Cross-sectional analysis of depressive symptom profiles and serum C-reactive protein levels: data from the Northern Finland 1966 birth cohort.

PURPOSE: Individuals with depression exhibit significantly higher levels of systemic inflammation than those without depression, particularly among those with atypical depression. However, this association has been less convincing at the population level among individuals without a formal depression diagnosis but with suggestive symptoms. Our aim was to clarify this association. MATERIALS AND METHODS: In a large birth cohort sample of the Finnish general population, we examined the cross-sectional association between high-sensitivity C-reactive protein (hsCRP) levels in venous blood samples and atypical/non-atypical depressive symptoms using the Beck Depression Inventory-II to screen 5443 middle-aged participants. RESULTS: As expected, depressive symptoms associated to elevated hsCRP-levels compared to non-depressed. Participants with the atypical subtype of depressive symptoms (n = 84) had an odds ratio (OR) of 2.59 (95% CI 1.40-4.81) for elevated hsCRP levels compared to the non-depressed group. Similarly, our findings indicate that participants with non-atypical symptoms (n = 440) also showed an OR of 1.42 (95% CI 1.05-1.92) when compared to the non-depressed group (n = 4919). CONCLUSIONS: These results provide additional support for previous research linking depression and inflammation and add to the field with a unique and sizeable study population. Furthermore, the current results support the notion that different types of depressive symptoms may be associated with inflammatory markers in slightly different ways.

Parental separation and offspring morbidity in adulthood: a descriptive study of the Northern Finland Birth Cohort 1966.

Aims: Rates of parental separation have increased dramatically in recent decades. We evaluated the association of individuals' childhood family structure with their somatic health over 46 years of follow-up. Methods: Data were drawn from the Northern Finland Birth Cohort, an ongoing project in which 12,058 participants born in 1966 have been followed from their 24th gestational week. Based on information supplied at age 14 years, family structure was categorised as 'single-parent family' and 'two-parent family'. The anthropometric information, data from blood samples and medical history were collected from postal questionnaires and clinical examinations routinely performed at the ages of 31 and 46 years. Results: The study population comprised a total of 10,895 individuals; 85% (n=9253) were offspring of two-parent families and 15% (n=1642) of single-parent families. Type 2 diabetes (P=0.032) or prediabetes (P=0.007), psychoactive drug problems (P<0.001) and sexually transmitted diseases (P<0.001) were more common in the single-parent family group than in the participants from two-parent families. In addition, among men back diseases (P=0.002), and among women hypertension (P=0.003) and ovary infection (P=0.024) were more frequent in individuals affected by parental death than in those from two-parent families. Conclusions: Our results indicate the association of childhood family structure with offspring morbidity during 46 years' follow-up. The lifetime morbidity was observed to be higher among offspring from a single-parent family compared to two-parent family offspring. Public and scientific concern about the consequences of parental separation on the offspring' health exist, therefore support from healthcare professionals and society is warranted.

Accumulation patterns of sedentary time and breaks and their association with cardiometabolic health markers in adults.

Breaking up sedentary time with physical activity (PA) could modify the detrimental cardiometabolic health effects of sedentary time. Our aim was to identify profiles according to distinct accumulation patterns of sedentary time and breaks in adults, and to investigate how these profiles are associated with cardiometabolic outcomes. Participants (n = 4439) of the Northern Finland Birth Cohort 1966 at age 46 years wore a hip-worn accelerometer for 7 consecutive days during waking hours. Uninterrupted ≥1-min sedentary bouts were identified, and non-sedentary bouts in between two consecutive sedentary bouts were considered as sedentary breaks. K-means clustering was performed with 65 variables characterizing how sedentary time was accumulated and interrupted. Linear regression was used to determine the association of accumulation patterns with cardiometabolic health markers. Four distinct groups were formed as follows: "Couch potatoes" (n = 1222), "Prolonged sitters" (n = 1179), "Shortened sitters" (n = 1529), and "Breakers" (n = 509). Couch potatoes had the highest level of sedentariness and the shortest sedentary breaks. Prolonged sitters, accumulating sedentary time in bouts of ≥15-30 min, had no differences in cardiometabolic outcomes compared with Couch potatoes. Shortened sitters accumulated sedentary time in bouts lasting <15 min and performed more light-intensity PA in their sedentary breaks, and Breakers performed more light-intensity and moderate-to-vigorous PA. These latter two profiles had lower levels of adiposity, blood lipids, and insulin sensitivity, compared with Couch potatoes (1.1-25.0% lower values depending on the cardiometabolic health outcome, group, and adjustments for potential confounders). Avoiding uninterrupted sedentary time with any active behavior from light-intensity upwards could be beneficial for cardiometabolic health in adults.

