Treatment-seeking behavior and cardiovascular morbidity among men with anabolic-androgenic steroid use: A cross-sectional study.

AIMS: To determine associations between anabolic-androgenic steroid (AAS) use-related morbidity including cardiovascular disease (CVD) and engagement to health services. METHODS: In this cross-sectional study, 90 males with at least 12 months cumulative current or former use of AAS were included. The participants were divided into a treatment-seeking group (TSG) and a non-treatment seeking group (non-TSG) based on their responses to a self-report web questionnaire. All participants were screened for symptoms that could be indicative of CVD through a clinical interview, and examined with blood samples, blood pressure measurements and transthoracic echocardiography. RESULTS: In the total sample (n = 90), mean age was 39 ± 11 years with cumulative AAS use of 12 ± 9 years. Among men in the TSG with current use there were higher prevalence of dyspnoea (50% vs 7%) and reduced left ventricular ejection fraction (LVEF) in conjunction with left ventricular hypertrophy (LVH) (36 vs. 9%) and/or high blood pressure (55% vs. 19%) compared to men in the non-TSG. Among men with current AAS use and established LVEF <50% (n = 25) or LVH (n = 21), 44% (11) and 43% (9) respectively, had never engaged health services due to AAS-related adverse effects. Deviant liver- and kidney parameters were frequently observed in the total sample but without between-group differences. CONCLUSIONS: Treatment-seeking behavior among current AAS users may be associated with increased levels of dyspnoea and established CVD. Despite objective signs of severe CVD among a substantial amount of study participants, it is of great concern that the majority had never sought treatment for AAS-related concerns.

Use of High-Dose Androgens Is Associated with Reduced Brain-Derived Neurotrophic Factor in Male Weightlifters.

INTRODUCTION: Use of high-dose androgens causes drastic changes in hormonal milieu and is associated with adverse medical, psychological, and cognitive effects. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of growth factors plays a critical role in neuroplasticity, with implications for cognitive function and mental health. The impact of long-term, high-dose androgen use on BDNF in a natural setting has not been investigated. This study examined the association between long-term androgen exposure and BDNF levels, and the links between BDNF, heavy resistance exercise, hormones, androgens, and mental health. METHODS: We measured serum levels of BDNF and sex steroid hormones in male weightlifters (N = 141) with a history of current (n = 59), past (n = 29), or no (n = 52) androgen use. All participants completed questionnaires assessing maximum strength and measures of anxiety and depression. Group differences in BDNF were tested using general linear models adjusting for age and associations between BDNF and strength, anxiety, and depression using Pearson's or Kendall's correlations. RESULTS: Both current (mean: 44.1 ng/mL [SD: 12.7]) and past (39.5 ng/mL [SD: 13.9]) androgen users showed lower serum BDNF levels compared to nonusing controls (51.5 [SD: 15.3], p < 0.001, ηp2 = 0.10). BDNF levels were negatively related to maximal strength, and with hormonal status in past androgen users, but no significant associations were found with measures of depression and anxiety. CONCLUSION: Lower circulating BDNF concentrations in current and past androgen users suggest that high-dose androgen exposure triggers persistent changes in BDNF expression. Further studies are needed to verify the relationship and its potential clinical implications.

Substantial early changes in bone and calcium metabolism among adult pharmacoresistant epilepsy patients on a modified Atkins diet.

