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Kirde-Eestis leviva Alutaguse vööndi sulfiid-grafiitgneisside levialal asuv Uljaste polümetalne anomaalia on pakkunud teadlastele huvi 1960. aastatest alates. Uljaste grafiitgneissides on kõrged grafiidi ja erinevate sulfiidide (peamiselt pürrotiini) sisaldused. Juba varasemalt on mainitud, et lisaks sulfiididele esineb grafiitgneissides madalates kogustes väärismetalle, mida on seostatud hüdrotermaalsete sündmustega. Lõuna-Soomes ja Kesk-Rootsis, mis moodustavad Eesti territooriumiga ühtse aluskorra ploki, kaevandatakse just neid samu metalle. Seetõttu ei ole välistatud, et ka Eesti maapõu võib peita endas perspektiivseid maagialasid. Käesoleva magistritöö eesmärgiks on uurida Uljaste puursüdamiku F188 sulfiidse maagistumisega seotud polümetallide levikut, mineraloogilisi assotsiatsioone ja geneesi ning hinnata mineralisatsiooni sündmuste vanuseid kasutades U/Pb keemilist dateerimist. Analüüside käigus tuvastati, et sügavustel 200.75–201.3, 213.4; 331.4 ja 344 m esines intervalle, mis on intensiivselt läbistunud hüdrotermaalsetest soontest. Just nendes intervallides tuvastati ümbritsevast kõrgemaid väärismetallide (Ag, Au) ja nendega kaasnevate elementide (Te, Bi) sisaldusi. Keemilise dateerimise tulemuste põhjal saame väita, et uraniniidi terad on valdavalt tekkinud ajavahemikus 1708–1783 ± 40 Ma, mis lubab oletada, et uraniniitide tekkega seotud hüdrotermaalsed protsessid on seotud Svekofenni orogeeni lõpufaasi ja postorogeense faasi algusega., https://www.ester.ee/record=b5541903

Rhizomes from Zingiber officinale Roscoe are traditionally used for the treatment of a plethora of pathophysiological conditions such as diarrhea, nausea, or rheumatoid arthritis. While 6-gingerol is the pungent principle in fresh ginger, in dried rhizomes, 6-gingerol is dehydrated to 6-shogaol. 6-Shogaol has been demonstrated to exhibit anticancer, antioxidative, and anti-inflammatory actions more effectively than 6-gingerol due to the presence of an electrophilic Michael acceptor moiety. In vitro, 6-shogaol exhibits anti-inflammatory actions in a variety of cell types, including leukocytes. Our study focused on the effects of 6-shogaol on activated endothelial cells. We found that 6-shogaol significantly reduced the adhesion of leukocytes onto lipopolysaccharide (LPS)-activated human umbilical vein endothelial cells (HUVECs), resulting in a significantly reduced transmigration of THP-1 cells through an endothelial cell monolayer. Analyzing the mediators of endothelial cell–leukocyte interactions, we found that 30 µM of 6-shogaol blocked the LPS-triggered mRNA and protein expression of cell adhesion molecules. In concert with this, our study demonstrates that the LPS-induced nuclear factor κB (NFκB) promoter activity was significantly reduced upon treatment with 6-shogaol. Interestingly, the nuclear translocation of p65 was slightly decreased, and protein levels of the LPS receptor Toll-like receptor 4 remained unimpaired. Analyzing the impact of 6-shogaol on angiogenesis-related cell functions in vitro, we found that 6-shogaol attenuated the proliferation as well as the directed and undirected migration of HUVECs. Of note, 6-shogaol also strongly reduced the chemotactic migration of endothelial cells in the direction of a serum gradient. Moreover, 30 µM of 6-shogaol blocked the formation of vascular endothelial growth factor (VEGF)-induced endothelial sprouts from HUVEC spheroids and from murine aortic rings. Importantly, this study shows for the first time that 6-shogaol exhibits a vascular-disruptive impact on angiogenic sprouts from murine aortae. Our study demonstrates that the main bioactive ingredient in dried ginger, 6-shogaol, exhibits beneficial characteristics as an inhibitor of inflammation- and angiogenesis-related processes in vascular endothelial cells.