Overweight, obesity and hyperandrogenemia are associated with gestational diabetes mellitus: A follow-up cohort study.

INTRODUCTION: The aim of the study was to determine the association of body mass index (BMI), self-reported symptoms or diagnosis of polycystic ovary syndrome (PCOS), and hyperandrogenemia with the occurrence of gestational diabetes mellitus (GDM) through reproductive life. MATERIAL AND METHODS: A cohort of women born in 1966 were investigated at ages 14, 31 and 46. Women with self-reported PCOS symptoms (presence of both oligo-amenorrhea and hirsutism) at age 31 or with formally diagnosed polycystic ovaries (PCO)/PCOS by age 46 formed the group of self-reported PCOS (srPCOS, n = 222) and were compared with women without self-reported PCOS symptoms or diagnosis (n = 1357). We investigated also the association of hyperandrogenism (hirsutism or biochemical hyperandrogenism) at age 31 with the occurrence of GDM throughout reproductive life. RESULTS: Self-reported PCOS alone was not a risk factor for GDM, but combined with overweight at age 31 (odds ratio [OR] 2.43, 95% confidence interval [CI] 1.22-4.86) or 46 (OR 3.04, 95% CI 1.58-5.83) srPCOS was associated with GDM when compared with normal weight controls. The association disappeared when comparing overweight srPCOS women with overweight controls. However, hyperandrogenemia at age 31, but not hirsutism, was associated with GDM even after adjustment for BMI. CONCLUSIONS: The increased risk of GDM in women with srPCOS was mostly attributed to overweight or obesity. Importantly, normal weight women with srPCOS did not seem to be at increased risk for developing GDM. However, hyperandrogenemia was associated with GDM even after adjustment for BMI. These findings strengthen the importance of weight management in reproductive-age women and suggest a noteworthy role of hyperandrogenemia in the pathophysiology of GDM.

Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts.

AIMS/HYPOTHESIS: Metabolomics technologies have identified numerous blood biomarkers for type 2 diabetes risk in case-control studies of middle-aged and older individuals. We aimed to validate existing and identify novel metabolic biomarkers predictive of future diabetes in large cohorts of young adults. METHODS: NMR metabolomics was used to quantify 229 circulating metabolic measures in 11,896 individuals from four Finnish observational cohorts (baseline age 24-45 years). Associations between baseline metabolites and risk of developing diabetes during 8-15 years of follow-up (392 incident cases) were adjusted for sex, age, BMI and fasting glucose. Prospective metabolite associations were also tested with fasting glucose, 2 h glucose and HOMA-IR at follow-up. RESULTS: Out of 229 metabolic measures, 113 were associated with incident type 2 diabetes in meta-analysis of the four cohorts (ORs per 1 SD: 0.59-1.50; p< 0.0009). Among the strongest biomarkers of diabetes risk were branched-chain and aromatic amino acids (OR 1.31-1.33) and triacylglycerol within VLDL particles (OR 1.33-1.50), as well as linoleic n-6 fatty acid (OR 0.75) and non-esterified cholesterol in large HDL particles (OR 0.59). The metabolic biomarkers were more strongly associated with deterioration in post-load glucose and insulin resistance than with future fasting hyperglycaemia. A multi-metabolite score comprised of phenylalanine, non-esterified cholesterol in large HDL and the ratio of cholesteryl ester to total lipid in large VLDL was associated with future diabetes risk (OR 10.1 comparing individuals in upper vs lower fifth of the multi-metabolite score) in one of the cohorts (mean age 31 years). CONCLUSIONS/INTERPRETATION: Metabolic biomarkers across multiple molecular pathways are already predictive of the long-term risk of diabetes in young adults. Comprehensive metabolic profiling may help to target preventive interventions for young asymptomatic individuals at increased risk.

Insulin resistance and systemic metabolic changes in oral glucose tolerance test in 5340 individuals: an interventional study.

