Pulmonary regurgitation (PR) is the most common late complication in patients after repair of tetralogy of Fallot (TOF). Most patients remain asymptomatic over years, but eventually, the compensatory ...mechanisms fail, leading to right ventricular (RV) dilation and dysfunction, limited exercise capacity, ventricular arrhythmia, and sudden death.
We aimed to evaluate associations between cardiac magnetic resonance (CMR) parameters and the need for either surgical or percutaneous pulmonary valve replacement (PVR) in asymptomatic patients with significant PR after repair of TOF.
Of 209 patients with repaired TOF who had undergone a CMR study, we selected 61 asymptomatic patients with moderate‑to‑severe PR and followed them for up to 4 years (mean SD, 21.4 13.7 months). We excluded patients with residual ventricular septal defect, a peak RV outflow tract gradient of 30 mm Hg or higher, or at least moderate tricuspid regurgitation.
Receiver operating characteristic curve analyses revealed that the ratio of RV to left ventricular (LV) volume (RV/ LV ratio; threshold >2.4) and PR fraction (PRF; threshold >33%) had acceptable discriminatory capacity to differentiate between patients requiring PVR and those treated conservatively. The Cox proportional hazards regression and the Kaplan–Meier curves revealed that the RV / LV ratio and PRF was significantly associated with the need for PVR. The combination of the RV / LV ratio and PRF provided significant discrimination in terms of survival without PVR (P <0.001; log‑rank test for trend).
The RV/ LV ratio and PRF were significantly associated with the need for PVR in asymptomatic patients with isolated moderate‑to‑severe PR after repair of TOF.
Provider: - Institution: - Data provided by Europeana Collections- artykuł z: Annales Universitatis Mariae Curie-Skłodowska. Sectio J, Paedagogia-Psychologia. Vol. 20 (2007), s. 234-238- All metadata ...published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
Antimicrobial peptides (AMPs), or host defence peptides, are short proteins in various life forms. Here we discuss AMPs, which may become a promising substitute or adjuvant in pharmaceutical, ...biomedical, and cosmeceutical uses. Their pharmacological potential has been investigated intensively, especially as antibacterial and antifungal drugs and as promising antiviral and anticancer agents. AMPs exhibit many properties, and some of these have attracted the attention of the cosmetic industry. AMPs are being developed as novel antibiotics to combat multidrug-resistant pathogens and as potential treatments for various diseases, including cancer, inflammatory disorders, and viral infections. In biomedicine, AMPs are being developed as wound-healing agents because they promote cell growth and tissue repair. The immunomodulatory effects of AMPs could be helpful in the treatment of autoimmune diseases. In the cosmeceutical industry, AMPs are being investigated as potential ingredients in skincare products due to their antioxidant properties (anti-ageing effects) and antibacterial activity, which allows the killing of bacteria that contribute to acne and other skin conditions. The promising benefits of AMPs make them a thrilling area of research, and studies are underway to overcome obstacles and fully harness their therapeutic potential. This review presents the structure, mechanisms of action, possible applications, production methods, and market for AMPs.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
One of the most promising methods against drug-resistant bacteria can be surface-modified materials with biocidal nanoparticles and nanocomposites. Herein, we present a nanocomposite with silver ...nanoparticles (Ag-NPs) on the surface of graphene oxide (GO) as a novel multifunctional antibacterial and antifungal material. Ultrasonic technologies have been used as an effective method of coating polyurethane foils. Toxicity on gram-negative bacteria (
Escherichia coli
), gram-positive bacteria (
Staphylococcus aureus
and
Staphylococcus epidermidis
), and pathogenic yeast (
Candida albicans
) was evaluated by analysis of cell morphology, assessment of cell viability using the PrestoBlue assay, analysis of cell membrane integrity using the lactate dehydrogenase assay, and reactive oxygen species production. Compared to Ag-NPs and GO, which have been widely used as antibacterial agents, our nanocomposite shows much higher antimicrobial efficiency toward bacteria and yeast cells.
Non-muscle actins have been studied for many decades; however, the reason for the existence of both isoforms is still unclear. Here we show, for the first time, a successful inactivation of the
...(CRISPR clones with inactivated
, CR-
) and
(CRISPR clones with inactivated
, CR-
) genes in human melanoma cells (A375) via the RNA-guided D10A mutated Cas9 nuclease gene editing CRISPR/Cas9(D10A) technique. This approach allowed us to evaluate how melanoma cell motility was impacted by the lack of either β actin coded by
or γ actin coded by
. First, we observed different distributions of β and γ actin in the cells, and the absence of one actin isoform was compensated for via increased expression of the other isoform. Moreover, we noted that γ actin knockout had more severe consequences on cell migration and invasion than β actin knockout. Next, we observed that the formation rate of bundled stress fibers in CR-
cells was increased, but lamellipodial activity in these cells was impaired, compared to controls. Finally, we discovered that the formation rate of focal adhesions (FAs) and, subsequently, FA-dependent signaling were altered in both the CR-
and CR-
clones; however, a more detrimental effect was observed for γ actin-deficient cells. Our research shows that both non-muscle actins play distinctive roles in melanoma cells' FA formation and motility.
