35 research outputs found

    Novice Teachers’ Well-Being at Work

    Get PDF
    Aim: Teachers’ first year at work after graduating is known to be challenging as the new teachers are developing their professionalism and finding their personal teaching styles. The purpose of this study was to analyze teachers’ well-being at work during their first work year; which factors strengthen and reduce their well-being. In addition, teachers’ perceptions of the connection between teacher education and well-being at work were studied. Method: This was a qualitative study and the data were obtained with the method of empathy-based stories (MES). Two frame stories were utilized for data collection. The research participants consisted of teachers (N = 14) who had worked from 1 to 4 years as classroom teachers. The data were analyzed with the content analysis methods. Results: Based on the results, the colleagues’ support and work community impacted the teachers’ well-being. Other important factors strengthening well-being were co-operation with parents and the size and features of the classroom. Successful teaching experiences also strengthened well-being. Well-being was weakened by difficulties in group management and school practices as well as the teachers’ fatigue. Pedagogical skills and abilities to develop one’s work provided by teacher education were seen to strengthen well-being. Conclusion: The findings suggest that despite the teaching task, more preparation is needed to teachers’ other tasks too. Furthermore, teachers need support to build a more realistic work role and professional identity. Measures to support transition to work should be developed. DOI: 10.5901/jesr.2014.v4n3p17

    Effects of 12-month home-based physiotherapy on duration of living at home and functional capacity among older persons with signs of frailty or with a recent hip fracture - protocol of a randomized controlled trial (HIPFRA study)

    Get PDF
    Background: Health concerns, such as frailty and osteoporotic fractures decrease functional capacity and increase use of health and social care services in the aging population. The ability to continue living at home is dependent on functional capacity, which can be enhanced by rehabilitation. We study the effects of a 12-month home-based physiotherapy program with 12-month follow-up on duration of living at home, functional capacity, and the use of social and health care services among older persons with signs of frailty, or with a recently operated hip fracture. Methods: This is a non-blinded, parallel group, randomized controlled trial performed in South Karelia Social and Health Care District, Finland (population 131,000). Three hundred community-dwelling older persons with signs of frailty (age >= 65) and 300 persons with a recent hip fracture (age >= 60) will be recruited. Frailty is screened by FRAIL questionnaire and verified by modified Fried's frailty criteria. Both patient groups will be randomized separately to a physiotherapy and a usual care arm. Individualized, structured and progressive physiotherapy will be carried out for 60 min, twice a week for 12 months at the participant's home. The primary outcome at 24 months is duration of living at home. Our hypothesis is that persons assigned to the physiotherapy arm will live at home for six months longer than those in the usual care arm. Secondary outcomes are functional capacity, frailty status, health-related quality-of-life, falls, use and costs of social and health care services, and mortality. Assessments, among others Short Physical Performance Battery, Functional Independence Measure, Mini Nutritional Assessment, and Mini-Mental State Examination will be performed at the participant's home at baseline, 3, 6, and 12 months. Register data on the use and costs of social and health care services, and mortality will be monitored for 24 months. Discussion: Our trial will provide new knowledge on the potential of intensive, long-term home-based physiotherapy among older persons at risk for disabilities, to enhance functional capacity and thereby to postpone the need for institutional care, and diminish the use of social and health care services.Peer reviewe

    Effects of 12-month home-based physiotherapy on duration of living at home and functional capacity among older persons with signs of frailty or with a recent hip fracture - protocol of a randomized controlled trial (HIPFRA study)