BACKGROUND: Insulin resistance (IR) is predictive for type 2 diabetes and associated with various metabolic abnormalities in fasting conditions. However, limited data are available on how IR affects metabolic responses in a non-fasting setting, yet this is the state people are mostly exposed to during waking hours in the modern society. Here, we aim to comprehensively characterise the metabolic changes in response to an oral glucose test (OGTT) and assess the associations of these changes with IR. METHODS: Blood samples were obtained at 0 (fasting baseline, right before glucose ingestion), 30, 60, and 120 min during the OGTT. Seventy-eight metabolic measures were analysed at each time point for a discovery cohort of 4745 middle-aged Finnish individuals and a replication cohort of 595 senior Finnish participants. We assessed the metabolic changes in response to glucose ingestion (percentage change in relative to fasting baseline) across the four time points and further compared the response profile between five groups with different levels of IR and glucose intolerance. Further, the differences were tested for covariate adjustment, including gender, body mass index, systolic blood pressure, fasting, and 2-h glucose levels. The groups were defined as insulin sensitive with normal glucose (IS-NGT), insulin resistant with normal glucose (IR-NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and new diabetes (NDM). IS-NGT and IR-NGT were defined as the first and fourth quartile of fasting insulin in NGT individuals. RESULTS: Glucose ingestion induced multiple metabolic responses, including increased glycolysis intermediates and decreased branched-chain amino acids, ketone bodies, glycerol, and triglycerides. The IR-NGT subgroup showed smaller responses for these measures (mean + 23%, interquartile 9-34% at 120 min) compared to IS-NGT (34%, 23-44%, P < 0.0006 for difference, corrected for multiple testing). Notably, the three groups with glucose abnormality (IFG, IGT, and NDM) showed similar metabolic dysregulations as those of IR-NGT. The difference between the IS-NGT and the other subgroups was largely explained by fasting insulin, but not fasting or 2 h glucose. The findings were consistent after covariate adjustment and between the discovery and replication cohort. CONCLUSIONS: Insulin-resistant non-diabetic individuals are exposed to a similar adverse postprandial metabolic milieu, and analogous cardiometabolic risk, as those with type 2 diabetes. The wide range of metabolic abnormalities associated with IR highlights the necessity of diabetes diagnostics and clinical care beyond glucose management.

Understanding the complexity of glycaemic health: systematic bio-psychosocial modelling of fasting glucose in middle-age adults; a DynaHEALTH study.

BACKGROUND: The prevention of the risk of type 2 diabetes (T2D) is complicated by multidimensional interplays between biological and psychosocial factors acting at the individual level. To address the challenge we took a systematic approach, to explore the bio-psychosocial predictors of blood glucose in mid-age. METHODS: Based on the 31-year and 46-year follow-ups (5,078 participants, 43% male) of Northern Finland Birth Cohort 1966, we used a systematic strategy to select bio-psychosocial variables at 31 years to enable a data-driven approach. As selection criteria, the variable must be (i) a component of the metabolic syndrome or an indicator of psychosocial health using WHO guidelines, (ii) easily obtainable in general health check-ups and (iii) associated with fasting blood glucose at 46 years (P < 0.10). Exploratory and confirmatory factor analysis were used to derive latent factors, and stepwise linear regression allowed exploration of relationships between factors and fasting glucose. RESULTS: Of all 26 variables originally considered, 19 met the selection criteria and were included in an exploratory factor analysis. Two variables were further excluded due to low loading (<0.3). We derived four latent factors, which we named as socioeconomic, metabolic, psychosocial and blood pressure status. The combination of metabolic and psychosocial factors, adjusted for sex, provided best prediction of fasting glucose at 46 years (explaining 10.7% of variation in glucose; P < 0.001). Regarding different bio-psychosocial pathways and relationships, the importance of psychosocial factors in addition to established metabolic risk factors was highlighted. CONCLUSIONS: The present study supports evidence for the bio-psychosocial nature of adult glycemic health and exemplifies an evidence-based approach to model the bio-psychosocial relationships. The factorial model may help further research and public health practice in focusing also on psychosocial aspects in maintaining normoglycaemia in the prevention of cardio-metabolic diseases.

Childhood growth patterns and cardiovascular autonomic modulation in midlife: Northern Finland 1966 Birth Cohort Study.

