The regional differences between countries in traffic safety: A cross-cultural study and Turkish Case

Road traffic accidents are a large problem everywhere in the world. However, regional differences in traffic safety between countries are considerable. For example, traffic safety records are much worse in Southern Europe and the Middle East than in Northern and Western Europe. Despite the large regional differences in traffic safety, factors contributing to different accident risk figures in different countries and regions have remained largely unstudied. The general aim of this study was to investigate regional differences in traffic safety between Southern European/Middle Eastern (i.e., Greece, Iran, Turkey) and Northern/Western European (i.e., Finland, Great Britain, The Netherlands) countries and to identify factors related to these differences. We conducted seven sub-studies in which I applied a traffic culture framework, including a multi-level approach, to traffic safety. We used aggregated level data (national statistics), surveys among drivers, and data on traffic accidents and fatalities in the analyses. In the first study, we investigated the influence of macro level factors (i.e., economic, societal, and cultural) on traffic safety across countries. The results showed that a high GNP per capita and conservatism correlated with a low number of traffic fatalities, whereas a high degree of uncertainty avoidance, neuroticism, and egalitarianism correlated with a high number of traffic fatalities. In the second, third, and fourth studies, we examined whether the conceptualisation of road user characteristics (i.e., driver behaviour and performance) varied across traffic cultures and how these factors determined overall safety, and the differences between countries in traffic safety. The results showed that the factorial agreement for driver behaviour (i.e., aggressive driving) and performance (i.e., safety skills) was unsatisfactory in Greece, Iran, and Turkey, where the lack of social tolerance and interpersonal aggressive violations seem to be important characteristics of driving. In addition, we found that driver behaviour (i.e., aggressive violations and errors) mediated the relationship between culture/country and accidents. Besides, drivers from "dangerous" Southern European countries and Iran scored higher on aggressive violations and errors than did drivers from "safe" Northern European countries. However, "speeding" appeared to be a "pan-cultural" problem in traffic. Similarly, aggressive driving seems largely depend on road users' interactions and drivers' interpretation (i.e., cognitive biases) of the behaviour of others in every country involved in the study. Moreover, in all countries, a risky general driving style was mostly related to being young and male. The results of the fifth and sixth studies showed that among young Turkish drivers, gender stereotypes (i.e., masculinity and femininity) greatly influence driver behaviour and performance. Feminine drivers were safety-oriented whereas masculine drivers were skill-oriented and risky drivers. Since everyday driving tasks involve not only erroneous (i.e., risky or dangerous driving) or correct performance (i.e., normal habitual driving), but also "positive" driver behaviours, we developed a reliable scale for measuring "positive" driver behaviours among Turkish drivers in the seventh study. Consequently, I revised Reason's model [Reason, J. T., 1990. Human error. Cambridge University Press: New York] of aberrant driver behaviour to represent a general driving style, including all possible intentional behaviours in traffic while evaluating the differences between countries in traffic safety. The results emphasise the importance of economic, societal and cultural factors, general driving style and skills, which are related to exposure, cognitive biases as well as age, sex, and gender, in differences between countries in traffic safety.

Childhood and adolescent antecedents of work stress and early atherosclerosis

Work stress is after musculoskeletal disorders the second most common work-related health problem in the European Union, affecting 28% of EU employees. Furthermore, a 50% excessive cardiovascular disease risk among employees with work stress is reported. High job demands combined with low job control according to the Job Demands-Job Control model, or high effort combined with low rewards according to Effort-Reward Imbalance model, are likely to produce work stress in the majority of employees. Atherosclerotic wall thickening is a validated marker of an increased risk of cardiovascular disease. This study examined the role of childhood and adolescent factors as antecedents of work stress and early atherosclerosis, and in the relationship between them. The Cardiovascular Risk in Young Finns Study, (the CRYF project) started in 1980 when the participants were at the age of three to 18 years. Follow-ups have been conducted every three years until 1992, after that in 1997 and 2001, and the latest is ongoing in 2008. The participants parents reported their socioeconomic position in 1980 and 1983, and their life satisfaction in 1983. Biological risk factors were measured in 1980 and 2001. Type A behaviour was reported in 1986, 1989 and 2001. In the 2001 follow-up when the participants were aged 24 to 39, work stress was assessed from responses to questionnaires on job demands-job control and effort-reward imbalance, and education. Ultrasound measurement of the carotid intima-media thickness (CIMT) was used to assess atherosclerosis. There were 755, 746, 1014 and 494 participants in studies I-IV, respectively. The results showed that low parental socioeconomic position and parental life dissatisfaction during childhood and adolescence predicted higher levels of job strain 18 years later, and that education mediated the relationship between parental socioeconomic position and job strain. Childhood and adolescent family factors were not related to the effort-reward imbalance. Parental life satisfaction was associated with high rewards at work among the men, and high parental socioeconomic position was associated with high reward among the women. Among the men, the eagerness-energy component of Type A behaviour across different developmental periods predicted increased CIMT. Among the women, hard-driving component of Type A behaviour predicted decreased CIMT. Low leadership characteristic in adolescence and early adulthood was associated with both high job strain and increased CIMT, and attenuated the relationship between job strain and CIMT to non-significance in men. The current findings add to the literature on the relationship between job strain and health literature in adopting a developmental perspective. The results imply that work stress does not completely originate from work. There are childhood and adolescent environmental and dispositional effects on work stress and CIMT several years later, and these partly seem to operate through educational attainment.

