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Background: Treatment of chronic insomnia is problematic and alternative methods besides drug therapy are sought out for. The aim of the study was to find out about the effects of Neurosonic-low frequency therapy chair on patients with primary insomnia. Therapy is based on Whole-Body Vibration (WBV). Methods: This pilot study consisted of 16 adults (12 men, 4 women; age range 28 - 65) that suffered from insomnia with an Insomnia Severity Index (ISI) of at least 15. They were randomized into control and intervention groups (8 + 8). Both groups received WBV-treatment for five times. At the start of the study control group had a three week period when they did not receive treatment. Measurements were taken using actigraphy, SCL-90-, WHO-5-, PSQI-, ISI-, EQ-5D-questionnaires and a structured sleep questionnaire based on the Basic Nordic Sleep Questionnaire. Results: After treatment ISI-scores decreased in both groups. After treatment the WHO-5- and EQ-5D VAS-score were also ameliorated. Treatment also lowered SCL-90 scores related to anxiety, obsessive compulsive and somatization symptoms. Conclusions: Our results indicate that WBV-treatment has beneficial effects for people suffering from primary insomnia. WBV-treatment also seems to relieve anxiety. No major adverse effects were detected. WBV-treatment may be useful for example in the treatment of insomnia in situations where pharmacological treatment is insufficient. Further studies should be done to have more information about the usefulness of WBV based therapy in treatment of insomnia.

Merkelcellskarcinom (MCC) är en ovanlig och agressiv neuroendokrin hudcancer vars cellulära ursprung är okänt. Genomet av Merkel cell polyomavirus (MCPyV) är integrerat i genomet av tumörcellerna i cirka 80% av MCC-tumörer. Baserat på proteinexpressionsmönster anses cellerna i MCC vara närmast besläktade med Merkelceller (mekanoreceptiva celler i huden). Av denna orsak har Merkelceller antagits vara ursprungscellen för MCC men detta har aldrig bevisats. Höga grader av PAX5- och TdT-expression har observerats i MCC, detta tyder på möjligheten att ursprungscellen för MCC inte är den postmitotiska Merkelcellen utan snarare en pro/pre- eller pre-B cell eftersom co-expression av PAX5 och TdT är begränsat till dessa celler under fysiologiska omständigheter. I denna studie undersöktes expressionen av PAX5 och TdT i 117 MCC-tumörer med immunohistikemi. Utav de 117 tumörerna som undersöktes expresserade 31.6% TdT, 22.2% expresserade PAX5 och graden av co-expression var 11.1%. Dessa expressionsgrader är betydligt lägre än vad som observerats i tidigare studier. Vidare observerades ett statistiskt signifikant samband mellan expressionen av TdT och närvaro av MCPyV DNA samt mellan expressionen av TdT och antalet kopior av MCPyV-genomet i tumörvävnaden. Inget statistiskt signifikant samband observerades mellan expressionen av PAX5 och/eller TdT och prognos vilket underminerar användningen av dessa markörer i kliniskt syfte.

Lymphangiogenesis is crucial for the formation of a fully functional lymphatic vasculature. Dysfunctional lymphatic vasculature is associated with many pathologies including lymphatic malformations, lymphedema, and inflammation. This thesis aimed to elucidate the function of the lymphatic endothelial cell expressed β1-integrin in postnatal lymphangiogenesis in mice. To investigate this, Itgb1 gene was conditionally deleted from the lymphatic vasculature of mouse pups at postnatal day two, using the Cre-Lox recombinase system. Ears of the mice were collected at postnatal day twenty-one, and immunostained for lymphatic vessel, mural cell, and extracellular matrix markers. Relative gene expression analysis was performed from whole ear lysates and isolated endothelial cells. Mice lacking Itgb1 gene presented a disorganized dermal lymphatic vascular network, characterized by dilated capillary and collecting vessels. Collecting vessel specification was abnormal showing persistent LYVE1 expression, lack of V-shaped lymphatic valves, and complete loss of smooth muscle cell coverage. Relative gene expression analysis of isolated endothelial cells revealed a decrease in Pdgfb, a gene associated with smooth muscle cell recruitment. These results indicate a significant role for β1-integrin in postnatal lymphangiogenesis and highlight the complexity of postanal lymph vessel formation. Nevertheless, further studies are needed to specify the mechanisms behind this phenotype. Increasing knowledge in this field is important, because pathologies related to lymphangiogenesis can cause debilitating symptoms and therefore there is a need for therapeutic options.

