Riikka Pellinen (toim.) The Second PhD student Symposium ... · 12.15-12.30 Kuosmanen Suvi: MicroRNA profiling of pericardial fluid samples from patients with heart failure 12.30-12.45

Publications of the University of Eastern FinlandReports and Studies in Health Sciences No 18

Riikka Pellinen (toim.)

The Second PhD student Symposium of the Faculty of

Health Sciences


The Second PhD student Symposium of the Faculty of Health Sciences

Publications of the University of Eastern Finland

Reports and Studies in Health Sciences

ISBN: 978-952-61-1787-4

RIIKKA PELLINEN (TOIM.)


Health Sciences

Abstracts

Publications of the University of Eastern Finland Reports & Studies in Health Sciences

18

University of Eastern Finland Faculty of Health Sciences

Kuopio 2015

Kopioniini Kuopio, 2015

Editors: Prof. Veli-Matti Kosma Prof. Hannele Turunen

Prof. Olli Gröhn Prof. Kai Kaarniranta

University lecturer Veli-Pekka Ranta Distribution:

Eastern Finland University Library P.O. Box 1627, FI-70211 Kuopio, Finland

tel. +358 207 87 2001 http://www.uef.fi/kirjasto

ISBN: 978-952-61-1787-4 (PDF) ISSNL: 1798-5722 ISSN: 1798-5730

The second PhD student Symposium of the Faculty of Health Sciences. Abstracts. Publications of the University of Eastern Finland. Reports and Studies in Health Sciences 18. 2015. 88 p.

ISBN: 978-952-61-1787-4 ISSN: 1798-5730 ABSTRACT The Faculty of Health Sciences offers high quality PhD training in the field of Health and Well-being, an area of expertise in the University of Eastern Finland. PhD training is offered by six Doctoral programs: Doctoral Programme in Nursing Science, Doctoral Programme of Public Health, Doctoral Programme of Clinical Research, Doctoral Programme in Drug Research, Doctoral Programme in Molecular Medicine, and Doctoral Programme in Nutritional Sciences. PhD students of the Faculty are integrated as researchers into the research groups at different departments of the Faculty. The unique structure of the faculty provides excellent opportunities for creating new research activities at the interfaces of clinical medicine, biomedicine, pharmacy and nursing science. This book compiles the abstracts of the 2nd PhD Symposium of the Health sciences to be held in Kuopio. Snellmania auditorium 201, on May 11, 2015.

Universal Decimal Classification: 577 National Library of Medicine Classification: QT 255, QU 20, QU 50, QU 58.5, QU 60, QU 75, QU 83, QU 85.6, QU 107, QU 135, QU 325, QU 475, QU 560, QV 21, QV 25, QV 32, QV 269, QV 628, QV 744, QW 168, QW 630.5, QW 900, QZ 200, QZ 202, QY 90, W 20.5, W 85, W 88, WA 245, WA 306, WB 330, WE 250, WE 755, WG 141.5, WK 810, WK 820, WL 102, WL 104, WL 108, WL 344, WL 356, WL 358.5, WM 203, WO 184, WP 522, WP 870, WQ 160 WQ 210.5, WQ 212, WQ 300, WR 660, WS 130, WS 280, WT 116, WT 155, WU 113, WW 270, WX 185, WY 18.5, WY 18.8, WY 87, WY 88 Biomedical Research; Clinical Trial; Ethics, Research; Congresses; Molecular Biology; Genetic Therapy; Genetic Vectors; Gene Transfer Techniques; Glioma/therapy; Vascular Endothelial Growth Factors; Collagen; Diabetes Mellitus, Type 2; Insulin; Sirtuins; Cardiovascular Diseases; Epilepsy; Neurodegenerative Diseases/therapy; Alzheimer Disease; Amyotrophic Lateral Sclerosis; Disease Models, Animal; Magnetic Resonance Imaging; Microarray Analysis; Signal Transduction; Placenta; Fetus; Vitamin D; Gene Expression Regulation; Gene Expression; Diet; Fatty Acids; Motor Activity; Metabolic Syndrome X; Pharmaceutical Preparations; Education, Pharmacy; Lifestyle; Depression; Drug Therapy; Nursing; Low Back Pain; Homocysteine; Physical Fitness; Lung Neoplasms; Osteoporosis, Postmenopausal; Neurodegenerative Diseases; Age Factors; Dentistry; Oral Health; Bone Marrow; Hyaluronic Acid; Parturition; Toxic Actions; Smoking; Quercetin; Ultraviolet Rays; Neoplasms; Sleep Disorders; Disphosphonates; Pharmacy; Sociology, Medical; Angiogenesis Inducing Agents; Adipose Tissue; Schizophrenia; Opioid Peptides; Stroke; Obesity; Pain; Patient Safety; Melanoma; Amines; Fermentation; Migraine Disorders; Amino Acids

Contents PROGRAM....................................................................................................................... 5

ORAL PRESENTATIONS .................................................................................................. 10

POSTERS ....................................................................................................................... 25

GRAPHICAL ABSTRACTS FROM COURSE ........................................................................ 68

DOCTORAL PROGRAMMES ........................................................................................... 75

DOCTORAL PROGRAMME OF CLINICAL RESEARCH ......................................................... 76 DOCTORAL PROGRAMME MOLECULAR MEDICINE ......................................................... 77 DOCTORAL PROGRAMME IN NURSING SCIENCE ............................................................. 78 DOCTORAL PROGRAMME OF PUBLIC HEALTH ................................................................ 79 DOCTORAL PROGRAMME IN DRUG RESEARCH ............................................................... 80 DOCTORAL PROGRAMME IN NUTRITIONAL SCIENCES .................................................... 82

NOTES ........................................................................................................................... 84

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FACULTY OF HEALTH SCIENCES, 2ND PHD SYMPOSIUM 2015 MAY 11, KUOPIO

Program Monday, May 11 8.30-8.40 Dean Hilkka Soininen: Opening of the symposium

Chaired by docent Anu Kauppinen and MSc Henna Martiskainen

8.40-8.55 Fashe Muluneh M.: Electrochemical, in vitro and in silico investigation of the metabolic bioactivation of pyrrolizidine alkaloids

8.55-9.10 Idehen Esther: Cervical cancer screening participation among immigrants in Finland: An analysis of country of origin

9.10-9.25 Imtiaz Bushra: Oophorectomy, hysterectomy, and risk of Alzheimer’s disease: A nationwide case-control study

9.25-9.40 Isanejad Masoud: Dietary protein intake is associated with better physical function and muscle strength among elderly women

9.40-9.50 Break

9.50-10.05 Rauhala Leena: The organic osmolyte betaine induces keratin 2 expression in rat epidermal keratinocytes – A genome-wide study in UVB irradiated 3D cultures

10.05-10.20 Kokko Petra: Serum 25-hydroxyvitamin D3 and the risk of cancer in Eastern Finnish men: the Kuopio ischaemic heart disease risk factor study (KIHD)

10.20-10.35 Lehtola Heidi: Stroke in patients with atrial fibrillation: does concomitant carotid artery stenosis matter?

10.35-12.15 Poster session with buffet lunch

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12.15-12.30 Kuosmanen Suvi: MicroRNA profiling of pericardial fluid samples from patients with heart failure

12.30-12.45 Pölönen Petri: Analysis of the KEAP1-NRF2 pathway across cancers reveals its potential to act as an oncogenic driver

12.45-13.00 Graphical abstract awards

Presentation of winning graphical abstracts

13.00-13.10 Graphical abstract 1




13.40-14.45 Posters and coffee

14.45-15.00 Raninen Kaisa: Exhaled breath reflects metabolic changes induced by diet

15.00-15.15 Junkkari Antti: Health-related quality of life in patients with idiopathic normal pressure hydrocephalus

15.15-15.30 Takalo Mari: Characterization of Alzheimer’s disease risk gene ubiquilin-1 in human brain and in in vitro and in vivo models

15.30-15.45 Turunen Elina: The Preoperative nurse’s role in surgery process – an integrative literature review

15.45 Closing words

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POSTERS 1. Afrin Nadia: Do falls predict postmenopausal fractures? 2. Bah Aissa: Female sex, age and time delay to cardioversion as risk factors in

the cardioversion of acute atrial fibrillation. The FinCV Study 3. Cui Lili: The cerebral embolism evoked by intra-arterial delivery of allogeneic

bone marrow mesenchymal stem cells in rats 4. del Amo Eva M.: Intravitreal clearance and volume of distribution of

compounds in rabbits: In silico prediction and pharmacokinetic simulations for drug development

5. Dorjdagva Javkhlanbayar: Income-related inequality in health care utilization in Mongolia, 2008-2012

6. Etchi Daniel Tabe: Determinants of ethnic variations in health service utilization and associations with chronic diseases among the Kurdish, Russian and Somali migrants in Finland

7. Heikkinen Emma: Fentanyl pharmacokinetics in pregnant sheep after intravenous and transdermal administration to the ewe

8. Heikkinen Noora: Frontal grey matter volume is reduced among adolescent alcohol users

9. Ihantola Emmi-Leena: Characterization of circulating follicular helper T cells in type 1 diabetes patients and autoantibody-positive at-risk subjects

10. Ishchenko Yevheniia: Serine 288 stabilized non-sensitized receptor states preventing entering into sensitized and desensitized states

11. Koistinen Ville: Mass spectrometry–based analysis of whole grain phytochemicals using metabolomics approach

12. Korhonen Eveliina: UVB irradiation increases IL-1 β and IL-18 secretion from human corneal epithelial cells by inducing inflammasome activation

13. Kwegyir-Afful Emma: Randomized controlled trials are needed to close the evidence-gap in the prevention of preterm birth

14. Kärkkäinen Jussi: Acute mesenteric ischemia is a more common cause than expected of acute abdomen in the elderly

15. Kärkkäinen Olli: Rye bran induced changes in the metabolic profile in plasma, muscle and liver of mice

16. Laiterä Tiina: Increased γ-secretase activity in idiopathic normal pressure hydrocephalus patients with β-amyloid pathology

17. Martiskainen Henna: Transcriptomics and mechanistic elucidation of Alzheimer’s disease risk genes in the brain and in vitro models

18. Marttinen Mikael: SEPT5 and its potential role in the molecular pathogenesis of Alzheimer’s disease

19. Navia-Paldanius Dina: Inhibitor profiling of the human α/ β- hydrolase domain containing (ABHD11) using activity based protein profiling (ABPP)

20. Nurminen Veijo: Gene regulatory networks of vitamin D receptor 21. Pelkonen Mikko: The type II transmembrane serine proteases hepsin and

TMPRSS3 are associated with breast cancer survival 22. Pentikäinen Saara: Mastication process and early phase digestion of rye and

wheat breads

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23. Peters Björn: Effects of sucrose in micro- and pilot scale freeze-drying on secondary protein structures assessed by FTIR-ATR

24. Piippo Niina: NLRP3 inflammasome activation by impaired cellular degradation in human ARPE-19 cells

25. Prantner Viktória: Structural and functional analysis of the VDR-DNA interactions

26. Puljula Elina: Synthesis of bisphosphonate monoesters 27. Puris Elena: A cocktail approach: a valuable tool to study pharmacokinetic

and drug metabolism with liquid chromatography-mass spectrometry 28. Rautiainen Suvi: Diffusion Imaging and Apparent Diffusion Coefficient 29. Saarelainen Laura: Incidence of benzodiazepine and related drug use in

persons with and without Alzheimer’s disease – the nationwide, register-based MEDALZ-study

30. Seitovirta Jaana: How to recognize the rewarding factors from nurses’ point of view?

31. Semenova Maria: Health and social care services in two Karelias – availability and satisfaction in the sparsely populated areas

32. Sihvola Virve: Biomarker discovery of the KEAP1-NRF2 –pathway activating drug candidates

33. Siitonen Piia: Pupils’ Chronic Conditions and Medicine Use in School – Teachers’ Perceptions and Experiences

34. Soininen Suvi K.: Cellular and nuclear concentrations and cytotoxicity of anticancer drug doxorubicin and its liposomal formulations in two carcer cell types

35. Tarvonen Pirkko-Liisa: Impact of an intervention on children’s dental caries in Democratic People’s Republic of Korea

36. Thapa Rinez: The increased anti-leishmania activity of bubarvaquone using mesoporous silicon nanoparticles

37. Tuomarila Marie: Overexpression of MicroRNA-200c predicts poor outcome in patients with PR-negative breast cancer

38. Ucal Sebahat: TETA inhibits polyamine uptake and suppresses cell growth 39. Venäläinen Taisa: Cross-Sectional Associations of Plasma Fatty Acid

Composition with Plasma Concentration of Leptin in Finnish Children 40. Viisanen Tyyne: Effector T cell resistance to Treg suppression in type 1

diabetes patients and autoantibody-positive at-risk subjects 41. Väkeväinen Kati: Characterization of the microbial populations in atole agrio,

a traditional Mexican fermented beverage 42. Yasmin Amna: Magnetic resonance spectroscopy (MRS) of post-traumatic

epileptogenesis

GRAPHICAL ABSTRACTS FROM COURSE (Not presented)

43. Guerrero Toro Cindy: Pro-nociceptive effects of ATP and its derivatives in rat trigeminal ganglia

44. Hytti Maria: Fisetin and Luteolin decrease oxidative stress-induced inflammation and cytotoxicity in ARPE-19 cells

45. Jalkanen Henna: Eating behaviour and food intake in children ages 6-8 years 46. Jawhar Deen Ashik: Rab10-mediated endocytosis of Hyaluronan synthase

HAS3 regulates hyaluronan synthesis and cell adhesion to collagen

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47. Kyyriäinen Jenni: PDGFR-β-expressing NG2 cells relocate to hippocampal subfields vulnerable to neurodegenation after status epilepticus

48. Lipponen Anssi: Profiling of transcriptome in experimental traumatic brain injury

49. Paterno Jussi: Quality of life in patients with age-related macular degeneration (AMD)

50. Thanigai Arasu Uma: Extracellular Vesicles as carriers of Hyaluronan (HA) and their role as novel biomarkers

51. Vuorio Taina: The expression of soluble VEGFR3 in an atherosclerotic mouse model increases cholesterol levels and accelerates atherogenesis

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Oral presentations

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ELECTROCHEMICAL, IN VITRO AND IN SILICO INVESTIGATION OF THE METABOLIC BIOACTIVATION OF PYRROLIZIDINE ALKALOIDS Muluneh M. Fashe; Risto O. Juvonen; Aleksanteri Petsalo; Minna Rahnasto-Rilla; Seppo Auriola; Pasi Soininen; Jouko Vepsäläinen; Markku Pasanen School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland. Pyrrolizidine alkaloids (PAs), esters of amino alcohols and complex carboxylic acids, are plant secondary metabolites that often contaminate human foods such as wheat and honey. The alkaloids are not toxic per se but require metabolic bioactivation to putative intermediate reactive metabolites known as pyrrolic esters (i.e., didehydropyrrolizidine alkaloids). The pyrrolic esters of PAs are believed to be formed by cytochrome P450 mediated hydroxylation of the amino alcohol base at the C3 or C8 followed by spontaneous dehydration and structural rearrangements. However, the mechanism of the formation as well as the site of oxidation that leads to the formation of these intermediates remains elusive. In this study, utilizing electrochemical and biological methods of oxidations and in silico methods such as ligand-based (i.e., electrophilic Fukui function and bond dissociation energy) and structure-based (i.e., molecular docking), we showed that: (1), the putative reactive metabolites can be produced and detected by an electrochemical cell coupled online to mass-spectrometry; (2), the pyrrolic esters were very unstable and immediately degraded to a small stable but reactive metabolite identified as (3H-pyrrolizin-7-yl)methanol; (3), according to the in silico modeling, the site of hydroxylation was at the C3 of the amino alcohol moiety; and (4) the structural variation of the individual PAs played significant role in facilitating the toxic pyrrolic ester or nontoxic N-oxide formation. The new reactive metabolite, (3H-pyrrolizin-7-yl)methanol was prepared by organic synthesis and the findings of the current study generate substantial information about the metabolism of hepatotoxic Pas.

