Rasvakudoksen aineenvaihdunta lihavuudessa

ABSTRACT Obesity is a major health problem and is increasing rapidly both in developed and developing countries worldwide. Treatment of obesity is difficult, expensive and often fails. Obesity increases the likelihood for many diseases, such as type 2 diabetes, coronary heart disease, metabolic syndrome, hyperlipidemia and some types of cancer. We still lack a meaningful understanding of the factors behind this complex disease and therefore any proper means to battle it. Only lately, adipose tissue and especially its mitochondria have been recognized as important contributors to whole-body energy balance and the development of obesity. This thesis investigates the biological pathways in adipose tissue that lead to the development of metabolic complications in early-onset obesity in young healthy twins. The aim was to study how acquired obesity affects adipose tissue and adipocyte function and how these link to whole body metabolism. The rare weight-discordant monozygotic (MZ) co-twin setting used in this study, is uniquely positioned to disentangle acquired and inherited metabolic pathways to disease in obesity. MZ twin pairs discordant for obesity enable controlling for genetic background, age, sex and early environmental influences. As MZ twins are fully identical at the level of genome sequence, the observed differences between the co-twins can be assumed to be acquired. This is a major strength of our study regarding a polygenic and multifactorial trait as obesity. Adipocyte hypertrophy in adipose tissue is one of the main features of obesity. The first study of the thesis investigated adipose tissue hypertrophy and hyperplasia in acquired obesity and its associations to whole body metabolism and gene expression pathways of the adipose tissue. We showed a high within-pair resemblance in adipocyte size and number suggesting that the adipocyte phenotype is genetic or due to shared environmental factors. Hypertrophy (large size) and low number of adipocytes in acquired obesity was related to metabolic dysfunction in obesity and associated with the disturbances in mitochondrial function and with increased cell death within the adipose tissue. In the second study we investigated how transcriptional pathways of subcutaneous adipose tissue and the liver fat associate with metabolically healthy obesity a phenomenon where some of the obese individuals stay free from metabolic complications usually associated with weight gain. We showed for the first time in twins that the amount of liver fat is a key clinical determinant of metabolic health and that low liver fat associates with maintenance of high mitochondrial transcription and lack of inflammation in subcutaneous adipose tissue. In further investigations we addressed mitochondrial biogenesis and oxidative metabolism in detail. The third and fourth studies concentrated on mitochondrial biogenesis in adipose tissue and in adipocytes, respectively. The novel findings in the third study were that obesity is related to reduced mitochondrial mass and oxidative metabolic activity in subcutaneous adipose tissue, both in the nuclear and in the mitochondrial transcription level, as well as decreased protein levels in the OXPHOS system, especially OXPHOS complex subunits I and IV. The mitochondrial dysfunction paralleled whole body insulin resistance and low-grade systemic inflammation. Remarkably, these changes were seen already at the early stages of acquired obesity. In the fourth study, we showed that the global downregulation of mitochondrial transcriptional signature in acquired obesity originates at least partly from the adipocyte cells of adipose tissue. This research resulted in better understanding of the factors behind metabolic complications in acquired obesity. Development of obesity seems to associate with mitochondrial dysfunction in adipose tissue. The decreased function of mitochondria was evident at the level of both nuclear gene expression level and mitochondrial gene expression, as well as mitochondrial protein levels. These changes associated with metabolic disturbances of obesity. With rare obesity-discordant MZ twins we have been able to show that the changes are not genetic but result from acquired factors. However, as there was a remarkable similarity of adipocyte size and especially number between the co-twins, responses to obesity may have a partial genetic basis. With low capacity to adipocyte hypertrophy, excess fat may accumulate to liver and other tissues. Liver fat content is a clear determinant of metabolic health in acquired obesity. The results of my thesis as a whole suggest that obesity-associated metabolic disturbances might be halted by improving mitochondrial number and/or activity in adipose tissue.TIIVISTELMÄ Lihavuus on nykyisin yksi merkittävimpiä kehittyneiden maiden kansanterveydellisiä ongelmia ja lisääntymässä nopeasti. Lihavuuden lääketieteellinen hoito on vaikeaa, kallista ja epäonnistuu usein. Lihavuus aiheuttaa metabolisia