Poeorr6191

The Pooled Uranium Miners Analysis (PUMA) study draws together information from cohorts of uranium miners from Canada, the Czech Republic, France, Germany and the USA.

Vital status and cause of death were ascertained and compared with expectations based upon national mortality rates by computing standardized mortality ratios (SMRs) overall and by categories of time since first hire, calendar period of first employment and duration of employment as a miner.

There were 51 787 deaths observed among 118 329 male miners [SMR = 1.05; 95% confidence interval (CI) 1.04, 1.06]. The SMR was elevated for all cancers (n = 16633, SMR = 1.23; 95% CI 1.21, 1.25), due primarily to excess mortality from cancers of the lung (n = 7756, SMR = 1.90; 95% CI 1.86, 1.94), liver and gallbladder (n = 549, SMR = 1.15; 95% CI 1.06, 1.25), larynx (n = 229, SMR = 1.10; 95% CI 0.97, 1.26), stomach (n = 1058, SMR = 1.08; 95% CI 1.02, 1.15) and pleura (n = 39, SMR = 1.06; 95% CI 0.75, 1.44). Lung-cancer SMRs increased with duration of cause of death. The persistent elevation of SMRs with time since first hire as a uranium miner underscores the importance of long-term follow-up of these workers.

Vegetarian diets are becoming increasingly popular in the USA. Limited research has examined the health consequences of vegetarian diets during pregnancy. We comprehensively examined associations of vegetarianism during pregnancy with maternal and neonatal outcomes.

We used data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development's Fetal Growth Studies-Singletons, a prospective multi-site cohort of 1948 low-risk pregnant women of four races/ethnicities (White, Black, Hispanic, Asian/Pacific Islander) in the USA (2009-2013). Vegetarianism was self-reported and also defined based on dietary patterns measured using a self-administered first-trimester food-frequency questionnaire (full [lacto-ovo and vegan], pesco-, semi- and non-vegetarians). Neonatal outcomes included birthweight and neonatal anthropometric measures, small for gestational age, small for gestational age with neonatal morbidity and preterm delivery. Maternal outcomes included gestational weight gain, gesta neonatal size, potentially via the mothers' reduced gestational weight gain. Notably, vegetarianism was not associated with small-for-gestational-age-related morbidities or other adverse maternal outcomes.

Fibrinolytic enzymes are effective and highly safe in treating cardiovascular and cerebrovascular diseases. Therefore, screening fibrinolytic enzyme-producing microbial strains with excellent fermentation performance is of great value to industrial applications. The fibrin plate method was used in screening strains with high yields of fibrinolytic enzymes from different fermented food products, and the screened strains were preliminarily identified using molecular biology. Then, the strains were used for solid-state fermentation of soybeans. Moreover, the fermentation product douchi was subjected to fibrinolytic activity measurement, sensory evaluation, and biogenic amine content determination. The fermentation performance of each strain was comprehensively evaluated through principal component analysis. Finally, the target strain was identified based on strain morphology, physiological and biochemical characteristics, 16S rDNA sequence, and phylogenetic analysis results. A total of 15 Bacillus species with high fibrinolysin activity were selected. Their fibrinolytic enzyme-producing activity levels were higher than 5,500 IU/g. Through molecular biology analysis, we found 4 strains of Bacillus subtilis, 10 strains of Bacillus amyloliquefaciens, and 1 strain of Bacillus velezensis. The principal component analysis results showed that SN-14 had the best fermentation performance and reduced the accumulation of histamine and total amine, the fibrinolytic activity of fermented douchi reached 5,920.5 ± 107.7 IU/g, and the sensory score was 4.6 ± 0.3 (out of 5 points). Finally, the combined results of physiological and biochemical analyses showed SN-14 was Bacillus velezensis. The high-yield fibrinolytic and excellent fermentation performance strain Bacillus velezensis SN-14 has potential industrial application.

Trypanosoma cruzi is the causative agent of Chagas disease. There are only two approved treatments, both of them unsuitable for the chronic phase, therefore the development of new drugs is a priority. Trypanosoma cruzi arginine kinase (TcAK) is a promising drug target since it is absent in humans and it is involved in cellular stress responses. In a previous study, possible TcAK inhibitors were identified through computer simulations resulting the best compounds capsaicin and cyanidin derivatives. Here, we evaluate the effect of capsaicin on TcAK activity and its trypanocidal effect. Although capsaicin produced a weak enzyme inhibition, it had a strong trypanocidal effect on epimastigotes and trypomastigotes (IC50 = 6.26 µM and 0.26 µM, respectively) being 20-fold more active on trypomastigotes than mammalian cells. Capsaicin was also active on the intracellular cycle reducing by half the burst of trypomastigotes at approximately 2 µM. Considering the difference between the concentrations at which parasite death and TcAK inhibition occur, other possible targets were predicted. Capsaicin is a selective trypanocidal agent active in nanomolar concentrations, with an IC50 57-fold lower than benznidazole, the drug currently used for treating Chagas disease.

