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  • Vulli, Jaana (Helsingin yliopisto, 2013)
    A small set of highly conserved signaling molecules performs a great number of tasks in different animals and developmental contexts. Among them, the bone morphogenetic proteins (BMPs) constitute a group of growth and differentiation factors that are involved in numerous developmental processes affecting cell proliferation, apoptosis and differentiation. In the fruit fly, Drosophila melanogaster, three BMP type proteins have been identified, each of which has a homolog in mammals. Decapentaplegic (Dpp) is a BMP2/4 type protein which plays a major role in dorsal-ventral patterning of the early embryo. It participates in midgut development, patterning and growth of imaginal tissues, wing vein formation and maintenance of germline stem cells in the germarium. Dpp is a morphogen which requires a second BMP type protein, Screw (Scw) or Glass bottom boat (Gbb) to be able to form proper concentration gradients in developing tissues. Scw and Gbb belong to the BMP5/6/7/8 subfamily and their expression domains are different; Scw is specifically expressed during the early events of embryogenesis, while Gbb has more functional roles during later stages of fly development, like wing morphogenesis. BMP type proteins are produced as large proproteins that require proteolytic cleavage prior to secretion and extracellular gradient formation. This study concentrated on the cleavage of Dpp and Scw to reveal the meaning of post-translational modifications in concentration gradient formation and BMP signaling. Three furin recognition sites were identified in the Dpp proprotein. Mutational analyses indicate that the upstream optimal furin site of the prodomain (furin site (FS) II) is critical for producing ligands and creating a long range concentration gradient in a wing imaginal disc. Cleavage of the other two FSs produce the differently sized Dpp ligands that contribute to BMP gradient formation in the early embryo and wing imaginal disc. It was noted that the cleavage requirements of BMP2/4 type proteins in different species vary to establish species-specific regulation of BMP signaling. Discovery of the scwE1 allele, that causes dominant negative effect in embryos heterozygous for a hypomorphic dpp allele, gave more information about how the cleavage patterns of prodomains can contribute to creating diversity in the regulation of signaling. The mutation responsible for the dominant negative function in scwE1 was located in the cleavage site that is in the prodomain of Scw. Mutational analyses showed that the mature ligand of ScwE1 is produced in lower amounts and in complex with an N-terminal prodomain peptide. ScwE1 preferentially binds Dpp and disrupts normal gradient formation possibly through interactions with molecules within the extracellular matrix. Phylogenetic analyses and functional studies of BMP cleavage mutants propose a mechanism by which post-translational regulation of proproteins modulates BMP signaling.
  • Sund, Jukka (Helsingin yliopisto, 2014)
    Nanotechnology has been one of the major success stories of the early 21st century. The foundation for this success rests on the discovery that a small size confers completely new properties on materials. Nowadays, engineered nanomaterials (ENMs) are used in a plethora of applications such as paints, cosmetics, food products and electronics. These new properties, however, potentially make ENMs more reactive in biological systems than their large-scale counterparts. Already, asbestos-like effects have been described in mice after exposure to certain forms of carbon nanotubes (CNTs), while nano-sized titanium dioxide (nTiO2) has been shown to evoke inflammation in mouse lung. Therefore, extensive nanosafety studies have to be performed to ensure that no adverse effects are suffered by either workers or end-users of ENM products. This thesis has investigated the biological effects of ENMs by proteomic methods, first by evaluating the uptake and interactions of ENMs with plasma and cellular proteins followed by an analysis of the effects of ENM exposure on the intracellular proteome and secretome of human primary macrophages. The results revealed that ENM interactions with cellular proteins were governed by the surface reactivity of ENMs, whereas interactions with plasma proteins seemed to depend on the combination of both surface reactivity and active recognition, namely tagging of ENMs by opsonin proteins. The binding of cellular proteins to ENMs and subsequent interference with cellular processes might represent a novel cause of ENM toxicity, especially since transmission electron microscopy (TEM) micrographs indicated that several ENM species could be visualized free in the cytoplasm. The cytoplasmic protein expression changes after exposure to silica coated and uncoated nTiO2 revealed that silica coated TiO2 induced stronger protein expression changes in the macrophages. Most of the proteins with altered expression were related to phagocytosis, oxidative stress and inflammation. These proteome changes indicate that macrophages are actively engulfing ENMs and processing them. Moreover, the up-regulation of oxidative stress related proteins might be an indication of oxidative burst. Finally, nTiO2 treatment evoked acetylation of cytoplasmic proteins, a previously uncharacterized phenomenon in cells exposed to ENMs. The results from the macrophage secretome analysis showed that asbestos and long rigid carbon nanotubes (R CNTs) produced a similar response, while protein secretion profile of macrophages exposed to long tangled carbon nanotubes (T CNTs) exhibited a distinct profile. Bioinformatic analysis revealed that R CNTs evoked secretion of inflammation and apoptosis related proteins, possibly because of lysosomal damage. Functional assay confirmed that R CNT exposure triggered apoptosis in macrophages, while T CNTs and asbestos did not. This thesis offers new knowledge concerning the biological effects of engineered nanomaterials. Proteomic methods proved to be useful in the ENM-protein interaction studies revealing that it would be beneficial to include the ENM-protein interaction experiments as part of the routine ENM characterization when assessing the health effects of ENMs. By employing quantitative proteomics, we obtained a global view of both cytoplasmic and secreted proteome changes of macrophages exposed to different ENMs.
