The Eastern enlargements of the European Union (EU) since the early 2000s have included post-transitional economies at a lower level of development than the existing member states and thus, have ...significantly affected the East-West migration flows and labour markets on both sides. This has provided a distinctive opportunity to study the effects of liberalisation and to identify economic factors leading to migration flows with the purpose of enabling better estimations of future migration trends. In this research, a panel data analysis with pair of country fixed effects and time fixed effects is used to explore several pull and push factors of the East-West EU migration flows in the period from 2000 to 2017. Results indicate that emigration rate responds rather quickly to the changes in GDP per capita and unemployment rate of the youth population in immigration country, with statistically significant elasticity coefficients, suggesting that international migration contributes significantly to adjusting the labour supply to fluctuations in economic activity.
This paper is part I in a series of two describing the fate of alkali metals and phosphorus during cocombustion of rapeseed cake pellets in a 12 MW thermal CFB boiler. In paper I the results of using ...the mixture of wood chips and wood pellets as a base fuel are described. Up to 45% on energy basis of rapeseed cake was cocombusted during a 4 h test. Two approximately 12 h tests with energy fractions of rapeseed cake of 12 and 18% were performed with limestone as a varying parameter. Fuels were characterized by means of chemical fractionation and standard methods. Elemental mass balances were calculated for ingoing and outgoing streams of the boiler. In addition SEM/EDX analyses of ashes were performed. Gaseous (KCl + NaCl) as well as HCl and SO2 were measured upstream of the convection pass, where deposit samples were also collected with a deposit probe. The deposit samples were analyzed semiquantitatively by means of SEM/EDX. The elemental mass balances show accumulation of alkali metals and phosphorus in the boiler. Analyses of bed material particle cross sections show the presence of phosphorus compounds within a K-silicates matrix between the agglomerated sand particles, indicating a direct attack of gaseous potassium compounds on the bed surface followed by adhesion of ash particles rich in phosphorus. Build-up of deposit during the cocombustion tests mainly took place on the windward side of the probe; where an increase of K, Na, and P has been observed. Addition of limestone prevented formation of K-silicates and increased retention of phosphorus in the bed, most probably due to formation of high-melting calcium phosphates. During the tests with limestone, an increase of potassium chloride upstream of the convection pass and a decrease of phosphorus in the fly ash fraction could be noticed. Agglomeration and slagging/fouling when cofiring wood with rapeseed cake may be linked to its high content of organically bonded phosphorusphytic acid saltstogether with high contents of water-soluble alkali metals chlorides and sulfates in the fuel mixture.
Vancomycin-resistant enterococci (VRE), especially
Enterococcus faecium
, have emerged as significant nosocomial pathogens and patients with impaired host defenses are at a particular risk of VRE ...infection. The most common occurrence is asymptomatic colonization of the gastrointestinal tract that can persist for a long time and serve as a reservoir for transmission of VRE to other patients. We present a case of a patient who was diagnosed with acute myelogenous leukemia and suffered from bone marrow aplasia following induction therapy. The patient received prolonged broad-spectrum antimicrobial therapy. During hospital stay, the patient developed
Clostridium difficile
infection (CDI) and was found to be colonized with a strain of
Enterococcus faecium
resistant to vancomycin during therapy for CDI. This case also highlights the role of risk factors that could contribute to development of resistance, particularly CDI. Early detection of VRE colonization or infection is a crucial component in hospital program designed to prevent transmission of nosocomial infections. Surveillance cultures of such patients should be mandatory.
Rat inferior caval vein (ICV) ligation (up to the right ovarian vein (ROV)) commonly represents a recapitulation of Virchow: with ligation leading to vessel injury, stasis, thrombosis and hemodynamic ...changes. We revealed that BPC 157’s therapy collectively attenuated or counteracted all these events and the full syndrome.
We applied BPC 157 (10 μg, 10 ng/kg) as an early regimen or as a delayed therapy. Assessment includes gross assessment by microcamera; microscopy, venography, bleeding, blood pressure, ECG, thermography, MDA and NO-level in plasma and ICV, and gene expression.
Direct vein injury, thrombosis, thrombocytopenia, prolonged bleeding were all counteracted. Also, rapid presentation of collaterals and redistribution of otherwise trapped blood volume (bypassing through the left ovarian vein (LOV) and other veins), with venous hypertension, arterial hypotension and tachycardia counteraction were shown. BPC 157-rats presented raised plasma NO-values, but normal MDA-values; in ICV tissue reverted low NO-values and counteracted increased MDA-levels. Altered expression of EGR, NOS, SRF, VEGFR and KRAS in ICV, ROV and LOV revealed increased or decreased levels, while some genes continuously remained unchanged.