Exploring Problem Decomposition in Conceptual Design

Design embraces several disciplines dedicated to the production of artifacts and services. These disciplines are quite independent and only recently has psychological interest focused on them. Nowadays, the psychological theories of design, also called design cognition literature, describe the design process from the information processing viewpoint. These models co-exist with the normative standards of how designs should be crafted. In many places there are concrete discrepancies between these two in a way that resembles the differences between the actual and ideal decision-making. This study aimed to explore the possible difference related to problem decomposition. Decomposition is a standard component of human problem-solving models and is also included in the normative models of design. The idea of decomposition is to focus on a single aspect of the problem at a time. Despite its significance, the nature of decomposition in conceptual design is poorly understood and has only been preliminary investigated. This study addressed the status of decomposition in conceptual design of products using protocol analysis. Previous empirical investigations have argued that there are implicit and explicit decomposition, but have not provided a theoretical basis for these two. Therefore, the current research began by reviewing the problem solving and design literature and then composing a cognitive model of the solution search of conceptual design. The result is a synthetic view which describes recognition and decomposition as the basic schemata for conceptual design. A psychological experiment was conducted to explore decomposition. In the test, sixteen (N=16) senior students of mechanical engineering created concepts for two alternative tasks. The concurrent think-aloud method and protocol analysis were used to study decomposition. The results showed that despite the emphasis on decomposition in the formal education, only few designers (N=3) used decomposition explicitly and spontaneously in the presented tasks, although the designers in general applied a top-down control strategy. Instead, inferring from the use of structured strategies, the designers always relied on implicit decomposition. These results confirm the initial observations found in the literature, but they also suggest that decomposition should be investigated further. In the future, the benefits and possibilities of explicit decomposition should be considered along with the cognitive mechanisms behind decomposition. After that, the current results could be reinterpreted.

Montessorivälineet esiopetuksessa : Montessoriohjaajakoulutuksen saaneiden lastentarhanopettajien käsityksiä montessorivälineiden soveltuvuudesta esiopetuksessa

Tutkimuksessa selvitettiin montessorivälineiden soveltuvuutta suomalaiseen esiopetukseen montessoriohjaajakoulutuksen saaneiden lastentarhanopettajien arvioimina. Tutkimuksen ensimmäisenä tehtävänä oli selvittää, missä määrin montessorivälineitä käytettiin esiopetuksessa. Tutkimuksessa kartoitettiin montessorivälineiden osuutta vastaajien lapsiryhmien toimintamateriaaleista sekä mahdollisia esteitä niiden määrän lisäämiselle. Samoin selvitettiin, kuinka tärkeäksi montessorivälineiden merkitys koettiin opetussuunnitelman tavoitteiden toteutumisessa. Lisäksi kartoitettiin montessorivälineiden käytön laajuutta vastaajien työyhteisössä sekä mahdollisia esteitä välineiden laajemmalle käytölle. Tutkimuksen toisena tehtävänä oli selvittää, miten montessorivälineet tukevat lapsikeskeiselle esiopetukselle asetettuja tavoitteita yksilöllisyyden, sosiaalisten taitojen kehittymisen, omatoimisuuden ja aktiivisuuden, leikin merkityksen sekä välineistön monipuolisuuden suhteen. Tutkimuksen kohderyhmäksi valittiin mahdollisimman kattavasti ne montessoriohjaajat, jotka olivat saaneet myös lastentarhanopettajakoulutuksen. Kohderyhmä käsitti 74 henkilöä. Tutkimus suoritettiin postikyselynä joulukuussa 1996 ja tammikuussa 1997. Tutkimuksen vastausprosentiksi muodostui 79,3 %. Tutkimuksen tulokset osoittivat, että montessorivälineiden osuus vastaajien lapsiryhmien käytössä olevista toimintamateriaaleista oli merkittävä. Tämä korostui erityisesti montessoripäiväkodeissa, -leikkikouluissa ja päiväkodin montessoriryhmissä. Kaikissa toimipaikoissa montessorivälineitä ei ollut riittävästi, vaikka kiinnostus niitä kohtaan oli suuri. Montessorivälineiden osuuden lisäämistä vaikeuttivat mm. taloudelliset esteet. Montessorivälineiden merkitys opetussuunnitelman tavoitteiden toteutumisenkannalta osoittautui tärkeäksi. Tulosten perusteella suppeammallakin montessorivälinemäärällä oli opetussuunnitelman tavoitteiden kannalta suuri merkitys. Montessorivälineiden käytön laajuus vastaajientyöyhteisössä vaihteli toimipaikoittain. Koulutuksen puute ilmeni merkittävimmäksi esteeksi montessorivälineiden laajemmalle käytölle vastaajien työyhteisössä. Tutkimuksen tulosten perusteella montessorivälineillä työskentely tukee vahvasti lapsikeskeisen esiopetuksen kannalta tärkeitä tavoitteita yksilöllisyyden, omatoimisuuden ja aktiivisuuden sekä sosiaalisten taitojen kehittymisen suhteen. Montessorivälineiden katsottiin soveltuvan hyvin esiopetukseen myös monipuolisuutensa ansiosta. Leikin merkitys ei montessorivälineillä työskentelyssä ollut keskeisessä asemassa. Sen sijaan montessorivälineillä työskentelyssä painottuivat leikki, työ ja oppiminen. Avainsanat: Montessori-pedagogiikka, montessorivälineet, lapsikeskeinen esiopetus, toimintamateriaalit Keywords: Montessori-pedagogy, Montessori materials, child-centered pre-school education, activity mater

