Gaucher disease in Brazil: a comprehensive 16 year retrospective study on survival, cost, and treatment insights.

Background: Gaucher's disease (GD), a lysosomal storage disorder, poses significant treatment challenges. This 23-year study assesses survival rates and treatment efficacy in Brazilian GD patients, integrating data from a 16-year cohort (2000-2015) and the TABNET/DATASUS medicines distribution data (1999-2022). Objective: To investigate the survival of GD patients in Brazil, identifying key risk factors and evaluating the impact of treatments funded by the Brazilian National Health System (SUS). Methodology: A 16-year retrospective cohort study was conducted using the National Database of SUS. Patients diagnosed with GD and treated with Enzyme Replacement Therapy (ERT) or Substrate Synthesis Inhibition (SSI) from 2000 to 2015 were included. Survival analysis was performed using Kaplan-Meier method and Cox proportional hazards model. The data from TABNET/DATASUS system from 1999 to 2022 was used to assess the trend in drug distribution beyond the main cohort. Results: The study included 1,234 patients. Survival rates at 5 and 10 years were 93.2% and 88.5%, respectively, with age and comorbidities like diabetes, cardiovascular diseases, and Parkinson's disease significantly affecting survival. Patients who received doses lower than DDD (n = 880) demonstrated a survival probability of 91.8%. In contrast, those with doses equal to the DDD (n = 15) showed a 100% survival probability, as no events were observed in this group. The greater than DDD group (n = 339) exhibited a survival probability of 81%. A log-rank test indicated a borderline statistical significance (p = 0.058) in the survival distributions among the different DDD adherence, with the lower dose group showing a favorable trend. Conclusion: This study provides insights into the survival rates and associated risk factors for GD patients in Brazil, contributing to the global understanding of GD and its management. While we acknowledge the inherent limitations of relying largely on electronic medical records and categorical codes, our findings underscore the need for early diagnosis, timely initiation of treatment, effective management of comorbidities, and personalized dosing strategies to improve patient outcomes. Future studies should aim to incorporate clinical verification of electronic data to further enhance the reliability and applicability of these findings.

Genomic diversity study of highly crossbred cattle population in a Low and Middle Tropical environment.

Milk production in tropical regions plays a crucial role both economically and socially. Typically, animals are utilized for dual purposes and are genetically obtained by an intense crossbreeding between Zebu and/or locally adapted breeds, alongside specialized breeds for dairy production. However, uncontrolled mating and crossbreeding may affect the establishment of an effective animal breeding program. The objective of this study was to evaluate Genomic diversity of highly crossbred cattle population in a Low and Middle Tropical environment. All sampled animals were genotyped using the Genessek GGP Bovine 100 chip (n = 859) and public genomic information from eight breeds were employed as reference. The genetic structure of the population was estimated using a Principal Component, Bayesian clustering and a linkage disequilibrium analysis. PCA results revealed that PC1 explained 44.39% of the variation, associated with the indicus/taurus differentiation, and PC2 explained 14.6% of the variation, attributed to the differentiation of Creole and European components. This analysis underscored a low population structure, attributed to the absence of genealogical tracking and the implementation of non-directed crossbreeding. The clustering shows an average contribution of Zebu, Creole, and European Taurine components in the population was 53.26%, 27.60%, and 19.13%, respectively. While an average LD of 0.096 was obtained for a maximum distance of 400 kb. The LD value was low in this population, probably due to the almost no selection applied and the recombination events that occurred during its development. These findings underscore the value of crossbreeding in tropical dairy production but emphasize the importance of directing the mattings.

Diversity of Genetic and Vegetative Compatibility Group of Colletotrichum coccodes Isolates from Chile Using Amplified Fragment Length Polymorphism Markers.

Colletotrichum coccodes (Wallr.) Hughes is an asexual fungus with five vegetative compatibility groups. It was postulated that C. coccodes was isolated at the center of origin of potato at one time, and due to the movement of potato around the globe, the fungus was established on each continent but became bottlenecked and genetically unable to form stable heterokaryons via vegetative compatibility grouping (VCG) studies. The objectives of this study were (i) to determine if the VCGs around the world are related to the VCGs in Chile, (ii) to determine the diversity of C. coccodes populations in Chile, and (iii) to find any evidence for a cryptic sexual life cycle for this fungus. Worldwide C. coccodes populations have been found to be genetically correlated and belong to one or more C. coccodes-identified VCGs. The most distributed VCG in Chile was VCG2, which is the most common VCG in North America. We hypothesize that one or more VCGs had spread from Chile to the rest of the world. Precautions and further studies should be investigated by using other molecular markers and gene sequencing.

