determined by digital puncture in 240 children of two CAIFs, the perinatal data were obtained from the child>s card and a survey to family was used to obtain ancestry data. Results The prevalence of anemia was 22.5% in the entire sample, being slightly higher in CAIF2 (27.4%) than in CAIF1 (18.4%). The frequency of anemia is significantly lower in children who had exclusive breastfeeding until 6 months of age, while the other variables analyzed were not associated with anemia. Conclusions. The prevalence of anemia observed is lower than 2011 suggesting that the policies of iron fortification of food and administration of prophylactic iron to children between 6 and 24 months has been positive. Additionally, the lower anemia frequency observed in CAIF1 than observed in CAIF2 indicates the importance.

Introdução. A anemia é um problema de saúde pública importante em nosso pais, sendo a anemia por deficiência de ferro a mais frequente. A frequência de anemia no interior do pais é maior ao observado em Montevideo. Porém, não existem dados específicos do Departamento de Salto. Objetivos. Determinar a prevalência de anemia em crianças de 6 a 48 meses que concorrem a dois Centros de Atenção da Primeira Infância (CAIF) da cidade do Salto e analisar os fatores de risco associado. Metodologia. Determinaramse os níveis de hemoglobina por punção digital em 240 crianças dos CAIF, relevaramse os antecedentes perinatais das carteiras das crianças e os dados de ancestralidade por médio de um questionário aos responsáveis das crianças. Resultados. Na amostra completa, a prevalência de anemia foi de 22,5%, com uma porcentagem levemente maior no CAIF2 (24,4%) em comparação com o CAIF1 (18,4%). A frequência de anemia foi significativamente menor nas crianças que tiveram lactância materna exclusiva até os 6 meses de idade, entanto que o resto das variáveis analisadas não apresentaram associações com à anemia. Conclusão. A diminuição observada da frequência de anemia quando comparada com o reportado em 2011 sugere que as políticas de fortificação com ferro dos alimentos e de administração profilática com ferro em crianças entre 6 e 24 meses tem sido positiva. Adicionalmente, a menor frequência de anemia observada no CAIF1 indica a importância da ação coordenada entre os serviços de saúde e sociedade.

A PVC-pipe device as a sanitary barrier for improving rainwater quality for drinking purposes in the Brazilian semiarid region.

We evaluate the behavior of a device designed to automatically divert and store the first flush of harvested rainwater in cisterns. The first phase (PI) was conducted with artificial precipitation in an experimental installation seeking to identify how many millimeters of rainwater should be diverted to preserve the rainwater quality. In the second phase (PII), we designed a PVC-pipe device to store the first millimeter of rainwater, and tested it in field (a rural area in Brazil) during two real rainfall events. In the third phase (PIII), the device and a hand pump were assayed for two years using eight cisterns in a rural area where people drink the rainwater. PI results indicated that the most significant pollution of the rainwater is flushed with the first millimeter of rain, and diversion promoted the removal of 98% and 100% of the total coliforms and Escherichia coli, respectively. The bacteriological behavior was maintained in the subsequent phases. The device was able to preserve the quality of the rainwater most of the time, satisfying drinking requirements for the parameters of turbidity and color. The satisfactory performance of the device was confirmed in the field, behaving as a sanitary barrier for rainwater quality protection.

Cimentação adesiva dos retentores de fibra de vidro: o que precisamos saber? / Adhesive cementation of fiber posts: what we need to know?

Este artigo descreveu, através de uma revisão da literatura, conceitos atuais acerca da cimentação adesiva de pinos de fibra de vidro. Já que a união entre cimento resinoso, pino e dentina assume um papel importante na longevidade do tratamento protético restaurador. Na presente revisão, foram discutidos tópicos como a influência da espessura do cimento, as estratégias adesivas que podem ser utilizadas e fatores que podem influenciar na escolha do tipo de cimento resinoso a ser utilizado, os métodos indicados para a inserção desses cimentos no interior do conduto radicular e os conceitos referentes ao tratamento de superfície, tanto do pino de fibra como da superfície dentinária.

This paper has described through current literature concepts the adhesive cementation of fiberglass posts since the adhesive union between resin cement, post and dentin plays an important role in the longevity of the restorative and prosthetic treatment. The present review discussed topics such as: the influence of cement thickness, the adhesive strategies that can be used and factors that may influence the choice of the type of resin cement to be used, the methods indicated for the insertion of these cements inside the root canal, and concepts regarding the surface treatment of both post and dentin surfaces.