All organizations must have training programs to improve the quality of service and increase productivity improvement in work, but in the health sector it is essential to develop training programs for nursing staff, because the treatment and care of patients must be the best. The general objective was: To determine the influence of training on the quality of service and productivity of nurses in a Hospital in Callao 2021. The methodology has had a paradigm - positivist model with a hypothetical - deductive method; The approach has been quantitative, applied type, non- experimental and cross-sectional design, using the survey technique and the instrument used by the questionnaire. The results of the General Hypothesis have been validated and it was confirmed that: Training significantly influences the quality of service and productivity of the nurses of a Hospital in Callao 2021. It was concluded that training significantly influences the quality of service and productivity of the nurses of a Hospital del Callao 2021, considering the results of the general hypothesis, these indicated an incidence of 99.7% and a significance value equal to 0,000.

The aim of this study was to evaluate the biocompatibility of epoxy-resin-based AHPlus, salicylate-based MTA-Fillapex and calcium silicate-based iRootSP root canal sealers. Cytotoxicity was assessed by XTT test. The extracts from sealers of different setting times were serially diluted. Cell viability was calculated as the percentage of the control group (100%). The optimal concentration of each sealer was used at genotoxicity test, and micronuclei formations were detected. Statistical analyses were done by using Kruskal–Wallis and Dunn post hoc test with Bonferroni correction. AHPlus and MTA-Fillapex showed the lowest percentage of cell viability at higher concentrations (1:1, 1:2, 1:4), especially at first 12 h. iRootSP showed higher viability at all concentrations and times than AHPlus and MTA-Fillapex. At genotoxicity assay, AHPlus increased the number of micronuclei. MTA-Fillapex slightly induced micronucleus formation (not significant) and iRootSP was not increased. In conclusion, calcium silicate-based iRootSP had lowest cytotoxic and genotoxic potential and can be considered as a highly biocompatible material. Selcuk University, Scientific Research Projects Coordination Unit (SUBAP No:12202014).

BACKGROUND: Concern that insecticide resistant mosquitoes are threatening malaria control has driven the development of new types of insecticide treated nets (ITNs) and indoor residual spraying (IRS) of insecticide. Malaria control programmes have a choice of vector control interventions although it is unclear which controls should be used to combat the disease. The study aimed at producing a framework to easily compare the public health impact and cost-effectiveness of different malaria prevention measures currently in widespread use. METHODS: We used published data from experimental hut trials conducted across Africa to characterise the entomological effect of pyrethroid-only ITNs versus ITNs combining a pyrethroid insecticide with the synergist piperonyl butoxide (PBO). We use these estimates to parameterise a dynamic mathematical model of Plasmodium falciparum malaria which is validated for two sites by comparing simulated results to empirical data from randomised control trials (RCTs) in Tanzania and Uganda. We extrapolated model simulations for a series of potential scenarios likely across the sub-Saharan African region and include results in an online tool (Malaria INtervention Tool [MINT]) that aims to identify optimum vector control intervention packages for scenarios with varying budget, price, entomological and epidemiological factors. FINDINGS: Our model indicates that switching from pyrethroid-only to pyrethroid-PBO ITNs could averted up to twice as many cases, although the additional benefit is highly variable and depends on the setting conditions. We project that annual delivery of long-lasting, non-pyrethroid IRS would prevent substantially more cases over 3-years, while pyrethroid-PBO ITNs tend to be the most cost-effective intervention per case averted. The model was able to predict prevalence and efficacy against prevalence in both RCTs for the intervention types tested. MINT is applicable to regions of sub-Saharan Africa with endemic malaria and provides users with a method of designing intervention packages given their setting and budget. INTERPRETATION: The most cost-effective vector control package will vary locally. Models able to recreate results of RCTs can be used to extrapolate outcomes elsewhere to support evidence-based decision making for investment in vector control. FUNDING: Medical Research Council, IVCC, Wellcome Trust. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Simple Summary A group of insecticides, called pyrethroids, are the main strategy for controlling the mosquito vectors of malaria. Pyrethroids are used in all insecticide-treated bednets, and many indoor residual spray programmes (in which insecticides are sprayed on the interior walls of houses). There are different types of pyrethroids within the class (e.g., deltamethrin and permethrin). Across the world, mosquitoes are showing signs of resistance to the pyrethroids, such as reduced mortality following contact. However, it is unclear if this resistance is uniform across the pyrethroid class (i.e., if a mosquito is resistant to deltamethrin, whether it is resistant to permethrin at the same level). In addition, it is not known if switching between different pyrethroids can be used to effectively maintain mosquito control when resistance to a single pyrethroid has been detected. This review examined the evidence from molecular studies, resistance testing from laboratory and field data, and mosquito behavioural assays to answer these questions. The evidence suggested that in areas where pyrethroid resistance exists, different mortality seen between the pyrethroids is not necessarily indicative of an operationally relevant difference in control performance, and there is no reason to rotate between common pyrethroids (i.e., deltamethrin, permethrin, and alpha-cypermethrin) as an insecticide resistance management strategy. Abstract Pyrethroid resistance is widespread in malaria vectors. However, differential mortality in discriminating dose assays to different pyrethroids is often observed in wild populations. When this occurs, it is unclear if this differential mortality should be interpreted as an indication of differential levels of susceptibility within the pyrethroid class, and if so, if countries should consider selecting one specific pyrethroid for programmatic use over another. A review of evidence from molecular studies, resistance testing with laboratory colonies and wild populations, and mosquito behavioural assays were conducted to answer these questions. Evidence suggested that in areas where pyrethroid resistance exists, different results in insecticide susceptibility assays with specific pyrethroids currently in common use (deltamethrin, permethrin, α-cypermethrin, and λ-cyhalothrin) are not necessarily indicative of an operationally relevant difference in potential performance. Consequently, it is not advisable to use rotation between these pyrethroids as an insecticide-resistance management strategy. Less commonly used pyrethroids (bifenthrin and etofenprox) may have sufficiently different modes of action, though further work is needed to examine how this may apply to insecticide resistance management.