Tarinakontekstin vaikutus sanojen muistamiseen kompleksisessa työmuistitehtävässä

Objectives. The sentence span task is a complex working memory span task used for estimating total working memory capacity for both processing (sentence comprehension) and storage (remembering a set of words). Several traditional models of working memory suggest that performance on these tasks relies on phonological short-term storage. However, long-term memory effects as well as the effects of expertise and strategies have challenged this view. This study uses a working memory task that aids the creation of retrieval structures in the form of stories, which have been shown to form integrated structures in longterm memory. The research question is whether sentence and story contexts boost memory performance in a complex working memory task. The hypothesis is that storage of the words in the task takes place in long-term memory. Evidence of this would be better recall for words as parts of sentences than for separate words, and, particularly, a beneficial effect for words as part of an organized story. Methods. Twenty stories consisting of five sentences each were constructed, and the stimuli in all experimental conditions were based on these sentences and sentence-final words, reordered and recombined for the other conditions. Participants read aloud sets of five sentences that either formed a story or not. In one condition they had to report all the last words at the end of the set, in another, they memorised an additional separate word with each sentence. The sentences were presented on the screen one word at a time (500 ms). After the presentation of each sentence, the participant verified a statement about the sentence. After five sentences, the participant repeated back the words in correct positions. Experiment 1 (n=16) used immediate recall, experiment 2 (n=21) both immediate recall and recall after a distraction interval (the operation span task). In experiment 2 a distracting mental arithmetic task was presented instead of recall in half of the trials, and an individual word was added before each sentence in the two experimental conditions when the participants were to memorize the sentence final words. Subjects also performed a listening span task (in exp.1) or an operation span task (exp.2) to allow comparison of the estimated span and performance in the story task. Results were analysed using correlations, repeated measures ANOVA and a chi-square goodness of fit test on the distribution of errors. Results and discussion. Both the relatedness of the sentences (the story condition) and the inclusion of the words into sentences helped memory. An interaction showed that the story condition had a greater effect on last words than separate words. The beneficial effect of the story was shown in all serial positions. The effects remained in delayed recall. When the sentences formed stories, performance in verification of the statements about sentence context was better. This, as well as the differing distributions of errors in different experimental conditions, suggest different levels of representation are in use in the different conditions. In the story condition, the nature of these representations could be in the form of an organized memory structure, a situation model. The other working memory tasks had only few week correlations to the story task. This could indicate that different processes are in use in the tasks. The results do not support short-term phonological storage, but instead are compatible with the words being encoded to LTM during the task.

Sovelletun rentoutuksen vaikutus psyykkiseen työhyvinvointiin ja sykevaihteluun

Research reveals that more than every fourth Finn experiences work-related exhaustion to some degree. Stress and exhaustion have psychological and physical expressions. The main physical factor in stress is the overloading of the autonomic nervous system, which can be measured for instance by variations of heart rate. Studies show that the work field, management and authority of the work, skill developmental possibilities, and social support inhibit stress overload. The practising of self-relaxation techniques possible inhibits working stress and exhaustion. In this study of preventive rehabilitation, the focus was on the effects of the training of applied relaxation on psychological and physiological variables of stress and empowerment of resources. Participants (n=73) were basically healthy and capable of working, 25-40 of age, workers from the field of mental work. They practised applied relaxation under group conduction for seven weeks. The aim was to learn to relax easily even in everyday occasions. The subjects were tested thirdly. After the first measurement, they were grouped into two groups, of which the first group started the relaxation training. The second group began practising half a year after the second measurement. The third measurement was done one year after the beginning of the study. It was hypothesised that the training of applied relaxation would significantly reduce stress on both psychological and physiological variables and that these variables would correlate positively. Results revealed that the training of applied relaxation reduced psychological stress symptoms rather modestly. The changes were more significant in women, who experienced a slight increase in self-directivity. Physical changes were slight decreases of the sympathetic activation. The correlations of psychological and physiological variables were modest. Some changes were reduced after the active training. There was a positive interrelation between experienced work-related demands of efficiency, insufficient social support and exhaustion. There was a tendency to significance between skill developmental possibilities and psychological stress symptoms. Further implications of the results were discussed.

Feeling Better, Performing Better? Holistically-Oriented Top Performance and Well-Being (HOPE) : Performance Enhancement and Its Perceived Impacts on Musicians

