Non-malignant silica-related diseases in a specialized outpatient clinic.

BACKGROUND: Uncontrolled occupational exposure to silica is still frequent in Brazil, with several recent records in the state of Minas Gerais. However, few national studies have addressed silica-related diseases other than silicosis. AIMS: To describe the occurrence of the main non-malignant silica-related diseases: silicosis, tuberculosis (TB), chronic obstructive pulmonary disease (COPD), and autoimmune diseases in a specialized outpatient clinic. METHODS: Case series study of 1525 patients exposed to silica, seen between 1984 and 2021, with descriptive findings of clinical and occupational data from the first medical evaluation. RESULTS: Medians of age and exposure time were 47 and 15 years, respectively, and 97% of patients were male. The prevalence of silicosis was 44%, of which 27% had large opacities. The main occupational sectors were underground gold mining (28%), precious and semi-precious stone work (20%), and artisanal mining (9%). Spirometries were abnormal in 55%, with obstructive disorder being the most common finding. COPD (25%), active TB or sequelae (12%), and connective tissue diseases (6%) were diagnosed in patients with and without silicosis. CONCLUSIONS: The percentage of silicosis appears to be alarming, even considering the biases of selective referrals. The patients were relatively young and already had a functional impact, caused not only by silicosis but by one or more silica-related diseases. COPD, TB, and connective tissue diseases proved to be frequent, leading to the need for specifics protocols to investigate them in individuals exposed to silica. By adopting strategies to combat silicosis, the prevention of other silica-related diseases is concomitantly promoted.

Does exposure to inflammatory particles modify the pattern of anion in exhaled breath condensate?

Exposure to environmental and occupational particulate matter (PM) induces health effects on the cardio-pulmonary system. In addition, associations between exposure to PM and metabolic syndromes like diabetes mellitus or obesity are now emerging in the literature. Collection of exhaled breath condensate (EBC) is an appealing non-invasive technique to sample pulmonary fluids. This hypothesis-generating study aims to (1) validate an ion chromatography method allowing the robust determination of different metabolism-related molecules (lactate, formate, acetate, propionate, butyrate, pyruvate, nitrite, nitrate) in EBC; (2) apply this method to EBC samples collected from workers exposed to quartz (a known inflammatory particle), to soapstone (a less inflammatory particle than quartz), as well as to controls. A multi-compound standard solution was used to determine the linearity range, detection limit, repeatability and bias from spiked EBC. The biological samples were injected without further treatment into an ion chromatograph with a conductivity detector. RTube® were used for field collection of EBC from 11 controls, 55 workers exposed to soapstone and 12 volunteers exposed to quartz dust. The analytical method used proved to be adequate for quantifying eight anions in EBC samples. Its sub-micromolar detection limits and repeatability, combined with a very simple sample preparation, allowed an easy and fast quantification of different glycolysis or nitrosative stress metabolites. Using multivariate discriminant analysis to maximize differences between groups, we observed a different pattern of anions with a higher formate/acetate ratio in the EBC samples for quartz exposed workers compared to the two other groups. We hypothesize that a modification of the metabolic signature could be induced by exposure to inflammatory particles like quartz and might be observed in the EBC via a change in the formate/acetate ratio.

Method validation of nanoparticle tracking analysis to measure pulmonary nanoparticle content: the size distribution in exhaled breath condensate depends on occupational exposure.

A particle exposure assessment based on the dose deposited in the lungs would be the gold standard for the evaluation of any resulting health effects. Measuring particles in exhaled breath condensate (EBC)-a matrix containing water and airway lining fluid-could help to evaluate particle retention in the lungs. This study aimed to (1) validate a nanoparticle tracking analysis (NTA) method for determining the particle number concentration and their hydrodynamic size distribution in EBC, and (2) apply this method to EBC collected from workers exposed to soapstone (n = 55) or quartz dust (n = 12) and controls (n = 11). A standard latex bead solution was used to determine the linear range, limit of detection (LOD), repeatability (coefficient of variation, CV), and bias in spiked EBC. An LM10 NanoSight instrument with NTA version 3.1 software was used for measurement. RTubes® were used for field collection of EBC. The repeatability obtained for a D50 size distribution in EBC showed less than 8% variability, with a bias <7%. The particle concentration was linear in the range ≤2.5 × 108 particles ml-1 with a LOD of 4 × 106 particles ml-1. A recovery of 117 ± 20% at 6.2 × 107 particles ml-1 was obtained with a CV <10% and a bias <20%. EBC from workers exposed to quartz, who experienced the largest exposure to silica particles, consistently exhibited a statistically significant (p < 0.01) higher concentration of particles in their EBC, with a size distribution shift towards larger values than the other groups. Results showed that the NTA technique performed well for characterizing the size distribution and concentrations of particles in EBC. The technique needs to be corroborated with a larger population of workers.

Genetic evaluation of milk yield in Alpine goats for the first four lactations using random regression models.

Random regression models have been used in evaluating test-day milk yield, providing accurate estimates of genetic values in animals. However, herd evaluation with only information from the first lactation may not be the best option from an economic perspective. Other factors should be taken into account, particularly other lactations. Our objective in this study was to analyze the genetic divergence between the first four lactations of Alpine goats. The RENPED software was used to perform descriptive statistics, check for errors in pedigree, recode the data, and for Pearson's and Spearman's correlations. The WOMBAT software was used to estimate the variance components and predict the breeding values. The CALC software was adopted to calculate the percentage of coincidence between the ranking of the animals and the animals kept in common at each lactation evaluation. The results show that selection using only the first lactation in small herds with a low degree of technology can be employed as a palliative measure, in view of the difficulty in evaluating all lactations. However, the selection of breeding goats and the production of catalogues should not be based only on the first lactation, because the results demonstrate inversions in the classification of the best breeders when other lactations are analyzed.