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CERVICAL CANCER SCREENING PARTICIPATION AMONGIMMIGRANTS IN FINLAND: AN ANALYSIS OF COUNTRY OFORIGINEsther Idehen1,2;Päivikki Koponen3;Teppo Juntunen3; Mari Kangasniemi1; Anna-Maija Pietilä1;Tellervo Korhonen1,2,3

1Department of Public Health & Clinical Nutrition, University of Eastern Finland,2University of Helsinki, and 3National Institute of Health & Welfare (THL),Finland.Objectives & Introduction: To explore factors associated with theimmigrant women's participation in the Pap test screening in Finland.Cervical cancer is one of the most common cancers in women worldwide.Early detection of this disease can be obtained using regular Pap tests. Withthe screening program for cervical cancer becoming an essential part of theFinnish healthcare system, a decline of about 70-80% in its incidence andmortality rates has been observed. Previous studies revealed low attendancerates among immigrants compared with natives Finns. Meanwhile, reasonsfor unsatisfactory participation have not been investigated.Methods: This study utilizes data from the Maamu study conducted by theNational Institute for Health and Welfare (THL) in 2010-2012. Participantswere immigrant women from Russia/Soviet Union, Somalia, Iraq or Iran,aged 18-64, with at least one year stay in Finland. Responses to Pap testparticipation within the last five years were available from 620 women aged25-60. For statistical analyses, the StataSe 13 software was used. Results &Conclusion: Significant differences in screening participation exist amongthese groups: The Russian (75%), Kurdish (61%), and Somali (30%).Education, literacy and marital status were associated with participation.Different factors are associated with Pap test utilization among the ethnicminorities groups. Thus, an appropriate culturally program designaccording to country of origin may increase the likelihood to participation.

OOPHORECTOMY, HYSTERECTOMY, AND RISK OF ALZHEIMER’S DISEASE: A NATIONWIDE CASE-CONTROL STUDY Bushra Imtiaz1, Marjo Tuppurainen2, Miia Tiihonen3, Miia Kivipelto1,4, Hilkka Soininen1, Sirpa Hartikainen3,5, Anna-Maija Tolppanen1

1. Institute of Clinical Medicine, UEF; 2.Department of Obstetrics and Gynecology, KUH; 3. Department of Pharmacy, UEF; 4. Aging Research Center (ARC), Sweden; 5. Kuopio Research Center of Geriatric Care, UEF Objective: To assess whether oophorectomy, hysterectomy, and hysterectomy with bilateral oophorectomy are related to risk of Alzheimer’s disease (AD), and whether the possible indication for surgery and use of HT modifies this association. Methods: Our nationwide register based case–control (1:1) study included all women with clinically-verified AD diagnoses, residing in Finland on December 31, 2005 (n of cases = 19,043, n of controls = 19,043). AD cases, diagnosed according to NINCS-ADRDA and the DSM-IV criteria, were identified from Special Reimbursement Register. Information on HT use and surgery was collected from national prescription register and hospital discharge register respectively. Most of the women (91.8%) were over 51 years of age when the surgery was performed. Results: Oophorectomy, hysterectomy, and hysterectomy with bilateral oophorectomy were associated with lower risk of AD (OR/95% CI: 0.85/0.75–0.97, 0.89/0.81–0.97 and 0.85/0.75–0.98, respectively) among women without the history of uterine/ovarian/cervical cancer irrespective of HT use. The association was not evident in women with uterine/ovarian/cervical cancer history (3.00 /0.20–44.87 for all surgeries). HT use >10 years was independently associated with reduced AD risk. Conclusion: Our findings indicate that oophorectomy with or without hysterectomy after commencement of natural menopause is not an important determinant of AD risk in older age and support the critical window hypothesis for HT use.

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DIETARY PROTEIN INTAKE IS ASSOCIATED WITH BETTER PHYSICAL FUNCTION AND MUSCLE STRENGTH AMONG ELDERLY WOMEN Masoud Isanejad [1], Jaakko Mursu [1], Joonas Sirola [2], Heikki Kröger [2], Marjo Tuppurainen [2], Toni Rikkonen [2], Arja Erkkilä [1]. [1] Institute of Public Health and Clinical Nutrition, University of Eastern Finland; [2] Department of Orthopaedics and Traumatology, Kuopio University Hospital Higher protein intake than RDA (0.8 g/ kg per body weight (BW)) might be beneficial to physical functional among elderly. We evaluated the association of protein intake with physical function in women aged 65 yr and older. In total 554 women in the OSTPRE-FPS study, filled a questionnaire on lifestyle factors and a 3-d food record in 2002. Body composition was measured by dual energy X-ray absorptiometry and physical function tests were performed at baseline and after 3 years. Women with higher protein intake (comparing categories of ≤ 0.8 vs. 0.81-1.19 vs. ≥ 1.2 g/ kg BW) had better performance in one leg stance (P<0.001), chair rise (P=0.042), standing with eyes closed for 10 s (P=0.050) and squat (P=0.027) and squat to the ground (P<0.001); they had faster gait speed 10 m (P<0.001) and greater short physical performance battery score (P<0.001) (calculated by scoring gait speed 10 m, chair rises and one leg stance) at the baseline. Further, higher protein intake was associated with less decline in one leg stance (P=0.007) and squat ability (P=0.012) as well as increased chair rise performance (P=0.001) over the 3 year follow-up. In conclusion, protein intake higher than the current RDA was positively associated with physical function in elderly women.

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THE ORGANIC OSMOLYTE BETAINE INDUCES KERATIN 2 EXPRESSION IN RAT EPIDERMAL KERATINOCYTES – A GENOME-WIDE STUDY IN UVB IRRADIATED 3D CULTURES Leena Rauhala*, Lasse Hämäläinen*, Thomas W. Dunlop, Petri Pehkonen, Geneviève Bart, Maarit Kokkonen, Markku Tammi, Raija Tammi, Sanna Pasonen-Seppänen * Equal contribution Institute of Biomedicine, University of Eastern Finland The moisturizing and supposedly protective properties of betaine have made it an attractive and common component for skin care products. Such widespread use intrigued us to characterize its molecular targets in keratinocytes and to explore, whether it modifies the effects of acute UVB exposure. Genome-wide expression analysis was performed on organotypic cultures of rat epidermal keratinocytes, treated either with betaine, UVB or their combination. Results were verified with qRT-PCR, western blotting and immunohistochemistry. Cell proliferation and differentiation were also analyzed. Among the 89 genes influenced by betaine, the differentiation marker keratin 2 showed the highest upregulation. Expression of Egr1, a transcription factor, and Purkinje cell protein 4, a regulator of Ca2+/calmodulin metabolism, also increased, while downregulated genes included several ion-channel components, such as Fxyd2. Bioinformatics analysis suggest that genes modulated by betaine are involved in DNA replication, might counteract UV-induced processes, and include many targets of transcription factors associated with cell proliferation and differentiation. Our results indicate that betaine controls unique gene expression pathways in keratinocytes, including some involved in differentiation.

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SERUM 25-HYDROXYVITAMIN D3 AND THE RISK OF CANCER IN EASTERN FINNISH MEN: THE KUOPIO ISCHAEMIC HEART DISEASE RISK FACTOR STUDY (KIHD) Petra Kokko1, Jaakko Mursu1, Jyrki Virtanen1, Sari Voutilainen1,Tarja Nurmi1, Tomi-Pekka Tuomainen1 1Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland OBJECTIVE & INTRODUCTION: As previous findings are inconsistent, we investigated the association between serum 25-hydroxyvitamin D3

[25(OH)D3] concentration and the risk of cancer in Finnish men. METHODS: 2552 men aged 42–60 years from the prospective, population based Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) free of cancer at baseline were studied. Serum 25(OH)D3 concentration was measured by high-performance liquid chromatography at baseline. Cancer-related information was obtained by record linkage from the Finnish Cancer Registry. RESULTS: During a mean follow-up of 20.1 years, 651 total, 231 prostate, 87 lung and 82 colorectal cancers occurred. The mean±SD serum 25(OH)D3 concentration was 43.3±18.9 nmol/L. After adjusting for age, examination year, seasonality, smoking, alcohol intake, BMI, physical activity, energy intake, family history of cancer, place of residence, education, and marital status, low vitamin D status (<32 nmol/L) was not statistically significantly associated with total (HR=1.02; 95% CI 0.82-1.26; P-trend 0.91), prostate (HR=0.70; 95% CI 0.49-1.00; P-trend 0.05), lung (HR=1.29; 95% CI 0.73-2.26; P-trend 0.42) or colorectal (HR=0.77; 95% CI 0.42-1.43; P-trend 0.50) cancer incidence, when compared with the highest tertile (>49 nmol/L), although the associations with prostate cancer reached borderline significance. CONCLUSIONS: More studies are needed to clarify the association of vitamin D status on cancer risk, especially prostate cancer risk.

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STROKE IN PATIENTS WITH ATRIAL FIBRILLATION: DOES CONCOMITANT CAROTID ARTERY STENOSIS MATTER? Heidi Lehtola, MD (1), Pirjo Mustonen PhD, MD (1), Juha EK Hartikainen MD, PhD (3), Tuomas Kiviniemi MD, PhD (2), Antti Ylitalo MD, PhD (4), Päivi Hartikainen MD, PhD (5), KE Juhani Airaksinen MD, PhD (2). (1) Department of Medicine, Keski-Suomi Central Hospital, Jyvaskyla, Finland, (2) Heart Center, Turku University Hospital and University of Turku, Turku, Finland, (3) Heart Center, Kuopio University Hospital, Kuopio, Finland, (4) Heart Center, Satakunta Central Hospital, Pori, Finland , (5) NeuroCenter, Neurology, Kuopio University Hospital, Kuopio, Finland Background: Atrial fibrillation (AF) and hemodynamically significant carotid artery stenosis (CAS) are both common etiological factors for ischemic stroke, but require different secondary preventive measures. Only little is known about whether the presence of concomitant CAS affects prognosis and stroke recurrence in AF patients. Objectives: Aim of the study was to compare risk factors, features of index stroke and prognosis after ischemic stroke in AF patients with and without CAS (>50%). Methods: The study population of this multicenter retrospective Fibstroke substudy (n=984) consisted of 184 cases of ischemic stroke or TIA with both AF and hemodynamically significant CAS (>50%) (CAS group) and 800 cases with only AF (non-CAS group). The patients were prospectively followed after index case for 3.69 years (mean, SD 2.52) during 2003-2012. Results: AF patients with significant CAS were older and had more risk factors for ischemic stroke (hypertension, coronary artery disease, other vascular disease, diabetes, heart failure) than AF patients without CAS. Consequently, median CHA2DS2-VASc score was significantly higher in CAS group (4 vs. 3, p<0.001). In CAS group AF was more often chronic. Patients in CAS group were more often on anticoagulation at the onset of stroke. Ischemic stroke recurrence rate (16.8 % vs.10.3 %, p=0.019) and 30-day all-cause mortality rate (7,6 % vs. 2,3 %, p<0.001) were significantly higher in CAS group. Presence of CAS (p=0.011, OR 2.62, 95-% CI 1.25-5.57) and increasing age (p<0.100, OR 1.13, 95-% CI 1.07-1.19 OR 1.13) were independent risk factors for 30-day mortality, and CAS (p=0.001, HR 1.85, 95-% CI 1.28-2.66) was also an independent risk factor for recurrent ischemic stroke in multivariate analysis. Conclusions: 30-day mortality was higher in CAS group. Despite similar anticoagulation after first stroke long term ischemic stroke recurrence rate was significantly higher in patients with AF and concomitant carotid artery stenosis.

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MICRORNA PROFILING OF PERICARDIAL FLUID SAMPLES FROM PATIENTS WITH HEART FAILURE Suvi M. Kuosmanen [1], Juha Hartikainen [2,3], Mikko Hippeläinen [3], Hannu Kokki [2,4], Anna-Liisa Levonen [1], Pasi Tavi [1]

[1] A.I.Virtanen Institute for Molecular Sciences and [2] School of Medicine, UEF, [3] Heart Center and [4] Anesthesia and Operative Services, Kuopio University Hospital Heart failure is a condition in which the heart is unable to sustain sufficient blood circulation to meet the needs of the body. Human heart is enclosed in a sac known as the pericardium, which is filled with pericardial fluid. Pericardial fluid contains hormones secreted by the heart and is known to reflect the cardiac function. MicroRNAs (miRNAs) are small, non-coding RNAs that control gene expression. MiRNAs can be secreted from the cells into the extracellular space or to the systemic circulation where they act as para- or endocrine signalling molecules. In this study, we sought to investigate whether pericardial fluid contains miRNAs and if so, whether they could be used to distinguish between different cardiovascular pathologies and disease stages. Pericardial fluid was collected from heart failure patients during open-heart surgery. MiRNA profiles of 51 patients were measured by qPCR using Exiqon human panels I and II. On the average, 256 microRNAs were detected per sample, and 70 miRNAs out of 742 profiled miRNAs were detected in every sample. The five most abundant miRNAs in pericardial fluid were miR-21-5p, miR-451a, miR-125b-5p, let-7b-5p and miR-16-5p. Although measured miRNA profiles did not separate the samples according to the clinical features of the patients, several previously identified heart failure marker miRNAs were detected. In addition, the profile appeared to be a result of an active and selective secretory process indicating that miRNAs may mediate the local crosstalk between cardiac cells.

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ANALYSIS OF THE KEAP1-NRF2 PATHWAY ACROSS CANCERS REVEALS ITS POTENTIAL TO ACT AS AN ONCOGENIC DRIVER Petri Pölönen[1,2], Hanna Leinonen[1], Sheila Reynolds[3], Kalle Leinonen[3], Matti Annala[4], Ilya Shmulevich[3], Matti Nykter[4], Anna-Liisa Levonen[1], and Merja Heinäniemi[1,2] [1] A.I. Virtanen Institute for Molecular Sciences, UEF, [2] Institute of Biomedicine, UEF, [3] Institute for Systems Biology, Seattle, USA, [4] Institute for Biomedical Technology, University of Tampere Nuclear factor E2 related factor 2 (NFE2L2, Nrf2) is an oxidative and electrophilic stress activated transcription factor (TF) with a protective role in normal cells. In cancer, the pathway can gain constitutive activity via several mechanisms, resulting in altered therapy response and disease prognosis. Here, we have comprehensively analyzed molecular and clinical profiles representing over 8000 patient samples across 20 tumor types to generate an unbiased view of Nrf2 overactivation. Our analysis highlights Nrf2 as a frequently mutated TF. Further, elevated activity was found to correlate with copy number and methylation changes at the NFE2L2 gene locus with potential to amplify the mutant Nrf2 levels. In squamous cell carcinomas, our network and genomics analysis implicated SOX2 as a putative upstream regulator of NFE2L2 expression, linking aberrant Nrf2 activity with the frequent amplification of chr3. Across tumors, Nrf2 has a major effect on metabolic pathway expression. In conjunction with smoking, elevated Nrf2 activity manifests as increased mutation rates, with potential to activate further oncogenes and disrupt critical tumor suppressor genes including TP53.

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EXHALED BREATH REFLECTS METABOLIC CHANGES INDUCED BY DIET Kaisa Raninen [1], Mikko Kolehmainen [2], Tomi-Pekka Tuomainen [1], Hannu Mykkänen[1], Kaisa Poutanen [1] and Olavi Raatikainen [1] [1] Institute of Public Health and Clinical Nutrition, University of Eastern Finland [2] Department of Environmental Sciences, University of Eastern Finland Exhaled breath offers a noninvasive way to measure metabolites produced by biochemical processes in cells and organs or generated as a result of the activity of intestinal microbiota. These metabolites can also originate from ingested from food or be inhaled from the environment. There is, however, a lack of studies on effects of diet or nutritional status on exhaled breath. We evaluated the potential of monitoring diet-induced changes in metabolism based on breath profiles analyzed by aspiration ion mobility spectrometry (AIMS). Exhaled breath alveolar samples were taken at fasting state after low versus high fibre diets (17 and 44 g/day for one week in randomized order, n=7) and during an aerobic exercise test (30 minutes cycling with cycle ergometer, n=9), and analyzed with ChemPro® 100, a hand-held gas detector based on AIMS technology. Principal component analysis was carried out as pre-processing and Hotelling’s T-test and linear discriminate regression models (LDRM) were applied to discriminate the exhaled breath profiles in different metabolic states. The exhaled breath profiles were different between the diets (Hotelling´s test, p=0.015, LDRM: R2= 0.71, sensitivity 0.71, specificity 0.71 and accuracy 0.71) and between the resting and the exercise states (p=0.012, R2=0.79, sensitivity 1.00, specificity 0.89 and accuracy 0.94).This indicates the potential of utilizing the exhaled breath profiles for detecting dietary changes, and encourages to continue monitoring exhaled breath as part of nutritional interventions.