Laminados cerâmicos CAD/CAM e escaneamento intraoral / CAD/CAM ceramic veneers and intra-oral scanning

Tratamentos reabilitadores estéticos têm se difundido nos dias atuais em função da evolução dos sistemas cerâmicos, aliados ao desenvolvimento tecnológico, possibilitando a realização de restaurações estéticas com mínima espessura e grande beleza, de uma forma mais rápida e precisa. Dessa forma, o objetivo deste trabalho foi a apresentação de um caso clínico, em que dois laminados cerâmicos foram confeccionados em dissilicato de lítio. Utilizou-se uma técnica de moldagem diferenciada (com escaneamento intraoral) e a confecção de um modelo digital (com impressora 3D). Atualmente, essas técnicas representam as novas possibilidades que a evolução digital tem disponibilizado para a Odontologia adesiva.

Aesthetic rehabilitation treatments have become widespread in the present day due to the evolution of the ceramic systems, combined with the technological development, enabling the accomplishment of aesthetic restorations with minimal thickness and beauty, in a faster and more precise way. In this way, the objective of this work was to present a clinical case, where two ceramic laminates were made in lithium disilicate. A diff erent dental impression technique (with intraoral scanning) and the creation of a digital model (with 3D printer) were used. Currently, these techniques represent the new possibilities that digital evolution has made available to adhesive dentistry.

O efeito do envelhecimento por fadiga na microestrutura de cerâmicas y-tzp sinterizadas por energia de micro-ondas / The effect of fatigue aging on the microstructure of y-tzp ceramics sintered by microwave energy

O objetivo deste trabalho foi avaliar o efeito da fadiga na microestrutura de uma cerâmica odontológica (Y-TZP) sinterizada pelo método convencional ou por energia de micro-ondas. A hipótese nula foi que a fadiga não irá gerar alterações na microestrutura deste material. Para isto, foram confeccionados, por meio de um sistema CAD/CAM, 84 discos de zircônia (VIPI block zircon) com características finais de 12 mm de diâmetro e 1,2 mm de espessura conforme a norma ISO 6872. Os espécimes foram separados em dois grupos: Grupo I ­ Sinterização convencional: ciclo estabelecido pelo fabricante (2 horas a 1530 °C) e Grupo II ­ sinterização por energia de micro-ondas (15 min a 1450 °C). Dez amostras por grupo foram submetidas ao teste monotônico (1000 KgF ­ 1mm/min) para a determinação da carga para fratura, utilizada como parâmetro para os testes de fadiga (método step-stress e fadiga dinâmica). O teste de fadiga step-stress foi realizado utilizando 4 perfis de carga, ultra-suave, suave, moderado e agressivo, até que ocorresse a fratura. A fadiga dinâmica foi realizada com o ensaio dos discos até fratura sob cinco taxas de tensão (1, 0,1, 0,01, 0,001 e 0,0001 MPa/s), e a partir disso foram calculados o coeficiente de crescimento de trincas e módulo de Weibull (confiabilidade) para cada grupo. Foram realizadas análises complementares de densidade, translucidez, microscopia eletrônica de varredura (MEV) e difratometria de Raios-X (DRX) de ambos os grupos para a caracterização dos materiais. Os resultados da fadiga step-stress não mostraram diferenças no comportamento dos espécimes de cada grupo. Na fadiga dinâmica, os métodos de fadiga também não mostraram diferenças no comportamento e tiveram coeficientes de crescimento de trinca similares. O modulo de Weibull mostrou maiores valores de confiabilidade para o grupo micro-ondas (m = 7,9) do que para o grupo de sinterização convencional (m = 6,7). Os valores de densidade também foram semelhantes para os grupos estudados, já a translucidez foi menor para o grupo micro-ondas. As imagens de MEV mostraram microestruturas similares entre grupos, apenas uma diferença no tamanho dos grãos foi observada, 0,53 µm para os grãos de microondas e 0,89 µm para os grãos dos espécimes sinterizados convencionalmente. Conclui-se que o processo de sinterização por microondas pode ser aplicado como alternativa de sinterização de zirconia ao dia-a dia laboratorial(AU)