  • Lietzén, Niina (Helsingin yliopisto, 2012)
    Proteomics is defined as large-scale study of proteins, and with current proteomic methods thousands of proteins can be characterized in a single experiment. Mass spectrometry (MS) has an important role in the characterization of complex protein samples. In addition, various bioinformatics tools have become increasingly important in the interpretation of complex proteomic data. The combination of proteomics and bioinformatics is nowadays an important tool to study cellular signaling mechanisms. When host cell recognizes the invading virus, multiple cell signaling cascades are activated resulting in antiviral immune responses, inflammation and programmed cell death of the infected cell. The detailed mechanisms of host cell defense responses activated upon viral infection are still partially unknown. The aim of this project was to develop and utilize proteomic and bioinformatic methods to characterize host responses to viral infection. Three different proteomic approaches were used in this project to study virus-induced changes in human epithelial cells and macrophages. Viral RNA-induced responses in HaCaT keratinocytes were studied using two-dimensional gel electrophoresis and MS. Influenza A virus-induced changes in the intracellular compartments and secretomes of human primary macrophages were characterized using iTRAQ labeling-based quantitative proteomics. Finally, viral RNA-triggered protein secretion from human primary macrophages was studied using SDS-PAGE, liquid chromatography and MS. In addition, two computational tools, Compid and Pripper, were developed to simplify the analysis of our proteomic data. Our studies showed that both influenza A virus and viral RNA trigger significant changes in the proteomes of macrophages and HaCaT keratinocytes. Virus-induced changes in the expression of 14-3-3 signaling proteins as well as rearrangement of host cell cytoskeleton were detected in HaCaT keratinocytes. Caspase-3-dependent apoptosis was detected in HaCaT keratinocytes and macrophages after viral stimulation. Our studies with macrophages also showed that several inflammatory pathways, and especially the NLRP3 inflammasome, are activated as a result of viral RNA and influenza A virus infection. Additionally, we showed that cathepsins, src tyrosine kinase and P2X7 receptor were involved in the inflammasome activation. Finally, we showed that viral stimulation triggered extensive protein secretion from macrophages. In conclusion, our proteomic experiments have given an in-depth view of cellular events activated in human primary macrophages and HaCaT keratinocytes after viral infection.