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HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH IDIOPATHIC NORMAL PRESSURE HYDROCEPHALUS Antti Junkkari [1]; Harri Sintonen [2]; Ossi Nerg [3]; Anne M Koivisto [4]; Risto P Roine [5]; Heimo Viinamäki [6]; Hilkka Soininen [7]; Juha E Jääskeläinen [8]; Ville Leinonen [9] [1] Neurosurgery of NeuroCenter, Kuopio University Hospital and University of Eastern Finland, [2] Hjelt Institute/Department of Public Health, University of Helsinki, [3] Neurology, Institute of Clinical Medicine, University of Eastern Finland. Neurology of NeuroCenter, Kuopio University Hospital, [4] Neurology, Institute of Clinical Medicine, University of Eastern Finland. Neurology of NeuroCenter, Kuopio University Hospital, [5] University of Eastern Finland, Kuopio Finland and Helsinki and Uusimaa Hospital District, Group Administration, [6] Department of Psychiatry, Kuopio University Hospital, and University of Eastern Finland, [7] Neurology, Institute of Clinical Medicine, University of Eastern Finland. Neurology of NeuroCenter, Kuopio University Hospital, [8] Neurosurgery of NeuroCenter, Kuopio University Hospital and University of Eastern Finland, [9] Neurosurgery of NeuroCenter, Kuopio University Hospital and University of Eastern Finland OBJECTIVE & INTRODUCTION: We explored factors affecting health-related quality of life (HRQoL) in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: Using the 15D instrument we evaluated HRQoL in 132 patients diagnosed with iNPH by clinical and neuroradiological examinations. The severity of iNPH symptoms was measured with the iNPH Grading Scale (INPHGS), depressive symptoms with the Beck Depression Inventory (BDI-21), and cognitive impairment with the Mini-Mental State Examination (MMSE). RESULTS & CONCLUSIONS: The mean (SD) 15D score (on a 0-1 scale) of patients with iNPH was significantly lower than that of an age- and gender-matched sample of the general population [0.718 (0.103) vs. 0.870 (0.106); p < 0.001]. The mean 15D score was lower in iNPH patients with moderate or severe depressive symptoms than in patients without depressive symptoms (p = 0.003). According to stepwise multiple linear regression analysis, a higher total iNPHGS score (b = -0.62, p < 0.001) and a higher BDI-21 total score (b = -0.201, p = 0.025) predicted a lower 15D score; in combination, these explained 51% of the variance in the 15D score (R2 = 0.506, p < 0.001). iNPH impairs patients’ HRQoL on multiple dimensions, similarly to other chronic diseases. Potentially treatable depressive symptoms contribute greatly to the HRQoL impairment of iNPH patients, but only if they are moderate or severe. The 15D portrayed HRQoL dimensions affected by iNPH in a similar way as broader assessment batteries, and thus is a potentially useful tool for treatment evaluation and cost-utility analysis.

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CHARACTERIZATION OF ALZHEIMER’S DISEASE RISK GENE UBIQUILIN-1 IN HUMAN BRAIN AND IN IN VITRO AND IN VIVO MODELS Mari Takalo [1,2], Teemu Natunen [1,2], Kaisa M.A. Kurkinen [1,2], Petra Mäkinen [1,2], Hilkka Soininen [2], Heikki Tanila [3], Mikko Hiltunen [1,2], Annakaisa Haapasalo [2] [1] Institute of Biomedicine, [2] Institute of Clinical Medicine – Neurology, and [3] A.I. Virtanen Institute; University of Eastern Finland, Kuopio, Finland

Ubiquilin-1 is genetically and functionally associated with Alzheimer’s disease (AD). It regulates the levels and trafficking of several AD-associated proteins and modulates stress conditions involved in neurodegeneration. Here, we studied ubiquilin-1 function and interactions in human post-mortem brain tissue, in vitro in neuron-microglial cell co-cultures during neuroinflammation, and in vivo in the brain of adult AD model mice (APPswe/PS1dE9). We found that ubiquilin-1 expression decreased in human brain in relation to AD pathology. In addition, there was a correlation between the levels of ubiquilin-1 and BACE1, a key enzyme in AD pathogenesis, in the brain samples. Accordingly, BACE1 levels were increased in neuron-microglia co-cultures and hippocampi of mice overexpressing ubiquilin-1. Furthermore, neuronal viability was decreased in ubiquilin-1-overexpressing co-cultures. Mechanistic studies in neuronal cells suggested that ubiquilin-1 regulates the stability and subcellular localization of BACE1. This study reveals a novel interaction between ubiquilin-1 and BACE1, which may affect the molecular pathogenesis, disease progression, and neurodegeneration in AD.

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THE PREOPERATIVE NURSE’S ROLE IN SURGERY PROCESS – AN INTEGRATIVE LITERATURE REVIEW Elina Turunen, M.Sc. PhD-student (1), Katri Vehviläinen-Julkunen, Professor (1, 2), Merja Miettinen, Docent (2) (1) Department of Nursing Science, University of Eastern Finland, (2) Kuopio University Hospital The development of surgery and anesthetic methods has led to shorter hospital stays. At the same time, surgical nursing has changed and new roles have been developed. There is evidence that nurse-led preoperative assessment provides a safe and effective way of assessing patients preoperatively. The preoperative nurse’s role is still unstandardized and it should be defined to achieve high quality care. The aim of an integrative review was to describe the role and outcomes of a preoperative nurse. The data were collected from two databases; PubMed and CINAHL (1.1.2004-30.9.2014). The preset inclusion and evaluation criteria were used. The data analysis was conducted by qualitative inductive content analysis, using abstraction and categorizing. Totally 95 articles were included in the review. The data provided three themes; the main components, the tools, and the outcomes of preoperative nursing. Preoperative nursing includes several components as the main focus is in communication with the patient and other professionals, coordination of the patient care, and providing individual patient and family centered care. Different tools such as scheduling systems and checklists can be useful. Preoperative nursing promotes safe and cost-effective patient care. The preoperative nurse’s role is essential in patient’s care pathways. A structured preoperative nursing model should be created within all healthcare organizations providing surgical care.

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Posters

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DO FALLS PREDICT POSTMENOPAUSAL FRACTURES? Nadia Afrin 1, Heli Koivumaa-Honkanen2, Toni Rikkonen1, Heikki Kröger3, Risto Honkanen1 1Clinical Research Center, BCRU (Bone and Cartilage research unit)/UEF, University of Eastern Finland, 2Psychiatry, 3Surgery, Kuopio University Hospital, Kuopio, Finland Objective: To access does falling history predict fractures in postmenopausal women. Introduction: Falling tendency and low BMD are risk factors for fractures in the elderly. The purpose of this study was to evaluate if fall history is a predictor of postmenopausal fractures. In addition, if fall risk predicts fractures differently according to type of fall and site of fracture, this association will also be estimated. Methods: Falls were asked in the 10-year postal enquiry of the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) Study in 1999 with. A total of 10210 women responded to the enquiry and fall questions. Women with falls were classified as single fallers (1 fall/year) and multiple fallers (2+ falls/year). Fractures in 1999-2004 were asked in 2004. Self-reports were confirmed by perusal of patient records. A total of 9759 women responded to fracture questions and 8744/9759 women had information on both falls and fractures. A total of 811/8744 women (9.3%) had sustained fractures during the 5-year follow-up. Odds ratios (OR) were computed with logistic regression.

Results: Women were 57-66 years old at baseline. Falling history predicted fractures with an OR of 1.41 (p<0.001). Single fall was related to fracture 38 % and multiple falls 45 % more often than no history of fall. Falls did not predict osteoporotic fractures (n=431)(OR 1.26 (ns) but predicted non-osteoporotic fractures (n=380)(OR=1.54)(p<0.001). Distal forearm fracture (n=313) was the most common fracture (OR=1.26)(ns). Only 24 women reported a hip fracture (OR=1.10)(ns). Ankle was the most common site of non-osteoporotic fracture (n=146)(OR=1.17)(ns) followed by rib (n=39)(OR=1.46)(ns).

Falls on same level were classified into slip (n=708) and nonslip falls (n=685). Slip falls predicted fractures slightly more (OR=1.43)(p=0.002) than nonslip fractures (OR=1.35)(p=0.023). Multiple & slip falls predicted non-osteoporotic fractures more (OR=2.04 (95% CI 1.34-3.09)) than single & slip falls (OR=1.29). Self-report of falls twice (in the 5-year and 10-year enquiry) increased the risk of future fracture more (OR=1.77 (95%CI1.41-2.24)) than self-report only once (5-year or 10-year)(OR=1.29 (95% CI 1.09-1.53)).

Conclusions: Fall history is a less powerful predictor of postmenopausal fracture than fracture history. However, repeated multiple falls should alert a clinician. Fall history is a candidate risk factor for inclusion in FRAX.

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FEMALE SEX, AGE AND TIME DELAY TO CARDIOVERSION AS RISK FACTORS IN THE CARDIOVERSION OF ACUTE ATRIAL FIBRILLATION. THE FINCV STUDY Aissa Bah (1), Ilpo Nuotio (2), Toni Grönberg (3), Antti Ylitalo (4), Marko Nikkinen (1), Juhani K.E. Airaksinen (3), Juha K.E. Hartikainen (1) (1) Heart Center, Kuopio University Hospital and University of Eastern Finland, (2) Department of Acute Internal Medicine, Turku University Hospital (3) Heart Center, Turku University Hospital (4) Department of Internal Medicine, Lapland Central Hospital and University of Oulu Female sex is a risk factor for thromboembolic complications (TEC) in chronic atrial fibrillation (AF). Women also have an increased risk of complications after cardioversion of acute AF (< 48 h). Whether this is due to sex or to comorbidities, and what is the interaction between age, sex and delay on the risk of TEC is not known. A total of 4715 electrical cardioversions (ECV) were performed in 2313 patients with acute AF without anticoagulation. The outcomes were failure of cardioversion, bradyarrhythmic complications after cardioversion, AF recurrence, and TEC within 30 days following the ECV. Their combined end-point or net harm was calculated and the interaction of age, sex and delay to cardioversion on the risk of TEC. Female patients were older, had more comorbidities and higher heart rate on admission than men. The failure of ECV was higher (6·7 % vs. 4·0 %, p<0·001), bradyarrhythmic complications were more common in women (1·9 % vs. 0·4 %, p<0·001) than in men and AF tended to reoccur more often during the follow-up (13·7 % vs. 11.7 %, p=0·055). Female sex was also associated with an increased risk of TEC (OR 2·12, CI 1·09-4·11, p=0·026). The net harm was higher in women (21·9 % vs. 16·0 %, p<0·001). Age, time delay from the onset of AF to cardioversion, and vascular disease were the other significant predictors of TEC. Female sex was associated with increased risk of complications and failure of cardioversion after ECV of acute AF. The risk of TEC was “acceptable” (< 0.5 %) in patients < 75 years and delay to ECV < 12 hours.

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THE CEREBRAL EMBOLISM EVOKED BY INTRA-ARTERIAL DELIVERY OF ALLOGENEIC BONE MARROW MESENCHYMAL STEM CELLS IN RATS Li-li Cui [1], Johannas Boltze [2], Barbara Lukomska [3], Jukka Jolkkonen [1] for the MEMS-IRBI consortium [1] Institute of Clinical Medicine-Neurology, University of Eastern Finland, [2] Fraunhofer Institute, University of Leipzig, [3] Mossakowski Medical Research Centre Objective & Introduction Intra-arterial (IA) cell infusion is an efficient delivery route to target organs, but related adverse events like micro-embolisms were recently reported. We tested the hypothesis that cell dose, infusion volume and infusion velocity might be related to the complications after IA cell delivery. Methods Forty-two rats were subjected to a sham middle cerebral artery occlusion procedure before being infused with allogeneic bone-marrow mesenchymal stem cells through the external carotid artery at different doses (0-1.0×106), infusion volumes (0.5-1.0 ml), and infusion times (3-6 min). Laser Doppler flowmetry and MRI was performed to reveal possible complications. Open field test was conducted to assess sensorimotor functions. Results & Conclusions There was a cell dose-related reduction in cerebral blood flow, an increase in embolic events as well as sensorimotor impairment. A low infusion velocity (0.5 ml/6 min) was associated with high rate of complications. Particularly cell dose but also infusion velocity should be considered before planning efficacy studies.

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INTRAVITREAL CLEARANCE AND VOLUME OF DISTRIBUTION OF COMPOUNDS IN RABBITS: IN SILICO PREDICTION AND PHARMACOKINETIC SIMULATIONS FOR DRUG DEVELOPMENT Eva M. del Amo1,2, Kati-Sisko Vellonen2, Heidi Kidron1, and Arto Urtti1,2 1Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland, 2School of Pharmacy, University of Eastern Finland, Kuopio, Finland Introduction. Diseases affecting the posterior segment of the eye are becoming more prevalent in the ageing populations and intravitreal injection is the effective way of administration. Objectives. Create a curated universal database of intravitreal volumes of distribution (Vss, ivt) and clearances (CLivt) of small molecular weight compounds and macromolecules. Develop quantitative structure property relationship (QSPR) and pharmacokinetic models for the estimation of vitreal drug concentrations based on the compound structure. Methods. Vss, ivt and CLivt values were determined from 40 small molecular weight compounds and 11 macromolecules using WinNonlin software. Multivariate analysis was used to build QSPR models for CLivt. Pharmacokinetic simulations of a drug delivery system using integrating QSPR model was applied to estimate vitreal drug concentration profiles. Results. A simple and reliable model for intravitreal CLivt was obtained: Log CLivt= -0.25269 - 0.53747 (LogHD) + 0.05189 (LogD7.4) The relevant descriptors were logD7.4 and hydrogen bond donor capacity. The model predicted reliably the internal and external test sets with a mean fold error of 1.50 and 1.33, respectively (Q2Y = 0.62). For 80% of the compounds the intravitreal Vss, ivt was 1.18 - 2.28 ml. The implementation of the predicted parameters into pharmacokinetic simulation models yielded good estimates of vitreous drug concentrations. Conclusions. The present work offers useful in silico tools to investigate a priori the intravitreal pharmacokinetic profiles for intravitreally injected drugs and delivery systems.

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INCOME-RELATED INEQUALITY IN HEALTH CARE UTILIZATION IN MONGOLIA, 2008-2012 Javkhlanbayar Dorjdagva1, Enkhjargal Batbaatar2, Bayarsaikhan Dorjsuren3, Jussi Kauhanen1 1Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 2Faculty of Economics and Business Sciences, University of Sannio, 3 Department of Health Systems Governance and Financing, WHO Objective: The aim of this paper is to evaluate the horizontal inequity in health care utilization and its change between 2007/2008 and 2012 in Mongolia. Methods: The data used in this study was taken from the nationwide cross-sectional data sets, the Household Socio-Economic Survey, collected in 2007/2008 and 2012 by the National Statistical Office of Mongolia. We employed the Erreygers’ concentration index to measure inequality in health services utilization. Horizontal inequity was estimated by a difference between actual and predicted use of health services. Results: The results show that the concentration indices for tertiary level, private outpatient and inpatient services were significantly positive, the contrary for family group practice/soum hospital outpatient services, in both years. After controlling for need, pro-rich inequity (p<0.01) was observed in the tertiary level, private outpatient, and general inpatient, services in both years. Pro-poor inequity (p<0.01) existed in family group practice/soum hospital outpatient services in both years. Degrees of inequity in tertiary level hospital, and private hospital outpatient services became more pro-rich, whereas in family group practice/soum hospital outpatient services became more pro-poor from 2007/2008 to 2012. While pro-rich inequity in inpatient services remained same from 2007/2008 to 2012. Conclusions: Equitable distribution of health care has well documented in health strategies and policies; however, the degree of inequity in delivery of health services has a tendency to increase in Mongolia.

