Abstract Skin diseases are common: one in every three of all general practice patients have at least one dermatological problem. However, epidemiological studies addressing the overall prevalence of skin diseases are sparse. The skin is the largest organ in the body and it has several vital and immunological functions. Cutaneous signs are often the first manifestation of many systemic diseases. The aim of this study was to determine the overall prevalence, and the distribution according to sex and socioeconomic status, of skin diseases in an adult population. The study particularly focused on multiple melanocytic naevi and their risk factors because multiple melanocytic naevi are the strongest risk factor for melanoma. A further aim was to analyse the association between cutaneous disorders and systemic conditions; specifically to determine whether abnormal skin findings in toe webs have an association with abnormal glucose metabolism and whether skin diseases have a relationship with systemic low-grade inflammation. For these purposes a comprehensive dermatological evaluation was performed as a part of the 46-year follow-up survey of the Northern Finland Birth Cohort 1966. Data on this cohort have been collected since birth. Numerous laboratory tests were also performed cross-sectionally during the 46-year follow-up survey, including an oral glucose tolerance test and the measurement of fasting plasma glucose and glycated haemoglobin fraction. High sensitivity C-reactive protein was measured as a marker of low-grade inflammation. Over half (60%) of the 1 932 individuals examined had at least one skin disorder requiring further treatment. The need for treatment was more common in males and those with lower socioeconomic status. Multiple melanocytic naevi were found in 12% of individuals; high educational level, male sex and fair skin type increased the risk. Abnormal skin findings in toe web spaces was associated with undiagnosed type 2 diabetes. Atopic eczema, rosacea and onychomycosis were associated with low-grade inflammation. This unique study with nearly 2 000 subjects reports for the first time the overall prevalence of skin diseases in an unselected Finnish population. Its findings support the previous postulate that skin diseases are common in adults and suggest that skin evaluation should be an essential part of routine medical examinations in clinical practice. / Tiivistelmä Ihotaudit ovat yleisiä, ja jopa 30 %:lla yleislääkärin potilaista on jokin ihoon liittyvä ongelma. Väestötason tutkimuksia ihotaudeista on kuitenkin niukasti. Iho on ihmisen suuri elin, ja sillä on useita tärkeitä tehtäviä, kuten osallistuminen immunologiseen puolustukseen. Monet yleissairaudet voivat näkyä iholla jo ennen taudin puhkeamista ja ihoilmentymät voivat olla varhaisia merkkejä piilevästä sairaudesta. Tämän tutkimuksen tarkoituksena oli määrittää ihotautien esiintyvyys aikuisväestössä sekä ihotautien jakautuminen sukupuolen ja sosiaalisen aseman suhteen. Lisäksi tarkoituksena oli selvittää runsasluomisuuden (yli 50 pigmenttiluomea) esiintyvyyttä ja sen riskitekijöitä, sillä runsasluomisuus on melanooman merkittävin riskitekijä. Tutkimuksen tavoitteena oli myös selvittää ihotautien yhteyttä yleissairauksiin, kuten poikkeavien varvasvälilöydösten yhteyttä häiriintyneeseen sokeriaineenvaihduntaan sekä matala-asteisen tulehduksen ja ihotautien välistä yhteyttä. Osana Pohjois-Suomen syntymäkohortti 1966:n 46-vuotistarkastusta tehtiin kokonaisvaltainen ihon tutkiminen yhteensä 1 932:lle tutkimushenkilölle vuosina 2012–13. Samassa yhteydessä tutkittavilta määritettiin paastoverensokeri ja pitkäaikainen verensokeri sekä tehtiin sokerirasitustesti sokeriaineenvaihdunnan häiriön toteamiseksi. Matala-asteisen tulehduksen arvioimiseksi määritettiin herkkä C-reaktiivinen proteiini. Tutkimusjoukon pitkäaikaiset taustatiedot perustuivat syntymäkohortin aiempiin aineistoihin. Tutkittavista 60 %:lla todettiin jokin hoitoa vaativa ihotauti. Hoidon tarve oli suurempaa miehillä ja matalammissa sosiaaliluokissa. Runsasluomisuutta esiintyi 12 %:lla, ja korkea koulutustaso, miessukupuoli ja vaalea ihotyyppi lisäsivät riskiä. Varvasväleissä esiintyvät muutokset liittyivät diagnosoimattomaan diabetekseen. Atooppinen ihottuma, ruusufinni ja kynsien sieni-infektioon sopivat muutokset olivat yhteydessä matala-asteiseen tulehdukseen. Tämä lähes 2 000 henkilön koko ihon kliiniseen tutkimukseen perustuva työ raportoi ensimmäistä kertaa ihotautien yleistä esiintyvyyttä suomalaisessa, valikoitumattomassa väestössä. Tutkimus tukee aiempaa oletusta, jonka mukaan ihotaudit ovat aikuisväestössä yleisiä; ihon tutkiminen tulisi olla oleellinen osa potilaan kliinistä perustutkimusta.