    Get PDF
    Abstract Background Health concerns, such as frailty and osteoporotic fractures decrease functional capacity and increase use of health and social care services in the aging population. The ability to continue living at home is dependent on functional capacity, which can be enhanced by rehabilitation. We study the effects of a 12-month home-based physiotherapy program with 12-month follow-up on duration of living at home, functional capacity, and the use of social and health care services among older persons with signs of frailty, or with a recently operated hip fracture. Methods This is a non-blinded, parallel group, randomized controlled trial performed in South Karelia Social and Health Care District, Finland (population 131,000). Three hundred community-dwelling older persons with signs of frailty (age ≥ 65) and 300 persons with a recent hip fracture (age ≥ 60) will be recruited. Frailty is screened by FRAIL questionnaire and verified by modified Fried’s frailty criteria. Both patient groups will be randomized separately to a physiotherapy and a usual care arm. Individualized, structured and progressive physiotherapy will be carried out for 60 min, twice a week for 12 months at the participant’s home. The primary outcome at 24 months is duration of living at home. Our hypothesis is that persons assigned to the physiotherapy arm will live at home for six months longer than those in the usual care arm. Secondary outcomes are functional capacity, frailty status, health-related quality-of-life, falls, use and costs of social and health care services, and mortality. Assessments, among others Short Physical Performance Battery, Functional Independence Measure, Mini Nutritional Assessment, and Mini-Mental State Examination will be performed at the participant’s home at baseline, 3, 6, and 12 months. Register data on the use and costs of social and health care services, and mortality will be monitored for 24 months. Discussion Our trial will provide new knowledge on the potential of intensive, long-term home-based physiotherapy among older persons at risk for disabilities, to enhance functional capacity and thereby to postpone the need for institutional care, and diminish the use of social and health care services. Trial registration ClinicalTrials.gov Identifier: NCT02305433 , Registered Nov 28, 2014

    Neck–Shoulder Region Training for Chronic Headache in Women : A Randomized Controlled Trial

    Get PDF
    Objectives: We investigated whether a specific exercise program for the neck–shoulder region reduces headache intensity, frequency, and duration, and how it influences neck disability among women with chronic headache compared to a control group. Design: Two-center randomized controlled trial. Subjects: 116 working-age women. Intervention: The exercise group (n = 57) performed a home-based program with six progressive exercise modules, over 6 months. The control group (n = 59) underwent six placebo-dosed transcutaneous electrical nerve stimulation sessions. Both groups performed stretching exercises. Main measures: The primary outcome was pain intensity of headache, assessed using the Numeric Pain Rating Scale. Secondary outcomes were frequency and duration of weekly headaches, and neck disability assessed using the Neck Disability Index. Generalized linear mixed models were used. Results: Mean pain intensity at baseline was 4.7 (95% CI 4.4 to 5.0) in the exercise group and 4.8 (4.5 to 5.1) in the control group. After 6 months the decrease was slight with no between-group difference. Headache frequency decreased from 4.5 (3.9 to 5.1) to 2.4 (1.8 to 3.0) days/week in the exercise group, and from 4.4 (3.6 to 5.1) to 3.0 (2.4 to 3.6) in the control group (between-group p = 0.017). Headache duration decreased in both groups, with no between-group difference. Greater improvement in the Neck Disability Index was found in the exercise group (between-group change −1.6 [95% CI −3.1 to −0.2] points). Conclusion: The progressive exercise program almost halved headache frequency. The exercise program could be recommended as one treatment option for women with chronic headache.publishedVersionPeer reviewe

    Effects of a 12-month home-based exercise program on functioning after hip fracture - Secondary analyses of an RCT

