TURKU TAKING STEPS TOWARDS FUTURE - technology supports physical activity

Physical activity (PA) is an important field of healthcare research internationally and within Finland. As technology devices and services penetrate deeper levels within society, the need for studying the usefulness for PA turns vital. We started this research work by reviewing literature consisting of two hundred research journals, all of which have found technology to significantly improve an individual’s ability to get motivation and achieve officially recommended levels of physical activity, like the 10000 steps a day, being tracked with the help of pedometers. Physical activity recommendations require sustained encouragement, consistent performance in order to achieve the long term benefits. We surveyed within the city of Turku, how the motivation levels and thirty three other criterions encompassing technology awareness, adoption and usage attitudes are impacted. Our aim was to know the factors responsible for achieving consistent growth in activity levels within the individuals and focus groups, as well as to determine the causes of failures and for collecting user experience feedback. The survey results were quite interesting and contain impeccable information for this field. While the focus groups confirmed the theory established by past studies within our literature review, it also establishes our research propositions that ict tools and services have provided and can further add higher benefits and value to individuals in tracking and maintain their activity levels consistently for longer time durations. This thesis includes two new models which dictate technology and physical activity adoption patterns based on four easy to evaluate criterions, thereby helping the healthcare providers to recommend improvements and address issues with an easy rule based approach. This research work provides vital clues on technology based healthcare objectives and achievement of standard PA recommendations by people within Turku and nearby regions.

Genetic, prenatal and postnatal determinants of weight gain and obesity in young children – The STEPS Study

Genetic, Prenatal and Postnatal Determinants of Weight Gain and Obesity in Young Children – The STEPS Study University of Turku, Faculty of Medicine, Department of Paediatrics, University of Turku Doctoral Program of Clinical Investigation (CLIPD), Turku Institute for Child and Youth Research. Conditions of being overweight and obese in childhood are common health problems with longlasting effects into adulthood. Currently 22% of Finnish boys and 12% of Finnish girls are overweight and 4% of Finnish boys and 2% of Finnish girls are obese. The foundation for later health is formed early, even before birth, and the importance of prenatal growth on later health outcomes is widely acknowledged. When the mother is overweight, had high gestational weight gain and disturbances in glucose metabolism during pregnancy, an increased risk of obesity in children is present. On the other hand, breastfeeding and later introduction of complementary foods are associated with a decreased obesity risk. In addition to these, many genetic and environmental factors have an effect on obesity risk, but the clustering of these factors is not extensively studied. The main objective of this thesis was to provide comprehensive information on prenatal and early postnatal factors associated with weight gain and obesity in infancy up to two years of age. The study was part of the STEPS Study (Steps to Healthy Development), which is a follow-up study consisting of 1797 families. This thesis focused on children up to 24 months of age. Altogether 26% of boys and 17% of girls were overweight and 5% of boys and 4% of girls were obese at 24 months of age according to New Finnish Growth references for Children BMI-for-age criteria. Compared to children who remained normal weight, the children who became overweight or obese showed different growth trajectories already at 13 months of age. The mother being overweight had an impact on children’s birth weight and early growth from birth to 24 months of age. The mean duration of breastfeeding was almost 2 months shorter in overweight women in comparison to normal weight women. A longer duration of breastfeeding was protective against excessive weight gain, high BMI, high body weight and high weight-for-length SDS during the first 24 months of life. Breast milk fatty acid composition differed between overweight and normal weight mothers, and overweight women had more saturated fatty acids and less n-3 fatty acids in breast milk. Overweight women also introduced complementary foods to their infants earlier than normal weight mothers. Genetic risk score calculated from 83 obesogenic- and adiposity-related single nucleotide polymorphisms (SNPs) showed that infants with a high genetic risk for being overweight and obese were heavier at 13 months and 24 months of age than infants with a low genetic risk, thus possibly predisposing to later obesity in obesogenic environment. Obesity Risk Score showed that children with highest number of risk factors had almost 6-fold risk of being overweight and obese at 24 months compared to children with lowest number of risk factors. The accuracy of the Obesity Risk Score in predicting overweight and obesity at 24 months was 82%. This study showed that many of the obesogenic risk factors tend to cluster within children and families and that children who later became overweight or obese show different growth trajectories already at a young age. These results highlight the importance of early detection of children with higher obesity risk as well as the importance of prevention measures focused on parents. Keywords: Breastfeeding, Child, Complementary Feeding, Genes, Glucose metabolism, Growth, Infant Nutrition Physiology, Nutrition, Obesity, Overweight, Programming

Steps towards more effective antitrust system in EU – The Damages Directive’s effect on victim’s right to compensation for antitrust harm