häiriöitä, kuten insuliiniresistenssiä, tyypin 2 diabetesta, sydänsairauksia, metabolista syndroomaa ja veren kohonneita rasva-arvoja. Lihavuuden syistä ei ole vielä kokonaisvaltaista ymmärrystä. Vasta viime vuosina on huomattu, että rasvakudos ja erityisesti sen mitokondrioiden eli solujen energiatehtaiden toiminta on keskeisessä asemassa koko kehon aineenvaihdunnassa ja lihavuuden kehittymisessä. Tämä väitöskirjatyö käsittelee nuorten terveiden kaksosten rasvakudoksen varhaisia aineenvaihduntamuutoksia ja insuliiniresistenssiä hankitussa lihavuudessa. Mielenkiinnon kohteena oli, kuinka lihavuus vaikuttaa rasvakudoksen ja rasvasolujen toimintaan ja koko kehon aineenvaihduntaan. Näitä muutoksia tutkittiin harvinaisten identtisten mutta eripainoisten kaksosten avulla. Tarkoitukseen käytetty suomalainen kaksosaineisto on kansainvälisesti merkittävä ja ainutlaatuinen. Kaksosasetelmassa voitiin ainutlaatuisesti kontrolloida geneettinen tausta, ikä, sukupuoli ja aikaiset rasvakudokseen vaikuttavat ympäristötekijät ja näin erottaa hankitut ja periytyvät syyt lihavuuden aiheuttamien ongelmien synnyssä. Lihavuudessa erityisesti rasvakudoksen solujen koko kasvaa. Ensimmäisessä väitöskirjan osatutkimuksessa selvitimme, miten rasvasolujen suuri koko yhdistyy rasvakudoksen geenien toimintaan ja koko kehon aineenvaihduntaan. Rasvasolujen lukumäärä kehossa näytti olevan geneettisesti säädelty. Rasvasolujen suuri koko ja kehon pieni rasvasolumäärä yhdistyivät metabolisiin ongelmiin ja geenireitteihin, jotka liittyivät heikentyneeseen mitokondrioiden toimintaan ja lisääntyneeseen rasvakudoksen solukuolemaan. Toisessa osatutkimuksessa selvitimme kehon rasvavarastojen ja rasvakudoksen geenireittien merkitystä metabolisesti terveillä lihavilla, joille ei näytä ilmaantuvan lihavuuteen liittyviä aineenvaihdunnan ongelmia. Havaitsimme, että maksan rasvamäärä voi olla kliininen merkki aineenvaihdunnan ongelmien kehittymisestä lihavuudessa. Matala maksan rasvapitoisuus ja metabolisesti terve lihavuus ilmiö olivat yhteydessä mitokondrioiden aktiivisuuteen ja vähäiseen rasvakudoksen tulehdukseen. Väitöskirjan kolmannessa ja neljännessä osatöissä tutkimme tarkemmin rasvakudoksen ja rasvasolujen mitokondrioiden toiminnan häiriötä lihavuudessa sekä mitokondrioiden toiminnan yhteyttä kehon aineenvaihduntamuutoksiin. Mitokondriot ovat rasvasolujen keskeisin elin. Ne ovat solun energiatehtaita, jotka tuottavat solun tarvitseman energian hapen välityksellä ja vastaavat muun muassa rasvahappojen poltosta ja monista aineenvaihdunnallisista tehtävistä. Mitokondrioilla on tumasta erillinen pieni genomi, joka koodaa 13:ta mitokondrion hengitysketjun proteiinia sekä niiden valmistamiseen tarvittavia molekyylejä. Kolmannessa väitöskirjatyössä näytimme, että hankittu lihavuus vähentää mitokondrioiden massaa ja hengitysketjun toimintaa rasvakudoksessa. Mitokondrioiden toiminnan vähentyminen oli näkyvissä niin tuman koodaamien mitokondriaalisten geenien ja niitä säätelevien geenien ilmentymisenä, mitokondrion omien geenien ilmentymisenä, kuin mitokondrion hengitysketjun proteiinien vähentyneinä määrinä. Näytimme myös ensimmäistä kertaa hengitysketjun komponenttien I ja IV vähentyneet määrät lihavuudessa. Mitokondrion huono toiminta yhdistyi aineenvaihdunnan ongelmiin, insuliiniresistenssiin ja tulehdusmerkkiaineiden suurentuneisiin pitoisuuksiin veressä. Sama mitokondrioiden toiminnan väheneminen ja sen yhteys kehon huonontuneeseen rasva- ja sokeriaineenvaihduntaan oli väitöskirjan neljännessä osatyössä nähtävissä rasvasoluissa. Huomattavaa oli, että muutokset mitokondrioiden toiminnassa ja kehon aineenvaihdunnassa olivat näkyvissä jo lihavuuden aikaisessa vaiheessa, nuorilla ja terveillä lihavilla kaksosilla. Lihavuuden kehittyminen näyttää olevan yhteydessä rasvakudoksen mitokondrioiden toiminnan häiriintymiseen. Häiriintynyt toiminta näyttäytyy sekä tuman koodaamien mitokondrioon liittyvien geenien ilmentymisen kuin mitokondrion omien geenien toiminnan ja rakenneosasten määrän vähenemisenä yhdistyen koko kehon insuliiniresistenssiin, tulehdukseen ja rasvakudoksen epäedullisiin aineenvaihdunnan muutoksiin. Harvinaisten identtisten mutta eripainoisten kaksosten avulla olemme voineet osoittaa, että muutokset geenien ilmenemisessä ja aineenvaihdunnassa johtuvat hankitusta lihavuudesta eivätkä geneettisistä tekijöistä. Geneettistä näyttää puolestaan olevan se, miten keho reagoi lihomiselle. Osa kaksosista kasvatti lihotessaan rasvasolun kokoa, toiset taas pystyivät lisäämään koon lisäksi rasvasolujensa määrää. Suuri rasvasolun koko ja vähäinen kapasiteetti lisätä niiden lukumäärää rasvakudoksessa näyttää aiheuttavan liian rasvan kertymistä maksaan ja muualle sisäelimiin. Maksan rasvapitoisuuden mukaan voidaan mahdollisesti erottaa ne lihavat, jotka ovat alttiita lihomisen aiheuttamille komplikaatioille ja insuliiniresistenssille. Väitöskirjani tuloksien perusteella lihavuuteen yhdistyviä metabolisia häiriöitä voidaan mahdollisesti estää lisäämällä ja parantamalla mitokondrioiden toimintaa rasvakudoksessa