The generation of genome-wide maps of histone modifications using chromatin immunoprecipitation sequencing is a standard approach to dissect the complexity of the epigenome. Interpretation and differential analysis of histone datasets remains challenging due to regulatory meaningful co-occurrences of histone marks and their difference in genomic spread. To ease interpretation, chromatin state segmentation maps are a commonly employed abstraction combining individual histone marks. learn more We developed the tool SCIDDO as a fast, flexible and statistically sound method for the differential analysis of chromatin state segmentation maps.

We demonstrate the utility of SCIDDO in a comparative analysis that identifies differential chromatin domains (DCD) in various regulatory contexts and with only moderate computational resources. We show that the identified DCDs correlate well with observed changes in gene expression and can recover a substantial number of differentially expressed genes (DEGs). We showcase SCIDDO's ability to directly interrogate chromatin dynamics, such as enhancer switches in downstream analysis, which simplifies exploring specific questions about regulatory changes in chromatin. By comparing SCIDDO to competing methods, we provide evidence that SCIDDO's performance in identifying DEGs via differential chromatin marking is more stable across a range of cell-type comparisons and parameter cut-offs.

The SCIDDO source code is openly available under github.com/ptrebert/sciddo.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.Co-consumption of D-xylose and D-glucose by Saccharomyces cerevisiae is essential for cost-efficient cellulosic bioethanol production. There is a need for improved sugar conversion rates to minimize fermentation times. Previously, we have employed evolutionary engineering to enhance D-xylose transport and metabolism in the presence of D-glucose in a xylose-fermenting S. cerevisiae strain devoid of hexokinases. Re-introduction of Hxk2 in the high performance xylose-consuming strains restored D-glucose utilization during D-xylose/D-glucose co-metabolism, but at rates lower than the non-evolved strain. In the absence of D-xylose, D-glucose consumption was similar to the parental strain. The evolved strains accumulated trehalose-6-phosphate during sugar co-metabolism, and showed an increased expression of trehalose pathway genes. Upon the deletion of TSL1, trehalose-6-phosphate levels were decreased and D-glucose consumption and growth on mixed sugars was improved. The data suggest that D-glucose/D-xylose co-consumption in high-performance D-xylose consuming strains causes the glycolytic flux to saturate. Excess D-glucose is phosphorylated enters the trehalose pathway resulting in glucose recycling and energy dissipation, accumulation of trehalose-6-phosphate which inhibits the hexokinase activity, and release of trehalose into the medium.

In the biological response to biomaterials, implant shell play a key role in immune and inflammatory reactions. Our hypothesis is that the capsules formed around nanotextured implants exhibit an immunohistochemical behavior different from those formed around polyurethane implants.

Evaluate through immunohistochemistry markers the capsules formed around nanotextured and polyurethane implants.

Sixty albino female Wistar rats were divided into two groups (nanotextured and polyurethane), with 30 animals in each group. A mini silicone implant was inserted on the back of the animals. After the determined period, the animals were euthanized, and the capsules formed around the implants were studied. The capsules in the 30-, 60- and 90-day subgroups were analyzed via immunohistochemistry to detect α-SMA, TGF-β, CD34 and CD68 markers, via picrosirius staining to determine the density of type I and III collagen fibers and via hematoxylin and eosin staining to assess capsule thickness. A Wilcoxon-Mann-Whitney test was used to compare the groups, and a Kruskal-Wallis test was used to compare the subgroups.

Lower α-SMA, TGF-β, CD34 and CD68 immunoexpression was observed in the nanotextured 30- and 60-day subgroups than in the corresponding polyurethane subgroups. In the 90-day subgroup, more pronounced α-SMA and CD34 immunoexpression was observed in the nanotextured group; however, TGF-β and CD68 immunoexpression remained lower. The nanotextured implants had reduced capsular thickness and greater formation of type I collagen in all the analyzed subgroups.

Nanotextured implants led to reduced immune and inflammatory reactions compared with polyurethane implants according to all analyzed variables.

Nanotextured implants led to reduced immune and inflammatory reactions compared with polyurethane implants according to all analyzed variables.

Crohn's disease (CD) arises through host-environment interaction. Abnormal gene expression results from disturbed pathway activation or response to bacteria. We aimed to determine activated pathways and driving cell types in paediatric CD.

- We employed contemporary targeted autoimmune RNA sequencing, in parallel to single-cell sequencing, to ileal tissue derived from paediatric CD and controls. Weighted-gene-co-expression-network-analysis (WGCNA) was performed and differentially expressed genes (DEGs) were determined. We integrated clinical data to determine co-expression modules associated with outcomes.

- Twenty-seven treatment-naive CD (TN-CD), 26 established-CD patients and 17 controls were included. WGCNA revealed a 31-gene signature characterising TN-CD patients, but not established-CD, or controls. The CSF3R gene is a hub within this module and is key in neutrophil expansion and differentiation. Antimicrobial genes including S100A12 and the calprotectin subunit S100A9 were significantly upregulated in TN CD compared to controls (p=2.