Low-grade gliomas (LGGs) constitute a major challenge for health care because of their location and nature. LGGs are often found in eloquent areas, and their infiltrative growth cause neurological reorganization, which complicates the mapping of important functions. Awake surgery in combination with direct electrical stimulation (DES) and intraoperative tests is a relatively new method for mapping the brain's functional limits, thus eliminating as much of the tumor as possible while maintaining important functions. At present there is no available intraoperative test for semantic processing in Swedish. Tests of specific linguistic abilities improves the specificity of mapping which reduces post-operative linguistic impairments. Intraoperative tests can thus contribute to increased quality of life in the patient group. This study was based on the Dutch Lingusistic Intraoperative Protocol (DuLIP) test battery to create a Swedish version of the subtest semantic odd word out (SOWO). SOWO tests semantic processing via lexical reading. The adjusted and extended version of SOWO was tested during a pilot trial on 26 standard-language people. The study has resulted in a new semantic intraoperative test in Swedish that will be clinically examined at University Hospital in Uppsala. Hopefully, the new test contributes to better treatment options for patients with LGG. / Lågmaligna tumörer (LGG) utgör en stor utmaning för vården på grund av deras lokalisation och karaktär. LGG återfinns ofta i elokventa områden och deras infiltrativa växtsätt orsakar neurologisk omorganisering, vilket komplicerar kartläggning av viktiga funktioner. Vakenkirurgi i kombination med direkt elektrisk stimulering (DES) och intraoperativa tester är en relativt ny metod för att kartlägga hjärnans funktionella gränser och därmed kunna avlägsna så stor del av tumören som möjligt samtidigt som viktiga funktioner kan bevaras. I dagsläget finns det inget tillgängligt intraoperativt test för semantisk bearbetning på svenska. Tester av specifika lingvistiska förmågor förbättrar specificiteten av kartläggningen vilket minskar postoperativa språkliga nedsättningar. Intraoperativa tester kan därmed bidra till ökad livskvalitet hos patientgruppen. Denna studie har utgått från det nederländska testbatteriet Dutch Lingusistic Intraoperative Protocol (DuLIP) för att skapa en svensk version av deltestet semantic odd word out (SOWO). SOWO testar semantisk bearbetning via lexikal läsning. Den anpassade och utökade versionen av SOWO pilottestades på 26 normalspråkiga personer. Studien har resulterat i ett nytt semantiskt intraoperativt test på svenska som ska prövas kliniskt på Akademiska sjukhuset i Uppsala. Förhoppningsvis bidrar det nya testet till bättre behandlingsmöjligheter för patienter med LGG.

