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Cardiovascular diseases (CVDs) are the leading cause of death worldwide and the major cause for them is atherosclerosis. Atherosclerosis is a state of chronic inflammation of the arterial wall, which slowly progresses to form plaques that can eventually obstruct blood flow. The resulting hypoxia in the tissues affected by the ischemia manifests as clinical symptoms such as chest pain. All this begins with chronically high LDL-C concentrations in the blood. LDL-C is transported into the intima of the arterial wall where it is modified with for example oxidizing enzymes. Intimal macrophages remove oxidized LDL via phagocytosis, which leads to lipid accumulation that turns macrophages into foam cells. At first, foam cells die via apoptosis as they are removed by other macrophages. At some point, macrophages cannot remove all the apoptotic material, which leads to a necrotic release of the cell contents. This creates a necrotic core in the center of the atherosclerotic plaque. The inflammatory environment makes vascular smooth muscle cells proliferate and form a fibrous cap to protect the prothrombotic necrotic core. Eventually the plaque can rupture, which leads to the formation of a thrombus and possibly even thrombosis. To prevent this, drugs including statins, ezetimibe and PCSK9 inhibitors are widely used along with certain dietary modifications. More options for diagnosing, preventing, and treating atherosclerosis are still needed to decrease the burden of atherosclerosis and CVDs on both the individual and healthcare systems. A potential example of such methods is presented in this review. This method utilizes synthetic LDL receptors to isolate LDL from the blood, which is needed for determining the quality of LDL particles. The knowledge of LDL quality helps predict the individual risk for developing atherosclerosis.

Social fobi(SF) definieras som en uttalad eller bestående rädsla för en eller flera olika sociala situationer. SF präglas av en förvrängd uppmärksamhet av social stimuli. Vi undersökte skillnader i självreferens processering i SF genom att rekrytera 20 friska kontroller och 38 personer med SF. Försökspersonerna undergick fMRI mätning medan de kategoriserade ord som visades till dem som positiva, negativa eller neutrala i kontext till en situation att de hör en grupp med personer säga ordet ifråga.SF gruppen delades itu och undergick ett randomiserat dubbelblindat experiment med escitalopram eller placebo i 7 dygn. Därefter utfördes fMRI mätningen pånytt med en liknande kategoriserings uppgift. Under experimentet uppföljdes nivån av ångest med självrapportering via STAI-Y1 frågeformulär. Vi observerade en ökning av aktivation i vänstra inferiora frontala gyrus till negativt socialt stimuli i den friska gruppen i kontrast till SF gruppen. Efter interventionen observerades normalisation i samma region i vänstra inferior frontala gyruset i escitalopram gruppen men inte i placebo gruppen. Vi observerade inga signifikanta skillnader i kliniska symptom utgående från frågeformulären. Vår slutsats är att vänstra inferiora frontala gyrus aktivation är nedsatt i SF och normaliseras av en korttidsbehandling av escitalopram förrän den kliniska effekten etableras.

Objectives: Sleep is sensitive to mental stress. Mental stress can be triggered by everyday psychosocially stressful life events evoking feelings of fear of social evaluation, social exclusion or pressure of attaining desired goals. Deterioration of subsequent sleep is in turn widely associated with different mental health outcomes. Here we examine, whether psychosocial stress experienced before night sleep affects non-rapid eye movement (NREM) sleep architecture and sleep spindles. Furthermore, we intend to elucidate whether the effects of stress are different between two halves of the night. To our knowledge this is the first study integrating these themes and covering the entire night EEG measurement. Methods: Subjects were 20- to 34-year-old healthy adults (n=34) distributed into two experimental groups, completing different virtual reality scenarios. Subjects of stress condition performed a public speaking task in front of an attentive virtual audience whereas the subjects of control condition listened a neutral presentation in otherwise identical except empty virtual seminar room. Following both virtual reality scenarios participants’ sleep parameter data were gathered with electroencephalography (EEG) during the following night in the sleep laboratory. Results and Conclusions: We found that participants in stress condition displayed significantly lower N2 proportion during the first half of the night in contrast to control condition, accompanying slight reduction in N3 and REM sleep. Psychosocial stress had no significant effect on the entire night sleep spindle parameters, compared to non-stressful condition. However, a significant interaction between group and time on central spindle density was found, as a significant increase of central spindle density in the stress group from first to second half of sleep. Thus, we conclude that pre-sleep psychosocially stressful experience is associated with decreased N2 proportion during the first half of the sleep and increased central spindle density from the first to second half of the sleep, and the pattern is significantly different compared to sleep after neutral experience. These findings might indicate potential sleep homeostatic mechanism, whereby the stress related reduction of N2 sleep observed earlier in the night may be compensated for by a denser appearance of spindles later in the night, thus promoting sleep continuity and compensating for effects which occurred closer to the stressor.

