CTX-M-type enzymes are a group of class A extended-spectrum β-lactamases (ESBLs) that are rapidly spreading among Enterobacteriaceae worldwide. More that 50 allotypes are known, clustered into six ...sub-lineages. The CTX-M-encoding genes have been captured from the chromosome of Kluyvera spp. on conjugative plasmids that mediate their dissemination among pathogenic enterobacteria. CTX-M-type ESBLs exhibit powerful activity against cefotaxime and ceftriaxone but generally not against ceftazidime, which has important implications for laboratory detection. However, several CTX-M variants with enhanced ceftazidimase activity have been detected. The rapid and massive spread of CTX-M-type ESBLs is rapidly changing the ESBL epidemiology and, in some geographical areas, these enzymes are now the most prevalent ESBLs in Enterobacteriaceae.
The safety of creating fish farms in agricultural settings was evaluated by growing Piaractus mesopotamicus in a pond, while crops where cultivated in a nearby field under a pesticide application ...regime typical of the Pampa region. Atrazine, glyphosate and its metabolite, aminomethylphosphonic acid (AMPA), were detected in the water of the pond at concentrations ranging between 92 and 118 μg/L for atrazine, 12 and 221 μg/L for glyphosate and 21 and 117 μg/L for AMPA. Atrazine and malathion were detected in fish muscles at concentrations ranging between 70 and 105 μg/kg for atrazine and 8.6 and 23.7 μg/kg for malathion. Compared to fish raised in a pisciculture, fish from the agricultural pond presented reduced values of pack cell volume, hemoglobin, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, together with significantly greater cholinesterase activity in both plasma and liver and reduced glutathione-S-transferase activity in the liver. A comet assay also demonstrated that P. mesopotamicus from the agricultural pond presented a significantly greater level of DNA damage in both erythrocytes and gill cells. Overall, the present study demonstrates that pisciculture ponds established in an agricultural setting may receive pesticides applied to nearby cultures and that these pesticides may be taken up by the fish and affect their physiology and health. The accumulation of pesticides residues in fish flesh may also present a risk to human consumers and should be closely controlled.
•Atrazine, Glyphosate and AMPA were detected in the water of the pond.•Atrazine and malathion were detected in fish muscle.•Exposure to pesticides caused DNA damage in the fish.•Exposure to pesticides inhibited GST activity in the liver.•Exposure to pesticides induced cholinesterase activity in both liver and plasma.
This article focus on the analysis of the reliability of multiple identical systems that can have multiple failures over time. A repairable system is defined as a system that can be restored to ...operating state in the event of a failure. This work under minimal repair, it is assumed that the failure has a power law intensity and the Bayesian approach is used to estimate the unknown parameters. The Bayesian estimators are obtained using two objective priors know as Jeffreys and reference priors. We proved that obtained reference prior is also a matching prior for both parameters, i.e., the credibility intervals have accurate frequentist coverage, while the Jeffreys prior returns unbiased estimates for the parameters. To illustrate the applicability of our Bayesian estimators, a new data set related to the failures of Brazilian sugar cane harvesters is considered.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite the widespread use of pesticides in the Pampa region of Argentina, mathematical models are rarely employed to predict pesticide fate due to the lack of regionally tested models and the ...absence of readily available databases to run such models. The objective of the current study was to perform a sensitivity analysis of the Pesticide in Water Calculator (PWC) model for the Pampa Region of Argentina. The sensitivity analysis was performed while simulating applications of 2,4-D (mobile, low Kd) and glyphosate (soil-binding, high Kd) in five localities of the Pampa region: Anguil, Paraná, Marcos Juárez, Pergamino and Tres Arroyos. The sensitivity of the various parameters involved in PWC modelling was evaluated though a two-steps sensitivity analysis which included a first screening of less sensitive parameters with Morris method, followed by a fully global sensitivity analysis of the remaining parameters using Sobol method. When ran under soil and climate conditions typical of the Pampa region of Argentina, PWC was most sensitive to 25% of the parameters evaluated. The sensitive parameters identified depended mainly on the nature of the pesticide molecule being modelled; the location and endpoint considered having much less influence on the sensitivity results. Sensitive parameters belonged to two main grand categories: (i) degradation rates of the pesticide in soil and water, and (ii) parameters descriptive of soil binding, runoff and erosion. The sensitivity analysis of the model PWC performed in the current study represents a crucial first step towards the development and expansion of probabilistic pesticide risk assessment in Argentina, and provides important parameterization criteria that will help obtaining more certain modelling results from PWC in Argentina and elsewhere.
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•A sensitivity analysis was performed for PWC for the Pampa region of Argentina.•PWC was most sensitive to 25% of the parameters evaluated.•Soil adsorption coefficient and water and soil half-lives are sensitive parameters.•Sensitive parameters depended on the nature of the pesticide modelled.
Many patients being treated for cancer use dietary supplements, particularly antioxidants, in the hope of reducing the toxicity of chemotherapy and radiotherapy. Some researchers have claimed, ...furthermore, that antioxidants also increase the effectiveness of cytotoxic therapy and have explicitly recommended their use. However, mechanistic considerations suggest that antioxidants might reduce the effects of conventional cytotoxic therapies. Preclinical data are currently inconclusive and a limited number of clinical studies have not found any benefit. Clinicians should advise their patients against the use of antioxidant dietary supplements during chemotherapy or radiotherapy. Such caution should be seen as the standard approach for any unproven agent that may be harmful.
