Varhaiskasvatuksen erityisopettajien puhetta tukevien ja korvaavien kommunikointimenetelmien käyttö

Tiivistelmä. Puheen ja kielen kehityksen haasteet ovat yleisiä lapsuudessa esiintyviä ongelmia, joihin varhaiskasvatuksessa voidaan puuttua monin eri keinoin. Tällaisia keinoja ovat puhetta tukevat ja korvaavat kommunikointimenetelmät eli AAC-menetelmät [Augmentative and Alternative Communication], joiden avulla voidaan kehittää lapsen kommunikointia, puheen ymmärtämistä, tuottamista ja vastaanottamista. Varhaiskasvatuksen erityisopettajilla on tärkeä tehtävä tuoda AAC-menetelmät tukea tarvitsevien lasten, henkilöstön ja muiden lasten käyttöön. Tutkimustieto AAC-menetelmistä on rajallista, ja tästä syystä Pro gradu -tutkielmamme tavoitteena on tutkia, millaisia AAC-menetelmiä varhaiskasvatuksen erityisopettajat käyttävät työssään, sekä millä tavoin he näitä menetelmiä ohjaavat tukea tarvitsevien lasten, muiden lasten sekä henkilöstön käyttöön. Tarkoituksena on myös selvittää, millaisia merkityksiä varhaiskasvatuksen erityisopettajat näkevät AAC-menetelmillä olevan lapsen kommunikoinnille ja kielen kehitykselle. Kartoitamme myös varhaiskasvatuksen erityisopettajien saamaa koulutusta AACmenetelmistä sekä mahdollisia lisäkoulutustoiveita. Tutkimuksemme toteutettiin laadullisena tutkimuksena, jonka aineisto kerättiin sähköisen kyselylomakkeen avulla. Puolistrukturoitu kyselylomake suunnattiin varhaiskasvatuksen erityisopettajille, ja kyselyn linkkiä jaettiin sekä sähköpostin että sosiaalisen median kautta. Kyselyyn vastasi 11 varhaiskasvatuksen erityisopettajaa. Tutkimusaineisto analysoitiin aineistolähtöisen sisällönanalyysin kautta. Tuloksista ilmenee, että varhaiskasvatuksen erityisopettajat käyttävät monipuolisesti erilaisia AAC-menetelmiä työssään. Tuloksissa nousee esille etenkin kuvakommunikaatio, tukiviittomat sekä kehonkieli ja selkeä puhe. Varhaiskasvatuksen erityisopettajat ohjaavat AAC-menetelmiä varhaiskasvatuksen arkeen pääosin mallintamalla niiden käyttöä itse sekä opettamalla menetelmien käyttöä henkilökunnalle, tukea tarvitseville lapsille ja muille lapsille. Varhaiskasvatuksen erityisopettajien mukaan AAC-menetelmät ovat tärkeitä etenkin tukea tarvitsevien lasten osallisuuden, tasa-arvon, minäpystyvyyden sekä kommunikoinnin ja kielen kehityksen kannalta. Erityisopettajat nostavat kuitenkin esille selkeän puutteen AAC-menetelmien koulutuksesta koskien niin perusopettajan koulutusta kuin täydennyskoulutusta. Tutkimustulostemme perusteella voidaan päätellä, että AAC-menetelmien avulla voidaan tukea lasten osallisuuden, tasa-arvon ja itseilmaisun toteutumista. Vaikka tutkimustulostemme mukaan varhaiskasvatuksen erityisopettajat käyttävät työssään monipuolisesti erilaisia AAC-menetelmiä, nousee aineistosta esille selkeä puute AAC-menetelmien koulutuksesta sekä lisäkoulutuksen tarve niin varhaiskasvatuksen erityisopettajien kuin varhaiskasvatuksen muun henkilökunnan koulutuksessa. Jatkotutkimusmahdollisuutena voitaisiin tutkia yleisesti varhaiskasvatuksessa työskentelevien ammattilaisten AAC-menetelmien osaamista ja käyttöä tukea tarvitsevan lapsen kanssa

GATA4-targeted compound exhibits cardioprotective actions against doxorubicin-induced toxicity in vitro and in vivo : establishment of a chronic cardiotoxicity model using human iPSC-derived cardiomyocytes

Doxorubicin is a widely used anticancer drug that causes dose-related cardiotoxicity. The exact mechanisms of doxorubicin toxicity are still unclear, partly because most in vitro studies have evaluated the effects of short-term high-dose doxorubicin treatments. Here, we developed an in vitro model of long-term low-dose administration of doxorubicin utilizing human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Moreover, given that current strategies for prevention and management of doxorubicin-induced cardiotoxicity fail to prevent cancer patients developing heart failure, we also investigated whether the GATA4-targeted compound 3i-1000 has cardioprotective potential against doxorubicin toxicity both in vitro and in vivo. The final doxorubicin concentration used in the chronic toxicity model in vitro was chosen based on cell viability data evaluation. Exposure to doxorubicin at the concentrations of 1-3 mu M markedly reduced (60%) hiPSC-CM viability already within 48 h, while a 14-day treatment with 100 nM doxorubicin concentration induced only a modest 26% reduction in hiPCS-CM viability. Doxorubicin treatment also decreased DNA content in hiPSC-CMs. Interestingly, the compound 3i-1000 attenuated doxorubicin-induced increase in pro-B-type natriuretic peptide (proBNP) expression and caspase-3/7 activation in hiPSC-CMs. Moreover, treatment with 3i-1000 for 2 weeks (30 mg/kg/day, i.p.) inhibited doxorubicin cardiotoxicity by restoring left ventricular ejection fraction and fractional shortening in chronic in vivo rat model. In conclusion, the results demonstrate that long-term exposure of hiPSC-CMs can be utilized as an in vitro model of delayed doxorubicin-induced toxicity and provide in vitro and in vivo evidence that targeting GATA4 may be an effective strategy to counteract doxorubicin-induced cardiotoxicity.Peer reviewe

