The susceptibility vessel sign on MR imaging has been reported to indicate acute occlusion from erythrocyte-rich thrombus. The purpose of this study was to evaluate the influence of the ...susceptibility vessel sign seen on MR imaging before treatment on the clinical outcome after mechanical thrombectomy for anterior circulation acute stroke.
We retrospectively included 73 consecutive patients who were treated for anterior circulation acute stroke by mechanical thrombectomy from December 2009 to September 2013. Each patient underwent MR imaging before mechanical thrombectomy. The presence (susceptibility vessel sign+) or absence of the susceptibility vessel sign (susceptibility vessel sign-) was recorded. Mechanical thrombectomy was performed either alone or in association with IV tPA according to the site and time after occlusion. Good functional outcome was defined by an mRS ≤ 2 at 3 months in susceptibility vessel sign+ and susceptibility vessel sign- groups. Patient clinical characteristics, initial NIHSS score and ASPECTS, site of occlusion, time between onset to groin puncture, TICI after mechanical thrombectomy, NIHSS score at day 1, and spontaneous hyperattenuation on CT at day 1 were also analyzed.
Fifty-three patients with susceptibility vessel sign+ and 20 with susceptibility vessel sign- were included in our study. mRS ≤ 2 at 3 months occurred in 65% patients in the susceptibility vessel sign+ group and 26% in the susceptibility vessel sign- group (P = .004). On multivariate analysis, the susceptibility vessel sign was the only parameter before treatment that could predict mRS ≤ 2 at 3 months (OR, 8.7; 95% CI, 1.1-69.4; P = .04).
Our study strongly suggests that the susceptibility vessel sign on MR imaging before treatment is predictive of favorable clinical outcome for patients presenting with anterior circulation acute stroke and treated with mechanical thrombectomy.
Genomic‐assisted breeding for climate‐smart coffee Ferrão, Maria Amélia G.; da Fonseca, Aymbire F. A.; Volpi, Paulo S. ...
The plant genome,
March 2024, 2024-Mar, 2024-03-00, 20240301, 2024-03-01, Letnik:
17, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Coffee is a universal beverage that drives a multi‐industry market on a global basis. Today, the sustainability of coffee production is threatened by accelerated climate changes. In this work, we ...propose the implementation of genomic‐assisted breeding for climate‐smart coffee in Coffea canephora. This species is adapted to higher temperatures and is more resilient to biotic and abiotic stresses. After evaluating two populations, over multiple harvests, and under severe drought weather condition, we dissected the genetic architecture of yield, disease resistance, and quality‐related traits. By integrating genome‐wide association studies and diallel analyses, our contribution is four‐fold: (i) we identified a set of molecular markers with major effects associated with disease resistance and post‐harvest traits, while yield and plant architecture presented a polygenic background; (ii) we demonstrated the relevance of nonadditive gene actions and projected hybrid vigor when genotypes from different geographically botanical groups are crossed; (iii) we computed medium‐to‐large heritability values for most of the traits, representing potential for fast genetic progress; and (iv) we provided a first step toward implementing molecular breeding to accelerate improvements in C. canephora. Altogether, this work is a blueprint for how quantitative genetics and genomics can assist coffee breeding and support the supply chain in the face of the current global changes.
Core Ideas
Sustainability of coffee production is threatened by accelerated climate changes.
Coffea canephora is more adapted to higher temperatures and resilient to biotic and abiotic stresses, which make the species a strategic candidate for the development of climate‐smart cultivars.
By integrating genome‐wide association analyses (GWAS) and Diallel populations, we described the genetic basis of coffee traits evaluated under drought weather conditions.
We identified a set of molecular markers with major effects associated with disease resistance and post‐harvest traits, while yield and plant architecture presented a polygenic background.
We emphasize the importance of genomic‐assisted breeding by proposing a recurrent selection scheme integrating genomic prediction and marker‐assisted selection.
A whole genome association study was performed in a phase 3 clinical trial conducted to evaluate a novel antipsychotic, iloperidone, administered to treat patients with schizophrenia. Genotypes of ...407 patients were analyzed for 334,563 single nucleotide polymorphisms (SNPs). SNPs associated with iloperidone efficacy were identified within the neuronal PAS domain protein 3 gene (NPAS3), close to a translocation breakpoint site previously observed in a family with schizophrenia. Five other loci were identified that include the XK, Kell blood group complex subunit-related family, member 4 gene (XKR4), the tenascin-R gene (TNR), the glutamate receptor, inotropic, AMPA 4 gene (GRIA4), the glial cell line-derived neurotrophic factor receptor-alpha2 gene (GFRA2), and the NUDT9P1 pseudogene located in the chromosomal region of the serotonin receptor 7 gene (HTR7). The study of these polymorphisms and genes may lead to a better understanding of the etiology of schizophrenia and of its treatment. These results provide new insight into response to iloperidone, developed with the ultimate goal of directing therapy to patients with the highest benefit-to-risk ratio.
