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  • Rytsölä, Perttu (2005)
    Tutkimuksen kohteena on Argentiinan vuoden 1978 jalkapallon maailmanmestaruuskilpailuiden aikainen yhteiskunta. Tutkimuksella on kaksi tavoitetta. Ensimmäinen tavoite on tarkastella kysymystä miksi Argentiinaa 1976–1982 hallinnut sotilasvalta järjesti maailmanmestaruuskilpailut. Vastaus annetaan sijoittamalla sotilasvallan toiminnasta tehtyä tutkimusta nationalismitutkimuksen ja Argentiinan yhteiskunnan viitekehykseen. Tutkimuksessa sovelletaan Michael Billigin kehittämää termiä banaali nationalismi. Banaalia nationalismia ovat arkipäiväiset yhteiskuntaa ylläpitävät toiminnot, kuten huippu-urheilu. Urheilujournalismi tarjoaa kansalaisille mahdollisuuden harjoittaa nationalistisia tunteitaan huippu-urheiluun. Sotilasvallan motiiveiksi nimetään sisäpoliittisesti rakenteellinen taistelu hegemoniasta ja ulkopoliittisesti maan ulkoisen kuvan parantaminen. Toinen tavoite on tarkastella kilpailujen ajan Argentiinan yhteiskunnallisesta tilanteesta välittynyttä lehdistökuvaa. Analyysin taustaksi tarkastellaan Argentiinan sotilasvallan ja median suhdetta. Tutkimusmenetelmänä käytetään kriittistä diskurssianalyysiä. Aineistosta nostetaan esiin teemoja, jotka johdetaan laajempiin diskursseihin. Johtopäätöksiä tarkastellaan nationalismitutkimuksen viitekehyksessä. Lehdistölähteinä käytetään argentiinalaista Clarín Edicion Internacional -julkaisua ajalta 16.5–3.7.1978 sekä Helsingin Sanomia ja brittiläistä The Times sanomalehteä ajalta 15.5–30.6.1978. Clarin Edicion Internacionalin uutisoinnista erotetaan ylpeysteema. Ylpeys viittaa muutoksen diskurssiin. Muutosta edeltää negatiivinen, ristiriitainen yhteiskunta. Maailmanmestaruuskilpailuiden aika on muutostilaa. Muutos tapahtuu argentiinalaisten oman toiminnan ansiosta. Tuloksena on positiviinen, yhtenäinen kansakunta. The Timesin uutisoinnista erotetaan kaksi kilpailevaa teemaa: Turvallisuusteema ja kisateema. Turvallisuusteema viittaa negatiiviseen diskurssiin: Argentiinan sisäisiin ristiriitoihin. Kisateema viittaa positiiviseen diskurssiin: Argentiinalaisten yhtenäisyyteen. Ajanjaksolla diskurssien suhteissa tapahtuu muutos. Alussa heikompi yhtenäisyys alistaa ristiriidat. Helsingin Sanomien uutisoinnista erotetaan kriittinen teema ja kannustusteema. Kriittinen teema viittaa negatiiviseen diskurssiin: Maata hallitsevaan sotilasvaltaan. Kannustusteema viittaa positiviiseen diskurssiin: Argentiinalaisten yhtenäisyyteen. Ajanjakson edetessä kannustusteema liittyy sotilasvaltadiskurssiin. Analyysissä tehtyjä johtopäätöksiä verrataan sotilasvallan maailmanmestaruuskilpailuille antamiin tavoitteisiin. Clarín Edicion Internacionalin ja The Timesin uutisoinnin perusteella sotilasvallan tavoitteet täyttyivät. Helsingin Sanomien uutisoinnin perusteella sotilasvalta ei onnistunut tavoitteissaan. Mediavälineiden uutisoinnin motiiveja ja eroja pohditaan niiden yhteiskunnallista taustaa vasten.
  • Monogioudi, Evanthia (Helsingin yliopisto, 2011)
    Protein modification via enzymatic cross-linking is an attractive way for altering food structure so as to create products with increased quality and nutritional value. These modifications are expected to affect not only the structure and physico-chemical properties of proteins but also their physiological characteristics, such as digestibility in the GI-tract and allergenicity. Protein cross-linking enzymes such as transglutaminases are currently commercially available, but also other types of cross-linking enzymes are being explored intensively. In this study, enzymatic cross-linking of β-casein, the most abundant bovine milk protein, was studied. Enzymatic cross-linking reactions were performed by fungal Trichoderma reesei tyrosinase (TrTyr) and the performance of the enzyme was compared to that of transglutaminase from Streptoverticillium mobaraense (Tgase). Enzymatic cross-linking reactions were followed by different analytical techniques, such as size exclusion chromatography -Ultra violet/Visible multi angle light scattering (SEC-UV/Vis-MALLS), phosphorus nuclear magnetic resonance spectroscopy (31P-NMR), atomic force (AFM) and matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOF MS). The research results showed that in both cases cross-linking of β-casein resulted in the formation of high molecular mass (MM ca. 1 350 kg mol-1), disk-shaped nanoparticles when the highest enzyme dosage and longest incubation times were used. According to SEC-UV/Vis-MALLS data, commercial β-casein was cross-linked almost completely when TrTyr and Tgase were used as cross-linking enzymes. In the case of TrTyr, high degree of cross-linking was confirmed by 31P-NMR where it was shown that 91 % of the tyrosine side-chains were involved in the cross-linking. The impact of enzymatic cross-linking of β-casein on in vitro digestibility by pepsin was followed by various analytical techniques. The research results demonstrated that enzymatically cross-linked β-casein was stable under the acidic conditions present in the stomach. Furthermore, it was found that cross-linked β-casein was more resistant to pepsin digestion when compared to that of non modified β-casein. The effects of enzymatic cross-linking of β-casein on allergenicity were also studied by different biochemical test methods. On the basis of the research results, enzymatic cross-linking decreased allergenicity of native β-casein by 14 % when cross-linked by TrTyr and by 6 % after treatment by Tgase. It can be concluded that in addition to the basic understanding of the reaction mechanism of TrTyr on protein matrix, the research results obtained in this study can have high impact on various applications like food, cosmetic, medical, textile and packing sectors.