  • Siljamäki, Pia (Helsingin yliopisto, 2014)
    Staphylococcus epidermidis (SE) is an opportunistic pathogen capable of infecting humans and animals. It is a frequent cause of hospital-acquired infections in humans and of intramammary infections (IMIs) in dairy cows. The protein expression profiles and the genomes of three SE strains, one associated with bovine mastitis (PM221), one representing a commensal/low-virulent human strain (ATCC12228 isolated from a healthy human host) and the third being a virulent human strain (RP62A isolated from a catheter-associated sepsis) were compared. At the genome and total proteome levels, the bovine strain PM221 was found to be more similar to ATCC12228 than to RP62A. The strain-specific differences found between PM221 and ATCC12228 are believed to have roles in adaptation and virulence. These findings may explain why ATCC12228 was able to cause persistent mastitis in an experimental infection study albeit with a milder clinical outcome than encountered with PM221. These findings strengthen the hypothesis that humans could represent an important source of SE-mediated infections in dairy cows. The exoproteome analysis revealed that the exoproteome of PM221 resembled more that of RP62A than the exoproteome of ATCC12228. The major part of the identified exoproteins was predicted to be cytoplasmic, indicating that these proteins might be surface-displayed moonlighting proteins or that they had been embedded in membrane vesicles. PM221 and RP62A were shown to be more efficient in non-classical protein secretion. These findings may explain the higher virulence capacity of PM221 than that of ATCC12228. Our studies also indicated that PM221 uses less aggressive strategies than RP62A when establishing an infection in vivo. Phenotypic tests indicated that SE may use several strategies to improve its adaptation to different environments; the virulent bovine and human strains (PM221 and RP62A) were able to use biofilm formation for colonization and adaptation, and PM221 and ATCC12228 could downregulate their tricarboxylic acid cycle activity and increase the formation of small colony variants to improve bacterial survival during the stationary phase. In addition, the bovine PM221 strain may possess an advantage since it has higher tributyrin activity in the milk environment, whereas the human strains may benefit from their higher urease and/or catalase activities helping these strains to survive in their ecological niches and indwelling medical devices. In conclusion, the present studies demonstrate that the SE species may exploit diverse strategies involving specific changes in their late stationary phase metabolism as well as in protein export strategies accompanied by increased production of certain enzymes in order to ensure better adaptation and/or successful infection.
  • Timonen, Marjut (Helsingin yliopisto, 2010)
    Boron neutron capture therapy (BNCT) is a radiotherapy that has mainly been used to treat malignant brain tumours, melanomas, and head and neck cancer. In BNCT, the patient receives an intravenous infusion of a 10B-carrier, which accumulates in the tumour area. The tumour is irradiated with epithermal or thermal neutrons, which result in a boron neutron capture reaction that generates heavy particles to damage tumour cells. In Finland, boronophenylalanine fructose (BPA-F) is used as the 10B-carrier. Currently, the drifting of boron from blood to tumour as well as the spatial and temporal accumulation of boron in the brain, are not precisely known. Proton magnetic resonance spectroscopy (1H MRS) could be used for selective BPA-F detection and quantification as aromatic protons of BPA resonate in the spectrum region, which is clear of brain metabolite signals. This study, which included both phantom and in vivo studies, examined the validity of 1H MRS as a tool for BPA detection. In the phantom study, BPA quantification was studied at 1.5 and 3.0 T with single voxel 1H MRS, and at 1.5 T with magnetic resonance imaging (MRSI). The detection limit of BPA was determined in phantom conditions at 1.5 T and 3.0 T using single voxel 1H MRS, and at 1.5 T using MRSI. In phantom conditions, BPA quantification accuracy of ± 5% and ± 15% were achieved with single voxel MRS using external or internal (internal water signal) concentration references, respectively. For MRSI, a quantification accuracy of <5% was obtained using an internal concentration reference (creatine). The detection limits of BPA in phantom conditions for the PRESS sequence were 0.7 (3.0 T) and 1.4 mM (1.5 T) mM with 20 × 20 × 20 mm3 single voxel MRS, and 1.0 mM with acquisition-weighted MRSI (nominal voxel volume 10(RL) × 10(AP) × 7.5(SI) mm3), respectively. In the in vivo study, an MRSI or single voxel MRS or both was performed for ten patients (patients 1-10) on the day of BNCT. Three patients had glioblastoma multiforme (GBM), and five patients had a recurrent or progressing GBM or anaplastic astrocytoma gradus III, and two patients had head and neck cancer. For nine patients (patients 1-9), MRS/MRSI was performed 70-140 min after the second irradiation field, and for one patient (patient 10), the MRSI study began 11 min before the end of the BPA-F infusion and ended 6 min after the end of the infusion. In comparison, single voxel MRS was performed before BNCT, for two patients (patients 3 and 9), and for one patient (patient 9), MRSI was performed one month after treatment. For one patient (patient 10), MRSI was performed four days before infusion. Signals from the tumour spectrum aromatic region were detected on the day of BNCT in three patients, indicating that in favourable cases, it is possible to detect BPA in vivo in the patient’s brain after BNCT treatment or at the end of BPA-F infusion. However, because the shape and position of the detected signals did not exactly match the BPA spectrum detected in the in vitro conditions, assignment of BPA is difficult. The opportunity to perform MRS immediately after the end of BPA-F infusion for more patients is necessary to evaluate the suitability of 1H MRS for BPA detection or quantification for treatment planning purposes. However, it could be possible to use MRSI as criteria in selecting patients for BNCT.