New candidate SNPs for genetic association with Alzheimer's disease: a linkage disequilibrium analysis for the FCGRIIB and PILRA genes.

Background: Two new SNPs have been recently associated to Alzheimer's disease in African American populations: FCGRIIB rs1050501 C/T, and PILRA rs1859788 A/G. The risk of Alzheimer's disease in FCGRIIB C and PILRA A allele carriers is three times higher than in non-carriers. However, the association between these and other single nucleotide polymorphisms (SNPs) has not been assessed. Methods: Linkage disequilibrium analysis, with r= 0.8 as a threshold value, was used to impute new candidate SNPs, on genomic data from both genes in 26 populations worldwide (n= 2504) from the 1000Genomes database. Results: Four SNPs (rs13376485, rs3767640, rs3767639 and rs3767641) were linked to rs1050501 and one (rs2405442) to rs1859788 in the whole sample. Conclusions: Five novel SNPs could be associated with Alzheimer's disease susceptibility and play a causal role, even if none of them are exon variants since their potential roles in the regulation of gene expression.

Antecedentes: Recientemente se han asociado dos nuevos polimorfismos de un solo nucleótido (SNP) a la enfermedad de Alzheimer en poblaciones afroamericanas: FCGRIIB rs1050501 C/T, y PILRA rs1859788 A/G. El riesgo de enfermedad de Alzheimer en los portadores de los alelos FCGRIIB C y PILRA A es tres veces mayor que en los no portadores. Sin embargo, no se ha evaluado la asociación entre estos y otros SNP. Métodos: Se utilizó el análisis de desequilibrio de ligamiento, con r2= 0,8 como valor umbral, para imputar nuevos SNPs candidatos, sobre datos genómicos de ambos genes en 26 poblaciones de todo el mundo (n= 2504) de la base de datos 1000Genomes. Resultados: Cuatro SNPs (rs13376485, rs3767640, rs3767639 y rs3767641) se vincularon al rs1050501 y uno (rs2405442) al rs1859788 en toda la muestra. Conclusiones: Cinco nuevos SNP podrían estar asociados con la susceptibilidad a la enfermedad de Alzheimer y desempeñar un papel causal, aunque ninguno de ellos sea una variante de exón, dado su papel potencial en la regulación de la expresión génica.

New candidate SNPs for genetic association with Alzheimer's disease: a linkage disequilibrium analysis for the FCGRIIB and PILRA genes / Nuevos SNP candidatos para la asociación genética con la enfermedad de Alzheimer: un análisis de desequilibrio de ligamiento para los genes FCGRIIB y PILRA

BACKGROUND: Two new SNPs have been recently associated to Alzheimer's disease in African American populations: FCGRIIB rs1050501 C/T, and PILRA rs1859788 A/G. The risk of Alzheimer's disease in FCGRIIB C and PILRA A allele carriers is three times higher than in non-carriers. However, the association between these and other single nucleotide polymorphisms (SNPs) has not been assessed. METHODS: Linkage disequilibrium analysis, with r= 0.8 as a threshold value, was used to impute new candidate SNPs, on genomic data from both genes in 26 populations worldwide (n= 2504) from the 1000Genomes database. RESULTS: Four SNPs (rs13376485, rs3767640, rs3767639 and rs3767641) were linked to rs1050501 and one (rs2405442) to rs1859788 in the whole sample. CONCLUSIONS: Five novel SNPs could be associated with Alzheimer's disease susceptibility and play a causal role, even if none of them are exon variants since their potential roles in the regulation of gene expression.

ANTECEDENTES: Recientemente se han asociado dos nuevos polimorfismos de un solo nucleótido (SNP) a la enfermedad de Alzheimer en poblaciones afroamericanas: FCGRIIB rs1050501 C/T, y PILRA rs1859788 A/G. El riesgo de enfermedad de Alzheimer en los portadores de los alelos FCGRIIB C y PILRA A es tres veces mayor que en los no portadores. Sin embargo, no se ha evaluado la asociación entre estos y otros SNP. MÉTODOS: Se utilizó el análisis de desequilibrio de ligamiento, con r2= 0,8 como valor umbral, para imputar nuevos SNPs candidatos, sobre datos genómicos de ambos genes en 26 poblaciones de todo el mundo (n= 2504) de la base de datos 1000Genomes. RESULTADOS: Cuatro SNPs (rs13376485, rs3767640, rs3767639 y rs3767641) se vincularon al rs1050501 y uno (rs2405442) al rs1859788 en toda la muestra. CONCLUSIONES: Cinco nuevos SNP podrían estar asociados con la susceptibilidad a la enfermedad de Alzheimer y desempeñar un papel causal, aunque ninguno de ellos sea una variante de exón, dado su papel potencial en la regulación de la expresión génica.