Kaksosten hankinnainen lihavuus

Vertaisarvioitu. English summary.Vertailemalla harvinaisia identtisiä mutta eripainoisia kaksosia voidaan selvittää lihavuuden vaikutusta aineenvaihduntaan DNA-sekvenssin samankaltaisuudesta riippumatta. Hankinnainen lihavuus vaikuttaa epäedullisesti veren rasvoihin, hyytymistekijöiden pitoisuuksiin ja tulehdusvälittäjäaineisiin sekä huonontaa endoteelitoimintaa ja altistaa ateroskleroosille. Tutkimusten perusteella rasvakudos on keskeisessä asemassa siinä, miten lihavuuden havaitut haitalliset aineenvaihdunnan muutokset syntyvät. Hankinnainen lihavuus liittyy rasvakudoksessa mitokondriotoiminnan heikentymiseen ja lievään tulehdukseen sekä insuliiniresistenssiin. Nämä muutokset heikentävät rasvakudoksen laajenemiskapasiteettia, jolloin ylimääräinen rasva alkaa varastoitua muihin kudoksiin, kuten maksaan, haimaan ja lihakseen, ja aiheuttaa aineenvaihdunnan laaja-alaisen häiriötilan. Erityisesti maksaan kertyvä rasva näyttää määrittävän lihavuuden haitallista metaboliaa.Peer reviewe

Transglutaminases and Obesity in Humans: Association of F13A1 to Adipocyte Hypertrophy and Adipose Tissue Immune Response

