Terveyden lukutaidon lisääminen suun terveydestä sekä sen yhteydestä yleisterveyteen : tietotesti työikäiselle sydänpotilaalle

Suun terveydellä sekä sydän- ja verisuonisairauksilla on todettu olevan yhteys. Tämä tutkimuksiin perustava tieto oli lähtökohtana opinnäytetyöllemme. Työmme kuuluu osaksi ”Työikäisen sydänpotilaan ja hänen perheensä sekä hoidonantajan ohjaaminen”-hanketta. Yhteistyökumppaneina työssämme ovat olleet Helsingin Yliopistollisen Keskussairaalan (HYKS) medisiinisen tulosyksikön Kardiologian klinikka, Operatiivisen tulosyksikön Sydän- ja Thoraxkirurgian klinikka, Helsingin sydänpiiri ry sekä Uudenmaan sydänpiiri ry. Opinnäytetyömme tavoitteena oli työikäisten sydänpotilaiden terveyden lukutaidon lisääminen suun terveydestä, sen hoidosta, yleisimmistä suun sairauksista ja näiden yhteydestä yleisterveyteen. Tarkoituksenamme oli luoda internetiin Sydänliiton sivuille tietotesti edellä mainituista asioista. Työmme teoreettinen viitekehys koostuu luotettavista tutkimuksista sekä alan kirjallisuudesta. Työmme sisältöä ja ulkoasua on hiottu seminaareissa sekä ohjaustuokioissa yhdessä ohjaajien, työelämän edustajien sekä luokkatoveriemme kanssa. Opinnäytetyömme tuotoksena oli tietotesti, joka julkaistiin Sydänliiton verkkosivuilla. Testi koostuu 16 kysymyksestä, jotka käsittelevät työmme aihealuetta kattavasti. Testasimme testiämme Uudenmaan sydänpiiri ry:n kahdeksalla sepelvaltimotautia sairastavalla työikäisellä potilaalla, joilta saimme arvokasta palautetta. Palautteen avulla hioimme testin julkaisuasua. Olemme myös kirjoittaneet alamme julkaisuun artikkelin opinnäytetyömme prosessista ja tuotoksesta. Työmme aihe nousi työelämästä ja koimme tuotoksemme ajankohtaiseksi sekä tarpeelliseksi. Tuotoksemme on helposti käytettävissä verkossa ja uskomme työikäisten sydänpotilaiden löytävän sen. Toivomme testimme herättävän mielenkiintoa suun terveyttä ja yleisterveyttä kohtaan sekä olevan hyödyksi mahdollisimman monelle. Jatkossa testiämme voisi kehittää eteenpäin kattamalla myös muita sairauksia, kuten diabetes.Studies have proven that oral health and cardiovascular diseases have a connection. This research-based knowledge was the fundamental starting point when we began our work to build this thesis, which is a part of the “Guiding of a working aged patient with cardiovascular disease, his family and nursing staff” project. The partners in our work were the Helsinki University Central Hospital (HUCH) and local Heart Associations. Our study’s main goal was to increase the oral health literacy rate among working aged patients with cardiovascular diseases. Additionally, we aimed to increase awareness towards the treatment available, the most common oral diseases and their relation to general health. The objective of this study was to create a questionnaire addressing the aforementioned subjects, which would appear on the Heart Association's websites. The theoretical framework of our work consists of research and literature related to the subject. The content and design of our work has been refined through seminars and participating in discussion seminars with tutors, representatives from working life and classmates. Our study's output was a questionnaire, which was released on the Heart Association's websites. The test consists of 16 questions about cleaning the mouth, oral diseases and the connection between oral health and general health. The topic of our work came from work life experiences and they felt that the topic was current and necessary. In the future, the questionnaire can be expanded to include other diseases such as diabetes. We hope that our work will benefit many people and raise interest and knowledge about oral hygiene

PMS2 expression decrease causes severe problems in mismatch repair

PMS2 is one of the four susceptibility genes in Lynch syndrome (LS), the most common cancer syndrome in the world. Inherited mutations in DNA mismatch repair (MMR) genes, MLH1, MSH2, and MSH6, account for approximately 90% of LS, while a relatively small number of LS families segregate a PMS2 mutation. This and the low cancer penetrance in PMS2 families suggest that PMS2 is only a moderate or low-risk susceptibility gene. We have previously shown that even a partial expression decrease in MLH1, MSH2, or MSH6 suggests that heterozygous LS mutation carriers have MMR malfunction in constitutive tissues. Whether and how PMS2 expression decrease affects the repair capability is not known. Here, we show that PMS2 knockdown cells retaining 19%, 33%, or 53% of PMS2 expression all have significantly reduced MMR efficiency. Surprisingly, the cells retaining expression levels comparable to PMS2 mutation carriers indicate the lowest repair efficiency.Peer reviewe