A Bayesian approach for de-duplication in the presence of relational data.

In this paper, we study the impact of combining profile and network data in solving record de-duplication problems. We also assess the influence of a range of prior distributions on the linkage structure, and explore the use of stochastic gradient Hamiltonian Monte Carlo methods as a faster alternative to obtain samples from the posterior distribution for network parameters. Our methodology is evaluated using the RLdata500 data, which is a popular dataset in the record linkage literature.

LD block disorder-specific pleiotropic roles of novel CRHR1 in type 2 diabetes and depression disorder comorbidity.

Major depressive disorder (MDD) and type 2 diabetes (T2D) are complex disorders whose comorbidity can be due to hypercortisolism and may be explained by dysfunction of the corticotropin-releasing hormone receptor 1 (CRHR1) and cortisol feedback within the hypothalamic-pituitary-adrenal axis (HPA axis). To investigate the role of the CRHR1 gene in familial T2D, MDD, and MDD-T2D comorbidity, we tested 152 CRHR1 single-nucleotide-polymorphisms (SNPs), via 2-point parametric linkage and linkage disequilibrium (LD; i.e., association) analyses using 4 models, in 212 peninsular families with T2D and MDD. We detected linkage/LD/association to/with MDD and T2D with 122 (116 novel) SNPs. MDD and T2D had 4 and 3 disorder-specific novel risk LD blocks, respectively, whose risk variants reciprocally confirm one another. Comorbidity was conferred by 3 novel independent SNPs. In silico analyses reported novel functional changes, including the binding site of glucocorticoid receptor-alpha [GR-α] on CRHR1 for transcription regulation. This is the first report of CRHR1 pleiotropic linkage/LD/association with peninsular familial MDD and T2D. CRHR1 contribution to MDD is stronger than to T2D and may antecede T2D onset. Our findings suggest a new molecular-based clinical entity of MDD-T2D and should be replicated in other ethnic groups.

Avaliação do sistema de vigilância em saúde do trabalhador relacionada aos acidentes de trabalho, antes e após a implantação do software de linkage Sentinela, em Porto Alegre, 2018-2021 / Evaluation of the occupational health surveillance system before and after the implementation of the Sentinela linkage software, in Porto Alegre, 2018-2021 / Evaluación del sistema de vigilancia de la salud del trabajador relacionada con los accidentes de trabajo, antes y después de la implementación del software de enlace Sentinela, en Porto Alegre, 2018-2021

O objetivo deste artigo é avaliar, segundo alguns atributos, o sistema de vigilância dos acidentes de trabalho antes e após a implantação do software Sentinela (2018-2021), com base em uma pesquisa descritiva de dados secundários, e efetuar recomendações. Foram analisadas variáveis da ficha de investigação, de acordo com os atributos qualidade dos dados (completitude e consistência), oportunidade e representatividade. Os resultados mostraram que, após o Sentinela, houve aumento da notificação de acidentes (66,16%), maior completitude das variáveis, com importante alteração na 'atividade econômica' (98,9%) e 'evolução' (96,3%), diminuição dos campos ignorados/em branco, com destaque para o campo 'evolução' (3,7%), e melhora na oportunidade de controle dos acidentes fatais (79 dias). Concluímos que a vigilância dos acidentes de trabalho tem excelente qualidade dos dados, é representativa, mas inoportuna. O Sentinela melhorou o sistema, tornando-o mais sensível na captação dos acidentes e permitindo-lhe ter informações de melhor qualidade. É necessária a avaliação rotineira dos atributos, para aprimoramento constante do sistema, assim como rever as rotinas das equipes de saúde, melhorando a oportunidade de controle por meio de suas ações