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DETERMINANTS OF ETHNIC VARIATIONS IN HEALTH SERVICE USE ASSOCIATED WITH CHRONIC DISEASES AMONG THE KURDISH, RUSSIAN AND SOMALI MIGRANTS IN FINLAND Etchi Daniel Tabe, Doctoral Programme in Public Health, UEF, Tiina Laatikainen School of Public health & Clinical Nutrition, UEF, Päivikki Koponen, National Institute for Health and Welfare THL As migration becomes increasingly recognized as a social determinant of health, the pitfalls of health inequalities faced by migrants call for more concern across Europe today, despite the objective of horizontal equity for health in the EU countries with comprehensive coverage. In the majority of these countries, migrants are faced not only with socio-cultural, socio-economic, and system-related barriers to health care, but also bear higher prevalence of major chronic diseases, compared to native born populations. In Finland, the largest population-based study on health and wellbeing of migrants (the MAAMU survey) has provided a literal snapshot of health inequality between the major migrant groups and the general population of Finland. The MAAMU study; coordinated by the national institute for health and welfare THL, entailed health interviews and examinations on 3000 randomly selected individuals from the national population registry, constituting migrants of Kurdish, Russian and Somalian origins, living in six of the largest cities in Finland. Results from this study showed wide variations in health-seeking behaviour, use of health services, and prevalence of chronic diseases such as diabetes and cardiovascular diseases and their associated risk factors between migrant groups and the general population. The present study is aimed at describing predictors of observed disparities in health and health service use, and also to elucidate the roles played by ethnicity, and system-related factors as barriers to adequate health service utilization among migrants in Finland. Analysis on secondary data from the MAAMU study and the HILMO health register will explore various measures of association between variables; to determine predictors of health-seeking behaviour, assess patterns of unmet treatment needs, and to identify predisposing factors influencing health service use. Results from this study are expected to enhance our understanding about migration-related, and health system-dependent barriers and facilitators of health service use by migrants. In this light, more would be learned about valuable indicators of health disparity, useful in promotional and intervention programs to foster integration of migrants and improvement of cultural competence in health care.

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FENTANYL PHARMACOKINETICS IN PREGNANT SHEEP AFTER INTRAVENOUS AND TRANSDERMAL ADMINISTRATION TO THE EWE Emma M. Heikkinen1, Hanna-Marja Voipio2, Sakari Laaksonen2, Linnea Haapala2, Juha Räsänen3,4, 7, Ganesh Acharya5, Tiina Erkinaro6, Mervi Haapsamo7, Heidi Hautajärvi8, Hannu Kokki3, 9, Merja Kokki3, 4, 9, Aki T. Heikkinen1,8 1 School of Pharmacy, University of Eastern Finland, 2 Laboratory Animal Centre, Department of Experimental Surgery, University and University Hospital of Oulu, 3 School of Medicine, University of Eastern Finland, 4 Department of Obstetrics and Gynecology, Kuopio University Hospital, 5 Women’s Health and Perinatology Research Group, Department of Clinical Medicine, UiT-The Arctic University of Norway, Tromsø, Norway, 6 Department of Anesthesiology, University Hospital of Oulu, 7 Department of Obstetrics and Gynecology, University Hospital of Oulu, 8Admescope Ltd, Oulu, Finland, 9 Anesthesia and Operative services, Kuopio University Hospital Fentanyl is used for analgesia during pregnancy in humans and animals. However, fentanyl pharmacokinetics during pregnancy has not been fully established. The aim of this study was to characterize fentanyl pharmacokinetics in pregnant sheep after intravenous and transdermal dosing during surgery. Pharmacokinetic parameters reported for non-pregnant sheep and nominal transdermal dose rate were utilized for a priori dose rate calculation to achieve fentanyl concentration of 0.5-2 ng/ml in maternal plasma. A total of 20 ewes in late gestation were used in two dosing protocols. One week before surgery 10 animals received 2 µg/kg fentanyl intravenous bolus, and on the operation day, transdermal fentanyl patches at 2 µg/kg/h nominal dose rate. Ewes were then given a 2 µg/kg intravenous bolus followed by an intraoperative 2.5 µg/kg/h infusion. The other 10 animals received fentanyl only as transdermal patches on the operation day. Plasma samples were analyzed with HPLC-MS. Population pharmacokinetic modeling was utilized for data analysis. Intra- and postoperative fentanyl concentrations were similar and slightly lower than the a priori predictions. Elimination and distribution clearances appeared to decrease during surgery. Fentanyl patches provided drug absorption for up to 5 days but the absorption rate was slower than the nominal rate and showed high inter-individual variability. Further research is warranted to evaluate the clinical relevance of the observations made in sheep.

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FRONTAL GREY MATTER VOLUME IS REDUCED AMONG ADOLESCENT ALCOHOL USERS Noora Heikkinen [1], E Niskanen [2], M Könönen [1], P Kivimäki [1], E Laukkanen [1], Ritva Vanninen [1] [1] University of Eastern Finland & Kuopio University Hospital, [2] Vaasa Central Hospital Objective & Introduction: Adult alcohol use disorder (AUD) often begins during adolescence. Studying adolescent alcohol use is critical in understanding AUD and its link to brain structure and functions. Methods: Subjects (aged 22–28y during MRI) were selected based on their score in the AUDIT-C survey, which tests for alcohol consumption behavior. Participant group (n=38, 18 males) and a control group (n=37, 18 males) were selected based on their AUDIT-C scores, and matched in terms of age, gender and education. All subjects underwent 3-T MRI of the brain. Voxel-based morphometry analysis was performed using VBM8 in SPM8 running under Matlab. Results & Conclusions: Grey matter volume was reduced among alcohol users in the left superior frontal gyrus as compared to control subjects. Separate ROI analyses of the cingulate and frontal regions showed additional areas with reduced grey matter volume in the left medial frontal gyrus and the cingulate gyrus of alcohol users. Frontal areas develop last during adolescence and are very important in cognitive, inhibitory and attention-demanding processes. Their decreased volume may be caused by alcohol’s neurotoxic effects or indicate the subjects’ premorbid brain structural changes predisposing them to excessive alcohol consumption and adult AUD.

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CHARACTERIZATION OF CIRCULATING FOLLICULAR HELPER T CELLS IN TYPE 1 DIABETES PATIENTS AND AUTOANTIBODY-POSITIVE AT-RISK SUBJECTS Emmi-Leena Ihantola [1], Tyyne Viisanen [1], Kirsti Näntö-Salonen [2], Riitta Veijola [3], Jorma Toppari [4], Mikael Knip [5], Heikki Hyöty [6], Jorma Ilonen [1,4], Tuure Kinnunen [1] [1] University of Eastern Finland, Kuopio; [2] Turku University Hospital, Turku; [3] University of Oulu; [4] University of Turku; [5] University of Helsinki; [6] University of Tampere OBJECTIVE & INTRODUCTION: Although type 1 diabetes (T1D) is thought to be a primarily T-cell-driven autoimmune disease, autoantibodies produced by B cells are the best currently available biomarker for early islet autoimmunity and disease risk. These antibodies are produced by autoreactive B cells the activation of which is largely dependent on the function of CD4+CXCR5+ follicular T helper cells (Tfh). A subset of peripheral blood memory CD4+ T cells also expresses CXCR5 and recent studies suggest that they represent the circulating memory counterpart of Tfh cells. METHODS: In the present study, we used multi-color flow cytometry to extensively analyze circulating Tfh (CD4+CD45RA-CXCR5+) cells in 32 recent-onset T1D subjects, 58 autoantibody-positive at-risk subjects and 93 age- and HLA-matched control children. B-cell phenotyping was also performed in the same individuals. RESULTS: We observed no differences in the frequencies of total CD4+CD45RA-CXCR5+ Tfh cells or subpopulations defined by recently described surface markers (CCR6/CXCR3, CXCR3/PD-1 and CCR7/PD-1) between the three study groups. However, the frequency of activated PD-1+ICOS+ Tfh cells was clearly elevated in the peripheral blood of T1D patients but not in autoantibody-positive subjects. No differences in different B-cell subpopulations were observed. CONCLUSION: An increased frequency of activated Tfh cells was observed in patients with recent-onset T1D but not in autoantibody-positive subjects. This finding suggests that the activation of Tfh cells, at least at the level of peripheral blood, is associated with the onset of the disease rather than correlates with the production of autoantibodies. Based on our current results, the analysis of circulating Tfh cells, at least with the current phenotyping markers available, cannot be considered as a biomarker of early T1D progression.

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SERINE 288 STABILIZED NON-SENSITIZED RECEPTOR STATES PREVENTING ENTERING INTO SENSITIZED AND DESENSITIZED STATES Yevheniia Ishchenko, Nataliia Novosolova, Kamil Khafizov, Geneviève Bart, Dmitry Fayuk, Andrei Skorinkin and Rashid Giniatullin Dept. of Neurobiology, A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland A specific region in the ectodomain of ATP-gated P2X receptors called 'left flipper' is an important receptor part for the normal function of P2X receptors contributing to ATP binding. Importantly, six subtypes of P2X receptors have a relatively conserved serine in the position 288 of the 'left flipper' whereas the P2X7 subtype has a phenylalanine. By combining patch clamp and modelling approach, we explored the role of the residue 288 in P2X7 receptor by replacing phenylalanine with serine and characterizing membrane currents generated by the WT or mutated P2X7 receptors. F288S mutation slowed down the deactivation subsequent to long applications of 1 mM ATP and delayed the slow component of deactivation after application of the specific P2X7 agonist BzATP. Moreover, F288S mutant was the reduced probability of a large pore opening observed with WT in response to 20s application of 1 mM ATP. Notably, pore opening is important for release of inflammatory agents from immune cells naturally expressing the pro-inflammatory P2X7 receptor. The specific mechanisms of P2X7 receptor functioning revealed in this project may help to design new medicines for neurodegenerative diseases or in chronic pain where the role of P2X7 receptors is well established.

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MASS SPECTROMETRY–BASED ANALYSIS OF WHOLE GRAIN PHYTOCHEMICALS USING METABOLOMICS APPROACH Ville Mikael Koistinen, Kati Hanhineva Institute of Public Health and Clinical Nutrition, University of Eastern Finland Whole grains are a rich source of several classes of phytochemicals, such as alkylresorcinols, benzoxazinoids and lignans. A high intake of whole grains has been linked to a reduced risk of some major non-communicable diseases, and it has been postulated that a complex mixture of phytochemicals works in synergy to generate beneficial health effects. LC-MS is a widely used method for the analysis of phytochemicals owing to its high sensitivity and dynamic range. In this study, we will analyze the phytochemical profile of whole-grain and processed rye and wheat bread with and without fermentation, using UPLC–qTOF–MS and a non-targeted metabolomics approach. As a result, we expect to identify the influences of different manufacturing processes on the phytochemicals of the final cereal product. Additionally, the gastrointestinal metabolism of the bread samples is studied in an in vitro model. The list of known grain metabolites is still far from complete because numerous compounds detectable in MS still lack structure elucidation, available reference compounds, or published MS/MS data. Further examination of the chemical properties of these unknown compounds is necessary to include them when addressing the research question of how whole grain phytochemicals affect health.

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UVB IRRADIATION INCREASES IL-1Β AND IL-18 SECRETION FROM HUMAN CORNEAL EPITHELIAL CELLS BY INDUCING INFLAMMASOME ACTIVATION Eveliina Korhonen [1], Niina Piippo [1], Maria Hytti [1], Kai Kaarniranta [2], and Anu Kauppinen [1,2] [1] Department of Ophthalmology, University of Eastern Finland, [2] Kuopio University Hospital Inflammasomes are cytoplasmic multiprotein complexes required for producing interleukin (IL)-1β and IL-18, which are early initiators of immune responses. The assembly of a complex induces the activation of caspase-1, which then cleaves IL-1β and -18 into their mature forms. The aim of our study was to investigate the ability of ultraviolet B (UVB) irradiation to activate the inflammasome signaling in human corneal epithelial cell (HCE) cultures. HCE cells were exposed to UVB (0,153 J/cm2) after priming with tumor necrosis factor alpha (TNF-α). Secretion of IL-1β and -18 was measured 24 h after the UVB irradiation using the ELISA method. In addition, the enzymatic activity of caspase-1 was detected from cell lysates. For examining the possible mechanism of inflammasome activation, the levels of extracellular ATP were determined. Our results indicate that UVB activates inflammasome signaling in HCE cells. Moreover, ATP levels were clearly increased after UVB irradiation compared to control samples. The present results suggest that inflammasomes can be activated by UVB radiation in the cornea, and potassium efflux through the ATP signaling may play a role in the activation process.

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RANDOMIZED CONTROLLED TRIALS ARE NEEDED TO CLOSE THE EVIDENCE-GAP IN THE PREVENTION OF PRETERM BIRTH Emma Kwegyir-Afful 2, Sharea Ijaz 1, Kimmo Räsänen 2, Jos Verbeek 1. Finnish Institute of Occupational Health PO Box 310 70701 Kuopio Finland University of Eastern Finland School of Medicine Institute of Public Health and Clinical Nutrition Kuopio, Finland. Background: Prematurity is a leading cause of infant morbidity and mortality in the world. Despite its dangers, the causes of preterm delivery are still unexplained. Heavy lifting during pregnancy has been advised against for a long time due to concerns of adverse pregnancy outcomes but existing evidence is inconclusive as to whether occupational physical activities such as lifting are implicated. Objective: The aim of this paper was to explore future directions in the research of effects of health education interventions against heavy lifting to prevent premature delivery. Our hypothesis is that, a reduction in heavy lifting during pregnancy will increase gestational age. Methods: A systematic search and appraisal of published literature was conducted in multiple electronic databases for clinical trials comparing pregnant women who received an intervention to prevent heavy lifting to those who did not. The findings were discussed in the light of global variation in pregnancy related practices and policies. Results/conclusions: We found a lack of clinical trials addressing this question. This finding is likely a reflection of certain existing legal and practical difficulties and the variation in priorities across nations. We discuss the resulting research implications in a global context to propose a practical solution for a future clinical trial that can reliably inform practice and policy.

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ACUTE MESENTERIC ISCHEMIA IS A MORE COMMON CAUSE THAN EXPECTED OF ACUTE ABDOMEN IN THE ELDERLY Jussi M Kärkkäinen [1,2], Tiina T Lehtimäki [3], Hannu Manninen [3,4] and Hannu Paajanen [2,4] [1] Heart Center, [2] Department of Gastrointestinal Surgery, [3] Department of Clinical Radiology, Kuopio University Hospital. [4] University of Eastern Finland Objective & Introduction: The incidence of acute mesenteric ischemia (AMI) increases exponentially with age. The significance of AMI as a differential diagnosis in elderly patients with acute abdomen may be underestimated. AMI is often found unexpectedly in a routine computed tomography of the acute abdomen. Methods: Consecutive patients hospitalized for AMI between 2009 and 2013 were retrospectively identified in a well-defined population. Acute appendicitis, ruptured abdominal aortic aneurysm, acute pancreatitis, and acute cholecystitis were used as reference diagnoses, and the age-specific incidence rates were calculated. In addition, long-term mortality risk was assessed for AMI survivors. Results: The in-hospital incidence rates of AMI, acute obstructive mesenteric ischemia, and non-obstructive mesenteric ischemia were 7.3, 4.5, and 2.0/100000/year, respectively. AMI was more common than ruptured abdominal aortic aneurysm, and the age-specific incidence of AMI was higher than the incidence of acute appendicitis in patients over age 75 years with acute abdomen. During the follow-up, the age-adjusted risk of death was 1.8 times higher in AMI survivors than in survivors of acute cholecystitis. Conclusion: AMI may be a more common cause of acute abdomen in elderly patients than is generally thought, emphasizing the importance of performing urgent computed tomography with contrast enhancement preferably in arterial and venous phases in these patients.