    Get PDF
    Background Long-term functional limitations are common after hip fractures. Exercise may alleviate these negative consequences but there is no consensus on an optimal training program. The objective was to study the effects of a 12-month home-based supervised, progressive exercise program on functioning, physical performance, and physical activity. Methods Secondary analysis of a randomized controlled trial targeting patients with surgical repair of a hip fracture, aged >= 60 years, Mini-Mental State Examination (MMSE) score of >= 12. The participants were randomized into Exercise (n = 61) or Usual care (n = 60). Assessments at baseline, 3, 6, and 12 months included Lawton's Instrumental Activities of Daily Living (IADL), Short Physical Performance Battery (SPPB), handgrip strength, and self-reported frequency of sessions of leisure-time physical activity. Analyzed using mixed-effects models. Results Participants' (n = 121) mean age was 81 years (SD 7), and 75% were women. The mean IADL score at baseline was 17.1 (SD 4.5) in the exercise group, and 17.4 (5.1) in the usual care group. The mean SPPB scores were 3.9 (1.6) and 4.2 (1.8), and handgrip strength was 17.7 (8.9) kg and 20.8 (8.0) kg, respectively. The age- and sex-adjusted mean changes in IADL over 12 months were 3.7 (95% CI 2.8-4.7) in the exercise and 2.0 (1.0-3.0) in the usual care group (between-group difference, p = 0.016); changes in SPPB 4.3 (3.6-4.9) and 2.1 (1.5-2.7) (p < 0.001); and changes in handgrip strength 1.2 kg (0.3-2.0) and 1.0 kg (-1.9 to -0.2) (p < 0.001), respectively. We found no between-group differences in changes in the frequency of leisure-time activity sessions. Conclusion A 12-month home-based supervised, progressive exercise program improved functioning and physical performance more than usual care among patients with hip fractures. However, the training did not increase leisure-time physical activity.Peer reviewe

    Older persons with signs of frailty in a home-based physical exercise intervention: baseline characteristics of an RCT

    Get PDF
    Background Increasing the level of physical activity among persons with signs of frailty improves physical functioning. There is a lack of long-term supervised physical exercise intervention studies including a validated definition of frailty. Aims To present baseline characteristics of persons with signs of frailty participating in a randomized long-term home-based physical exercise trial (HIPFRA), and to study associations between the severity of frailty, functional independence and health-related quality-of-life (HRQoL). Methods Three hundred persons, >= 65 years old and with signs of frailty (assessed by Fried ' s phenotype criteria) were recruited from South Karelia, Finland and randomized to a 12-month physiotherapist-supervised home-based physical exercise program (n = 150), and usual care (n = 150). Assessments at the participants' homes at baseline, and after 3, 6 and 12 months included the Short Physical Performance Battery (SPPB), the Functional Independence Measure (FIM), HRQoL (15D) and the Mini-Mental State Examination (MMSE). Results Eligibility was screened among 520 persons; 300 met the inclusion criteria and were randomized. One person withdrew consent after randomization. A majority (75%) were women, 182 were pre-frail and 117 frail. The mean age was 82.5 (SD 6.3) years, SPPB 6.2 (2.6), FIM 108.8 (10.6) and MMSE 24.4 (3.1) points, with no significant differences between the study groups. Inverse associations between the severity of frailty vs. FIM scores and HRQoL (p <0.001 for both) were found. Conclusions Our participants showed marked physical frailty without major disabilities. The severity of frailty seems to be associated with impaired functional independence and HRQoL.Peer reviewe

    Dialoginen kohtaaminen psykopaattisia piirteitä omaavan asiakkaan kanssa : Rikosseuraamustyöntekijän näkökulma