Introduction: Mobile devices provide medical students with easy access to medical information and educational resources. Since 2013, we’ve followed the study use of iPads among the medical students. In 2016, we observed a notable drop in the overall mobile device usage in the first cohort of medical students entering their clinical studies. Aim of the study: In this study, we sought to identify the hurdles for adopting mobile devices among three consecutive cohorts of medical students at the beginning of their clinical studies. We sought to answer the following questions: (1) How did the students assess their own and their clinical teachers’ ability to use iPads in learning and teaching? (2) How did the clinical before-class and in-class assignments support the students’ use of the new technology? (3) How did students use the mobile device with patients? Material and methods: The data were collected with online surveys among the first three cohorts of medical students who had studied with iPads and started their clinical studies in the spring of 2016, the autumn of 2016 and the autumn 2017. In this study we focused on the closed-ended multiple choice and 5-point Likert scale questions which we analysed by the distribution frequencies in the three cohorts. Results: The response rates ranged from 67.5% (3rd cohort) to 90.8% (1st cohort). Students rated their own ability of using the iPad in studies as good or excellent whereas their teachers’ ability to use these devices relatively low. The students wished for more pre-assignments (tests and videos) and in-class assignments (voting, tests and tasks) to stimulate their learning. Furthermore, they reported that clinical teachers seldom told them about applications related to their clinical field. The students primary use of mobile devices was for seeking information online. Students were hesitant in using the device in direct patient contact. Discussion: Our findings were consistent with previous research in observing a notable hesitance in using the mobile device with patients. These concerns were raised both among students and teachers. Furthermore, the teachers seldom communicated about suitable and quality medical applications. The clinical teachers require support and training in adopting mobile device compatible pre-class and in-class assignments in their instruction.

Liver transplantation (LT) procedure has evolved tremendously over the last 40 years and is nowadays a standard treatment for both end-stage liver disease and acute liver failure. Improved immunosuppressive medication, surgical methods, imaging and intensive care raise the probability of successful transplantation. Despite good prognosis of survival, acute rejection (AR) is still a significant clinical factor that negatively affects LT outcomes. In the last decade, whole genome-wide incompatibility between recipients and donors has emerged as a potential risk factor in both hematopoietic stem cell and kidney transplantations. The role of non-human leukocyte antigen (HLA) factors in LT outcomes has not been comprehensively established. Thus, the aim of this study is to compare patient and donor genomes pairwise, identify mismatches and further, analyze the effect of these mismatches on AR. After data preparation, 666 LT recipient-donor pairs were included in the analyses. Genotype imputation yielded 8 706 949 variants after quality control. From these variants, 28 225 missense variants were identified and utilized in the genome-wide mismatch analyses. In this study, we calculated genome-wide mismatches of missense variants to identify incompatibilities in all, transmembrane and secreted, transmembrane-only and liver-related proteins between recipients and donors. In addition, we analyzed the effect of mismatches in 40 common deletions and also the sum of deletion-mismatches. We estimated the association of genetic mismatches and time to AR by using Cox proportional hazards model adjusted with recipient and donor age, recipient and donor sex, cold-ischemia time, HLA I eplet mismatch and HLA II eplet mismatch. According to the findings of the study, there is no association between missense variant mismatches coding for either all, transmembrane and secreted, transmembrane-only or liver-related proteins and time to AR. There was also no association between quartiles of missense variant mismatches and time to AR. In the genomic collision model, we found mismatch in deletion-tagging variant rs1523688 to be associated with a decreased risk for AR (adjusted hazard ratio (HR) 0.38, 95% confidence interval (CI) 0.16–0.92, P-value 0.032) and mismatch in rs11985201 to be associated with an increased risk for AR (adjusted HR 1.44, 95% CI 1.04–2.00, P-value 0.030). However, neither of these P-values passed the Bonferroni corrected significance level of 0.00125. No association was observed between deletion mismatch sums and time to AR. In conclusion, we observed no statistically significant association between the genome-wide incompatibility and time to AR in the study cohort of 666 LT recipient-donor pairs. To increase detection power, large-scale studies are required to verify the role of genome-wide mismatches in LTs.

