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Abstract Introduction: Children with nonsyndromic cleft lip and/or palate have smaller consonant inventories, less accurate articulation, and more speech errors than their peers without clefts. Speech and dental arch relationships have widely been the primary outcome measure of palate repair. Aims: The aim was to evaluate the occurrence of misarticulations of the Finnish alveolar consonants /s/, /l/ and /r/ and their possible relationship with maxillary dental arch dimensions in 5-year-old children with unilateral cleft lip and palate (UCLP). Materials and methods: Subgroup analysis was conducted within a multicenter controlled trial of primary surgery (Scandcleft project). 46 Caucasian Finnish-speaking patients (29 boys) with non-syndromic complete UCLP were evaluated retrospectively. Production of the Finnish alveolar consonants /s/, /l/ and /r/ was assessed from standardized audio recordings at the mean age of 5.06 years (range 4.82-5.89). Articulation errors were categorized as either correct, distortion, substitution, or omission. Maxillary dental arch measurements were assessed using the technique of Moorrees from plaster casts taken at the same age. Additionally, the anterior and posterior palatal heights were measured. Aspin-Welch Unequal-Variance T-Test, Equal-Variance T-Test and Mann-Whitney U test were used in the statistical analyses. Kappa statistics were calculated to assess reliability. Results: Only one of the children articulated all the studied sounds correctly. 93.2% misarticulated /r/, 63.0% misarticulated /s/ and 39.1% misarticulated /l/. Distortions and substitutions were common. Omissions were sparse. There was no relationship between the occurrence of alveolar consonant misarticulations and the maxillary dental arch dimensions. Intra- and interrater agreements varied between moderate to excellent. Conclusions: Children with UCLP have a notable amount of alveolar consonant misarticulations. Maxillary dental arch dimensions were not related to the misarticulation of /s/, /l/ or /r/ in 5-year-old children with UCLP.

Alzheimer’s disease (AD) weakens the concerned person’s ability to repair their own speech. AD has also been shown to affect the use of gestures during speech. This study looks at the actions of persons with AD during self-repair sequences in a group context. and examines the length of the repair sequences, the number of repair initiations and repairs and their distribution among the people taking part in the discussions. The study also investigates how people with AD use manual gestures during self-repair sequences. The connection between word-searching and gestures was also examined. The research method is based on the theoretical frameworks of conversation analysis, multimodal interaction analysis and repair sequence theory. The research material consisted of self-repair sequences and the manual gestures within those sequences recorded from group therapy sessions directed at people diagnosed with dementia. The participants of the study were six females with AD. The video recordings were analyzed using ELAN- computer program. The speech and gestural interaction of the participants was annotated in temporal synchronicity. ELAN was able to provide numeric data, but some of the data was calculated manually. Due to a lack of research on this study’s topic, it was necessary to develop the method to be used in the study. The research data comprises 183 self-repair sequences. 91,8 % of those consisted of a single turn. The mean length of the sequences was 6,2 seconds. Within the self-repair sequences, there were 496 self-initiations and 26 other-initiations. Within the self-repair sequences, 216 self-repairs and 22 other-repairs were detected. Word-search was the most common type of self-repair (37 %). Three out of six subjects produced 92,9 % of the repair-sequences. Half of the self-repair-sequences contained manual gestures. 177 gestures were observed. Three of the subjects produced 96,6% of all the gestures. Two of them produced gestures during 60 % of their repair sequences while producing 87% of all gestures. The subject producing third most gestures did so in about one third of her repair sequences. The most-used gesture type was rhythmic gesture (37,2%). Of all gestures 67,8% were produced during word-searches. The method made it possible to describe, at a general level, the gesture use of persons with AD during repair-sequences containing self-repair. According to the results, there is a lot of individual diversity in the phenomenon. However, the skewness and small number of participants in the study make this assumption uncertain. The results imply that persons with AD use gestures to support their speech. It is possible that more gestures occur during word-searches. Therefore, the use of gestures must be taken into consideration during speech repair. It can also be assumed that persons with moderate stage of AD are able to perceive the problematic parts in their own speech and are able to produce repairs if they are given enough time to process.