  • Salminen, Heidi (Helsingin yliopisto, 2003)
  • Natunen, Jari (Helsingin yliopisto, 1999)
  • Oksanen, Esko (Helsingin yliopisto, 2009)
    Inorganic pyrophosphatases (PPases, EC hydrolyse pyrophosphate in a reaction that provides the thermodynamic 'push' for many reactions in the cell, including DNA and protein synthesis. Soluble PPases can be classified into two families that differ completely in both sequence and structure. While Family I PPases are found in all kingdoms, family II PPases occur only in certain prokaryotes. The enzyme from baker's yeast (Saccharomyces cerevisiae) is very well characterised both kinetically and structurally, but the exact mechanism has remained elusive. The enzyme uses divalent cations as cofactors; in vivo the metal is magnesium. Two metals are permanently bound to the enzyme, while two come with the substrate. The reaction cycle involves the activation of the nucleophilic oxygen and allows different pathways for product release. In this thesis I have solved the crystal structures of wild type yeast PPase and seven active site variants in the presence of the native cofactor magnesium. These structures explain the effects of the mutations and have allowed me to describe each intermediate along the catalytic pathway with a structure. Although establishing the ʻchoreographyʼ of the heavy atoms is an important step in understanding the mechanism, hydrogen atoms are crucial for the mechanism. The most unambiguous method to determine the positions of these hydrogen atoms is neutron crystallography. In order to determine the neutron structure of yeast PPase I perdeuterated the enzyme and grew large crystals of it. Since the crystals were not stable at ambient temperature, a cooling device was developed to allow neutron data collection. In order to investigate the structural changes during the reaction in real time by time-resolved crystallography a photolysable substrate precursor is needed. I synthesised a candidate molecule and characterised its photolysis kinetics, but unfortunately it is hydrolysed by both yeast and Thermotoga maritima PPases. The mechanism of Family II PPases is subtly different from Family I. The native metal cofactor is manganese instead of magnesium, but the metal activation is more complex because the metal ions that arrive with the substrate are magnesium different from those permanently bound to the enzyme. I determined the crystal structures of wild type Bacillus subtilis PPase with the inhibitor imidodiphosphate and an inactive H98Q variant with the substrate pyrophosphate. These structures revealed a new trimetal site that activates the nucleophile. I also determined that the metal ion sites were partially occupied by manganese and iron using anomalous X- ray scattering.
  • Lehtiö, Lari (Helsingin yliopisto, 2006)
    The first glycyl radical in an enzyme was described 20 years ago and since then the family of glycyl radical enzymes (GREs) has expanded to include enzymes catalysing five chemically distinct reactions. The type enzymes of the family, anaerobic ribonucleotide reductase (RNRIII) and pyruvate formate lyase (PFL) had been studied long before it was known that they are GREs. Spectroscopic measurements on the radical and an observation that exposure to oxygen irreversibly inactivates the enzymes by cleavage of the protein proved that the radical is located on a particular glycine residue, close to the C-terminus of the protein. Both anaerobic RNRIII and PFL, are important for many anaerobic and facultative anaerobic bacteria as RNRIII is responsible for the synthesis of DNA precursors and PFL catalyses a key metabolic reaction in glycolysis. The crystal structures of both were solved in 1999 and they revealed that, although the enzymes do not share significant sequence identity, they share a similar structure - the radical site and residues necessary for catalysis are buried inside a ten stranded $\ualpha $/$\ubeta $-barrel. GREs are synthesised in an inactive form and are post-translationally activated by an activating enzyme which uses S-adenosyl methionine and an iron-sulphur cluster to generate the radical. One of the goals of this thesis work was to crystallise the activating enzyme of PFL. This task is challenging as, like GREs, the activating component is inactivated by oxygen. The experiments were therefore carried out in an oxygen free atmosphere. This is the first report of a crystalline GRE activating enzyme. Recently several new GREs have been characterised, all sharing sequence similarity to PFL but not to RNRIII. Also, the genome sequencing projects have identified many PFL-like GREs of unknown function, usually annotated as PFLs. In the present thesis I describe the grouping of these PFL family enzymes based on the sequence similarity and analyse the conservation patterns when compared to the structure of E. coli PFL. Based on this information an activation route is proposed. I also report a crystal structure of one of the PFL-like enzymes with unknown function, PFL2 from Archaeoglobus fulgidus. As A. fulgidus is a hyperthermophilic organism, possible mechanisms stabilising the structure are discussed. The organisation of an active site of PFL2 suggests that the enzyme may be a dehydratase. Keywords: glycyl radical, enzyme, pyruvate formate lyase, x-ray crystallography, bioinformatics
  • Ekman, Aino (1935)
  • Jalava, Katri (2014)