OBJECTIVE: The aim of this study was to investigate whether the modified Atkins diet (MAD), a variant of the ketogenic diet, has an impact on bone- and calcium (Ca) metabolism. METHODS: Two groups of adult patients with pharmacoresistant epilepsy were investigated. One, the diet group (n = 53), was treated with MAD for 12 weeks, whereas the other, the reference group (n = 28), stayed on their habitual diet in the same period. All measurements were performed before and after the 12 weeks in both groups. We assessed bone health by measuring parathyroid hormone (PTH), Ca, 25-OH vitamin D (25-OH vit D), 1,25-OH vitamin D (1,25-OH vit D), phosphate, alkaline phosphatase (ALP), and the bone turnover markers procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide collagen type 1 (CTX-1). In addition, we examined the changes of sex hormones (estradiol, testosterone, luteinizing hormone, follicle-stimulating hormone), sex hormone-binding globulin, and leptin. RESULTS: After 12 weeks of MAD, we found a significant reduction in PTH, Ca, CTX-1, P1NP, 1,25-OH vit D, and leptin. There was a significant increase in 25-OH vit D. These changes were most pronounced among patients <37 years old, and in those patients with the highest body mass index (≥25.8 kg/m²), whereas sex and type of antiseizure medication had no impact on the results. For the reference group, the changes were nonsignificant for all the analyses. In addition, the changes in sex hormones were nonsignificant. SIGNIFICANCE: Twelve weeks of MAD treatment leads to significant changes in bone and Ca metabolism, with a possible negative effect on bone health as a result. A reduced level of leptin may be a triggering mechanism. The changes could be important for patients on MAD, and especially relevant for those patients who receive treatment with MAD at an early age before peak bone mass is reached.

Sex difference in human olfactory sensitivity is associated with plasma adiponectin.

Energy deprivation as well as hormones that regulate appetite and eating can influence olfactory function. This study investigated olfactory sensitivity for a food-related and a non-food odour prior to and after a meal, and its relationship to the energy-regulating hormones ghrelin and adiponectin. The olfactory sensitivity for orange and rose (PEA) odour in healthy, normal-weight volunteers (19 women, 45 men, 1 undisclosed individual) was not affected by the consumption of a meal. Olfactory sensitivity was not associated with concentrations of circulating ghrelin. However, olfactory sensitivity was higher for women than for men, indicating better olfactory performance. This difference between women and men was related to concentrations of plasma adiponectin, an adipose-specific hormone. Adiponectin may thus explain why sex differences in olfactory sensitivity emerge, and may also account for some of the inconsistencies in previous findings on sex differences. Our findings add to the limited literature on the impact of stomach and adipose tissue-derived hormones on olfactory sensitivity. Further studies are needed to establish a causal link between circulating adiponectin and a sex difference in olfactory sensitivity.

Effects of modified Atkins diet on thyroid function in adult patients with pharmacoresistant epilepsy.

INTRODUCTION: The use of ketogenic diet as a supplement to antiseizure medication (ASM) in refractory epilepsy has increased the past decades. This high-fat, low-carbohydrate diet mimics the metabolic state of fasting and is generally well-tolerated. However, the long-term adverse effects of the diet are unclear. The purpose of this study was to investigate whether the modified Atkins diet (MAD), a variant of the ketogenic diet, may have an impact on thyroid hormone levels. METHODS: We assessed thyroid function by measuring thyroid stimulation hormone (TSH), fT4, T3, fT3, and rT3 before diet start (baseline) and after 12 weeks on the diet in 53 adult patients with drug-resistant epilepsy. Further, we examined the correlation between the changes in thyroid function during dietary treatment and type of (i) change in seizure frequency, (ii) drugs in use, and (iii) degree of ketosis. RESULTS: After 12 weeks on the diet, we found a significant reduction in T3 and fT3 values (13.4% and 10.6%, respectively) and a significant increase in fT4 values (12.1%) compared with baseline. In addition, there was an insignificant increase in TSH and rT3. These changes were similar in women and men, and there was no correlation to drugs in use (enzyme-inducing vs. nonenzyme-inducing drugs), changes in seizure frequency, or level of ketosis. CONCLUSION: This study indicates that dietary treatment for epilepsy may bring about a modest fall in thyroid hormone levels. This could be relevant for those patients with low thyroid hormones and those treated with ASMs known to lower thyroid hormone levels. A cumulative effect of ASMs, low basal thyroid hormone levels, and ketogenic diet may therefore be of clinical importance in the case of thyroid hormones when treating patients with MAD.