Most musicians choose a career in music based on their love of the art and a desire to share it with others. However, being a performing musician is highly demanding. Despite considerable evidence of the great frequency of performance-related problems (e.g. debilitating performance anxiety) among professional musicians or aspiring musicians in the current Western classical music tradition these problems are seldom discussed openly. The existing system offers musicians very little help in learning how to build sustainable performance success into their musical career. This study it is first of its kind in Finland which addresses the issue on larger scale in a systematic way. I devised the HOPE intervention (Holistically-Oriented Top Performance and Well-Being Enhancement), in order to learn how to integrate professional peak performance and a sense of personal well-being into the lives and careers of musicians. Unlike most interventions in previous research, the HOPE intervention is explicitly holistic and aims at enhancing the whole musician, not just alleviating performance anxiety. Earlier research has not in principle focused on musicians´ psychological well-being or on their subjective perceptions. The main purpose of the study is to understand the perceived impacts of the specially devised HOPE intervention on the participants and particularly in four key areas: performing, playing or singing well-being, and overall (performing, playing or singing and well-being combined). Furthermore, it is hoped that a deeper understanding of performers´ development will be gained. The research method is interdisciplinary and mainly qualitative. The primary data consist of a series of linked questionnaires (before and after the intervention) and semi-structured follow-up interviews collected during action research-oriented HOPE intervention courses for music majors in the Sibelius Academy. With the longitudinal group called Hope 1, the core data were collected during a nine month HOPE intervention course and from follow-up interviews conducted six months later in 2003-2004. The core data of Hope 1 (nine participants) are compared with the perceived impacts on fifty-three other participants in the HOPE courses during the period since their inception, 2001-2006. The focus is particularly on participants´ subjective perceptions. Results of the study suggest that the HOPE intervention is beneficial in enhancing overall performance capacity, including music performance, and a personal sense of well-being in a music university setting. The findings indicate that within all key areas significant positive changes take place between the beginning and the end of a HOPE intervention course. The longitudinal data imply that the perceived positive changes are still ongoing six months after the HOPE intervention course is finished. The biggest change takes place within the area of performing and the smallest, in participants´ perception of their playing or singing. The main impacts include reduced feelings of stress and anxiety (an enhanced sense of well-being) as well as increased sense of direction and control in one's life. Since the results of the present research gave no other reason to believe otherwise, it is to be expected that the HOPE intervention and the results of the study can be exploited in other areas of human activity as well, especially where continuous professional top performance is a prerequisite such as in business or sports. Keywords: performance enhancement, professional top performance, subjective well-being, subjective perceptions, holism, coaching, music performance anxiety, studying music, music.

Keltaista ja kimaltavaa : kodin ja koulun yhteistyöstä koulun ja kodin yhteyteen

Through this study I aim to portray connections between home and school through the patterns of thought and action shared in everyday life in a certain community. My observations are primarily based upon interviews, writings and artwork by people from home (N=32) and school (N=13) contexts. Through the stories told, I depict the characters and characteristic features of the home-school interaction by generations. According to the material, in the school days of the grandparents the focus was on discipline and order. For the parents, the focus had shifted towards knowledge, while for the pupils today, the focus lies on evaluation, through which the upbringing of the child is steered towards favourable outcomes. Teachers and those people at home hold partially different understandings of home-school interaction, both of its manifested forms and potentials. The forms of contact in use today are largely seen as one-sided. Yearning for openness and regularity is shared by both sides, yet understood differently. Common causes for failure are said to lie in plain human difficulties in communication and social interaction, but deeply rooted traditions regarding forms of contact also cast a shadow on the route to successful co-operation. This study started around the idea, that home-school interaction should be steered towards the ex-change of constructive ideas between both the home and school environments. Combining the dif-ferent views gives to something to build upon. To test this idea, I drafted a practice period, which was implemented in a small pre-school environment in the fall of 1997. My focus of interest in this project was on the handling of ordinary life information in the schools. So I combined individual views, patterns of knowledge and understanding of the world into the process of teaching. Works of art and writings by the informants worked as tools for information processing and as practical forms of building home-school interaction. Experiences from the pre-school environ-ment were later on echoed in constructing home-school interaction in five other schools. In both these projects, the teaching in the school was based on stories, thoughts and performances put to-gether by the parents, grandparents and children at home. During these processes, the material used in this study, consisting of artwork, writings and interviews (N=501), was collected. The data shows that information originating from the home environments was both a motivating and interesting addition to the teaching. There even was a sense of pride when assessing the seeds of knowledge from one’s own roots. In most cases and subjects, the homegrown information content was seamlessly connected to the functions of school and the curriculum. This project initiated thought processes between pupils and teachers, adults, children and parents, teachers and parents, and also between generations. It appeared that many of the subjects covered had not been raised before between the various participant groups. I have a special interest here in visual expression and its various contextual meanings. There art material portrays how content matter and characteristic features of the adult and parent contexts reflect in the works of the children. Another clearly noticeable factor in the art material is the impact of time-related traditions and functions on the means of visual expression. Comparing the visual material to the written material reveals variances of meaning and possibilities between these forms of expression. The visual material appears to be related especially to portraying objects, action and usage. Processing through that making of images was noted to bring back memories of concrete structures, details and also emotions. This process offered the child an intensive social connection with the adults. In some cases, with children and adults alike, this project brought forth an ongoing relation to visual expression. During this study I end up changing the concept to ‘home-school collaboration’. This widely used concept guides and outlines the interaction between schools and homes. In order to broaden the field of possibilities, I choose to use the concept ‘school-home interconnection’. This concept forms better grounds for forming varying impressions and practices when building interactive contexts. This concept places the responsibility of bridging the connection-gap in the schools. Through the experiences and innovations of thought gained from these projects, I form a model of pedagogy that embraces the idea of school-home interconnection and builds on the various impres-sions and expressions contained in it. In this model, school makes use of the experiences, thoughts and conceptions from the home environment. Various forms of expression are used to portray and process this information. This joint evaluation and observation evolves thought patterns both in school and at home. Keywords: percieving, visuality, visual culture, art and text, visual expression, art education, growth in interaction, home-school collaboration, school-home interconnection, school-home interaction model.