Purpose The purpose of this paper is to find out how much the purchasing and lending of individual electronic books really cost. Additionally, this paper investigates which kind of approach would be cheaper and less time-consuming for library staff as well as library patrons – purchase or short-term loan. Design/methodology/approach This study was conducted at the Tallinn University of Technology (TalTech) Library. This is the only university library in Estonia where the Ebook Central platform is adapted on a large scale. For background information, all statistical data of expenditures and average prices of purchases and short-term loans during April 2013 and December 2018 were calculated and analysed. Through a case study, the time-driven activity-based costing (TDABC) method was used – all activities related to acquisition and lending of eBooks were identified, recorded in detail and analysed. More specifically, the study concerned eBooks offered in the Ebook Central platform and covered purchasing and short-term loan processes, such as receipt of order request, communication with the patron (if necessary) making a purchase or short-term loan, and feedback to the patron. Findings While analysing the results, it appeared there are many additional activities libraries can avoid during the eBook short-term loan process compared to purchasing. As a normality in TalTech library, purchase is always followed by a cataloguing process which increases the time and cost of this process in turn. On the basis of the current study, it can be said that short-term loan is a cheaper way to use eBooks; many activities related to the short-term loan of eBooks take remarkably less staff time and financial resources than eBooks acquisition/purchasing activities. When analysing the literature reviewed as well as collected statistical data, the problem may arise when the decision-maker librarian is not experienced, professional or long-sighted enough to understand the future behaviour of the patron or the usage of the specific eBook. When the usage reaches a certain point, it becomes an indicator of continuing future usage and so it makes sense to purchase the eBook, as the library pays no further charges once an eBook is owned. Originality/value Most studies reviewed by the author are based on the statistical data collected about expenditure, costs, usage, cost-per-use, etc. of short-term loans and purchases. While acquisitions costs, average cost per acquired item per year and cost per usage are easy to identify, it has been difficult to measure associated costs of acquisition, cataloging and circulation. The TDABC methodology seems to be one of the best tools for understanding cost behaviour and refining a cost system for university libraries. Based on the information known to the author, there is no study carried out using the TDABC methodology for analysing costs of eBook programmes.