The effect of an exercise program in pregnancy on vitamin D status among healthy, pregnant Norwegian women: a randomized controlled trial.

BACKGROUND: Vitamin D insufficiency is common in pregnant women worldwide. Regular prenatal exercise is considered beneficial for maternal and fetal health. There is a knowledge gap regarding the impact of prenatal exercise on maternal vitamin D levels. The objective of this study was to investigate whether a prenatal exercise program influenced serum levels of total, free and bioavailable 25-hydroxyvitamin D (25(OH)D) and related parameters. This is a post hoc analysis of a randomized controlled trial with gestational diabetes as the primary outcome. METHODS: Healthy, pregnant women from two Norwegian cities (Trondheim and Stavanger) were randomly assigned to a 12-week moderate-intensity exercise program (Borg perceived rating scale 13-14) or standard prenatal care. The intervention group (n = 429) underwent exercise at least three times weekly; one supervised group training and two home based sessions. The controls (n = 426) received standard prenatal care, and exercising was not denied. Training diaries and group training was used to promote compliance and evaluate adherence. Serum levels of 25(OH)D, parathyroid hormone, calcium, phosphate, magnesium and vitamin D-binding protein were measured before (18-22 weeks' gestation) and after the intervention (32-36 weeks' gestation). Free and bioavailable 25(OH)D concentrations were calculated. Regression analysis of covariance (ANCOVA) was applied to assess the effect of the training regime on each substance with pre-intervention levels as covariates. In a second model, we also adjusted for study site and sampling month. Intention-to-treat principle was used. RESULTS: A total of 724 women completed the study. No between-group difference in serum 25(OH)D and related parameters was identified by ANCOVA using baseline serum levels as covariates. The second model revealed a between-group difference in levels of 25(OH)D (1.9, 95% CI 0.0 to 3.8 nmol/L; p = 0.048), free 25(OH)D (0.55, 95% CI 0.10 to 0.99 pmol/L; p = 0.017) and bioavailable 25(OH)D (0.15 95% CI 0.01 to 0.29 nmol/L; p = 0.036). No serious adverse events related to regular exercise were seen. CONCLUSION: This study, a post hoc analysis, indicates that exercise may affect vitamin D status positively, and emphasizes that women with uncomplicated pregnancies should be encouraged to perform regular exercise. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00476567 , registered May 22, 2007.

New reference intervals for cortisol, cortisol binding globulin and free cortisol index in women using ethinyl estradiol.

Healthy women using contraceptives containing a low dose of an estrogen may have a higher serum concentration of cortisol (s-cortisol) and cortisol binding globulin (s-CBG) than the commonly used upper reference limits. There are no published reference intervals for s-cortisol, s-CBG, serum free cortisol index (s-FCI) or cortisol in saliva (sa-cortisol) for these women. The aim was to establish the above-mentioned reference intervals and document the differences in s-cortisol and s-CBG in one group of women using and another group not using ethinyl estradiol (EE). In this cross-sectional study, the reference limits presented were given as the 2.5 and 97.5 percentiles of the distribution of reference values in a population of 277 healthy volunteer women, aged 18-45 years. 157 women were not using any type of estrogen, while 120 women were using contraceptives containing a daily dose of 15-35 µg of EE. Serum and salivary cortisol, and serum CBG were measured using standard laboratory methods. S-FCI was calculated as s-cortisol/s-CBG. The reference intervals for s-cortisol in samples collected at 0800-1030 am in women using and not using EE contraception were: 284-994 nmol/L and 159-569 nmol/L respectively, and for s-CBG: 847-3366 nmol/L and 860-1940 nmol/L, respectively. For s-FCI and sa-cortisol, no clinically significant differences were found. Sa-cortisol may be the preferred measurand for evaluation of possible hypercortisolism in women using estrogens, since cortisol in saliva is not influenced by estrogen. If assessing morning s-cortisol and s-CBG in women using EE, we recommend using separate - and not the commonly used - reference intervals.