GATA-targeted compounds modulate cardiac subtype cell differentiation in dual reporter stem cell line

BackgroundPharmacological modulation of cell fate decisions and developmental gene regulatory networks holds promise for the treatment of heart failure. Compounds that target tissue-specific transcription factors could overcome non-specific effects of small molecules and lead to the regeneration of heart muscle following myocardial infarction. Due to cellular heterogeneity in the heart, the activation of gene programs representing specific atrial and ventricular cardiomyocyte subtypes would be highly desirable. Chemical compounds that modulate atrial and ventricular cell fate could be used to improve subtype-specific differentiation of endogenous or exogenously delivered progenitor cells in order to promote cardiac regeneration.MethodsTranscription factor GATA4-targeted compounds that have previously shown in vivo efficacy in cardiac injury models were tested for stage-specific activation of atrial and ventricular reporter genes in differentiating pluripotent stem cells using a dual reporter assay. Chemically induced gene expression changes were characterized by qRT-PCR, global run-on sequencing (GRO-seq) and immunoblotting, and the network of cooperative proteins of GATA4 and NKX2-5 were further explored by the examination of the GATA4 and NKX2-5 interactome by BioID. Reporter gene assays were conducted to examine combinatorial effects of GATA-targeted compounds and bromodomain and extraterminal domain (BET) inhibition on chamber-specific gene expression.ResultsGATA4-targeted compounds 3i-1000 and 3i-1103 were identified as differential modulators of atrial and ventricular gene expression. More detailed structure-function analysis revealed a distinct subclass of GATA4/NKX2-5 inhibitory compounds with an acetyl lysine-like domain that contributed to ventricular cells (%Myl2-eGFP+). Additionally, BioID analysis indicated broad interaction between GATA4 and BET family of proteins, such as BRD4. This indicated the involvement of epigenetic modulators in the regulation of GATA-dependent transcription. In this line, reporter gene assays with combinatorial treatment of 3i-1000 and the BET bromodomain inhibitor (+)-JQ1 demonstrated the cooperative role of GATA4 and BRD4 in the modulation of chamber-specific cardiac gene expression.ConclusionsCollectively, these results indicate the potential for therapeutic alteration of cell fate decisions and pathological gene regulatory networks by GATA4-targeted compounds modulating chamber-specific transcriptional programs in multipotent cardiac progenitor cells and cardiomyocytes. The compound scaffolds described within this study could be used to develop regenerative strategies for myocardial regeneration.Peer reviewe

Discovery of Small Molecules Targeting the Synergy of Cardiac Transcription Factors GATA4 and NKX2-5

Transcription factors are pivotal regulators of gene transcription, and many diseases are associated with the deregulation of transcriptional networks. In the heart, the transcription factors GATA4 and NKX2-5 are required for cardiogenesis. GATA4 and NKX2-5 interact physically, and the activation of GATA4, in cooperation with NKX2-5, is essential for stretch-induced cardiomyocyte hypertrophy. Here, we report the identification of four small molecule families that either inhibit or enhance the GATA4-NKX2-5 transcriptional synergy. A fragment-based screening, reporter gene assay, and pharmacophore search were utilized for the small molecule screening, identification, and optimization. The compounds modulated the hypertrophic agonist-induced cardiac gene expression. The most potent hit compound, N-[4-(diethylamino)phenyl]-5-methyl-3-phenylisoxazole-4-carboxamide (3, IC50 = 3 mu M), exhibited no activity on the protein kinases involved in the regulation of GATA4 phosphorylation. The identified and chemically and biologically characterized active compound, and its derivatives may provide a novel class of small molecules for modulating heart regeneration.Peer reviewe

Practice patterns in diagnostics, staging, and management strategies of gallbladder cancer among Nordic tertiary centers

Background and objective: Gallbladder cancer (GBC) is a rare malignancy in the Nordic countries and no common Nordic treatment guidelines exist. This study aimed to characterize the current diagnostic and treatment strategies in the Nordic countries and disclose differences in these strategies. Methods: This was a survey study with a cross-sectional questionnaire of all 19 university hospitals providing curative-intent surgery for GBC in Sweden, Norway, Denmark, and Finland. Results: In all Nordic countries except Sweden, neoadjuvant/downstaging chemotherapy was used in GBC patients. In T1b and T2, majority of the centers (15–18/19) performed extended cholecystectomy. In T3, majority of the centers (13/19) performed cholecystectomy with resection of segments 4b and 5. In T4, majority of the centers (12–14/19) chose palliative/oncological care. The centers in Sweden extended lymphadenectomy beyond the hepatoduodenal ligament, whereas all other Nordic centers usually limited lymphadenectomy to the hepatoduodenal ligament. All Nordic centers except those in Norway used adjuvant chemotherapy routinely for GBC. There were no major differences between the Nordic centers in diagnostics and follow-up. Conclusions: The surgical and oncological treatment strategies of GBC vary considerably between the Nordic centers and countries.publishedVersio

Changes in egg yolk lipid composition of hens fed with a by-product from black currant processing and its effects on sensory and foaming properties of eggs

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Production of n-3 enriched eggs: new promising resources of nutritionally important long chain fatty acids

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Production of omega-3 enriched eggs: new promising resources of nutritionally important long chain fatty acids

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Production of n-3 enriched eggs: new promising resources of nutritionally important long chain fatty acids

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Production of n-3 enriched eggs: new promising resources of nutritionally important long chain fatty acids

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