With the shift of focus on the part of museums towards a fuller consideration of the audience’s needs, a number of museums around the world have begun to contribute more actively and consciously to people’s welfare, including their physical and mental health and the inclusion of more vulnerable and marginalised social groups. Several museums in Estonia have joined in these efforts over the past few years. A specific example of such a museum innovation is the work that has been done with bullying prevention. To date, studies have shown that one in five children attending a school in Estonia is a victim of bullying and that bullying can cause anxiety and depression, or in other words, it can significantly affect one’s mental health. Although there are several organisations in Estonia dealing with this problem, more active co-operation with museums started only in 2018 when Kadriorg Art Museum and Tartu Art Museum, independently of one another, contacted the Foundation for the Bullying-Free School with the request to develop anti-bullying educational programmes for schools of general education. As a result of the co-operation, two versions of the museum lesson, ’Using art to combat bullying’, were prepared for both museums. The article addresses the questions of why the above art museums decided to undertake their bullying prevention initiative and how this concern and art mediation are combined in the structure of educational programmes and to some extent, in that of the exhibitions. There are several reasons for undertaking anti-bullying initiatives in art museums from the perspective of both schools and museums as well as the Foundation for the Bullying-Free School. As school children have become an important target group, museums have sought to adapt their programmes, as effectively as possible, to the needs of schools. Considering that schools likewise have become more proactive and systematic in their approach to bullying, museums have seen this as an opportunity to offer alternative anti-bullying lessons outside the classroom routine. The development of such a lesson has provided an opportunity to simultaneously offer schools a museum lesson which would combine two critical themes—bullying prevention and art mediation—as well as train instructors in how to intervene expertly in bullying situations and apply current theoretical approaches. An added bonus for the foundation is that the museum lesson enables them to introduce the Bullying-free School programme to the schools that have not yet joined it and offer further knowledge consolidation activities to the schools that have already enrolled in the programme. However, it is still a young initiative that needs further development in order to find more sustainable collaboration formats which would have a more long-term influence on school children than a single museum visit. It is likewise important that the museums should seek to tie bullying prevention more strongly to their broader strategic orientations, or otherwise they run the risk of it remaining an ephemeral experiment that is not grounded by continuous development or follow-up activities. Through discussions, cooperative role plays and a craft activity, the museum lesson, ’Using art to combat bullying’, combines mediation of art works and introduction to anti-bullying principles. Discussion of topics related to bullying through works of art enables children to analyse art works in the light of their own experience and to approach familiar situations from a novel angle provided by the artist’s perspective. The co-operative role plays help to test out in practice the conclusions of the discussions. To consolidate the recently gained knowledge children are tasked with drawing pictures and compiling a contract based on the pictures. Although it has not yet been possible to study in detail the impact of the lesson on the participants, an analysis of the existing data suggests that it is possible to impart simultaneously knowledge regarding the essence of art as well as social skills and attitudes. Art and bullying prevention act in partnership, so to speak, where they support each other without either of them becoming marginalised. One possible way of making the lesson more effective, however, would be the tightening of the interaction between the museum staff and teachers outside the lesson time so as to negotiate mutual expectations and exchange information regarding both the needs of a particular class and the specific adjustment of the lesson as well as follow-up activities. When examining the way in which the lesson was anchored to different exhibition environments, it became clear that the lesson could be combined with a variety of art expositions, including permanent displays and temporary exhibitions as well as displays of both historical and contemporary art. Regardless of the exhibition context, however, interaction between the curators and museum educators in the planning of spatial solutions and sound design could be further strengthened in order to deliver a more effective lesson. For curators and museum educators, the ongoing museum innovation holds the potential for initiating co-operation with many other target groups. However, given the limited resources, it is increasingly more important to choose priorities very carefully in order to align, as effectively as possible, the developments in the field with the local needs.