As a new insight, BPC 157 application largely attenuated or even completely eliminated all consequences of ICV ligation in rats.
A schematic depicting the mode of action of BPC 157 during ICV in rats.
BPC 157 Cytoprotection (cytoprotection concept in damaged stomach interpreted as endothelium recovery toward epithelium recovery 1involves controlling functions of two defensive systems, prostaglandins (PGs)-system (BPC 157 counteracts large scale of toxicity induced by NSAIDs, both COX 1-blockers and COX –blockers 4)and NO-system (5; 6; 7) (in addition to preserve endothelium maintenance (a common point for all cytoprotective agents to induce stomach cytoprotection 1), BPC 157 induces NO-release from stomach tissue homogenates 11). With major vessel essential obstruction, such as ICV, this particular endothelium protection should be generalized toward particular activation of blood vessels, seen once obstructed, with particular collateral vessels recruitment to bypass obstruction. Rapidly activated bypassing loop (LOV and other collaterals) and ligation-stop effectively bypassed may be likely related to the BPC 157 ability to interact with NO-system in different models and species and modulate its function as seen in particular with the counteraction of L-NAME-hypertension as well as counteraction of L-arginine-hypotension (5; 6; 7; 11). Likely along with the proposed involvement of the defensive systems, PGs-system and NO-system in BPC 157 endothelium protection in cytoprotection (1; 4; 5; 6; 7; 11), should be the effects of the BPC 157 on bleeding disorders (13; 34; 35), providing prevention and reversal of thrombosis after abdominal aorta anastomosis 13 as well as counteraction of prolonged bleeding and thrombocytopenias after amputation and anticoagulants (heparin, warfarin, aspirin) application, thought to be NO-system related (34; 35), and thereby, in ICV rats BPC 157 did not affect clotting parameters, thereby, attenuated thrombocytopenia and bleeding upon injury. Finally, further attention merits the evidence that with BPC 157 administration in rats which underwent ligation of ICV, these beneficial effects were combined with the altered EGR, NOS, SRF, VEGR and KRAS: increased (EGR, NOS, SRF, KRAS) or decreased (EGR, VEGFR, PLCɣ), while AKT1 remained unchanged in the ICV, as well as in the ROV and LOV. Consequently, particular pathways with both local and systemic relevance could be suggested. Of note, in ischemic colitis model induced by two ligations on left colic artery and vein, upon BPC 157 administration ligation-stops were effectively bypassed, interconnected loop of intestinal arcade vessels presented particular collateral vessels recruitment to bypass obstruction 36. Display omitted
Vancomycin-resistant Enterococcus faecium (VREfm) is an opportunistic pathogen among the highest global priorities regarding public and environmental health. Following One Health approach, we ...determined for the first time the antibiotic resistance and virulence genes, and sequence types (STs) affiliation of VREfm recovered simultaneously from marine beach waters, submarine outfall of a wastewater treatment plant and an offshore discharge of untreated sewage, and compared them with the surveillance VREfm from regional university hospital in Croatia to assess the hazard of their transmission and routes of introduction into the natural environment. Importantly, VREfm recovered from wastewater, coastal bathing waters and hospital shared similar virulence, multidrug resistance, and ST profiles, posing a major public health threat. All isolates carried the vanA gene, while one clinical isolate also possessed the vanC2/C3 gene. The hospital strains largely carried the aminoglycoside-resistance genes aac(6′)-Ie-aph(2″)-Ia, and aph(2″)-Ib and aph(2″)-Id, which were also predominant in the environmental isolates. The hyl gene was the most prevalent virulence gene. The isolates belonged to 10 STs of the clonal complex CC17, a major epidemic lineage associated with hospital infections and outbreaks, with ST117 and ST889 common to waterborne and hospital isolates, pointing to their sewage-driven dissemination.
To gain better insight into the diversity of accompanying taxons in the surveyed water matrices, microbiome taxonomic profiling was carried out using Illumina-based 16S rDNA sequencing and their resistome features predicted using the PICRUSt2 bioinformatics tool. An additional 60 pathogenic bacterial genera were identified, among which Arcobacter, Acinetobacter, Escherichia-Shigella, Bacteroides and Pseudomonas were the most abundant and associated with a plethora of antibiotic resistance genes and modules, providing further evidence of the hazardous effects of wastewater discharges, including the treated ones, on the natural aquatic environment that should be adequately addressed from a sanitary and technological perspective.