OBJECTIVES: To test the hypothesis that age and body mass index (BMI) at BMI peak during infancy and at BMI rebound in childhood are related to cardiovascular autonomic modulation in adulthood. METHODS: At the age of 46 years, a sample (n = 5861) of the participants of the Northern Finland Birth Cohort 1966 took part in follow-up examinations. Heart rate variability (HRV), baroreflex sensitivity (BRS) and low-frequency oscillations of systolic blood pressure (LFSBP) were measured during sympathetic stimulus by standing. BMI at various ages was calculated from frequent anthropometric measurements collected from child welfare clinical records. BRS and LFSBP were available for 1243 participants with BMI peak data and 1524 participants with BMI rebound data, and HRV for 2137 participants with BMI peak data and 2688 participants with BMI rebound data. RESULTS: Age at BMI rebound had a significant inverse association with LFSBP (beta = -0.071, p = 0.006) after all adjustments (p < 0.001) and was also directly associated with BRS (beta = 0.082, p = 0.001) independently of birth and maternal factors (p = 0.023). BMI at BMI peak and at BMI rebound was inversely associated with high-frequency component of HRV (HF) (beta = -0.045, p = 0.036 for BMI at peak; beta = -0.043, p = 0.024 for BMI at rebound) and directly associated with the ratio of low- and high-frequency components of HRV (LF/HF ratio) (beta = 0.084, p = < 0.001 for BMI at peak; beta = 0.069, p < 0.001 for BMI at rebound). These associations remained significant after all adjustments (p < 0.05 for all). CONCLUSIONS: This novel study shows that younger age at BMI rebound and higher BMI at BMI peak and at BMI rebound are associated with higher levels in markers suggestive of augmented sympathetic and reduced vagal cardiovascular modulation in midlife.

Intensity and temporal patterns of physical activity and cardiovascular disease risk in midlife.

Physical activity (PA) and sedentary time (SED) are associated with the risk of cardiovascular disease (CVD), but the temporal patterns of these behaviors most beneficial for cardiovascular health remain unknown. We aimed to identify the intensity and temporal patterns of PA and SED measured continuously by an accelerometer and their relationship with CVD risk. At the age of 46 years, 4582 members (1916 men; 2666 women) of the Northern Finland Birth Cohort 1966 study underwent continuous measurement of PA with Polar Active (Polar Electro, Finland) accelerometers for one week. X-means clustering was applied based on 10 min average MET (metabolic equivalent) values during the measurement period. Ten-year risk of CVD was estimated using the Framingham risk model. Most of the participants had low risk for CVD. Four distinct PA clusters were identified that were well differentiable by the intensity and temporal patterns of activity (inactive, evening active, moderately active, very active). A significant difference in 10-year CVD risk across the clusters was found in men (p = 0.028) and women (p < 0.001). Higher levels of HDL cholesterol were found in more active clusters compared to less active clusters (p < 0.001) in both genders. In women total cholesterol was lower in the moderately active cluster compared to the inactive and evening active clusters (p = 0.001). Four distinct PA clusters were recognized based on accelerometer data and X-means clustering. A significant difference in CVD risk across the clusters was found in both genders. These results can be used in developing and promoting CVD prevention strategies.

Associations of fitness and physical activity with orthostatic responses of heart rate and blood pressure at midlife.

Cardiorespiratory fitness (CRF) and physical activity (PA) are associated with autonomic function, but their associations to orthostatic autonomic responses are unclear in epidemiological setting. We hypothesized that higher CRF and PA would associate with higher immediate vagal responses and lower incidence of adverse findings during orthostatic test. At age of 46, 787 men and 938 women without cardiorespiratory diseases and diabetes underwent an orthostatic test (3-minutes sitting, 3-minutes standing) with recording of RR intervals (RRi) and blood pressure (BP) by finger plethysmography. Acute responses of RRi (30:15 ratio) and BP were calculated. CRF was measured by a submaximal step test and daily amount of moderate-to-vigorous PA (MVPA) for 2 weeks by wrist-worn accelerometer. Lifelong PA was based on questionnaires at ages of 14, 31, and 46. High CRF was significantly associated with higher RRi 30:15 ratio (adjusted standardized ß = 0.17, P < 0.001) and milder acute decrease of systolic BP while standing (ß = 0.10, P = 0.001), while MVPA was not (ß = 0.04 for RRi 30:15 ratio and ß = 0.05 for systolic BP acute response). High lifelong PA was significantly associated with higher RRi 30:15 ratio (ß = 0.08, P = 0.002) but not with acute systolic BP response. Those in the lowest tertile of CRF had 9.2-fold risk (P = 0.002) of having postural orthostatic tachycardia syndrome compared to more fit. Cardiorespiratory fitness and lifelong physical activity, but not current physical activity, were independently associated with higher cardiac vagal response to orthostasis. The present results underscore the importance fitness and lifelong physical activity in prevention of abnormal autonomic function and related cardiovascular risk.