Abstract
Coffee is one of the most important beverages and trade products in the world. Among the multiple research initiatives focused on coffee sustainability, plant breeding provides the best ...means to increase phenotypic performance and release cultivars that could meet market demands. Since coffee is well adapted to a diversity of tropical environments, an important question for those confronting the problem of evaluating phenotypic performance is the relevance of genotype-by-environment interaction. As a perennial crop with a long juvenile phase, coffee is subjected to significant temporal and spatial variations. Such facts not only hinder the selection of promising materials but also cause a majority of complaints among growers. In this study, we hypothesized that trait stability in coffee is genetically controlled and therefore is predictable using molecular information. To test it, we used genome-based methods to predict stability metrics computed with the primary goal of selecting coffee genotypes that combine high phenotypic performance and stability for target environments. Using 2 populations of Coffea canephora, evaluated across multiple years and locations, our contribution is 3-fold: (1) first, we demonstrated that the number of harvest evaluations may be reduced leading to accelerated implementation of molecular breeding; (2) we showed that stability metrics are predictable; and finally, (3) both stable and high-performance genotypes can be simultaneously predicted and selected. While this research was carried out on representative environments for coffee production with substantial crossover in genotypic ranking, we anticipate that genomic prediction can be an efficient tool to select coffee genotypes that combine high performance and stability across years and the target locations here evaluated.
In order to assess possible human effects associated with glyphosate formulations used in the Colombian aerial spray program for control of illicit crops, a cytogenetic biomonitoring study was ...carried out in subjects from five Colombian regions, characterized by different exposure to glyphosate and other pesticides. Women of reproductive age (137 persons 15-49 yr old) and their spouses (137 persons) were interviewed to obtain data on current health status, history, lifestyle, including past and current occupational exposure to pesticides, and factors including those known to be associated with increased frequency of micronuclei (MN). In regions where glyphosate was being sprayed, blood samples were taken prior to spraying (indicative of baseline exposure), 5 d after spraying, and 4 mo after spraying. Lymphocytes were cultured and a cytokinesis-block micronucleus cytome assay was applied to evaluate chromosomal damage and cytotoxicity. Compared with Santa Marta, where organic coffee is grown without pesticides, the baseline frequency of binucleated cells with micronuclei (BNMN) was significantly greater in subjects from the other four regions. The highest frequency of BNMN was in Boyacá, where no aerial eradication spraying of glyphosate was conducted, and in Valle del Cauca, where glyphosate was used for maturation of sugar cane. Region, gender, and older age (≥35 yr) were the only variables associated with the frequency of BNMN measured before spraying. A significant increase in frequency of BNMN between first and second sampling was observed in Nariño, Putumayo, and Valle immediately (<5 d) after spraying. In the post-spray sample, those who reported direct contact with the eradication spray showed a higher quantitative frequency of BNMN compared to those without glyphosate exposure. The increase in frequency of BNMN observed immediately after the glyphosate spraying was not consistent with the rates of application used in the regions and there was no association between self-reported direct contact with eradication sprays and frequency of BNMN. Four months after spraying, a statistically significant decrease in the mean frequency of BNMN compared with the second sampling was observed in Nariño, but not in Putumayo and Valle del Cauca. Overall, data suggest that genotoxic damage associated with glyphosate spraying for control of illicit crops as evidenced by MN test is small and appears to be transient. Evidence indicates that the genotoxic risk potentially associated with exposure to glyphosate in the areas where the herbicide is applied for coca and poppy eradication is low.
Previous studies of RAE1, a conserved WD40 protein, in Schizosaccharomyces pombe and mouse revealed a role in mRNA export and cell cycle progression in mitotic cells. Studies of RAE1 in Drosophila ...showed that the protein localizes to the nuclear envelope and is required for progression through the G1 phase of the cell cycle but not RNA export in tissue culture cells. Drosophila RAE1 also plays an essential developmental role, as it is required for viability and synaptic growth regulation as a component of an E3 ubiquitin ligase complex. Here we describe characterization of a new Drosophila rae1 mutant that is viable but results in male sterility. The mutant showed striking defects in primary spermatocyte nuclear integrity, meiotic chromosome condensation, segregation, and spindle morphology. These defects led to a failure to complete meiosis but allowed several aspects of spermatid differentiation to proceed, including axoneme formation and elongation. A GFP-RAE1 fusion protein that rescued most of the cytological defects showed a dynamic localization to the nuclear envelope, chromatin and other structures depending on the stage of spermatogenesis. A role for RAE1 in male meiosis, as well as mitotic cells, was also indicated by the defects induced by expression of rae1-RNAi. These studies in Drosophila provide the first evidence for an essential meiotic role of RAE1, and thus define RAE1 as a protein required for both meiotic and mitotic cell cycles.