    Get PDF
    Rikosseuraamustyöntekijän ja asiakkaan dialoginen kohtaaminen on avainasemassa paitsi asiakassuhteen rakentumisen kannalta, myös rikosseuraamusalan työn vaikuttavuuden eli rikosten uusimisriskin alentamisen kannalta. Tässä työssä tutkimme rikosseuraamustyöntekijöiden kokemuksia siitä, miten asiakkaan mahdolliset psykopaattiset ominaisuudet heijastuvat vuorovaikutukseen ja sitä kautta dialogisuuden toteutumiseen rikosseuraamustyöntekijän ja hänen psykopaattisia piirteitä omaavan, ehdonalaisesti vankilasta vapautuneen asiakkaansa välillä. Nykytutkimuksen valossa näyttää siltä, että persoonallisuushäiriöt ovat yliedustettuina niin vankeinhoidon kuin myös sosiaali- ja terveyspalveluiden asiakkaissa peruspopulaatioon nähden. Tämä pätee myös psykopaattisiin persoonallisuuden piirteisiin. Asiakkaan psykopaattiset piirteet saattavat asettaa asiakastyöskentelylle omat erityishaasteensa, sillä psykopaattisuuden oireita ovat petollisuus, vastuuttomuus, tunnekylmyys sekä empatiakyvyn ja katumuksen puute. Haastattelututkimuksemme tulokset antoivat viitteitä siitä, että rikosseuraamustyöntekijät kokivat aidon dialogisen kohtaamisen häiriintyvän, jos asiakkaalla oli normaalia enemmän psykopaattisia persoonallisuuden piirteitä. Persoonallisuuden psykopaattisuus heijastui myös henkilön vuorovaikutustyyliin. Lisäksi rikosseuraamustyöntekijät kokivat mahdollisuutensa vaikuttaa rikosten uusimisriskiin heikentyneen, kun kyseessä oli psykopaattisia piirteitä omaava asiakas.The Dialogical Interaction with a Client that has Psychopathic Personality Traits - A Probation Supervisor´s Perspective The dialogical interaction is the key factor in building a relationship between the probationary supervisor and the customer. This applies also to the effectiveness concerning the work in order to lessen the risk of renewed delinquency. Our main interest was to examine, how the psychopathic traits of the customer’s personality affect the dialogical interaction between the probationary supervisor and the customer who had been released from prison on probation. According to the resent research, personal disorders are over-represented among the prison population as well as among the customers of the social branch and health care in general, when compared to the population in average. This is the case also with the psychopatic personality characteristics. These psychopathic personality traits may set spesific demands concerning the interaction between the customer and his/her probationary supervisor. This is related to the fact that the symptoms of psychopathy are deceptiveness, shallow emotions, irresponsibility and lack of empathy or remorse. The results of our survey among probationary supervisors indicate that they found it hard to create and maintain a dialogical interaction, if the customer had plenty of psychopathic traits in his/her personality. The psychopathic personality features were reflected on the way the customer interacted with the probationary supervisor. In addition to this, the probationary supervisors felt that their ability to lessen the risk of renewed delinquency was weakened, if the customer had more psychopathic personality features than an average person

    Työstä palautuminen ja työn voimavarat keski-iässä

    No full text
    Työstä palautumisessa on kysymys työn vaatimusten ja työn voimavarojen keskinäisestä tasapainosta sekä työn ja vapaa-ajan välisestä suhteesta. Keski-iässä voimavarojen vahvistamisen kannalta on tärkeää saada käyttää työssä osaamistaan monipuolisesti ja kokea pystyvänsä vaikuttamaan omaan työhön. Kokemus työstä palautumisesta ja suhde omaa työtä kohtaan heijastavat työntekijän henkilökohtaisia käsityksiä, jotka ovat muodostuneet vuorovaikutuksessa sosiaalisen ympäristön ja yhteiskunnan arvojen kanssa. Tämän pro gradu -tutkielman tarkoituksena oli tarkastella keski-ikäisten työstä palautumista heidän työhön ja vapaa-aikaan liittyvien käsitystensä kautta. Tutkielman aineistona käytettiin Lapsesta aikuiseksi -pitkittäistutkimusta (JYLS; Jyväskylä Lognitudinal Study of Personality and Social Development), josta tässä tutkimuksessa hyödynnettiin 50-vuotiaana kerättyä aineistoa. Tämän tutkielman otos koostui 215 tutkimukseen osallistuneesta miehestä ja naisesta. Psykologista työstä palautumista mitattiin kyselyn avulla. Suhdetta työhön ja vastaajien näkemystä palautumista edistävistä asioista analysoitiin heidän avoimiin kysymyksiin antamiensa vastausten perusteella. Analysoinnin tuloksena muodostettiin kaksi uutta muuttujaa: työn voimavarat ja palautumista edistävät muutostoiveet. Tutkimusmenetelminä hyödynnettiin sisällönanalyysiä ja khiin neliö-testiä. Pohtiessaan suhdettaan työhön ja työstä palautumista keski-ikäiset nostivat esille useita työn voimavaratekijöitä: mielekkyys, osaaminen, sosiaalinen tuki, taitojen hyödyntäminen, itsenäisyys ja toimeentulo. Kolme neljäsosaa vastanneista toivoi elämäänsä palautumista lisääviä muutoksia seitsemällä alueella: vapaa-ajan lisääminen, vapaa-ajan toiminnan muuttaminen, mielen hyvinvointi ja tasapaino, aikaa ihmissuhteille, muutokset työ- tai perheolosuhteissa, terveyden- tai elämäntilanteen parantuminen sekä toimeentulon paraneminen tai määrittelemättömät muutokset. Ensisijaiseksi koettu työn voimavara ei ollut selkeästi yhteydessä palautumiseen. Muutostoiveen ja palautumisen välistä yhteyttä ei löytynyt. Johtopäätös: Työstä palautumiseen keski-iässä liittyvät oleellisesti työn voimavarat, jotka koetaan yksilöllisesti. Työn mielekkyys on erityisesti keski-ikäisille tärkeä työn voimavara

