Genetic susceptibility to asbestos and tobacco smoke related non-malignant pleuropulmonary changes

Both tobacco smoke and asbestos fibers enter the body mainly by inhalation. In the lungs, they may evoke oxidative stress, alter the protease-antiprotease balance, induce innate and adaptive immune responses, and create persistent inflammation leading eventually to lung injury. The type and severity of lung injury induced by foreign compounds varies greatly between individuals, even with similar exposure history. These differences are believed to originate from the complex interplay between genetic, epigenetic, environmental, and life course factors. In this thesis, the roles of several genes encoding proteins involved in xenobiotic metabolism (EPHX1, GSTM1, GSTM3, GSTP1, GSTT1, and NAT2), protease-antiprotease balance (MMP1, MMP9, MMP12, SERPINE2, and TIMP2), innate immunity (NLRP3 and CARD8), and inflammation (TNF, TGFB1, and GC) were studied in the development of asbestos and tobacco smoke exposure related nonmalignant pleural and pulmonary changes, peripheral obstruction, and impairment of pulmonary diffusing capacity in two clinically and radiologically examined cohorts of Finnish construction workers. The results indicate that polymorphisms of xenobiotic metabolizing genes are potential modifiers of the risk of developing pleural and pulmonary changes related to asbestos and tobacco smoke exposures. The most convincing evidence came from GSTT1; the deletion of this gene was significantly associated with several types of changes in the whole study population and in both of the study cohorts separately. In addition, certain genotype in GSTM3 gene was associated with lowered pulmonary function. Furthermore, gene polymorphisms in metalloproteinase MMP9, metalloproteinase inhibitor TIMP2, and inflammatory cytokines TNF and TGFB1 were associated with different emphysema subtypes and/or lung function. Together with the finding that certain genotypes of the serine protease inhibitor gene SERPINE2 predispose to panlobular emphysema, they imply that polymorphisms of genes involved in protease-antiprotease balance likely contribute to the development of pulmonary emphysema and bronchial obstruction, and different molecular mechanisms may explain the development of different emphysema subtypes. The present results also indicate that genetic variation in innate immunity related genes might have an important role in coping with asbestos exposure. One finding supporting this view was the association between interstitial lung fibrosis and polymorphism of NLRP3, an essential component of the NLRP3 inflammasome complex. Polymorphism in another member of the complex, CARD8, was associated with the greatest thickness of pleural plaques. In conclusion, the results of this thesis work show that genetic variation is an important modifier of the risks for developing non-malignant lung diseases related to external exposures. The present findings may also help to clarify the molecular mechanisms behind these diseases, expediting their prevention and the development