Eosinophil-derived neurotoxin levels in early childhood and association with preschool asthma – A prospective observational study

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Fetal thoracic circumference in mid-pregnancy and infant lung function

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.Background and Aim: Impaired lung function in early infancy is associated with later wheeze and asthma, while fetal thoracic circumference (TC) predicts severity of neonatal lung hypoplasia. Exploring fetal origins of lung function in infancy, we aimed to determine if fetal TC in mid‐pregnancy was associated with infant lung function. Methods: From the prospective Scandinavian general population‐based PreventADALL mother–child birth cohort, all 851 3‐month‐old infants with tidal flow‐volume measurements in the awake state and ultrasound fetal size measures at 18 (min–max 16–22) weeks gestational age were included. Associations between fetal TC and time to peak tidal expiratory flow to expiratory time (tPTEF/tE) were analyzed in linear regression models. To account for gestational age variation, we adjusted TC for simultaneously measured general fetal size, by head circumference (TC/HC), abdominal circumference (TC/AC), and femur length (TC/FL). Multivariable models were adjusted for maternal age, maternal asthma, pre‐pregnancy body mass index, parity, nicotine exposure in utero, and infant sex. Results: The infants (47.8% girls) were born at mean (SD) gestational age of 40.2 (1.30) weeks. The mean (SD) tPTEF/tE was 0.39 (0.08). The mean (SD) TC/HC was 0.75 (0.04), TC/AC 0.87 (0.04), and TC/FL 4.17 (0.26), respectively. Neither TC/HC nor TC/AC were associated with infant tPTEF/tE while a week inverse association was observed between TC/FL and tPTEF/tE (β ^ = −0.03, 95% confidence interval [−0.05, −0.007], p = 0.01). Conclusion: Mid‐pregnancy fetal TC adjusted for fetal head or abdominal size was not associated with tPTEF/tE in healthy, awake 3‐month‐old infants, while a weak association was observed adjusting for fetal femur length.publishedVersio

Eczema distribution in girls and boys during infancy: A cohort study on atopic dermatitis

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The skin microbiome in the first year of life and its association with atopic dermatitis

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Fecal Microbiota Nutrient Utilization Potential Suggests Mucins as Drivers for Initial Gut Colonization of Mother-Child-Shared Bacteria

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Gut bacteria at 6 months of age are associated with immune cell status in 1-year-old children

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Birth mode is associated with development of atopic dermatitis in infancy and early childhood

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Maternal human papillomavirus infections at mid-pregnancy and delivery in a Scandinavian mother–child cohort study

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The effect of nicotine-containing products and fetal sex on placenta-associated circulating midpregnancy biomarkers

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Identification and Characterization of Biomarkers using Magnetic Resonance Metabolomics : – Metabolic portraits of cancers and aerobic fitness