Transglutaminases TG2 and FXIII-A have recently been linked to adipose tissue biology and obesity, however, human studies for TG family members in adipocytes have not been conducted. In this study, we investigated the association of TGM family members to acquired weight gain in a rare set of monozygotic (MZ) twins discordant for body weight, i.e., heavy–lean twin pairs. We report that F13A1 is the only TGM family member showing significantly altered, higher expression in adipose tissue of the heavier twin. Our previous work linked adipocyte F13A1 to increased weight, body fat mass, adipocyte size, and pro-inflammatory pathways. Here, we explored further the link of F13A1 to adipocyte size in the MZ twins via a previously conducted TWA study that was further mined for genes that specifically associate to hypertrophic adipocytes. We report that differential expression of F13A1 (ΔHeavy–Lean) associated with 47 genes which were linked via gene enrichment analysis to immune response, leucocyte and neutrophil activation, as well as cytokine response and signaling. Our work brings further support to the role of F13A1 in the human adipose tissue pathology, suggesting a role in the cascade that links hypertrophic adipocytes with inflammation

Cross-Sectional and Longitudinal Associations Between Quality of Parent–Child Interaction and Language Ability in Preschool-Age Children With Developmental Language Disorder

Publisher Copyright: © 2022 American Speech-Language-Hearing Association.Purpose: This study explores whether the quality of parent–child interaction is associated with language abilities cross-sectionally and longitudinally up to preschool-age among children with developmental language disorder (DLD). Method: Participants were 97 monolingual children with DLD and their parents from the Helsinki Longitudinal SLI study, HelSLI (baseline, age in years;months, M = 4;3, SD = 0;10), of which 71 pairs were followed longitudinally (age in years;months, M = 6;6, SD = 0;5). Video recordings from three play sessions were scored for child, parent, and dyadic behavior using Erickson’s sensitivity scale protocol and mutually responsive orientation at baseline. Children’s expressive and receptive language and language reasoning ability were assessed at baseline, and expressive and receptive language were assessed at follow-up. Results: At baseline, engaged child behavior, parent’s supportive guidance, and fluent and attuned dyadic behavior were associated with better receptive language ability, and engaged child behavior and dyadic synchrony were posi-tively associated with language reasoning ability in 3-to 6-year-olds. The child’s positive engagement and fluent and attuned dyadic behavior at baseline were associated with better expressive and receptive language abilities at follow-up in 6-to 7-year-olds, respectively. Conclusions: Fluent and attuned dyadic behavior is associated with better receptive language ability in preschool-age children. Parent behavior alone was not associated with language ability. A connected and mutually attuned parent– child relationship could be a protective factor for language development for children with DLD.Peer reviewe

Evaluation of the effect of donor weight on adipose stromal/stem cell characteristics by using weight-discordant monozygotic twin pairs

Background Adipose stromal/stem cells (ASCs) are promising candidates for future clinical applications. ASCs have regenerative capacity, low immunogenicity, and immunomodulatory ability. The success of future cell-based therapies depends on the appropriate selection of donors. Several factors, including age, sex, and body mass index (BMI), may influence ASC characteristics. Our aim was to investigate the effect of acquired weight on ASC characteristics under the same genetic background using ASCs derived from monozygotic (MZ) twin pairs. Methods ASCs were isolated from subcutaneous adipose tissue from five weight-discordant (WD, within-pair difference in BMI > 3 kg/m(2)) MZ twin pairs, with measured BMI and metabolic status. The ASC immunophenotype, proliferation and osteogenic and adipogenic differentiation capacity were studied. ASC immunogenicity, immunosuppression capacity and the expression of inflammation markers were investigated. ASC angiogenic potential was assessed in cocultures with endothelial cells. Results ASCs showed low immunogenicity, proliferation, and osteogenic differentiation capacity independent of weight among all donors. ASCs showed a mesenchymal stem cell-like immunophenotype; however, the expression of CD146 was significantly higher in leaner WD twins than in heavier cotwins. ASCs from heavier twins from WD pairs showed significantly greater adipogenic differentiation capacity and higher expression of TNF and lower angiogenic potential compared with their leaner cotwins. ASCs showed immunosuppressive capacity in direct cocultures; however, heavier WD twins showed stronger immunosuppressive capacity than leaner cotwins. Conclusions Our genetically matched data suggest that a higher weight of the donor may have some effect on ASC characteristics, especially on angiogenic and adipogenic potential, which should be considered when ASCs are used clinically.Peer reviewe