Display omitted
•Hospital and environmental vancomycin-resistant Enterococcus faecium were studied.•VREfm enter marine environment by outfalls of treated and untreated wastewater.•VanA genotype predominates among hospital and waterborne isolates in Croatia.•Hospital and environmental VREfm carry similar virulence and resistance genes.•Microbiome analysis revealed accompanying pathogenic taxa and resistance genes.
RNF213, encoding a giant E3 ubiquitin ligase, has been recognized for its role as a key susceptibility gene for moyamoya disease. Case reports have also implicated specific variants in RNF213 with an ...early-onset form of moyamoya disease with full penetrance. We aimed to expand the phenotypic spectrum of monogenic RNF213-related disease and to evaluate genotype-phenotype correlations.
Patients were identified through reanalysis of exome sequencing data of an unselected cohort of unsolved pediatric cases and through GeneMatcher or ClinVar. Functional characterization was done by proteomics analysis and oxidative phosphorylation enzyme activities using patient-derived fibroblasts.
We identified 14 individuals from 13 unrelated families with (de novo) missense variants in RNF213 clustering within or around the Really Interesting New Gene (RING) domain. Individuals presented either with early-onset stroke (n = 11) or with Leigh syndrome (n = 3). No genotype-phenotype correlation could be established. Proteomics using patient-derived fibroblasts revealed no significant differences between clinical subgroups. 3D modeling revealed a clustering of missense variants in the tertiary structure of RNF213 potentially affecting zinc-binding suggesting a gain-of-function or dominant negative effect.
De novo missense variants in RNF213 clustering in the E3 RING or other regions affecting zinc-binding lead to an early-onset syndrome characterized by stroke or Leigh syndrome.
There is a growing interest for use of cocoa shell for the enrichment of different food products and for resolving problem of disposal of shell. High voltage electrical discharge (HVED) is a ...non‐thermal technology that could solve problems linked to use of cocoa shell (contaminants and undesirable components). This paper investigated the broader impact of HVED on the properties of cocoa shells and how much influence drying (freeze‐ and oven‐ drying), which needs to be conducted, actually has on these properties. After the treatments, oil binding capacity increased in freeze‐dried samples from 1.598 to 2.054 g/g. Also, water was easier to remove from HVED‐treated oven‐dried samples (by 1.75%). HPLC analysis showed that HVED caused better preservation of (−)‐epicatechin and (−)‐epicatechin gallate after oven‐drying. Klason lignin contents slightly increased and differential scanning calorimetry showed higher thermostability of cocoa shell especially after HVED and freeze‐drying because peak shifted for 11.54°C.
Practical applications
Cocoa shell is a valuable by‐product of the chocolate industry, and it presents a problem for the environment. High voltage electrical discharge (HVED) would be a sustainable solution for this problem. After the HVED treatment, drying process is needed, and this study presents insights in a combination of these two technologies on cocoa shell properties. These results show that cocoa shells can be modified with these processes and are suitable for application in different food products.
Fibromyalgia (FM) is a chronic pain syndrome with number of symptoms that present challenge in terms of diagnosis and treatment. Patients with FM show abnormal profile of purines in plasma. In this ...work, we measured serum activities of enzymes involved in purine metabolism, namely total adenosine deaminase (ADE) and its isoforms (ADE1 and ADE2), ecto-ATPase, and 5′-nucleotidase (5′-NT). We also measured activity of dipeptidyl peptidase IV (DPPIV) and prolyl endopeptidase (PEP). Spectrophotometric and fluorometric methods were used for enzyme activity determinations. Enzyme activities were measured in sera of 24 patients with FM that were not undergoing pharmacological treatment during the study. Control group comprised 32 healthy control subjects. Significantly higher activities of total ADE (
P
= 0.025) and ADE2 (
P
= 0.011) were observed in FM patients, while no significant differences in ADE1, ecto-ATPase, and 5′-NT activities (
P
> 0.05) were found when compared to healthy controls. Moreover, increase in the activity of DPPIV (
P
= 0.015) and lower activity of PEP (
P
= 0.011) were also found in the FM group. ROC analysis pointed to different diagnostic sensitivities/specificities for individual enzyme activities measured as follows: ADE (50.0/87.5), ADE2 (41.7/90.6), DPPIV (62.5/71.9), and PEP (83.3/62.5). ADE2 and PEP were shown to be independent predictors of FM, while combination of the two gives AUC of 0.786 (95 % confidence interval of 0.656–0.885,
P
< 0.05). Our results are showing that serum activities of ADE2 and PEP could be useful as biomarkers for FM diagnosis. However, relatively low diagnostic sensitivity of ADE2 and specificity of PEP must be taken into account.
