Simple Summary Most ovarian cancer patients initially show a response to primary treatments, but the development of refractory disease is a major problem. Currently, there are no blood-based prognostic biomarkers, and the prognosis of a patient is determined by the International Federation of Gynecology and Obstetrics (FIGO) stage and residual disease after cytoreductive surgery. In this study, we developed and validated a novel test based on the ratio of two circulatory lipids that enables the prognostic stratification of ovarian cancer patients at the time of diagnosis, prior to any oncological treatments. The translational relevance of this test is to find those patients with poor prognosis early on, and to identify patients that are at high risk of recurrence despite complete cytoreduction. Thus, the test enables the early direction of novel targeted therapies to those ovarian cancer patients at greatest risk of recurrence and death. Epithelial ovarian cancer (EOC) generally responds well to oncological treatments, but the eventual development of a refractory disease is a major clinical problem. Presently, there are no prognostic blood-based biomarkers for the stratification of EOC patients at the time of diagnosis. We set out to assess and validate the prognostic utility of a novel two-lipid signature, as the lipidome is known to be markedly aberrant in EOC patients. The study consisted of 499 women with histologically confirmed EOC that were prospectively recruited at the university hospitals in Turku (Finland) and Charite (Berlin, Germany). Lipidomic screening by tandem liquid chromatography-mass spectrometry (LC-MS/MS) was performed for all baseline serum samples of these patients, and additionally for 20 patients of the Turku cohort at various timepoints. A two-lipid signature, based on the ratio of the ceramide Cer(d18:1/18:0) and phosphatidylcholine PC(O-38:4), showed consistent prognostic performance in all investigated study cohorts. In the Turku cohort, the unadjusted hazard ratios (HRs) per standard deviation (SD) (95% confidence interval) were 1.79 (1.40, 2.29) for overall and 1.40 (1.14, 1.71) for progression-free survival. In a Charite cohort incorporating only stage III completely resected patients, the corresponding HRs were 1.59 (1.08, 2.35) and 1.53 (1.02, 2.30). In linear-mixed models predicting progression of the disease, the two-lipid signature showed higher performance (beta per SD increase 1.99 (1.38, 2.97)) than cancer antigen 125 (CA-125, 1.78 (1.13, 2.87)). The two-lipid signature was able to identify EOC patients with an especially poor prognosis at the time of diagnosis, and also showed promise for the detection of disease relapse.

Purpose: To refine the diagnostic criteria for Terrien marginal degeneration (TMD) based on experience in 3 Nordic countries. Methods: This is a retrospective, multicenter, hospital-based cross-sectional study of 49 eyes of 29 white patients in tertiary referral centers in Finland, Sweden, and Denmark from 1998 to January 2018. The median follow-up was 3 years. Symptoms, best corrected visual acuity, astigmatism, corneal thickness, curvature and cavities, stage, and progression were analyzed. Results: TMD was diagnosed equally likely between 15 and 86 years of age (median, 47 years). Twenty patients (69%) had bilateral disease, and 62% were men. Seventeen patients (59%) had symptoms including blurred vision and ocular surface disease symptoms without inflammatory signs. Eight patients (28%) had slightly reduced corneal sensitivity. Median best corrected visual acuity was 20/25 (range, 20/16-20/200) and astigmatism was 2.6 diopters (D) (range, 0-10) with a mean progression of 0.41 D per year (range, 0-5.4). Age and astigmatism were not correlated. All eyes had peripheral vascularization, lipid deposits, and hyperreflectivity throughout thinned peripheral stroma and its anterior edge. The thinning progressed in 15 patients (52%). Of 26 patients, 8 (31%) had single or confluent paralimbal intrastromal cavities, most commonly superiorly. By Suveges classification, the stage was 2 (92%) or 3 (8%). Minimum corneal thickness and corneal curvature were loosely associated, leading to different stages in Wang classification in 34 eyes (69%). Conclusions: TMD is defined by peripheral corneal thinning, superficial neovascularization, lipid deposition at the leading edge, absence of ulceration and inflammation, and frequently cavitation. The most sensitive way to follow its progression is anterior segment optical coherence tomography.