    Zebrafish as a Genetic Model to Study Tuberculosis

    Get PDF
    Tuberkuloosi on yhä maailmanlaajuinen terveysongelma, sillä joka vuosi siihen sairastuu 10 miljoonaa ihmistä ja yli miljoona kuolee. Tuberkuloosin aiheuttaa Mycobacterium tuberculosis, joka leviää ilmateiden kautta. Tartunta voi johtaa erilaisiin tuloksiin oireettomasta latentista tilasta aktiiviseen tautiin. Koska tämänhetkiset hoitomuodot ovat riittämättömiä, taistelussa tuberkuloosia vastaan tarvitaan uusia lähestymistapoja. On näytetty, että isännän geneettinen tausta vaikuttaa M. tuberculosis-tartunnan lopputulokseen. Siksi seulomalla isännän geneettisten vaihteluiden vaikutusta mykobakteeri-infektion taudinkulkuun saadaan uutta tietoa, joka on hyödyllistä uusia hoitomuotoja kehitettäessä. Tuberkuloositutkimusta on hidastanut hyvien eläinmallien puute. Hyvä malli jäljittelisi tuberkuloosin taudinkulkua, mutta olisi silti sujuva käyttää ja huomioisi myös eettiset näkökohdat. Seeprakala on kasvattanut suosiotaan immunologisena tutkimusmallina. On myös olemassa monenlaisia menetelmiä tuottaa seeprakalalle sekä satunnaisia että kohdennettuja mutaatioita. Seeprakalan luontainen taudinaiheuttaja, Mycobacterium marinum, on M. tuberculosis -bakteerin läheinen sukulainen. Se aiheuttaa seeprakalassa koko elimistöön vaikuttavan taudin. Erityisesti M. marinum -infektio seeprakalan poikasessa on vakiintunut tuberkuloosimalli. Väitöskirjatutkimuksessa selvitettiin aikuisen seeprakalan M. marinum -infektion käytettävyyttä tuberkuloosimallina. Tämän väitöskirjan ensimmäinen tavoite oli tutkia kyseisen infektion kulkua aikuisessa seeprakalassa histologisilla menetelmillä ja transkriptiotason tutkimuksella. Toinen tavoite oli tutkia interleukiini 10 (il10) -geenin tehtäviä M. marinum -infektion aikana. Lopullinen tavoite oli tehdä geneettinen seulonta ja tunnistaa isännän geenejä, joilla on tehtävä seeprakalan puolustautuessa mykobakteeri-infektiota vastaan. Päästäksemme ensimmäiseen tavoitteeseemme värjäsimme M. marinum -bakteerin pitkittäisistä kudosleikkeistä, jotka oli otettu aikuisesta seeprakalasta infektion eri vaiheissa. Tutkimus osoitti, että infektoitaessa pienellä M. marinum -annoksella granuloomien ja infektoituneiden elinten lukumäärä vakiintui neljännestä viikosta eteenpäin. Suurella annoksella infektoitaessa infektoituneiden elinten lukumäärä oli korkeampi ja granuloomien lukumäärä kasvoi infektion edetessä. Selvittääksemme M. marinum -bakteerin aiheuttamaa immuunivastetta tarkemmin teimme koko genomin kattavan transkriptomianalyysin munuaisnäytteistä seeprakalan pääasiallinen verta muodostava elin). Tutkimus osoitti, että 14 päivää infektoinnin jälkeen synnynnäiseen immuunivasteeseen liittyvät prosessit olivat rikastuneet positiivisesti säädeltyjen geenien joukossa, kun taas rasva-aineenvaihduntaan liittyvät prosessit olivat rikastuneet negatiivisesti säädeltyjen geenien joukossa. Käytimme il10e46 -mutanttiseeprakalalinjaa tutkiaksemme il10-geenin tehtäviä M. marinum infektion aikana seeprakalassa. Kyseisessä linjassa on mutaatio, joka aiheuttaa toimimattoman proteiinin syntymisen. Näytimme, että kyseisen mutaation suhteen homotsygootit kalat selvisivät villityypin kontrollikaloja paremmin M. marinum -infektion aikana ja kantoivat vähemmän bakteeria 8/9 viikon kuluttua pienellä bakteeriannoksella infektoimisesta. Nämä tulokset viittaavat parantuneeseen vastustuskykyyn