  • Belevich, Ilya (Helsingin yliopisto, 2007)
    Terminal oxidases are the final proteins of the respiratory chain in eukaryotes and some bacteria. They catalyze most of the biological oxygen consumption on Earth done by aerobic organisms. During the catalytic reaction terminal oxidases reduce dioxygen to water and use the energy released in this process to maintain the electrochemical proton gradient by functioning as a redox-driven proton pump. This membrane gradient of protons is extremely important for cells as it is used for many cellular processes, such as transportation of substrates and ATP synthesis. Even though the structures of several terminal oxidases are known, they are not sufficient in themselves to explain the molecular mechanism of proton pumping. In this work we have applied a complex approach using a variety of different techniques to address the properties and the mechanism of proton translocation by the terminal oxidases. The combination of direct measurements of pH changes during catalytic turnover, time-resolved potentiometric electrometry and optical spectroscopy, made it possible to obtain valuable information about various aspects of oxidase functioning. We compared oxygen binding properties of terminal oxidases from the distinct heme-copper (CcO) and cytochrome bd families and found that cytochrome bd has a high affinity for oxygen, which is 3 orders of magnitude higher than that of CcO. Interestingly, the difference between CcO and cytochrome bd is not only in higher affinity of the latter to oxygen, but also in the way that each of these enzymes traps oxygen during catalysis. CcO traps oxygen kinetically - the molecule of bound dioxygen is rapidly reduced before it can dissociate. Alternatively, cytochrome bd employs an alternative mechanism of oxygen trapping - part of the redox energy is invested into tight oxygen binding, and the price paid for this is the lack of proton pumping. A single cycle of oxygen reduction to water is characterized by translocation of four protons across the membrane. Our results make it possible to assign the pumping steps to discrete transitions of the catalytic cycle and indicate that during in vivo turnover of the oxidase these four protons are transferred, one at a time, during the P→F, F→OH, Oh→Eh, and Eh→R transitions. At the same time, each individual proton translocation step in the catalytic cycle is not just a single reaction catalyzed by CcO, but rather a complicated sequence of interdependent electron and proton transfers. We assume that each single proton translocation cycle of CcO is assured by internal proton transfer from the conserved Glu-278 to an as yet unidentified pump site above the hemes. Delivery of a proton to the pump site serves as a driving reaction that forces the proton translocation cycle to continue.
  • Manner, Jukka (Helsingin yliopisto, 2003)
  • Kolehmainen, Leena (Helsingin yliopisto, 2005)
  • Meinander, Kristian (Helsingin yliopisto, 2014)
    The highly prostate specific serine protease kallikrein-related peptidase 3 (KLK3, also known as prostate specific antigen, PSA) is widely used as a biomarker for prostate cancer and it has also been postulated that it may play a part in tumour growth. Especially interestesting is the antiangiogenic effect exerted by proteolytically active KLK3 in cell line models. In order to stimulate the proteolytic activity of KLK3, a series of peptides have been developed by phage display methodology. Even though the peptides are quite potent KLK3 stimulators, they are not directly suitable for in vivo studies or use as drugs. Even though there are many natural and unnatural biologically active peptides, they suffer from rapid clearance via the liver and kidneys and proteolytic degradation of the compounds both in the gastrointestinal tract and other parts of the body. This gives peptides a poor oral bioavailability meaning that they are usually administered as intravenous or intramuscular injections. Several different strategies have been developed in order to access compounds with improved bioavailability including modifications of the peptide structure, development of pseudopeptides and development of small molecular weight peptidomimetics. This thesis concentrates on the further development of the two most potent peptides known to stimulate KLK3, i.e. B-2 and C-4. The main part of the work was concentrated on the replacement of disulphide bridges in the peptides in order to both gain more information on which residues are necessary for obtaining the biological activity and at the same time also gain information on how changes to the geometry of the disulphide bridge affects the activity. A series of different disulphide bridge mimicking building blocks were designed and synthesised with the intention of using them in a protocol for solid-phase synthesis of KLK3 stimulating peptides. Unfortunately, the use of these building blocks in the synthesis of pseudopeptides based on C-4 turned out to be an unsurmountable challenge and the synthesis had to be completed using a different strategy in which the key step was the use of ring-closing metathesis (RCM) for the cyclisation of the partly completed pseudopeptide. Pleasingly, the synthesis of pseudopeptide analogues of the B-2 peptide using the building blocks was more successful. In total three pseudopeptide analogues of C-4 and four of B-2 were synthesised and shown to retain the biological activity of the parent peptides. Based on the information from the synthesised pseudopeptides and a molecular modelling study, a 4-quinolone based peptidomimetic was designed to mimic the C-4 peptide and a synthetic protocol was devised to access this compound. Even though the synthesis of the desired target compound has so far not been successful, the synthetic protocol that was designed has given access to a number of 1,2,8-trisubstituted 4-quinolone derivatives.