    Vesijohtoverkoston häiriöt aiheuttavat usein vatsatautiepidemioita, joissa aiheuttajina on useita patogeenisiä organismeja. Tässä tutkimuksessa selvitettiin itäsuomalaisen kunnan laaja vesivälitteinen epidemia käyttäen monitieteistä lähestymistapaa hyödyntäen kehittyneitä epidemiologisia, tilastollisia ja spatiaalisia menetelmiä. Maanrakennustöistä johtunut putkirikko sattui vesijohtoverkostoon Vuorelassa, Siilinjärvellä 4. heinäkuuta, 2012. Kaksi viikkoa myöhemmin terveyskeskukseen alkoi tulla poikkeuksellisen paljon vatsa-suolisto-oireisia potilaita, joten välittömät kontrollitoimet aloitettiin. Määritetyllä epidemia-alueella asui 2931 asukasta, joista 473 (16 %) vastasi nettipohjaiseen kyselytutkimukseen. Potilas- ja vesinäytteet tutkittiin usean mikrobin varalta ja jatkotutkimuksina tehtiin molekyylibiologisia tyypityksiä ja mikrobien kokonaislajimääritys. Tutkimuksessa kehitettiin menetelmä, jonka avulla pystyimme laskemaan etäisyyden putkirikkoon vesijohtoverkostoa pitkin. Kyselytutkimuksessa saatuja vastauksia ja etäisyyttä putkirikosta käytettiin useissa univariaatti- ja monimuuttujamalleissa selittäjinä. Lisäksi käytimme analysointiin spatiaalista logistista regressiomenetelmää. Pääasialliset oireet olivat vatsakipu, pahoinvointi ja ripuli. Taudinkuva oli lievä, oireiden kesto oli keskimäärin kolme päivää. Potilas- ja vesinäytteistä todettiin useita patogeenejä joiden tiedetään aiheuttavan lievää vatsatautia ja/tai kuvaavan ulostesaastutusta vedessä, muun muassa sapoviruksia, yksi Campylobacter jejuni, arkobakteereita ja erilaisia E. coleja (EHEC, EPEC, EAEC ja EHEC). Taudinkuvan perusteella tehtiin tapausmääritelmä, jota käytettiin vastemuuttujana tilastollisissa malleissa. 4 Käsittelemättömän vesijohtoveden juominen epidemia-alueella aiheutti kohonneen riskin sairastua, RR (riskisuhde, altistuneiden osuus sairastuneissa suhteessa altistuneiden osuuteen terveissä) oli 5.6 (95 %:n luottamusväli 1.9-16.4). Tämä riski kasvoi juodun veden määrän suhteessa eli todettiin ns. annosvasteisuus. Jokaiselle asukkaalle laskettiin etäisyys putkirikosta vesijohtoverkostoa pitkin käyttäen tässä tutkimuksessa kehitettyä menetelmää. Mitä lähempänä henkilö asui putkirikkopaikkaa, sitä suurempi riski hänellä oli sairastua. Nuoremmat henkilöt sairastuivat vanhempia herkemmin. Sekä log- että logistisessa monimuuttujamallissa tilastollisesti merkitseviksi selittäjiksi osoittautuivat ikä (käänteisesti), etäisyys putkirikosta (käänteisesti) ja vesijohtoveden juominen. Lisäksi ns. spatiaalinen tekijä (kuvaten tartunnan leviämistä henkilöstä toiseen, mittausvirhettä etäisyysmuuttujassa ja veden epälineaarista virtausta vesijohtoverkostossa) oli merkitsevä. Tässä tutkimuksessa käytetyt uudenlaiset menetelmät paransivat epidemian lähteen selvittämistä ja auttoivat määrittämään epidemian laajuuden ja sairastuneiden määrän. Näitä menetelmiä voidaan hyödyntää epidemiaselvityksissä jatkossa.
  • Fossi, Marja (Helsingin yliopisto, 2006)
    Brachyspira pilosicoli causes porcine intestinal spirochaetosis, which is manifested by a mild, persistent diarrhoea among weaned pigs at the age of 7-14 weeks. The growth of diseased pigs is retarded and their feed conversion is lowered, resulting in diminished production. These studies were designed to investigate the molecular epidemiology of B. pilosicoli in Finnish sow herds and to improve laboratory diagnostics for B. pilosicoli. Infectivity of the rare hippurate-negative biotype of B. pilosicoli was examined by an infection trial and eradication of B. pilosicoli from a sow herd was demonstrated. A high genetic diversity was observed among 131 B. pilosicoli strains obtained from 49 sow herds located in the two major pork production areas of Finland. A high discriminatory power of pulsed-field gel electrophoresis (PFGE) was established with either SmaI or MluI used as a restriction enzyme. Common genotypes between the herds were rare, and no clustering of the genotypes according to the two geographical areas was observed. A single genotype could persist in a herd for several years; however, genetic recombination among B. pilosicoli strains might occurr. The epidemic nature of B. pilosicoli infection in Finnish pig farms was shown, and the role of migrating vectors or fomites for horizontal transmission was assessed as minor. The high discriminatory power of PFGE was further exploited to investigate hippurate-negative phenotypes of B. pilosicoli. No relationship between hippurate-negativity and genotypes of B. pilosicoli was detected. This finding was substantiated by comparative analyses of 16S rDNA nucleotide sequences of hippurate-negative and -positive isolates; different nucleotide positions of the strains were not predictive of the hippurate hydrolysis reaction. B. pilosicoli isolates from the same herd could possess an identical genome despite having a different capacity for hydrolysing hippurate. The congruent phylogeny of hippurate-negative and -positive B. pilosicoli was further ascertained by an ultrastructural study; the two biotypes shared all of the features unique to the species B. pilosicoli. In conclusion, the expression of hippurate hydrolysis can vary within a single B. pilosicoli clone, and thus, the hippurate test can not be used alone for differentiation of porcine B. pilosicoli. An occasional hippurate-negativity can disturb the phenotype-based differential diagnostics of B. pilosicoli. A B. pilosicoli-specific D-ribose test was therefore established to strengthen the diagnostics protocol. Sixty unrelated B. pilosicoli strains and 35 strains of other porcine Brachyspira species were studied for D-ribose utilization by an indirect method based on recording the pH reduction of a broth culture in the presence of D-ribose. All B. pilosicoli strains, regardless of the hippurate reaction, could utilise D-ribose, whereas the strains of the other Brachyspira species were D-ribose-negative. These results enabled the construction of an amended classification scheme for phenotypic differentiation of porcine B. pilosicoli. Experimental pigs were inoculated either with a hippurate-negative B. pilosicoli strain or with a B. pilosicoli type strain. Somewhat unexpectedly, the pigs in both trial groups remained healthy. Only the hippurate-negative B. pilosicoli strain could be reisolated from two of eight infected pigs. An explanation for the silent infection or lack of infection may lie in the challenge procedure, strain attenuation, environmental conditions, absence of concomitant enteropathogens or the feeding regimen. The pathogenicity of hippurate-negative B. pilosicoli should be further studied in modified conditions for trial pigs. Eradication of a chronic B. pilosicoli infection without total depopulation was attempted in a 60-sow farrowing herd. The principles for eradication of B. hyodysenteriae, the cause of swine dysentery, were applied. Special attention was paid to sanitary measures, relocation of animals according to age groups to nearby shelters, husbandry principles and adequate medication. The eradication was successful; the diarrhoea of the young growers disappeared, and B. pilosicoli was not detected in any sample during the 4.5-year follow-up.
