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Goals: According to Developmental Origins of Health and Disease hypothesis, maternal prenatal factors are associated with offsprings’ health and susceptibility for non-communicable disease. In previous studies, maternal cortisol and sleep difficulty have been separately associated with multiple negative outcomes for the offspring. However, little is known about the association of maternal sleep difficulty and cortisol during pregnancy. The goal of this thesis is to examine the association of sleep difficulty and maternal diurnal cortisol during early pregnancy. Methods: The study sample (N=310) comes from the prospective pregnancy cohort study “The InTraUterine sampling in early pregnancy” (ITU). Sleep difficulty was assessed with Pittsburgh Sleep Quality Index at early pregnancy on average 18.20 (sd=1.73) weeks gestation (between 12.43–21.86 weeks gestation). Salivary cortisol was measured seven times a day for one day: upon waking, 15 minutes after awakening, 30 minutes after awakening, at 10 a. m., at noon, at 17 p. m., and at bedtime. Salivary cortisol samples were collected between gestation weeks 12–20, on average at 18.88 weeks’ gestation (sd=1.48). General linear model and mixed design analysis of variance were used to study the association of sleep difficulty and diurnal salivary cortisol. Anxiety and depression symptoms, maternal age and education were included as covariates in general linear model analyses. Results: The total number of different kinds of sleep difficulties was not associated with salivary cortisol upon waking or at bedtime or cortisol awakening response, mean diurnal cortisol concentration, diurnal cortisol slope or diurnal cortisol change. Some specific types of sleep difficulties were associated with diurnal cortisol. Namely, greater sleep latency was associated with higher awakening cortisol and higher mean cortisol concentration. Daytime dysfunction was associated with lower awakening cortisol level and sleep disturbance (physical symptoms, that disturb sleep) was associated with flatter diurnal cortisol slope. Conclusions: Even though the total number of different kinds of sleep difficulties was not associated with diurnal cortisol, the results of this thesis suggest a possible association between specific type of maternal sleep difficulties and diurnal cortisol during early pregnancy. Longitudinal study protocols are needed to identify the possible causal mechanism between possible associations of specific sleep difficulties with cortisol during pregnancy. To examine biological fetal programming mechanisms, follow up on offspring birth weight, cognitive development and mental health should be included in these studies.

Objectives. Children and youth gain many positive physical, individual and social skills by participating in organized sport activities. According to previous research, children’s sport participation, especially team sports, protects them against psychiatric problems, but the findings of studies comparing team and invidual sports are not consistent. Evidence is also inconsistent in regards whether the effects are similar for boys and girls. Little is known about the effect of child’s psychiatric history to the association of sport participation and current symptoms. The objective of this study was to investigate the associations of sport participation and sport relatedness on team/individual continuum with psychiatric symptoms in 7–11-year-old children, taking into account child’s sex and history of borderline level psychiatric problems. Methods. The data in this study was a sample (N=1267) of PREDO follow-up study (The Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction, concerning 7–11-year-old children. Information about sport participation was reported by mothers, answering open questions about their child’s sport participation in the social competence section of CBCL/6–11 questionnaire (Child Behaviour Checklist). Sport participation was categorized dichotomously (yes/no) and 4-point scale was used to categorize sport relatedness. Information about children’s internalizing, externalizing and total problems was reported by mothers, answering the psychiatric problems section of CBCL/6–11 questionnaire. The associations between sport participation, sport relatedness and psychiatric problems were examined with linear regression models. Results and conclusions. Child’s participation in organized sports was associated with fewer internalizing, externalizing and total problems compared to no sports, and team sports requiring continuous team work was associated with fewest internalizing problems. These findings are consistent with previous research. The favorable effects of sport participation were more common for boys. Children with a history of borderline level externalizing problems didn’t obtain the protective effects of team sports requiring continuos team work, compared to independent physical exercise or individual sports. The results indicate that the protective effects of sport participation and team sports differ according to child’s sex and history of psychiatric problems.