of more efficient therapies.Sekä asbestikuidut että tupakansavu kulkeutuvat elimistöön lähinnä hengityselimistön kautta. Keuhkoissa ne voivat aiheuttaa reaktiivisten happiyhdisteiden, sytokiinien ja muiden tekijöiden välittämän tulehdustilan, sekä johtaa tukikudosten hallitsemattomaan tuhoutumiseen ja erilaisiin keuhkosairauksiin. Perinnöllisten tekijöiden uskotaan yhdessä ympäristön altisteiden ja muiden elämäntapahtumien kanssa muokkaavan riskiä erilaisten keuhkomuutosten kehittymiselle ja vaikeusasteelle. Tässä väitöskirjatyössä tutkittiin useiden vierasaineiden muokkaamiseen (EPHX1, GSTM1, GSTM3, GSTP1, GSTT1 ja NAT2), luonnolliseen immuniteettiin (NLRP3 ja CARD8), tulehdukseen (TNF, TGFB1 ja GC), ja tukikudosten hajottamiseen (MMP1, MMP9, MMP12, SERPINE2 ja TIMP2) liittyvien proteiinien geenien monimuotoisuuden merkitystä hyvänlaatuisten keuhkomuutosten synnyssä. Potilasaineisto koostui kahdesta otoksesta suomalaisia asbestille ja tupakansavulle altistuneita rakennustyöntekijöitä, joille oli tehty huolelliset kliiniset ja radiologiset tutkimukset. Tulokset osoittavat, että vierasaineiden muokkaamiseen osallistuvien proteiinien perinnöllisellä muuntelulla on vaikutusta asbesti- ja tupakka-altistumiseen liittyvien hyvänlaatuisten keuhkomuutosten kehittymiseen. Tärkeä tätä näkemystä tukeva löydös liittyy GSTT1 entsyymiin, jonka geenipuutoksen havaittiin altistavan sekä vaikealle keuhkokudoksen fibroosille ja emfyseemalle että kaasujenvaihtokapasiteetin alenemiselle. Lisäksi GSTM3 entsyymin geenin tietyn muodon havaittiin olevan yhteydessä alentuneeseen keuhkotoimintaan. Löydösten perusteella myös luonnolliseen immuniteettiin liittyvillä proteiineilla ja geeneillä saattaa olla tärkeä rooli asbestialtistuksen aiheuttaman vasteen kehittymisessä. Tätä tukee havainto inflammasomikompleksin keskeisen osan, NLRP3:n geenimuodon yhteydestä keuhkokudoksen fibroosiin. Toisen kompleksin osan, CARD8:n geenin tietty muoto taas liitettiin keuhkopussin plakkien paksuuteen. Eri emfyseematyyppien ja keuhkotoiminnan häiriöiden kehittymiseen liittyviä muotoja löydettiin lisäksi useista tukikudoksen hajottamiseen liittyvien proteiinien (SERPINE2, MMP9 ja TIMP2) ja sytokiinien (TNF ja TGFB1) geeneistä. Esimerkiksi proteiinien hajottamista rajoittavan SERPINE2:n tietty geenimuoto liitettiin panlobulaariseen emfyseemaan ja proteiineja hajottavan MMP9:n ja tulehdussytokiini TGFB1:n geenit sentrilobulaariseen emfyseemaan. Nämä havainnot tukevat näkemystä, jonka mukaan tukikudosten hajottaminen liittyy keskeisesti hyvänlaatuisten keuhkomuutosten kehittymiseen tupakansavulle altistuneilla, ja lisäksi ne selventävät rakenteellisesti erilaisten emfyseematyyppien syntymiseen johtavia tekijöitä. Tämän väitöskirjatyön tulosten perusteella geneettisellä muuntelulla on tärkeä rooli hyvänlaatuisten keuhkomuutosten kehittymisessä asbestille ja tupakansavulle altistuneiden keskuudessa. Tulokset selventävät myös keuhkomuutosten syntyyn johtavia molekulaarisia mekanismeja, mikä auttaa edistämään näiden sairauksien ehkäisemistä ja tehokkaampien hoitomuotojen kehittämistä

