Non-oncotic albumin functions such as transport, antioxidant and immunomodulatory capacities may be associated with the beneficial effects of albumin therapy in liver disease patients. For ...acute-on-chronic liver failure (ACLF) patients, characterized mainly by severe systemic inflammation and organ failure, plasma exchange with human serum albumin (PE-A5%) may be an effective treatment. In fact, the effects of PE-A5% on short-term survival in patients with ACLF are currently under investigation (APACHE phase 3 trial, NCT03702920). To characterize albumin levels with intact structure (effective albumin) in patients with ACLF compared with healthy controls (HC) and to assess the effect of PE-A5% treatment on eAlb levels in patients with ACLF.
Plasma samples from 10 patients included in the Pilot-APACHE trial (NCT01201720) were assessed. This was a prospective, open-label, non-controlled study in which ACLF patients were treated with six PE-A5% for 10 days. At baseline, results were compared with HC (n=10). Albumin post-translational modifications (PTMs) were determined by mass spectrometry (LC_ESI_qTOF-MS). Native albumin (%) (the primary structure preserved form without PTMs) and effective albumin levels (mg/mL) (calculated as (total albumin x native albumin)/100)) were evaluated. Results were expressed as median (IQR).
At baseline, ACLF patients showed a significantly lower proportion of native albumin, 19.4% (10.0-28.5), compared with HC, 51.3% (49.0-52.6), P<0.0001. Similarly, effective albumin levels, 6.8 mg/mL (3.5-8.9), were lower than HC, 19.8 mg/mL (18.9-20.7), P<0.0001. This reduction in native albumin was associated with higher cysteinylated and glycated isoforms. After six PE-A5%, native albumin (27.6% (17.1-35.3), p=0.036) and effective albumin (10.4 mg/mL (6.4-13.8); p=0.0067) were significantly increased. Remarkably, this effect was observed right after each PE-A5% session.
ACLF patients presented albumin structural abnormalities that led to decreased effective albumin levels. PE-A5% not only improved non-oncotic albumin functions1 but increased structurally preserved albumin in these patients.
1J Hepatol 2018;68(Suppl1):S105-S364
Dravet syndrome (DS) is an epileptic syndrome caused by mutations in the
gene encoding the α1 subunit of the sodium channel Nav1.1, which is associated with febrile seizures that progress to severe ...tonic-clonic seizures and associated comorbidities. Treatment with cannabidiol has been approved to reduce seizures in DS, but it may also be active against these comorbidities. The aim of this study was to validate a new mouse model of DS having lower mortality than previous models, which may serve to further evaluate therapies for the long-term comorbidities. This new model consists of heterozygous conditional knock-in mice carrying a missense mutation (A1783V) in
gene expressed exclusively in neurons of the CNS (Syn-Cre/Scn1a
). These mice have been used here to determine the extent and persistence of the behavioral deterioration in different postnatal days (PND), as well as to investigate the alterations that the disease produces in the endocannabinoid system and the contribution of inflammatory events and impaired neurogenesis in the pathology. Syn-Cre/Scn1a
mice showed a strong reduction in hindlimb grasp reflex at PND10, whereas at PND25, they presented spontaneous convulsions and a greater susceptibility to pentylenetetrazole-induced seizures, marked hyperactivity, deficient spatial working memory, lower levels of anxiety, and altered social interaction behavior. These differences disappeared at PND40 and PND60, except the changes in social interaction and anxiety. The analysis of CNS structures associated with these behavioral alterations revealed an elevated glial reactivity in the prefrontal cortex and the dentate gyrus. This was associated in the dentate gyrus with a greater cell proliferation detected with Ki67 immunostaining, whereas double-labeling analyses identified that proliferating cells were GFAP-positive suggesting failed neurogenesis but astrocyte proliferation. The analysis of the endocannabinoid system of Syn-Cre/Scn1a
mice confirmed reductions in CB
receptors and MAGL and FAAH enzymes, mainly in the cerebellum but also in other areas, whereas CB
receptors became upregulated in the hippocampus. In conclusion, Syn-Cre/Scn1a
mice showed seizuring susceptibility and several comorbidities (hyperactivity, memory impairment, less anxiety, and altered social behavior), which exhibited a pattern of age expression similar to DS patients. Syn-Cre/Scn1a
mice also exhibited greater glial reactivity and a reactive response in the neurogenic niche, and regional changes in the status of the endocannabinoid signaling, events that could contribute in behavioral impairment.