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RYE BRAN INDUCED CHANGES IN THE METABOLIC PROFILE IN PLASMA, MUSCLE AND LIVER OF MICE Olli Kärkkäinen 1, Jenna Pekkinen 2, Marko Lehtonen 1, Kaisa Poutanen 2, Seppo Auriola 1, Hannu Mykkänen 2 and Kati Hanhineva 2 1 School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, FI-70211, Kuopio, Finland, 2 Institute of Public Health and Clinical Nutrition, Clinical Nutrition, University of Eastern Finland, FI-70211, Kuopio, Finland Objective & Introduction Whole-grain rich diets have been associated with decreased risk of lifestyle related chronic diseases as well as e.g. improved insulin sensitivity and decreased inflammatory responses. However, biological mechanisms behind these effects are not yet well understood. Our objective was to use multi-organ approach to investigate changes in metabolic profile in mice fed with rye containing diets. Methods We had three study groups: 1) high-fat control diet, 2) high-fat diet enriched with intact rye bran and 3) high-fat diet enriched with bioprocessed rye bran. We used non-targeted HILIC-ESI-qTOF-MS metabolite profiling to measure changes in plasma, muscle and liver samples. Data analysis consisted of data preprocessing, statistical analysis and meta-analysis to detect commonly altered metabolites between different organs and study groups. Results & Conclusions Meta-analysis revealed that both study groups receiving rye enriched diets had increased levels of betaine metabolites in all measured sample types compared to high-fat control group. These results are in line with previous studies placing betaine metabolites as candidate molecules behind beneficial health properties of rye containing diets.

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INCREASED Γ-SECRETASE ACTIVITY IN IDIOPATHIC NORMAL PRESSURE HYDROCEPHALUS PATIENTS WITH Β-AMYLOID PATHOLOGY Tiina Laiterä1,2*, Timo Sarajärvi3*, Annakaisa Haapasalo3, Lakshman Puli4, Tarja Kauppinen3, Petra Mäkinen3, Tuomas Rauramaa5,6, Heikki Tanila4, Juha E. Jääskeläinen1,2, Irina Alafuzoff7, Hilkka Soininen3,8, Ville Leinonen1,2*, and Mikko Hiltunen3§* 1Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland, Kuopio, Finland, 2Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland, 3Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland , 4A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland, 5Institute of Clinical Medicine - Pathology, University of Eastern Finland, Kuopio, Finland, 6Department of Pathology, Kuopio University Hospital, Kuopio, Finland, 7Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden , 8Department of Neurology, Kuopio University Hospital, Kuopio, Finland *Equal contribution Objective & introduction: The potential similarity between the brain pathology of idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer disease (AD) is intriguing and thus further studies focusing on the underlying molecular mechanisms may offer valuable information for diagnostics and the development of treatments for iNPH. Methods: β- and γ-secretase activities were investigated in relation to amyloid-β (Aβ) pathology in the samples collected from iNPH and AD patients. β- and γ-secretase activities were measured from the frontal cortical biopsies of 26 patients with suspected iNPH and from the inferior temporal cortex of 74 AD patients. Results & conclusions: In Aβ+ iNPH samples γ-secretase activity was significantly increased (~1.6-fold) when compared to Aβ- iNPH samples (p = 0.009). In the AD samples differences in the γ-secretase activity were not observed with respect to disease severity (mild, moderate and severe). Conversely, β-secretase activity was unaltered in iNPH samples, while it was significantly increased in relation to disease severity in the AD patients. These results show for the first time increased γ-secretase but not β-secretase activity in the biopsy samples from the frontal cortex of iNPH patients with AD-like Aβ pathology. The opposite was observed in these secretase activities in AD with respect to neurofibrillary pathology. Thus iNPH and AD patients appear to have marked differences in the cellular mechanisms responsible for the production of Aβ.

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TRANSCRIPTOMICS AND MECHANISTIC ELUCIDATION OF ALZHEIMER’S DISEASE RISK GENES IN THE BRAIN AND IN VITRO MODELS Henna Martiskainen [1,2], J Viswanathan [2], N-P Nykänen [3], M Kurki [2], H Soininen [2], A Haapasalo [2], H J Huttunen [3], M Hiltunen [1,2] Institutes of [1] Biomedicine and [2] Clinical medicine – Neurology, University of Eastern Finland, [3] Neuroscience Center, University of Helsinki Several risk genes for Alzheimer’s disease (AD) have been identified, but their effects on disease pathogenesis remain elusive. Assessing the expression of these genes in the affected brain areas may help to identify their possible functions. Protein-fragment complementation assay (PCA) can reveal their effects on disease-associated pathways. The expression of genes involved in the pathogenesis or affecting the risk of AD was assessed in the post-mortem brain samples from 60 subjects with varying degree of AD-related neurofibrillary pathology. PCA was performed in HEK293T cells. AD-related neurofibrillary pathology associated with altered expression of risk genes FRMD4A, MS4A6A, CLU and TREM2. Using PCA, we found that down-regulation of FRMD4A associated with increased APP-β-secretase interaction, increased amyloid-β40 secretion and altered phosphorylation of tau. Taken together, we show that the expression of FRMD4A, MS4A6A, CLU, and TREM2 is altered in relation to increasing AD-related neurofibrillary pathology, and that FRMD4A may be associated with amyloidogenic and tau-related pathways in AD. In conclusion, studying the gene expression in the brain and the disease-associated pathways in vitro may provide mechanistic insights on how these genes contribute to AD pathogenesis.

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SEPT5 AND ITS POTENTIAL ROLE IN THE MOLECULAR PATHOGENESIS OF ALZHEIMER’S DISEASE Mikael Marttinen1,2, Kaisa M.A. Kurkinen1,2, Hilkka Soininen2, Annakaisa Haapasalo2 and Mikko Hiltunen1,2

1 Institute of Biomedicine 2Institute of Clinical Medicine – Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital Septins are a highly conserved family of guanosine triphosphate-binding proteins, which provide several candidates possibly involved in the underlying mechanisms of synaptic dysfunction in neurodegenerative diseases including Alzheimer’s disease (AD). Particularly SEPT5 has been shown to interact with syntaxin-1 of the SNARE complex and regulate synaptic vesicle (SV) localization at the presynaptic terminal. Furthermore, SEPT5 interacts with SEPT2/4/8, which all have been suggested to impact SV recycling. A central pathological feature in AD is amyloid-β (Aβ)-mediated synaptotoxicity. Thus, SEPT5 is an interesting target for further studies in the molecular pathogenesis of AD. Here, we have investigated the possible alterations in SEPT5 mRNA expression in relation to the AD-related neurofibrillary pathology in the temporal cortex of human brain. Furthermore, we investigated whether the siRNA-mediated down-regulation of SEPT5 in human SH-SY5Y neuroblastoma cells impacts amyloid precursor protein (APP) processing and Aβ production. Our data shows that the expression of SEPT5 is decreased in relation to AD-related neurofibrillary pathology in the brain, and that the down-regulation of SEPT5 reduces β-secretase (BACE1), soluble APPβ and Aβ levels in vitro. Our results suggest a role for SEPT5 in the regulation of post-translational levels and activity of BACE1 and subsequently Aβ generation.

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INHIBITOR PROFILING OF THE HUMAN Α/Β-HYDROLASE DOMAIN CONTAINING 11 (ABHD11) USING ACTIVITY BASED PROTEIN PROFILING (ABPP) Dina Navia-Paldanius1, Jayendra Patel2, Teija Parkkari2, Tapio Nevalainen2, Jarmo T. Laitinen1 and Juha Savinainen1

1School of Medicine, Institute of Biomedicine/Physiology, 2School of Pharmacy, University of Eastern Finland Serine hydrolases (SH) are crucial enzymes in many biological processes. Several of these enzymes are targets of approved drugs for numeral diseases, including metabolic, neurodegenerative and infectious diseases. Still, most of the human SHs remain poorly characterized with respect of their physiological substrates and inhibitors profiles. To explore the (patho)physiological role of SHs in human body, development of selective inhibitors is crucial. ABHD11 is a poorly characterized mitochondrial SH with a broad tissue distribution. The physiological role and substrate profile of ABHD11 are unknown and only a few described ABHD11 inhibitors can be found from the literature. To investigate the inhibition and selectivity of ABHD11 compared to human lysophospholipase A2 (LYPLA2) and arylformamidase (AFMID), we transiently transfected HEK293 cells with cDNAs of these SHs. Cell lysates of these SHs were pooled to facilitate screening and the inhibition was analysed by a competitive ABPP methodology by using a fluorescent fluorophosphonate probe TAMRA-FP. From over 250 compounds tested, we found three ABHD11-selective compounds with a nanomolar range potency. In order to map possible off-targets, we test the most potent compounds in mouse brain and various human cell proteomes.

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GENE REGULATORY NETWORKS OF VITAMIN D RECEPTOR Veijo Nurminen, Antonio Neme, Jussi Ryynänen, Sami Heikkinen, Sabine Seuter, Carsten Carlberg Institute of Biomedicine, UEF The vitamin D metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is the high affinity ligand of the transcription factor vitamin D receptor (VDR) and therefore a direct regulator of transcription. RNA-seq analysis of THP-1 human monocytes indicated more than 170 genes to be significantly (p < 0.001) stimulated after 4 h incubation with 1,25(OH)2D3. These include the genes encoding for the transcription factors BCL6, NFE2, POU4F2 and FOXF1, which are controlled by either one or two VDR binding sites within their chromosomal domains. The latter are defined via 3-dimensional DNA loop formation, mediated by the transcription factor CTCF being highly conserved in its genome-wide loci. BCL6 had preference for further analysis, since the gene was well responsive to 1,25(OH)2D3 and there was chromatin immunoprecipitation sequencing (ChIP-seq) data available for the transcription factor. A 24 h incubation of THP-1 cells with 1,25(OH)2D3 resulted in a significant (p < 0.001) change in the mRNA expression of more than 850 genes, of which 245 were at least 2-fold up-regulated. About half of the latter genes are secondary 1,25(OH)2D3 targets, since they do not carry any VDR binding site within their chromosomal domain. ChIP-seq and FAIRE-seq data indicated that the majority of these domains contain 1,25(OH)2D3-inducible BCL6 binding sites. We followed the secondary transcriptional response to 1,25(OH)2D3 for eight representative gene examples and confirmed the binding of CTCF and BCL6 to their respective chromosomal domains. In conclusion, our study indicated that in monocytes most of the physiological responses to 1,25(OH)2D3 involve the action of the transcription factor BCL6.

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THE TYPE II TRANSMEMBRANE SERINE PROTEASES HEPSIN AND TMPRSS3 ARE ASSOCIATED WITH BREAST CANCER SURVIVAL Mikko Pelkonen1, Kaisa Luostari1, Hermanni Ahonen1, Bozena Berdel1, Vesa Kataja2, Ylermi Soini1, Veli- Matti Kosma1, Arto Mannermaa1 1) Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland 2) Institute of Clinical Medicine, Oncology, University of Eastern Finland Hepsin (TMPRSS1) and TMPRSS3 are type II transmembrane serine proteases (TTSPs) that are involved in cancer progression. TTSPs remodel extracellular matrix (ECM) and, when dysregulated, promote tumor progression and metastasis. This study investigated whether the gene and protein expression levels of these TTSPs were associated with breast cancer characteristics or survival. Immunohistochemical staining was used to evaluate hepsin levels in 372 breast cancer samples and TMPRSS3 levels in 373 samples. TMPRSS1 mRNA expression was determined in 125 invasive and 16 benign breast tumor samples, and TMPRSS3 mRNA expression was determined in 167 invasive and 23 benign breast tumor samples. The gene and protein expression levels were analyzed for associations with breast cancer-specific survival and clinicopathological parameters. Low TMPRSS1 and TMPRSS3 mRNA expression levels were independent prognostic factors for poor breast cancer survival during the 20-year follow-up (TMPRSS1 P = 0.023 and TMPRSS3 P = 0.013). Low expression of the two genes at the mRNA and protein levels associated with poorer survival (P-values 0.015-0.042). Grade III tumors, large tumor size, and metastasis were associated with low mRNA and protein expression levels. The results suggest that the TTSPs hepsin and TMPRSS3 may have similar biological functions in the molecular pathology of breast cancer. Low mRNA and protein expression levels of the studied TTSPs were prognostic markers of poor survival in breast cancer.

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MASTICATION PROCESS AND EARLY PHASE DIGESTION OF RYE AND WHEAT BREADS Saara Pentikäinen 1, Nesli Sozer 1, Riitta Törrönen 2, Johanna Närväinen 1, Ulla Holopainen-Mantila 1, Anna-Marja Aura 1, Kaisa Poutanen 1,2 1 VTT Technical Research Centre of Finland, 2 Institute of Public Health and Clinical Nutrition, University of Eastern Finland Rye and wheat breads differ significantly in terms of both raw material and processing, resulting in different composition and structure. These differences are reflected in postprandial insulin responses, which have repeatedly and constantly been lower for rye bread. Little is known about the mastication process and degradation of breads in the early phase of digestion and the role of these in postprandial responses. 15 young, healthy females masticated 4 test breads in a random order. Test breads were refined wheat bread, whole meal rye bread, refined rye bread and refined rye bread with 5% gluten addition. The participant masticated the piece of bread (2x2x2 cm) until subjective swallowing point. The mastication process was characterized by measuring electrical activity of facial muscles by electromyography (EMG). Early phase starch hydrolysis rate by salivary alpha-amylase of bolus samples was measured in vitro. There were no differences between the breads in the number of chewing strokes, chewing time or time of EMG activity. However, mastication of whole meal rye bread required significantly more work compared to refined wheat bread. Refined rye bread with added gluten required significantly more work per bite than refined wheat bread. There was a trend towards lower starch hydrolysis rate in rye breads compared to wheat bread. The differences between breads in mastication-induced disintegration might offer explanations for previously observed differences in postprandial insulin responses.

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EFFECTS OF SUCROSE IN MICRO- AND PILOT SCALE FREEZE-DRYING ON SECONDARY PROTEIN STRUCTURES ASSESSED BY FTIR-ATR Björn-Hendrik Peters [1], Ferdinand Molnár [1], Jarkko Ketolainen [1]

[1] School of Pharmacy, University of Eastern Finland, Finland Objective. Microscale freeze-drying offers strongly needed short process cycles for early stage formulation development. To investigate scale dependent effects of sucrose, model protein secondary structures were compared between formulations prepared at microscale and pilot scale. Methods. Formulations consisted of 1% lysozyme (Dalian Greensnow, China) with increasing concentrations of sucrose (Sigma-Aldrich). Microscale freeze-drying was performed on a THMS350V heating stage (Linkam Scientific, UK). For pilot scale freeze-drying a Lyostar II system (SP Scientific) was utilized. Spectra were collected using a Nicolet 8700 FT-IR spectrometer (Thermo Fisher Scientific) and consist of 256 scans at a resolution of 2 cm-1. Principal component analysis of smoothed 2nd derivative amide I spectra was performed utilizing SIMCA-P+ (Umetrics AB, Sweden). Results. A sucrose concentration dependent shift from β-sheet (1641.15 cm-

1, 1630.55 cm-1) and β-turn (1689.36 cm-1) structures to α-helices (1653.69 cm-

1, 1652.72 cm-1) was observed. Furthermore, reduced variation between micro- and pilot scale samples at increased sucrose content was indicated. Conclusions. The results indicate that stabilization efforts undertaken at microscale could be transferred to pilot scale vial freeze-drying.