This article aims to evaluate the occupational health surveillance system before and after the implementa-tion of the Sentinela software (2018-2021), according to some attributes and based on descriptive research using secondary data, and to make recommendations. Variables of the accident investigation report were analysed, according to the attributes of data quality (completeness and consistency), opportunity and rep-resentativeness. The results have revealed that after Sentinela, there was an increase in the notification of accidents (66.16%), greater completeness of the variables, with an important change in 'economic activity' (98.9%) and 'evolution' (96.3%), a decreased in blank fields/information missing, with emphasis on the 'evolution' field (3.7%), and an improvement in the opportunity to control fatal accidents (79 days). We have concluded that the surveillance of the occupational accidents has excellent data quality, is representative, but inopportune. The Sentinela has improved the system, making it more sensitive in capturing accidents, allowing it to provide better quality of information. An evaluation of the attributes is routinely necessary to constantly improve the system, as well as reviewing the routines of health professionals, improving the opportunity to control by their actions

El objetivo de este artículo es evaluar, según algunos atributos, el sistema de vigilancia de los accidentes de trabajo antes y después de la implementación del software Sentinela (2018-2021), por medio de una investigación descriptiva de datos secundarios, y hacer recomendaciones. Fueron analizadas variables de la ficha de investigación de accidentes, de acuerdo con los atributos de calidad de los datos (completitud y consistencia), oportunidad y representatividad. Los resultados demostraron que, después del Sentinela, ha habido un aumento de la notificación de accidentes (66,16 %), una mayor completitud de las variables, con un cambio importante en 'actividad económica' (98,9 %) y 'evolución' (96,3 %), una disminución de campos ignorados/en blanco, con énfasis en el campo 'evolución' (3,7%), y mejora en la probabilidad de control de los accidentes mortales (79 días). Concluimos que la vigilancia de los accidentes de trabajo tiene excelente calidad de datos, es representativa, pero inoportuna. El Sentinela ha mejorado el sistema, haciéndolo más sensible en la captación de los accidentes y permitiéndole tener informaciones de mejor calidad. La evaluación de los atributos con regularidad es necesaria para el perfeccionamiento constante del sistema, así como la revisión de las rutinas de los equipos de salud, mejorando la oportunidad de control a través de sus acciones

Ridge regression and deep learning models for genome-wide selection of complex traits in New Mexican Chile peppers.

BACKGROUND: Genomewide prediction estimates the genomic breeding values of selection candidates which can be utilized for population improvement and cultivar development. Ridge regression and deep learning-based selection models were implemented for yield and agronomic traits of 204 chile pepper genotypes evaluated in multi-environment trials in New Mexico, USA. RESULTS: Accuracy of prediction differed across different models under ten-fold cross-validations, where high prediction accuracy was observed for highly heritable traits such as plant height and plant width. No model was superior across traits using 14,922 SNP markers for genomewide selection. Bayesian ridge regression had the highest average accuracy for first pod date (0.77) and total yield per plant (0.33). Multilayer perceptron (MLP) was the most superior for flowering time (0.76) and plant height (0.73), whereas the genomic BLUP model had the highest accuracy for plant width (0.62). Using a subset of 7,690 SNP loci resulting from grouping markers based on linkage disequilibrium coefficients resulted in improved accuracy for first pod date, ten pod weight, and total yield per plant, even under a relatively small training population size for MLP and random forest models. Genomic and ridge regression BLUP models were sufficient for optimal prediction accuracies for small training population size. Combining phenotypic selection and genomewide selection resulted in improved selection response for yield-related traits, indicating that integrated approaches can result in improved gains achieved through selection. CONCLUSIONS: Accuracy values for ridge regression and deep learning prediction models demonstrate the potential of implementing genomewide selection for genetic improvement in chile pepper breeding programs. Ultimately, a large training data is relevant for improved genomic selection accuracy for the deep learning models.

Honduras HIV cohort: HLA class I and CCR5-Δ32 profiles and their associations with HIV disease outcome.

IMPORTANCE: We identify both canonical and novel human leukocyte antigen (HLA)-HIV associations, providing a first step toward improved understanding of HIV immune control among the understudied Honduras Mestizo population. Our results are relevant to understanding the protective or detrimental effects of HLA subtypes in Latin America because their unique HLA diversity poses challenges for designing vaccines against HIV and interpreting results from such vaccine trials. Likewise, the description of the HLA profile in an understudied population that shows a unique HLA immunogenetic background is not only relevant for HIV immunology but also relevant in population genetics, molecular anthropology, susceptibility to other infections, autoimmune diseases, and allograft transplantation.