Background: To assess whether the use of point-of-care testing (POCT) and early assessment team (EAT) model shortens emergency department (ED) length of stay (LOS). Methods: This observational study was performed in three phases in a metropolitan ED with 57,000 annual visits. Data were collected from adult ambulatory patients who were discharged home. Phase 1 served as a control (n=1559 in one month). In phase 2, a comprehensive POCT panel including complete blood count, sodium, potassium, glucose, C-reactive protein, creatinine, alkaline phosphatase, alanine aminotransferase, bilirubin, amylase, and D-dimer was launched (n=1442 in one month). In phase 3 (n=3356 in subsequent two months), POCT approach continued. In addition, the working process was changed by establishing an EAT consisting of an emergency medicine resident and a nurse. The team operated from 12 noon to 10 p.m. was. The primary outcome was LOS (hh:mm) in the ED. Waiting times for patients requiring laboratory testing were analysed also, including time from admission to laboratory blood sampling (A2S interval), time from blood sampling to results ready (S2R interval) and time from results to discharge (R2D interval). Results: Median LOS of patients requiring laboratory tests in phase 1 was 3:51 (95% confidence interval 03:38–04:04). During phase 2, introduction of POCT reduced median LOS by 29 minutes to 03:22 (03:12–03:31, p=0.000). In phase 3, the EAT model reduced median LOS further by 17 minutes to 03:05 (02:59–03:12, p=0.033). Altogether, the process was expedited by 46 minutes compared with the phase 1. Surprisingly, A2S interval was unaffected by the interventions among all patients needing laboratory testing. In comparison to phase 1, shortening of S2R interval was observed in phase 2 and 3, and that of R2D interval in all patients with laboratory assessments in phase 3. Conclusions: The advantage of POCT alone compared with central laboratory seemed to lie in shorter waiting times for results and earlier discharge home. Moreover, POCT and EAT model shorten LOS additively compared with conventional processes. However, a longer time is seemingly needed to adopt a new working process in the ED, and to establish its full benefit.

Lipid droplets (LDs) are ubiquitous intracellular storage organelles, consisting of a core of energy rich neutral lipids surrounded by a phospholipid monolayer. Research in the past decade has expanded the view on LDs from simple, passive cytosolic inclusions to dynamic organelles which play an important role in many cellular processes. Furthermore, there is mounting evidence for links between LD biology and human pathologies, such as metabolic disorders, non-alcoholic fatty liver disease and cardiovascular diseases. Thus, understanding the basic biology of LD formation is crucial. LD biogenesis is thought to occur in the microdomains of endoplasmic reticulum (ER), due to the accumulation of neutral lipids between the two leaflets of the ER bilayer before budding into the cytosol. Many proteins are involved in this early formation, but no single indispensable protein has been discovered. After assembly, these early LDs grow through lipid deposition from the ER, and with lipid synthesis on the droplet monolayer. During LD growth, LDs are thought to retain connection to the ER. A protein important for LD biogenesis is seipin. This oligomeric ER protein has been found to localize at contact sites between the ER and LDs. Mutations in seipin give rise to three distinct diseases in humans; BSCL2, seipinopathy and Celia’s encephalopathy. The role of seipin in the formation of LDs and the pathogenesis of these diseases is still unknown. Work from numerous model systems has shown seipin to be important for LD biogenesis and adipocyte differentiation. LD formation is a complex process which is still poorly understood, and seipin likely collaborates with other proteins during LD assembly. In this thesis, APEX2-mediated proteome mapping combined with LC-MS/MS, is set up to identify proteins involved in LD biogenesis. In this technology, an engineered ascorbate peroxidase, APEX2, is genetically inserted to the intracellular region of interest where it rapidly biotinylates nearby endogenous proteins upon exposure to biotin-phenol and hydrogen peroxide. Biotinylated proteins can then be enriched by using streptavidin beads and identified with a mass spectrometry. The aim using this technology is to unravel new interaction partners of seipin and proteins important for LD formation, which is a crucial step for understanding LD formation and diseases related to it.