Weight-for-length, early weight-gain velocity and atopic dermatitis in infancy and at two years of age: a cohort study.

BACKGROUND: Overweight and atopic dermatitis (AD) are major health problems in most industrialised countries, but the relationship between overweight and AD in infants and young children is unclear. We investigated if weight-for-length at birth, in infancy and at two years, as well as early weight-gain velocity, are associated with the development of AD in early life. METHODS: Cohort study of infants (n = 642), all living in south-east Norway, hospitalized with acute bronchiolitis (n = 404) or recruited from the general population (n = 238), examined at mean age 5.1 months (enrolment) and at a two-year follow-up visit (n = 499; 78%) at mean age 24.6 months. Exposures were weight-for-length (g/cm) at birth, enrolment and two-year follow-up, and early weight-gain velocity (gram/month from birth to enrolment). Excessive weight-for-length was defined as weight-for-length >95th percentile of WHO child-growth standards. Data on weight-for-length at the three time points were obtained for 435, 428 and 473 children. AD was diagnosed according to the Hanifin & Rajka criteria or from a history of physician-diagnosed AD. We performed multivariate analyses with weight-for-length at birth, at enrolment and at the two-year follow-up visit and with early weight gain velocity for the endpoint AD at each visit. RESULTS: In adjusted analyses, excessive weight-for-length at enrolment was associated with concurrent AD (OR 3.03; 95% CI 1.23-7.50) and with AD at two years (OR 2.40; 1.11-5.17). In infants without AD, weight-for-length at enrolment increased the risk of AD at two years, with OR being 1.02 (95% CI 1.00-1.04) per increased gram/cm. AD at two years was not associated with concurrent excessive weight-for-length, nor was AD at any time associated with weight-for-length at birth or with early weight-gain velocity. CONCLUSIONS: The results suggest that overweight in infancy may contribute to the development of AD in early life, highlighting the need for child health-care professionals to address potential overweight and atopic disease when advising infants' caregivers. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00817466 , EudraCT number, 2009-012667-34.

Supraphysiological testosterone levels from anabolic steroid use and reduced sensitivity to negative facial expressions in men.

RATIONALE: Anabolic-androgenic steroids (AAS) are used to improve physical performance and appearance, but have been associated with deficits in social cognitive functioning. Approximately 30% of people who use AAS develop a dependence, increasing the risk for undesired effects. OBJECTIVES: To assess the relationship between AAS use (current/previous), AAS dependence, and the ability to recognize emotional facial expressions, and investigate the potential mediating role of hormone levels. METHODS: In total 156 male weightlifters, including those with current (n = 45) or previous (n = 34) AAS use and never-using controls (n = 77), completed a facial Emotion Recognition Task (ERT). Participants were presented with faces expressing one out of six emotions (sadness, happiness, fear, anger, disgust, and surprise) and were instructed to indicate which of the six emotions each face displayed. ERT accuracy and response time were recorded and evaluated for association with AAS use status, AAS dependence, and serum reproductive hormone levels. Mediation models were used to evaluate the mediating role of androgens in the relationship between AAS use and ERT performance. RESULTS: Compared to never-using controls, men currently using AAS exhibited lower recognition accuracy for facial emotional expressions, particularly anger (Cohen's d = -0.57, pFDR = 0.03) and disgust (d = -0.51, pFDR = 0.05). Those with AAS dependence (n = 47) demonstrated worse recognition of fear relative to men without dependence (d = 0.58, p = 0.03). Recognition of disgust was negatively correlated with serum free testosterone index (FTI); however, FTI did not significantly mediate the association between AAS use and recognition of disgust. CONCLUSIONS: Our findings demonstrate impaired facial emotion recognition among men currently using AAS compared to controls. While further studies are needed to investigate potential mechanisms, our analysis did not support a simple mediation effect of serum FTI.