Background Metabolic profiling identifies seasonal variance of serum metabolites in humans. Despite the presence of seasonal disease patterns, no studies have assessed whether serum metabolites vary seasonally in dogs. Hypothesis There is seasonal variation in the serum metabolite profiles of healthy dogs. Animals Eighteen healthy, client-owned dogs. Methods A prospective cohort study. Serum metabolomic profiles were assessed monthly in 18 healthy dogs over a 12-month period. Metabolic profiling was conducted using a canine-specific proton nuclear magnetic resonance spectroscopy platform, and the effects of seasonality were studied for 98 metabolites using a cosinor model. Seasonal component was calculated, which describes the seasonal variation of each metabolite. Results We found no evidence of seasonal variation in 93 of 98 metabolites. Six metabolites had statistically significant seasonal variance, including cholesterol (mean 249 mg/dL [6.47 mmol/L] with a seasonal component amplitude of 9 mg/dL [0.23 mmol/L]; 95% confidence interval [CI] 6-13 mg/dL [0.14-0.33 mmol/L], P < .008), with a peak concentration of 264 mg/dL (6.83 mmol/L) in June and trough concentration of 236 mg/dL (6.12 mmol/L) in December. In contrast, there was a significantly lower concentration of lactate (mean 20 mg/dL [2.27 mmol/L] with a seasonal component amplitude of 4 mg/dL [0.42 mmol/L]; 95% CI 2-6 mg/dL [0.22-0.62 mmol/L], P < .001) during the summer months compared to the winter months, with a peak concentration of 26 mg/dL (2.9 mmol/L) in February and trough concentration of 14 mg/dL (1.57 mmol/L) in July. Conclusions and Clinical Importance We found no clear evidence that seasonal reference ranges need to be established for serum metabolites of dogs.

Mercury (Hg) is a heavy metal acknowledged as a worldwide contaminant that accumulates in organisms and biomagnifies in food webs. The organic methylmercury (MeHg) species is harmful to animals, including humans, and mainly derived from the diet. The dietary Hg consumed by fish is mostly removed through the intestine, but some of the MeHg bioaccumulates, especially in the white muscle tissue of fish. Perch (Perca fluviatilis) and roach (Rutilus rutilus) are commonly found fish species in Finland. Perch has additional im-portance as it is the national fish of Finland, a popular food fish, as well as a monitoring species used to evaluate the chemical status of lakes. Seasonal variation of Hg in muscle tissue of fish is supposedly caused by starvation in winter, which condenses Hg in the muscle, and growth dilution in summer, which refers to fast somatic growth during the growing season, which dilutes Hg in the muscle. Similar to winter, spawning has also been found to condense Hg in muscle tissue of fish due to high energy investment into gonad development. Seasonal variation of Hg and variables driving seasonal changes have been shown to differ between fish species. Seasonal variation has been studied mainly during the open-water season. However, less is known about how winter conditions under ice affect Hg levels in fish. In this MSc thesis, I asked (Q1) How total mercury (THg) content in the muscle tissue of perch and roach change annually? (Q2) How THg bioaccumulation in the muscle tissue of perch and roach change annually? (Q3) What are the factors explaining annual variation in THg content in the muscle tissue of perch and roach? The practical application of results was to discuss if annual variation should be considered in monitoring programs and human health questions. The materials used in this study were collected from Lake Pääjärvi monthly from March 2020 to March 2021. Fish were collected using gillnet series. Length, weight, sex, sexual maturity, stomach fullness, Fulton’s condition factor (K), and muscle THg were determined from each fish. The annual length-corrected THg content variation was tested using analysis of variance. The annual THg bioaccumulation variation in the relationship between muscle and fish length was tested using simple linear regression analysis, and the seasonal variation in THg bioaccumulation was tested with LOESS regression analysis. Variables affecting seasonal variation were tested with stepwise multiple linear regression analysis. THg content of perch was the highest in winter and spring and the lowest in fall, while roach showed no significant seasonal variation. THg bioaccumulation of both species was highest in winter, spring, and early summer and lowest in fall. Perch displayed more substantial seasonal variation than roach. Biological and environmental variables that explained the THg content of perch were length, ice thickness, gonadosomatic index (GSI), light, and condition factor. Variables that explained the THg content of roach were length, sex, and total phosphorus (Tot-P). This study confirmed that starvation in winter, growth dilution in summer, and spawning in spring/early summer are vital factors driving seasonal variation. Due to evident seasonal variation, monitoring month should be pre-set in current monitoring programs.