Hormone profiling, including anti-Müllerian hormone (AMH), for the diagnosis of polycystic ovary syndrome (PCOS) and characterization of PCOS phenotypes.

Objective was to evaluate serum anti-Müllerian hormone (AMH) levels in polycystic ovary syndrome (PCOS) and in its different phenotypes in relation to clinical, endocrine and metabolic parameters using a new automated VIDAS® method and to compare it with the Gen II method. Study design was multi-center study including 319 PCOS women and 109 healthy controls. Serum AMH levels measured using VIDAS® were significantly higher in PCOS women than controls (p < .001), and they correlated with those measured using the AMH Gen II method. An AMH cutoff value of 42.1 pmol/L distinguished PCOS women from controls with 67% sensitivity and 83% specificity. The PCOS women with three Rotterdam criteria or hyperandrogenism displayed significantly higher AMH levels compared with those with two Rotterdam criteria or normoandrogenism. In PCOS, AMH levels correlated positively with luteinizing hormone (LH), androgen and sex hormone-binding globulin (SHBG) levels and negatively with BMI, abdominal obesity, follicle-stimulating hormone (FSH), fasting glucose and insulin, and insulin resistance. In conclusion, AMH evaluated using the VIDAS® method distinguished PCOS patients from healthy controls relatively well, especially in those with more severe phenotypes. Further studies are needed to establish whether AMH measurements can distinguish PCOS patients with different metabolic risk factors.

Musculoskeletal pains and cardiovascular autonomic function in the general Northern Finnish population.

BACKGROUND: Heart rate variability (HRV) and baroreflex sensitivity (BRS) measurements provide means for the objective assessment of cardiovascular autonomic function. As previous studies have associated chronic pain with abnormal autonomic function, we aimed to characterize the relationship between the number of musculoskeletal pain sites (NPS), pain intensity, and cardiovascular autonomic function among the population-based Northern Finland Birth Cohort 1966. METHODS: At the age of 46, cohort members self-reported their musculoskeletal pains (enabling the determination of NPS [0-8] and pain intensity [Numerical Rating Scale, NRS, 0-10]) and underwent clinical assessments of cardiovascular autonomic function in seated and standing positions (HRV variables: heart rate [HR] and root mean square of successive differences in beat-to-beat intervals [rMSSD] for the entire cohort; BRS variables: low-frequency systolic blood pressure variability [SBPV] and cross-spectral baroreflex sensitivity [BRS] for those attending the examination in Oulu, Finland). Extensive confounder data were also collected (body mass index, physical activity, smoking, Hopkins Symptom Checklist-25, comorbidities, and medications). The full samples included 4186 and 2031 individuals (HRV and BRS samples, respectively). Three subanalyses focused on individuals with intense and frequent pain, individuals with symptoms of depression and anxiety, and the relationship between pain intensity and autonomic parameters. RESULTS: Linear regression models showed varying associations between NPS, pain intensity, and cardiovascular autonomic parameters. However, after all adjustments NPS was only associated with one outcome among women (BRS, standing: beta = - 0.015, p = 0.048) and two among men (HR, seated: beta = - 0.902, p = 0.003; HR, standing: beta = - 0.843, p = 0.014). Pain intensity was not associated with any outcome after full adjustments. Significant sex*pain interactions were found in the data. CONCLUSIONS: Our data suggest that musculoskeletal pain has, at most, a limited independent association with cardiovascular autonomic function. Future studies should carefully account for the potential confounders and sex interactions that this study revealed.

The Association Between Low Grade Systemic Inflammation and Skin Diseases: A Cross-sectional Survey in the Northern Finland Birth Cohort 1966.

