Cross-Cultural Adaptation and Validation of the Finnish Version of the Michigan Hand Outcomes Questionnaire

Background and Aims: Michigan Hand Outcomes Questionnaire is a widely used patient-reported outcome measure in hand surgery. The aim of this study was to translate and validate the Michigan Hand Outcomes Questionnaire into Finnish for Finnish patients with hand problems following international standards and guidelines. Material and Methods: The original English Michigan Hand Outcomes Questionnaire was translated into Finnish. Altogether, 115 patients completed the Finnish Michigan Hand Outcomes Questionnaire, and reference outcomes: Disabilities of the Arm and Shoulder, EQ-5D 3L and pain intensity on a visual analog scale. Grip and key pinch forces were measured. After 1-2 weeks, 63 patients completed the Finnish Michigan Hand Outcomes Questionnaire the second time. The Michigan Hand Outcomes Questionnaire was analyzed for internal consistency, repeatability, correlations with the reference outcomes, and factor analysis. Results: Cronbach's alpha ranged from 0.90 to 0.97 in all the Michigan Hand Outcomes Questionnaire subscales, showing high internal consistency. The intraclass correlation coefficient showed good to excellent test-retest reliability ranging from 0.66 to 0.91 in all the Michigan Hand Outcomes Questionnaire subscales. In factor analysis, the structure with six subscales was not confirmed. All the subscales correlated with Disabilities of the Arm and Shoulder score, and five subscales correlated with EQ-5D index. Conclusion: The Finnish version of the Michigan Hand Outcomes Questionnaire showed similar properties compared to the original English version and thus can be used as patient-reported outcome measure for Finnish patients with hand problems.Peer reviewe

HLA and non-HLA genes and familial predisposition to autoimmune diseases in families with a child affected by type 1 diabetes

Genetic predisposition could be assumed to be causing clustering of autoimmunity in individuals and families. We tested whether HLA and non-HLA loci associate with such clustering of autoimmunity. We included 1,745 children with type 1 diabetes from the Finnish Pediatric Diabetes Register. Data on personal or family history of autoimmune diseases were collected with a structured questionnaire and, for a subset, with a detailed search for celiac disease and autoimmune thyroid disease. Children with multiple autoimmune diseases or with multiple affected first-or second-degree relatives were identified. We analysed type 1 diabetes related HLA class II haplotypes and genotyped 41 single nucleotide polymorphisms (SNPs) outside the HLA region. The HLA-DR4-DQ8 haplotype was associated with having type 1 diabetes only whereas the HLA-DR3-DQ2 haplotype was more common in children with multiple autoimmune diseases. Children with multiple autoimmune diseases showed nominal association with RGS1 (rs2816316), and children coming from an autoimmune family with rs11711054 (CCR3-CCR5). In multivariate analyses, the overall effect of non-HLA SNPs on both phenotypes was evident, associations with RGS1 and CCR3-CCR5 region were confirmed and additional associations were implicated: NRP1, FUT2, and CD69 for children with multiple autoimmune diseases. In conclusion, HLA-DR3-DQ2 haplotype and some non-HLA SNPs contribute to the clustering of autoimmune diseases in children with type 1 diabetes and in their families

Lypsylehmien ruokinnan järjestäminen – pitkän aikavälin taloustarkastelu

Maatilan toimintaa kehitettäessä toimintavaihtoehtojen määrä kytkeytyy suunnittelun aikajänteeseen. Pitkälläaikavälillä on mahdollista tehdä paljon ja suuria muutoksia, mutta lyhyellä aikavälillä vaihtoehtojenmäärä voi olla hyvinkin rajoitettu. Kummallakin aikavälillä maatalousyrittäjän tavoitteena on tuottojen jakustannusten erotuksen maksimointi.Ruokinta vaikuttaa tuottojen suuruuteen, sillä eri rehuyhdistelmät muuttavat maitotuotoksen määrääja laatua. Lisäksi niillä on vaikutusta eläinten terveyteen. Maidontuotannossa ruokinta muodostaa keskeisenkustannuserän, joka vaihtelee ruokintavaihtoehdoittain. Kustannukset muodostuvat rehujen hankinnasta,käsittelystä ja eläinten ruokinnasta. Vaihtoehtoiset ruokintateknologiat muuttavat myös kustannussuhteita.Lehmän ruokinnan ja maitotuotoksen välisen yhteyden selvittäminen on haasteellinen tehtävä, sillävaihtoehtoisten ruokintakombinaatioiden määrä on suuri ja niiden ravitsemusfysiologiset vaikutuksetpoikkeavat toisistaan. Haasteellisuutta lisää myös se, että tarkasteluun on otettava mukaan maitotilan omienrehujen tuotanto ja siihen liittyvät prosessit (kasvifysiologia, maatalousteknologia jne.) ja niiden määräämätreunaehdot. Tutkimus on rajattu siten, että siinä tarkastellaan muutamia keskeisimpiä rehuja. Sisäruokintakaudenaikana karkearehuna käytetään tilalla tuotettua säilörehua, jota täydennetään väkirehulla(ohra-rypsirouheseos). Kasvukauden aikana kokoaikaisen sisäruokinnan lisäksi vaihtoehtoina on laidunnustai osittainen laidunnus, sillä laidun on lypsylehmälle luonnollista rehua.Tässä tutkimuksessa lypsylehmien ruokintaa tarkastellaan pitkän aikavälin taloudellisena optimointiongelmana.Tutkimuksessa luodaan lineaarinen optimointimalli, joka tekee mahdolliseksi tarkastellarehuntuotannon eri osatekijöitä talouden näkökulmasta. Mallilla verrataan eri toimintavaihtoehdoista saatavientuottojen ja kustannusten erotusta. Optimointimallin pohjana on Seppälän ym. (2002) laatima sisäruokintakaudenoptimointimalli, joka on päivitetty vastaamaan nykyistä tuotantoteknologiaa ja jota onlaajennettu kattamaan myös laidunkausi.Eri rehuyhdistelmien tuotosvaikutus on määritetty MTT:n tuotantokokeiden pohjalta, kuten mm.vähenevät rajatuotokset ja rehujen väliset korvautuvuussuhteet ja niihin liittyvät rajoitukset. MTT:n koetulostenpohjalta on määritetty säilörehun laadun (D-arvo) ja sadon (kg ka/ha) muutokset kasvukauden edetessäsekä kevätkorjuun ajoittumisen vaikutus syyssadon laatuun ja määrään. Teknologiset mahdollisuudetja rajoitteet perustuvat pääosin Työtehoseuran tutkimustuloksiin. Laidunkauden osalta responssit perustuvatMTT:n laidunkokeisiin ja TTS:n työnmenekkitutkimusten tuloksiin