Population analysis of the CLOCK rs3749474T-rs4864548A haplotype and its relationship with obesity. / Análisis poblacional in silico del haplotipo CLOCK rs3749474T-rs4864548A y su relación con obesidad.

It has been suggested that the rs3749474T/rs4864548A haplotype of the CLOCK gene increases the risk of obesity, but the population variability of these alleles and the haplotype is unknown. This research aims to determine the linkage between the rs3749474T and rs4864548A alleles from the database of 1000Genomes to confirm the existence of the TA haplotype polymorphisms of these alleles and their frequency in five macro populations. Linkage disequilibrium and haplotype frequencies for 2504 individuals from 26 populations were analyzed using the r statistic and Fisher's exact test. There is a high frequency of the TA haplotype in Latin America (44.8%), a high linkage disequilibrium (r2= 0.92) worldwide between these alleles, a high differentiation between macro populations, and a high homogeneity. The evidence warrants further studies on the association between this haplotype and the risk of obesity and overweight in Latin American populations.

Se ha sugerido que el haplotipo rs3749474T/rs4864548A del gen CLOCK aumentaría el riesgo de obesidad, pero se desconoce el patrón de variabilidad poblacional de estos alelos y del haplotipo. El objetivo de este estudio es determinar el nivel de ligamiento entre los alelos de riesgo rs3749474T y rs4864548A a partir de la base de datos 1000Genomes para confirmar la existencia del haplotipo TA de los polimorfismos rs3749474-rs4864548 del gen CLOCK y su frecuencia cinco macro poblaciones. Se analizó el desequilibrio de ligamiento y las frecuencias haplotípicas para 2504 individuos, de 26 poblaciones, utilizando el estadístico r y la prueba exacta de Fisher. Existe una alta frecuencia del haplotipo TA en Latinoamérica (44,8%), un alto desequilibrio de ligamiento (r= 0,92) a nivel mundial entre esos alelos, una alta diferenciación entre macro poblaciones y una alta homogeneidad al interior de ellas. La evidencia presentada permite sugerir la realización de posteriores estudios de asociación entre este haplotipo y el nivel de riesgo de obesidad y sobrepeso en poblaciones latinoamericanas.

Population analysis of the CLOCK rs3749474T-rs4864548A haplotype and its relationship with obesity / Análisis poblacional in silico del haplotipo CLOCK rs3749474T-rs4864548A y su relación con obesidad

Se ha sugerido que el haplotipo rs3749474T/rs4864548A del gen CLOCK aumentaría el riesgo de obesidad, pero se desconoce el patrón de variabilidad poblacional de estos alelos y del haplotipo. El objetivo de este estudio es determinar el nivel de ligamiento entre los alelos de riesgo rs3749474T y rs4864548A a partir de la base de datos 1000Genomes para confirmar la existencia del haplotipo TA de los polimorfismos rs3749474-rs4864548 del gen CLOCK y su frecuencia cinco macro poblaciones. Se analizó el desequilibrio de ligamiento y las frecuencias haplotípicas para 2504 individuos, de 26 poblaciones, utilizando el estadístico r y la prueba exacta de Fisher. Existe una alta frecuencia del haplotipo TA en Latinoamérica (44,8%), un alto desequilibrio de ligamiento (r= 0,92) a nivel mundial entre esos alelos, una alta diferenciación entre macro poblaciones y una alta homogeneidad al interior de ellas. La evidencia presentada permite sugerir la realización de posteriores estudios de asociación entre este haplotipo y el nivel de riesgo de obesidad y sobrepeso en poblaciones latinoamericanas.

It has been suggested that the rs3749474T/rs4864548A haplotype of the CLOCK gene increases the risk of obesity, but the population variability of these alleles and the haplotype is unknown. This research aims to determine the linkage between the rs3749474T and rs4864548A alleles from the database of 1000Genomes to confirm the existence of the TA haplotype polymorphisms of these alleles and their frequency in five macro populations. Linkage disequilibrium and haplotype frequencies for 2504 individuals from 26 populations were analyzed using the r statistic and Fisher's exact test. There is a high frequency of the TA haplotype in Latin America (44.8%), a high linkage disequilibrium (r2= 0.92) worldwide between these alleles, a high differentiation between macro populations, and a high homogeneity. The evidence warrants further studies on the association between this haplotype and the risk of obesity and overweight in Latin American populations.