Low grade inflammation is associated with many noncommunicable diseases. The association between skin diseases in general and systemic inflammation has not previously been studied at the population level. A whole-body investigation on 1,930 adults belonging to Northern Finland Birth Cohort 1966 was performed and high sensitive C-reactive protein (CRP) level was measured as a marker of low grade inflammation in order to determine the association between low grade inflammation and skin diseases in an unselected adult population. After adjustment for confounding factors the following skin disorders were associated with low grade inflammation in multinomial logistic regression analysis: atopic eczema (OR 2.2, 95% CI 1.2-3.9), onychomycosis (OR 2.0, 1.2-3.2) and rosacea (OR 1.7, 1.1-2.5). After additionally adjusting for body mass index and systemic diseases, the risks for atopic eczema (OR 2.4, 1.3-4.6) and onychomycosis (OR 1.9, 1.1-3.1) remained statistically significant. In conclusion, low grade inflammation is present in several skin diseases.

Raccoon dog model shows preservation of bone during prolonged catabolism and reduced physical activity.

The raccoon dog (Nyctereutes procyonoides) is a promising animal model capable of preventing disuse-induced osteoporosis. Previous data suggest that this species resembles bears in the preservation of bone mass and biomechanical properties during prolonged passivity and catabolism. This longitudinal study examined the osteological properties of tibiae in farm-bred raccoon dogs that were either fed or fasted (n=6 per group) for a 10 week period. Peripheral quantitative computed tomography was utilized and plasma markers of bone turnover measured before fasting and at 9 weeks followed by mechanical testing (three-point bending), micro-computed tomography and Fourier transform infrared imaging at 10 weeks. Passive wintering with prolonged catabolism (body mass loss 32%) had no significant effects on bone mineralization, porosity or strength. The concentration of C-terminal telopeptide of type I collagen, indicative of bone resorption, increased in the plasma of the fasted raccoon dogs, while the bone formation markers were unchanged. The levels of 25-hydroxyvitamin D were reduced in the fasted animals. Based on these data, the preservation of bone in wintering raccoon dogs shares characteristics with that of bears with no apparent decrease in the formation of bone but increased resorption. To conclude, raccoon dogs were able to minimize bone loss during a 10 week period of catabolism and passivity.

Uterine fibroids and cardiovascular risk.

STUDY QUESTION: Are uterine fibroids associated with increased cardiovascular risk? SUMMARY ANSWER: This study reports an association between increased serum lipids and metabolic syndrome with an increased risk of uterine fibroids. WHAT IS KNOWN ALREADY: Recent studies suggest similarities in biological disease mechanisms and risk factors for fibroids and atherosclerosis: obesity, hypertension and abnormal serum lipids. These findings are awaiting confirmation that a population-based follow-up study could offer with extensive health examination data collection linked with a national hospital discharge register. STUDY DESIGN, SIZE, DURATION: The Northern Finland Birth Cohort (NFBC1966) is a population-based long-term follow-up study including all children with estimated date of delivery in 1966 in the Northern Finland area. The data were collected from national registries, postal questionnaires and clinical health examinations. The study population for this study comprised all females included in the NFBC1966 that underwent an extensive clinical health examination at age 46 years (n = 3635). PARTICIPANTS/MATERIALS, SETTING, METHODS: All females included in the NFBC1966 who were alive and traceable (n = 5118) were invited for the 46-year follow-up study; 3268 (63.9%) responded, returned the postal questionnaire and attended the clinical examination. Uterine fibroid cases were identified through the national hospital discharge register that has data on disease diagnoses based on WHO ICD-codes. Uterine fibroid codes, ICD-9: 218 and ICD-10: D25 were used for case identification. Self-reported fibroid cases were identified through the postal questionnaire. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 729 fibroid cases were identified, including 293 based on hospital discharge registries. With adjustment for BMI, parity, education and current use of exogenous hormones the risk of prevalent fibroids rose significantly for every 1 mmol/l increase in LDL (OR = 1.13, 95% CI: 1.02-1.26 for all cases) and triglycerides (OR = 1.27, 95% CI: 1.09-1.49 for all cases). Metabolic syndrome associated with hospital discharge-based fibroid diagnosis (OR = 1.48, 95% CI: 1.09-2.01). Additionally every 1 unit increase in waist-hip ratio associated with fibroids (OR = 1.32, 95% CI: 1.10-1.57). LIMITATIONS, REASONS FOR CAUTION: The case ascertainment may present some limitations. There was likely an under-identification of cases and misclassification of some cases as controls; this would have diluted the effects of reported associations. The data analysed were cross-sectional and therefore cause and effect for the associations observed cannot be distinguished. WIDER IMPLICATIONS OF THE FINDINGS: Increased serum lipids and metabolic syndrome are associated with increased risk of uterine fibroids. Along with central obesity these findings add to an increased risk for cardiovascular disease among women with fibroids. These observations may suggest that there are shared predisposing factors underlying both uterine fibroids and adverse metabolic and cardiac disease risk, or that metabolic factors have a role in biological mechanisms underlying fibroid development. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Academy of Finland, University Hospital Oulu, University of Oulu, Finland, Northern Finland Health Care Foundation, Duodecim Foundation, ERDF European Regional Development Fund-Well-being and health: Research in the Northern Finland Birth Cohort 1966. The authors declare no conflict of interest.