The objective of this work was to evaluate the microstructure and fatigue behavior of a dental ceramic (Y-TZP) sintered by conventional method or by microwave energy. The null hypothesis was that the fatigue will not effect the microstructure of this material. 84 zirconia discs (VIPI block zircon) with final characteristics of 12 mm in diameter and 1.2 mm in thickness according to ISO 6872 were made using a CAD/CAM system. The specimens were divided in two groups: Group I - Conventional sintering: cycle established by the manufacturer (2 hours at 1530 °C) and Group II - sintering by microwave energy (15 min at 1450 °C). Ten samples per group were submitted to monotonic test (1000 KgF - 1mm/min) to determine the load to fracture, used as a parameter for fatigue tests (step-stress and dynamic fatigue). The step-stress fatigue test was performed using 4 load profiles, ultramild, mild, moderate and aggressive, until the fracture. The dynamic fatigue was performed by testing the disks to fracture under five constant stress rates (1, 0.1, 0.01, 0.001 and 0.0001 MPa/s), and from this the crack growth coefficient and Weibull module (reliability) were measured for each group. Additional analyzes of density, translucency, scanning electron microscopy (SEM) and X-ray diffractometry (XRD) for both groups were carried out to characterize the materials. The results of stepstress fatigue test did not show differences in the specimens behavior of each group. Dynamic fatigue also showed no differences in behavior and had similar crack growth coefficients. The Weibull modulus showed higher reliability values for the microwave group (m = 7.9) than for the conventional sintering group (m = 6.7). The density values were also similar for the studied groups, since the translucency was lower for the microwave group. SEM images showed similar microstructures between groups, only a difference in grain size was observed, 0.53 µm for microwave grains and 0.89 µm for the conventionally-sintered grains. It is concluded that the microwave sintering process can be applied as an alternative to zirconia sintering to daily laboratory work(AU)

The -(α)(5.2) Deletion Detected in a Uruguayan Family: First Case Report in the Americas.

In Uruguay, α-thalassemia (α-thal) mutations were introduced predominantly by Mediterranean European immigrant populations and by slave trade of African populations. A patient with anemia with hypochromia and microcytosis, refractory to iron treatment and with normal hemoglobin (Hb) electrophoresis was analyzed for α-thal mutations by multiplex gap-polymerase chain reaction (gap-PCR), automated sequencing and multiplex ligation-dependent probe amplification (MLPA) analyses. Agarose gel electrophoresis of the multiplex gap-PCR showed a band of unexpected size (approximately 700 bp) in the samples from the proband and mother. Automated sequencing of the amplified fragment showed the presence of the -(α)(5.2) deletion (NG_000006.1: g.32867_38062del5196) [an α-thal-1 deletion of 5196 nucleotides (nts)]. The MLPA analysis of the proband's sample also showed the presence of the -(α)(5.2) deletion in heterozygous state. We report here the presence of the -(α)(5.2) deletion, for the first time in the Americas, in a Uruguayan family with Italian ancestry, detected with a previously described multiplex gap-PCR.

Ceramic Repair Without Hydrofluoric Acid.

PURPOSE: To evaluate the bond strength between composite resin and feldspathic ceramic following repair protocols with and without hydrofluoric acid and aging by thermocycling. MATERIALS AND METHODS: Forty-eight glass feldspathic ceramic blocks (8 x 8 x 6 mm) were divided into three groups on the basis of their surface repair treatment: 1. 10% hydrofluoric acid + Signum Ceramic Primer I + Signum Ceramic Primer II (control group); 2. abrasive rubber tips + Signum Ceramic Primer I + Signum Ceramic Primer II (test group); 3. Signum Ceramic Primer I + Signum Ceramic Primer II (negative control group). The treated surface of each block was built up with composite and then sectioned to produce nontrimmed bars (adhesive area = 1 mm²). Half of the bars from each group were aged by 6000 cycles of 30-s immersions in water baths at 5°C and 55°C, with a transfer time of 2 s. The other bars were immediately subjected to microtensile bond strength testing. The mean bond strength for each block was then recorded and submitted to two-way ANOVA and Tukey's test (α = 0.05). RESULTS: The aging protocol influenced the bond strength values of all groups (p = 0.000). The non-aged groups submitted to surface treatment protocols 1 (13.1 ± 2.5 MPa) and 2 (11.5 ± 5.1 MPa) presented the highest bond strength values. CONCLUSIONS: The interface bond strength of all groups was susceptible to aging. Surface treatment protocol 2, with abrasive rubber tips and no hydrofluoric acid, appeared to be the most promising option, as the resulting bond strength values were similar to those of the control group.