Exploring the electronic structure of [RuF5NO]2- ion by the generation of a metastable state (MS1).

Some mononitrosyl complexes of transition metals exhibit one or two metastable states (linkage isomers, MS1 and MS2) when irradiated at low temperatures with appropriate wavelengths. In this work, the generation of metastable state one (MS1) (or Ru-ON linkage isomer) in K2[RuF5NO].H2O at 77 K was studied by sample excitation using laser light in a wide range of wavelengths. The effects of irradiation was monitored by infrared spectroscopy. ν(NO) in the ground state was shifted by -161 cm-1 when the complex was excited to MS1, a magnitude similar to that observed in other transition metal nitrosyls for a such state. We report on the excitation and deactivation of metastable states by using a wide variety of laser lines. A novel method for exploring the electronic structure of [RuF5NO]2- through the generation of MS1 is proposed. For this purpose, a sample was carefully irradiated with the same intensity of light for all laser lines in the spectral region 260-1064 nm. The integrated area under the ν(NO)MS1 band was used as a measure of MS1 population. The profile peaks of the MS1 population (ν(NO)MS1 band area) vs. the irradiation wavelength fit well with those of the electronic spectrum of the [RuF5NO]2- ion in an aqueous solution. The onset temperature for MS1 decay in K2[RuF5NO].H2O, at approximately 180 K, is slightly lower than the average reported for other ruthenium-nitrosyl systems.

Genetic analysis and QTL mapping of domestication-related traits in chili pepper (Capsicum annuum L.).

Chili pepper (Capsicum annuum L.) is one of the oldest and most phenotypically diverse pre-Columbian crops of the Americas. Despite the abundance of genetic resources, the use of wild germplasm and landraces in chili pepper breeding is limited. A better understanding of the evolutionary history in chili peppers, particularly in the context of traits of agronomic interest, can contribute to future improvement and conservation of genetic resources. In this study, an F2:3 mapping population derived from a cross between a C. annuum wild accession (Chiltepin) and a cultivated variety (Puya) was used to identify genomic regions associated with 19 domestication and agronomic traits. A genetic map was constructed consisting of 1023 single nucleotide polymorphism (SNP) markers clustered into 12 linkage groups and spanning a total of 1,263.87 cM. A reciprocal translocation that differentiates the domesticated genome from its wild ancestor and other related species was identified between chromosomes 1 and 8. Quantitative trait locus (QTL) analysis detected 20 marker-trait associations for 13 phenotypes, from which 14 corresponded to previously identified loci, and six were novel genomic regions related to previously unexplored domestication-syndrome traits, including form of unripe fruit, seedlessness, deciduous fruit, and growth habit. Our results revealed that the genetic architecture of Capsicum domestication is similar to other domesticated species with few loci with large effects, the presence of QTLs clusters in different genomic regions, and the predominance of domesticated recessive alleles. Our analysis indicates the domestication process in chili pepper has also had an effect on traits not directly related to the domestication syndrome. The information obtained in this study provides a more complete understanding of the genetic basis of Capsicum domestication that can potentially guide strategies for the exploitation of wild alleles.

The impact of epistasis in the heterosis and combining ability analyses.

The current theoretical knowledge concerning the influence of epistasis on heterosis is based on a simplified multiplicative model. The objective of this study was to assess how epistasis affects the heterosis and combining ability analyses, assuming additive model, hundreds of genes, linkage disequilibrium (LD), dominance, and seven types of digenic epistasis. We developed the quantitative genetics theory for supporting the simulation of the individual genotypic values in nine populations, the selfed populations, the 36 interpopulation crosses, 180 doubled haploids (DHs), and their 16,110 crosses, assuming 400 genes on 10 chromosomes of 200 cM. Epistasis only affects population heterosis if there is LD. Only additive × additive and dominance × dominance epistasis can affect the components of the heterosis and combining ability analyses of populations. Epistasis can have a negative impact on the heterosis and combining ability analysis of populations, leading to wrong inferences regarding the identification of superior and most divergent populations. However, this depends on the type of epistasis, percentage of epistatic genes, and magnitude of their effects. Except for duplicate genes with cumulative effects and non-epistatic genic interaction, there was a decrease in the average heterosis by increasing the percentage of epistatic genes and the magnitude of their effects. The same results are generally true for the combining ability analysis of DHs. The combining ability analyses of subsets of 20 DHs showed no significant average impact of epistasis on the identification of the most divergent ones, regardless of the number of epistatic genes and magnitude of their effects. However, a negative effect on the assessment of the superior DHs can occur assuming 100% of epistatic genes, but depending on the epistasis type and the epistatic effect magnitude.