Ravintoa keholle, ruokaa mielelle : vertailututkimus pohjoismaisten nuorten ruokatottumuksista kotona ja koulussa

Aims. The main meals that youngsters have during the day are eaten at home and at school. In the Nordic countries breakfast and supper are often eaten with other members of the family. The way that Nordic countries arrange the school lunch and the frequency of family meals differ between countries. However, the challenges related to eating habits of the young are surprisingly similar. The aim of this study is to discuss how the Nordic countries could support youngsters’ healthy eating habits. This study was carried out as a part of a Nordic research project and it completed the work done by Kauppinen (2009) and Niemi (2009) in their Master’s Theses. The research questions are: 1. How do the youngsters evaluate their own eating habits and those of their family? 2. How do the youngsters evaluate the influence of home, family and school on their own eating habits? 3. What kind of relationship exists between eating at home and at school according to the data? Data and methods. A quantitative internet-based survey was used to collect data (N=1539) on the 9th graders conceptions and understandings. The survey consisted of respondents from Finland (N=586), Sweden (N=427), Denmark (N=295) and Norway (N=246). In this study the whole data to the appropriate extent was analyzed. The analysis was done with the SPSS-software and included examination of means, standard deviations, cross-tabulations, Pearson´s correlations, Chi-squared -tests, t-tests and one-way analysis of variance (ANOVA). The results were compaired between the countries and between sexes. Results and discussion. The studied youngsters evaluated their own eating habits positively. There were statistically signifigant differences (p< .05) between countries concerning the people who influence the youngsters’ healthy eating habits. Youngsters from Finland and Sweden considered making healthy choices at school easier than those from Denmark and Norway. Also eating a so called healthy lunch at school was more common in Finland and in Sweden. Eating breakfast and eating a healthy meal at school had a statistically significant interconnection (p< .001). The differences between sexes were not equal between the countries. The results supported those from previous studies, but also raised ideas for further study. Youngsters’ near environments should support their possibilities to make healthy choices and to participate to the decicion making process. Co-operation between the Nordic countries and between the home and the school is important. Listening to the youngsters’ own voice is a challence and a possibility for developing both home economics education and research in this area. Key words: Nordic countries, youngsters, healthy eating habits, eating at home, school meals

Koulun profiloitumisen haavoittuvuus : Tapaustutkimus opettajien vaihtuvuuden vaikutuksista Montessori-menetelmää soveltavassa yhdysluokassa 1-2

Tutkimuksen tavoitteena oli selvittää koulujen profiloitumisen ja opettajien vaihtuvuuden välistä yhteyttä. Nykyisen koulutuspolitiikan mukaisesti koulujärjestelmämme päätäntävalta on siirtynyt yhä enemmän koulujen tasolle ja mahdollistaa siten kouluille oikeuden päättää melko itsenäisesti tarjoamansa opetuksen sisällöistä, tavoitteista ja menettelytavoista. Kouluilla on myös oikeus laatia omat opetussuunnitelmansa ja näin profiloitua haluamalleen painotusalueelle. Työvoiman liikkuvuuden myötä myös opettajat vaihtavat työpaikkaansa. Käytännössä tämä tarkoittaa opettajien siirtymistä kouluista ja tehtävistä toisiin eripituisten työskentelyjaksojen jälkeen. Tällaisesta vaihtuvuudesta ja sen vaikutuksista koulun työskentelyilmapiiriin sekä kaikkiin koulumaailman osapuoliin voidaan kuitenkin olla montaa eri mieltä. Erityisesti vaikutukset johonkin pienempään opetusyksikköön voivat olla melkoiset. Tutkimus toteutettiin eräässä helsinkiläisen ala-asteen koulussa, keskittyen opettajien vaihtuvuuden tarkasteluun Montessori-pedagogiikalla opetettavassa yhdysluokassa. Tutkimukseen sisällytettiin Montessori-luokan oppilaat, heidän vanhempansa sekä koulun opettajat. Tutkimus suoritettiin kirjallisuuteen perehtyen, luokkaa observoiden, oppilaita ja opettajia haastatellen sekä vanhemmilla kirjoitelmia teettäen. Aineiston suppeuden ja tutkimuksen case study -luonteen vuoksi vaihtuvuuden moninaisia vaikutuksia ilmentäviä tutkimustuloksia ei kuitenkaan voida yleistää. Avainsanat: profiloituminen, vaihtuvuus, vaihtuvuuden vaikutukset, Montessori-pedagogiikka Keywords: profilation, changing, effects of changing, Montessori method

The role of catechol-O-methyltransferase (COMT) and the effects of COMT inhibition in brain and in cardiovascular and renal pathophysiology