  • Grimaldi-Toriz, Sharon (Helsingin yliopisto, 2009)
    The aim of this study was to measure seasonal variation in mood and behaviour. The dual vulnerability and latitude effect hypothesis, the risk of increased appetite, weight and other seasonal symptoms to develop metabolic syndrome, and perception of low illumination in quality of life and mental well-being were assessed. These variations are prevalent in persons who live in high latitudes and need balancing of metabolic processes to adapt to environmental changes due to seasons. A randomized sample of 8028 adults aged 30 and over (55% women) participated in an epidemiological health examination study, The Health 2000, applying the probability proportional to population size method for a range of socio-demographic characteristics. They were present in a face-to-face interview at home and health status examination. The questionnaires included the modified versions of the Seasonal Pattern Assessment Questionnaire (SPAQ) and Beck Depression Inventory (BDI), the Health Related Quality of Life (HRQoL) instrument 15D, and the General Health Questionnaire (GHQ). The structured and computerized Munich Composite International Diagnostic Interview (M-CIDI) as part of the interview was used to assess diagnoses of mental disorders, and, the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria were assessed using all the available information to detect metabolic syndrome. A key finding was that 85% of this nationwide representative sample had seasonal variation in mood and behaviour. Approximately 9% of the study population presented combined seasonal and depressive symptoms with a significant association between their scores, and 2.6% had symptoms that corresponded to Seasonal Affective Disorder (SAD) in severity. Seasonal variations in weight and appetite are two important components that increase the risk of metabolic syndrome. Other factors such as waist circumference and major depressive disorder contributed to the metabolic syndrome as well. Persons reported of having seasonal symptoms were associated with a poorer quality of life and compromised mental well-being, especially if indoors illumination at home and/or at work was experienced as being low. Seasonal and circadian misalignments are suggested to associate with metabolic disorders, and could be remarked if individuals perceive low illumination levels at home and/or at work that affect the health-related quality of life and mental well-being. Keywords: depression, health-related quality of life, illumination, latitude, mental well-being, metabolic syndrome, seasonal variation, winter.
  • Rintakoski, Simo (Helsingin yliopisto, 2014)
    In Denmark, Finland, Norway and Sweden the National Dairy Disease Registers (NDDRs) collect and store disease information at the individual cow level. Because these registers are monitored nationally they offer access to data that cover most of the dairy population in each country. Data from these registers are used, for example, for herd health and animal welfare assessments, production management, genetic evaluations and epidemiologic research. Since the register data are not usually designed for research purposes their quality is unknown. Understanding the magnitude of data loss during data transfer and human influence in disease recording process is important. The knowledge will enhance the ability to improve register quality, which in turn will improve reliability of frequency measure calculations from the register data. This thesis investigated the quality (measured as completeness and correctness) of the Finnish NDDR and compared register qualities among the four countries. In Finland the quality of recorded information was excellent, but approximately 17% of disease information was lost during the data transfer steps. A large proportion of the data loss was due to artificial insemination (AI) technicians not transferring events. The majority of those events occurred close to culling of the cow, suggesting early removal of the cow health cards so that AI technician did not have access to those cards. Additionally, fewer diagnostic events were transferred from purchased cows compared to those born on farm suggesting problems with animal identification. An efficient way to improve completeness in the Finnish NDDR is to have veterinarians electronically transfer diagnostic information during farm visits. The Finnish system has already been modified accordingly. This thesis also showed how register quality for four reproductive disorders (metritis, retained placenta, assisted calving and oestrous disturbances) varied among the four countries. Metritis and oestrous disturbance events were well represented in the NDDRs. Farmer-observed completeness (the proportion of all farmer observations that were recorded in the NDDR) was around 0.80 and did not differ significantly among the countries. Assisted calving and retained placenta events showed more among-country variation. Farmer-observed completeness was highest in Denmark and lowest in Finland, ranging between 0.31 and 0.89. The comparison of completeness-adjusted incidences to incidences calculated from the registers showed that incidences were underestimated for assisted calving and retained placenta. Underestimation was highest in Finland. This thesis also demonstrated how both farmer and veterinary intentions toward starting veterinary treatment of mild clinical mastitis could explain the reasons for different mastitis incidence rates among the countries. The results suggest that when intentions towards veterinary treatment are greater, mild cases receive veterinary treatment more often than when intentions are reduced. Therefore, greater farmer and veterinarian intentions can increase the disease incidence calculated from the NDDR data. According to the study, intentions were greater in Denmark than in other countries.