M. marinum -bakteeria vastaan. il10e46/e46-mutanteilla tnfb ja il1b tulehdussytokiinien ilmentyminen oli lisäksi vähentynyt mahdollisesti kuvastaen infektion hitaampaa etenemistä. interferoni gamma 1 -geenin ilmentyminen oli lisääntynyt ja T-auttajasolu 1 (Th1) -vaste vahvistunut il10e46/e46-mutanteilla mahdollisesti selittäen parantuneen vastustuskyvyn. Suoritimme geneettisen seulonnan tunnistaaksemme geenejä, joilla on merkitystä aikuisen seeprakalan puolustautuessa mykobakteeri-infektiota vastaan. Tunnistimme 10 mutanttiseeprakalalinjaa, jotka selviytyivät huonommin ja yhden linjan, joka selviytyi paremmin pienen M. marinum -bakteeriannoksen aiheuttaman infektion aikana. Herkin linja, jonka tunnistimme, mutant463, kantoi 14 päivää infektoinnin jälkeen merkittävästi enemmän bakteeria verrattuna villityypin kaloihin. Tämä viittaa ennemmin heikentyneeseen vastustuskykyyn kuin heikentyneeseen sietokykyyn M. marinum -bakteeria kohtaan. Teimme myös mutant463-linjalle transkriptomianalyysin. Tulokset osoittivat, että mutant463-seeprakaloilla oli 27 geenin ilmentyminen heikentynyt munuaissoluissa villityypin kaloihin verrattuna 14 päivää infektoinnin jälkeen. Näiden geenien joukossa on seitsemän geeniä, joilla on tunnettu tai ennustettu immunologinen tehtävä. Ensimmäisessä osatyössä näytimme, että seeprakalan M. marinum -infektion histologiset piirteet muistuttavat tuberkuloosin piirteitä. Toisen osatyön tulokset il10- geenin tehtävistä sopivat yhteen aiemman kirjallisuuden kanssa, sillä ne korostavat Th1-vasteen osuutta vastustuskyvyssä mykobakteeria kohtaan. Nämä tulokset vahvistavat käyttämäämme tuberkuloosimallia. Lisäksi kolmannessa osatyössä tunnistimme geenejä, joilla on mahdollisesti tehtävä immuunipuolustuksessa mykobakteeri-infektiota vastaan. Näiden geenien tehtävien varmentamiseksi ja tarkentamiseksi on tarpeen tehdä lisätutkimuksia.Tuberculosis is still a major global health issue, with 10 million new cases and over one million casualties each year. Tuberculosis is caused by M. tuberculosis, which spreads via airways. This infection may result in a wide spectrum of outcomes, from an asymptomatic latent state to active disease. Due to the insufficiency of current treatments, new approaches to combat tuberculosis are needed. Host genetics has been shown to affect the outcome of M. tuberculosis infection. Therefore, screening the effect of different genetic variations of the host on the progression of mycobacterial infection provides information useful for developing new treatments. Moreover, the research on tuberculosis has been impeded by the lack of good animal models that mimic the progression of tuberculosis and are still feasible to use whilst meeting ethical challenges. The zebrafish has become more and more popular as an immunological research model. There are various tools available to carry out both forward and reverse genetic modifications in the zebrafish. Moreover, Mycobacterium marinum is a close relative of M. tuberculosis and a natural zebrafish pathogen. It causes a systemic infection in zebrafish. The M. marinum infection in zebrafish larvae is an especially well-established tuberculosis model. Thus our group considered the M. marinum infection in adult zebrafish as an advantageous tuberculosis model. The first aim of this thesis was to study the progression of M. marinum infection in adult zebrafish with histological