Modulating gut microbiota in a mouse model of Graves' orbitopathy and its impact on induced disease

BACKGROUND: Graves' disease (GD) is an autoimmune condition in which autoantibodies to the thyrotropin receptor (TSHR) cause hyperthyroidism. About 50% of GD patients also have Graves' orbitopathy (GO), an intractable disease in which expansion of the orbital contents causes diplopia, proptosis and even blindness. Murine models of GD/GO, developed in different centres, demonstrated significant variation in gut microbiota composition which correlated with TSHR-induced disease heterogeneity. To investigate whether correlation indicates causation, we modified the gut microbiota to determine whether it has a role in thyroid autoimmunity. Female BALB/c mice were treated with either vancomycin, probiotic bacteria, human fecal material transfer (hFMT) from patients with severe GO or ddH2O from birth to immunization with TSHR-A subunit or beta-galactosidase (βgal; age ~ 6 weeks). Incidence and severity of GD (TSHR autoantibodies, thyroid histology, thyroxine level) and GO (orbital fat and muscle histology), lymphocyte phenotype, cytokine profile and gut microbiota were analysed at sacrifice (~ 22 weeks). RESULTS: In ddH2O-TSHR mice, 84% had pathological autoantibodies, 67% elevated thyroxine, 77% hyperplastic thyroids and 70% orbital pathology. Firmicutes were increased, and Bacteroidetes reduced relative to ddH2O-βgal; CCL5 was increased. The random forest algorithm at the genus level predicted vancomycin treatment with 100% accuracy but 74% and 70% for hFMT and probiotic, respectively. Vancomycin significantly reduced gut microbiota richness and diversity compared with all other groups; the incidence and severity of both GD and GO also decreased; reduced orbital pathology correlated positively with Akkermansia spp. whilst IL-4 levels increased. Mice receiving hFMT initially inherited their GO donors' microbiota, and the severity of induced GD increased, as did the orbital brown adipose tissue volume in TSHR mice. Furthermore, genus Bacteroides, which is reduced in GD patients, was significantly increased by vancomycin but reduced in hFMT-treated mice. Probiotic treatment significantly increased CD25+ Treg cells in orbital draining lymph nodes but exacerbated induced autoimmune hyperthyroidism and GO. CONCLUSIONS: These results strongly support a role for the gut microbiota in TSHR-induced disease. Whilst changes to the gut microbiota have a profound effect on quantifiable GD endocrine and immune factors, the impact on GO cellular changes is more nuanced. The findings have translational potential for novel, improved treatments. Video abstract

ANALYSIS OF ACCESSIBILITY AND QUALITY OF DENTAL SERVICES

Osnova obravnavanega problema diplomskega dela je doseganje, merjenje in prepoznavanje realnega stanja kakovosti ter v okviru tega tudi dejavnikov in mere dostopnosti do storitev zobozdravstvene dejavnosti v Sloveniji. Izbrana tematika se odraža predvsem v oddaljenosti minule reforme slovenskega zobozdravstvenega sistema, ki je kot odsev zastaranosti sistema pripeljala do nastanka ovir doseganja ciljne kakovosti in dostopnosti storitev. Za razumevanje pomena omenjenih vidikov delovanja zobozdravstvene sfere smo se natančneje poglobili v sam področni sistem ter izpostavili njegove značilnosti. Opravljena je bila raziskava o dojemanju dejanskega stanja kakovosti in dostopnosti zobozdravstvenega področja z vidika statusa študentov. Uporabili smo metodo anketnega vprašalnika ter na podlagi pridobljenih odgovorov naredili kvantitativno analizo. Ugotovili smo, da je slovenski zobozdravstveni sistem za doseganje želenega evropskega standarda kakovosti in dostopnosti ponudbe zobozdravstvenih storitev potreben poglobljene prenove, ki bo doprinesla rešitve trenutni obremenjenosti zdravstvene blagajne in motenosti razvoja sistema za njegovo nadgradnjo in prilagoditev dosedanjim ter prihodnjim družbenim spremembam pri doseganju maksimalne ravni kakovosti in dostopnosti izvajanja storitev. Diplomsko delo se opira na preučevanje zobozdravstvenega področja zdravstvenega sistema. Prispevek je namenjen področju menedžmenta v zdravstveni stroki za vključitev ugotovitev izvedene raziskave o kakovosti in dostopnosti današnjega zobozdravstvenega sistema v predloge njegovih izboljšav.The basis of the problem addressed in this thesis is the achievement, measurement and identification of the real state of quality and, within this, the factors and measures of accessibility to dental services in Slovenia. The chosen topic is mainly reflected in the remoteness of the past reform of the Slovenian dental system, which, as a reflection of the obsolescence of the system, led to the emergence of obstacles to the achievement of the target quality and accessibility of services. In order to understand the significance of these aspects of the dental sphere, we have looked more closely at the dental system itself and highlighted its characteristics. A survey was carried out on the perception of the actual situation of quality and accessibility of the dental field from the point of view of the status of full-time students. A questionnaire survey method was used and a quantitative analysis was carried out on the basis of the responses obtained. We came to the conclusion that in order to achieve the desired European standard of quality and accessibility of dental services, the Slovenian dental system is in need of an in-depth overhaul, which will bring solutions to the current burden on the health budget and the disruption of the development of the system to upgrade it and adapt it to the current and future social changes. The thesis is based on the study of the dental area of the health system. Therefore, its contribution is intended for the dental profession to integrate the findings of the research carried out on today\u27s dental system into proposals for its improvement