Tendência temporal da prevalência e mortalidade infantil das anomalias congênitas no Brasil, de 2001 a 2018 / Temporal trends in prevalence and infant mortality of birth defects in Brazil, from 2001 to 2018

Resumo As anomalias congênitas (AC) configuram um relevante problema para a saúde pública global, afetando em média de 3% a 6% dos recém-nascidos em todo o mundo. No Brasil, ocupam a segunda posição entre os principais grupos de causas de óbito infantil. Assim, estudos amplos são necessários para mostrar o impacto das AC na saúde infantil. O presente estudo descreve a tendência temporal da prevalência e da mortalidade infantil por AC entre nascidos vivos (NV) no Brasil e em suas cinco regiões de 2001 a 2018, utilizando dados vinculados entre as bases de dados do Sistema de Informações sobre Nascidos Vivos (SINASC) e do Sistema de Informações sobre Mortalidade (SIM). A prevalência e mortalidade infantil por AC mostrou-se crescente no Brasil na maioria das regiões, principalmente no Norte e no Nordeste. Aquelas do aparelho osteomuscular foram as mais prevalentes ao nascimento (29,8/10.000 NV); as do aparelho circulatório passaram para a segunda posição (12,7/10.000 NV) após a vinculação das bases e representam a primeira causa de morte desse grupo. A técnica de vinculação de dados aplicada corrigiu a prevalência nacional das AC em 17,9% no período analisado, após serem recuperadas as AC notificadas no SIM, mostrando ser uma boa ferramenta para melhorar a qualidade das informações das AC.

Abstract Congenital anomalies (CA) are a relevant problem for global public health, affecting about 3% to 6% of newborns worldwide. In Brazil, these are the second main cause of infant mortality. Thus, extensive studies are needed to demonstrate the impact of these anomalies on births and deaths. The present study describes the temporal trends of prevalence and infant mortality due to CA among live births in Brazil and regions, from 2001 to 2018, using the related data between the Live Birth Information System (SINASC, acronym in Portuguese) and the Mortality Information System (SIM, acronym in Portuguese). The prevalence and infant mortality due to CA has increased in Brazil and in most regions, especially in the Northeast and North. CAs in the musculoskeletal system were the most frequent at birth (29.8/10,000 live births), followed by those in the circulatory system (12.7/10,000 live births), which represented the primary cause of death in this group. The applied linkage technique made it possible to correct the national prevalence of CA by 17.9% during the analyzed period, after retrieving the anomalies reported in SIM, thereby proving to be a good tool to improve the quality of information on anomalies in Brazil.

National data linkage assessment of live births and deaths in Mexico: Estimating under-five mortality rate ratios for vulnerable newborns and trends from 2008 to 2019.

BACKGROUND: Linked datasets that enable longitudinal assessments are scarce in low and middle-income countries. OBJECTIVES: We aimed to assess the linkage of administrative databases of live births and under-five child deaths to explore mortality and trends for preterm, small (SGA) and large for gestational age (LGA) in Mexico. METHODS: We linked individual-level datasets collected by National statistics from 2008 to 2019. Linkage was performed based on agreement on birthday, sex, residential address. We used the Centre for Data and Knowledge Integration for Health software to identify the best candidate pairs based on similarity. Accuracy was assessed by calculating the area under the receiver operating characteristic curve. We evaluated completeness by comparing the number of linked records with reported deaths. We described the percentage of linked records by baseline characteristics to identify potential bias. Using the linked dataset, we calculated mortality rate ratios (RR) in neonatal, infants, and children under-five according to gestational age, birthweight, and size. RESULTS: For the period 2008-2019, a total of 24,955,172 live births and 321,165 under-five deaths were available for linkage. We excluded 1,539,046 records (6.2%) with missing or implausible values. We succesfully linked 231,765 deaths (72.2%: range 57.1% in 2009 and 84.3% in 2011). The rate of neonatal mortality was higher for preterm compared with term (RR 3.83, 95% confidence interval, [CI] 3.78, 3.88) and for SGA compared with appropriate for gestational age (AGA) (RR 1.22 95% CI, 1.19, 1.24). Births at <28 weeks had the highest mortality (RR 35.92, 95% CI, 34.97, 36.88). LGA had no additional risk vs AGA among children under five (RR 0.92, 95% CI, 0.90, 0.93). CONCLUSIONS: We demonstrated the utility of linked data to understand neonatal vulnerability and child mortality. We created a linked dataset that would be a valuable resource for future population-based research.