Cytocompatibility of Medical Biomaterials Containing Nickel by Osteoblasts: a Systematic Literature Review

The present review is based on a survey of 21 studies on the cytocompatibility of medical biomaterials containing nickel, as assessed by cell culture of human and animal osteoblasts or osteoblast-like cells. Among the biomaterials evaluated were stainless steel, NiTi alloys, pure Ni, Ti, and other pure metals. The materials were either commercially available, prepared by the authors, or implanted by various techniques to generate a protective layer of oxides, nitrides, acetylides. The observation that the layers significantly reduced the initial release of metal ions and increased cytocompatibility was confirmed in cell culture experiments. Physical and chemical characterization of the materials was performed. This included, e.g., surface characterization (roughness, wettability, corrosion behavior, quantity of released ions, microhardness, and characterization of passivation layer). Cytocompatibility tests of the materials were conducted in the cultures of human or animal osteoblasts and osteoblast-like cells. The following assays were carried out: cell proliferation and viability test, adhesion test, morphology (by fluorescent microscopy or SEM). Also phenotypic and genotypic markers were investigated. In the majority of works, it was found that the most cytocompatible materials were stainless steel and NiTi alloy. Pure Ni was rendered and less cytocompatible. All the papers confirmed that the consequence of the formation of protective layers was in significant increase of cytocompatibility of the materials. This indicates the possible further modifications of the manufacturing process (formation of the passivation layer)

Efflux Protein Expression in Human Stem Cell-Derived Retinal Pigment Epithelial Cells

Retinal pigment epithelial (RPE) cells in the back of the eye nourish photoreceptor cells and form a selective barrier that influences drug transport from the blood to the photoreceptor cells. At the molecular level, ATP-dependent efflux transporters have a major role in drug delivery in human RPE. In this study, we assessed the relative expression of several ATP-dependent efflux transporter genes (MRP1, -2, -3, -4, -5, -6, p-gp, and BCRP), the protein expression and localization of MRP1, MRP4, and MRP5, and the functionality of MRP1 efflux pumps at different maturation stages of undifferentiated human embryonic stem cells (hESC) and RPE derived from the hESC (hESC-RPE). Our findings revealed that the gene expression of ATP-dependent efflux transporters MRP1, -3, -4, -5, and p-gp fluctuated during hESC-RPE maturation from undifferentiated hESC to fusiform, epithelioid, and finally to cobblestone hESC-RPE. Epithelioid hESC-RPE had the highest expression of MRP1, -3, -4, and P-gp, whereas the most mature cobblestone hESC-RPE had the highest expression of MRP5 and MRP6. These findings indicate that a similar efflux protein profile is shared between hESC-RPE and the human RPE cell line, ARPE-19, and suggest that hESC-RPE cells are suitable in vitro RPE models for drug transport studies. Embryonic stem cell model might provide a novel tool to study retinal cell differentiation, mechanisms of RPE -derived diseases, drug testing and targeted drug therapy

Protein misfolding and dysregulated protein homeostasis in autoinflammatory diseases and beyond.

Cells have a number of mechanisms to maintain protein homeostasis, including proteasome-mediated degradation of ubiquitinated proteins and autophagy, a regulated process of ‘self-eating’ where the contents of entire organelles can be recycled for other uses. The unfolded protein response prevents protein overload in the secretory pathway. In the past decade, it has become clear that these fundamental cellular processes also help contain inflammation though degrading pro-inflammatory protein complexes such as the NLRP3 inflammasome. Signaling pathways such as the UPR can also be co-opted by toll-like receptor and mitochondrial reactive oxygen species signaling to induce inflammatory responses. Mutations that alter key inflammatory proteins, such as NLRP3 or TNFR1, can overcome normal protein homeostasis mechanisms, resulting in autoinflammatory diseases. Conversely, Mendelian defects in the proteasome cause protein accumulation, which can trigger interferon-dependent autoinflammatory disease. In non-Mendelian inflammatory diseases, polymorphisms in genes affecting the UPR or autophagy pathways can contribute to disease, and in diseases not formerly considered inflammatory such as neurodegenerative conditions and type 2 diabetes, there is increasing evidence that cell intrinsic or environmental alterations in protein homeostasis may contribute to pathogenesis