CONQUERING STRESS AT WORK IN MIKROGRAFIJA LTD.

V diplomskem delu smo znotraj področja stres predstavili povzročitelje stresa, načine premagovanja stresa in posledice stresa, tako v privatnem življenju, kot tudi na delovnem mestu. Opredelili smo pojme stres in njegove vplive pri delu, stresna reakcija ter posledice stresa. V podjetju Mikrografija d.o.o. smo analizirali trenutno prisotnost stresa na delovnem mestu, njegove vplive na zaposlene in načine s katerimi zaposleni in organizacija stres premagujejo. Rezultati ankete so pokazali, da so zaposleni v povprečju včasih pod vplivom stresa na delovnem mestu, ki pa vpliva na njihovo delo. Večinoma zaposleni stres premagujejo s pomočjo prijateljev ali ob gledanju televizije in poslušanju glasbe. V organizaciji pa včasih ali redko skrbijo za premagovanje stresa zaposlenih.The content of this disertation are the areas of stress in which we present the causes of stress, ways of overcoming stress and the effects of stress, both in private life, as well as in the workplace. We define the concepts of stress and its effects at work, stress reaction and the consequences of stress. At the company Mikrografija Ltd. we analysed the presence o stress in the workplace, its effects on employees and the ways by which employees and the organization overcome stress. Results showed that employees are sometimes under the influence of stress in the workplace, which affects their work. In most cases, employees overcome stress with the help from friends or watching television and listening to music. The organization, however, sometimes or rarely helps them to overcome their stress

The theme of the water in picture books for children in pre-school age

Vsebina diplomskega dela se nanaša na kakovostne leposlovne slikanice, katerih tema je voda. Obravnavali smo šest kakovostnih leposlovnih slikanic, s katerimi smo otrokom v predšolskem obdobju približali različne zvrsti in vrste literarnih besedil. V teoretičnem delu diplomskega dela je predstavljen pomen branja kakovostnih slikanic v predšolskem obdobju, definicija kakovostne slikanice, interakcija med besedilom in ilustracijo v slikanicah ter pomen odrasle osebe kot bralnega zgleda.This bachelor’s thesis is based on quality fiction picture books about water. We dealt with six quality fiction books which helped introducing various types and genres of literary texts to children in the pre-school period. The theoretical part of the thesis stresses the importance of reading quality fiction picture books in the pre-school period, the definition of a quality fiction picture book, the interaction between the text and the illustrations in picture books, and the significance of an adult person as a reading model