Amaç: Düzenli transfüzyonlar, transfüzyona bağımlı talasemide (TDT) kalp, karaciğer ve akciğer gibi kritik organlarda ilerleyici demir birikmesine neden olur. Bu çalışmada TDT'li hastalarda solunum fonksiyon bozukluğunu ve solunum fonksiyon bozukluğunu etkileyen faktörlerin değerlendirilmesi amaçlanmıştır.Gereç ve Yöntem: Sağlık bilimleri üniversitesi, Adana Eğitim Ve Araştırma Merkezi Çocuk Hematolojisi / Onkoloji Ünitesi’nde TDT nedeniyle takip ve tedavi edilmekte olan hastalar içinden solunum fonksiyon testi yapılan hastalar retrospektif olarak değerlendirildi.Bulgular: Solunum fonksiyon testleri 40 TDT tanılı hastada (19 kadın; 21 erkek) yapıldı. Tanı sırasındaki ortalama yaş 6.63 ± 5.74 ay, ortalama vücut kitle indeksi 18.57 ± 2.27 kg / m², ortalama transfüzyon programı süresi 151.67 ± 50.48 ay idi. Splenektomi oranı%48 idi. Bütün hastalar demir şelasyon tedavisi kullanıyordu. Solunum fonksiyon testlerinde hastaların%57,5’inde olan normal bulgular, %27,5’inde küçük hava yolu tıkanıklığı bulguları ile restriktif akciğer disfonksiyonu ve%15’inde izole restriktif disfonksiyon saptandı. Solunum fonksiyonlarında yaş, cinsiyet, transfüzyon programı süresi, ferritin ve hemoglobin düzeyleri, splenektomi varlığı veya şelasyon tedavisi tipi açısından istatistiksel olarak anlamlı bir fark saptanmadı. Ferritin düzeyi 2500 ng / dl'nin üzerinde olan hastalarda zorlu ekspiratuar hacim (FEV1) ve zorlu vital kapasite (FVC) için anlamlı olarak düşük değerler bulundu.Sonuç: Çalışmamızda, solunum semptomu olmayan TDT tanılı hastaların yaklaşık yarısında kısıtlayıcı solunum fonksiyon bozukluğu tespit edildi. Yüksek ferritin düzeyleri solunum disfonksiyonunu işaret edebileceğinden hastaların bu açıdan yakın takip edilmesi uygun olacaktır.

Cellulase enzymes deconstruct recalcitrant cellulose into soluble sugars, making them a biocatalyst of biotechnological interest for use in the nascent lignocellulosic bioeconomy. Cellobiohydrolases (CBHs) are cellulases capable of liberating many sugar molecules in a processive manner without dissociating from the substrate. Within the complete processive cycle of CBHs, dissociation from the cellulose substrate is rate limiting, but the molecular mechanism of this step is unknown. Here, we present a direct comparison of potential molecular mechanisms for dissociation via Hamiltonian replica exchange molecular dynamics of the model fungal CBH, Trichoderma reesei Cel7A. Computational rate estimates indicate that stepwise cellulose dethreading from the binding tunnel is 4 orders of magnitude faster than a clamshell mechanism, in which the substrate-enclosing loops open and release the substrate without reversing. We also present the crystal structure of a disulfide variant that covalently links substrate-enclosing loops on either side of the substrate-binding tunnel, which constitutes a CBH that can only dissociate via stepwise dethreading. Biochemical measurements indicate that this variant has a dissociation rate constant essentially equivalent to the wild type, implying that dethreading is likely the predominant mechanism for dissociation.

Background: Hydrothermal methods are commonly applied in pretreatment of lignocellulose for enhanced enzymatic hydrolysis and further conversion to biofuels and chemicals. The pretreatment partially disassemble and solubilize cell wall polymers. Besides mono- and oligosaccharides, the soluble degradation products include various phenolic compounds, which may affect the efficiency of enzymatic hydrolysis. Results: The phenolic compounds were isolated from pretreatment liquor and their effects on cellulolytic enzymes were investigated. The major enzymes in crystalline cellulose degradation, cellobiohydrolases, were inhibited by the oligophenolics and phenolic-carbohydrate conjugates the latter of which could be mitigated by other enzymes, i.e. xylanases and endoglucanases. Hydrolytic activity of a commercial enzyme cocktail containing lytic polysaccharide monooxygenase (LPMO) was enhanced in presence of low concentrations of phenolics.Conclusions: The effects of the pretreatment liquor phenolics is dependent on enzyme concentration and type of the phenolic compounds. For optimized performance, the pretreatment conditions and enzyme cocktail composition should be designed to promote oxidative activities for enhanced hydrolysis, degradation of the oligosaccharides linked to phenolics and resistance to oligophenolic compounds.