In this study, we evaluate the performance of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for rapid detection of carbapenemase activity in ...Enterobacterales in clinical microbiology laboratories during a multicenter networking validation study. The study was divided into three different stages: "software design," "intercenter evaluation," and "clinical validation." First, a standardized procedure with an online software for data analysis was designed. Carbapenem resistance was detected by measuring imipenem hydrolysis and the results were automatically interpreted using the Clover MS data analysis software (Clover BioSoft, Spain). Second, a series of 74 genotypically characterized Enterobacterales (46 carbapenemase-producers and 28 non carbapenemase-producers) were analyzed in 8 international centers to ensure the reproducibility of the method. Finally, the methodology was evaluated independently in all centers during a 2-month period and results were compared with the reference standard for carbapenemase detection used in each center. The overall agreement rate relative to the reference method for carbapenemase resistance detection in clinical samples was 92.5%. The sensitivity was 93.9% and the specificity, 100%. Results were obtained within 60 min and accuracy ranged from 83.3 to 100% among the different centers. Further, our results demonstrate that MALDI-TOF MS is an outstanding tool for rapid detection of carbapenemase activity in Enterobacterales in clinical microbiology laboratories. The use of a simple in-house procedure with online software allows routine screening of carbapenemases in diagnostics, thereby facilitating early and appropriate antimicrobial therapy.
As opposed to most literature on the history of family firms, this article focuses on the continuance of business -products, services, markets- which is not the same as the longevity of the firm, ...understood as the maintenance of ownership, control or management, or of the business family, with its kinship connections, succession of generations, etc.
The article aims at demonstrating how a business can be perpetuated regardless of firms or owning families. For this purpose, it studies the case of an olive oil business related to several families and companies (most of them family firms) from 1857 to the present day. The history of this olive oil business explains how it persisted throughout the years with its factories, products and trademarks being transferred from firm to firm and from owner to owner. The work also underlines how, in this process, each new firm and each new owner claimed the accumulated heritage as their own.
The article insists on the continuation of the business activity and highlights the relevance of studying, not only companies and owning families, but the businesses they develop.
Background
Food protein‐induced enterocolitis (FPIES) is an uncommon, non‐IgE‐mediated food allergy that usually debuts in infancy with profuse vomiting, lethargy, and pallor 2–4 h following ...ingestion of the offending food. Its immune mechanism is not known. We aimed to describe the clinical features and outcome of children with fish‐FPIES as well as to investigate on cellular immune response implicated.
Methods
Prospective and follow‐up clinical study of children with FPIES by fish over a period between 2004 and 2013 was conducted. Measurement in vitro of both cytokine production in peripheral blood mononuclear cells (PBMCs) and expression of HLA‐DR in monocyte‐derived dendritic cells stimulated with fish extracts.
Results
Sixteen children (seven male and nine female) were included, with a mean age of onset at 10 months. Diagnosis was established after a median of 4 reactions. Twelve patients were treated in emergency room, and two were admitted in intensive care. Patch tests were positive in six patients. Skin prick tests (SPTs) and specific IgE to all fish tested were negative. Only three children reached tolerance at a mean age of 4.5 years. Eight children avoided fish because of positive oral food challenge (OFC) after 6 years of age. Other patients have not been challenged because of parent refusal to OFC or a recent diagnosis. TNF‐α was increased in patients, and a significant elevation of the HLA‐DR marker was also observed in these patients vs. control donors.
Conclusions
FPIES caused by fish in many cases presents with severe clinical manifestations. Patch test has poor diagnostic value, and OFC is the gold standard to test tolerance. The cytokine TNF‐α may be implicated in the clinical symptoms. Higher expression of HLA‐DR in dendritic cells has also been detected in our patients.