Preventing White Adipocyte Browning during Differentiation In Vitro : The Effect of Differentiation Protocols on Metabolic and Mitochondrial Phenotypes

Mitochondrial dysfunction in white adipose tissue is strongly associated with obesity and its metabolic complications, which are important health challenges worldwide. Human adipose-derived stromal/stem cells (hASCs) are a promising tool to investigate the underlying mechanisms of such mitochondrial dysfunction and to subsequently provide knowledge for the development of treatments for obesity-related pathologies. A substantial obstacle in using hASCs is that the key compounds for adipogenic differentiation in vitro increase mitochondrial uncoupling, biogenesis, and activity, which are the signature features of brown adipocytes, thus altering the white adipocyte phenotype towards brown-like cells. Additionally, commonly used protocols for hASC adipogenic differentiation exhibit high variation in their composition of media, and a systematic comparison of their effect on mitochondria is missing. Here, we compared the five widely used adipogenic differentiation protocols for their effect on metabolic and mitochondrial phenotypes to identify a protocol that enables in vitro differentiation of white adipocytes and can more faithfully recapitulate the white adipocyte phenotype observed in human adipose tissue. We developed a workflow that included functional assays and morphological analysis of mitochondria and lipid droplets. We observed that triiodothyronine- or indomethacin-containing media and commercially available adipogenic media induced browning during in vitro differentiation of white adipocytes. However, the differentiation protocol containing 1 mu M of the peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist rosiglitazone prevented the browning effect and would be proposed for adipogenic differentiation protocol for hASCs to induce a white adipocyte phenotype. Preserving the white adipocyte phenotype in vitro is a crucial step for the study of obesity and associated metabolic diseases, adipose tissue pathologies, such as lipodystrophies, possible therapeutic compounds, and basic adipose tissue physiology.Peer reviewe

Preventing White Adipocyte Browning during Differentiation In Vitro : The Effect of Differentiation Protocols on Metabolic and Mitochondrial Phenotypes

Mitochondrial dysfunction in white adipose tissue is strongly associated with obesity and its metabolic complications, which are important health challenges worldwide. Human adipose-derived stromal/stem cells (hASCs) are a promising tool to investigate the underlying mechanisms of such mitochondrial dysfunction and to subsequently provide knowledge for the development of treatments for obesity-related pathologies. A substantial obstacle in using hASCs is that the key compounds for adipogenic differentiation in vitro increase mitochondrial uncoupling, biogenesis, and activity, which are the signature features of brown adipocytes, thus altering the white adipocyte phenotype towards brown-like cells. Additionally, commonly used protocols for hASC adipogenic differentiation exhibit high variation in their composition of media, and a systematic comparison of their effect on mitochondria is missing. Here, we compared the five widely used adipogenic differentiation protocols for their effect on metabolic and mitochondrial phenotypes to identify a protocol that enables in vitro differentiation of white adipocytes and can more faithfully recapitulate the white adipocyte phenotype observed in human adipose tissue. We developed a workflow that included functional assays and morphological analysis of mitochondria and lipid droplets. We observed that triiodothyronine- or indomethacin-containing media and commercially available adipogenic media induced browning during in vitro differentiation of white adipocytes. However, the differentiation protocol containing 1 mu M of the peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist rosiglitazone prevented the browning effect and would be proposed for adipogenic differentiation protocol for hASCs to induce a white adipocyte phenotype. Preserving the white adipocyte phenotype in vitro is a crucial step for the study of obesity and associated metabolic diseases, adipose tissue pathologies, such as lipodystrophies, possible therapeutic compounds, and basic adipose tissue physiology.Peer reviewe

Mitochondria-related transcriptional signature is downregulated in adipocytes in obesity : a study of young healthy MZ twins