  • Ning, Feng (Helsingin yliopisto, 2013)
    The objectives of this study were to investigate: 1) what the major risk factors are that have contributed to the rise in prevalence of type 2 diabetes in Chinese adults, and whether the joint effect of a family history of diabetes along with obesity on the risk of diabetes in the Chinese differs from that in the Finns; 2) the impact of the homeostasis model assessment of insulin resistance and beta cell function on glucose metabolism in relation to aging in people of Asian origin; 3) the relative risk for cardiovascular disease (CVD) mortality and morbidity associated with fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) within the normoglycemic range in European populations. This study was based on datasets of the Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in Asia (DECODA) and in Europe (DECODE) studies comprising 10307 men and 13429 women aged 30 to 74 years from 11 Asian cohorts, and 12566 men and 10874 women aged 25 to 90 years from 19 European cohorts. Type 2 diabetes and intermediate hyperglycemia in this study were determined by a 2-h 75g oral glucose tolerance test according to the World Health Organization/International Diabetes Federation criteria of 2006. The odds ratios for the prevalence of type 2 diabetes and intermediate hyperglycemia were estimated using logistic regression analysis. Cox proportional hazards analysis was performed to estimate the association between plasma glucose and CVD mortality and morbidity, adjusting for conventional cardiovascular risk factors. Between 2001 and 2006, the age-standardized prevalence of type 2 diabetes increased from 5.2% to 14.2% in men and from 7.2% to 14.5% in women in rural areas, from 12.6% to 19.4% in men and from 10.2% to 16.6% in women in urban areas in Qingdao, China. Age, family history of diabetes and waist circumference was independent risk factors for diabetes in both sexes and in both urban and rural areas (P less than 0.01 for all). A high level of education and a high income were inversely associated with the increased prevalence in all populations except in rural men (P less than 0.05). Obesity and a family history of diabetes were major risk factors for type 2 diabetes in men and women from China and Finland. Their synergetic effect on type 2 diabetes was significant in Finnish men, but not in Finnish women or the Chinese. The prevalence of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) increased with age in populations of Asian origin except IFG in the Indians living in India and in African men living in Mauritius. The age-related increase was more prominent for IGT than for IFG in both men and women. Adjustment for insulin resistance and beta cell function reduced the differences among age groups for all ethnic groups, but the risk gradient between age groups still remained significant for IGT. Within normoglycemic range, individuals whose baseline 2hPG did not return to FPG levels (Group II, 2hPG > FPG) were older and had higher baseline body mass index (BMI), blood pressure and fasting insulin levels compared with those whose baseline 2hPG did (Group I, 2hPG ≤ FPG) in Europeans. Hazard ratios (95% confidence intervals) for CVD mortality were 1.22 (1.05-1.41) in men, and 1.40 (1.03-1.89) in women for Group II versus Group I, adjusting for age, study cohort, BMI, FPG, total serum cholesterol, smoking status and hypertension status. The corresponding hazard ratios for the incidence of coronary heart disease, ischemic stroke and composite CVD events were 1.13 (0.93-1.37), 1.40 (1.06-1.85) and 1.20 (1.01-1.42) in men, and 1.33 (0.83-2.13), 0.94 (0.59-1.51) and 1.11 (0.79-1.54) in women, respectively. The increasing trends for CVD mortality and morbidity did not change substantially after additional adjustment for fasting insulin concentrations. In conclusion, this study confirmed the impact of established risk factors of age, obesity and a family history of diabetes on the risk of diabetes among the Chinese, which is consistent with literature, but the interaction between the risk factors might be different between ethnicities and requires further investigation. This study also disclosed the deleterious effect of high normal 2hPG levels on CVD mortality and morbidity, which has not been widely investigated previously. The findings further support the view that the CVD risk extends well below the diabetes diagnostic value based on the post-challenge glucose levels, and may have certain clinical implications regarding diabetes diagnosis and glycemic management targets.
  • Lumme, Sonja (2003)
    Tutkielman tarkoituksena on tutustua tilastollisiin menetelmiin, joita käytetään arvioidessa riskiä sairastua syöpään. Tapaus-verrokkitutkimusasetelma on yksi epidemiologiassa eniten käytetyistä menetelmistä, joita käytetään riskin arvioimisessa. Tapaus-kohorttitutkimusasetelma on yksi tapaus-verrokkitutkimusasetelman versio. Työssä on tarkasteltu asetelmia tutkimuksen suunnittelun, aineistojen keräämisen ja analysoimisen näkökulmista. Tutkielma liittyy Suomen Syöpärekisterin ja NBSBCCC:n (Nordic Biological Specimen Banks working group on Cancer Causes and Control) yhteisiin projekteihin, joissa arvioidaan syöpäriskiä veripankkiaineistoja hyödyntäen. Näissä projekteissa on herännyt kysymys, voidaanko toisia tutkimuksia varten aiemmin kerätyistä tapaus-verrokkiaineistoista tehdä vertailukohortti tapaus-kohorttitutkimukselle ja millä edellytyksin se voitaisiin tehdä? Kysymys on tärkeä, sillä jos aiemmin kerätyt aineistot muodostavat luotettavan vertailukohortin, voidaan biologisia näytteitä käyttävissä hankkeissa säästää kustannuksissa. Menetelmiä sovellettiin kahteen biologiseen aineistoon. Nämä aineistot liittyvät NBSBCCC:n tutkimuksiin, joissa on tutkittu papilloomaviruksen ja eri syöpien välistä yhteyttä. Tämän työn toisessa aineistossa on tutkittu pään ja kaulan alueen syöpiä ja toisessa peräaukon ja sitä ympäröivän ihon syöpiä. Papilloomavirusta kantavilla yksilöillä havaittiin olevan tilastollisesti merkitsevästi suurempi riski sairastua kyseisiin syöpiin. Tulokset olivat samansuuntaisia riippumatta analysointimenetelmästä. Tutkielmassa on pohdittu ehtoja, jotka mahdollistavat tapaus-verrokkiaineistojen käyttämisen uudelleen tapaus-kohorttitutkimuksessa. Nämä ehdot koskevat sekä aineistojen keräämistä että aineistojen analysoimista. Tuloksena on, että aiemmin kerätyt tapaus-verrokkiaineistot voivat muodostaa tapaus-kohorttiaineistolle vertailuryhmän, jos vaadittavat ehdot otetaan huomioon tutkimuksessa. Tärkeimmät lähteet: Barlow, W. E. (1994): Robust Variance Estimation for the Case-Cohort Designs. Biometrics 50(4): 1064-72. Barlow, W. E. – Ichikawa, L. – Rosner, D. – Izumi, S. (1999): Analysis of Case-Cohort Designs. Journal of Clinical Epidemiology 52(12): 1165-72. Gail, M. H. – Benichou, J. (toim.) (2000): Encyclopedia of epidemiologic methods. John Wiley & Sons, New York. Prentice, R. L. (1986): A case-cohort design for epidemiologic cohort studies and disease prevention trials. Biometrika 73(1): 1-11.