Abstract Depression, anxiety and sleep disorders have been reported to be associated with low level of inflammation, i.e., low-grade inflammation, but mainly in males. The evidence has mainly been based on laboratory or clinical studies with small sample sizes or epidemiological studies with elderly subpopulations. In this study the association of low-grade inflammation with depression, anxiety, and sleep disturbances was investigated using the Northern Finland 1966 Birth Cohort (NFBC 1966). In women, the effect of hormonal factors, menopause and the use of oral contraceptives/hormone replacement therapy on the association between low-grade inflammation and depression was also studied by using the Pieksämäki Study data. In 31-year follow-up of NFBC 1966 (N=6007), the depressive and anxiety symptoms were assessed by Hopkins Symptom Checklist-25 (HSCL-25) and sleep disorders by 15-D questionnaires, while the marker of low-grade inflammation, plasma concentration of high sensitivity C-reactive protein (hs-CRP), was measured. In the Pieksämäki study a representative sample of inhabitants in the town of Pieksämäki were invited to clinical examination. Depressive symptoms were obtained by Beck’s Depression Inventory-21, and hs-CRP was measured (512 women). The results of this study revealed that at epidemiological level, elevated hs CRP levels of ≥1.0 mg/L increased the probability of current depressive symptoms of single depressive episode in the two highest subgroups (i.e., HSCL-25 mean scores ≥1.75 and ≥2.01) 1.4- and 1.7- fold in males, respectively. In addition, anxiety symptoms (HSCL-25 anxiety scale mean score ≥1.75) increased independently the probability of elevated hs-CRP levels (>3.0 mg/L) in males over 2-fold. Risk ratio of 1.3 was found for males with moderate to severe sleep disturbances and elevated hs-CRP levels (≥1.0 mg/L). Regarding females, a positive correlation between elevated hs-CRP levels and depressive symptoms was found only among peri- and postmenopausal women not using exogenous hormones. The results suggest that low-grade inflammation is associated not only with depression but also with anxiety and sleep disturbances in young adult men. In women, hormonal factors may have an effect on the association between low-grade inflammation and depression. Further investigations are called for to confirm these findings and furthermore, to determine the possible role of low-grade inflammation in the pathophysiology of these disorders. / Tiivistelmä Depressio, ahdistuneisuushäiriöt ja unihäiriöt on yhdistetty elimistön matala-asteiseen tulehdustilaan, joskin pääasiallisesti vain miehillä. Tulosten yleistettävyyttä ovat rajoittaneet tutkimusten pienet otoskoot tai painottuminen iäkkäisiin väestöaineistoihin. Tässä tutkimuksessa selvitettiin matala-asteisen tulehduksen yhteyttä depressioon, ahdistuneisuuteen ja unihäiriöihin Pohjois-Suomen syntymäkohortti 1966 -aineistossa. Lisäksi Pieksämäki-tutkimuksen aineistossa selvitettiin naisilla menopaussin ja ehkäisyvalmisteiden/vaihdevuosihormonikorvaushoidon vaikutusta depression ja matala-asteisen tulehduksen väliseen yhteyteen. Pohjois-Suomen syntymäkohortti 1966 -tutkimuksen 31-vuotisseurannassa kartoitettiin 6007 henkilöltä masennus- ja ahdistuneisuusoireita Hopkins Symptom Checklist-25 -arviointiasteikolla (HSCL-25) ja unihäiriöitä 15-D-kyselyllä. Lisäksi mitattiin matala-asteisen tulehduksen mittarina käytetyn herkän C-reaktiivisen proteiinin (CRP) pitoisuus. Pieksämäki-tutkimuksessa edustava otos Pieksämäen asukkaista kutsuttiin kliiniseen tutkimukseen ja depressiivisiä oireita kartoitettiin Beckin 21-osioisella arviointiasteikolla ja mitattiin herkkä CRP (512 naista). Nuorilla aikuisilla miehillä, joiden herkkä CRP oli kohonnut (≥1.0 mg/l), todettiin 1.7-kertainen masennusoireiden riski, kun katkaisupisteenä käytettiin HSCL-25-kyselyn masennuskeskiarvopistettä ≥2.01. Ahdistuneisuusoireet (HSCL-25-kyselyn ahdistuneisuuskeskiarvopisteet ≥1.75) lisäsivät kohonneen herkän CRP:n riskiä (>3.0 mg/l) yli kaksinkertaiseksi miehillä. Keskivaikeasta tai vaikeasta unihäiriöstä kärsivillä todettiin 1.3-kertainen kohonneen herkän CRP:n (≥1.0 mg/l) riski. Naisilla positiivinen yhteys masennuksen ja kohonneen herkän CRP:n välillä todettiin vain peri- ja postmenopausaalisilla naisilla, jotka eivät käyttäneet hormonikorvaushoitoa tai suun kautta otettavia ehkäisyvalmisteita. Tutkimustulokset viittaavat matala-asteisen tulehduksen liittyvän depressioon, ahdistukseen ja unihäiriöön nuorilla aikuisilla miehillä. Naisilla hormonaaliset seikat mahdollisesti vaikuttavat depression ja matala-asteisen tulehduksen väliseen yhteyteen. Tulevaisuuden tutkimushaasteena on selvittää matala-asteisen inflammaation mahdollinen merkitys depression, ahdistuneisuuden ja unihäiriöiden patofysiologiassa.