A web-based textbook for learning programming in JavaScript

Z namenom ustvarjanja okolja za učenje programiranja JavaScripta v slovenskem jeziku smo preučili možnost učenja z vizualnimi programskimi jeziki. Pregledali smo že obstoječa okolja na spletu za učenje programskih jezikov. Z ugotovitvami smo sestavili spletni učbenik za učenje osnovnih konceptov programskega jezika JavaScript. S pomočjo knjižnice Blockly in zbirke nalog smo zagotovili, da je spletni učbenik interaktiven in enostaven za uporabo.With the purpose of creating an environment for learning programming in Javascript, we studied the possibility of using visual programming languages. We made an overview of already existing web platforms for learning programming. With our findings we built a web-based textbook for learning basic JavaScript concepts. With the help of Blockly library and a collection of exercises, we ensured that the textbook is interactive and easy to use

COMBINATORICS WITH THE COMPUTER PROGRAMME MATHEMATICA

Diplomsko nalogo v grobem razdelimo na dva dela. Prvi del, ki obsega drugo in tretje poglavje, je namenjen spoznavanju programskega paketa Mathematica. V drugem poglavju opišemo zgradbo dokumenta (t.i. notebook) in palet, ki so namenjene lažjemu delu s programom. V nadaljevanju sledijo uporaba paketov, pravila sintakse in uvažanje ter izvažanje dokumentov. V tretjem poglavju obravnavamo računanje z osnovnimi matematičnimi operacijami in funkcijami vgrajenimi v paket. Predstavimo tudi temeljno računanje z izrazi, funkcijami, enačbami, matrikami, diferencialnim in integralnim računom. Zraven podamo ukaze in njihove razlage s konkretnimi primeri. V drugem delu (v četrtem in petem poglavju) podrobneje opišemo delo s paketom Combinatorica na področju kombinatorike in teorije grafov. V četrtem poglavju za lažjo obravnavo najprej predstavimo osnove kombinatorike ter ukaze povezane s kombinatoriko. V petem poglavju opišemo osnovne pojme teorije grafov in risanje grafov, katerih imena so že vgrajena v programu Mathematica. Nazadnje spoznamo risanje poljubnega grafa in ukaze za določanje Eulerjevega in Hamiltonovega grafa.This graduation thesis has been basically divided into two main parts, of which the First Part including the Chapters 2 and 3 has introduced the Mathematica package. The Chapter 2, however, introduces the construction of a document (i.e. the notebook) and pallets meant to less requiring way of dealing with the programme to be followed further by the use of the packages, the syntax regulations as well as by the importing and exporting documents. The Chapter 3 discusses package incorporated basic mathematical operations and functions involved in the calculating itself. Beside, fundamental calculating including expressions, functions, equations, matrixes as well as the differential and integral computation, which have been provided commands and explanations based on true examples have been subjected to the same chapter. The Second Part (Chapter 4 and 5), the operating with the Combinatorica package being involved into the field of the theory of combinations and the theory of graphs have been introduced. In order to make discussion easier, the Chapter 4 introduces the basis of the theory of combinations as well as related commands. The Chapter 5 clearly states basic conceptions on the theory of graphs and designing them already being incorporated into the Mathematica. Finally, the creation of an optional graph as well as the definition of the Euler and Hamilton graphs has been taught to sum up

Concept of manual wheelchair for easier overcoming of architectural barriers and with different seating position