Catechol-O-methyltransferase (COMT) metabolizes catecholamines such as dopamine (DA), noradrenaline (NA) and adrenaline, which are vital neurotransmitters and hormones that play important roles in the regulation of physiological processes. COMT enzyme has a functional Val158Met polymorphism in humans, which affects the subjects COMT activity. Increasing evidence suggests that this functional polymorphism may play a role in the etiology of various diseases from schizophrenia to cancers. The aim of this project was to provide novel biochemical information on the physiological and especially pathophysiological roles of COMT enzyme as well as the effects of COMT inhibition in the brain and in the cardiovascular and renal system. To assess the roles of COMT and COMT inhibition in pathophysiology, we used four different study designs. The possible beneficial effects of COMT inhibition were studied in double-transgenic rats (dTGRs) harbouring human angiotensinogen and renin genes. Due to angiotensin II (Ang II) overexpression, these animals exhibit severe hypetension, cardiovascular and renal end-organ damage and mortality of approximately 25-40% at the age of 7-weeks. The dTGRs and their Sprague-Dawley controls tissue samples were assessed with light microscopy, immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR) and high-pressure liquid chromatography (HPLC) to evaluate the tissue damages and the possible protective effects pharmacological intervention with COMT inhibitors. In a second study, the consequence of genetic and pharmacological COMT blockade in blood pressure regulation during normal and high-sodium was elucidated using COMT-deficient mice. The blood pressure and the heart rate were measured using direct radiotelemetric blood pressure surveillance. In a third study, the effects of acute and subchronic COMT inhibition during combined levodopa (L-DOPA) + dopa decarboxylase inhibitor treatment in homocysteine formation was evaluated. Finally, we assessed the COMT enzyme expression, activity and cellular localization in the CNS during inflammation-induced neurodegeneration using Western blotting, HPLC and various enzymatic assays. The effects of pharmacological COMT inhibition on neurodegeneration were also studied. The COMT inhibitor entacapone protected against the Ang II-induced perivascular inflammation, renal damage and cardiovascular mortality in dTGRs. COMT inhibitors reduced the albuminuria by 85% and prevented the cardiovascular mortality completely. Entacapone treatment was shown to ameliorate oxidative stress and inflammation. Furthermore, we established that the genetic and pharmacological COMT enzyme blockade protects against the blood pressure-elevating effects of high sodium intake in mice. These effects were mediated via enhanced renal dopaminergic tone and suggest an important role of COMT enzyme, especially in salt-sensitive hypertension. Entacapone also ameliorated the L-DOPA-induced hyperhomocysteinemia in rats. This is important, since decreased homocysteine levels may decrease the risk of cardiovascular diseases in Parkinson´s disease (PD) patients using L-DOPA. The Lipopolysaccharide (LPS)-induced inflammation and subsequent delayed dopaminergic neurodegeneration were accompanied by up-regulation of COMT expression and activity in microglial cells as well as in perivascular cells. Interestingly, similar perivascular up-regulation of COMT expression in inflamed renal tissue was previously noted in dTGRs. These results suggest that inflammation reactions may up-regulate COMT expression. Furthermore, this increased glial and perivascular COMT activity in the central nervous system (CNS) may decrease the bioavailability of L-DOPA and be related to the motor fluctuation noted during L-DOPA therapy in PD patients.

Effects of oral calcium sensitizers on experimental heart failure

Suun kautta annosteltava kalsiumherkistäjä parantaa sydämen vajaatoimintaan liittyvää pumppausvajetta kokeellisissa sydämen vajaatoimintamalleissa Huolimatta viime vuosikymmenien lääketieteellisestä kehityksestä krooninen sydämen vajaatoiminta on silti edelleen vakava, elämänlaatua voimakkaasti rajoittava sairaus. Kalsiumherkistäjät ovat uusi, sydämen pumppausvoimaa lisäävä lääkeryhmä. Levosimendaani, kotimaista alkuperää oleva kalsiumherkistäjä, on kliinisessä käytössä akuutin vajaatoiminnan hoitoon suonensisäisesti ja lyhytaikaisesti annosteltavana valmisteena. Levosimendaanilla on aktiivinen metaboliitti, OR-1896, jonka oletetaan olevan vuorokauden mittaisen levosimendaani-infuusion jälkeen havaittujen useita päiviä kestävien hyödyllisisten vaikutuksisten takana. Levosimendaanin kroonisen, suun kautta tapahtuvan annostelun vaikutuksista tieto on vähäisempää, mutta sillä näyttää olevan positiivisia vaikutuksia potilaiden raportoimana. FM Marjut Louhelainen on selvittänyt väitöskirjassaan suun kautta annosteltavan levosimendaanin ja sen pitkäkestoisen aktiivisen metaboliitin vaikutuksia kroonisen vajaatoiminnan hoidossa käyttämällä sekä hypertensiivisen sydäntaudin että 2 tyypin diabeteksen komplisoimaan sydäninfarktin kokeellisia malleja. Tutkimuksessa selvitettiin lisäksi vajaatoimintaan johtavia molekyylitason tapahtumia sydänlihaksessa. Tutkimuksessa osoitettiin, että krooninen suun kautta annosteltu hoito sekä kalsiumherkistäjä levosimendaanilla että sen aktiivisella metaboliitilla estää hypertensiiviseen sydämen vajaatoiminnan aikaasaamaa sydämen uudelleenmuovaantumista ja siihen liittyvää kuolleisuutta. Nämä vaikutukset välittyivät vähentyneen sydänlihassoluhypertrofian, solukuolleisuuden ja neurohumaraalisen aktivaation kautta. Levosimendaanin ja OR-1896:n osoitettiin myös parantavan sydämen pumppausfunktiota tyyppi 2 diabeteksen komplisoimassa sydäninfarktissa. Ei-diabeettiseen tilanteeseen verrattuna diabetekseen liittyvä infarktin jälkeinen vajaatoiminnan kehitys oli yhteydessä lisääntyneeseen tulehdukseen, fibroosiin, solukuolemaan, neurohumoraaliseen aktivaatioon ja ennenaikaiseen kudoksen vanhenemiseen. Sekä levosimendaani, että OR-1869 vähensivät tulehduksen, fibroosin ja solukuoleman merkkejä ja vaimensi neurohumoraalista aktivaatiota. OR-1896 myös vähensi solujen vanhenemiseen liittyvien merkkiaineiden ilmentymistä. Väitöskirjassa todettiin, että suun kautta annosteltuna sekä levosimendaani, että sen aktiivinen metaboliitti OR-1896, omaavat terapeuttista potentiaalia sekä hypertensiivisen sydäntaudin hoitoon että sydäninfarktin jälkeisen vajaatoiminnan estoon. FM Marjut Louhelaisen farmakologian alaan kuuluva väitöskirja Effects of oral calcium sensitizers on experimental heart failure tarkastetaan Helsingin yliopiston Lääketieteellisessä tiedekunnassa perjantaina 29.01.2010 klo 12 (Biomedicum Helsinki, luentosali 2, Haartmaninkatu 8, Helsinki). Vastaväittäjänä toimii professori Raimo Tuominen, Helsingin yliopiston Farmasian tiedekunnasta ja kustoksena professori Eero Mervaala Helsingin yliopiston Lääketieteellisestä tiedekunnasta.