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NLRP3 INFLAMMASOME ACTIVATION BY IMPAIRED CELLULAR DEGRADATION IN HUMAN ARPE-19 CELLS Niina Piippo[1], Ayhan Korkmaz [2], Maria Hytti[1], Eveliina Korhonen [1], Kati Kinnunen [1,3], Kai Kaarniranta[1,3], Mustafa Atalay [2], and Anu Kauppinen[1,3] [1] Department of Ophthalmology, UEF, [2] Department of Physiology, UEF, [3] Kuopio University Hospital NLRP3 is a pattern recognition receptor sensing intracellular danger. It responds to a great diversity of signals ranging from invading pathogens to endogenous molecules. After activation, it coordinates the formation of the inflammasome complex followed by the secretion of the pro-inflammatory cytokines IL-1b and -18. Details how all these different signals can activate the same receptor have remained unresolved. In this study, we inhibited proteasomal degradation of ARPE-19 cells by treating cells with MG-132 as well as autophagy by bafilomycin A1 to model aged retinal pigment epithelial cells. With ELISA, western blot, siRNA treatments, and real-time PCR we monitored the inflammasome activation and probed for the possible activation mechanism(s). We observed increased levels of intracellular 4-hydroxynonenal (HNE), which alludes to increased oxidative stress, as well as increased extracellular ATP, which implicates to potassium efflux resulting e.g. from the activation of ATP receptors on the cell surface. In conclusion, declined cellular degradation activates NLRP3 inflammasomes in human ARPE-19 cells, and oxidative stress and potassium efflux may contribute to the activation process.

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STRUCTURAL AND FUNCTIONAL ANALYSIS OF THE VDR-DNA INTERACTIONS Viktória Prantner1, Paavo Honkakoski1, Ferdinand Molnár1

1School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland Objectives & Introduction: Vitamin D receptor’s (VDR) DNA-binding domain (DBD) recognises and binds VDR response elements (REs). VDREs are mostly formed by two hexameric half-sites with RGKTCA (R = A/G & K = G/T) consensus organised to direct repeat with three bases separating the half-sites (DR3). Apo VDR can bind DR3s also as a homodimer whereas holo VDR forms a heterodimer with retinoid X receptor (RXR). Methods: To date there are three VDR-VDR-DNA and one RXR-VDR-DNA crystal structure available. The binding to VDREs depends on the nature DNA-protein interaction e.g. monomer binding contribution and number of contacts. We calculated these parameters using programs from the CCP4 structural bioinformatics suite. In addition to in silico analysis we have provided data for VDR-RE binding from CYP24, CYP2B6 and CYP3A4 gene promoters. An approximation of structural data with transactivation assays have been also performed. Results & Conclusion: The analysis shows 88, 85, and 83 contacts for rOC, cDR3, and mSPP, respectively (cutoff 3.5Å). The interacting surface ratio for VDR-DNA-binding contribution is (upstream: downstream) 38.5:61.5% for rOC, 46.2:53.8% for the cDR3 and a reversed ratio of 57.3:42.7% for mSPP. Interestingly, for RXR-VDR it is 56.2:44.8% with higher contribution from RXR. In cells apo RXR-VDR performs the best on CYP24 RE. On CYP3A4 it has higher constitutive but lower ligand effect (6 to 11 fold) compared to CYP2B6, where the ligand effect is double compared to the apo heterodimer (2 to 6 fold).

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SYNTHESIS OF BISPHOSPHONATE MONOESTERS Elina Puljula, Janne Weisell, Jouko Vepsäläinen and Petri Turhanen School of Pharmacy, Biocenter Kuopio, University of Eastern Finland, PL 1627, 70210, Kuopio, Finland Bisphosphonates are used in the treatment of bone disorders, such as osteoporosis. Lately, bisphosphonate esters have also become of interest, since many esterified bisphosphonates have shown direct anticancer activity. Bisphosphonate monoesters are also structural analogs of several interesting compounds, such as phosphoantigens and mevalonate pathway intermediates, IPP (isopentenyl pyrophosphate) and DMAPP (dimethylallyl pyrophosphate). This inspired us to synthesize a series of bisphosphonate monoesters. Monoesters of a clinically used bisphosphonate, medronate, were synthesized by using a known method. Additionally, a purification method based on recent findings on the bisphosphonates’ binding affinity for hydroxyapatite was developed.

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A COCKTAIL APPROACH: A VALUABLE TOOL TO STUDY PHARMACOKINETIC AND DRUG METABOLISM WITH LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY Elena Puris [1], Aleksanteri Petsalo [2], Markku Pasanen [1], Risto Juvonen [1] [1] Department of Pharmacology and Toxicology, University of Eastern Finland; [2] Department of Pharmaceutical Chemistry, University of Eastern Finland The cytochrome P450 (CYPs) enzyme superfamily is of great importance in the process of biotransformation of xenobiotics and endogenous compounds. Phenotyping of CYPs allows evaluating the effect of drug therapies, different conditions, genetic polymorphism on enzyme activity and plays a crucial role in drug development, toxicological research and clinical practice. Two main phenotyping methods exist: selective and cocktail approach. The cocktail approach is a valuable strategy used for simultaneous investigation of activities of multiple CYPs in a single test. In my PhD research, modern liquid chromatography-mass spectrometry (LC-MS) techniques based on previous studies will be further developed and validated for the assessment of the metabolic effects of obesity surgery (Roux-en-Y gastric bypass, RYGB) utilizing cocktail approach both in vitro and in vivo. The proposed micro-dosing n-in-one assay utilizing nine drugs and their probe metabolites is the first attempt to such extensive evaluation of CYP metabolism in vivo. The developed micro-dose cocktail approach of nine different CYP probes with sensitive LC-MS detection is aimed to be used as a tool in clinical drug interaction studies of new investigational drugs and in targeted drug therapies.

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PREOPERATIVE AXILLARY STAGING WITH 3.0-T BREAST MRI: CLINICAL VALUE OF DIFFUSION IMAGING AND APPARENT DIFFUSION COEFFICIENT Suvi Rautiainen, Mervi Könönen, Reijo Sironen, Amro Masarwah, Mazen Sudah, Juhana Hakumäki, Ritva Vanninen, Anna Sutela

The axillary staging in newly diagnosed breast cancer is under major evolution. The aims of this study were to define the diagnostic performance of 3.0-T diffusion-weighted imaging (DWI) in the detection of axillary metastases in newly diagnosed breast cancer, to assess apparent diffusion coefficients (ADCs) for histopathologically confirmed metastatic lymph nodes in a clinical setting. Altogether 52 consecutive breast cancer patients underwent magnetic resonance imaging and DWI in addition to axillary ultrasound. ADCs of axillary lymph nodes were analysed by two breast radiologists and ultrasound-guided core biopsies were taken. In a separate reading by one radiologist two types of region of interests were used for a smaller group of patients. Altogether 56 axillae (121 lymph nodes) were included in the statistical analysis. Metastatic axillae (51.8%) had significantly lower ADCs (p<0.001). Mean ADCs were 0.663-0.676 x 10-

3 mm2/s for the histologically confirmed metastatic LNs and 1.100-1.225 x 10-3 mm2/s for the benign. The sensitivity, specificity, and accuracy of DWI were 72.4%, 79.6%, and 75.9%, respectively with threshold ADC 0.812 x 10-3 mm2/s. Region of interest with information on the minimum value increased the diagnostic performance (area under the curve 0.794 vs. 0.619). Even though ADCs are significantly associated with histopathologically confirmed axillary metastases the diagnostic performance of axillary DWI remains moderate and ultrasound-guided core biopsies or sentinel lymph node biopsies cannot be omitted.

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INCIDENCE OF BENZODIAZEPINE AND RELATED DRUG USE IN PERSONS WITH AND WITHOUT ALZHEIMER’S DISEASE – THE NATIONWIDE, REGISTER-BASED MEDALZ-STUDY Laura Saarelainen [1], Heidi Taipale [1], Marjaana Koponen [1], Antti Tanskanen [2], Anna-Maija Tolppanen [1], Jari Tiihonen [2], Sirpa Hartikainen [1] [1] School of Pharmacy, University of Eastern Finland, [2] Department of Clinical Neuroscience, Karolinska Institutet Objective & Introduction: Although benzodiazepines and related drugs (BZDR) are rarely recommended for the treatment of behavioral and psychological symptoms of dementia (BPSD), frequent use has been reported. We investigated the incidence of BZDR use in a cohort of persons with and without Alzheimer’s disease (AD) during a five-year follow-up. Methods: The study was based on the Finnish MEDALZ (Medication use and Alzheimer’s disease) cohort. Persons diagnosed with AD during 2005–2011 (n=70,718) were identified from the Special Reimbursement Register and the control cohort from a nationwide register including all residents. Incident use of BZDRs, including benzodiazepines and Z-drugs, was investigated from two years before to three years after the diagnosis of AD. Data on BZDR use were obtained from the Prescription register. Results & Conclusions: The incidence of BZDR use was higher in the AD cohort starting from one year before the diagnosis and was at highest at six months after the diagnosis of AD (incidence rate ratio 2.5, 95% confidence interval 2.3–2.6). The use of benzodiazepines was predominant in the AD cohort and, after the diagnosis, the incidence of benzodiazepine use remained more than three times higher than in the control cohort. More consideration is needed when treating BPSDs as concomitant use of BZDRs complicates the monitoring of antidementia drug treatment and, furthermore, severe adverse drug reactions are associated with BZDR use in older persons.

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HOW TO RECOGNIZE THE REWARDING FACTORS FROM NURSES’ POINT OF VIEW? Jaana Seitovirta [1], Tarja Kvist [1], Lasse Mitronen [2], Katri Vehviläinen-Julkunen [1] [1] Department of Nursing Science, University of Eastern Finland, Kuopio, [2] School of Business, Aalto University, Helsinki Previous studies have demonstrated that rewarding has significant effects on nursing outcomes and performance. This research produces information about nurses’ experiences and perceptions of rewarding in Finnish public special-, primary- and private health care. The aim is to recognize the rewarding factors from nurses’ point of view and to create a model for well-designed rewarding. Qualitative and quantitative methods are chosen as the research strategy. In qualitative research, the data (n=30) was conducted as an interview study and analyzed with a content analysis method. These interviews deepened the understanding about nurses’ rewarding. The nurses’ perceptions of rewarding and the background factors’ connection to them are studied with a quantitative method. The instrument (NPR= Nurses’ Perceptions of Rewarding -Scale) will be developed for this study. A specialist panel of nine nurses evaluated the developed instrument focusing on its clarity and necessity. The Instrument will be pre-tested with 10 registered nurses. The pilot study will be carried out with a discretionary sample to ensure the validity and the reliability among 450 nurses and the data will be analyzed statistically and multivariable methods by using the SPSS-program. The results of the study are expected to reform rewarding in Finnish health care.

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HEALTH AND SOCIAL CARE SERVICES IN TWO KARELIAS – AVAILABILITY AND SATISFACTION IN THE SPARSELY POPULATED AREAS Maria Semenova [1], Tiina Laatikainen [1], Tiina Vlasoff [2] [1] Institute of Public Health and Clinical Nutrition, University of Eastern Finland [2] North Karelia Centre for Public Health Objective & Introduction: The research project “Health and social care services in two Karelias – availability and satisfaction in the sparsely populated areas in the North Karelia and the Republic of Karelia” is a part of the of multidisciplinary development cross-border program ENPI CBC Karelia; project “Health in Focus” 2013-2014. The project aim is evaluation of the health and social care services utilization aspects (population needs, availability, accessibility, perceived quality of the services) as well as population’s participation possibilities in the various social- and health-related activities. Methods: The study material consists of self-administered questionnaires sent to 3000 respondents aged 20-70+ years old in the Republic of Karelia and the Northern Karelia during the autumn 2013 - winter 2014. The study data are comparable with The Regional Health and Wellbeing Study (ATH) (2011-2013). Results & Conclusion: The response rate was 52% in the North Karelia and 74, 9% in the Republic of Karelia. Self-perceived health status, levels of trust etc. varied between age groups and regions. The obstacles to health and social services accessibility included poor information accessibility (scanty Internet access among the elderly population, changes in the appointment systems).

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BIOMARKER DISCOVERY OF THE KEAP1-NRF2 -PATHWAY ACTIVATING DRUG CANDIDATES Virve Sihvola (1), Emilia Kansanen (1), Anna-Liisa Levonen (1) 1) Department of Biotechnology and Molecular Medicine, A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland Nuclear factor E2-related factor 2 (Nrf2) has a cytoprotective role in tissues by regulating many antioxidant genes and therefore protecting against the deleterious effects of reactive oxygen species (ROS). Inasmuch as ROS play a role in the pathogenesis of many inflammatory and degenerative diseases, it has a major impact in the development of inflammatory diseases. Therefore drugs that activate the system are of major interest in drug development. The aim of this study is to define other cytoprotective stress responses induced by Keap1-Nrf2 pathway activating electrophilic drug candidates in a cell culture model and in a mouse model and also to examine the potential biomarkers for the compounds. The compounds of interest are electrophilic drug candidates OA-NO2, TBE-31 and Bardoxolone. First, the optimal concentrations for these compounds were determined in vitro using human umbilical vein endothelial cells (HUVEC). The mRNA and protein expression levels of known target genes of the Keap1-Nrf2 pathway, Heat shock response, and ER-stress response were determined. After the initial in vitro screening, OA-NO2, TBE-31 and Bardoxolone will be administrated to mice, and the tissue and blood expression of the genes of interest will be determined. This study will identify novel biomarkers to monitor the efficacy of novel electrophilic drug candidates.

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PUPILS’ CHRONIC CONDITIONS AND MEDICINE USE IN SCHOOL – TEACHERS’ PERCEPTIONS AND EXPERIENCES Piia Siitonen[1], Riina Rytkönen[1], Sirpa Kärkkäinen[2], Kirsti Vainio[1] [1]School of Pharmacy, University of Eastern Finland, [2]School of Applied Educational Science and Teacher Education, University of Eastern Finland Objective & Introduction: In Finland, over 20% of children have at least one chronic disease. Many of these children who need medications might require them during school time. The aim of this study was to explore teachers’ perceptions and experiences of pupil’s chronic diseases and their medicine use during school time. Methods: Thirty-five semi-structured interviews were conducted among teachers of primary and lower secondary schools in Eastern Finland. Qualitative inductive content analysis was used to analyse the data. Results & Conclusions: In lower secondary school, pupils use medicines independently, and teachers were not aware of their medications. However, in primary school, children need teachers to assist in their medications. Teachers wanted to be more aware about pupil’s health conditions and medicines they need. Also training about chronic conditions and emergency medications was perceived as essential. In general, teachers are relying on school nurses regarding to medication administration, but the limited presence of school nurse was perceived as a challenge. Teachers needed more co-operation with families and health care providers, clear guidance instructing medication management, and clarity regarding roles of school staff in medication administration practices.

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CELLULAR AND NUCLEAR CONCENTRATIONS AND CYTOTOXICITY OF ANTICANCER DRUG DOXORUBICIN AND ITS LIPOSOMAL FORMULATIONS IN TWO CARCER CELL TYPES Suvi K. Soininen[1], Kati-Sisko Vellonen[1], Heta Koivisto[1], Arto Urtti[1,2], Marika Ruponen[1] [1]School of Pharmacy, University of Eastern Finland, Kuopio, Finland; [2]Centre for Drug Research, University of Helsinki, Helsinki, Finland Objective & Introduction. Nucleus is target site for an anticancer drug doxorubicin (DOX). The side-effects of DOX can be reduced by its encapsulation into liposomes. However, relationship of intracellular kinetics to cytotoxicity (i.e. effect) is not well understood. In this study, intracellular concentrations and cytotoxicity of DOX and liposomal DOX were evaluated in two cell types. Methods. The cellular and nuclear concentrations and cytotoxicity of DOX, pH-sensitive liposomal DOX (L-DOX) and pegylated liposomal DOX (CAELYX®) in rat glioma (BT4C) and human kidney carcinoma (Caki-2) cell lines were quantified as function of time by mass spectrometry and cell viability assay. Results & Conclusions. Due to the surface pegylation, the cellular uptake of CAELYX® was significantly lower (31 ‒ 136-fold) than of DOX and L-DOX. This explained also its low cytotoxicity in both cell lines. The nuclear concentrations of DOX, L-DOX and CAELYX® were at higher level (2.4 ‒ 52-fold) in Caki-2 cells than in BT4C cells, but in Caki-2 cells the cytotoxicity of L-DOX and CAELYX® were undetectable even at high exposures, and DOX was less toxic (84-fold) than in BT4C cells. Interestingly, in the case of CAELYX® all the uptaken drug was found in nuclei in both cell lines. Overall, no correlation between the nuclear concentrations and cytotoxicities were observed. This indicates that cell type characteristics (i.e. resistance) contribute to the target site concentrations and cytotoxicities of DOX and its formulations.