Ameloblastic carcinoma – systematic literature review and a case report Aim of this study: The purpose of this study is to increase awareness of a rare malignant odontogenic tumor, ameloblastic carcinoma (AC). By increasing knowledge of this disease, AC patients can be diagnosed better and guide the treatment and follow up of the patients. Material and methods: In this study, literature dealing with AC in English was systematically reviewed from PubMed. In addition, one newly diagnosed AC patient case with HUSLAB pathology, University Hospital of Helsinki, Finland is reported. Results: Altogether, 33 studies fulfilling inclusion criteria were published between the years 1993 to 2021. There were studies of AC from almost all continents. There was a total of 211 patients in these articles. Sixty-one percent of the AC patients were men. The average age of the patients was 46.9 years. Most commonly, AC occured in the mandible. Primary AC was slightly more common than secondary malignant ameloblastoma derived AC. All AC patients were symptomatic. The most common symptoms were swelling, bleeding, pain, dysphagia, dysphonia, facial nerve paralysis, ulcer, drainage, trismus and tooth mobility. Metastases occurred in 22.4% of AC patients. The most common form of treatment is surgery. Thirty-eight different immunohistochemical markers were evaluated in the studies. Ki-67 alone appeared more than in one study (5 studies). Ki-67 proliferation index was higher in AC than in benign ameloblastoma in all five studies. Conclusions: Ameloblastic carcinoma is a rare odontogenic tumor which occurs in adult people, most often in the mandible. One fifth of patients had metastases. According to the studies on Ki-67, Ki-67 could serve as a useful marker in distinguishing AC from ameloblastoma. This can be important, as distinguishing between benign and malignant ameloblastoma histopathologically is often difficult.

Tiivistelmä Tiedekunta: Helsingin yliopisto lääketieteellinen tiedekunta Koulutusohjelma: Lääketieteen koulutusohjelma Opintosuunta: Lääketieteen lisensiaatti Tekijä: Suvi Tolonen Työn nimi: Ammattialtistus suunielun syövän riskitekijänä -kirjallisuuskatsaus Työn laji: Syventävä tutkielma Kuukausi ja vuosi: 12/2021 Sivumäärä: 22, liitteet 5 Avainsanat: oropharyngeal neoplasm, oropharynx, neoplasm, occupation, work Säilytyspaikka: E-thesis Muita tietoja: Tiivistelmä: Suunielun syöpä oli vuonna 2018 maailmanlaajuisesti 24. yleisin syöpätyyppi ja uusia suunielun syövän diagnooseja tehtiin yhteensä 92 887. Suunielun syövän tärkeimmät riskitekijät ovat nykytiedon mukaan tupakointi, runsas alkoholin käyttö sekä krooninen papilloomavirusinfektio suunielun alueella. Suunielun syövän ilmaantuvuus on lisääntynyt tasaisesti viimeisten vuosikymmenten aikana. Syytä tälle ei täysin tunneta, vaikkakin lisääntyneiden suunielun papilloomavirusinfektioiden ja niiden aiheuttamien suunielun syöpien on ajateltu selittävän osittain ilmaantuvuuden lisääntymistä. Tässä kirjallisuuskatsauksessa haluttiin selvittää ammatin ja työperäisten altisteiden vaikutusta suunielun syövän syntyyn. Kirjallisuuskatsausta varten etsittiin huhti-toukokuussa 2021 PubMed tietokannasta aihetta koskevat artikkelit. Yhteensä PubMed tietokannasta löydettiin 479 artikkelia, joista jäi karsimisen jälkeen jäljelle 18 ammatin ja suunielun syövän yhteyttä käsitelevää artikkelia. Kirjallisuuskatsauksen perusteella löytyi viitteitä siitä, että eräät ammatit, joissa altistutaan työuran aikana suurelle määrälle erilaisia kemikaaleja, viruksia, orgaanisia yhdisteitä tai erilaisia karsinogeenisiä yhdisteitä saattavat lisätä suunielun syövän syntymisen riskiä. Tällaisia riskiammatteja olivat artikkelien perusteella esimerkiksi asfaltti- ja asbestityöntekijän sekä automekaanikon ammatit. Joissain tapauksissa artikkelien tulokset ammatin ja suunielun syövän yhteydestä olivat ristiriitaisia. Esimerkiksi maataloudessa työskentelevien ja puupölylle altistuvien työntekijöiden kohdalla oli eriäviä näkemyksiä suunielun syöpään sairastumisen riskistä. Altistuminen radonille tai hitsauskaasuille työssä ei näyttänyt kirjallisuuskatsauksen perusteella lisäävän suunielun syövän synnyn riskiä. Suunielun syövän ja ammattialtistuksen välistä yhteyttä on tutkittu vielä melko vähän. Jatkossa tarvitaan lisää tutkimusta, jotta voidaan sanoa, onko tietyillä ammattiryhmillä kohonnut riski sairastua suunielun syöpään.

