Kullerpeptiidide kasutamine ajuhaiguste ravis

Väitekirja elektrooniline versioon ei sisalda publikatsiooneÜhiskonna keskmise eluea suurenemise tulemusel kasvab vananemisega seotud kesknärvisüsteemi haiguste, näiteks Alzheimeri ja Parkinsoni tõve, sagedus. Nende haiguste puhul puudub tõhus ravi haiguse kulu peatamiseks või patsientide terveks ravimiseks. Neurodegeneratiivsed haigused pole iseenesest letaalsed, kuid haiguse progresseeruv kulg muudab patsiendid kõrvalabist sõltuvaks. Seevastu ajukasvajad on väga kehva prognoosiga – hoolimata ravist ei ületa agressiivsemate ajukasvajate korral patsiendide elulemus 1,5 aastat. Kesknärvisüsteemi haiguste ravi on keeruline, kuna seda kaitsevad erinevad füüsilised ja funktsionaalsed barjäärid, mille eesmärgiks on takistada patogeenide, toksiinide ja vererakkude sisenemist ajukoesse. Olulisimad nendest mehhanismidest on vere-aju barjäär ning vere-tserebrospinaalvedeliku barjäär, millest vaid väga kindlate omadustega molekulid on võimelised läbi tungima. Enamikele molekulidele ning ka 99% ravimitele on need tõkked läbipääsmatud. Vananemisega seotud neuroloogiliste haiguste ravi parandamiseks on oluline parendada nende haiguste diagnoosimist. Selleks on vaja identifitseerida ja valideerida molekulaarseid markereid, mis võimaldavad haigusi diagnoosida varasemas staadiumis. Eelistatult juba enne kliiniliste sümptomite avaldumist. Järgmine oluline samm neuroloogiliste haiguste ravis on leida molekulaarsed transportsüsteemid, mille abil saaks ravimeid viia läbi kaitsva barjääri, et need jõuaksid haigusest haaratud koeni. Üks strateegia, mis võiks parandada ajuhaiguste ravi, on nanotehnoloogia rakendamine. Vere-aju barjääri läbivad kullermolekulid on võimalik kinnitada ravimitega laaditud nanoosakeste pinnale. Sel viisil oleks võimalik ajukoesse transportida ka ravimeid, mis on koekultuuri süsteemis näidanud efektiivsust kasvajarakkude hävitamisel või neuronite kaitsmisel, kuid vereringesse süstituna ei suuda iseseisvalt aju kaitsvaid tõkkeid läbida. Käesoleva prekliinilise töö eesmärgiks oli leida peptiidid, mis akumuleeruvad ajus ning mida saab rakendada kullermolekulidena kontrastainete ja/või ravimite transportimiseks. Parimate kullermolekulide välja valimiseks töötasime välja väga täpse kvantitatiivse metoodika, mis võimaldab erinevaid kullerpeptiide raku- ja loomkatsetes omavahel võrrelda.Neurological diseases, especially age-related disorders, are widespread and due to aging population their frequency is expected to rise rapidly. The most common age-related brain diseases are neurodegenerative disorders - Alzheimer's disease and Parkinson's disease, and brain tumors. For all of these diseases, there is no effective treatment that could cure patients or stop the disease progression. Neurodegenerative diseases are not lethal, but the progressive course of the disease makes patients dependent on their caregivers and healthcare system. On the contrary, brain tumors have a very poor prognosis despite multimodal treatment, patients with most aggressive type of tumors live less than 1.5 years. The treatment of neurological diseases is hampered because the central nervous system is protected by a variety of molecular mechanisms that prevent pathogens, toxins and blood cells from entering the brain tissue. The most important protective mechanisms are the blood-brain barrier and blood-cerebrospinal fluid barrier. These barriers are impermeable to most molecules, including 99% of drugs. In order to improve the treatment of age-related neurological disorders, it is important to advance the diagnosis. New molecular markers are needed to make the diagnosis at a earlier stage, before the onset of clinical symptoms. The next crucial step is to find molecules that are able to transport drugs across the protective barriers to reach the affected brain tissue. An important strategy that could improve the treatment of brain diseases is application of nanotechnology. Brain targeting ligands can be attached to the surface of nanoparticles and drugs could be encapsulated inside the nanoparticles. In this way, it is possible to deliver drugs that have shown efficacy in cell assays by killing tumor cells or protecting neurons, but cannot, by themselves, pass through protective barriers in the brain when injected into the bloodstream. The aim of this preclinical work was to find peptides that would be able to accumulate in the brain and could be used as targeting ligands in various neurological diseases to deliver contrast agents or drugs into affected tissue. To select the best targeting ligands, we developed a highly sensitive quantitative methodology that allows to compare targeting peptides in cell and animal experiments.https://www.ester.ee/record=b532986