Det kommer ske en stor utbyggnad av elektrolys för produktion av vätgas i Sverigeoch övriga världen. För att sänka produktionskostnaden och därmed göra vätgasenbilligare analyserar denna rapport vilket behov av syrgas och värme som en landbaserad fiskodling har, samt hur mycket syrgas och värme fiskodlingen skulle behövaköpa från en elektrolysör. Analysen visar att de arter som används i studien - tilapia(Oreochromis, Oreochromis,. Alcolapia), regnbåge (Oncorhynchus mykiss) och lax(Salmo salar) - i en odling som producerar 40 ton fisk om året skulle förbruka cirka1,16 procent av syrgasen och cirka 0,35 procent av värmen från en 3 MW PEMelektrolysör. Försäljningsvärdet av syrgasen och värmen från en 3 MW elektrolysörberäknas till cirka 695 000 SEK/år för syrgasen och cirka 1 830 000 SEK/år för värmen. Den genomsnittliga kostnaden för syrgas och värme för arterna i studien i enodling på 40 ton/år beräknas till 8900 SEK/år för syrgasen och 6400 SEK/år förvärmen i en landbaserad fiskodling. / There will be a major expansion of electrolysis for production of hydrogen in Sweden and the rest of the world. To reduce production costs and thus make hydrogencheaper, this report analyzes how much oxygen and heat a fish farm consumes andtherefore would need to buy from an electrolyser. The analysis shows that the species used in the study - tilapia (Oreochromis, Oreochromis, Alcolapia), rainbow(Oncorhynchus mykiss) and salmon (Salmo salar) - in a farm that produces 40 tonsof fish per year would consume 1.16 percent of the oxygen and 0,35 percent of theheat produced from a 3 MW PEM electrolyzer. The value of the oxygen and theheat from a 3 MW electrolyser is calculated at SEK 694,939/year for the oxygenand SEK 1,829,813/year for the heat. The average cost for the species in the studyin a 40 tonne/year fish farm is calculated at SEK 8,900/year for the oxygen and SEK6,400/year for the heat in a land-based fish farm.

NOVEL METABOLIC REGULATORS AND PROINFLAMMATORY FACTORS IN THE ETIOPATHOGENESIS OF TYPE 2 DIABETES MELLITUS AND OBESITY: THE INFLUENCE OF PHARMACOLOGICAL AND DIETARY INTERVENTIONS MUDr. Miloš Mráz Doctoral Thesis ABSTRACT (EN) Identifying novel factors involved in the etiopathogenesis of obesity, diabetes mellitus and their complications has become one of the primary scopes of metabolic research in the last years. The aim of the present study was to evaluate the role of recently discovered metabolic and inflammatory regulators including fibroblast growth factors 19 and 21 and chemotactic cytokines in the development of obesity and type 2 diabetes mellitus (DM2). A total number of 182 patients were included into the study. They were divided into 3 groups - patients with obesity but without type 2 diabetes mellitus, individuals with obesity and type 2 diabetes mellitus and healthy control normal-weight subjects. Selected interventions included 2 to 3 weeks of very-low-calorie diet (VLCD - energy content 2500 kJ/day), 3 months of administration of PPARα receptor agonist fenofibrate and acute hyperinsulinemia during hyperinsulinemic isoglycemic clamp. Our results indicate that the increase of circulating FGF-21 levels after VLCD and fenofibrate treatment could contribute to positive metabolic effects of these...