  • Koskentausta, Terhi (Helsingin yliopisto, 2006)
    Children with intellectual disability are at increased risk for emotional and behavioural problems, but many of these disturbances fail to be diagnosed. Structured checklists have been used to supplement the psychiatric assessment of children without intellectual disability, but for children with intellectual disability, only a few checklists are available. The aim of the study was to investigate psychiatric disturbances among children with intellectual disability: the prevalence, types and risk factors of psychiatric disturbances as well as the applicability of the Finnish translations of the Developmental Behaviour Checklist (DBC-P) and the Child Behavior Checklist (CBCL) in the assessment of psychopathology. The subjects comprised 155 children with intellectual disability, and data were obtained from case records and five questionnaires completed by the parents or other carers of the child. According to case records, a psychiatric disorder had previously been diagnosed in 11% of the children. Upon careful re-examination of case records, the total proportion of children with a psychiatric disorder increased to 33%. According to checklists, the frequency of probable psychiatric disorder was 34% by the DBC-P, and 43% by the CBCL. The most common diagnoses were pervasive developmental disorders and hyperkinetic disorders. The results support previous findings that compared with children without intellectual disability, the risk of psychiatric disturbances is 2-3-fold in children with intellectual disability. The risk of psychopathology was most significantly increased by moderate intellectual disability and low socio-economic status, and decreased by adaptive behaviour, language development, and socialisation as well as living with both biological parents. The results of the study suggest that both the DBC-P and the CBCL can be used to discriminate between children with intellectual disability with and without emotional or psychiatric disturbance. The DBC-P is suitable for children with any degree of intellectual disability, and the CBCL is suitable at least for children with mild intellectual disability. Because the problems of children with intellectual disability differ somewhat from those of children without intellectual disability, checklists designed specifically for children with intellectual disability are needed.
  • Ketola, Sirpa (Helsingin yliopisto, 2014)
    Vertigo and dizziness are among the most frequent complaints in primary care. The symptoms are usually self-limited, and the clinical course is benign, with full recovery. In many cases, however, vertigo and dizzy spells recur, leading to impairment and chronic outcome. A number of studies have documented a high prevalence of psychiatric comorbidity in vertiginous patients. Vertigo and dizzy symptoms themselves can provoke psychological distress, because recurrent unpredictable attacks can induce fear of losing control, concern of serious illness, and worry about severe attacks compromising one s ability to adapt. Recurrent spells can also provoke earlier mental problems. Yet the degree of subjective handicap and emotional distress has shown no close relationship to measures of vertigo symptom severity. Psychiatric disorders do not cause vertigo or dizziness, but can, together with vertigo and dizzy symptoms, lead to persistent complaints. Anxiety and depression are the most common disorders associated with vertigo and dizziness. Vertigo and dizziness in children is not rare. One population-based study found a prevalence of vertigo of 14% (Russell and Abu-Arafeh 1999). The etiology varies, but usually involves organic causes. Psychiatric etiology is investigated only after the exclusion of organic etiology. Psychosomatic symptoms are common in children and adolescents, often reflecting problems in psychosocial background. The first study aimed to evaluate the adapting ability of patients with Ménière s disease based on the sense of coherence scale. Data were collected with two different postal questionnaires involving 547 recipients (Study I). Studies II and III evaluated the prevalence of psychiatric symptoms in vertiginous patients. This study group comprised 100 vertiginous subjects from a randomly selected community sample participating in a vertigo prevalence study in the Helsinki University Hospital district. The investigative program entailed a neuro-otological examination and psychiatric evaluation in questionnaire form. Study IV assessed the prevalence of psychiatric disorders in a group of 119 children and adolescents between the ages of 7 months to 17 years who had visited the ear, nose and throat clinic with a primary complaint of vertigo. An otologist and a psychiatrist reviewed and evaluated each patient s detailed medical history. The results indicate a high sense of coherence (SOC) to represent deeper contentment in life and less psychological distress despite the chronic disease. Although SOC scores did not relate to the severity of illness, subjects with low SOC scores exhibited more symptoms of both vertigo and psychological distress (Study I) than did subjects with high SOC scores. In Studies II and III, the prevalence of depressiveness was 19%, and the prevalence of symptoms of