"Kun on sairas, sitten minä puhun sairaudesta". Neljän afaattisen puhujan kertomuksia aivoverenkiertohäiriöstä elämäntarinan muuttajana.

Aivoverenkiertohäiriöt ovat laajaa väestönosaa koskettava, vaikeaa invaliditeettia aiheuttava sairaus. Afaattinen oirekuva on tyypillisesti seurausta aivoverenkiertohäiriöstä. Perinteisesti afasiaa on tutkittu lääketieteellisillä tai lingvistisillä mittareilla. Narratiivinen näkökulma keskittyy ihmisen tuottaman kertomuksen sisällön tutkimiseen lähtökohtanaan se, että jokaisella ihmisellä on elämäkerrallinen tarina joka on mahdollista tuoda esiin tutkimuksen kohteeksi. Ihmisen yksilöllisestä elämäntarinasta saatava subjektiivinen tieto tuo uutta, arvokasta ja kokemusperäistä näkökulmaa perinteisesti objektiivisin menetelmin lähestyttyihin aiheisiin. Tämän tutkimuksen tarkoituksena oli tarkastella afaattisten puhujien omaan kokemukseen perustuvia kertomuksia aivoverenkiertohäiriöön sairastumisesta ja sen vaikutuksesta elämän kulkuun. Aineisto kerättiin Pirkanmaan AVH-yhdistyksen kautta neljältä afaattiselta henkilöltä kahdenkeskisillä haastatteluilla. Afaattiset puhujat saivat kertoa omin sanoin elämästään ennen sairastumista, kuvailla sairastumistilannetta sekä kertoa, millaista elämä on ollut sairastumisen jälkeen. Haastattelut äänitettiin, litteroitiin ja analysoitiin sisällöstä saadun informaation perusteella. Afaattisten puhujien kertomuksissa oli havaittavissa viisi toisilleen yhteistä teemaa: kokemus sairastumisesta, toimintakyky ja sen muutos, kokemus itsestä, sosiaaliset suhteet sekä kokemus afasiasta. Näiden yhteisten teemojen sisällä haastateltujen kertomussisältöjä väritti ennen kaikkea yksilöllisyys ja ainutlaatuisuus. Narratiiveille tyypilliset sävymaailmat ja elämäntarinalliset projektit olivat myös henkilökohtaisia. Aivoverenkiertohäiriöön sairastuminen ja sen seurauksena tullut afaattinen oirekuva ei muokannut sairastuneiden elämän etenemistä identtiseksi. Yhteisestä kokemuksesta, eli sairastumisesta, huolimatta afaattisten puhujien kuvaukset elämänmuutoksen herättämistä kokemuksista vaihtelivat runsaasti. Afasiaa tutkittaessa ja afasiakuntoutusta suunniteltaessa on tärkeää huomioida sairastumisen ja afasian kokemuksen yksilöllisyys. Afaattisen puhujan on olennaista olla oman kuntoutuksensa aktiivinen toimija, jolla on mahdollisuus vaikuttaa kuntoutuksen sisältöön ja etenemiseen. Oman elämäntarinan jakaminen ja itselle tapahtuneista elämää mullistaneista asioista kertominen on terapeuttinen kokemus, joka tukee tapahtuneen jäsentämistä. Myös terveydenhuollon ammattihenkilöstö hyötyy kokemusperäisen tiedon huomioimisesta kuntoutuksen suunnittelussa ja toteuttamisessa. Tässä voidaan hyödyntää esimerkiksi edellä mainittuja kertomusten yhteisiä teemoja. Puheterapeutilla on merkittävä rooli afaattisen puhujan elämäntarinallisen katkoksen täyttämisessä, sairastumisen kriisin käsittelyssä ja elämän uuden suunnan löytämisessä. Terveydenhuollon ammattihenkilön ja asiakkaan yhteistyö ja molempien asiantuntijuuden huomioonottaminen kuntoutustoiminnassa on tärkeä piirre asiakaslähtöisessä kuntoutustyössä

Response of Deep Subsurface Microbial Community to Different Carbon Sources and Electron Acceptors during similar to 2 months Incubation in Microcosms

Acetate plays a key role as electron donor and acceptor and serves as carbon source in oligotrophic deep subsurface environments. It can be produced from inorganic carbon by acetogenic microbes or through breakdown of more complex organic matter. Acetate is an important molecule for sulfate reducers that are substantially present in several deep bedrock environments. Aceticlastic methanogens use acetate as an electron donor and/or a carbon source. The goal of this study was to shed light on carbon cycling and competition in microbial communities in fracture fluids of Finnish crystalline bedrock groundwater system. Fracture fluid was anaerobically collected from a fracture zone at 967 m depth of the Outokumpu Deep Drill Hole and amended with acetate, acetate + sulfate, sulfate only or left unamended as a control and incubated up to 68 days. The headspace atmosphere of microcosms consisted of 80% hydrogen and 20% CO2. We studied the changes in the microbial communities with community fingerprinting technique as well as high-throughput 16S rRNA gene amplicon sequencing. The amended microcosms hosted more diverse bacterial communities compared to the intrinsic fracture zone community and the control treatment without amendments. The majority of the bacterial populations enriched with acetate belonged to clostridial hydrogenotrophic thiosulfate reducers and Alphaproteobacteria affiliating with groups earlier found from subsurface and groundwater environments. We detected a slight increase in the number of sulfate reducers after the 68 days of incubation. The microbial community changed significantly during the experiment, but increase in specifically acetate-cycling microbial groups was not observed.Peer reviewe