Maternal obesity and childhood obesity are major problems for the public economy. Maternal obesity or the mother’s gestational diabetes mellitus may put the child at risk for accelerating growth in the first few months of life. Accelerating growth in early infancy is a risk factor for obesity in later childhood and adulthood. This study examined the effect of the mother’s genetic risk for obesity, defined by testing for SNP genetic variations associated with obesity, on the connection between the mother’s pre-pregnancy obesity and the early growth profiles of the offspring. This study is a secondary analysis of the RADIEL study. RADIEL is a gestational diabetes study, the material for which was assembled in the areas of the Hospital District of Helsinki and Uusimaa and the South Karelia Central Hospital in the years of 2008 to 2013. The women selected for the study were women who were either planning a pregnancy or who were pregnant with their gestational weeks being 20 or less. They were all at risk for gestational diabetes, either by having a BMI of at least 30 kg/m2 or by having had gestational diabetes in a prior pregnancy. The follow-up visits for the mothers took place in every trimester of pregnancy and after birth at 6 weeks, 6 months, and 12 months. There was also a follow-up study for the mothers and children 5 years after the birth. In addition, records of birth were collected from the maternity hospitals and records of the children’s growth were collected from child care centers. The mother’s genetic predisposition for obesity was modelled by testing for 49 single nucleotide polymorphisms (SNPs) and by creating a polygenic risk score for obesity (BMI-PRS) from them, which was used for grouping the mothers in groups of low, medium, and high genetic risk. Based on growth records from child care centers, the children’s growth was modelled in growth profiles, which were grouped into the ascending, descending, and intermediate growth profile groups based on the growth trends in the first few months of life. In the study, a positive connection between the BMI-PRS and maternal pre-pregnancy obesity was found. The BMI-PRS also had a statistically significant positive association with the connection between maternal pre-pregnancy obesity and the offspring’s early growth profiles. The connection between maternal pre-pregnancy obesity and the offspring’s ascending early growth profile was only found in the high risk BMI-PRS group. No association was found between the BMI-PRS and gestational diabetes or the BMI-PRS and the connection between gestational diabetes and early growth profiles. According to the results, the mother’s genetic risk for obesity affects the connection between maternal pre-pregnancy obesity and the offspring’s early growth, but further research is needed on this topic.

Aims. The social support received from family, friends and other social relations has a notable influence on an individual's psychological well-being. It has been consistently shown that social support helps to reduce the symptoms of depressive and anxiety disorders and has been connected to better quality of life. Psychotherapeutic interventions have been shown to have a positive effect on perceived social support, but both the effect of individual therapies and the stability of the effect have been studied seldom. The aim of this study is to examine and compare how the perceived social support developed in short- and longterm psychodynamic psychotherapy and solution-focused therapy. Methods. The study was conducted as a part of the Helsinki Psychotherapy Study (HPS). The study population consisted of 326 Finnish adult outpatients suffering from depressive and/or anxiety disorders. The patients were randomized into solution-focused therapy (SFT; n=97), long-term (LPP; n=128) or short-term (SPP; n=101) psychodynamic psychotherapy. The perceived social support was measured by A brief inventory of social support and integration (BISSI) questionnaire. The participants answered the questionnaire six times, once in a year, during the 5-year follow-up period. The development of social support in the therapies was analysed by linear mixed models. Results and Conclusions. The perceived social support had increased slightly more in LPP than in SPP at the end of the LPP therapy. No significant differences between SFT and the psychodynamic therapies were found at any follow-up point. In LPP and SFT a notable increase in perceived social support occurred during the first year of the follow-up, and the change was still significant at the five-year follow-up point. In SPP the increase occurred slower and the positive change at the five-year follow-up was somewhat lesser than in other therapies. The results provide preliminary knowledge of the relatively equal and stable positive effect of solution-focused therapies and short- and long-term psychodynamic psychotherapies on the perceived social support.