Low mitochondrial activity in adipose tissue is suggested to be an underlying factor in obesity and its metabolic complications. We aimed to find out whether mitochondrial measures are downregulated in obesity also in isolated adipocytes. We studied young adult monozygotic (MZ) twin pairs discordant (n = 14, intrapair difference Delta BMI ae 3 kg/m(2)) and concordant (n = 5, Delta BMI <3 kg/m(2)) for BMI, identified from ten birth cohorts of 22- to 36-year-old Finnish twins. Abdominal body fat distribution (MRI), liver fat content (magnetic resonance spectroscopy), insulin sensitivity (OGTT), high-sensitivity C-reactive protein, serum lipids and adipokines were measured. Subcutaneous abdominal adipose tissue biopsies were obtained to analyse the transcriptomics patterns of the isolated adipocytes as well as of the whole adipose tissue. Mitochondrial DNA transcript levels in adipocytes were measured by quantitative real-time PCR. Western blots of oxidative phosphorylation (OXPHOS) protein levels in adipocytes were performed in obese and lean unrelated individuals. The heavier (BMI 29.9 +/- 1.0 kg/m(2)) co-twins of the discordant twin pairs had more subcutaneous, intra-abdominal and liver fat and were more insulin resistant (p <0.01 for all measures) than the lighter (24.1 +/- 0.9 kg/m(2)) co-twins. Altogether, 2538 genes in adipocytes and 2135 in adipose tissue were significantly differentially expressed (nominal p <0.05) between the co-twins. Pathway analysis of these transcripts in both isolated adipocytes and adipose tissue revealed that the heavier co-twins displayed reduced expression of genes relating to mitochondrial pathways, a result that was replicated when analysing the pathways behind the most consistently downregulated genes in the heavier co-twins (in at least 12 out of 14 pairs). Consistently upregulated genes in adipocytes were related to inflammation. We confirmed that mitochondrial DNA transcript levels (12S RNA, 16S RNA, COX1, ND5, CYTB), expression of mitochondrial ribosomal protein transcripts and a major mitochondrial regulator PGC-1 alpha (also known as PPARGC1A) were reduced in the heavier co-twins' adipocytes (p <0.05). OXPHOS protein levels of complexes I and III in adipocytes were lower in obese than in lean individuals. Subcutaneous abdominal adipocytes in obesity show global expressional downregulation of oxidative pathways, mitochondrial transcripts and OXPHOS protein levels and upregulation of inflammatory pathways. The datasets analysed and generated during the current study are available in the figshare repository.Peer reviewe

Ammattikorkeakouluopettajien monialainen sosiaali- ja terveydenhuollon tiedonhallinnan osaaminen