2 Abstract 2.1 Purpose To review indications, patient characteristics, frequency, and safety for surgical tracheostomies performed by otolaryngologist – head and neck surgeons in a single tertiary care center. 2.2 Methods Surgical tracheostomies performed by otolaryngologist – head and neck surgeons at Helsinki University Hospital between Jan 2014 and Feb 2017 were retrospectively reviewed. Patient demographics, surgical data, peri- and postoperative mortality information were collected from the hospital charts. Minimum follow-up was 18 months. 2.3 Results Total population was 255, with a majority (n = 181; 71%) of males. The majority of patients (n = 178; 70%) were classified as ASA 3 or 4. A total of 198 (78%) patients suffered from head and neck cancer. Multiple (14 altogether) indications for tracheostomy were identified, and simultaneous major head and neck tumor surgery was common (in 58%). Altogether, 163 (64%) patients were decannulated during follow-up with a median cannulation period of 9 days (range, 1 - 425). The surgical mortality was 0.4%. 2.4 Conclusion Simultaneously performed major tumor surgery was the most common indication for a tracheostomy. A notable number of patients had impaired physical status, but relatively insignificant comorbidities. Almost two thirds of the patients were decannulated during follow-up, although some patients remained tracheostomy-dependent for a prolonged period. Tracheostomy was found to be a safe procedure. 2.5 Key Words Airway, surgical tracheostomy, mortality, ENT 2.6 Level of Evidence 2b

Peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) is a transcriptional coactivator involved in mitochondrial biogenesis, oxidative stress response, and energy metabolism. PGC-1α is part of an energy sensing network that translates environmental influences into alterations in gene expression of mainly mitochondrial molecular pathways. A role in neuroprotection has been implicated for PGC-1α in the context of mitochondrial expression networks. Our research group has previously established a transgenic mouse line with stable overexpression of PGC-1α in brain neurons. Transgenic overexpression of PGC-1α is associated with an enhanced functional state of mitochondrial energy production. In the context of neurodegenerative processes, brain neurons of PGC-1α transgenic mice are protected against oxidative stressors in the MPTP mouse model of Parkinson's Disease. To further characterize the transcriptional activity of PGC-1α regulated gene networks in brains of transgenic mice, a quantitative real-time PCR based system was established. Gene expression was measured for a subset of genes found to be differentially regulated in a microarray based screening of RNA obtained from hippocampus and cortex of PGC-1α transgenic mice. Increased PGC-1α gene expression was found in hippocampus and cortex of PGC-1α transgenic mice, and their translation into protein was confirmed immunohistochemically. Expression analysis revealed significant changes in mRNA levels of PGC-1α controlled molecular pathways involved in mitochondrial energy production and antioxidant responses. Furthermore, alterations in the expression of some non-mitochondrial genes with established links to neurodegeneration were observed. Furthermore, a change in GABAA receptor subunit expression was detected. In accordance with previous studies on the PGC-1α transgenic mouse line, these findings suggest that differential gene expression associated with PGC-1α overexpression contributes to an enhanced functional state of neurons in hippocampus and cortex of PGC-1α transgenic mice. Increased knowledge about the transcriptional modulation of neuronal genes regulated by PGC-1α can lead to better insights into mechanisms governing neurodegeneration and neuroprotective pathways. Pharmacological modulation of PGC-1α activity may be a feasible approach for neuroprotective treatments in neurodegenerative diseases, such as Parkinson's Disease.

To be published later.

To improve patient flow in inpatient instances, the whole care process must be mapped and analyzed. This observational study was performed during one month, to identify direct and indirect factors impacting patient flow, to further enable the planning of appropriate countermeasures to diminish patient boarding, whilst improving patient flow and overall satisfaction. The core of lean methodology is to provide the quality services whilst avoiding waste and ridding the process of unnecessary work. Patients and caregivers were followed in person whilst simultaneously collecting timestamps and conducting observations. The results helped uncover issues potentially causing significant bottlenecks and thus delays in patient care. Due to the limited nature of the project, further investigations are in order before conclusions are made. (119)