Controlled ovarian hyperstimulation leads to high progesterone and estradiol levels during early pregnancy.

STUDY QUESTION: Are there differences in estrogen and progesterone secretion in singleton pregnancies, up to Week 11, between spontaneous pregnancies, after controlled ovarian hyperstimulation and fresh embryo transfer (COH + ET) and after frozen embryo transfer in a spontaneous cycle (FET)? SUMMARY ANSWER: Serum progesterone and estradiol (E2) concentrations after COH + ET were higher in early pregnancy, lasting up to Week 7-8, than FET and spontaneous pregnancies, while hormone levels after FET did not differ from spontaneous pregnancies. WHAT IS ALREADY KNOWN: The risk of adverse perinatal outcomes after COH + ET seems to be increased when compared with spontaneous pregnancies. One of the reasons suggested for this is related to ovarian hyperstimulation. STUDY DESIGN, SIZE, DURATION: This was a prospective cohort study consisting of three different groups of pregnant women which were followed-up weekly until Week 11 of their pregnancies. The spontaneous pregnancy group consisted of 41 women, the COH + ET group consisted of 39 and the FET group consisted of 30 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women in the control group with spontaneous conception were recruited from local prenatal clinics. Women in the COH + ET and FET groups were recruited from the Reproductive Unit of Oulu University Hospital. At each visit, a three-dimensional ultrasonography was performed to examine the ovarian volumes and vascularization. A blood sample was drawn to analyse progesterone and E2 levels. The pregnancy outcome was included in the analysis. MAIN RESULTS AND THE ROLE OF CHANCE: At pregnancy Week 5, the serum progesterone levels were higher after the COH + ET (median 312, inter-quartile range 183-480 nmol/l), when compared with the spontaneous (63, 52-80 nmol/l; P < 0.001) and FET (74, 48-96 nmol/l; P < 0.001) pregnancies. At Week 11, the P (189, 124-260 nmol/l) was still higher in the COH + ET group (FET 101, 78-120 nmol/l, P < 0.001; spontaneous 115, 80-139 nmol/l, P < 0.01) than the other two groups. The E2 levels at Week 5 were also significantly higher after COH + ET (4.1, 2.2-6.6 nmol/l) than in the spontaneous pregnancies (1.1, 0.7-1.6 nmol/l, P < 0.001) or after FET (0.7, 0.6-0.9 nmol/l, P < 0.001). The volume of the ovaries and the intraovarian vasculature in the COH + ET group were significantly higher when compared with the other two groups (P < 0.001). The birthweight was negatively correlated with the serum P (R -0.340, P < 0.01) and E2 (R= -0.275, P < 0.05) in pregnancy Weeks 5-8. In the multivariate analysis evaluating the factors affecting birthweight of the newborn, the significant factors were the length of gestation, maternal height and progesterone or E2 secretion during Weeks 5-8. LIMITATIONS, REASONS FOR CAUTION: Because of the low number of patients in this study, larger cohort studies are required to confirm the findings. WIDER IMPLICATIONS OF THE FINDINGS: The findings here indicate that COH-induced increased luteal activity should be evaluated by measuring steroid levels or the ovarian size or vascularity, rather than number of oocytes retrieved. If unphysiologically high steroid activity during pregnancy after COH contributes to the risk of adverse perinatal outcomes after fresh embryo transfer, milder stimulation protocols or even freezing of all of the embryos should be considered. STUDY FUNDING/COMPETING INTERESTS: This study was supported by a research grant from the Academy of Finland. The authors declare no conflicts of interest.

Physiological adaptations to prolonged fasting in the overwintering striped skunk (Mephitis mephitis).