anxiety, 12%. A total of 68% of subjects reported psychiatric symptoms, the most common of which was personality disorder. Comorbidity between depressive, anxiety and personality symptoms were ample and related significantly to reduced functional capacity. In Study IV, the prevalence of psychogenic vertigo was 8%. Major depression was the most common disorder, and 2.5% of patients suffered from somatization disorder. The psychiatric distress commonly reflected psychosocial problems and affected seriously on daily life functioning. In conclusion, this study found that psychiatric symptoms are common in vertiginous patients. Comorbidity may lead to a more debilitating course of vertigo independently of an organic cause or the severity of vertigo symptoms. Feelings of disability correlated with psychological distress. In children and adolescents, vertigo symptoms with compromised daily functioning, together with psychosocial stress factors, should invoke at least the possibility of psychiatric distress. Keywords: vertigo, depression, anxiety, personality disorder, comorbidity, disability, coping, chronic 
  • Josefsson, Kim (Helsingin yliopisto, 2013)
    Few prospective studies have studied the development and outcomes of personality from childhood to adulthood in the light of the psychobiological theory. This study takes personality, as defined by the psychobiological theory, as the core focus and explores the predictors, development, and outcomes of adulthood personality. This study also seeks to answer an important theoretical question in personality psychology: are there observable qualitative differences between temperament and character? The participants come from the Cardiovascular Risk in Young Finns Study (CRYF), which started in 1980. It consists of six different birth cohorts that were from three to eighteen years old in 1980. There have been eight follow-ups since then, the latest in 2012. The participants parents answered questions about home environment in 1983. Personality was measured in 1997, 2001, and 2007, depressive symptoms in 1997, 2001, and 2007, and well-being in 2001. There were 2814, 1083, 1940, and 1911 participants in studies I-IV, respectively. The results showed that character developed towards greater maturity in adulthood, although Self-transcendence decreased with age. Self-transcendence was the strongest predictor of overall personality change. Regarding temperament, Novelty Seeking decreased and Persistence increased slightly with age. Temperament and character traits followed different kinds of developmental trajectories. Parental care-giving and home-environment were more strongly associated with offspring character traits reflecting personality maturity (Self-directedness and Cooperativeness) than with offspring temperament traits. The differences were most evident in the cumulative effects model. Self-directedness and Cooperativeness were positively associated with well-being. Self-transcendence increased both positive and negative affect. High Harm Avoidance and low Self-directedness strongly related to depressive symptoms. In addition, sensitive (NHR) and fanatical people (ScT) were especially vulnerable to depressive symptoms. Temperament and character had qualitative differences, which has important theoretical significance. Character was strongly influenced by childhood family environment and was strongly associated with well-being. Character development should be facilitated when trying to reduce ill-being and increase well-being.
  • Pyhälä, Riikka (Helsingin yliopisto, 2012)
    Improvements in neonatal intensive care during the last few decades have led to a remarkable improvement in the survival rates of preterm infants born with very low birth weight (< 1500 g; VLBW). However, VLBW may have a cost for the physical, psychosocial and cognitive development of the survivors. Nevertheless, there has been little research into the long-term consequences of VLBW that last till or emerge in adulthood. In addition, there have been relatively few studies on whether the adult outcomes of VLBW depend on sex or fetal growth. Within the Helsinki Study of Very Low Birth Weight Adults, we studied whether young adults with VLBW differ from term-born adults in psychological and psychophysiological functioning as well as in recollections of parenting, and whether potential group differences are modified by sex or intrauterine growth. The original cohort comprised 335 VLBW infants born between 1978 and 1985, treated at the Children s Hospital of Helsinki University Central Hospital, and discharged alive. A total of 373 infants born at term at the same birth hospitals were identified to form a control group. At the first follow-up visit in young adulthood (mean age 22.5 years), 166 VLBW (42.8% men) and 172 term-born control adults (40.1% men) participated. Of the VLBW participants, 33.1% were born small for gestational age (SGA; birth weight for gestational age < -2 SD), which was used as a crude indicator of poorer intrauterine growth. In conjunction with the first visit, the participants filled in questionnaires on personality, romantic attachment and the parenting behavior of their parents. In addition, blood pressure reactivity to psychosocial stress was measured in a subsample of 44 VLBW