Anatomian tuntemus on olennainen osa hammaslääkärin osaamisen perustaa. Suomessa hammaslääketieteen peruskoulutukseen sisältyvä anatomian opetus toteutetaan suurimmaksi osaksi kahden ensimmäisen vuoden eli prekliinisen vaiheen aikana yhdessä lääketieteen opiskelijoiden kanssa. Tutkimuksen tavoitteena on tarkastella Helsingin yliopiston hammaslääketieteen koulutusohjelman prekliinisen vaiheen anatomian opetuksen kattavuutta sekä hammaslääketieteen ja lääketieteen opiskelijoiden kokemuksia anatomian opetuksesta ja opiskelusta moniammatillisessa ympäristössä. Opetuksen kattavuuden arvioinnissa aineistona on vuoden 2018 prekliinisten opintojaksojen ydinainesanalyysit. Vertailuaineistona toimii brittiläisen The Anatomical Society -järjestön laatima anatomian ydinopetussuunnitelma. Vertailu tehtiin Microsoft Excel -ohjelman avulla. Lisäksi opiskelijoiden kokemuksien kartoittamiseen käytettiin kyselyaineistoa, joka kerättiin lomekkeella, jonka lähetettiin Helsingin yliopiston 3.-6. vuoden hammaslääketeiteen ja yleislääketieteen opiskelijoille toukokuussa 2021. Vastauksia tuli 117. Vastausprosentti oli 15%. Vastausten tilastollinen analyysi tehtiin IBM SPSS -ohjelmalla. Tutkimuksessa ilmeni, että Helsingin yliopiston prekliinisen vaiheen anatomian opetus ei kata osittain tai kokonaan 42,2% brittiläisen hammaslääketieteellisen ydinopetussuunnitelman osatavoitteista, mutta opetukseen sisältyi ydinopetussuunnitelman ulkopuolisia asioita. Tämän ylimääräisen opetuksen osuus anatomian opetuksesta vaihteli 8,3-78,4% välillä opintojaksoittain. Tutkimuksessa hammaslääketieteen opiskelijat arvioivat saamansa anatomian opetuksen vähemmän hyödylliseksi ja vähemmän oleelliseksi kuin lääketieteen opiskelijat. Huolimatta yhteisistä opinnoista myös vastaajien arviot omasta eri anatomisten rakenteiden osaamisesta erosivat koulutusohjelmien välillä. Kummankin koulutusohjelman opiskelijat arvioivat keskimäärin, että yhteisopetus on ”enemmän yleislääketieteen opiskelijoille suunnattu”. Tutkimuksen avulla löydettiin selviä epäkohtia anatomian opetuksessa. Nämä epäkohdat voivat heijastella laajemmin prekliinisen vaiheen yhteisopetuksen toteuttamisen mahdollisia ongelmia, joihin on syytä pureutua, jotta prekliiniset opinnot vastaisivat paremmin hammaslääkärikoulutuksen tarpeita ja opiskelijoiden odotuksia.

High-grade serous ovarian cancer (HGSOC) is the most common histological type of epithelial ovarian cancer with the five-year survival rate of approximately only 40%. Platinum-based chemotherapy together with surgical cytoreduction is the standard of care in HGSOC. Platinum compounds bind to DNA causing intra- and interstrand cross-links ultimately leading to severe DNA damage in the form of DNA double-strand breaks. Functional DNA repair mechanisms, most importantly homologous recombination (HR), are crucial in repairing these double-strand breaks and maintaining genomic integrity. HR deficiency is found in approximately 50% of HGSOC tumours making these tumours sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase (PARP) inhibitors. The androgen receptor (AR) has been reported to be expressed widely in the normal ovarian surface epithelium as well as in malignant ovarian cancer cells. With the current evidence pointing towards the involvement of AR signalling in the maintenance of HR as well as driving radiation resistance, combined or sequential use of anti-androgen therapies together with platinum-based compounds might function as a novel therapeutic approach and lead to the accumulation of DNA damage within HGSOC tumours. Blocking AR signalling in prostate cancer cells receiving androgen deprivation therapy has already been shown to functionally impair HR and result in the upregulation of PARP mediated pathways. To investigate the expression levels of AR within the human primary HGSOC tumour specimens, immunofluorescent immunohistochemistry together with reverse transcriptase polymerase chain reaction were performed. The androgen receptor was found to be expressed in approximately 75% of the patient samples with ≥10% nuclear AR staining. Intriguingly, the AR expression did not differ between primary and metastatic tumours or between chemo-naïve and chemotherapy treated samples. Moreover, the effects of AR inhibition and stimulation on the functional HR capacity of HGSOC cells was examined to elucidate the role of AR signalling in the homologous recombination DNA repair pathway. Receptor manipulation with an antagonist enzalutamide prior to gamma radiation led to a significant decrease in the HR capacity of HR- proficient and AR positive commercial HGSOC cell line OAW28. Furthermore, agonist treatment with dihydrotestosterone increased the HR capacity within these cells. A deeper understanding on the interactions between HR and AR signalling can be utilized in the development of future therapeutic strategies against platinum resistant HGSOC. Pharmaceutically induced HR deficiency has the potential to provide opportunities for a wide range of combination treatment strategies using standard of care chemotherapy in conjunction with molecularly targeted agents towards DNA damage response proteins as well as widen the therapeutic possibilities for the use of PARP inhibitors.