Maternal vitamin A and D status in second and third trimester of pregnancy and bone mineral content in offspring at nine years of age.

Introduction: Maternal nutritional and vitamin status during pregnancy may have long-term effects on offspring health and disease. The aim of this study was to examine the associations between maternal vitamin A and D status in pregnancy and offspring bone mineral content (BMC) at nine years of age. Methods: This is a post-hoc study of a randomized control trial including 855 pregnant women from two Norwegian cities; Trondheim and Stavanger. The women were randomized into an exercise intervention or standard antenatal care. Mother and child pairs for the present study were recruited from those still living in Trondheim after 8-10 years. Serum vitamin A (retinol) and vitamin D (25(OH)D) were measured in the 2nd and 3rd trimesters of pregnancy, and active vitamin D (1,25(OH)2D) in serum was measured in a subgroup. Spine BMC and trabecular bone score were measured in the children at nine years of age. Associations were analyzed with linear regression models. Results: A total of 119 mother and child pairs were included in the analyses. Vitamin A insufficiency (retinol< 1.05 µmol/L) and vitamin D deficiency (25(OH)D< 50 mmol/L) increased from ~7% to ~43% and from ~28% to ~33%, respectively, from the 2nd to the 3rd trimester. An increase in serum 1,25(OH)2D from the 2nd to the 3rd trimester was observed in the subgroup. There was a negative association between serum retinol in the 2nd trimester and spine BMC in the boys, but not in the girls, when adjusted for maternal and child confounders. No other associations between maternal serum vitamin A or D and BMC in the children were found. Conclusion: We observed a high prevalence of vitamin A insufficiency and vitamin D deficiency during pregnancy. A negative association between mid-pregnancy vitamin A status and spine BMC was observed in boys, but not girls, while no associations were found between maternal vitamin D status and child BMC. The implications of optimal vitamin A and D status in pregnancy for offspring bone health, remains a subject for further investigations.

Elevated interleukin 8 and matrix metalloproteinase 9 levels are associated with myocardial pathology in users of anabolic-androgenic steroids.

AIMS: In the current paper, we aim to explore the effect of both current and former long-term anabolic-androgenic steroid (AAS) use on regulation of systemic inflammatory markers and mediators of extracellular matrix (ECM) remodelling and their association with hormones and echocardiographic myocardial pathology in weightlifters. METHODS AND RESULTS: In a cross-sectional study, 93 weightlifting AAS users, of whom 62 were current and 31 were past users, with at least 1-year cumulative AAS use (mean 11 ± 7 accumulated years of AAS use), were compared with 54 non-using weightlifting controls (WLCs) using clinical interview, blood pressure measurements, and echocardiography. Serum levels of interleukin (IL)-6, IL-8, tumour necrosis factor (TNF), interferon (IFN)-γ, growth differentiation factor (GDF)-15, and matrix metalloproteinase (MMP)-9, sex hormones, and lipids were analysed. It was found that serum levels of IL-8, GDF-15, and MMP-9 were significantly increased in current AAS users compared with former users and WLCs. Matrix metalloproteinase 9, but not IL-8, correlated consistently with sex hormone levels, and sex hormone levels correlated consistently with mean wall thickness, in current users. Moreover, HDL cholesterol was significantly lower in current vs. former AAS users and significantly inversely correlated with MMP-9 in current users. Further, in current users, MMP-9 and IL-8 correlated with markers of myocardial strain, and MMP-9 also correlated with indices of cardiac mass, which was not seen in former users. Mediation analyses suggested that MMP-9 could partly explain hormone-induced alterations in markers of myocardial damage in current users. CONCLUSION: Long-term AAS is associated with increased levels of markers of inflammation and ECM remodelling, which seems to have a hormone-dependent (MMP-9) and a hormone-independent (IL-8) association with markers of myocardial dysfunction.