Uvod: Oseba na invalidskem vozičku se v svojem življenju srečuje z različnimi ovirami, pomembnejše med njimi so fizične oziroma arhitekturne ovire. Čeprav se po raziskavah urbanistično okolje pozitivno spreminja invalidom v prid, še vedno ostaja velik delež okolja, ki je za osebe na invalidskem vozičku težko dostopno. Možni zapleti pri uporabnikih invalidskih vozičkov, ki so velikokrat posledica dolgotrajnega sedenja, se odražajo v motnjah delovanja prebavil in sečil, bolečinah, mišičnih krčih, dihanju, pojavijo se urološki problemi ter lahko tudi razjede zaradi pritiska. Namen: Namen diplomskega dela je bil izdelati invalidski voziček na ročni pogon, ki bi reševal težave uporabnikov invalidskih vozičkov na področju zdravstvenega stanja in na področju mobilnosti ter primerjava izdelanega invalidskega vozička s takim, ki ga pacienti danes najpogosteje uporabljajo. Metode dela: Izdelali smo invalidski voziček in testirali njegovo uporabnost. Opazovali smo kako se obnesejo večja sprednja kolesa, kakšna je mobilnost in okretnost vozička v primerjavi z običajnim modelom. Rezultati: S konceptnim invalidskim vozičkom smo želeli udobnost pri vožnji samega ter preprečiti spremembe zdravstvenega stanja uporabnikov, ki nastajajo zaradi vsakodnevne uporabe vozička. Voziček je sestavljen iz aluminijastega ogrodja. Sedež je iz poliuretanske pene ter ima možnost aplikacije dodatnega sistema za nagib sedežne enote naprej za 15 stopinj, kolesa so iz jekla in imajo polne gume. Voziček ima trikolesni okvir, pri čemer sta dve večji kolesi spredaj in eno manjšo kolo zadaj. Konceptni voziček je bil pri testiranju pri nekaterih nalogah boljši od standardnega, pri drugih pa slabši. Razprava in zaključek: Sama ideja razvoja konceptnega invalidskega vozička izhaja iz poslušanja ter opazovanja uporabnikov ter pregleda zdravstvenih težav s katerimi se uporabniki invalidskih vozičkov soočajo. Med samim razvojem in izdelavo vozička smo naleteli na mnoge ovire in težave, ki smo jih skušali rešiti. Pri izdelavi nas je vodila želja po izboljšanju invalidskih vozičkov in s tem izboljšanju življenjskih pogojev uporabnikov invalidskih vozičkov. Težave je povzročilo preširoko področje reševanja problemovIntroduction: Wheelchair users are in their lives faced with various obstacles. The most important are physical or architectural obstacles. Although researches show positive changes in the urban environment, from which disabled persons benefit, a large proportion of terrain remains difficult to access for people on a wheelchair. Possible complications in wheelchair users, often caused by prolonged sitting, reflect themselves in disorders of gastrointestinal and urinary tract functions, pain, muscle spasms, breathing problems, urological problems and may also lead to pressure ulcers. Aim: The aim of the diploma work is to build a manual wheelchair with which would users better deal their problems related to wheelchair, and to compare it with currently used standard wheelchair. Methods: We wanted to build a wheelchair and then test it. We then observed whether larger front wheels prove more effective, as well as its mobility and agility in comparison to others. Results: The concept of a wheelchair was to improve the comfort of driving the wheelchair itself, both in the area of the user’s health and in overcoming daily obstacles. The wheelchair consists of an aluminium frame, a seat made is of polyurethane foam and has the ability of applying an additional 15 degrees forward inclination system for the seat unit. The wheels are made of steel and have full tires. The wheelchair has three wheels, two large in the front and one small wheel in the back. Testing of a concept wheelchair revealed that it was better in one hand but on the other hand was better standard wheelchair. Discussion and conclusions: The idea of the concept wheelchair stems from listening to and observing users during their daily activities and reviewing the health problems the users face. During the development and construction of the wheelchair there were many obstacles and difficulties which we managed to solve. Entire time there was a desire to further enhance wheelchairs, which would help to improve the living conditions of their users. The problems arose because it was chosen a rather wide range of solutions to problem

The Physical Ability Test As a Criterion of Physical Preparedness of Professional Firefighters in Slovenia