Androgen receptor in transcriptional regulation and carcinogenesis

Androgens control a variety of developmental processes that create the male phenotype and are important for maintaining male fertility and normal functions of tissues and organs that are not directly involved in procreation. Androgen receptor (AR) that mediates the biological actions of androgens is a member of the nuclear receptor superfamily of ligand-inducible transcription factors. Although AR was cloned over 15 years ago, the mechanisms by which it regulates gene expression are not well understood. A growing body of in vitro experimental evidence suggests that a complex network of proteins is involved in the androgen-dependent transcriptional regulation. However, the process of AR-dependent transcriptional regulation under physiological conditions is largely elusive. In the present study, a series of experiments were performed, including quantitative chromatin immunoprecipitation (ChIP) assays, to investigate AR-mediated transcription process using living prostate cancer cells. Our results show that the loading of AR and recruitment of coactivators and RNA polymerase II (Pol II) to both the promoter and enhancer of AR target genes are a transient and cyclic event that in addition to hyperacetylation, also involves dynamic changes in methylation, phosphorylation of core histone H3 in androgen-treated LNCaP cells. The dynamics of testosterone (T)-induced loading of AR onto the proximal promoters of the genes clearly differed from that loaded onto the distal enhancers. Significantly, more holo-AR was loaded onto the enhancers than the promoters, but the principal Pol II transcription complex was assembled on the promoters. By contrast, the pure antiandrogen bicalutamide (CDX) complexed to AR elicited occupancy of the PSA promoter, but was unable to load onto the PSA enhancer and was incapable of recruiting Pol II, coactivators and following changes of covalent histone modifications. The partial antagonist cyproterone acetate (CPA) and mifepristone (RU486) were capable of promoting AR loading onto both the PSA promoter and enhancer at a comparable efficiency with androgen in LNCaP cells expressing mutant AR. However, CPA- and RU486-bound AR not only recruited Pol II and coactivator p300 and GRIP1 onto the promoter and enhancer, but also recruited the corepressor NCoR onto the promoter as efficiently as CDX. In addition, we demonstrate that both proteasome and protein kinases are implicated in AR-mediated transcription. Even though proteasome inhibitor MG132 and protein kinase inhibitor DRB (5, 6-Dichlorobenzimidazole riboside) can block ligand-dependent accumulation of PSA mRNA with same efficiency, their use results in different molecular profiles in terms of the formation of AR-mediated transcriptional complex. Collectively, these results indicate that transcriptional activation by AR is a complicated process, which includes transient loading of holo-AR and recruitment of Pol II and coregulators accompanied by a cascade of distinct covalent histone modifications; This process involves both the promoter and enhancer elements, as well as other general components of the cell machineries e.g. proteasome and protein kinase; The pure antiandrogen CDX and the partial antagonist CPA and RU486 exhibit clearly different profiles in terms of their ability to induce the formation of AR-dependent transcriptional complexes and the histone modifications associated with the target genes in human prostate cancer cells. Finally, by using quantitative RT-PCR to compare the expression of sixteen AR co-regulators in prostate cancer cell lines, xenografts, and clinical prostate cancer specimens we suggest that AR co-regulators protein inhibitor of activated STAT1 (PIAS1) and steroid receptor coactivator 1(SRC1) could be involved in the progression of prostate cancer.