Red yeasts from leaf surfaces and other habitats : three new species and a new combination of Symmetrospora (Pucciniomycotina, Cystobasidiomycetes)

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Väga väikese gestatsioonivanusega enneaegsed lapsed Eestis: ravitulem ja prognostilised tegurid

Väitekirja elektrooniline versioon ei sisalda publikatsioone.Meditsiini arenguga on suurenenud VVGV (sünd <32. täisrasedusnädalat) vastsündinute elulemus, kuid lapsed on ohustatud erinevatest arenguhäiretest. VVGV laste tervisetulemit 2 aasta vanuses peetakse perinataalabi kvaliteedi oluliseks indikaatoriks. Uurimistöö eesmärkideks oli kirjeldada VVGV laste ravitulemit ja ägedat respiratoorset haigestumist Eestis, leida ebasoodsa tulemi riskitegurid ning hinnata riigi peri- ja neonataalabi kvaliteeti. Rahvastikupõhine edasivaatav kohortuuring hõlmas aastatel 2007-2008 sündinud 360 VVGV last. Perinataalsed andmed saadi neonataalsest uuringuregistrist. Varast tulemit esmase haiglaravi lõpul võrreldi 264 VVGV lapse võrdluskohordiga aastatest 2002-2003. Hilist tulemit enneaegsusele korrigeeritud 2 aasta vanuses hinnati 2007. aastal sündinud 155-l VVGV lapsel ja võrreldi ajalisena sündinud laste tulemiga. Järelkontrollil hinnati laste somaatilist, neurosensoorset ja arengulist tulemit. Äge respiratoorne haigestumus selgitati vanemate küsitluse teel. Uuringuperioodidel suurenes oluliselt VVGV laste elulemus (78 vs 85%), kusjuures perinataalabi oli hilisemal perioodil proaktiivsem ja neonataalne ravi vähem invasiivne. Elulemuse paranemisega püsis neonataalsete haigustega elulejate osakaal muutumatuna, kuid võrreldes kõrge sissetulekuga riikidega suhteliselt suurena. Järelkontrollil esines mõõdukas/raske arenguhäire 12%-l VVGV lastest: tserebraalparalüüs 8%-l, kognitiivse arengu mahajäämus 5%-l ja kõne arengu mahajäämus 10%-l. Kognitiivse, kõne ja motoorse arengu keskmine koondskoor Bayley testil oli VVGV lastel 0,5 SD võrra madalam kui ajalisena sündinutel. Samuti olid oluliselt väiksemad VVGV laste keskmine kaal, pikkus ja peaümbermõõt ning ägeda respiratoorse haigestumise korral esines neil oluliselt enam vilistavat hingamist ning haiglaravi vajadust. Ebasoodsa tervisetulemi peamiseks riskiteguriks oli hiliseid puudeid ennustavate neonataalsete haiguste põdemine esmasel haiglaravil. VVGV laste elulemus Eestis on võrdväärne arenenud meditsiiniabiga riikidega, kuid laste varane haigestumus ja tervisehäirete esinemine 2 aasta vanuses jääb osaliselt suuremaks. Tervishoiu peamiseks väljakutseks on vähendada VVGV enneaegsete neonataalset haigestumist, säilitades suure elulejate osakaalu.Advances in perinatal care have improved the survival of VLGA (born <32 weeks' gestation) infants dramatically, but these infants remain at substantial risk for a wide spectrum of long-term morbidities. Therefore, it is mandatory that any assessment of quality of care for VLGA infants includes the long-term outcome. The aims of the studies were to describe outcome and acute respiratory morbidity of VLGA infants in Estonia, to identify risk factors for adverse outcome, and to benchmark the quality of perinatal services in the country. A nationwide prospective cohort study comprised 360 live-born VLGA infants born in Estonia in 2007–2008. Perinatal data were collected to the neonatal research register. A historical cohort of 264 VLGA infants born in 2002–2003 was selected for analysis of changes in the short-term outcome. A sub-cohort of 155 surviving VLGA infants born in 2007 was compared with a matched full-term control group at 2 years of corrected age. The infants underwent physical, neurological, and developmental assessment. Acute respiratory morbidity was identified by parental interviews. The survival until discharge increased significantly (78% in 2002-2003 vs 85% in 2007-2008) with proactive perinatal management and less invasive neonatal care and without concomitant increases in neonatal morbidity. However, the morbidity rates were higher when compared with comparable data from high income countries. At follow-up, neurodevelopmental impairment was noted in 12% of VLGA infants, with 8% affected by cerebral palsy, 5% with cognitive delay, and 10% with language delay. The mean Cognitive, Language, and Motor Composite Scores assessed using the Bayley-III scales were in VLGA group in excess of 0.5 SD lower than in full-term infants. Wheezing during respiratory infections and somatic growth failure were significant problems among VLGA infants. Major neonatal morbidities, predictive of poor long-term outcome, were the main risk factors for adverse outcomes. The results showed that for VLGA infants in Estonia, the survival is comparable and the rates of early morbidities and impairments at 2 years are partly higher when compared to similar studies from high income countries. The challenge for perinatal services in Estonia is to reduce neonatal morbidity of VLGA infants without compromising their survival