  • Kolehmainen, Pekka (Helsingin yliopisto, 2014)
    Human parechovirus (HPeV) and Ljungan virus (LV) are non-enveloped, single-stranded RNA viruses that form the genus Parechovirus in the family Picornaviridae. The interest in these viruses has notably increased over the past 15 years because of their strengthened associations to human and animal diseases. HPeV types 1 and 3 have been associated with more severe infections in young children, such as infections of the central nervous system (CNS) and sepsis-like disease. Rodent-infecting LV has been suggested to possess zoonotic potential and induce various human diseases. However, the proof for this remains lacking. This study aimed to describe the epidemiological features of HPeVs in Finland and in the Netherlands, to examine the connection between HPeV-induced infection and human diseases and to study the circulation of LV in Finland. The epidemiological analysis of stool samples, collected from 1996 to 2007, revealed that HPeVs are highly common in healthy Finnish children. HPeV was primarily detectable in children under 2 years of age. Altogether, 39% of the study participants tested positive for HPeV at least once during the study period. HPeVs circulated throughout the year, with a distinct seasonal peak in October-November. The results indicated that not only the previously described HPeV1 but also HPeV genotypes 3 and 6 circulate in Finland. Microneutralisation assays, which were set up to detect HPeV1 to 6, the most common genotypes in Europe, provided a deeper understanding of HPeV seroprevalence in the Finnish and Dutch populations. Seropositivity for HPeV1, 2 and HPeV4 to 6 was high and moderate in adults, in contrast to seropositivity for HPeV3, which was extremely low. The serological data demonstrate that HPeV types 1 to 6 might be even more prevalent than previously assumed. All six HPeV types circulate in Finland. In addition to HPeV detection in background populations, we presented the first cases of severe infection in neonates with HPeV4 and, subsequently, the first isolation of this genotype in Finland. Five hospitalised neonates with a sepsis-like disease in the fall of 2012 were positive for HPeV. Four of these children had HPeV4, indicating a potential small epidemic of this genotype, whereas one HPeV remained untyped. In addition, we detected HPeV3 in a neonate with suspected viral sepsis in October 2011 and another untyped HPeV in a child with symptoms corresponding to acute disseminated encephalomyelitis in May 2012. Following these findings, we promoted the addition of HPeV detection to routine diagnostics of young children. To extend the knowledge regarding other parechoviruses in Finland, we studied LV antibody prevalence in both humans and rodents. The seroprevalence detected for LV was 38% in humans and 18% in bank voles (Myodes glareolus). The observation of LV antibodies in humans is relatively high because LV has never been isolated from humans. These results suggest that an LV or LV-like virus, in addition to HPeVs, circulates frequently among human populations in Finland.
  • Kirchner, Sascha (Helsingin yliopisto, 2014)
    Background: The control of Potato virus Y (PVY, genus Potyvirus, family Potyviridae) is one of the greatest challenges in seed potato production worldwide. PVY can cause substantial economic losses. It reduces the growth of potato plants and the quality and quantity of yield. Therefore, when virus incidence exceeds set thresholds, the potatoes cannot be sold as seed but have to be sold at a lower price for consumption. PVY is transmitted in a non-persistent manner by winged forms of many aphid species. This mode of transmission is characterised by short probing activity, which is sufficient for acquisition and transmission of the virus. Because of these underlying epidemiological factors, PVY is difficult to control. Around 2005, the High grade (HG) seed potato production area in Finland, which is one of the northernmost intensive crop production areas of the world, saw a marked increase in the incidence of PVY in potato seed lots. Therefore, it became necessary to investigate the epidemiology of PVY and establish measures of PVY control in this region. ----- Aims: 1) To characterise the species composition and phenology of the aphid fauna. 2) To determine the incidence of aphid species with documented ability to transmit PVY and to use a modelling approach to determine their relative importance as vectors including timing of virus transmission. 3) To compare the application of straw mulch, mineral oil and birch extract with chemical practices for control of PVY vectors. Methods: The area under study was Tyrnävä-Liminka (latitude 64°) in Finland. Studies were carried out in the potato growing seasons from 2007 to 2012. Aphid flight activity was monitored by yellow pan traps (YPT) placed in 4 8 seed potato fields per year and by one suction trap. Aphid identification was done by morphological characteristics and by DNA barcoding based on a 658-bp long region of the mitochondrial gene for cytochrome c oxidase I (COI). A cluster analysis was used to categorise phenology of species. Incidence of PVY was measured by testing leaves collected two weeks after plant emergence and in the progeny tubers after harvest by enzyme-linked immunosorbent assay (ELISA). To determine the most important time of transmission of PVY, and the main vectors, the seasonal increase in PVY incidence was modelled using aphid counts in traps, the relative vector efficiencies of the aphids, virus resistance of cultivars, and the initial infection rate of the seed tubers as explanatory variables in generalised linear mixed modelling. In addition, small scale experiments (SSE) were conducted in three years and large scale (LSE) field trials in two years. SSE were set up to compare applications of straw mulch, mineral oil and birch extract with chemical control of PVY vectors. LSE were conducted in growers fields to test efficacy of straw mulch to control PVY at farm scale. ---- Results: A total of 58,528 winged aphid individuals were classified into 83 taxa based on morphology: Of these, 34 species were further characterised by DNA barcoding. Four phenology clusters were found. The late-peak cluster was dominated by heteroecious species and the mid-peak cluster was dominated by monoecious species feeding on herbaceous plants. Total abundance showed a recurring triennial cycle according to the catch of aphids using the suction trap in the years 2000-2010. The most abundant species was Rhopalosiphum padi. It occurred mainly at the end of the potato growing season. The highly polyphagous species, Aphis fabae and Aphis gossypii were found to peak at the beginning of the potato growing season. Results of the modelling approach showed that the incidence of seedborne PVY infection and the early-season flight of Aphis fabae are the most important factors contributing to the incidence of PVY in the yield. Other aphid species play a negligible role as vectors of PVY. In the SSEs, only straw mulch reduced of PVY incidence significantly in the progeny tubers, with the reduction ranging from 50% to 70% in all three years. Incidence of PVY was reduced by mineral oil in two years (by 43% to 58%) and by the synthetic pyrethroid insecticide esfenvalerate by 29% in one year. In the LSE, straw mulch significantly reduced PVY in the progeny tubers by 25% to 47%. Average tuber yield following the straw mulch treatment was generally but not significantly higher than that in the untreated control in all experiments. ---- Conclusion: The results demonstrate that early season flight activity of Aphis fabae determines PVY incidence in the HG seed potato production area of Finland with a generally low vector pressure. Furthermore, straw mulch emerges as a reliabe and effective measure in diminishing the spread of PVY in areas with early vector flight activity.