Objectives. In Western Countries, like Finland, religiosity has simultaneously changed and declined. Respectively, nonbeliever identities have increased, but they haven’t received much research attention. Comparisons between believers and nonbelievers have been popular in the past research, and they’ve revealed differences in religious attitudes, intuitive and analytical thinking styles and ontological confusions. The aim of this research was to examine if those factors contribute to differences between groups formed based on nonbeliever identities. Believers were included to the study as a reference category. Methods. The data was collected as a part of the Uncovering the Hidden Nature of Unbelief research project. It consisted of 2112 adult Finns (age 18 to 84) who attended a survey. Religious and nonreligious identities were assessed by asking subjects to choose an option they felt most affiliated. Ontological confusions were assessed by the shortened version of the Core Knowledge Confusions scale, and thinking styles with the shortened version of Rational Experimental Inventory (REI). Two other Likert-scales were used to assess Belief to God and religious attitudes. Differences between the identity groups and factors contributing to them were analyzed by multivariate analysis of anova and discriminant analysis. Results and discussion. Most of the participants identified as atheists or agnostics. Differences between identity groups were detected in all of the factors examined: belief to god, religious attitudes, thinking styles and ontological confusions. Based on these differences, the participants were divided into four groups. A combination of belief to god, religious attitudes and intuitive thinking style formed a factor contributing to most differences between these groups. The results indicate that nonbelievers compose perhaps a more heterogenous group than assumed earlier, also when cognitive factors are taken into acknowledge. This is something to be taken into account in further studies.

Artikkelin abstrakti: Introduction: Risk stratification in the emergency departments (EDs) is in critical need for new applications due to ED overcrowding and hospitalization of older people. We aimed to evaluate the expediency, efficiency and safety of a prognostic biomarker, soluble urokinase plasminogen activator receptor (suPAR), as a tool for the risk assessment of patients arriving at the ED. Methods: We performed a comparative cross-sectional study in two emergency departments (EDs), suPAR measurements being incorporated into routine blood sampling in the intervention ED. The primary outcome was the number of discharges from the ED. The importance of the outcomes was examined by appropriate multi- or bivariate analysis. Results: The absolute and relative number of discharges were similar between the intervention and control groups [121 (55,3%) vs 62 (55,9%)]. No significant differences between the groups were seen in the length of stays in the ED. Patients with low suPAR values were more likely discharged and patients with high suPAR values more likely admitted to hospital. Two admitted patients with low suPAR values could have been discharged safely. Conclusion: The utilization of suPAR did not increase the risk for neither positive nor negative outcomes. Low suPAR values could be potential in discharging more patients safely. Instead of unselected patient populations, the benefits of suPAR measurements in the ED could emerge in the assessment of a more precisely determined and selected group of patients.

Undersökningens syfte var att utreda hur återupplivningsverksamheten ser ut på de fyra kretssjukhus som tillhör HNS men inte HUCS. Sjukhusen har alla operativ verksamhet och ett sammanlagt befolkningsunderlag på över 400000 invånare. Målet var att utreda hur återupplivningen är organiserad, hur återupplivningsskolning genomförs samt hur återupplivningsresultat samlas in. Liknande studier har inte tidigare gjorts på regionalnivå. Svarsprocenten på den elektroniska enkät som skickades till sjukhusens återupplivningsansvariga läkare och sköterska med ansvar återupplivningsskolning steg till 100 %. Resultaten visar att man idag följer Gängse vård-instruktionerna bättre än tidigare. Idag finns det skötare med ansvar för återupplivningsskolning och läkare med återupplivningsansvar på alla sjukhus. Frekvensen av återupplivningsskolning är fortfarande lägre än rekommenderat, men högre än tidigare. 75 % av sjukhusen har en MET-grupp. Alla sjukhus använder inte HNS officiella återupplivningsblankett och rapporteringen görs inte enligt Utstein-modellen. Undersökningen lyfter fram så väl brister som styrkor i återupplivningsverksamheten. Men med denna kunskap möjliggörs skräddarsydd utveckling av återupplivningsverksamheten på sjukhusen.