The Rise and Fall of Theatre NO99 in Estonia: A Case of Political and Discursive Change

The article focuses on the establishment and closing down of Theatre NO99 (2005-2018), one of the most nationally and internationally acclaimed theatres of Estonia. These events are analysed from two perspectives: (1) the political, because in both cases the Estonian Ministry of Culture made quite radical decisions that had a strong effect for the theatre field in general; (2) the discursive, to understand how NO99 legitimized its beginning and justified the ending. The latter is compared to the discourse of the written media to understand the dialogue between these two discourses. Pierre Bourdieu’s field theory is used to show how the external and internal forces influenced the position taking of NO99 in the Estonian theatre field and how paradoxical and even impossible it is for an avant-garde state theatre to balance between autonomous and heteronomous principals of hierarchization

Do You Feel the Same? Different Dominants of Theatrical Experience

The aim of this article is to present an exploratory study of reception research of theatrical experiences of general audiences of spoken theatre performances in Tartu, Estonia. The research is based on a quantitative survey of the audiences of eight spoken theatre performances. Factor analysis is used to assemble 24 different performance characteristics into five factors: Aesthetic, Entertainment, Personally Challenging, Complexity and Conventionality Factor. The factor analysis also points out some possible overlaps (characteristics that could be included into different factors at the same time) between factors, particularly between the Aesthetic and Personally Challenging Factor. These overlaps could be explained by (1) the limits of the quantitative survey, (2) the language and (3) the performances included in the survey. The overlaps, from the perspective of the viewer being inspired, challenged and excited by the performance, are due to the reason that the performances are personally touching as well as demanding and are performed by skilful performers. The article discusses the point that aesthetically challenging performances can be thematically or artistically demanding for the viewer, if the viewer has a personal relationship to the theme

Is Theatre Personally and Socially Relevant? Empirical Insight into Theatrical Experience

In the years 2009–2015, a comparison of theatre systems in seven smaller European cities was conducted and named the STEP City Study. The study also included reception research, conducted with an extensive questionnaire, and qualitative research comprised of focus groups and interviews with audience members. One of the surprising results showed that, generally, the spectators enjoyed the performances a lot, but at the same time, did not rate them as very personally or socially relevant. That is why we decided to explore the notion of relevance in this article, or in other words, to examine what we are measuring when we ask the audience if the performance was relevant for them. In this study, we combine audience research and performance analysis of the shows that were evaluated as the most personally or socially relevant. The shows had either existential or contemporary political topics, were created in rather traditional ways, and did not stand out in any particularly innovative theatrical approach. We also conclude that relevance is a complex issue expressed in different dimensions of theatrical experience and cannot be straightforwardly measured

Vastsündinute jälgimine Tallinna perearstipraksistes

Töö eesmärgiks oli hinnata vastsündinute jälgimise vastavust terve lapse jälgimise juhendile, vastsündinu terviseseisundit ning emade rahulolu perearsti ja -õe tegevusega. Ankeetküsitluse meetodil uuriti 256 ema, kelle lapsed sündisid kahes Tallinna sünnitusmajas 2007. aastal. Selgus, et juhendi kohaselt jälgis vastsündinuid 24% perearstidest ja 2% pereõdedest. Ligi pooled emadest jätkasid vastsündinu tervisekontrolli sünnitusmajade juures. Ligi kahel kolmandikul vastsündinutest esines terviseprobleeme, mille lahendas ühel neljandikul juhtudest perearst, ülejäänud said võrdselt abi kas lastehaigla vastuvõtutoast või mujalt. Seevastu on perearstikeskuste külastamine sage ja vastab ettenähtule. Uuritavad väljendasid rahulolu pereõega ligi 60%-l ja perearstiga 85%-l juhtudest. 95,7% emadest soovis lastearsti osalemist vastsündinu jälgimises. Eesti Arst 2009; 88(7−8):461−46