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IMPACT OF AN INTERVENTION ON CHILDREN’S DENTAL CARIES IN DEMOCRATIC PEOPLE’S REPUBLIC OF KOREA Tarvonen Pirkko-Liisa1,2, Sipilä Kirsi1,3,4,5, Yang Gon Suk6, Kim Jong Kil7, Lamidi Marja-Leena, Suominen Anna L1,3 1 Institute of Dentistry, University of Eastern Finland, Finland, 2 Oral Health Care, Social and Health Services, City of Helsinki, Finland , 3 Oral and Maxillofacial Department, Kuopio University Hospital, Finland , 4 Institute of Dentistry, University of Oulu, Finland, 5 Department of Oral and Maxillofacial Surgery, Medical Research Centre Oulu, Oulu University Hospital, Finland, 6 Korea Education Fund, DPRK , 7 Dental Faculty, Pyongyang Medical College, Kim Il Sung University, DPRK, 8 Faculty of Health Sciences, University of Eastern Finland Objective & Introduction: The aim was to compare the change in dental caries prevalence in two interventions of the Children’s Oral Health Promotion Programme (COHPP). Methods: A longitudinal study among children who had participated into COHPP for six years in Pyongyang, Democratic People’s Republic of Korea (DPRK). Children in Group I (n=250) received intensified prevention and were examined by dentist at 7 years (2007), 10 years (2010) and 13 years (2013). Children in Group II (n=250) were provided with less intense prevention and were examined by dentists at 7 years (2010) and 10 years (2013). The change in the sum of decayed teeth (dt+DT) was used as an outcome of the study. Associations between the change in the number of dt+DT and group status were determined by Poisson regression. Results & Conclusions: Mean number of dt+DT decreased in both groups during the follow-up. The intensified intervention showed no additional benefit compared to the less intense intervention. The association between the group status and the change in the number of dt+DT was not statistically significant when adjusted for gender and school. The research provides information on the oral health status of children in DPRK and on the impact of a low-cost prevention programme for developing countries.

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THE INCREASED ANTI-LEISHMANIA ACTIVITY OF BUBARVAQUONE USING MESOPOROUS SILICON NANOPARTICLES Thapa R1, Tandon R2, Mäkelä S1, Nissinen T3, Xu W3, Rytkönen J1, Peters B1, Lehto VP3, Madhubala R2, Närvänen A1. 1School of Pharmacy, University of Eastern Finland, Finland, 2 Jawaharlal Nehru University, New Delhi, India, 3 Department of Applied Physics, University of Eastern Finland, Finland Leishmaniasis is caused by protozoa with different type of skin and visceral infections, where the visceral infection is lethal when it is not treated. Until now the therapy is based on several non-specific and toxic compounds, which typically produce resistance during the therapy. Bubarvaquone (BPQ) is a potential therapeutic agent against leishmaniasis. However, BPQ is not used for human therapy due to the very high hydrophobicity and toxicity. To improve the efficiency of BPQ, we have used inorganic mesoporous silicon nanoparticles (PSi) to optimize the solubility and cellular internalization of BPQ. The nanoparticles were coated with avidin in order to change the relative hydrophobicity and facilitate the conjugation of antibodies. The antiprotozoal activity of BPQ-nanoparticle complexes were tested with the mouse macrophages infected with leishmania donovani (LD) amastigotes. Using 12.5 µg of the particles in 1 ml of culture medium corresponding to 2 µM concentration of BPQ the number of the amastigotes in infected macrophages was reduced about 75%. Particles, conjugated with IgM class antibodies against major leishmania surface antigen, lipophosphoglygan (LPG), did not interfere to the internalization to the cells in vitro. Mesoporous silicon nanoparticles are made from inorganic silicon and they have shown to be non-toxic for cells and they are optimal carriers for anti-protozoa drugs with low bioavailability.

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OVEREXPRESSION OF MICRORNA-200C PREDICTS POOR OUTCOME IN PATIENTS WITH PR-NEGATIVE BREAST CANCER

M. Tuomarila1, K. Luostari

1, Y. Soini

1, V. Kataja

2, V.-M. Kosma

1, A. Mannermaa

1

1) Institute of Clinical Medicine, Clinical Pathology and Forensic Medicine, University of Eastern Finland 2) Institute of Clinical Medicine, Oncology, University of Eastern Finland MicroRNA-200c is a member of the miR-200 family, and known to be dysregulated in invasive breast carcinoma. MiR-200c maintains the epithelial-mesenchymal transition and inhibits cell migration and invasion. Recent studies showed that miR-200c regulated steroid hormone receptors, estrogen receptors (ER), and progesterone receptors (PR). Here, we detected miR-200c in 172 invasive breast carcinomas from a prospective cohort enrolled in Kuopio, between 1990 and 1995. MiR-200c expression was determined with q-PCR, and results were compared to clinicopathological variables and patient outcome. We found that PR status combined with miR-200c expression was a significant marker of outcome. High miR-200c expression was associated with reduced survival in PR-negative cases (P = 0.002); low miR-200c expression indicated reduced survival in PR-positive cases (P = 0.004). In PR-negative cases, high miR-200c expression was associated with shortened relapse-free survival (P = 0.001), increased local/distant recurrence (P = 0.006), and more frequent distant metastasis (P = 0.015). We also found that high grade and low stage tumors were correlated with high miR-200c expression (P = 0.002 and P = 0.013, respectively). Our results indicated that miR-200c might play a role in invasive breast carcinoma. Furthermore, miR-200c combined with PR status provided a refined predictor of outcome. This data may provide a basis for new research target–PR-regulated microRNAs in breast cancer.

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TETA INHIBITS POLYAMINE UPTAKE AND SUPPRESSES CELL GROWTH Sebahat Ucal[1], Mervi T. Hyvönen[1], Sirpa Peräniemi[1], Jouko Vepsäläinen[1], Leena Alhonen[1], Tuomo A. Keinänen[1] [1] Department of Pharmaceutical Chemistry, School of Pharmacy, University of Eastern Finland The polyamines (PAs) spermidine (Spd) and spermine are present in all eukaryotic cells. They regulate important cellular functions, such as proliferation and differentiation. PAs are also recognized as biomarkers of cancer. Increased PA biosynthesis is a well-known promoter of carcinogenesis, and mutations in ornithine decarboxylase (ODC), is a hallmark of several cancer types. Difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, is in clinical use against African sleeping sickness. It has been extensively tested as a cancer therapeutic, both alone and in combination with other drugs. It is very effective cytostatic agent in vitro, but its clinical efficacy has been limited by the compensatory increase of the uptake of extracellular PAs into tumor tissue. Triethylenetetramine (TETA) is a charge-deficient isosteric analog of Spd and efficient Cu2+ chelator. It has been used as a drug for Wilson’s disease. Also preclinical in vivo and in vitro studies show that TETA may be a promising anticancer agent. Here we tested the anticancer efficacy of TETA alone and in combination with DFMO. According to our results, TETA markedly inhibited cell growth, suppressed PA uptake and completely prevented DFMO-induced increase in PA uptake in DU145 cells. The suppression of growth was attributed to its ability to induce ODC-antizyme, decrease ODC activity and reduce intracellular Putrescine and Spd pools. Thus, TETA-DFMO represents a promising combination anticancer therapy, and should be tested in vivo.

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CROSS-SECTIONAL ASSOCIATIONS OF PLASMA FATTY ACID COMPOSITION WITH PLASMA CONCENTRATION OF LEPTIN IN FINNISH CHILDREN Taisa Venäläinen1,2, Vanessa de Mello2, Ursula Schwab2, Jyrki Ågren1, Aino-Maija Eloranta1, Virpi Lindi1, Timo Lakka1

1Institute of Biomedicine, University of Eastern Finland; 2Institute of Public Health and Clinical Nutrition, University of Eastern Finland Objective: We investigated the associations of proportions of fatty acids (FA) in plasma cholesteryl esters (CE), phospholipids (PL) and triacylglycerols (TG) with plasma concentration of leptin among Finnish children. Methods: The subjects were a population sample of 376 children aged 6-8 years examined at baseline in the Physical Activity and Nutrition in Children study. Plasma FA composition was measured by gas chromatography and plasma concentration of leptin by radioimmunoassay. Data were analyzed using linear regression models. Results: Higher proportions of myristic acid and lower proportions of cis-vaccenic acid in plasma CE, PL and TG were associated with higher plasma concentration of leptin. In CE, higher proportion of gamma-linolenic acid and lower proportion of arachidonic acid were associated with higher leptin concentration. In PL, higher proportion of linoleic acid and lower proportions of nervonic and arachidonic acids were associated with higher leptin concentration. In TG, higher proportions of palmitic, stearic and gamma-linolenic acids and lower proportions of linoleic, oleic, cis-vaccenic and docosapentaenoic acids were related to higher leptin concentration. Conclusions: Higher proportions of gamma-linolenic acid and SFA, especially myristic acid, and lower proportions of many MUFA and PUFA in plasma are associated with plasma concentration of leptin in children. FA in plasma TG fraction seem to have the strongest associations with plasma leptin concentration.

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EFFECTOR T CELL RESISTANCE TO TREG SUPPRESSION IN TYPE 1 DIABETES PATIENTS AND AUTOANTIBODY-POSITIVE AT-RISK SUBJECTS Viisanen Tyyne[1], Ihantola Emmi-Leena[1], Näntö-Salonen Kirsti[2], Veijola Riitta[3], Toppari Jorma[4], Knip Mikae[5], Pihlajamäki Jussi[1], Ilonen Jorma[1.4], Kinnunen Tuure[1] [1]University of Eastern Finland, Kuopio [2]Turku University Hospital, Turku [3]University of Oulu [4]University of Turku [5]University of Helsinki OBJECTIVE AND INTRODUCTION: Defects in immune regulation appear to be important for the pathogenesis of type 1 diabetes (T1D). Several studies have shown that CD4+CD25- T effector cells (Teffs) are not efficiently suppressed in vitro by CD4+CD25+ regulatory T cells (Tregs) in patients with T1D. The underlying mechanisms behind Teff resistance in T1D are not sufficiently understood but increased STAT3 phosphorylation through proinflammatory cytokine IL-6 signaling has been associated with Teff resistance in patients with multiple sclerosis. Moreover, the important question whether the defect in Treg suppression of effector T cells precedes the onset of clinical T1D remains unanswered. METHODS: We aimed to determine the degree of Teff resistance to Treg suppression at different stages of T1D development by analyzing effector T cells isolated from the peripheral blood samples of autoantibody-positive at-risk subjects as well as T1D patients with recent-onset disease. We have optimized our Treg suppression assay to specifically detect defects in Teff cells by 1) using an antigen-presenting cell-free stimulation system (anti-CD2/CD3/CD28-coated microbeads), 2) using a single source of in vitro expanded Tregs from a healthy donor and 3) using purified memory CD4+CD25- T cells as Teffs. RESULTS: In line with previous studies, we observed that the effector T cells of T1D patients with recent-onset disease were resistant to Treg-mediated suppression. Interestingly, effector T cells from autoantibody-positive at-risk subjects appeared also to be resistant. STAT3 inhibition experiments demonstrated that this resistance is largely mediated by increased STAT3-phosphorylation in the effector T cells of the subjects. CONCLUSIONS: Our results suggest that the resistance of effector T cells to Treg suppression arises already before the clinical manifestation of type 1 diabetes and appears to be associated with increased STAT3 phosphorylation in effector T cells.

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CHARACTERIZATION OF THE MICROBIAL POPULATIONS INATOLE AGRIO, A TRADITIONAL MEXICAN FERMENTEDBEVERAGEVakevainen K[1], Valderrama A[2], Espinosa J[3], Centurión D[3], Sainz T[4],Díaz-Ruiz G[2], von Wright A[1], Plumed-Ferrer C[1], Wacher C[2][1]Institute of Public Health and Clinical Nutrition, University of Eastern Finland,[2]Universidad Nacional Autónoma de México, [3]Universidad Juárez del Estadode Tabasco, [4]UAM-XOCHIMILCOIn Latin America, fermented foods are an important part of the diet. Thesefoods are made of plants or animal materials by spontaneous fermentationdriven by the microbiota naturally present in raw materials. Fermentationcan improve the microbiological safety, quality, nutritional value andorganoleptic properties of foods. However, fermentations should becontrolled and predictable. This can be achieved by using defined mixturesof microbes as starter cultures. Lactic acid bacteria (LAB) are the mostcommon microorganisms found in both traditional and starter-guidedindustrial fermentations. The aim of this study was to characterize themicrobial populations of atole agrio, a traditional fermented Mexicanbeverage. Atole agrio is prepared by spontaneous fermentation of maize andwater. Total mesophiles, LAB, yeasts, molds and Enterobacteriaceae weremeasured by plating technique, as well as the pH. The results showedrelatively low levels of LAB (6.7 log cfu/ml) throughout the fermentation.The average level for total mesophiles was 8.3, yeasts and molds 6.9 andEnterobacteriaceae 5.8 log cfu/ml. The pH decreased from 7.5 to 4.5. Due tothe short period of fermentation, the microbial community remainedrelatively stable. However, increasing the initial levels of LAB could alterthe total microbial community and improve the organoleptic properties ofthe product. The research will continue by improving the quality andorganoleptic properties of atole agrio by applying the LAB strain embossingthe best growth properties as a starter.

MAGNETIC RESONANCE SPECTROSCOPY (MRS) OF POST-TRAUMATIC EPILEPTOGENESIS Amna Yasmin1, Riikka Immonen1, Olli Gröhn1 and Asla Pitkänen1

Department of Neurobiology, A.I. Virtanen Institute, University of Eastern Finland Traumatic brain injury (TBI) may lead to post traumatic epilepsy later in life. The cortical tissue surrounding the impact injury site has been suggested to play a key role in initiating seizures. Conventional magnetic resonance imaging (MRI) detects several structural alterations across trauma brain, however, in this perilesional cortex the tissue appears normal. Proton Magnetic resonance spectroscopy (1H-MRS) offers a non-invasive approach to quantify cellular metabolite concentrations. Previous TBI studies showed altered metabolite concentrations (reduced NAA, increased Cho, and increased myo-inositol levels) in regions that appear normal at MR imaging, indicating that 1H-MRS has potential to detect neuronal injury, plastic changes and gliosis following TBI. The aim of study was to determine metabolic profile of up to 15 in vivo detectable neurochemicals in perilesional cortical area in clinically relevant lateral fluid percussion injury (LFPI) rat model and correlate MRS findings with MRI, EEG and histological outcomes. 1H-MRS was carried out at 9.4 Tesla high field magnet at 1 month and 3 months (progressive) post injury from single perilesional voxel (1*3*5mm) by PRESS (TE 11ms, TR 2500ms, 320/640 averages for sham/TBI). Spectra were analysed by LC model, only metabolites SD%≤ 20 were included. Our results indicated markedly increased myo-inositol levels in the perilesional cortex, indicating gliosis. The elevated glutathione may reflect potential on-going oxidative stress. Phosphocholines are linked to membrane turnover. Together these findings could suggest persistent local inflammation following TBI.