Tutkimuksen tarkoitus: Tarkoituksena oli tehdä kirjallisuuskatsaus Hodgkinin lymfoomasta, jossa tauti ja sen hoitovaihtoehdot kuvataan pääpiirteisesti. Lisäksi viime vuosina HUS syöpäkeskuksessa Hodgkinin lymfooman uusilla biologisilla lääkkeillä brentuksimabivedotiinilla (BV) tai programmed death ligandi 1(PD1) -estäjillä hoidetuista potilaista tehtiin analyysi, jonka tavoitteena oli kartoittaa näiden lääkkeiden tehoa ja haittoja lymfooman hoidossa. Materiaalit ja menetelmät: Kirjallisuuskatsausta varten etsittiin PubMedistä aiheeseen liittyviä artikkeleita, käyttäen esimerkiksi hakusanoja ”Hodgkin lymphoma”, ”brentuximabvedotin” ja ”PD1-inhibitor”. Analyysia varten kerätty aineisto koostuu HUS Syöpäkeskuksessa vuosien 2016 ja 2019 välillä brentuksimabivedotiini tai PD1- estäjähoitoa saaneista potilaista. Potilastietoja kerättiin sähköisistä hoitokertomuksista. Aineiston perusteella laskettiin BV- ja PD1-estäjälääkkeiden hoitovasteen kesto ennen syövän uusimista sekä kokonaiselossaoloaika. Lisäksi kerättiin ylös tieto hoitokertomukseen potilaiden raportoimista hoitojen haittavaikutuksista. Tulokset: Potilaista (N=11) noin puolet oli naisia ja puolet miehiä. Sairastumisen mediaani-ikä oli 23 vuotta. Diagnoosihetkellä syöpä oli paikallinen yhdellä ja levinnyt kymmenellä potilaalla. Kaikki aineiston potilaat saivat jossain kohtaa PD1-estäjähoitoa, yhdeksän potilasta sai lisäksi myös brentuksimabivedotiinihoitoa. Sekä brentuksimabivedotiini että PD1-estäjähoidolla autologiseen tai allogeeniseen kantasolusiirtoon päästiin etenemään noin kolmasosan potilaista kohdalla. Kaikkien aineiston potilaiden tauti uusiutui BV-hoidon jälkeen. PD1-estäjähoidon jälkeen HL uusiutui noin puolella potilaista. Seurannan päättyessä kolme potilasta oli kuollut. Elossa olevista potilaista syöpä oli uusiutunut tai hoitoja oli yhä käynnissä kolmasosalla, loput potilaat olivat remissiossa. Suurin osa potilaista raportoi jotain haittoja PD1- tai BV-hoitoon liittyen, suurin osa näistä haitoista oli lieviä. Hoidon keskeytykseen johtaneita haittoja oli yhdellä PD1- estäjää saaneella potilaalla. Johtopäätökset: Aineisto tukee uusien biologisten lääkkeiden käyttöä edeltävästi paljon hoitoja saaneiden Hodgkinin lymfoomapotilaiden kohdalla. Lääkkeillä voidaan päästä etenemään potentiaalisesti kuratiivisiin kantasolusiirteisiin.