Immunomodulatory effects of probiotic bacteria in healthy adults

Probiooteilla kantakohtaisia vaikutuksia ihmisen immuunijärjestelmään terveillä aikuisilla Probiooteilla on kantakohtaisia tulehduksen välittäjäaineita vähentäviä vaikutuksia ja probioottien yhdistelmien vaikutukset eroavat yksittäisten kantojen vaikutuksista selviää TtM Riina Kekkosen tuoreesta väitöstutkimuksesta. TtM Riina Kekkonen on selvittänyt väitöskirjassaan eri probioottikantojen vaikutuksia immuunivasteeseen valkosolumallissa sekä terveillä aikuisilla lumekontrolloiduissa kliinisissä tutkimuksissa. Aikaisemmin probioottien vaikutuksia on tutkittu lähinnä allergian ja erilaisten vatsavaivojen ehkäisyssä ja hoidossa. Probiootteja sisältäviä tuotteita käyttävät kuluttajat ovat kuitenkin useimmiten terveitä aikuisia, ja probioottien vaikutus terveiden aikuisten immuunijärjestelmään on ollut puutteellisesti selvitettyä. Valkosolumallissa probioottikantojen havaittiin poikkeavan toisistaan niiden kyvyssä aktivoida immuunivasteen välittäjäaineiden, sytokiinien, tuotantoa. Anti-inflammatorisia, eli tulehdusta lievittäviä vaikutuksia nähtiin lähinnä Bifidobacterium ja Propionibacterium sukuihin kuuluvilla kannoilla. Streptococcus ja Leuconostoc sukuihin kuuluvat kannat puolestaan aktivoivat Th1 tyyppistä, soluvälitteistä immuunivastetta. Eri probioottien kombinaatiot eivät saaneet aikaan voimakkaampaa aktivaatiota yksittäisiin kantoihin verrattuna, joka viittaa probioottien keskinäiseen kilpailuun niiden ollessa kontaktissa ihmisen solujen kanssa. Probioottikantojen valinta kliinisiin tutkimuksiin tehtiin niiden anti-inflammatoristen ominaisuuksien perusteella. Parhaita anti-inflammatorisia kantoja olivat B. lactis ssp. animalis Bb12 ja P. freudenreichii ssp. shermanii JS, joiden lisäksi tutkimuksiin valittiin myös L. rhamnosus GG (LGG) hyvin tutkittuna referenssikantana. Solutöiden tulokset eivät olleet täysin verrannollisia kliinisen työn tuloksiin, koska LGG näytti omaavan parhaat anti-inflammatoriset ominaisuudet kliinisissä tutkimuksissa vaikka solutyössä sen aikaansaamat vasteet olivat melko vaimeita. Kolmen viikon kliinisessä tutkimuksessa terveillä aikuisilla LGG alensi mm. tulehdusta kuvaavan C-reaktiivisen proteiinin ja inflammatoristen sytokiinien määrää. Pidemmässä kolmen kuukauden pituisessa kliinisessä tutkimuksessa LGG:llä ei ollut vaikutusta terveiden aikuisten infektiosairastavuuteen, mutta LGG lyhensi vatsavaivojen kestoa. Probioottien vaikutukset immuunijärjestelmään näyttävät olevan kantakohtaisia ja erityisesti Lactobacillus rhamnosus GG:llä havaittiin anti-inflammatorisia vaikutuksia. Valkosolumallia ei tulisi käyttää ainoana probioottikantojen skriinausmenetelmänä niiden immunologisia vaikutuksia selvitettäessä, koska solutöiden tulokset eivät olleet täysin verrannollisia kliinisten tutkimusten tuloksiin. Sen sijaan veren perifeeristen lymfosyyttien eristäminen ja niiden aktivoitumisen selvittäminen lyhytaikaisessa kliinisessä tutkimuksessa voisi toimia suhteellisen helppona skiinausmenetelmänä.

The role of probiotics in Helicobacter pylori infection

Helicobacter pylori (H. pylori) infection is a major cause of chronic gastritis and peptic ulcer disease, and it is also designated as a class-I carcinogen for stomach cancer. The role of probiotics in the treatment of gastrointestinal infections is increasingly documented as an alternative or complement to antibiotics, with the potential to decrease the use of antibiotics or reduce their adverse effects. These studies were conducted to investigate the role of probiotics in the treatment of H. pylori infection. Various aspects included: an investigation of the effects of a probiotic combination consisting of Lactobacillus rhamnosus GG, L. rhamnosus LC705, Propionibacterium freudenreichii ssp. shermanii JS and Bifidobacterium breve Bb99 or B. lactis Bb12 as a supplementation to H. pylori eradication therapy, with special reference to tolerability, effectiveness, and microbiota alterations following the treatment; discovering the role of probiotics in vivo with H. pylori infected and uninfected patients, as well as with an in vitro model of H. pylori infection. The probiotic combination therapy was able to reduce significantly the total symptom score, which takes into account both the frequency and the severity of the adverse effects, during the eradication treatment. The supplementation did not improve the success of the eradication treatment significantly, though some difference was seen in the eradication percentages (91% vs. 79%). The quantities of predominant bacterial groups were altered significantly following the triple treatment. Probiotics slightly counteracted the effects of anti-H. pylori treatment, monitored as significantly less alterations in the total numbers of aerobes and lactobacilli/enterococci group bacteria. After probiotic intervention, L. rhamnosus GG adhered to a minority of the patients upper gastrointestinal mucosa, but all of the probiotics survived well through the gastrointestinal tract transit with and without antimicrobial treatment. Probiotic intervention decreased gastrin-17 levels in H. pylori infected patients and appeared to decrease the 13C-urea breath test values. In in vitro Caco-2 cell line experiments, probiotics inhibited H. pylori adhesion to intestinal epithelial cells. Both L. rhamnosus strains, P. freudenreichii ssp. shermanii JS and the combination inhibited the H. pylori-induced acute cell leakage. Simultaneously, both L.rhamnosus strains and the combination transiently improved the epithelial barrier function. The pro-inflammatory effects prevailed when the probiotics were used in combination. According to this series of studies, probiotic combination could have some potential in reducing adverse effects induced by H. pylori eradication treatment and beneficial effects on H. pylori infected subjects.