Tutkimme artikkelissamme tulojen ja onnellisuuden suhdetta, sekä sen ekologisia vaikutuksia. Aineistona käytämme EU:n tulo- ja elinolotilastoja ja sen hyvinvointimoduulia vuodelta 2013. Aineisto kattaa 32 eurooppalaisesta maasta ja yli 300 000 ihmistä. Ensinnäkin osoitamme, että tulojen ja onnellisuuden -suhde muodostaa niin sanotun S-käyrän. Tämä tarkoittaa, että tulot-muuttuja menettää voimansa ennustaa koettua hyvinvointia tulojakauman molemmissa päissä. Tämä koetun hyvinvoinnin satioituminen sopii yhteen absoluuttisen tuloteorian kanssa. Teorian mukaan onnellisuus kasvaa tulojen mukana siihen tulotasoon asti, jossa perustarpeet ovat täysin tyydytettyjä. Tämä koskee kolmea keskeistä mittaria, jotka nykykäsityksen mukaan tavoittavat koetun hyvinvoinnin keskeiset pääulottuvuudet: elämän arviointi (life evaluation), mielekkyys (meaningfulness) ja emotionaalinen hyvinvointi (emotional well-being). Näiden muuttujien sati-aatiopisteet ovat 98., 99. ja 88. persentiilien kohdalla. Toiseksi osoitamme, että itsearvioidut vähimmäistarpeet tyydyttyvät tulotason saavuttaessa noin tuhat euroa kuukaudessa. Tämä taso on korkeampi kuin kirjallisuudessa vakiintunut käsitys. Kolmanneksi osoitamme, että kyseiset tulotasot eivät ole ekologisesti kestäviä nykyisten politiikkatoimien ympäristössä. Vähimmäistarpeiden taso ylittää planeetan kestävyyden rajat vähintään kertoimella 1.7. Satiaatiopisteessä kestävyyden rajat ylittyvät jo vähintään kertoimella 20. Tuloksemme viittaavat siihen, että tarvitaan voimakasta harjoitetun politiikan muutosta, jotta kaikkien perustarpeet voidaan tyydyttää ekologisesti kestävällä tavalla.

Aims. Shame-prone people have been found to be prone to both cognitive externalization of blame and aggressive behavior. Aggression and externalization of blame have also been linked to narcissistic personality in several studies. The present study sought further evidence on the mediating role of externalization of blame with regards the relationship between shame proneness and aggression and narcissism and aggression. Methods. Total of 564 volunteer students, aged from 18 to 57 years of age, participated in this study. The participants had answered an e-form, including background information, the Narcissistic Personality Inventory (NPI), TOSCA-3 meter for measuring shame proneness and tendency to externalize blame, and the Anger Response Inventory (ARI). Explorative factor analyzes were used for analyzing the data. The relationships between shame proneness, narcissism, externalization of blame and verbal and physical aggression were further studied using mediation analysis with bootstrapping. Results and Conclusions. In the present study, the earlier results regarding the presence of both direct and indirect links of shame proneness and narcissism to verbal aggression were repeated. In contrast to earlier studies, where externalization of blame was shown to mediate the connection between shame proneness and physical aggression entirely, also a direct link between these constructs was found in this study. In addition, the study provided also indications of the presence of both direct and indirect links between narcissism and physical aggression. The results thus show that externalization of blame mediates the relationship of both shame proneness and narcissism to both verbal and physical aggression. Overall, the study has its contributions to the research of shame proneness and narcissism and provides a partial answer to the question why aggression occurs.