Impacto da energia de micro-ondas na sinterização da zircônia odontológica / Impact of sintering process on the microstructural of dental ceramics

O objetivo deste trabalho foi avaliar o efeito do método de sinterização, convencional e por meio de energia micro-ondas, sobre as características microestruturais e propriedades mecânicas de cerâmicas à base de zircônia Y-TZP. A hipótese nula foi que a sinterização realizada por forno de micro-ondas não influencia na resistência à flexão biaxial de discos Y-TZP, tanto dos discos envelhecidos por meio de uma cicladora termomecânica, quanto nos grupos não-ciclados. Cem amostras em forma de discos de cerâmica VIPI Block Zirconn (12 x 1,2 mm) foram usinados de acordo com as normas ISO 6872 para o ensaio de flexão biaxial e foram separados em grupos de acordo com o método de sinterização e de envelhecimento termomecânico: Grupo I: Sinterização convencional e sem ciclagem mecânica; Grupo II: Sinterização convencional + ciclagem termomecânica; Grupo III: Sinterização em micro-ondas e sem ciclagem termomecânica; Grupo IV: Sinterização em micro-ondas + ciclagem termomecânica. Os corpos de prova foram submetidos à flexão biaxial após a sinterização para os grupos não ciclados e após a ciclagem para os grupos os quais foram submetidos ao envelhecimento (1.200.000 ciclos, carga de 45 N e frequência de 2,8 Hz, biaxial, imersos em água 37 °C). Foi realizada análise qualitativa das amostras por meio de um microscópio eletrônico de varredura e difração de raios-X em oito amostras (n = 2) para todos os grupos. Para a análise estatística foi utilizado o módulo Weibull (m), sendo que não houve diferença significativa quando comparado à ciclagem, porém houve quando comparado o método. O mesmo ocorreu quando foi aplicada a análise de variância (α = 5%). Conclui-se que o protocolo de sinterização praticado neste estudo não teve sucesso na sinterização da zircônia odontológica, e o termociclagem não afeta as características microestruturais e mecânicas da Y-TZP

The objective of this study was to evaluate the impact of the sintering method, conventional and through microwave energy on the microstructural characteristics and mechanical properties of ceramics based on Y- TZP zirconia. The null hypothesis is that sintering is carried out by microwave oven has no effect on the biaxial flexural strength Y- TZP disc , both discs aged by means of a thermo cycler , and in the non- cycled groups. One hundred samples in the form of VIPI Block Zirconn ceramic discs (12 x 1.2 mm) were machined in accordance with ISO 6872 standards for biaxial bending test and were divided into groups according to the method of sintering and thermomechanical aging: Group I: conventional and without mechanical cycling sintering ; Group II : conventional + thermomechanical cycling sintering ; Group III: microwave sintering and without thermomechanical cycling ; Group IV: in microwave sintering + thermomechanical cycling . The specimens were subjected to biaxial bending after sintering for non-cycled groups and after cycling for groups which were submitted to aging ( 1,200,000 cycles , 45 N load and frequency of 2.8 Hz, biaxial, immersed in water 37 °C). Qualitative analysis was performed on samples using a scanning electron microscope and X-ray diffraction samples in eight samples(n = 2) for all groups. For statistical analysis the Weibull modulus (m) was used , and there was no significant difference when compared to cycling, but there was compared the method. The same happened when the analysis of variance (α = 5%) was applied. It follows that sintering protocol performed in this study had no success in dental zirconia sintering and thermal cycling does not affect the microstructure and mechanical properties of Y- TZP

Water quality and microbial diversity in cisterns from semiarid areas in Brazil.

Harvesting rainwater is a common practice worldwide, particularly in areas with no access to a public water supply or insufficient groundwater reserves. More than two million people living in semiarid regions of Brazil consume rainwater stored in cisterns, and little information is available regarding the water quality. Despite the initial good quality of the rainwater, its harvest and storage can introduce contaminants that must be eliminated before consumption. To evaluate the influence of handling, cistern age and precipitation on the quality of harvested rainwater, we monitored seven cisterns in the semiarid Brazilian Northeast over 4 years. Microbial and physicochemical parameters were monitored once a month, and denaturant gradient gel electrophoresis (DGGE) was performed at the end of the monitoring period. Coliform bacteria were detected in 100% of samples, while Escherichia coli were observed in 73.8%. The alkalinity and conductivity were the highest for the recently built cisterns due to the dissolution of construction materials. The DGGE of the 16S r DNA did not reveal the presence of E. coli. Instead, DGGE bands sequencing indicated that species primarily affiliated with Alphaproteobacteria were present in all cisterns, indicating the presence of microbial ecosystems capable of purifying and stabilizing the stored rainwater.