Background Obesity, in particular abdominal adiposity, is associated with elevated fatty acids and pro-inflammatory adipokines, which are linked to ectopic fat storage and insulin resistance. During menopause, there is a redistribution of fat from the peripheral to abdominal depots. This transition is associated with an increased risk of type 2 diabetes and cardiovascular diseases. We hypothesized that a Paleolithic diet, with high proportions of lean meat, fish, vegetables, fruits, and oils, but devoid of dairy products and cereals, might have long-term beneficial effects on inflammation, fat metabolism, and circulating fatty acids. These effects might potentially reduce the risk of metabolic complications in postmenopausal women that are obese.  Methods Postmenopausal women with obesity were studied before, after six months, and after 24 months of one of two specified ad libitum diets. One diet was a Paleolithic diet, in which approximately 30% of the total energy (E%) was protein, 30 E% was fat, and 40 E% was carbohydrate. The other diet was a prudent control diet, consistent with Nordic Nutrition recommendations of 15 E% protein, 25 E% fat, and 55 E% carbohydrate. Dietary intakes of polyunsaturated fatty acids and protein were validated objectively by measuring circulating and urinary biomarkers. Anthropometrics and diet reports were analyzed, and abdominal subcutaneous fat samples were evaluated for the expression of proteins key in inflammation and fat metabolism and for lipoprotein lipase mass and activity. In addition, blood samples were analyzed to determine concentrations of specific serum proteins, serum lipids, and the fatty acids carried in cholesterol esters. Results The Paleolithic diet group reported reduced intakes of saturated fatty acids and carbohydrates and elevated intakes of protein and unsaturated fatty acids, compared to baseline. The elevated intakes of polyunsaturated fatty acids and protein were objectively verified for this group. After 24 months, both diets were found to have beneficial effects on the expression of inflammation-related genes in adipose tissue and pro-inflammatory factors in the circulation. Compared to the control group, the Paleolithic diet group exhibited more pronounced reductions of circulating cardiometabolic risk factors, including the ratio of triglycerides to high density lipoprotein, lipogenic index, specific fatty acids, and indices of desaturase activities. After six months, the Paleolithic group also exhibited more pronounced reductions in lipogenesis-promoting factors, including the expression of key proteins in fat synthesis, the activity of lipoprotein lipase, and the activity of stearoyl-CoA desaturase 1, compared to the control group. Conclusion Long-term weight loss in postmenopausal obese women was accompanied by reductions in low-grade inflammation in adipose tissue and in the circulation. In addition, a Paleolithic diet, with a high content of unsaturated fatty acids and a low content of refined carbohydrates, appeared to provide greater reductions in cardiometabolic risk factors associated with insulin resistance and lipogenesis, compared to a prudent control diet. / Bakgrund De senaste decennierna har förekomsten av övervikt och fetma ökat kraftigt i stora delar av världen. Detta beror på en kombination av olika faktorer såsom specifika gener vilka främjar fettinlagring, men kanske främst ett överintag av energirik mat i kombination med minskad fysisk aktivitet. Fetma och specifikt bukfetma, vilket tilltar hos kvinnor efter klimakteriet (postmenopausala), ökar risken för höjda blodfettsnivåer och låggradig inflammation, vilket kan leda till utveckling av typ 2-diabetes samt hjärt- och kärlsjukdomar. Kost och viktnedgång är avgörande för bibehållen hälsa och av stort intresse är att urbefolkningar runt om i världen har låg förekomst av fetma, diabetes, hjärt- och kärlsjukdom, troligtvis kopplat till olika livsstilsfaktorer som högre fysisk aktivitet samt kostfaktorer.  