Background: People with Down syndrome (DS) show clinical signs of accelerated ageing. Causative mechanisms remain unknown and hypotheses range from the (essentially untreatable) ...amplified-chromosomal-instability explanation, to potential actions of individual supernumerary chromosome-21 genes. The latter explanation could open a route to therapeutic amelioration if the specific over-acting genes could be identified and their action toned-down. Methods: Biological age was estimated through patterns of sugar molecules attached to plasma immunoglobulin-G (IgG-glycans, an established “biological-ageing-clock”) in n = 246 individuals with DS from three European populations, clinically characterised for the presence of co-morbidities, and compared to n = 256 age-, sex- and demography-matched healthy controls. Isogenic human induced pluripotent stem cell (hiPSCs) models of full and partial trisomy-21 with CRISPR-Cas9 gene editing and two kinase inhibitors were studied prior and after differentiation to cerebral organoids. Findings: Biological age in adults with DS is (on average) 18.4–19.1 years older than in chronological-age-matched controls independent of co-morbidities, and this shift remains constant throughout lifespan. Changes are detectable from early childhood, and do not require a supernumerary chromosome, but are seen in segmental duplication of only 31 genes, along with increased DNA damage and decreased levels of LaminB1 in nucleated blood cells. We demonstrate that these cell-autonomous phenotypes can be gene-dose-modelled and pharmacologically corrected in hiPSCs and derived cerebral organoids. Using isogenic hiPSC models we show that chromosome-21 gene DYRK1A overdose is sufficient and necessary to cause excess unrepaired DNA damage. Interpretation: Explanation of hitherto observed accelerated ageing in DS as a developmental progeroid syndrome driven by DYRK1A overdose provides a target for early pharmacological preventative intervention strategies. Funding: Main funding came from the “Research Cooperability” Program of the Croatian Science Foundation funded by the European Union from the European Social Fund under the Operational Programme Efficient Human Resources 2014–2020, Project PZS-2019-02-4277, and the Wellcome Trust Grants 098330/Z/12/Z and 217199/Z/19/Z (UK). All other funding is described in details in the “Acknowledgements”.
People with Down syndrome (DS) show clinical signs of accelerated ageing. Causative mechanisms remain unknown and hypotheses range from the (essentially untreatable) amplified-chromosomal-instability ...explanation, to potential actions of individual supernumerary chromosome-21 genes. The latter explanation could open a route to therapeutic amelioration if the specific over-acting genes could be identified and their action toned-down.
Biological age was estimated through patterns of sugar molecules attached to plasma immunoglobulin-G (IgG-glycans, an established "biological-ageing-clock") in n = 246 individuals with DS from three European populations, clinically characterised for the presence of co-morbidities, and compared to n = 256 age-, sex- and demography-matched healthy controls. Isogenic human induced pluripotent stem cell (hiPSCs) models of full and partial trisomy-21 with CRISPR-Cas9 gene editing and two kinase inhibitors were studied prior and after differentiation to cerebral organoids.
Biological age in adults with DS is (on average) 18.4-19.1 years older than in chronological-age-matched controls independent of co-morbidities, and this shift remains constant throughout lifespan. Changes are detectable from early childhood, and do not require a supernumerary chromosome, but are seen in segmental duplication of only 31 genes, along with increased DNA damage and decreased levels of LaminB1 in nucleated blood cells. We demonstrate that these cell-autonomous phenotypes can be gene-dose-modelled and pharmacologically corrected in hiPSCs and derived cerebral organoids. Using isogenic hiPSC models we show that chromosome-21 gene DYRK1A overdose is sufficient and necessary to cause excess unrepaired DNA damage.
Explanation of hitherto observed accelerated ageing in DS as a developmental progeroid syndrome driven by DYRK1A overdose provides a target for early pharmacological preventative intervention strategies.
Main funding came from the "Research Cooperability" Program of the Croatian Science Foundation funded by the European Union from the European Social Fund under the Operational Programme Efficient Human Resources 2014-2020, Project PZS-2019-02-4277, and the Wellcome Trust Grants 098330/Z/12/Z and 217199/Z/19/Z (UK). All other funding is described in details in the "Acknowledgements".
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