Identifisering og karakterisering av biomarkører ved bruk av magnetisk resonans metabolomics Kreft og kardiovaskulære sykdommer er ledende dødsårsaker i industriland og i mange utviklingsland. De eksisterende kliniske og patologiske verktøy for disse sykdommene er ikke tilstrekkelige for å gi presis prediksjon av respons eller optimal individualisert behandling. Det er derfor et stort behov for å identifisere og implementere nye biomarkører for å oppnå bedre prediktiv, forebyggende og målrettet medisin. Endring i cellenes stoffskifte er en viktig faktor i utviklingen av kreft og kardiovaskulær sykdom og derfor et viktig område innen biomedisinsk forskning. Studiet av små molekylære metabolitter i kroppsvæsker og vevsprøver (metabolomics), kan ved hjelp av magnetisk resonans spektroskopi (MRS) og multivariate dataanalyser, gi ny innsikt innenfor dette feltet. Identifikasjon av nye metabolske biomarkører for prediksjon, diagnose og behandlingsrespons av kardiovaskulær sykdom og kreft, har potensiale til å øke total overlevelse og pasientens livskvalitet, i tillegg til å spare samfunnet for store utgifter. Økt forekomst av livsstilssykdommer er en trussel mot folkehelsen, og det er behov for mer effektive forebyggings- og behandlingsstrategier. Flere studier har vist at forekomsten av metabolsk syndrom og kardiovaskulær sykdom er relatert til kondisjonsnivå. Lav maksimal aerob kapasitet er foreslått som en prediktiv faktor for kardiovaskulær død. De eksakte molekylære mekanismene bak dette er uklare. Studier basert på metabolomics har resultert i unike funn som kan gi informasjon om de underliggende mekanismene til koronar hjertesykdom, kreft, kosthold og livsstil. Innen kreftforskning har metabolomics også et potensiale som et ekstra verktøy i diagnostisering og risikovurdering. Videre vil det være et relevant verktøy for å finne optimal individualisert behandling, med andre ord kun behandle pasienter som med størst sannsynlighet har effekt av en spesifikk behandling og dermed kan unngå unødvendig behandling. Hovedmålet med forskningen presentert i denne avhandlingen var å evaluere bruken av metabolomics basert på bruk av høyoppløselig MRS og multivariat dataanalyse for å identifisere og karakterisere mulige biomarkører for ulike helsetilstander. Avhandlingen består av tre artikler hvor anvendelsen av MR metabolomics til å identifisere biomarkører for kondisjon, astrocytom grad og endringer i bukhinne-/pleuravæske fra kreftpasienter etter kjemoterapi ble evaluert. Studiene ble utført i prøvematerialer fra et bredt spekter av mennesker, og spenner fra friske frivillige til pasienter med avansert kreftsykdom. I den første studien ble kondisjonsavhengige forskjeller i serumnivåer av fritt kolin og fosfatidylkolin i en gruppe friske frivillige observert. Resultatene viser at kolinmetabolitter er potensielle tidlige markører for kardiovaskulær sykdomsrisiko og bør studeres nærmere. I neste studie ble muligheten for å differensiere diffuse hjernesvulster av Grad II og IV astrocytom basert på metabolske profil vist. I det siste arbeidet ble metabolske markører for kjemoterapirelaterte endringer i bukhinnevæske fra pasienter med eggstokkreft identifisert. Denne avhandlingen har vist nytten av MR metabolomics og multivariat dataanalyse i utredningsfasen av biomarkører. Videre har nytten av MR baserte metabolomics teknikker for å finne molekylære signaturer av kreft og kondisjon blitt studert. Dette kan bidra ytterligere til den vitenskapelige forståelsen av underliggende biologi av svulster og kondisjon.Cancer and cardiovascular disease are the leading cause of mortality in the developed countries and in many developing countries. The existing clinical and pathological tools for both these diseases are insufficient for accurate response prediction, or for an individualized treatment. There is a compelling need for identification and development of new biological markers to achieve a new era of predictive, preventive and targeted medicine. Altered cellular metabolism is an important factor in the pathogenesis of cancer and cardiovascular disease and has become a major area of biomedical research. Metabolomics, the study of small molecular metabolites present in biofluids and tissue samples using magnetic resonance spectroscopy may hold the power to bring new insights on this subject. Identification of metabolic biomarkers for cardiac disease and cancer risk prediction, diagnosis and treatment response could have the power to increase overall survival and the patient quality of life, in addition to saving huge expenses for the society. Increased prevalence of lifestyle-related diseases is an impending threat to public health, and calls for effective prevention and treatment strategies. Several studies have indicated that the occurrence of metabolic syndrome and cardiovascular disease are related to the exercise capacity. Low maximal aerobic capacity is suggested as a predictive factor for cardiovascular deaths. However, the exact molecular mechanisms behind this are unclear and are difficult to explore. Metabolomics based approach may provide potential information in this direction and has resulted in unique findings in relation to coronary heart disease, cancer, diet, and lifestyle. The potential benefits of metabolomics within cancer research would be to serve as an additional tool in diagnosis and risk evaluation. In addition, targeting of specific patients who are more likely to benefit from a specific treatment than those who may not benefit from it or may be harmed is highly relevant. The main objective of the research presented in this thesis was to evaluate the use of high resolution magnetic resonances (MR) spectroscopy together with multivariate analysis based metabolomics for identifying and characterizing potential biomarkers of health-disease continuum. This thesis consists of three papers in which the applicability of MR metabolomics in identifying biomarkers of aerobic fitness, astrocytoma grading and chemotherapy dependent changes in malignant serous effusion was investigated. Metabolomic studies were performed on a broad range of subjects ranging from healthy volunteers to patients with advanced stage of malignancies. In the first study, aerobic fitness dependent differences in serum levels of free choline and phosphatidylcholines in a group of healthy volunteers were observed. These choline metabolites are potential early markers of CVD risk and should be studied further. In the next study, the possibility of differentiating diffuse World Health Organization Grade II and IV astrocytoma based on their metabolic profiles were shown. In the third paper, metabolic markers of chemotherapy related changes in ovarian serous carcinoma effusions were identified. The usefulness of MR metabolomics together with multivariate data analysis in the exploratory phase of biomarker discovery has been illustrated in this thesis. Furthermore, the usefulness of MR based metabolomic techniques in capturing molecular signatures of cancers and aerobic fitness has been explored and may contribute further to the scientific understanding of underlying tumor biology and aerobic fitness