Lactase is a digestive enzyme, and its principal function is to break down lactose, a disaccharide found in milk. The main site for lactase expression is the intestines, however, it is also expressed in other tissues, including the brain. Because the primary substrate, lactose, is not present in the central nervous system, it can be assumed that lactase serves another function besides lactose breakdown outside the digestive system. In C57BL/6NCrl mice, lactase expression is higher in the ventral hippocampus after chronic social defeat stress in comparison to controls. This suggests that lactase expression is to some extent affected by stress. Although lactose metabolism is only necessary for mammals, some other animals – including the zebrafish (Danio rerio) – possess a gene that codes for lactase. Research on the zebrafish lactase gene is scarce, and the expression pattern of its two transcripts, the primary lct-201 and the secondary lct-202, is not known. This study focused on measuring lactase expression in adult wild type zebrafish – both on the gene and on the protein level as enzymatic activity. The effect of stress on lactase expression was also examined by applying two different stress models: netting handling stress as a form of physiological stress, and chronic social defeat as a model for psychosocial stress. Real-time polymerase chain reaction (q-RT-PCR) showed lct-201 expression in all five tissues investigated in this study – the forebrain, the mid-hindbrain, higher intestines, lower intestines, and skeletal muscle, whereas lct-202 was only expressed in the higher and lower intestines. The expression level of lct-201 in the muscle was only fifth of that in the lower intestines. Lactase activity assay on the whole brain and whole intestines displayed enzymatic activity in both tissues, with the activity in the intestines being more than seven-fold compared to the brain. q-RT-PCR on both stressed and control fish whole brain and intestines revealed higher lactase expression in the stressed fish intestines, however, the effect was only seen with a primer pair targeting both transcripts simultaneously, and not for either of them separately. Lactase expression was on average approximately 40 % higher in physiologically and 55 % higher in psychosocially stressed fish in comparison to their respective controls. Neither physiological nor psychosocial stress affected lactase expression in the brain. These findings suggest that the two zebrafish lactase transcripts have distinct expression patterns, which might imply different functional roles for lct-201 and lct-202. Furthermore, these results indicate that lactase is expressed in the zebrafish brain, suggesting that it has a specific function in the central nervous system. Based on the findings in this study, lactase gene expression might be connected to experienced stress – both physiological and psychosocial.

Ovarian cancer is the third most common gynecological cancer worldwide. Most ovarian cancers are high-grade serous ovarian cancers (HGSOC). HGSOC is usually diagnosed after metastasis due to lack of early symptoms. The prognosis is poor due to the lack of symptoms and chemoresistance that often develops. Stromal cells in cancers can both restrict and promote the tumor progression as well as modulate cancer cells’ response to therapy. Knowledge of differences in stromal cell subpopulations between different metastatic sites as well as of how chemotherapy affects the subpopulations is lacking, making developing new treatments targeting the tumor stroma difficult. The aims of this study were to characterize the stromal cell populations in HGSOC tumors and in healthy tubal tissue and to analyze the differences in subpopulations between different tumors. We used single-cell RNA-sequencing to characterize the stromal subpopulations in sixty-five tumor samples collected from different metastatic tissues both before and after chemotherapy and in five healthy tubal samples. We found eighteen stromal subpopulations in HGSOC and healthy tubal tissues. Ten subpopulations were cancer-associated fibroblasts including five previously characterized subtypes and five novel subtypes. Additionally, we found for example mesothelial cells, endothelial cells, and ovarian stromal cells. We demonstrated that certain cell populations are enriched in different metastatic tissues. Additionally, we demonstrated that stromal subpopulations differ between tumors collected before and after chemotherapy. Our results show that there are significant systematic differences in stromal subpopulations between HGSOC tumors from different conditions. Understanding these differences together with the knowledge of how these cells affect the tumor progression will enable the development of treatments targeting the tumor stroma.

Objectives: The present study tests the hypothesis of the association of an asphyxic insult, as defined by a low perinatal Apgar score to cognitive performance on adulthood, which has not been the objective in previous studies. The study questions are whether the low Apgar score without other symptoms predisposes one to a lower educational attainment, lower speech production capabilities and other cognitive impairments in adulthood. Based on previous studies conducted on younger individuals, the hypotheses were that individuals with a low Apgar score 1) have lower educational attainment and 2) perform worse on tasks that stress speech production than controls. Additionally, it was analyzed whether the individuals with a low Apgar score have lower 3) general intelligence, 4) verbal intelligence, 5) perceptual organization, 6) attentional skills and executive functions and 7) memory functions than controls. Methods: The participants were selected from a birth cohort of 22359 deliveries during 1971–1974 that had been followed-up until the latest measurements in 2014–2016, when the participants were aged 40–45 years of age. Asphyxia group consisted of participants with an Apgar score below 7 at least two times at 1, 5, and 15 minutes after delivery without other perinatal risk conditions (N = 80). Control group consisted of participants without any perinatal risk conditions (N = 83). It was analyzed whether the asphyxia group had an increased risk for attaining maximally a secondary level education. Measures of cognition were conducted with standardized neuropsychological tests. Childhood maladaptive living environment was included in the analyses as a covariate. Logistic regression was used in the analyses of educational attainment. In the neuropsychological tests, t-tests were conducted for the unadjusted analyses and analyses of covariance for the adjusted analyses with the covariate. Results and conclusions: The individuals who had suffered asphyxia had higher likelihood to remain in the secondary level education. They performed worse on reading speed, semantic verbal fluency, semantic abstract reasoning and on a task of processing and psychomotor speed. After adjustment for the childhood living environment, their general intelligence was also lower than controls. It was confirmed that the consequences of perinatal asphyxia extend to adulthood. Based on the results, it was assumed that the temporal cortex and basal ganglia are especially sensitive to asphyxic insults. It is suggested that the individuals, who have suffered from perinatal asphyxia, will be followed-up at the onset of their studies and provided with environmental support to avoid academic underachievement.