TWIST1 is a major regulator of epithelial mesenchymal transition process, essential in cancer metastasis. Cancer cells increase glucose uptake capabilities to meet their high energy requirements. In this study, we explored the potential role of TWIST1 on glucose transport into the 293T cells in an insulin-dependent and insulin-independent manner. For this purpose, the ectopic expression of TWIST1 was successfully performed by electroporation. The altered mRNA expressions of GLUT-1, -3, -4, and -12, insulin receptor (InsR), and insulin receptor substrate (IRS)-1 and -2 were assessed in control and TWIST1-overexpressing cells. Glucose uptake rates of the cells were evaluated by fluorometric glucose uptake assay. Our findings showed that the transcriptional expression levels of GLUT-1, -3, and -12 genes were significantly upregulated by TWIST1. However, TWIST1 did not alter the mRNA and protein expressions of the InsR, its substrates (IRS-1 and -2), and GLUT-4 genes in 293T cells which are main factors for insulin-stimulated glucose uptake pathway. Also, the glucose transport activities were significantly increased in TWIST1-overexpressing cells compared to controls due to fetal bovine serum (FBS) stimulation, but there was a slight non-significant difference in insulin stimulation. Thus, our data suggest that TWIST1 could promote glucose uptake independently of insulin and is possible to be evaluated as a metabolic marker in cancer. Further investigations are needed to clarify the precise molecular mechanisms underlying the cells' glucose uptake and consumption during tumorigenesis.

Ginger (Zingiber officinale Roscoe) is widely used as medicinal plant. According to the Committee on Herbal Medicinal Products (HMPC), dried powdered ginger rhizome can be applied for the prevention of nausea and vomiting in motion sickness (well-established use). Beyond this, a plethora of pre-clinical studies demonstrated anti-cancer, anti-oxidative, or anti-inflammatory actions. 6-Shogaol is formed from 6-gingerol by dehydration and represents one of the main bioactive principles in dried ginger rhizomes. 6-Shogaol is characterized by a Michael acceptor moiety being reactive with nucleophiles. This review intends to compile important findings on the actions of 6-shogaol as an anti-inflammatory compound: in vivo, 6-shogaol inhibited leukocyte infiltration into inflamed tissue accompanied with reduction of edema swelling. In vitro and in vivo, 6-shogaol reduced inflammatory mediator systems such as COX-2 or iNOS, affected NFκB and MAPK signaling, and increased levels of cytoprotective HO-1. Interestingly, certain in vitro studies provided deeper mechanistic insights demonstrating the involvement of PPAR-γ, JNK/Nrf2, p38/HO-1, and NFκB in the anti-inflammatory actions of the compound. Although these studies provide promising evidence that 6-shogaol can be classified as an anti-inflammatory substance, the exact mechanism of action remains to be elucidated. Moreover, conclusive clinical data for anti-inflammatory actions of 6-shogaol are largely lacking.

Set in the Habitats Directive as priority habitat, fixed dunes with herbaceous vegetation (grey dunes) occur around the coasts of Europe. As a part of many coastal dune systems these habitats are especially complex and low resilience and need special attention from the conservation and management perspectives. Nearly a decade we have studied representative examples of fixed dunes in Estonia. Due to growing anthropogenic pressure and ongoing global changes it is vital to distinguish the changes and analyse general trends of development of grey dunes. The selected sites Keibu (located on the NW coast of mainland Estonia) and Ruhnu (located on the eastern coast of Ruhnu Island) are representative examples in Estonia, with a coverage of a geographical range and ecological variation. Both sites are part of conservation and monitoring areas. In each site, we have compiled a landscape profile to visualize the topography, vegetation and soils. he study was carried out on perpendicular to shoreline landscape profiles in order to express the full spectrum of coastal dune plant communities and surface deposits from shores towards inland. Both, natural and human impacts have been considered in the assessment of changes in the structure and functioning of the grey dunes in Estonia. The results show that changes in dune landscapes can be rapid, especially on sandy beaches due to stronger storm surges in recent decades. The inland areas are more affected by human activity and the changes there are well reflected. The gradual loss of open sandy habitats on the sites is evident during the last 100 years and show the overall development trends of dynamic coastal dune landscapes. This study has proven that these areas need permanent observation to assess the level of changes. It is vital to contribute to the decision making processes concerning their optimal use and conservation needs to maintain their resilience.