methods and transcriptional analysis. The second aim was to study the role of interleukin 10 (il10) during this infection. The final aim was to perform a forward genetic screen to identify host genes having a role in the defense against mycobacterial infection in zebrafish. To reach the first aim, we used Ziehl-Neelsen staining to identify M. marinum in longitudinal tissue sections taken from adult zebrafish at different time-points of the infection. Importantly, analysis showed that in low-dose M. marinum infection, the number of granulomas and affected organs remained stable from four weeks post infection onwards, whereas in a high-dose infection the number of affected organs was higher and granuloma numbers kept rising along the course of infection. To further characterize the immune response to M. marinum, we did a whole genome- level transcriptome analysis from the kidney (the main hematopoietic organ of fish) samples. Analysis revealed that at 14 days post infection (dpi), innate immune response related processes were enriched among the upregulated genes and many lipid metabolism-related processes were enriched among the downregulated genes. To study the role of il10 during M. marinum infection in zebrafish, we used a mutant zebrafish line, il10e46, having a non-sense mutation resulting in a truncated protein product. We showed that these homozygous mutated fish had improved survival during M. marinum infection compared to wild type (WT) control fish and decreased bacterial burden at 8/9 weeks post low-dose infection, indicating improved resistance against M. marinum. In addition, il10e46/e46 mutants had decreased expression of the pro-inflammatory cytokines tnfb and il1b possibly reflecting a slower progression of infection. Most importantly however, il10e46/e46 mutants showed improved interferon gamma 1 (ifng1) expression and a shift towards a T helper 1 (Th1) cell response, which provides a potential explanation for the improved resistance. In order to identify genes participating in the immune defense against mycobacterial infection in adult zebrafish, we performed a forward genetic screen. We identified ten mutant zebrafish lines with impaired survival and one line with improved survival following low-dose infection with M. marinum. The most susceptible line, mutant463, showed a significantly higher bacterial burden compared to WT control fish at 14 dpi, indicating impaired resistance rather than tolerance against M. marinum. We also included mutant463 in the transcriptome analysis we performed. The results showed impaired expression of 27 genes in zebrafish kidney cells at 14 dpi compared to WT. These included seven genes with known or predicted immunological roles. In the first original publication, we showed that the histological features of M. marinum infection in adult zebrafish are similar to tuberculosis. Results from the experiments with il10 mutants in the second original publication are in line with earlier literature highlighting the role of the Th1 response in resistance against mycobacterial infection. This further validates the feasibility of our model in studying tuberculosis infection. Moreover, in the third original communication we found genes potentially required for defense against mycobacterial infection. Further studies are warranted to confirm and characterize the roles of these genes in more detail
    corecore