V diplomski nalogi sem raziskoval in testiral fizično pripravljenost poklicnih gasilcev v Sloveniji. Najprej sem opisal delo in poklic gasilca. Osredotočil sem se na gibalne sposobnosti, saj se v vsakdanjiku gasilca izkazujejo kot najpomembnejše za kvaliteto njihovega dela ter preprečevanje poškodb tako na intervenciji kot v zavodu. Ker se poklicne enote razlikujejo, sem se pozanimal o delovanju vseh 14 enot in zbral podatke o možnosti fizične aktivnosti v službenem času, vodeni vadbi ter ali je ta obvezna. Zbral sem tudi fotografije telovadnih prostorov, ki so jim na voljo. Zanimalo me je, ali se izvajajo vsakoletni gibalni testi, s katerimi preverijo upad ali napredek fizične pripravljenost zaposlenih gasilcev. Glede na opremo in gibalne sposobnosti, ki so potrebne za opravljanje poklica gasilca, sem sestavil primer enostavnega gibalnega testa, sestavljenega iz vaj, ki testirajo posebej izpostavljene gibalne sposobnosti. Test sem uporabil na 45 gasilcih Poklicne gasilske enote Celje. Gibalni test je sestavljen iz dveh delov. Prvi se navezuje na gasilsko stroko in se lahko izvaja v enoti Izobraževalnega centra za zaščito in reševanje Pekre v Mariboru in na Igu pri Ljubljani. Drugi del se lahko izvaja znotraj vsake enote ter je sestavljen iz šestih vaj, ki nam prikažejo hitrost in vzdržljivost poklicnega gasilca, moč mišic zgornjih okončin, moč mišic spodnjih okončin, moč mišic trupa, gibljivost in zmožnost ravnotežja. Na podlagi pridobljenih podatkov sem opredelil starostne skupine in izdelal kriterije, na podlagi katerih se rezultat vsake vaje oceni z oceno od 1 do 5. Tako pridobljena povprečna ocena nam prikaže fizično pripravljenost poklicnega gasilca. Na primeru Poklicne gasilske enote Celje se je gibalni test, ki je rezultat naloge, izkazal kot izvedljiv in primeren. Skupna povprečna ocena 3,24 kaže na dobro stanje fizične pripravljenosti testiranih poklicnih gasilcev, pri čemer pa smo opazili najizrazitejše primanjkljaje pri preizkušanju moči mišic rok in gibljivosti. Diplomsko delo povzema trenutno stanje skrbi za fizično pripravljenost poklicnih gasilcev in ponuja predlog za načrtovanje enotnega rednega testiranja psihofizičnih sposobnosti poklicnih gasilcev, ki bi omogočalo spremljanje stanja in napredka posameznikov. Na podlagi preverjenega stanja pa je moč načrtovati usmerjeno vadbo za vzdrževanje oz. izboljšanje napredka.In my thesis, I researched and tested the physical preparedness of professional firefighters in Slovenia. I first described the work and profession of a firefighter. I focused on movement skills, since they daily prove to be paramount for the quality of the firefighters’ work and the prevention of their injuries both duing the intervention and at the unit. As the professional firefighters’ department units differ I looked into the working of all 14 units and gathered information on the possibility of physical activity during working time, the possibility of having a guided exercise and whether it was mandatory. I also collected photos of the gym spaces available to them. I was interested whether annual physical ability tests are conducted to check the decline or progress of physical fitness of employed firefighters. Given the equipment and the physical ability required to work as a firefighter, I have put together an example of a simple physical ability test consisting of exercises that test particularly displayed movement skills. I have conducted the test on 45 firefighters at the Professional Fire Brigade Celje. The physical ability test is made up from two parts. The first part is related to the firefighter profession and can be implemented in the department of the Educational Center for Protection and Rescue Pekre in Maribor and in Ig near Ljubljana. The second part can be carried out inside every unit and is made up from six exercises that indicate the speed and endurance of a professional firefighter, upper limb muscle strength, lower limb muscle strength, torso muscle strength, agility and balance ability. Based on the collected data I defined the age groups and developed criteria based on which the result of each exercise is evaluated with a score of 1 to 5. Thus obtained average grades show us the physical preparedness of a professional firefighter. In case of the Professional Fire Brigade Celje, the physical test that resulted from this assignment has proven feasible and appropriate. The overall average score of 3.24 indicates a good physical preparedness of the tested professional firefighters, with the most pronounced deficits in testing arm strength and mobility. This thesis summarizes the current state of care for the physical preparedness of the professional firefighters and offers a proposal for planning a uniform regular testing of psychophysical abilities of professional firefighters, which would allow monitoring the individual’s condition and progress. Based on the condition check, it is possible to plan a targeted and focused exercise to maintain or improve progress