Long-term use of anabolic-androgenic steroids (AASs) can increase inflammation and mediators of extracellular matrix (ECM) remodeling, which potentially could be involved in myocardial pathology seen in individuals using such steroids.Anabolic-androgenic steroid use increased levels of inflammatory marker IL-8 and marker of ECM remodelling matrix metalloproteinase-9 (MMP-9).Interleukin-8 and MMP-9 were both associated with myocardial pathology in current, but not former, users, suggesting that these markers are associated with the risk of myocardial damage during AAS use.

Clinical and Biochemical Characteristics of Untreated Adult Patients With Resistance to Thyroid Hormone Alpha.

Background: Thyroid hormone resistance due to pathogenic variants in thyroid hormone receptor alpha (THRA) is rare and descriptions of patients are sparse. The disorder is probably underdiagnosed as patients may have normal thyroid function tests. Treatment with thyroxine in childhood improves clinical symptoms. However, it is not clear if treatment has beneficial effects if started in adulthood. Cases: We investigated 4 previously untreated Caucasian adult first-degree-related patients with the THRA c.788C > T, p.(Ala263Val) variant identified by a gene panel for intellectual disability in the index patient. Clinical data and previous investigations were obtained from medical reports. Results: During childhood and adolescence, short stature, short limbs, metacarpals, and phalanges, and delayed bone age maturation were observed. Delayed motor and language development and decreased intellectual and learning abilities were described. Abdominal adiposity, round face, and increased head circumference were common features. All individuals complained of tiredness, constipation, and low mood. While thyrotropin (TSH) and free thyroxine (FT4) were within the reference range, free triiodothyronine (FT3) was high. FT4/FT3 ratio and reverse T3 were low. Other main features were low hemoglobin and high LDL/HDL ratio. Conclusion: Investigation of 4 first-degree-related adult patients with untreated resistance to thyroid hormone alpha (RTHα) revealed more pronounced phenotype features and hypothyroid symptoms than previously described in patients treated with levothyroxine from childhood or adolescence. The delay in diagnosis is probably due to normal thyroid function tests. We suggest that THRA analysis should be performed in patients with specific clinical features, as treatment in early childhood may improve outcomes.

The association between infant salivary cortisol and parental presence in the neonatal intensive care unit during and after COVID-19 visitation restrictions: A cross-sectional study.

OBJECTIVES: Parent-infant interaction in the neonatal intensive care unit (NICU) promotes health and reduces infant stress. During the COVID-19 pandemic, however, NICUs restricted parent-infant interaction to reduce viral transmission. This study examined the potential relationship between pandemic visitation restrictions, parental presence and infant stress as measured by salivary cortisol. METHODS: A two-NICU cross-sectional study of infants with gestational age (GA) 23-41 weeks, both during (n = 34) and after (n = 38) visitation restrictions. We analysed parental presence with and without visitation restrictions. The relationship between infant salivary cortisol and self-reported parental NICU presence in hours per day was analysed using Pearson's r. A linear regression analysis included potential confounders, including GA and proxies for infant morbidity. The unstandardised B coefficient described the expected change in log-transformed salivary cortisol per unit change in each predictor variable. RESULTS: Included infants had a mean (standard deviation) GA of 31(5) weeks. Both maternal and paternal NICU presence was lower with versus without visitation restrictions (both p ≤0.05). Log-transformed infant salivary cortisol correlated negatively with hours of parental presence (r = -0.40, p = .01). In the linear regression, GA (B = -0.03, p = .02) and central venous lines (B = 0.23, p = .04) contributed to the variance in salivary cortisol in addition to parental presence (B = -0.04 p = .04). CONCLUSION: COVID-19-related visitation restrictions reduced NICU parent-infant interaction and may have increased infant stress. Low GA and central venous lines were associated with higher salivary cortisol. The interaction between immaturity, morbidity and parental presence was not within the scope of this study and merits further investigation.