The quick digital transformation (DT) in society has affected the development of service in health and social services strongly during the last five years. The digitalization has resulted in a change in the paradigm, which has required a strong reaction from education to respond to the needs of competence in working life. The students who graduate from a university of applied sciences must be provided with sufficient readiness to operate in working life and to cope with change. The precondition is that the educators of health and social care, business, service design and IT keep up with the development of digitalization. The purpose of this study was to evaluate the informatics competences of the educators at the universities of applied sciences with an emphasis on the operational environments of health and social services. The survey is a part of the SotePeda 24/7 project. The survey was sent to Finnish universities of applied sciences (22) participating in the project in April- May 2019. The survey form was based on national and international evidence-based information. The form included 12 fields of competence and their contents. 172 answers were obtained after three reminders. A factor analysis was conducted utilizing the maximum likelihood method and the result was 18 factors. The largest load factor was named as the information management and digitalization competence factor. This article discusses the informatics variables loaded for this factor in the survey. The correspondence and discriminant analyses conducted in the study showed the competences vary in different education fields. The biggest differences in informatics competence were found in the social services education field, whereas the competences of the educators of the health care education were good and extremely good more evenly. In other fields participating in the study there were big differences inside single education fields regarding the informatics competences of health and social services.Nopea yhteiskunnan digitaalinen muutos (Digital Transformation, DT) on vaikuttanut viimeisten viiden vuoden aikana vahvasti sosiaali- ja terveydenhuollon palvelukehitykseen. Digitalisaatio on synnyttänyt paradigman muutoksen, mihin koulutuksen on pitänyt vahvasti reagoida vastatakseen vaadittaviin työelämän osaamistarpeisiin. Ammattikorkeakoulusta valmistuvalle ammattilaiselle on koulutuksessa taattava riittävät valmiudet toimia työelämässä ja selviytyä muutoksesta. Edellytyksenä on, että sosiaali- ja terveysalan, liiketalouden, palvelumuotoilualan ja IT-alan opettajat hallitsevat digitalisaation kehityksen. Tutkimuksen tarkoituksena oli arvioida ammattikorkeakouluopettajien sosiaali- ja terveydenhuollon digitaalisessa toimintaympäristössä tarvittavaa tiedonhallinnan osaamista. Tutkimus on osa SotePeda 24/7 -hanketta. Hankkeessa mukana oleville Suomen ammattikorkeakouluille (22) lähetettiin huhti-toukokuussa 2019 kyselylomake, joka pohjautui kansalliseen ja kansainväliseen näyttöön perustuvaan tietoon. Lomakkeessa oli 12 osaamisaluetta sisältöineen. Vastauksia saatiin kolmen muistutuksen jälkeen 172. Aineisto analysoitiin faktorianalyysillä hyödyntäen maximum likelihood menetelmää, ja tuloksena saatiin 18 faktoria. Suurimman latauksen saanut faktori nimettiin tiedonhallinnan ja digitaalisuuden osaamisen faktoriksi. Tässä artikkelissa tarkastellaan kyselyssä tälle faktorille latautuneita tiedonhallinnan muuttujia. Korrespondenssianalyysit ja tarkentavat erotteluanalyysit osoittivat osaamisen eroavan eri koulutusaloilla. Sosiaalialalla tiedonhallinnan osaamisessa oli koulutusaloista isommat erot kuin terveysalan opettajilla, joiden osaaminen oli tasaisemmin hyvää ja erittäin hyvää. Sosiaali- ja terveydenhuollon tiedonhallinnan osaamisessa oli muilla tutkimukseen osallistuvilla aloilla isoja eroja oman koulutusalan sisällä

First trimester serum placental growth factor and hyperglycosylated human chorionic gonadotropin are associated with pre-eclampsia : a case control study

Background: To study whether maternal serum hyperglycosylated human chorionic gonadotropin (hCG-h) improves first trimester prediction of pre-eclampsia when combined with placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A) and maternal risk factors. Methods: Gestational-age-adjusted concentrations of hCG, hCG-h, PlGF and PAPP-A were analysed in serum samples by time-resolved immunofluorometric assays at 8-13 weeks of gestation. The case-control study included 98 women who developed pre-eclampsia, 25 who developed gestational hypertension, 41 normotensive women with small-for-gestational-age (SGA) infants and 177 controls. Results: Of 98 women with pre-eclampsia, 24 women developed preterm pre-eclampsia (diagnosis <37 weeks of gestation) and 13 of them had early-onset pre-eclampsia (diagnosis <34 weeks of gestation). They had lower concentrations of PlGF, PAPP-A and proportion of hCG-h to hCG (% hCG-h) than controls. In receiver-operating characteristics (ROC) curve analysis, the area under the curve (AUC) for the combination of PlGF, PAPP-A, % hCG-h, nulliparity and mean arterial blood pressure was 0.805 (95% confidence interval, CI, 0.699-0.912) for preterm pre-eclampsia and 0.870 (95% CI 0.750-0.988) for early-onset pre-eclampsia. Without % hCG-h the AUC values were 0.756 (95% CI 0.651-0.861) and 0.810 (95% CI 0.682-0.938) respectively. For prediction of gestational hypertension, the AUC for % hCG-h was 0.708 (95% CI 0.608-0.808), but for other markers the AUC values were not significant. None of the AUC values were significant for the prediction of SGA infants in normotensive women. Conclusions: First trimester maternal serum % hCG-h tended to improve prediction of preterm and early-onset pre-eclampsia when combined with PlGF, PAPP-A and maternal risk factors.Peer reviewe