In this study, we set out to gain insight into women’s childbirth experiences in Helsinki University Central Hospital. We examined the effect the mode of delivery has on maternal satisfaction. Additionally, we aimed to identify other possible factors influencing the maternal childbirth experience. The childbirth experiences of 600 randomly selected women who gave birth in Helsinki University Hospital between 2018-2019 were analysed. The data was collected from patient record system Obstetrix, and it comprised of 100 women from each of the following groups: spontaneous vaginal delivery, induced vaginal delivery, vaginal delivery by vacuum extraction, elective caesarean section, emergency caesarean section and crash caesarean section. Maternal satisfaction was assessed from scores women had given on the Visual Analogue Scale and how they had described their experience to midwives. Microsoft Excel was used for the recording of the data and statistical software IBM SPSS Statistics 24 was used for statistical analysis. We found the mode of delivery to significantly affect maternal satisfaction with childbirth. Spontaneous vaginal delivery is the fulfilling mode of delivery, followed by elective caesarean section and induced vaginal delivery. Maternal satisfaction decreased with unplanned interventions, with crash caesarean section being the least satisfying mode of delivery. However, several other factors influenced the childbirth experience, too. Caregiver behavior has a significant effect women’s satisfaction. Women who suffer from fear of childbirth during pregnancy experience childbirth more negatively. We suggest further research on the treatment of fear of childbirth.

Objectives: During The Cardiovascular Risk in Young Finns (LASERI) -longitudinal study, a large amount of psychological traits have been measured. A temperament or personality inventory has not been previously made with a Finnish data. The goals of this study are 1) to find the orthogonal factors, that best simplify the variance of the psychological traits measured in the LASERI-study, 2) to create a prototype of a personality inventory that measures these newfound factors using an inductive approach, 3) to study the properties of the created prototype as well as the connections between it and depression, and 4) to develop ways to improve the prototype. Methods: A large amount of factor analyses were made to the questions of eleven psychological inventories used on 2879 test subjects in the LASERI-study in the years 1997 – 2012. The factors present most often were chosen as the structure of the prototype. Occurrence rate and reliability were used to limit the amount of questions. The structure of the prototype was studied using explorative factor analysis, its reliability using Cronbach’s alpha and split-half method, the social variables using variance analysis, and the connections between the prototype and depression using logistic regression. Results and conclusions: The Nine Factor Inventory (9FI), the created prototype of a personality meter consists of nine factors that have good reliabilities and psychological interpretations. The structure is a fine way to simplify the variance of the psychological traits measured in the LASERI-study. The test subjects got different results from 9FI depending on their sex, age, and the point of the measurement. The amount of common variance between 9FI and experienced depression was 6,8 %. A plethora of ideas how to better create a personality meter or how to improve 9FI were made.

New treatment methods are urgently needed for glioblastoma (GBM), the most common malignant primary brain tumor in adults, that currently lacks any curative treatment. Targeted therapeutic approaches have shown promising results already, but common drug delivery vehicles come with efficacy issues and are restricted by their safety and toxicity profiles. Exosomes, cell-produced nanosized vesicles, have emerged as a new potential carrier for gene therapies in cancer treatment due to their natural material transport properties, biocompatibility, and specificity in transporting cargo to the target cells. These extracellular vesicles have the additional advantage of being able to cross the blood-brain-barrier (BBB), which makes them especially valuable for brain malignancies, such as glioblastomas. So far, gene therapy approaches in exosomes have focused on RNA in cancer treatment, but research findings are limited with plasmid-based gene therapies using exosomes. The main concern has been whether the increased plasmid size would decrease the transfection efficiency of the plasmid into the exosomes. This study aimed at setting-up exosomes as plasmid-based gene therapy nanocarriers. To achieve this, different plasmid-based gene therapies were tested, including the targeting of common aberrations of GBM cells to impair proliferation and the use of cytotoxins to induce apoptosis in the target cells. The plasmids were transfected into exosomes and subsequently inoculated into patient-derived glioblastoma cells with the aim of decreasing the number of glioblastoma cells. The findings of this study demonstrate a successful set-up of an exosome-based gene therapy in patient-derived glioblastoma cells by using engineered HEK293FT cell derived exosomes consisting of a plasmid-based combination gene therapy encoding the cytotoxins Granzyme B and Diphtheria toxin fragment A.