and 37 control adults. At the second follow-up visit, three years later (mean age 25.0 years), 113 VLBW (44.2% men; 37.2% SGA) and 105 control adults (42.9% men) participated, and their academic achievement was self-reported and neurocognitive abilities were tested. In addition, the parents of the participants filled in questionnaires on their own parenting behaviors. In comparison to the term-born adults, the VLBW adults scored lower in all the neurocognitive tests, and they had more often received remedial education, although they did not differ in years of education or in their grade point averages (Study I). The VLBW adults also showed a higher diastolic blood pressure reactivity to psychosocial stress (Study II). Sex and being born SGA modified the results concerning personality, romantic attachment and parenting. In the personality assessment, all the VLBW adults reported less fun seeking indicating less spontaneous eagerness for new, potentially rewarding actions, but only the VLBW-SGA women reported more behavioral inhibition than the term-born women (Study III). In relation to their romantic attachment style, the VLBW adults, with the exception of the VLBW-SGA women, reported less anxiety than the controls, indicating less concerns over being rejected by their partner. In contrast, the VLBW-SGA women reported increased attachment-related avoidance behavior (Study IV). In relation to parenting, the VLBW women reported that their mothers had been more protective and authoritarian than did women in the term-born group, but there were no group differences in parental care. The parents of the VLBW adults reported more supportive parenting than the parents of the term-born adults (Study V). In conclusion, we found that the VLBW adults differed from those born at term in all the areas of functioning included in the thesis. Of the VLBW adults, more alterations were found in women and in those with poor intrauterine growth. Overall, according to the results in young adulthood, VLBW may be related to vulnerabilities such as lower neurocognitive abilities and increased blood pressure reactivity; however, it may also give rise to potentially protective factors, such as higher parental involvement. Knowledge of the different vulnerabilities and protective factors could be utilized in planning interventions and optimal measures of support among preterm children and their families.
  • Gustavsson-Lilius, Mila (Helsingin yliopisto, 2010)
    Previous empirical research has shown that positive, i.e. salutogenic, psychological resources and social support, have health-promoting effects in stressful life situations. In the present study the associations between sense of coherence (SOC), dispositional optimism, partner support, psychological distress, and quality of life among cancer patients and their partners were examined. The data was collected from Helsinki University Central Hospital in 1997 2000 by self-report questionnaires approximately 2, 8, and 14 months post diagnosis. Participants in studies I-IV were 155, 123, 153, and 147 cancer patients and their partners, respectively. The sample of the present study consisted of physically relatively well-functioning patients, whose overall psychological wellbeing was generally good as compared to the healthy population. Partners in this study, however, reacted more strongly to their partners illness and treatment. The partners displayed e.g. higher levels of anxiety and depression than the patients. The results of this study indicated that cancer patients and their partners with strong SOC and who are optimistic report fewer symptoms of distress. Moreover, patients who display an optimistic attitude to life, who receive support from their partner, and who control how they express anger have a better quality of life. The findings also confirmed that the role of the partner is significant in coping with cancer. The symptoms of depression and anxiety in patients and partners were associated, and the partner s optimism seemed to protect also the patient from elevated levels of anxiety. The role of the partner was also highlighted in the couples anger-expression styles. The patients and partners tendency to inhibit anger was associated with decreased partner support and worse patient quality of life. Finally, in the present study we found substantial gender differences. For the patients, partner support was more significant for the women than for the men. Furthermore, for the female patients, the husband s tendency to openly express anger (anger-out) had a negative impact on their psychological quality of life, whereas the wives high anger-out seemed to predict good psychological quality of life in the men. Also, in this study the female partners reported higher levels of anxiety and depression as compared to the male partners. The results of the present study extend the previous literature on positive psychological resources and psychological wellbeing among cancer couples. Furthermore, these findings support the theory on SOC and optimism as health-promoting factors. However, the construct of SOC seems to include other important elements besides optimism. The findings of this study are applicable in designing new rehabilitation programmes for cancer patients and their partners.