Objectives: Low birth weight has been associated with impaired cognitive abilities especially in childhood and young adulthood. However, the role of a low Apgar score on cognitive functions remains unclear. Apoliprotein E (APOE) gene allele ε4 has been linked to older people’s cognition, but the influence of APOE alleles on cognition of children or middle-aged is not well understood. The present study investigated the effects of low birth weight (< 2000 g) and low Apgar scores (< 7) on later cognitive performance and on the stability of cognitive functions from childhood to middle age. In addition, the influence of APOE ε2 and ε4 alleles on risk group subjects’ cognitive performance was evaluated. It was hypothesized that the groups with perinatal risk factors have impaired cognitive abilities in all the domains and have lower stability within these abilities compared to controls. Low birth weight was hypothesized to contribute lower cognitive abilities more than a low Apgar score. It was also assumed that APOE ε4 allele impairs cognitive performance only at midlife, not in childhood. Methods: The subjects with low birth weight (n = 66) and/or a low Apgar score (n = 60) were selected from a birth cohort born during 1971–1974. The control subjects (n = 95) were free from perinatal risk factors. Cognitive performance was evaluated using Wechsler’s intelligence test. All the subjects completed the test at the age of 40 (n = 221) and some also at the age of 9 (n = 190). The differences between the groups were computed with the analysis of covariance, where family socioeconomic status was controlled. Differences in the stability of cognitive abilities were evaluated with repeated measures ANOVA and correlation analysis. The effect of APOE ε2 and ε4 alleles on cognitive performance was computed with t-test. Results and conclusions: The subjects with low birth weight reached lower scores in all the cognitive domains compared to controls. At midlife, there was also a trend towards lower general intelligence in individuals with a low Apgar score. The lowest stability in cognitive performance between childhood and middle-age was observed among those born with a low birth weight. However, the difference in the stability was not significant between the groups. APOE ε4 allele was related to lower ability of perceptual reasoning in childhood and middle age. According to the results, the effects of low birth weight on cognitive functions seem to extend to middle age. However, it is assumed that environmental factors have an important role in later development in people with low birth weight. Based on the results, the APOE ε4 allele might impact already on early cognitive development. In the future, it is important to examine if this initial impairment in perceptual reasoning is related to abnormal aging among those with APOE ε4 allele.

Aims of the study. Evidence suggests that a slow breathing method called resonance frequency breathing may improve sleep quality, but many previous studies have suffered from methodological shortcomings. Music listening is a popular self-help strategy to promote sleep, but previous research assessing the efficacy of music in improving sleep has yielded inconsistent results. Sleep is known to promote the retention of newly learned material, but the effects of slow breathing and music listening on overnight declarative memory consolidation are unknown. This study explores the effects of two interventions, slow breathing approximating resonance frequency and music listening, on objective sleep quality and overnight declarative memory consolidation. Methods. This study was a randomized, controlled trial with a crossover design. 20 participants (10 females) were randomly allocated to an experimental group, who did a 30-minute slow breathing exercise, or a comparison group, who listened to relaxing music for 30 minutes. Participants’ sleep was measured on two consecutive nights with polysomnography. On one night, participants completed their assigned intervention before going to bed; the other night was used as a no-treatment control condition. Memory performance was measured with a word pair association task. Linear mixed-effects modeling was used to analyze the data. Results and conclusions. Slow breathing improved declarative memory performance, but it did not improve sleep quality when compared to the control condition. Music listening did not affect memory performance, but it improved sleep quality as manifested in reduced wake after sleep onset, decreased duration of stage N1, stage N2, and non-REM sleep, and an increased percentage of stage N3 sleep when compared to the control condition. The results suggest that music listening can improve objective sleep quality and slow breathing can promote overnight learning, but more research is needed to understand the exact mechanisms underlying these associations.