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Graphical abstracts from course (not presented)

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Guerrero Toro Cindy: Pro-nociceptive effects of ATP and its derivatives in rat trigeminal ganglia

Hytti Maria: Fisetin and Luteolin decrease oxidative stress-induced inflammation and cytotoxicity in ARPE-19 cells

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Jalkanen Henna: Eating behavior and food intake in children ages 6-8 years

Jawhar Deen Ashik: Rab10-mediated endocytosis of Hyaluronan synthase HAS3 regulates hyaluronan synthesis and cell adhesion to collagen

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PDGFR-Β-EXPRESSING NG2 CELLS RELOCATE TO HIPPOCAMPAL SUBFIELDS VULNERABLE TO NEURODEGENERATION AFTER STATUS EPILEPTICUS Jenni Kyyriäinen1, Xavier Ekolle Ndode-Ekane1, Asla Pitkänen1 1Epilepsy Research Laboratory, A.I. Virtanen Institute, University of Eastern Finland Interaction between platelet derived growth factor receptor β (PDGFR-β) and urokinase-type plasminogen activator receptor (uPAR) increases cell survival. To understand the PDGFR-β/uPAR interaction, we characterized the expression of PDGFR-β in the hippocampus after status epilepticus (SE). Status epilepticus was induced in adult male C57BL/6JOlaHsd mice by intrahippocampal injection of kainic acid. Animals were sacrificed at 1d, 4d and 7d post-SE, for immunohistochemical assessment of PDGFR-β positive cells. The total number of the cells was estimated using unbiased stereology. In the normal hippocampus, PDGFR-β-positive cells were homogeneously distributed. After SE, ipsilaterally, the total number of cells did not differ with controls. Interestingly, the cells relocated to the hilus and CA3 subfield. Their total number in the hilus at 4d and 7d increased by 179% and 227% (p<0.05). In the CA3 area, at 7d, their number increased by 201% when compared to controls (p<0.05). Contralaterally, the cell distribution was same as in controls. However, the total number of cells dropped to 58% of control values at 1d and then increased to 72% at 4d and 81% at 7d (p<0.05). Double labelling revealed that the cells where either NG2 cells or astrocytes. This data suggest that, after an epileptogenic brain injury, PDGFR-β cells accumulate into hippocampal subfields vulnerable to severe damage, indicating a possible role in neuroprotection.

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PROFILING OF TRANSCRIPTOME IN EXPERIMENTAL TRAUMATIC BRAIN INJURY IN RATS Anssi Lipponen[1], Mikko Hiltunen[2], Jussi Paananen[3], Noora Puhakka[1] and Asla Pitkänen[1][1] A.I. V Institute, University of Eastern Finland; [2] Institute of Biomedicine, University of Eastern Finland; [3] Bioinformatics Center, University of Eastern Finland Traumatic brain injury (TBI) is estimated to cause 10-20% of all acquired epilepsies. After the initial damage caused to the head, secondary damage develops over time consisting changes which can lead to epileptogenesis. Brain areas have distinct gene expression profiles and alterations in molecular functions and pathways can be different between brain areas in post TBI epileptogenesis. To address this question, TBI was induced with lateral fluid-percussion injury to adult rats (n=5). Five sham-operated rats served as controls. At 3 months post-TBI coronal slices were sectioned to sample the cortex, thalamus and hippocampus for transcriptome sequencing (RNA-Seq). In the cortex 4964, thalamus 1966 and hippocampus 1 gene was differentially expressed as compared to controls (adj.P<0.05). A totally of 1353 genes had altered expression in both cortex and thalamus. Hippocampus did not have parallel alterations with other brain areas. Analysis of molecular functions indicated down regulation in ion channels. This preliminary result suggests that a long-lasting down regulation of genes coding for ion channels after TBI in the cortex, thalamus and hippocampus maybe involved in post-traumatic epilepsy.

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QUALITY QUALITY OF LIFE IN PATIENTS WITH AGE-RELATED MACULAR DEGENERATION (AMD) Jussi Paterno [1], Kai Kaarniranta [1]. Department of Ophthalmology, University of Eastern Finland In Finland 100 000 persons live with the eye disease called AMD. With our aging population AMD’s rate will increase. In senior citizens, half of the vision impairment is due wet AMD. Its progression leads to rapid vision impairment in few weeks time. Fortunately, the revolution in treatment of wet AMD has occured within last decade. Now copious drug choises can be used to treat effectively the injurious wet AMD manifestations, by injections inside the eye. On the flip side is how costly and long lasting this treatment can be, and how the treatment appears only delay vision impairment. Current belief is that the treatment is cost-effective with existing drugs, as on the average a typical AMD patient will benefit from the treatment. This is traditionally measured by visual acuity (VA). However, it is also important to focus on quality of life (QOL). We will evaluate the burden of wet AMD in the Finnish elderly by using domestic 15D questionnare to measure QOL. The aim is to validate 15D with other questionnares previously used as QOL indicators in AMD. We will also estimate how treatment will affect to VA, QOL and quality-adjusted life years (QALYs) in wet AMD patients. This will provide vital knowledge how to optimize current AMD treatment protocols.

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Thangiai Arasu Uma: Extracellular Vesicles as carriers of Hyaluronan (HA) and their role as novel biomarkers

Vuorio Taina: The expression of soluble VEGFR3 in an atherosclerotic mouse model increases cholesterol levels and accelerates atherogenesis

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Doctoral Programmes

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DOCTORAL PROGRAMME OF CLINICAL RESEARCH The Doctoral Program of Clinical Research (DPCR, http://www2.uef.fi/fi/dpcr ) is a multidisciplinary program that covers all the specialties in clinical medicine. The purpose of the program is to support the process of doctoral theses, particularly those related to clinical research or clinical materials. It serves researchers in all health care units that are part of the special responsibility area (ERVA) of Kuopio University Hospital (KUH) and cooperates with The National Graduate School of Clinical Investigation (CLIGS).

The purpose of the training provided by the doctoral program is to create professionals with skills for independent and team-based clinical research projects. Therefore, it is recommended that all doctoral students in the DPCR attend the courses Introduction to Clinical Research (1 ECTS) and Seminar series of the Graduate School of Clinical Research (2 ECTS) as well as Introductory Course for a Clinical Researcher (5 ECTS; web-course) provided by the Science Service Center of KUH. In addition, it is recommended that all doctoral students attend and present their results in at least one international scientific conference.

Students apply in the DPCR according to UEF instructions. The Applicant should have either completed or currently ongoing applicable Master's degree (MD etc.) and ongoing or planned research project suitable for doctoral dissertation project with a research plan approved by supervisors for the doctoral dissertation.

The leader of the DPCR is Professor Anne Remes ([email protected]). The contact persons are the Coordinator of the Doctoral Program, docent Ville Leinonen ([email protected]) and Project Coordinator Saara Happo ([email protected]).

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http://www2.uef.fi/fi/dpcr

mailto:[email protected]



DOCTORAL PROGRAMME MOLECULAR MEDICINE

The Doctoral Program in Molecular Medicine (DPMM) (http://www2.uef.fi/fi/DPMM) is an interdisciplinary doctoral training program with the purpose of training researchers as international experts in modern biomedicine. Molecular medicine studies the causes and mechanisms of origin of diseases on a molecular level and strives to find methods to treat and prevent these diseases.

Research fields in the program range from basic laboratory sciences and diagnostics to applied clinical research. The doctoral program concentrates on the research of major diseases, such as cardiovascular diseases, type 2 diabetes, obesity, neurological diseases, inflammations, and cancer, as well the possibilities provided by stem cell technologies in the treatment of various diseases.

DPMM offers high quality PhD training by organizing scientific courses, seminar series and providing PhD supervision. PhD students work as researchers in the groups belonging to the program.

Doctoral training is organized by A. I. Virtanen Institute and School of Medicine in the University of Eastern Finland. Director of DPMM is Academy Professor Seppo Ylä-Herttuala. Contact person: Coordinator Joanna Huttunen, [email protected].

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http://www2.uef.fi/fi/DPMM


DOCTORAL PROGRAMME IN NURSING SCIENCE – systematic education for future researchers and experts Katri Vehviläinen-Julkunen, professor, director of the Doctoral Programme in Nursing Science; Tarja Kvist, PhD, university researcher; Reeta Lamminpää, PhD -student, MSc

Why doctoral education in nursing science? Doctoral education in nursing started in 1930’s in the United States of America. The need for PhD prepared nurses has been globally evident. Changes in the health care systems and new innovations in care settings as well as several challenges in the society are highlighting the need for a systematic doctoral education. PhD educated nurses with researcher training are needed in clinical practice, leadership positions and educational institutions as well as in research. In Finland, since 1979, doctoral education has been offered in nursing and health sciences. Since then a total of 100 PhDs have got their doctoral degree in UEF. What UEF is offering and how networking is arranged? In the University of Eastern Finland doctoral education in nursing science is arranged within the framework of the Doctoral Programme in Nursing Science (DPNursing, http://www2.uef.fi/fi/dpnursing) provided by the Faculty of Health Sciences. The programme arranges PhD-courses and seminars in the field of nursing science discipline and transferrable skills. The purpose of the DPNursing is to train excellent, internationally oriented researchers and experts with doctoral education for a variety of national and international duties. Other aims are to improve their research careers and to strengthen multidisciplinary research. Annually 6-8 doctoral degrees are granted. The Doctoral Programme (DPNursing) in UEF works in close cooperation with the Finnish Doctoral Education Network in the field (a network of five universities – University of Eastern Finland, University of Oulu, University of Tampere, University of Turku and Åbo Akademi). The network has been financed by the Academy of Finland. The Network coordinates doctoral courses in nursing science with the participating universities. Annually 6-8 courses with 6 ECTS are offered by the network. Courses are held by international and national experts. The course calendar includes topics such as qualitative and quantitative research methods, action research, perspectives on preventive nursing and nursing education research, health services research and research ethics. Doctoral training involves an opportunity for collaboration in multidisciplinary doctoral programmes, too. Students can benefit from training and education provided by international networks and doctoral schools. How to apply? Students are selected to the programme twice a year. Students apply the right to perform postgraduate studies in the Doctoral Programme in Nursing Science according to UEF instructions. Application form and instructions can be found at UEF Graduate School Internet site.

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http://www2.uef.fi/fi/dpnursing

DOCTORAL PROGRAMME OF PUBLIC HEALTH -Top Quality Research with a Mission of Health Promotion

Jussi Kauhanen, Mika Venojärvi

Institute of Public Health and Clinical Nutrition, University of Eastern

Finland;

The Doctoral Programme in Public Health (DPPH) at the University of

Eastern Finland introduces doctoral students to a multidisciplinary world

of health-related phenomena and research. Students enter our programme

with different backgrounds and prior degrees. Health itself, however, is

always at focus in our training, as well as health promotion as the practical

goal. But the research methodology and theoretical foundations can be

tracked to multiple scientific disciplines. Students are often surprised to

learn that there may be various ways to solve scientific problems, and this

in part makes the doctoral training in public health so fascinating. The

main educational goal of the Doctoral Programme is to train academic

professionals to meet high international standards in scientific research,

higher education, public sector administration, NGO’s, and private sector,

both in the settings of national and international cooperation. Our doctoral

student body is a sort of microcosm, since currently about half of the

students are non-Finnish in origin. So multiculturality is yet another word

to describe us.

Do you find these to be interesting prospects for you? Then go ahead and

contact us at:

http://www2.uef.fi/fi/dpph/etusivu

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http://www2.uef.fi/fi/dpph/etusivu

DOCTORAL PROGRAMME IN DRUG RESEARCH

-in a nutshell The Doctoral Programme in Drug Research (DPDR, http://www2.uef.fi/fi/dpdrugresearch) is a multidisciplinary programme that covers all topics of drug research and toxicology at the UEF. DPDR is an active member in the national FinPharma network.

Studies at the DPDR DPDR students will perform their studies according to the degree requirements of the programme which are listed in the UEF postgraduate study guide. After receiving acceptance from the Faculty, DPDR student design their personal study plans (Figure) and begin training in transferable skills and subject-specific areas that are provided by the Faculty and DPDR, FPDP and other Doctoral programs, respectively. FPDP joint meetings contribute to networking and career development.

The entrance examination guarantees that basic knowledge about research and activities in pharmacy is obtained and the research plan defense provides practice for the actual PhD defense and also a valuable source of scientific input to research problems.

Figure. Post-graduate study process at the DPDR.

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http://www2.uef.fi/fi/dpdrugresearch

Research at the DPDR

Research in the School of Pharmacy (http://www.uef.fi/en/farmasian-laitos/research) has been organized into six strategic research areas, to which research groups belong:

• Drug design and discovery • Drug-like properties of drug substances (ADMET research) • New drug formulations and process analysis techniques (PAT) • Evaluation of efficacy of drug treatment • Neurobiology and pharmacology • Toxicology

The PhD students conduct their research in projects associated with these areas under the guidance of their supervisors. Increasingly, cross- and multidisciplinary research projects

National collaboration

The FinPharma Doctoral Program (FPDP; www.fpdp.fi) is a national network for coordinated training in drug research and toxicology for PhD students. The main participating Doctoral Programs are from Universities of Helsinki, Eastern Finland, and Turku. Some supervisor and student members belong to Universities of Oulu, Tampere, Åbo Akademi and Jyväskylä. FPDP activities are organized in four sections (Drug Discovery, Pharmacy, Clinical Drug Research and Toxicology).

FPDP enhances national and international networking by the four sections’ courses and other activities, by awarding travel grants to domestic and international courses and laboratory visits and by cooperation with the pharmaceutical industry, regulatory authorities and societies.

All members of the local Doctoral Programs belong automatically to the FPDP, conform to its regulations, and can utilize its activities.

FPDP is directed by professor Raimo Tuominen and the coordinator is Ilkka Reenilä, both at the University of Helsinki.

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http://www.fpdp.fi/

DOCTORAL PROGRAMME IN NUTRITIONAL SCIENCES The purpose of the Doctoral Programme in Nutritional Sciences is to provide interdisciplinary doctoral training for students of nutritional sciences and its neighbouring disciplines who are interested in the interlink between nutrition and health and the relevancy of nutrition in the promotion of health and treatment of diseases. The main research lines at the Unit of Clinical Nutrition are ‘Diet and Chronic Disease’, ‘Food and Health’ and ‘Food Biotechnology and Safety’ and they all serve the common goal to identify the role of diet, foods and food components in the maintenance of health and treatment of diseases. Besides routine clinical methods, we also apply the systems biology tools to analyze the underlying tissue-level effects of the studied dietary modifications. Main food items in our studies have been whole grains, fish and berries. More information: http://www2.uef.fi/en/dpntr/tutkimusryhmat. At the moment around 20 students belong to the Doctoral Programme in Nutritional Sciences. Their background education on master level is in most of the cases nutrition, but there are also students with the background of e.g. medicine, food chemistry, molecular biotechnology, animal physiology or molecular biology. How to apply and postgraduate training Students apply the right to perform postgraduate studies in the Doctoral Programme in Nutritional Sciences according to UEF instructions. http://www2.uef.fi/en/dpntr/hakeminen Students perform their postdoctoral studies according to the degree requirements of the programme. Degree requirements and postgraduate courses offered by UEF graduate school and Doctoral programmes can be found in WebOodi or in the UEF postgraduate study guide. More information: http://www2.uef.fi/en/dpntr/jatkokoulutus

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http://www2.uef.fi/en/dpntr/tutkimusryhmat

http://www2.uef.fi/en/dpntr/hakeminen

http://www2.uef.fi/en/dpntr/jatkokoulutus

Contact information Director: Jussi Pihlajamäki, professor, clinical nutrition, jussi.pihlajamaki (at) uef.fi Contact person: Leila Karhunen, PhD, senior lecturer, leila.karhunen (at) uef.fi

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Notes

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Publications of the University of Eastern FinlandReports and Studies in Health Sciences No 18



Health Sciences


The Second PhD student Symposium of the Faculty of Health Sciences

Publications of the University of Eastern Finland

Reports and Studies in Health Sciences

ISBN: 978-952-61-1787-4

Documents

Riikka Pellinen (toim.) The Second PhD student Symposium ... · 12.15-12.30 Kuosmanen Suvi: MicroRNA profiling of pericardial fluid samples from patients with heart failure 12.30-12.45