Définies dans la Directive Habitats comme habitat prioritaire, des dunes fixées à végétation herbacée (dunes grises) apparaissent autour des côtes européennes. Faisant partie de nombreux systèmes de dunes côtières, ces habitats sont particulièrement complexes, ont une faible résilience et nécessitent une attention particulière du point de vue de la conservation et de la gestion. Pendant près d’une décennie, nous avons étudié des exemples représentatifs de dunes fixées en Estonie. En raison de la pression anthropique croissante et des changements globaux actuels, il est essentiel de distinguer ces changements et d’analyser les tendances générales du développement des dunes grises. Les sites sélectionnés, Keibu (situé sur la côte NO de l’Estonie continentale) et Ruhnu (située sur la côte est de l’île de Ruhnu), sont des exemples représentatifs de l’Estonie, avec une couverture de portée géographique et de variation écologique. Les deux sites font partie de zones de conservation et de surveillance. Sur chaque site, nous avons compilé un profil de paysage pour visualiser la topographie, la végétation et les sols. Cette étude a été réalisée sur des profils de paysages perpendiculaires au rivage afin d’exprimer tout le spectre des communautés végétales de dunes côtières et des dépôts de surface des rivages vers l’arrière-pays. Les impacts naturels et humains ont été pris en compte dans l’évaluation des modifications de la structure et du fonctionnement des dunes grises en Estonie. Les résultats montrent que les changements dans les paysages de dunes peuvent être rapides, en particulier sur les plages de sable, en raison des fortes ondes de tempête des dernières décennies. Les zones intérieures sont plus touchées par l’activité humaine et les changements y sont bien reflétés. La perte progressive d’habitats sableux ouverts sur les sites est évidente au cours des 100 dernières années et montre les tendances globales de développement des paysages dynamiques de dunes côtières. Cette étude a prouvé que ces zones nécessitent une observation permanente pour évaluer le niveau de changement. Il est essentiel de contribuer aux processus de prise de décision concernant leur utilisation optimale et leurs besoins en matière de conservation afin de préserver leur résilience.

[Image: see text] Leuktriene B4 receptor 2 (BLT2) is a G-protein coupled receptor modulation of which is discussed to be a therapeutic option for healing of intestinal lesions. In this work, new BLT2 agonists were identified by a virtual screening of a repurposing library and in vitro assay of the most promising compounds. Irbesartan, an approved type-1 angiotensin II receptor (AT1) antagonist, was identified as a moderate BLT2 agonist. An initial SAR study on the irbesartan scaffold was performed resulting in the discovery of a new potent BLT2 agonist (8f, EC(50) = 67.6 nM). Irbesartan and 8f were shown to promote proliferation of epithelial colon cells, an effect which was reversible by a BLT2 antagonist.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has placed enormous strain on intensive care units (ICUs) in Europe. Ensuring access to care, irrespective of COVID-19 status, in winter 2020-2021 is essential. METHODS: An integrated model of hospital capacity planning and epidemiological projections of COVID-19 patients is used to estimate the demand for and resultant spare capacity of ICU beds, staff and ventilators under different epidemic scenarios in France, Germany and Italy across the 2020-2021 winter period. The effect of implementing lockdowns triggered by different numbers of COVID-19 patients in ICUs under varying levels of effectiveness is examined, using a 'dual-demand' (COVID-19 and non-COVID-19) patient model. RESULTS: Without sufficient mitigation, we estimate that COVID-19 ICU patient numbers will exceed those seen in the first peak, resulting in substantial capacity deficits, with beds being consistently found to be the most constrained resource. Reactive lockdowns could lead to large improvements in ICU capacity during the winter season, with pressure being most effectively alleviated when lockdown is triggered early and sustained under a higher level of suppression. The success of such interventions also depends on baseline bed numbers and average non-COVID-19 patient occupancy. CONCLUSION: Reductions in capacity deficits under different scenarios must be weighed against the feasibility and drawbacks of further lockdowns. Careful, continuous decision-making by national policymakers will be required across the winter period 2020-2021.