Sydämen vajaatoimintapotilaiden heikosta ennusteesta johtuen uusien lääkeaineiden kehitys ja tutkiminen on tärkeää. Tutkimuksen tavoitteena oli selvittää levosimendaanin ja kahden uuden lääkeaineen, mitoTEMPO:n sekä omecamtiv mecarbil:n suoria ja lääkealtistuksen vaikutuksia rotan sydämen mitokondrioihin. Joko terveen tai iskemia-reperfuusivaurion omaavan rotan sydämestä otettiin kudosnäyte, jonka mitokondriot eroteltiin PBI shredder laitteella. Mitokondrioiden hapenkulutusta mitattiin kahdella eri protokollalla Oroboros oxygraph 2k laitteella. Kontrolliin verrattuna iskemia-reperfuusiovaurio kasvatti mitokondrioiden hapenkulutusarvoja ja heikensi kytkentäastearvoja. Ennen vauriota suorittu rottien altistaminen omecamtiv mecarbille tai mitoTEMPO:lle sai aikaan hapenkulutusarvojen ja mitokondrioiden kytkentäastearvojen siirtymisen kohti kontrolliarvoja. Levosimendaanialtistuksen seurauksena mitokondrioiden kytkentäastearvot pysyivät vaurioituneen sydämen tasolla. MitoTEMPO oli ainut lääkeaine, jolla näyttäisi olevan suoria vaikutuksia mitokondrioihin. Tutkimus osoitti, että käytetty tutkimusmenetelmä on toistettava ja helppo toteuttaa. Jatkossa tulos mahdollistaa saman tutkimusmenetelmän käytön muiden eläinten näytteiden ja potilasnäytteiden tutkimiseen. Lisäksi tutkimuksen perusteella omecamtiv mecarbil ja mitoTEMPO suojaavat sydämen mitokondrioita iskemiareperfuusiovaurioilta.

Tutkielman tarkoituksena oli tuottaa kirjallisuuskatsaus karieksen diagnostiikassa käytettävistä optisista karieksen havainnointimenetelmistä. Tutkielmassa käsitellään aluksi karieksen havainnointia visuaalisesti ja röntgentutkimuksin ja lopuksi perehdytään karieksen optisiin havainnointimenetelmiin. Aineisto kerättiin PubMed -tietokannasta. Hakusanoina käytettiin: VistaCam, DIAGNOcam, NILT, fluorescence and caries, DIAGNOdent, occlusal caries detection ja approximal caries detection. Optisia karieksen havainnointimenetelmiä ovat esimerkiksi DIAGNOcam (DC) ja VistaCam (VC). Optiset karieksen havainnointimenetelmät ovat ei-ionisoivia kuvausmenetelmiä, joissa laite tuottaa valon eri aallonpituuksia. DC-kamera tuottaa röntgenkuvien kaltaisia mustavalkoisia kuvia. DC:ssa aallonpituudeltaan 780 nm valoa johdetaan valokuitua pitkin pehmytkudoksen läpi ja sieltä hampaan kruunua pitkin okklusaalipintaa vasten olevaan sensoriin. Sensori rekisteröi hampaan läpäisseen valon ja tuottaa digitaalisen kuvan. VC-kameran toiminta perustuu fluoresenssiin. VC-laite tuottaa valoa kahdesta LED-valonlähteestä, joiden aallonpituus on 405 nm. Laitteen kamera rekisteröi fluoresenssin ja tuottaa digitaalisen kuvan, missä rakenteet näkyvät eri värein ja numeerisina arvoina 0-4. Kirjallisuuden perusteella DC ja VC ovat hyviä apuvälineitä visuaalisen havainnoinnin ja röntgentutkimuksien lisäksi, mutta eivät kuitenkaan ensisijaisia menetelmiä. Ensisijaisia kariesdiagnostiikan menetelmiä ovat visuaalinen havainnointi ja röntgentutkimus. DC-kuvia verrattiin useissa tutkimuksissa bitewing-kuviin ja DC-laitteen havainnointikyky kariesvaurioissa oli yhtä hyvä tai parempi kuin bitewing-kuvissa. VC-laitteesta oli vähemmän tutkimuksia kuin DC-laitteesta, mutta ne osoittivat VC:n olevan hyvä apuväline okklusaalipinnan kariesvaurioiden havainnoimisessa. Ei-invasiisivisena, ionisoivaa säteilyä lähettämättömänä DC- ja VC tutkimus voitaisiin toistaa usein ja tutkimus voitaisiin tehdä myös suuhygienistin toimesta.