High-Throughput Microsatellite Markers Development for Genetic Characterization of Emerging Sporothrix Species.

Sporotrichosis is the main subcutaneous mycosis worldwide transmitted by animal or plant vectors and often escalates to outbreaks or epidemics. The current cat-transmitted sporotrichosis driven by Sporothrix brasiliensis has become a significant public health issue in South America. Transmission dynamics remain enigmatic due to the lack of development of polymorphic markers for molecular epidemiological analysis. This study used a high-throughput mining strategy to characterize simple sequence repeat (SSR) markers from Sporothrix genomes. A total of 118,140-143,912 SSR loci were identified (82,841-98,369 unique markers), with a 3651.55-3804.65 SSR/Mb density and a majority of dinucleotides motifs (GC/CG). We developed a panel of 15 highly polymorphic SSR markers suitable for genotyping S. brasiliensis, S. schenckii, and S. globosa. PCR amplification revealed 240 alleles in 180 Sporothrix isolates with excellent polymorphic information content (PIC = 0.9101), expected heterozygosity (H = 0.9159), and discriminating power (D = 0.7127), supporting the effectiveness of SSR markers in uncovering cryptic genetic diversity. A systematic population genetic study estimated three clusters, corresponding to S. brasiliensis (population 1, n = 97), S. schenckii (population 2, n = 49), and S. globosa (population 3, n = 34), with a weak signature of mixed ancestry between populations 1 and 2 or 3 and 2. Partitioning of genetic variation via AMOVA revealed highly structured populations (ΦPT = 0.539; Nm = 0.213; p < 0.0001), with approximately equivalent genetic variability within (46%) and between (54%) populations. Analysis of SSR diversity supports Rio de Janeiro (RJ) as the center of origin for contemporary S. brasiliensis infections. The recent emergence of cat-transmitted sporotrichosis in northeastern Brazil indicates an RJ-Northeast migration resulting in founder effects during the introduction of diseased animals into sporotrichosis-free areas. Our results demonstrated high cross-species transferability, reproducibility, and informativeness of SSR genetic markers, helping dissect deep and fine-scale genetic structures and guiding decision making to mitigate the harmful effects of the expansion of cat-transmitted sporotrichosis.

Telemonitoring of the Continuum of Care of Hepatitis C During the COVID-19 Pandemic in Brazil.

Introduction: To accomplish elimination of hepatitis C virus (HCV) by 2030, as proposed by the World Health Organization, the Brazilian Ministry of Health outlined the Hepatitis C Elimination Plan, which provides coverage of all critical steps in the continuum of care (CoC) of hepatitis C. As expected, the advent of COVID-19 pandemic has disrupted the CoC of hepatitis C worldwide. The Brazilian Liver Institute launched a remote patient monitoring (RPM) program to assist the general population at risk in HCV testing and to provide linkage and retention to care for HCV-positive subjects. The RPM program was also designed to relink HCV-positive patients lost to follow-up during the COVID-19 pandemic due to their limited access to the health care system. Methods: The HCV telemonitoring number was highly advertised in Brazilian media. The RPM program was conducted by dedicated health care personnel trained to follow a predefined script designed to provide awareness, ensure consistent information for educational purposes, and recruit eligible participants to be tested for HCV. Results: From August 2020 to December 2021, 3,738 subjects entered in contact with RPM. There were 26,884 interactions (mean 7.2 interactions per participant), mostly by WhatsApp (78%). Twenty out of those 221 subjects (9%) who tested were HCV positive. Those subjects altogether with 128 other patients with HCV, tested elsewhere, were followed in the HCV CoC. Up to now, 94% of them were linked to care, 24% are undergoing treatment and 8% achieved sustained virological response (SVR). Conclusions: Our preliminary results showed that HCV CoC telemonitoring was a feasible and useful strategy to follow HCV at-risk subjects through all cascade of care until SVR during the COVID-19 health care disruption. It could be used beyond the defervescence of SARS-CoV-2 pandemic to ensure linkage to care of those HCV-positive patients.