  • Ahola, Aila (Helsingin yliopisto, 2012)
    Diabetes is characterized by a number of metabolic disturbances. Self-management, that aims at normalizing these disturbances, constitutes the backbone of diabetes treatment. A number of factors may affect how patients take care of themselves. Knowledge of the current treatment guidelines is not sufficient alone, but must be translated into compliance. Also various psychological determinants, such as depression, may affect how patients take care of themselves. Sense of coherence (SOC), which refers to the extent to which individuals are able to use various resources to sustain and improve health, offers another kind of an approach to the issue of diabetes management. The aim of this thesis was to investigate the adherence with dietary recommendations in patients with type 1 diabetes, and to study the association between self-reported and measured compliance with recommendations. We also investigated the relevance of the SOC in diabetes self care, patients per-ceptions of their disease, and microvascular complications. Moreover the associations between depression and the metabolic syndrome and mortality were evaluated. The thesis is part of the Finnish Diabetic Nephropathy (FinnDiane) study. Compliance with dietary guidelines was highest for the intake of protein, alcohol, and sucrose. A substantial proportion of the participants consumed less carbohydrates, and fibre than recommended. Sodium chloride and saturated fatty acid intakes frequently exceeded the recommendations. Of the micronutrients, the recommendations for vitamin D, folate and iron were most frequently unmet. Self-reported compliance with dietary recommendations was reflected in more frequently meeting the recommendations for carbohydrates, total fat, saturated fatty acids, and alcohol intakes. Despite this, the observed frequencies of meeting the actual guidelines among these patients were, for many nutrients, only modest (e.g., 55% for carbohydrates and 35% for saturated fatty acids). In women, higher SOC score (indicating stronger SOC) was associated with more prudent food choices. In men, the SOC scores were positively associated with higher level of physical activity. Weak SOC was associated with higher HbA1c levels among women. In men, weak SOC was associated with the presence of diabetic nephropathy. Four factors were formed from the diabetes questionnaire (conceptions of HbA1c, complications, diabetes control, and hypoglycaemia). Higher factor scores describing less favourable self-reports were observed for conceptions of HbA1c and hypoglycaemia among those with weak SOC. Moreover, in men, weak SOC was associated with the complications factor. In women, the metabolic syndrome was a more frequent observation among those with symptoms of depression. Of the individual components of the metabolic syndrome, the BDI score was associated with the waist and triglyceride components in women. Purchases of antidepressant agents reduced the 10-year cumulative survival, mostly so among women with such purchases at around the baseline visit. The purchasers of antidepressant agents died mostly of chronic diabetic complications, while the predominant underlying cause of death among non-purchasers were cardiovascular diseases.
  • Talala, Kirsi (Helsingin yliopisto, 2013)
    Mental health problems have shown to be highly prevalent and associated with socio-economic factors in populations worldwide. Persistent or increasing health inequalities are a common phenomenon, however, few studies have explored socioeconomic differences in mental health over time. Psychological distress refers to non-specific psychopathology, which includes symptoms such as depression, insomnia and stress. Psychological distress is prevalent (5 - 48%) and known to be associated with lower quality of life, mental and physical morbidity and mortality. Moreover, psychological distress has been proposed as one probable explanation in mediating the socio-economic gradient in health and mortality. Few studies have examined prevalence trends in psychological distress and changes in socio-economic differences in psychological distress over time, or the contribution of psychological distress to the socio-economic differences in cause-specific mortality. This study aimed to explore these topics. The database was Health Behaviour and Health among the Finnish Adult Population -survey (AVTK, 1979 - 2002) linked with Statistics Finland socio-economic register data, and the Finnish Cause of Death Register follow-up. Outcome measures for psychological distress included self-reported depression, insomnia and stress. Socio-economic status was measured by education, employment status and household income. Mortality data consisted of suicide, accidents and violence, alcohol-related causes of death and coronary heart disease mortality. The overall prevalence of psychological distress was 14 - 20%. Insomnia and stress increased among both genders, whereas depression decreased among women. Socio-economic differences were demonstrated in all psychological distress measures. High risk groups for psychological distress were the unemployed, retired respondents (<65 years) and those with no partner. Those with the lowest household incomes experienced more depression and stress. However, some of the associations were curvilinear and converse. Most notably, stress was most common among the highest educated. Socio-economic differences in psychological distress did not change substantially over time. Depression, insomnia and extremely high stress accounted for some of the socio-economic differences in unnatural but not in CHD mortality. The increase in the prevalence of insomnia and stress, and persistent socio-economic differences in psychological distress present a perceptible public health challenge. However, reversed gradients, especially in stress, should be considered in detail. Improvement of psychological distress in certain socio-economic groups may reduce some of the socio-economic differences, particularly in unnatural mortality.