Seleção, acasalamento e genotipagem seletiva e outras estratégias de amostragem na detecção de QTL / Selection, mating, and selective genotyping and other strategies of sampling on QTL detection

Foram simuladas diferentes estratégias de seleção para estimar o desempenho fenotípico e a endogamia média na seleção assistida por marcadores, em características quantitativas com valores de herdabilidade de 0,10; 0,40 e 0,70. O sistema de simulação genética (Genesys) foi utilizado para a simulação de três genomas (cada qual constituído de uma única característica cuja distinção estava no valor da herdabilidade), e das populações base e inicial. Cada população inicial foi submetida à seleção assistida por marcadores por 20 gerações consecutivas. Avaliaram-se estratégias de acasalamento entre os genitores selecionados, em diferentes intensidades de seleção (tamanhos populacionais), por meio do acasalamento seletivo entre os melhores e os piores, acasalamento apenas entre os melhores e/ou entre os piores e acasalamento aleatório. Em todos os cenários combinando herdabilidade e intensidade, o acasalamento estratégico utilizando a metodologia da genotipagem seletiva foi superior aos demais, tornando-se mais eficaz na detecção de QTL e, consequentemente, no incremento do valor fenotípico e na minimização das médias endogâmicas ao longo das gerações. Ao utilizar a estratégia seletiva de amostragem, menor tamanho populacional é requerido para otimizar a detecção de QTL à medida que o valor da herdabilidade da característica aumenta.

Different strategies of selection were simulated to estimate the phenotypic performance and average inbreeding in selection assisted by markers, for quantitative traits with heritability values of 0.10, 0.40, and 0.70. The genetic simulation system (Genesys) was used for the simulation of three genomes (each one consisting of a single characteristic which distinction was the value of heritability) and base and original populations. Each initial population was subjected to selection assisted by markers for 20 consecutive generations. Strategies of mating between the parents selected in different intensities of selection (population size) were evaluated by selective mating between the best and worst, mating only among the best and/or among the worst and random mating. In all scenarios combining heritability and intensity, the strategic mating using the methodology of selective genotyping was superior to the others, becoming more effective in detecting QTL and, consequently, in the increase of phenotypic value and in the minimization of the inbred average over the generations. By using the selective sampling strategy, smaller population size to optimize the detection of QTL is required, since the value of the heritability of the characteristic increases.

Comparação de metodologias de seleção sob oscilação genética / Comparison of selection methodologies under genetic drift

Determinou-se o número adequado de repetições na comparação de métodos de seleção tradicionais e associados a marcadores moleculares, com diferentes tamanhos efetivos e sob diferentes sistemas de acasalamento dos reprodutores selecionados, usando simulação com o programa GENESYS. Para comparar os diferentes métodos de seleção utilizaram-se populações com tamanhos efetivos de 18,18 (TE1) e de 66,66 (TE2) e uma, 10 e 30 repetições por geração, avaliando-se os valores fenotípicos médios. Para as situações com apenas uma repetição, os resultados apresentaram incoerências, independentemente do tamanho efetivo (TE1 ou TE2) ou do sistema de acasalamento (RAA - reprodutores acasalados aleatoriamente, EIC - exclusão de irmãos completos ou EICMI - exclusão de irmãos completos e meio-irmãos). Observou-se que a oscilação genética influencia o ganho genético, principalmente, em populações com pequeno tamanho efetivo e que um valor mínimo de 10 repetições por geração é necessário para assegurar a consistência dos resultados obtidos pelos métodos de seleção.

This work was carried out to determine the required number of replicates for comparison of conventional and molecular marker-associated selection methods in distinct effective population sizes and different mating systems, by simulations using the software GENESYS. Effective populational size of 18.18 (ES1) and 66.66 (ES2), and one, 10, and 30 replicates per generation were used to compare the different selection methods, based on mean phenotypic values. Incongruences results were observed when a single replicate was considered independently of effective size (ES1or ES2) and the mating system (random mating; exclusion of full-sibs or exclusion of both full and half-sibs). Genetic oscillation influenced the genetic gain, mainly in populations of small effective size. Furthermore, at least 10 replicates per generation were required to obtain sound consistent results for both selection methods.

Assessing correlations between spirometry and Shwachman-Kulczycki score in children and adolescents.

A retrospective observational study was carried out to analyze the correlations between formal pulmonary function tests and the Shwachman-Kulczycki (SK) score. Forty-six Brazilian cystic fibrosis (CF) patients, clinically stable, aged 7-19 years, were included. Clinical and radiological findings of the SK score system and spirometry variables were assessed by independent observers in a blinded manner. The strongest correlation (r = 0.75; 95% CI, 0.59-0.85; P < 0.001) was found for forced expiratory volume in 1 sec (FEV1). Despite some peculiarities of our patients, the results are in agreement with studies undertaken in industrialized countries, showing good correlation between FEV1 and SK score and its usefulness in managing CF. Accordingly, in countries where pulmonary function testing is not available, the SK score remains a valuable parameter on which to base treatment results.