  • Markkula, Annukka (Helsingin yliopisto, 2013)
    Listeria monocytogenes causes potentially fatal illness to susceptible people and is found in various foods. It typically enters processed foods via a contaminated processing environment, in which it may have persisted for years. To study the role of raw material as a potential source of contamination of food processing plants by L. monocytogenes, the prevalence and genetic diversity of this species in tonsils of pigs and in raw fish was examined. A total of 14% and 4% of tonsils of pigs and raw fish, respectively, harboured L. monocytogenes. From 38 pig tonsil isolates and 11 raw fish isolates, 24 and nine different types were recovered using pulsed-field-gel electrophoresis (PFGE) typing. The results indicate that a wide variety of L. monocytogenes strains enters pork slaughterhouses and fish processing plants in the raw materials, which are thus potential sources of direct or indirect contamination of processing plants by this pathogen. Since identical PFGE types were recovered from both raw and processed fish, it is likely that raw fish are an initial source of the L. monocytogenes found in processed fish. Some strains entering a plant along with raw fish may contaminate and persist in the processing environment, causing recurrent contamination of the final products via contact surfaces. Alternatively, L. monocytogenes strains in raw fish may survive non-listericidal processes, resulting in contamination of the final product. To identify novel factors contributing to survival of L. monocytogenes in food processing environment, the roles of specific genes in stress response were investigated, using flhA and motA that encode flagellar factors involved in cold stress tolerance, and lmo0866, lmo1246, lmo1450, and lmo1722 encoding DEAD-box RNA helicases involved in cold, heat acid, alkali, osmotic, ethanol, and oxidative stress tolerance. Increased relative transcription levels of flhA, motA, lmo0866, lmo1450, and lmo1722, restricted growth of the single gene deletion mutant strains EGD-eΔflhA, EGD-eΔmotA, Δlmo0866, Δlmo1450, and Δlmo1722 at 3°C, and increased minimum growth temperatures of Δlmo0866, Δlmo1450, and Δlmo1722 revealed that FlhA, MotA, Lmo0866, Lmo1450, and Lmo1722 had roles in growth of L. monocytogenes EGD-e under cold stress conditions. The restricted growth of Δlmo0866 in 3.5% ethanol, and its increased maximum growth temperature and growth rate at 42.5°C, indicated that Lmo0866 had roles also in ethanol and heat stress tolerance of strain EGD-e. The role of Lmo1450 in the growth of strain EGD-e under heat, alkali, and oxidative stress conditions was shown by the restricted growth rate of Δlmo1450 at 42.5°C, in pH 9.4, and in 5 mM H2O2. The slightly decreased growth rate and maximum optical density of Δlmo1246 at 3°C indicated that the role of Lmo1246 in cold stress tolerance was negligible. Under all the other conditions, the growth of Δlmo1246 and the wild-type EGD-e were identical, suggesting that Lmo1246 had no role in growth of L. monocytogenes EGD-e under heat, pH osmotic, ethanol, or oxidative stress conditions. The deletion of flhA, motA, lmo0866, lmo1450, and lmo1722 impaired the motility of strain EGD-e, whereas the motility of Δlmo1246 did not differ from that of the wild type. This indicates that DEAD-box RNA helicases Lmo0866, Lmo1450, and Lmo1722 have roles in motility of strain EGD-e. Moreover, these results suggest that motility and cold stress tolerance of L. monocytogenes are linked, and that motile flagella may be needed for full cold stress tolerance of strain EGD-e.