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Abstract
The principal component of the protein homeostasis network is the ubiquitin-proteasome system. Ubiquitination is mediated by an enzymatic cascade involving, i.e. E3 ubiquitin ligases, many ...of which belong to the cullin-RING ligases family. Genetic defects in the ubiquitin-proteasome system components, including cullin-RING ligases, are known causes of neurodevelopmental disorders. Using exome sequencing to diagnose a pediatric patient with developmental delay, pyramidal signs and limb ataxia, we identified a de novo missense variant c.376G>C; p.(Asp126His) in the FEM1C gene encoding a cullin-RING ligase substrate receptor. This variant alters a conserved amino acid located within a highly constrained coding region and is predicted as pathogenic by most in silico tools. In addition, a de novo FEM1C mutation of the same residue p.(Asp126Val) was associated with an undiagnosed developmental disorder, and the relevant variant (FEM1CAsp126Ala) was found to be functionally compromised in vitro. Our computational analysis showed that FEM1CAsp126His hampers protein substrate binding. To further assess its pathogenicity, we used the nematode Caenorhabditis elegans. We found that the FEM-1Asp133His animals (expressing variant homologous to the FEM1C p.(Asp126His)) had normal muscle architecture yet impaired mobility. Mutant worms were sensitive to the acetylcholinesterase inhibitor aldicarb but not levamisole (acetylcholine receptor agonist), showing that their disabled locomotion is caused by synaptic abnormalities and not muscle dysfunction. In conclusion, we provide the first evidence from an animal model suggesting that a mutation in the evolutionarily conserved FEM1C Asp126 position causes a neurodevelopmental disorder in humans.
Arctic fjords ecosystems are highly dynamic, with organisms exposed to various natural stressors along with productivity clines driven by advection of water masses from shelves. The benthic response ...to these environmental clines has been extensively studied using traditional, morphology-based approaches mostly focusing on macroinvertebrates. In this study we analyse the effects of glacially mediated disturbance on the biodiversity of benthic macrofauna and meiobenthos (meiofauna and Foraminifera) in a Svalbard fjord by comparing morphology and eDNA metabarcoding. Three genetic markers targeting metazoans (COI), meiofauna (18S V1V2) and Foraminifera (18S 37f) were analyzed. Univariate measures of alpha diversity and multivariate compositional dissimilarities were calculated and tested for similarities in response to environmental gradients using correlation analysis. Our study showed different taxonomic composition of morphological and molecular datasets for both macrofauna and meiobenthos. Some taxonomic groups while abundant in metabarcoding data were almost absent in morphology-based inventory and vice versa. In general, species richness and diversity measures in macrofauna morphological data were higher than in metabarcoding, and similar for the meiofauna. Both methodological approaches showed different patterns of response to the glacially mediated disturbance for the macrofauna and the meiobenthos. Macrofauna showed an evident distinction in taxonomic composition and a dramatic cline in alpha diversity indices between the outer and inner parts of fjord, while the meiobenthos showed a gradual change and more subtle responses to environmental changes along the fjord axis. The two methods can be seen as complementing rather than replacing each other. Morphological approach provides more accurate inventory of larger size species and more reliable quantitative data, while metabarcoding allows identification of inconspicuous taxa that are overlooked in morphology-based studies. As different taxa may show different sensitivities to environmental changes, both methods shall be used to monitor marine biodiversity in Arctic ecosystems and its response to dramatically changing environmental conditions.
•Taxonomic composition of morphological and molecular datasets differ.•Sediment eDNA is less efficient for macrofauna than for meiobenthos.•Alpha Diversity of macrofauna drops in glacial bay.•Meiofauna and Foraminifera diversity change gradually along the fjord axis.•Metabarcoding is a complementary method to morphological analyses.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Ant rescue behaviour belongs to the most interesting subcategories of prosocial and altruistic behaviour encountered in the animal world. Several studies suggested that ants are able to identify what ...exactly restrains the movements of another individual and to direct their rescue behaviour precisely to that object. To shed more light on the question of how precise the identification of the source of restraint of another ant is, we investigated rescue behaviour of red wood ant
workers, using a new version of an artificial snare bioassay in which a nestmate victim bore two wire loops on its body, one (acting as a snare) placed on its petiole and an additional one on its leg. The tested ants did not preferentially direct their rescue behaviour towards the snare. Moreover, the overall strategy adopted by the most active rescuers was not limited to precisely targeted rescue attempts directed towards the snare, but consisted of frequent switching between various subcategories of rescue behaviour. These findings highlight the importance of precise identification of cognitive processes and overall behavioural strategies for better understanding of causal factors underlying animal helping behaviour in light of new facts discovered by testing of various successive research hypotheses.
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Hemophilia A is a genetically conditioned disease leading to hemostatic disorders due to factor VIII (FVIII) deficiency. The treatment of hemophilia has evolved throughout the past years and has ...significantly changed. One of the newest drugs for prophylactic treatment is the humanized bispecific IgG antibody - emicizumab, which binds with factor IXa and factor X, bridging those factors and thus mimicking the activity of factor VIII.
The literature search was done via the PubMed database, with the emphasis on clinical trials and case reports, describing the off-label emicizumab use. This review presents an extensive summary and considers the advantages and disadvantages (side-effects) of emicizumab, describing additional clinical situations, where emicizumab has been successfully used. In our review, we cover information about the mechanisms of action, indications, and efficacy and discuss some chosen case reports about off-label emicizumab use.
Its convenient administration method (subcutaneous) and frequency of injections (from once a week to once a month) makes it a more comfortable treatment, limiting injection-site reactions, hospital stays, costs of prophylaxis, and significantly increasing patients' quality of life. Adverse effects are scarce and rarely serious - the most common ones are reactions at the injection-site and upper respiratory tract infections.
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