The Impact of Vanilla and Lemon Aromas on Sensory Perception in Plant-Based Yogurts Measured with Static and Dynamic Methods

The application of cross-modal interaction is a potential strategy to tackle the challenges related to poor sensory properties, such as thin mouthfeel, in plant-based yogurts. Thus, we aim to study the influence of aroma compounds possibly congruent with sweetness on the perceived sensory profile. Descriptive analysis and temporal dominance of sensations (n = 10 × 4) with a trained panel were conducted with and without a nose clip. One unflavored sample and samples flavored with either lemon or vanilla aromas were included (vanilla; 0.05%; 0.1%; lemon: 0.025%; 0.05%). Odor intensity, thick, sticky, and melting sensation, sweetness, and grain-like flavor were evaluated on an unstructured 10-cm line scale with anchors and reference samples. The results demonstrate how vanilla and lemon aromas suppressed grain-like flavor and enhanced odor intensity and sweetness. The following order was detected among samples in perceived sweetness intensity: unflavored < lemon < vanilla. The two sessions with and without nose clip differed statistically in sweetness, highlighting that the aromas impacted the perceived sweetness but not the mouthfeel in vanilla samples. The study suggests that congruent aromas could modify the perceived sweetness in plant-based yogurts; however, aroma or perceived sweetness does not impact the mouthfeel in plant-based yogurts. While the odor–taste interaction in such products is evident, the study highlights that aroma compounds alone do not modify mouthfeel

INCORPORATING EVIDENCE-BASED REHABILITATION INTO CLINICAL PRACTICE GUIDELINES

Objective: Rehabilitation is often neglected in clinical practice guidelines, even when there is evidence for its effectiveness. The Current Rehabilitation development project, documented in this article, aimed to develop processes and structures to incorporate evidence and good practice on rehabilitation and functional capacity into the Finnish national Current Care Guidelines. Design: Descriptive assessment. Methods: The 3-year Current Rehabilitation development project was launched in 2012. It began with an assessment of existing rehabilitation evidence on the Current Care Guideline database and a query to Finnish rehabilitation experts. The project group developed and compiled tools for Current Care editors and guideline panels. The editorial team continued to monitor changes in rehabilitation evidence in the guidelines. Results: During the years 2012-2014, a total of 54 guidelines were published, and rehabilitation was incorporated into 31 of them. The number of rehabilitation-related evidence summaries increased from 49 to 164. During the next 3 years an additional 41 guidelines were published. Rehabilitation was incorporated to 24 of them, and the number of rehabilitation-related evidence summaries increased from 78 to 136. Conclusion: The level of evidence criteria used for rehabilitative interventions were the same as for symptomatic or curative interventions. Evidence showing the effectiveness of rehabilitation increased substantially during the project.Peer reviewe