Syfte Vårt syfte var att undersöka metabola förändringar i fettväv och cirkulation hos postmenopausala kvinnor med fetma kopplat till en 24 månaders paleolitisk kostintervention. Den paleolitiska kosten, som ingick i studien består av en hög andel magert kött, fisk, grönsaker, frukt, nötter, oliv- och rapsolja och där mjölkprodukter och spannmål är uteslutna. Vår hypotes var att en paleolitisk kost med hög andel protein och omättade fettsyror har fördelaktiga långtidseffekter på inflammation, fettmetabolism och cirkulerande fettsyror jämfört med en kost baserad på Nordiska näringsrekommendationer med ett högt intag av kolhydrater. Metoder Postmenopausala kvinnor med fetma studerades före, vid sex månader och efter 24 månaders intag, utan energirestriktioner, av antingen en paleolitisk kost eller en kost enligt Nordiska näringsrekommendationer. Kroppsmätningar, kostregistreringar, genuttryck av nyckelproteiner i inflammation och fettmetabolism i fettväv samt koncentrationer av blodfetter, specifika proteiner och fettsyror bestämdes i plasma. Resultat I linje med rekommendationerna så rapporterade gruppen som åt den paleolitiska kosten ett minskat intag av mättat fett och kolhydrater samt ett ökat intag av protein och omättat fett jämfört med baslinjenivåerna. Det ökade intaget av fleromättade fettsyror och protein bekräftades med objektiva mätmetoder. Efter 24 månaders intervention uppvisade båda grupperna en jämförbar viktnedgång och en minskning av flertalet proinflammatoriska faktorer i såväl fettväv som i cirkulation. Den grupp som åt paleolitisk kost uppvisade en kraftigare reduktion av cirkulerande kardiometabola riskfaktorer som index för fettsyntes och desaturaser, specifika fettsyror samt kvoten triglycerider till HDL (high density lipoprotein). Efter sex månader bidrog den paleolitiska kosten också till en mer påtaglig minskning av faktorer involverade i fettinlagring, som uttryck av specifika nyckelproteiner i fettsyntes, aktivitet för lipoprotein lipas och stearoyl-CoA desaturase 1 index jämfört med kontrollkosten. Slutsatser En långvarig viktminskning hos postmenopausala kvinnor med fetma åtföljs av en minskad låggradig inflammation i fettväv och i cirkulation. En paleolitisk kost med hög andel omättade fettsyror och låga halt kolhydrater är kopplat till en kraftigare minskning av riskparametrar för insulinresistens och nyckelfaktorer för fettinlagring jämfört med en kontrollkost enligt Nordiska näringsrekommendationer.

NOVEL METABOLIC REGULATORS AND PROINFLAMMATORY FACTORS IN THE ETIOPATHOGENESIS OF TYPE 2 DIABETES MELLITUS AND OBESITY: THE INFLUENCE OF PHARMACOLOGICAL AND DIETARY INTERVENTIONS MUDr. Miloš Mráz Doctoral Thesis ABSTRACT (EN) Identifying novel factors involved in the etiopathogenesis of obesity, diabetes mellitus and their complications has become one of the primary scopes of metabolic research in the last years. The aim of the present study was to evaluate the role of recently discovered metabolic and inflammatory regulators including fibroblast growth factors 19 and 21 and chemotactic cytokines in the development of obesity and type 2 diabetes mellitus (DM2). A total number of 182 patients were included into the study. They were divided into 3 groups - patients with obesity but without type 2 diabetes mellitus, individuals with obesity and type 2 diabetes mellitus and healthy control normal-weight subjects. Selected interventions included 2 to 3 weeks of very-low-calorie diet (VLCD - energy content 2500 kJ/day), 3 months of administration of PPARα receptor agonist fenofibrate and acute hyperinsulinemia during hyperinsulinemic isoglycemic clamp. Our results indicate that the increase of circulating FGF-21 levels after VLCD and fenofibrate treatment could contribute to positive metabolic effects of these...