Non-typhoid serovars of
are one of the main causes of bacterial food-borne infections worldwide. For the treatment of severe cases of salmonellosis in adults, fluoroquinolones are amongst the drugs ...of choice. They are categorized by the World Health Organization (WHO) as "critically important with highest priority in human medicine". In the present study, two clinical
serovar Corvallis isolates (HUA 5/18 and HUA 6/18) from a Spanish hospital, selected on the basis of fluoroquinolone resistance, were characterized. The MICs of ciprofloxacin, determined by E-test, were 0.5 and 0.75 µg/mL for HUA 5/18 and HUA 6/18, respectively, and both were also resistant to pefloxacin but susceptible to nalidixic acid. Whole genome sequencing (WGS) of the isolates was performed with Illumina platform, and different bioinformatics tools were used for sequence analysis. The two isolates belonged to ST1541, and had the Thr57Ser substitution in the ParC protein which is also found in ciprofloxacin susceptible isolates. However, they harbored identical ColE plasmids of 10 kb carrying the
gene. In these plasmids, the gene was flanked by defective versions of IS
-like and IS
-like insertion sequences. HUA 5/18 and HUA 6/18 were also phenotypically resistant to streptomycin, sulfonamides and tetracycline, with the responsible genes:
,
,
and
(A) genes, being located on a IncQ1 plasmid. ColE plasmids with the
gene are widely spread among multiple serovars of
from different samples and countries. These mobilizable plasmids are playing an important role in the worldwide spread of
. Thus, their detection in hospitals is a cause of concern which deserves further attention.
LABOR MARKET EQUILIBRIUM WITH REHIRING FERNÁNDEZ-BLANCO, JAVIER
International economic review (Philadelphia),
August 2013, Volume:
54, Issue:
3
Journal Article
Peer reviewed
Consistent with the empirical evidence, this article analyzes a labor market in which separations are not permanent and reactivated firms prefer to rehire former employees instead of seek new ones. ...Workers engage in job search due to the uncertain prospects of rehiring. If firms can commit to wages contingent on rehiring, they backload wages to provide incentives for workers to reduce their unobservable search effort. Under risk aversion and incomplete markets, if productivity at reactivation is sufficiently high, the tension between wage backloading and consumption smoothing leads to excessive search in equilibrium.
This publication presents a dataset of Spanish roundabouts aerial images taken from a UAV, along with annotations in PASCAL VOC XML files that indicate the position of vehicles within them. ...Additionally, a CSV file is attached containing information related to the location and characteristics of the captured roundabouts. This work details the process followed to obtain them: image capture, processing, and labeling. The dataset consists of 985,260 total instances: 947,400 cars, 19,596 cycles, 2262 trucks, 7008 buses, and 2208 empty roundabouts in 61,896 1920 × 1080 px JPG images. These are divided into 15,474 extracted images from 8 roundabouts with different traffic flows and 46,422 images created using data augmentation techniques. The purpose of this dataset is to help research into computer vision on the road, as such labeled images are not abundant. It can be used to train supervised learning models, such as convolutional neural networks, which are very popular in object detection.
Linked Open Data promises to provide guiding principles to publish interlinked knowledge graphs on the Web in the form of findable, accessible, interoperable, and reusable datasets. We argue that ...while as such, Linked Data may be viewed as a basis for instantiating the FAIR principles, there are still a number of open issues that cause significant data quality issues even when knowledge graphs are published as Linked Data. First, to define boundaries of single coherent knowledge graphs within Linked Data, a principled notion of what a dataset is, or, respectively, what links within and between datasets are, has been missing. Second, we argue that to enable FAIR knowledge graphs, Linked Data misses standardised findability and accessability mechanism via a single entry link. To address the first issue, we (i) propose a rigorous definition of a naming authority for a Linked Data dataset, (ii) define different link types for data in Linked datasets, (iii) provide an empirical analysis of linkage among the datasets of the Linked Open Data cloud, and (iv) analyse the dereferenceability of those links. We base our analyses and link computations on a scalable mechanism implemented on top of the HDT format, which allows us to analyse quantity and quality of different link types at scale.
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