Abstract Introduction Inhaled mannitol has beneficial effects on lung function, mucociliary clearance, quality of life and sputum properties. This trial examined the efficacy of inhaled mannitol in ...children with cystic fibrosis (CF). Methods The efficacy of inhaled mannitol in children with CF aged 6–17 years was assessed in a phase 2, randomised, placebo-controlled crossover study. Subjects were randomly assigned to mannitol 400 mg every 12 h or matching placebo for 8 weeks, followed by an 8 week washout and an 8 week period with the alternate treatment. The primary endpoint was the absolute change from baseline in ppFEV1 (percent predicted FEV1). Results A total of 92 subjects were studied, with a mean age of 12 years and mean baseline ppFEV1 of 72.2%. During mannitol treatment ppFEV1 was 3.42% (p = 0.004) higher compared to placebo or a 4.97% (p = 0.005) relative difference; relative change from baseline FEF25-75 was 10.52% (p = 0.013). During mannitol treatment, acute post-treatment sputum weight was higher (p = 0.012). In pre-specified subgroups (rhDNase use, age, and disease severity), the treatment differences consistently favoured mannitol. The most common AEs were cough and pulmonary exacerbations. Pulmonary exacerbation AEs were approximately 30% lower in the mannitol group. Conclusions In children with CF, inhaled mannitol was associated with significant improvements in lung function and sputum weight, irrespective of rhDNase use, age or disease severity. Inhaled mannitol was well tolerated and was associated with a reduced incidence of pulmonary exacerbation AEs. (Clinical Trials.Gov: NCT 01883531)
Administration of certain drugs (for example, antiarrhythmics, antihistamines, antibiotics, antipsychotics) may occasionally affect myocardial repolarization and cause prolongation of the QT ...interval. We performed a whole genome association study of drug-induced QT prolongation after 14 days of treatment in a phase 3 clinical trial evaluating the efficacy, safety and tolerability of a novel atypical antipsychotic, iloperidone, in patients with schizophrenia. We identified DNA polymorphisms associated with QT prolongation in six loci, including the CERKL and SLCO3A1 genes. Each single nucleotide polymorphism (SNP) defined two genotype groups associated with a low mean QT change (ranging from -0.69 to 5.67 ms depending on the SNP) or a higher mean QT prolongation (ranging from 14.16 to 17.81 ms). The CERKL protein is thought to be part of the ceramide pathway, which regulates currents conducted by various potassium channels, including the hERG channel. It is well established that inhibition of the hERG channel can prolong the QT interval. SLCO3A1 is thought to play a role in the translocation of prostaglandins, which have known cardioprotective properties, including the prevention of torsades de pointes. Our findings also point to genes involved in myocardial infarction (PALLD), cardiac structure and function (BRUNOL4) and cardiac development (NRG3). Results of this pharmacogenomic study provide new insight into the clinical response to iloperidone, developed with the goal of directing therapy to those patients with the optimal benefit/risk ratio.
Better treatment of obstructed small airways is needed in cystic fibrosis. This study investigated whether efficient deposition of dornase alfa in the small airways improves small airway obstruction. ...In a multicentre, double-blind, randomised controlled clinical trial, cystic fibrosis patients on maintenance treatment with 2.5 mL dornase alfa once daily were switched to a smart nebuliser and randomised to small airway deposition (n = 24) or large airway deposition (n = 25) for 4 weeks. The primary outcome parameter was forced expiratory flow at 75% of forced vital capacity (FEF(75%)). FEF(75%) increased significantly by 0.7 sd (5.2% predicted) in the large airways group and 1.2 sd (8.8% pred) in the small airways group. Intention-to-treat analysis did not show a significant difference in treatment effect between groups. Per-protocol analysis, excluding patients not completing the trial or with adherence <70%, showed a trend (p = 0.06) in FEF(75%) Z-score and a significant difference (p = 0.04) between groups in absolute FEF(75%) (L · s(-1)) favouring small airway deposition. Improved delivery of dornase alfa using a smart nebuliser that aids patients in correct inhalation technique resulted in significant improvement of FEF(75%) in children with stable cystic fibrosis. Adherent children showed a larger treatment response for small airway deposition.
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