DNA:n korjausmekanismien häiriöt ja niiden lääketieteellinen merkitys

English summar

Western diet enhances intestinal tumorigenesis in Min/ plus mice, associating with mucosal metabolic and inflammatory stress and loss of Apc heterozygosity

Western-type diet (WD) is a risk factor for colorectal cancer, but the underlying mechanisms are poorly understood. We investigated the interaction of WD and heterozygous mutation in the Apc gene on adenoma formation and metabolic and immunological changes in the histologically normal intestinal mucosa of Apc(Min/+) (Min/ +) mice. The diet used was high in saturated fat and low in calcium, vitamin D, fiber and folate. The number of adenomas was twofold higher in the WD mice compared to controls, but adenoma size, proliferation or apoptosis did not differ. The ratio of the MM to wild-type allele was higher in the WD mice, indicating accelerated loss of Apc heterozygosity (LOH). Densities of intraepithelial CD3 epsilon(+) T lymphocytes and of mucosal FoxP3(+) regulatory T cells were higher in the WD mice, implying inflammatory changes. Western blot analyses from the mucosa of the WD mice showed suppressed activation of the ERK and AKT pathways and a tendency for reduced activation of the mTOR pathway as measured in phosphoS6/S6 levels. The expression of pyruvate dehydrogenase kinase 4 was up-regulated in both mRNA and protein levels. Gene expression analyses showed changes in oxidation/reduction, fatty acid and monosaccharide metabolic pathways, tissue organization, cell fate and regulation of apoptosis. Together, our results suggest that the high-risk Western diet primes the intestine to tumorigenesis through synergistic effects in energy metabolism, inflammation and oxidative stress, which culminate in the acceleration of LOH of the Apc gene. (C) 2016 Elsevier Inc. All rights reserved.Peer reviewe

Mlh1 deficiency in normal mouse colon mucosa associates with chromosomally unstable colon cancer

Colorectal cancer (CRC) genome is unstable and different types of instabilities, such as chromosomal instability (CIN) and microsatellite instability (MSI) are thought to reflect distinct cancer initiating mechanisms. Although 85% of sporadic CRC reveal CIN, 15% reveal mismatch repair (MMR) malfunction and MSI, the hallmarks of Lynch syndrome with inherited heterozygous germline mutations in MMR genes. Our study was designed to comprehensively follow genome-wide expression changes and their implications during colon tumorigenesis. We conducted a long-term feeding experiment in the mouse to address expression changes arising in histologically normal colonic mucosa as putative cancer preceding events, and the effect of inherited predisposition (Mlh1(+/-)) and Western-style diet (WD) on those. During the 21-month experiment, carcinomas developed mainly in WD-fed mice and were evenly distributed between genotypes. Unexpectedly, the heterozygote (B6.129-Mlh1tm1Rak) mice did not show MSI in their CRCs. Instead, both wildtype and heterozygote CRC mice showed a distinct mRNA expression profile and shortage of several chromosomal segregation gene-specific transcripts (Mlh1, Bub1, Mis18a, Tpx2, Rad9a, Pms2, Cenpe, Ncapd3, Odf2 and Dclre1b) in their colon mucosa, as well as an increased mitotic activity and abundant numbers of unbalanced/atypical mitoses in tumours. Our genome-wide expression profiling experiment demonstrates that cancer preceding changes are already seen in histologically normal colon mucosa and that decreased expressions of Mlh1 and other chromosomal segregation genes may form a field-defect in mucosa, which trigger MMR-proficient, chromosomally unstable CRC.Peer reviewe

DNA methylation changes and somatic mutations as tumorigenic events in Lynch syndrome-associated adenomas retaining mismatch repair protein expression

Background: DNA mismatch repair (MMR) defects are a major factor in colorectal tumorigenesis in Lynch syndrome (LS) and 15% of sporadic cases. Some adenomas from carriers of inherited MMR gene mutations have intact MMR protein expression implying other mechanisms accelerating tumorigenesis. We determined roles of DNA methylation changes and somatic mutations in cancer-associated genes as tumorigenic events in LS-associated colorectal adenomas with intact MMR. Methods: We investigated 122 archival colorectal specimens of normal mucosae, adenomas and carcinomas from 57 LS patients. MMR-deficient (MMR-D, n 49) and MMR-proficient (MMR-P, n 18) adenomas were of particular interest and were interrogated by methylation-specific multiplex ligation-dependent probe amplification and Ion Torrent sequencing. Findings: Promoter methylation of CpG island methylator phenotype (CIMP)-associated marker genes and selected colorectal cancer (CRC)-associated tumor suppressor genes (TSGs) increased and LINE-1 methylation decreased from normal mucosa to MMR-P adenomas to MMR-D adenomas. Methylation differences were statistically significant when either adenoma group was compared with normal mucosa, but not between MMR-P and MMR-D adenomas. Significantly increased methylation was found in multiple CIMP marker genes (1612, NEUROGI,CRABP1, and CDKN2A) and TSGs (SERPI and SFRP2) in MMR-P adenomas already. Furthermore, certain CRC-associated somatic mutations, such as KRAS, were prevalent in MMR-P adenomas. Interpretation: We conclude that DNA methylation changes and somatic mutations of cancer-associated genes might serve as an alternative pathway accelerating LS-associated tumorigenesis in the presence of proficient MMR. Fund: Jane and Aatos Erkko Foundation, Academy of Finland, Cancer Foundation Finland, Sigrid juselius Foundation, and HiL1FE. (C) 2019 Published by Elsevier B.V.Peer reviewe