Chronic inflammation-related diseases are characterized by persistent leukocyte infiltration into the underlying tissue. The vascular endothelium plays a major role in this pathophysiological condition. Only few therapeutic strategies focus on the vascular endothelium as a major target for an anti-inflammatory approach. In this study, we present the natural compound-derived carbazole derivative C81 as chemical modulator interfering with leukocyte-endothelial cell interactions. An in vivo assay employing intravital microscopy to monitor leukocyte trafficking after C81 treatment in postcapillary venules of a murine cremaster muscle was performed. Moreover, in vitro assays using HUVECs and monocytes were implemented. The impact of C81 on cell adhesion molecules and the NFκB signaling cascade was analyzed in vitro in endothelial cells. Effects of C81 on protein translation were determined by incorporation of a puromycin analog-based approach and polysome profiling. We found that C81 significantly reduced TNF-activated leukocyte trafficking in postcapillary venules. Similar results were obtained in vitro when C81 reduced leukocyte-endothelial cell interactions by down-regulating cell adhesion molecules. Focusing on the NFκB signaling cascade, we found that C81 reduced the activation on multiple levels of the cascade through promoted IκBα recovery by attenuation of IκBα ubiquitination and through reduced protein levels of TNFR1 caused by protein translation inhibition. We suggest that C81 might represent a promising lead compound for interfering with inflammation-related processes in endothelial cells by down-regulation of IκBα ubiquitination on the one hand and inhibition of translation on the other hand without exerting cytotoxic effects.

Objective: To determine the cumulative effects of Mediterranean fever gene polymorphisms and mutations in patients with ?nflammatory bowel diseases. Methods: The case-control study was conducted from January, 2012, to January, 2016,at Cukurova University, Turkey, and comprised patients diagnosed with inflammatory bowel diseases and followed up at the Children Gastroenterology Department. By using molecular methods, 12 Mediterranean fevergene variants most frequently observed in the country were examined in all the diagnosed cases. The results were compared with age-matched healthy population data from the Genetic Diseases Diagnosis and Treatment Centre. Data was analysed using Graph Pad Prism. Results: Of the 151 subjects, 46(30.4%) were cases and 105(69.5%) were controls. Among the cases, there were 23(50%) subjects with a mean age of 14.8±3 years who had ulcerative colitis, and 23(50%) with mean age 14.5±3.2 years who had Crohn’s disease. The mean age of the controls was 16.4±3.2 years (p=0.716). Patients with ulcerative colitishad high frequencies of C allele in D102D T>C variant, G allele in G138G A>G variant, A allele in A165A C>A variant and A allele in R202Q G>A variant. Those with Crohn’s disease frequently had wild type of R202Q G>A variant. Also, D102D T>C / R314R C>T haplotype was common at a certain level in the UC group. Conclusions: Mediterranean fever gene variant was more frequently found in cases with ulcerative colitis compared to the controls. Key Words: MEFV, IBD, FMF, Polymorphism, Children. Continuous....

RNA-based therapeutics have emerged as one of the most powerful therapeutic options used for the modulation of gene/protein expression and gene editing with the potential to treat neurodegenerative diseases. However, the delivery of nucleic acids to the central nervous system (CNS), in particular by the systemic route, remains a major hurdle. This review will focus on the strategies for systemic delivery of therapeutic nucleic acids designed to overcome these barriers. Pathways and mechanisms of transport across the blood-brain barrier which could be exploited for delivery are described, focusing in particular on smaller nucleic acids including antisense oligonucleotides (ASOs) and small interfering RNA (siRNA). Approaches used to enhance delivery including chemical modifications, nanocarrier systems, and target selection (cell-specific delivery) are critically analyzed. Learnings achieved from a comparison of the successes and failures reported for CNS delivery of ASOs versus siRNA will help identify opportunities for a wider range of nucleic acids and accelerate the clinical translation of these innovative therapies.