Wintertime physiology of captive striped skunks (Mephitis mephitis) in response to cold ambient temperature (Ta) and fasting was investigated with body temperature (Tb) and activity recordings and analyses of hematology, plasma biochemistry and tissue fatty acids (FA). After 105 days of food deprivation, the skunks were in phase II of fasting indicated by the elevated plasma nonesterified FA and glycerol but no accumulation of nitrogen end products. Shorter-chain saturated and monounsaturated FA together with C18-20 n-3 polyunsaturated FA were preferentially mobilized. Individual amino acids responded to fasting in a complex manner, while essential and nonessential amino acid sums remained stable. Increases in hemoglobin and hematocrit suggested dehydration. The activity levels were lower in mid-January-early March, and the activity bouts were mostly displayed between 17:00-23:00 h. Daily torpor was observed in two females with 29 and 46 bouts. The deepest torpor (Tb<31 °C) occurred between dawn and early afternoon and lasted for 3.3 ± 0.18 h. The average minimum Tb was 29.2 ± 0.15 °C and the lowest recorded Tb was 25.8 °C. There was significant relation between the average 24-h Tb and Ta. Increases in wintertime Ta, as predicted by climate change scenarios, could influence torpor patterns in the species.

Full-length visfatin levels are associated with inflammation in women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common gynaecological endocrinopathy characterized by oligomenorrhea, amenorrhoea, clinical and/or biochemical hyperandrogenism and polycystic ovaries. Abdominal deposition of excess body fat and metabolic diseases like insulin resistance and compensatory hyperinsulinemia are commonly observed in PCOS subjects. It has been suggested that visfatin is an adipokine secreted from the abdominal fat influencing glucose metabolism and might therefore contribute to the metabolic disturbances in PCOS. MATERIALS AND METHODS: We measured circulating full-length visfatin levels with a specific enzyme immunoassay (AdipoGen Inc, Incheon, South-Korea) in 57 women with self-reported symptoms of PCOS (hirsutism and/or oligomenorrhea) and ultrasound confirmed polycystic ovaries, and in 57 controls from the Northern Finland 1966 Birth Cohort and explored its association with metabolic and inflammatory parameters. RESULTS: Polycystic ovary syndrome cases had higher body mass index (BMI) (25·7 vs. 24·1 kg/m(2)) and waist circumference (83·2 vs. 78·8 cm) compared to controls, yet there was no difference in plasma visfatin levels between them. In contrast, visfatin significantly correlated with C-reactive protein (CRP) in the control group and with white blood cell count (WBC) in both groups. In linear regression analysis, adjusted for PCOS, smoking, socioeconomic status, BMI or waist circumference, serum lipids and markers of glucose metabolism and hormone status, only WBC remained significantly associated with plasma visfatin levels. CONCLUSION: Our results suggest that circulating visfatin levels correlate with WBC and CRP but are not associated with PCOS, obesity or metabolic markers, suggesting that visfatin may act as a proinflammatory cytokine.

The effects of an abundant ectoparasite, the deer ked (Lipoptena cervi), on the health of moose (Alces alces) in Finland.

The deer ked (Lipoptena cervi, Diptera, Hippoboscidae) is a haematophagous parasitic fly of the moose (Alces alces) and other cervids, and it is very common in southern and central parts of Finland. The aim of this study was to determine how the intensive parasitism caused by the deer ked affects the health and welfare of the moose. Moose blood samples (n = 78) were collected from deer ked-infested and ked-free regions at 62-68° N and analysed for haematology and clinical chemistry. In addition, tissue samples of moose (n = 23) were collected from a deer ked-infested region at 62° N to determine how the parasite load correlates to several physiological variables of the host. The differences in the blood and plasma values between the deer ked-free and ked-infested animals were minor. In the infested regions, the moose had higher mean corpuscular haemoglobin concentrations unlikely to have been caused by the parasitism. The intensities of deer keds had no consistent correlations with the values of plasma clinical chemistry, endocrinology, amino acids, tissue enzyme activities or body energy stores. However, the hepatic percentages of several individual n-3 polyunsaturated fatty acids (PUFA) and the n-3 PUFA sum correlated inversely with the intensity and density of deer keds. Although a wide array of physiological variables was determined, only minor effects caused by the heavy deer ked parasitism could be detected, suggesting that the moose might tolerate this parasite relatively well.