DNA hypermethylation appears early and shows increased frequency with dysplasia in Lynch syndrome-associated colorectal adenomas and carcinomas

Abstract Background Lynch syndrome (LS) is associated with germline mutations in DNA mismatch repair (MMR) genes. The first “hit” to inactivate one allele of the predisposing MMR gene is present in every cell, contributing to accelerated tumorigenesis. Less information is available of the nature, timing, and order of other molecular “hits” required for tumor development. To this end, MMR protein expression and coordinated promoter methylation were examined in colorectal specimens prospectively collected from LS mutation carriers (n = 55) during colonoscopy surveillance (10/2011–5/2013), supplemented with retrospective specimens. Results Loss of MMR protein corresponding to the gene mutated in the germline increased with dysplasia, with frequency of 0 % in normal mucosa, 50–68 % in low-grade dysplasia adenomas, and 100 % in high-grade dysplasia adenomas and carcinomas. Promoter methylation as a putative “second hit” occurred in 1/56 (2 %) of tumors with silenced MMR protein. A general hypermethylation tendency was evaluated by two gene sets, eight CpG island methylator phenotype (CIMP) genes, and seven candidate tumor suppressor genes linked to colorectal carcinoma (CRC). Hypermethylation followed the same trend as MMR protein loss and was present in some low-grade dysplasia adenomas that still expressed MMR protein suggesting the absence of a “second hit.” To assess prospectively collected normal mucosa for carcinogenic “fields,” the specimen donors were stratified according to age at biopsy (50 years or below vs. above 50 years) and further according to the absence vs. presence of a (previous or concurrent) diagnosis of CRC. In mutation carriers over 50 years old, two markers from the candidate gene panel (SFRP1 and SLC5A8) revealed a significantly elevated average degree of methylation in individuals with CRC diagnosis vs. those without. Conclusions Our findings emphasize the importance and early appearance of epigenetic alterations in LS-associated tumorigenesis. The results serve early detection and assessment of progression of CRC

Cancer-Predicting Gene Expression Changes in Colonic Mucosa of Western Diet Fed Mlh1(+/-) Mice

Peer reviewe

Hiki, ähky ja loikka - Osallistujien pedagogisia mietteitä ja ideoita hankkeen varrelta

DIGIJOUJOU-hankkeessa työskennelleet opettajat ovat hankkeen toimintavuosien 2017-2019 aikana pohtineet opetuksen ja oppimisen digitaalisuutta ja joustavuutta eri näkökulmista: mitä digitaalisuus ja joustavuus suomen ja ruotsin opiskelussa tarkoittaa, miten soveltaa, lisätä ja kehittää digitaalisuutta ja joustavuutta omassa opetuksessa ja opiskelijoiden oppimisessa. Hankelaisten blogikirjoituksissa näemme askeleita opettajien omasta ja yhdessä muiden kanssa oppimisesta hankkeen edetessä; epävarmuus muuttuu varmuudeksi, ajoittainen digiähky oman asiantuntijuuden kasvuksi ja joustavuus osaksi opettajan arkipedagogiikkaa. Antoisia ja inspiroivia lukuhetkiä! Lisätietoa: https://digijoujou.aalto.fi/Lärarna i DIGIJOUJOU-projektet har under projektets verksamhetsår 2017-2019 reflekterat över digitalisering och exibilitet från olika perspektiv; vad betyder digitalisering och exibilitet i lärandet av finska och svenska, hur ska man implementera, öka och utveckla dessa i den egna undervisningen och i hur studerande lär sig finska och svenska. I projektdeltagarnas bloginlägg får vi inblick i hur allas lärandeprocess i projektet framskrider; osäkerhet utvecklas till säkerhet, digikaoset får ordning och exibilitet blir en del av den egna sakkunnigheten och pedagogiken. Med önskan om givande och inspirerande läsning! Mer information: https://digijoujou.aalto.fi