Rapid Reactivation of Deep Subsurface Microbes in the Presence of C-1 Compounds

Microorganisms in the deep biosphere are believed to conduct little metabolic activity due to low nutrient availability in these environments. However, destructive penetration to long-isolated bedrock environments during construction of underground waste repositories can lead to increased nutrient availability and potentially affect the long-term stability of the repository systems, Here, we studied how microorganisms present in fracture fluid from a depth of 500 m in Outokumpu, Finland, respond to simple carbon compounds (C-1 compounds) in the presence or absence of sulphate as an electron acceptor. C-1 compounds such as methane and methanol are important intermediates in the deep subsurface carbon cycle, and electron acceptors such as sulphate are critical components of oxidation processes. Fracture fluid samples were incubated in vitro with either methane or methanol in the presence or absence of sulphate as an electron acceptor. Metabolic response was measured by staining the microbial cells with fluorescent dyes that indicate metabolic activity and transcriptional response with RT-qPCR. Our results show that deep subsurface microbes exist in dormant states but rapidly reactivate their transcription and respiration systems in the presence of C-1 substrates, particularly methane. Microbial activity was further enhanced by the addition of sulphate as an electron acceptor. Sulphate- and nitrate-reducing microbes were particularly responsive to the addition of C-1 compounds and sulphate. These taxa are common in deep biosphere environments and may be affected by conditions disturbed by bedrock intrusion, as from drilling and excavation for long-term storage of hazardous waste.Peer reviewe

The Impact of Vanilla and Lemon Aromas on Sensory Perception in Plant-Based Yogurts Measured with Static and Dynamic Methods

The application of cross-modal interaction is a potential strategy to tackle the challenges related to poor sensory properties, such as thin mouthfeel, in plant-based yogurts. Thus, we aim to study the influence of aroma compounds possibly congruent with sweetness on the perceived sensory profile. Descriptive analysis and temporal dominance of sensations (n = 10 × 4) with a trained panel were conducted with and without a nose clip. One unflavored sample and samples flavored with either lemon or vanilla aromas were included (vanilla; 0.05%; 0.1%; lemon: 0.025%; 0.05%). Odor intensity, thick, sticky, and melting sensation, sweetness, and grain-like flavor were evaluated on an unstructured 10-cm line scale with anchors and reference samples. The results demonstrate how vanilla and lemon aromas suppressed grain-like flavor and enhanced odor intensity and sweetness. The following order was detected among samples in perceived sweetness intensity: unflavored < lemon < vanilla. The two sessions with and without nose clip differed statistically in sweetness, highlighting that the aromas impacted the perceived sweetness but not the mouthfeel in vanilla samples. The study suggests that congruent aromas could modify the perceived sweetness in plant-based yogurts; however, aroma or perceived sweetness does not impact the mouthfeel in plant-based yogurts. While the odor–taste interaction in such products is evident, the study highlights that aroma compounds alone do not modify mouthfeel

Epilithic Microbial Community Functionality in Deep Oligotrophic Continental Bedrock

The deep terrestrial biosphere hosts vast sessile rock surface communities and biofilms, but thus far, mostly planktic communities have been studied. We enriched deep subsurface microbial communities on mica schist in microcosms containing bedrock groundwater from the depth of 500 m from Outokumpu, Finland. The biofilms were visualized using scanning electron microscopy, revealing numerous different microbial cell morphologies and attachment strategies on the mica schist surface, e.g., bacteria with outer membrane vesicle-like structures, hair-like extracellular extensions, and long tubular cell structures expanding over hundreds of micrometers over mica schist surfaces. Bacterial communities were analyzed with amplicon sequencing showing that Pseudomonas, Desulfosporosinus, Hydrogenophaga, and Brevundimonas genera dominated communities after 8-40 months of incubation. A total of 21 metagenome assembled genomes from sessile rock surface metagenomes identified genes involved in biofilm formation, as well as a wide variety of metabolic traits indicating a high degree of environmental adaptivity to oligotrophic environment and potential for shifting between multiple energy or carbon sources. In addition, we detected ubiquitous organic carbon oxidation and capacity for arsenate and selenate reduction within our rocky MAGs. Our results agree with the previously suggested interaction between the deep subsurface microbial communities and the rock surfaces, and that this interaction could be crucial for sustaining life in the harsh anoxic and oligotrophic deep subsurface of crystalline bedrock environment.Peer reviewe

Nitrogen release in decomposition of boreal mor and peat as affected by enchytraeid worms

Peer reviewe