BACKGROUND:Human or recombinant apolipoprotein A-I (apoA-I) has been shown to increase high-density lipoprotein–mediated cholesterol efflux capacity and to regress atherosclerotic disease in animal ...and clinical studies. CSL112 is an infusible, plasma-derived apoA-I that has been studied in normal subjects or those with stable coronary artery disease. This study aimed to characterize the safety, tolerability, pharmacokinetics, and pharmacodynamics of CSL112 in patients with a recent acute myocardial infarction.
METHODS:The AEGIS-I trial (Apo-I Event Reducing in Ischemic Syndromes I) was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging phase 2b trial. Patients with myocardial infarction were stratified by renal function and randomized 1:1:1 to CSL112 (2 g apoA-I per dose) and high-dose CSL112 (6 g apoA-I per dose), or placebo for 4 consecutive weekly infusions. Coprimary safety end points were occurrence of either a hepatic safety event (an increase in alanine transaminase >3 times the upper limit of normal or an increase in total bilirubin >2 times the upper limit of normal) or a renal safety event (an increase in serum creatinine >1.5 times the baseline value or a new requirement for renal replacement therapy).
RESULTS:A total of 1258 patients were randomized, and 91.2% received all 4 infusions. The difference in incidence rates for an increase in alanine transaminase or total bilirubin between both CSL112 arms and placebo was within the protocol-defined noninferiority margin of 4%. Similarly, the difference in incidence rates for an increase in serum creatinine or a new requirement for renal replacement therapy was within the protocol-defined noninferiority margin of 5%. CSL112 was associated with increases in apoA-I and ex vivo cholesterol efflux similar to that achieved in patients with stable coronary artery disease. In regard to the secondary efficacy end point, the risk for the composite of major adverse cardiovascular events among the groups was similar.
CONCLUSIONS:Among patients with acute myocardial infarction, 4 weekly infusions of CSL112 are feasible, well tolerated, and not associated with any significant alterations in liver or kidney function or other safety concern. The ability of CSL112 to acutely enhance cholesterol efflux was confirmed. The potential benefit of CSL112 to reduce major adverse cardiovascular events needs to be assessed in an adequately powered phase 3 trial.
CLINICAL TRIAL REGISTRATION:URLhttps://clinicaltrials.gov. Unique identifierNCT02108262.
Colostrum and milk are essential sources of antibodies and nutrients for the neonate, playing a key role in their survival and growth. Slight abnormalities in the timing of ...colostrogenesis/lactogenesis potentially threaten piglet survival. To further delineate the genes and transcription regulators implicated in the control of the transition from colostrogenesis to lactogenesis, we applied RNA-seq analysis of swine mammary gland tissue from late-gestation to farrowing. Three 2nd parity sows were used for mammary tissue biopsies on days 14, 10, 6 and 2 before (-) parturition and on day 1 after (+) parturition. A total of 15 mRNA libraries were sequenced on a HiSeq2500 (Illumina Inc.). The Dynamic Impact Approach and the Ingenuity Pathway Analysis were used for pathway analysis and gene network analysis, respectively.
A large number of differentially expressed genes were detected very close to parturition (-2d) and at farrowing (+ 1d). The results reflect the extraordinary metabolic changes in the swine mammary gland once it enters into the crucial phases of lactogenesis and underscore a strong transcriptional component in the control of colostrogenesis. There was marked upregulation of genes involved in synthesis of colostrum and main milk components (i.e. proteins, fat, lactose and antimicrobial factors) with a pivotal role of CSN1S2, LALBA, WAP, SAA2, and BTN1A1. The sustained activation of transcription regulators such as SREBP1 and XBP1 suggested they help coordinate these adaptations.
Overall, the precise timing for the transition from colostrogenesis to lactogenesis in swine mammary gland remains uncharacterized. However, our transcriptomic data support the hypothesis that the transition occurs before parturition. This is likely attributable to upregulation of a wide array of genes including those involved in 'Protein and Carbohydrate Metabolism', 'Immune System', 'Lipid Metabolism', 'PPAR signaling pathway' and 'Prolactin signaling pathway' along with the activation of transcription regulators controlling lipid synthesis and endoplasmic reticulum biogenesis and stress response.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bovine milk is important for human nutrition, but its fat content is often criticized as a risk factor in cardiovascular disease. Selective breeding programs could be used to alter the fatty acid ...(FA) composition of bovine milk to improve the healthiness of dairy products for human consumption. Here, we performed a genome-wide association study (GWAS) on bovine milk to identify genomic regions or specific genes associated with FA profile and to investigate genetic differences between the Italian Simmental (IS) and Italian Holstein (IH) breeds. To achieve this, we first characterized milk samples from 416 IS cows and 436 IH cows for their fat profile by gas chromatography. Subjects were genotyped with single nucleotide polymorphism array and a single-marker regression model for GWAS was performed. Our findings confirm previously reported quantitative trait loci strongly associated with bovine milk fat composition. More specifically, our GWAS results revealed significant signals on chromosomes Bos taurus autosome 19 and 26 for milk FA. Further analysis using a gene-centric approach and pathway meta-analysis identified not only some well-known genes underlying quantitative trait loci for milk FA components, such as FASN, SCD, and DGAT1, but also other significant candidate genes, including some with functional roles in pathways related to “Lipid metabolism.” Highlighted genes related to FA profile include ECI2, PCYT2, DCXR, G6PC3, PYCR1, and ALG12 in IS, and CYP17A1, ACO2, PI4K2A, GOT1, GPT, NT5C2, PDE6G, POLR3H, and COX15 in IH. Overall, the breed-specific association outcomes reflect differences in the genetic backgrounds of the IS and IH breeds and their selective breeding histories.
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