  • Rautiainen, Henna (Helsingin yliopisto, 2008)
    Primary biliary cirrhosis (PBC) is caused by an autoimmune inflammation of the small bile ducts. It results to destruction of bile ducts, accumulation of the bile in the liver, and cirrhosis. The prevalence and incidence of PBC is increasing in the Western world. The prevalence is highest in the USA (402 per million) and incidence in Scotland (49/million/year). Our aim was to assess the epidemiology of PBC in Finland. Patients for the epidemiological study were searched from the hospital discharge records from year 1988 to 1999.The prevalence rose from 103 to 180/million from 1988 to 1999, an annual increase of 5.1%. The incidence rose from 12 to 17 /million/year, an annual increase of 3.5%. The age at death increased markedly from 65 to 76 years. The risk of liver related deaths diminished over time. The treatment of PBC is based on Ursodeoxycholic acid (UDCA). During 20 years 50% of patients end up with cirrhosis. Our treatment option was to combine budesonide, a potent corticosteroid with a high first pass metabolism in the liver, to UDCA and evaluate the liver effects and systemic effects such as bone mass density (BMD) changes. Our aim was to find out if combination of laboratory tests would serve as a surrogate marker for PBC and help reducing the need for liver biopsy. Non-cirrhotic PBC patients were randomized to receive budesonide 6 mg/day combined to UDCA 15 mg /kg/day or UDCA alone for three years. The combination therapy with UDCA and budesonide was effective: stage improved 22%, fibrosis 25%, and inflammation 32%. In the UDCA group the changes were: 20% deterioriation in stage and 70% in fibrosis, but a 10% improvement in inflammation. BMD in femoral neck decreased by 3.6% in the combination group and by 1.9% in the UDCA group. The reductions in lumbar spine were 2.8% and 0.7%. Pharmacokinetics did not differ between the stages of PBC. HA, PIIINP, bile acids, and AST were significantly different within stages I-III and could differentiate the mild fibrosis (F0F1) from the moderate (F2F3). The combination of these individual markers (PBC-score) further improved the accuracy. The area under the ROC of the PBC score, using a cut of value 66, had a sensitivity of 81.4% and a specificity of 65.2% to classify the stage of PBC. The prevalence of PBC in Finland increases, which results from increasing incidence and improved survival. The combination of budesonide and UDCA improves liver histology compared to UDCA alone in non-cirrhotic stages of PBC. The treatment may reduce BMD. Hyaluronic acid, PIIINP, AST, and bile acids may serve as tools to monitor the treatment response in the early stages of PBC. The budesonide and UDCA combination therapy is an option for those patients who do not receive full response from UDCA and are still at the non-cirrhotic stage of PBC.
  • Palo, Riikka (Helsingin yliopisto, 2013)
    Previously reported differences in transfusion practices suggest that transfusion protocols and clinical transfusion decisions may often be inappropriate. To change and monitor practices requires a follow-up system. A healthcare-integrated data-gathering system could provide the required information about blood use. The purpose of this observational study was to create a follow-up system for blood use and to gather information about transfused patients and transfusion practices in Finland. Data came from ten Finnish hospital districts (five university and five tertiary-care hospital districts) between the years 2002 and 2005. The collection process involved combining data from pre-existing electronic medical records applied for different purposes. This information was combined from these electronic systems by use of personal identification numbers and data expressed as hospital episodes. Variation in blood-use practices still existed between hospitals. For example, the percentage of red blood cell (RBC) receivers ranged in Finnish hospitals from 12% to 57% during primary knee-arthroplasty surgery. The most typical blood-transfused patient was an over 65-year-old woman receiving 2 units of RBCs. RBC products were usually transfused in pairs (such as in two-four-six units). In over 30% of FFP transfusions, plasma was given without any guidance from coagulation tests. Among moderately anemic parturients, transfusion of 0 to 2 units of RBC had no effect on length of hospitalization. Duration of hospitalization was, however, considerably longer in these anemic patients than for average Finnish mothers (5.2 days versus 3.5 days). Most of the platelet (PLT) products were transfused to hematological patients (43%). Only 1% of surgical patients received PLTs. Severity of underlying condition in surgical patients had an effect on prevalence of blood transfusions. Variability in blood-use practices suggests inappropriate blood use. Moreover, RBC transfusion in paired units is a questionable practice. FFP transfusions, not based on coagulation tests, suggest inappropriate use of plasma as well. In parturients, mild anemia treated with 1 to 2 units of RBCs does not shorten hospitalization time. This supports the current recommended thresholds for RBC transfusion. Improvement efforts concerning PLT-use practices may be directed to users of high doses of PLTs; to hematological patients, but also to digestive tract surgery and cardiac surgery patients. Knowledge of severity of the underlying disease as affecting the transfusion requirement may facilitate optimization of blood use.
  • Poikonen, Eira (Helsingin yliopisto, 2011)
    Candida species are an important cause of nosocomial bloodstream infections in hospitalized patients worldwide, with associated high mortality, excess length of stay and costs. Main contributors to candidemias is profound immunosuppression due to serious underlying condition or intensive treatments leading to an increasing number of susceptible patients. The rank order of causative Candida species varies over time and in different geographic locations. The aim of this study was to obtain information on epidemiology of candidemia in Finland, to identify trends in incidence, causative species, and patient populations at risk. In order to reveal possible outbreaks and assess the value of one molecular typing method, restriction enzyme analysis (REA), in epidemiological study, we analyzed C. albicans bloodstream isolates in Uusimaa region in Southern Finland during eight years. The data from the National Infectious Disease Register were used to assess the incidence and epidemiological features of candidemia cases. In Helsinki University Central Hospital (HUCH) all patients with blood culture yielding any Candida spp. were identified from laboratory log-books and from Finnish Hospital Infection Program. All the patients with a stored blood culture isolate of C. albicans were identified through microbiology laboratory logbooks, and stored isolates were genotyped with REA in the National Institute for Health and Welfare (former KTL). The incidence of candidemia in Finland is globally relatively low, but increased between between 1990s and 2000s. The incidence was highest in males >65 years of age, but incidence rates for patients <1-15 years were lower during 2000s than during 1990s. In HUCH the incidence of candidemia remained low and constant during our 18 years of observation, but a significant shift in patient-populations at risk was observed, associated with patients treated in intensive care units, such as premature neonates and surgical patients. The predominating causative species in Finland and in HUCH is C. albicans, but the proportion of C. glabrata increased considerably. The crude one-month case fatality was constantly high between 28-33%. REA differentiated efficiently between C. albicans blood culture isolates and no clusters were observed in the hospitals involved, despite of abundant transfer of patients among them. Candida spp. are an important cause of nosocomial blood stream infections in Finland, and continued surveillance is necessary to determine the overall trends and patient groups at risk, and reduce the impact of these infections in the future. Molecular methods provide an efficient tool for investigation of suspected outbreak and should be available in the future in Finland, also.
  • Blomqvist, Soile (Helsingin yliopisto, 2004)