Frequency and spectrum of hemoglobinopathy mutations in a Uruguayan pediatric population.

Hemoglobinopathies are the most common recessive diseases worldwide but their prevalence in Uruguay has not been investigated. In this study, 397 unrelated outpatient children from the Pereira Rosell Hospital Center (CHPR), as well as 31 selected patients with microcytic anemia and 28 ß-thalassemia carriers were analyzed for hemoglobinopathies by using biochemical and molecular biology methods. Parametric and non-parametric methods were used to compare the hematological indices between groups of genotypes. Of the 397 patients in the first group, approximately 1% (0.76% HbS and 0.25% ß-thalassemia) had a mutation in the HBB gene and 3.3% had ß-thalassemia. These mutations had a heterogeneous distribution that varied according to individual ancestry. HbS was found exclusively in individuals with declared African ancestry and had a carrier frequency of 2.2%. The frequency of α-thalassemia carriers in outpatients of European and African ancestry was 1.2% and 6.5%, respectively. In contrast, the frequency of α-thalassemia carriers in patients with microcytic anemia was 25.8%, significantly higher (p < 0.01) than that observed in the sample as a whole and in Afro-descendants and Euro-descendants. Significant differences were observed in the hematological parameters between individuals with thalassemia genotypes and those with a normal genotype. These results indicate that hemoglobinopathies are a relevant health problem in Uruguay.

Beta-globin gene cluster haplotypes in Afro-Uruguayans from two geographical regions (South and North).

The beta-globin gene cluster haplotypes were identified in 52 and 40 chromosomes from two Afro-Uruguayan populations located in the South and North of the country, respectively. In both regions, the 5' haplotype 2 (+ - - - -), characteristic of non-African populations, was the most frequent, reflecting a strong process of admixture in Afro-Uruguayans (0.355 and 0.262, respectively). The haplotypes 3 (- - - - +) and 4 (- + - - +), characteristics of African sub-Saharan populations, present inverse frequencies in North and South: whereas in the South haplotype 3 is the second most frequent (0.232), and haplotype 4 presents a low frequency (0.019), in the North haplotype 4 is the third most frequent (0.140), and haplotype 3 only reaches an intermediate frequency (0.088). The pairwise F(ST) and the exact test of differentiation show genetic heterogeneity between both regions. Nei's genetic distance show that South and North present affinities with Bantu groups, although the North present the smallest genetic distance with the Mandenka, a Senegalese population. With respect to 3' haplotypes, haplotype I was the most frequent in both populations, followed by haplotype II, characteristic of sub-Saharan Africans. The high frequencies of haplotype III-Asian could indicate admixture with Native American populations. The differences observed between both Uruguayan regions could be explained by microevolutionary events as genetic drift, founder effects, differential admixture, and/or distinct origin of the African slaves introduced in those regions.

Asociación de hemoglobina S (HbS) y beta talasemia en dos pacientes del Centro Hemato-Oncológico del Hospital Pereira Rossell / Association between S haemoglobin and S-thalassemia in two patients of the Haematologic and Oncologic Centre of the Pereira Rossell Children Hospital

Associación del alelo b S que produce hemoglobina S (HbS) y de un alelo de beta talasemia (btal), ocurre principalmente en poblaciones que tienen simultáneamente ascendencia africana y mediterránea, y provoca un síndrome drepanocítico denominado HbS-beta talasemia. Este síndrome presenta una gran heterogeneidad clínica y genética debida en gran parte al alelo talasémico presente. Los individuos que portan un alelo talasémico b 0 presentan, en general, un curso clínico similar a los homocigotas para el alelo b S de la HbS. En cambio, los que portan un alelo b + presentan un curso clínico variable, dependiendo de la reducción en la síntesis de cadena de beta globina. En este estudio se describe el caso clínico de dos pacientes con HbS-beta talasemia que consultaron en el Centro Hemato-Oncológico Pediátrico del Hospital Pereira Rossell. Se analizó el genotipo de los dos pacientes por medio de secuenciación automática del gen de la beta globina. Se demostró la presencia del alelo talasémico b + IVS-1-110- A en uno de los pacientes y del alelo b 0 codón39 C-T en el otro paciente, por lo cual ambos son heterocigotos compuestos b S/b tal. Se discute la relación entre los datos clínicos y paraclínicos con los resultados del diagnóstico molecular. También se discute la importancia del diagnóstico molecular en relación con la composición y estructura de la población uruguaya.