Kaikkien kansalaisten ja yritysten, jotka kärsivät vahinkoa Euroopan Unionin kilpailusääntöjen (SEUT 101 ja 102 artiklan) rikkomisen vuoksi, on voitava vaatia korvauksia vahingon aiheuttaneelta osapuolelta. Euroopan unionin tuomioistuin on ratkaisuillaan Courage ja Manfredi vahvistanut vahinkoa kärsineen oikeuden saada korvausta kärsimästään vahingosta. Suomessa kilpailuoikeudellista vahingonkorvausta koskeva oikeuskäytäntö on ollut vähäistä, vaikkakin viime aikoina on annettu muutama merkittävä vahingonkorvausratkaisu, näistä kenties tunnetuimpana asvalttikartelliratkaisu. Kilpailuoikeuden rikkomisesta vahinkoa kärsineet saavat kuitenkin vain harvoin korvausta kärsimästään vahingosta, mikä on ollut seurausta erilaisista lainsäädännöllisistä ja menettelyistä johtuvista esteistä jäsenvaltioiden säännöissä. Komission pitkään kestänyt lainsäädäntöhanke EU:n kilpailuoikeuden täytäntöönpanojärjestelmän selkeyttämiseksi päättyi marraskuussa 2014, kun Euroopan parlamentin ja neuvoston direktiivi tietyistä säännöistä, joita sovelletaan jäsenvaltioiden ja Euroopan unionin kilpailuoikeuden rikkomisen johdosta kansallisen lainsäädännön nojalla nostettuihin vahingonkorvauskanteisiin (2014/104/ EU) hyväksyttiin. Direktiivi julkaistiin Euroopan unionin virallisessa lehdessä 5. joulukuuta 2014, ja jäsenvaltioilla on 27.12.2016 asti aikaa implementoida direktiivi osaksi kansallista lainsäädäntöä. Direktiivin tavoitteena on EU:n kilpailusääntöjen tehokas täytäntöönpano sekä kilpailuoikeuden julkisoikeudellisen ja yksityisoikeudellisen täytäntöönpanon selkeyttäminen. Lisäksi direktiivi pyrkii varmistamaan, että vahingonkärsijät voivat saada täyden korvauksen kärsimästään vahingosta, sekä poistamaan esteitä ja pienentämään kustannuksia vahingon todistamisessa, samalla harmonisoiden eri jäsenmaissa toimivien yritysten oikeussuojan tasoa. Tarkastelen pro gradu –tutkielmassani kilpailuoikeudellisen vahingonkorvauksen kehitystä sekä uuden EU:n vahingonkorvausdirektiivin vaikutuksia erityisesti vahingonkärsijän näkökulmasta, eli sitä kuinka direktiivi vaikuttaa vahingonkärsijän mahdollisuuteen saada korvausta kärsimästään vahingosta, joka johtuu EU:n kilpailusääntöjen rikkomisesta. Lisäksi tarkastelen lyhyesti direktiivin tuomia muutoksia Suomen lainsäädäntöön. Tutkielmani loppupäätelmä on, että vaikka vahingonkorvausdirektiivi ei täydellisesti paranna vahingonkärsijän asemaa, se selkeyttää monella tavalla kilpailuoikeudellisten vahingonkorvauskanteiden nykyistä tilaa, ja saattaa tietyssä määrin rohkaista vahingonkärsijiä hakemaan korvausta kärsimästään vahingosta.

Glycosylation and Glycodiversification in Polyketide Antibiotics: Unraveling Biosynthetic Steps in Nogalamycin Formation

Soil-dwelling Streptomyces bacteria are known for their ability to produce biologically active compounds such as antimicrobial, immunosuppressant, antifungal and anticancer drugs. S. nogalater is the producer of nogalamycin, a potential anticancer drug exhibiting high cytotoxicity and activity against human topoisomerases I and II. Nogalamycin is an anthracycline polyketide comprising a four-ring aromatic backbone,a neutral deoxy sugar at C7, and an amino sugar attached via an O–C bond at C1 and a C–C bond between C2 and C5´´. This kind of attachment of the amino sugar is unusual thus making the structure of the compound highly interesting. The sugar is also associated with the biological activity of nogalamycin, as it facilitates binding to DNA. Furthermore, the sugar moieties of anthracyclines are often crucial for their biological activity. Together the interesting attachment of the amino sugar and the general reliance of polyketides on the sugar moieties for bioactivity have made the study of the biosynthesis of nogalamycin attractive. The sugar moieties are typically attached by glycosyltransferases, which use two substrates: the donor and the acceptor. The literature review of the thesis is focused on the glycosylation of polyketides and the possibilities to alter their glycosylation patterns. My own thesis work revolves around the biosynthesis of nogalamycin. We have elucidated the individual steps that lead to its rather unique structure. We reconstructed the whole biosynthetic pathway in the heterologous host S. albus using a cosmid and a plasmid. In the process, we were able to isolate new compounds when the cosmid, which contains the majority of the nogalamycin gene cluster, was expressed alone in the heterologous host. The new compounds included true intermediates of the pathway as well as metabolites, which were most likely altered by the endogenous enzymes of the host. The biological activity of the most interesting new products was tested against human topoisomerases I and II, and they were found to exhibit such activities. The heterologous expression system facilitated the generation of mutants with inactivated biosynthetic genes. In that process, we were able to identify the functions of the glycosyltransferases SnogE and SnogD, solve the structure of SnogD, discover a novel C1-hydroxylase system comprising SnoaW and SnoaL2, and establish that the two homologous non-heme α-ketoglutarate and Fe2+ dependent enzymes SnoK and SnoN catalyze atypical reactions on the pathway. We demonstrated that SnoK was responsible for the formation of the additional C–C bond, whereas SnoN is an epimerase. A combination of in vivo and in vitro techniques was utilized to unravel the details of these enzymes. Protein crystallography gave us an important means to understand the mechanisms. Furthermore, the solved structures serve as platforms for future rational design of the enzymes.