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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 informativemarkers (AIMs). The sample ancestrywas 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). Neurotoxicitywas significantly associatedwith 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. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effect of the type of preheated resin composite on the microtensile bond strength (µTBS) between dentin and feldspathic ceramic inlays. Thirty healthy human premolars received inlay preparations for feldspathic ceramic restorations and were then divided into three treatment groups according to the luting agent (n = 10): Conventional Resin Cement (RC), Preheated Nanofilled Methacrylate-Based Resin composite (MB), and Preheated Microhybrid Silorane-Based Resin composite (SB). The composite resin was preheated to 55 °C, considering the cementation group. After cementation, the sets were cut into slabs with a bonding area of 1 mm2 to be further submitted to the µTBS test (0.5 mm/min, and10 Kgf load cell). One-way ANOVA and Tukey test (p <.5) were performed to analyze the bond strength data (MPa). Failures were observed under a stereomicroscope and representative specimens were evaluated using a Scanning Electron Microscopy (SEM). ANOVA revealed that the type of luting agent utilized was significant (p =.001). Bond strength values for the RC (7.37 ± 1.27 MPa)A and MB (6.98 ± 1.96 MPa)A treatment groups were similar and greater than the SB (4.74 ± 1.65 MPa)B. Adhesive failures between the cementing agent and ceramic were prevalent for the treatment groups. The preheated nanofilled methacrylate resin-based composite technique can promote bond strength similar to resin cement, whereas preheated silorane-based resin composite as a luting agent should be seen with caution. Thus, we concluded that the type of luting agent has influenced the µTBS of feldspathic restoration to dentin. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• MWZ can be prepared 6 times faster than CZ while preserving structural durability. • Degradation in flexural fatigue of as-sintered zirconia is due primarily to SCG. • MWZ possesses a slightly higher Weibull modulus than CZ. • MWZ and CZ exhibit similar resistance to SCG. • Accelerated fatigue testing protocols must cover a wide range of stress-rates. 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). 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. 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. Dental 3Y-TZP with similar structural durability can be fabricated six-times faster by microwave than conventional sintering. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article presents a study which showed that TPM and NUDT15 genes are related to mercaptopurine intolerance in acute lymphoblastic leukaemia patients from Uruguay. Topics discussed include the cumulative frequency of TPMT and NUDT15 variants and relevance of results to other Latin-American countries with different European and Native-American contributions.

The notion of a divided city is at the core of A cidade é uma só? (2011), directed by Adirley Queirós, which employs a strategy of blurring the borders between document and fiction, exploring the tension that emerges in a network of displacements: on the one hand, there is the movement between past - the historical context of the 1970s Brasília - and present; on the other hand, there is the characters' movement across the city spaces. The film itself displaces its focus from the center to the margins, to characters who live in the periphery who are the counterpoint to the divided people, the divided city, not only to show their disparities but also to break limits, to dissolve and disturb separating lines. [ABSTRACT FROM AUTHOR]

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)5.2deletion (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)5.2deletion in heterozygous state. We report here the presence of the –(α)5.2deletion, for the first time in the Americas, in a Uruguayan family with Italian ancestry, detected with a previously described multiplex gap-PCR. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the Β (beta)-globin gene cluster of two Afro-Uruguayan populations in the South and North part of Uruguay. The study collected blood samples from 46 unrelated and healthy Afro-Uruguayans, wherein the genomic DNA was removed from blood samples by routine techniques. Conclusion shows that the variations observed between both Uruguayan regions can be explained by microevolutionary events such as genetic drift and differential mixing.

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. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Salas-Hernández, Galleguillos, Carrasco, López-Cortés, Redal, Fonseca-Mendoza, Esperón, González-Martínez, Lares-Asseff, Lazarowski, Loera-Castañeda, Remírez, Martínez, Vargas, Rios-Santos, Macho, Cayún, Perez, Gutierrez, Cerpa, Leiva, Calfunao, Xajil, Sandoval, Suárez, Gonzalez, Echeverría-Garcés, Sullón-Dextre, Cordero-García, Morales, Avendaño, Sánchez, Bastone, Lara, Zuluaga-Arias, Soler, Da Luz, Burgueño-Rodríguez, Vital, Reyes-Reyes, Huaccha, Ariza, Tzul, Rendón, Serrano, Acosta, Motta-Pardo, Beltrán-Angarita, Brand, Jiménez, Hidalgo-Lozada, Romero-Prado, Escobar-Castro, Umaña-Rivas, Vivas, Lagos, Martínez, Quesada, Calfio, Arias, Lavanderos, Cáceres, Salazar-Granara, Varela and Quiñones.)

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.

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.

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.

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.

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 β-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% β-thalassemia) had a mutation in the HBB gene and 3.3% had β-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.