Analysis of Control and Protection of High-voltage Electrical Devices

Käesoleva lõputöö eesmärgiks on analüüsida kõrgepingeseadmete juhtimist ja kaitset. Lõputöös on kirjeldatud Eesti elektrisüsteemi ja elektrivõrkude liigitust. Kirjanduse põhjal on kirjeldatud kõrgepinge põhilised kommutatsiooni ja mõõteaparaate ning näiteid on toodud Tartu alajaamast. Kirjeldatud on alajaama ülesehitust ja struktuuri ning kõrgepingeseadmete juhtimis- ja kaitsevõimalusi. Lõputöö analüütilises osas antakse ülevaade Tartu alajaama primaarseadmetest ja analüüsitakse nende juhtimist ja kaitset. Kirjeldatakse ka alajaama alalis- ja vahelduvvoolu tarbimist ning andmesidet.Alalüüsi lõpptulemusena soovitakse välja selgitada milliseid kõrgepingeseadmeid alajaamas kasutatakse ning kuidas toimub nende juhtimine ja kaitse ning millisel viisil toimub kõrgepingeseadmete side alajaama ja juhtimiskeskusega.This article is mainly about concept of Estonian high-voltage power grid and equipment used to control and protect high voltage electrical devices. This articel gives a review about the main high-voltage switching devices. In the final chapter of this thesis, the author has analysed high -voltage electrical devises in Tartu main substation. The purpose was to find out what kind of protection and control equipment are used in high-voltage power grid. To achive the purpose the author repeatedly went to the Tartu main substation to gather information

Veebilehekülje kommunikatsioon sotsiaalturunduslikes kampaaniates

The aim of this thesis was to clear up the role of web pages as a channel of social marketing campaign in the organisers’ and the target groups’ point of view; also, if and how does the internet complete the assignments as a marketing channel. To find, how it would be possible to use the World Wide Web more effectively as a message forwarder. In the present paper I used four campaigns of social marketing, three of which were conducted in 2006 and one in 2007: “Kasvame koos, laps ei ole nukk”, “Jää puhtaks!”, “Ära osale loosimises!” and “Narkojutud ei lõpe kunagi hästi”. The important unifying sign of these campaigns is the web page address, which is quite emphasized in every advertisement. During the pilot research, I conducted expert-interviews with the organisers of the campaigns of social marketing and in-depth interviews with the represantatives of the target groups, analysing the frequency of visits on the campaign related web pages. Searching for answers to the questions: Which is the role of a web page as a channel of a social marketing campaign? How is the existance of a web page revealed? Do the representatives of the target groups notice the reference to the web page in the advertisements or not, and if they do or do not then on what reasons? How do the representatives of the target groups see the web pages and how to use the web more effectively as a message forwarder? Through which mediums would the information of web pages reach the target groups quickest? The results of the conducted survey show that the web pages of social marketing campaigns have an important role completing the advertising campaign and messages, and forwarding concrete information which could help people change their behaviour. To reveal the web page addresses, the references of the web sites are usually added to all the other campaign related materials and that is where the idea ends. This is the reason why it often happens that the web page addresses added to several materials do not actually reach the target audience. Mainly, it is because of the design of the campaign’s visuals which do not allow the web page address to be visible enough, if at all. Also, the advertising campaign often cannot generate any interest on the topic among the target group. Rather, it is the web page itself which have high quality and everything else necessary. Unfortunately, the information on the web site is often also missed by the visitor because of the unatractiveness and enormous amount of text on the page. The representatives of the target groups find the web pages of the campaigns of social marketing informative but not very attractive so they will not spend much time visiting them. Internet is regarded the best channel for reciving information on web pages so when planning a campaign, several internet-solutions should be more emphasized. In conclusion, one could say that a web page is the right medium to complete the assignments appointed and to open the topics of the social marketing campaigns, but media campaigns and advertisements cannot bring people to web pages and the web pages themselves remain dull for the target audience.http://www.ester.ee/record=b3754986*es

Lõhustav osteokondriit: olemus ja ravi põlveliigese näitel

http://www.ester.ee/record=b457402