Plasma-Metanephrines in Patients with Autoimmune Addison's Disease with and without Residual Adrenocortical Function.

PURPOSE: Residual adrenocortical function, RAF, has recently been demonstrated in one-third of patients with autoimmune Addison's disease (AAD). Here, we set out to explore any influence of RAF on the levels of plasma metanephrines and any changes following stimulation with cosyntropin. METHODS: We included 50 patients with verified RAF and 20 patients without RAF who served as controls upon cosyntropin stimulation testing. The patients had abstained from glucocorticoid and fludrocortisone replacement > 18 and 24 h, respectively, prior to morning blood sampling. The samples were obtained before and 30 and 60 min after cosyntropin stimulation and analyzed for serum cortisol, plasma metanephrine (MN), and normetanephrine (NMN) by liquid-chromatography tandem-mass pectrometry (LC-MS/MS). RESULTS: Among the 70 patients with AAD, MN was detectable in 33%, 25%, and 26% at baseline, 30 min, and 60 min after cosyntropin stimulation, respectively. Patients with RAF were more likely to have detectable MN at baseline (p = 0.035) and at the time of 60 min (p = 0.048) compared to patients without RAF. There was a positive correlation between detectable MN and the level of cortisol at all time points (p = 0.02, p = 0.04, p < 0.001). No difference was noted for NMN levels, which remained within the normal reference ranges. CONCLUSION: Even very small amounts of endogenous cortisol production affect MN levels in patients with AAD.

Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy.

Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.

100 YEARS OF VITAMIN D: Combined hormonal contraceptives and vitamin D metabolism in adolescent girls.

Objective: Combined hormonal contraceptive (CHC) use has been associated with higher total 25-hydroxyvitamin D (25(OH)D) levels. Here, we investigate the relation between CHC use and vitamin D metabolism to elucidate its clinical interpretation. Methods: The cross-sectional Fit Futures 1 included 1038 adolescents. Here, a subgroup of 182 girls with available 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)2D), 24,25-dihydroxyvitamin D (24,25(OH)2D), vitamin D-binding protein (DBP) and measured free 25(OH)D levels, in addition to parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23), was investigated. Vitamin D metabolites were compared between girls using (CHC+) and not using CHC (CHC-). Further, the predictability of CHC on 25(OH)D levels was assessed in a multiple regression model including lifestyle factors. The ratios 1,25(OH)2D/25(OH)D and 24,25(OH)2D/25(OH)D (vitamin D metabolite ratio (VMR)) in relation to 25(OH)D were presented in scatterplots. Results: CHC+ (n = 64; 35% of the girls) had higher 25(OH)D levels (mean ± s.d., 60.3 ± 22.2) nmol/L) than CHC- (n = 118; 41.8 ± 19.3 nmol/L), P -values <0.01. The differences in 25(OH)D levels between CHC+ and CHC- were attenuated but remained significant after the adjustment of lifestyle factors. CHC+ also had higher levels of 1,25(OH)2D, 24,25(OH)2D, DBP and calcium than CHC-, whereas 1,25(OH)2D/25(OH)D, PTH, FGF23 and albumin were significantly lower. Free 25(OH)D and VMR did not statistically differ, and both ratios appeared similar in relation to 25(OH)D, irrespective of CHC status. Conclusion: This confirms a clinical impact of CHC on vitamin D levels in adolescents. Our observations are likely due to an increased DBP-concentration, whereas the free 25(OH)D appears unaltered.

Plasma α-Glutathione S-Transferase in Patients with Chronic Mesenteric Ischemia and Median Arcuate Ligament Syndrome.

Background: Chronic mesenteric ischemia (CMI) due to either atherosclerosis of the mesenteric arteries or median arcuate ligament syndrome (MALS) is an underdiagnosed entity. The etiology of MALS and its existence have been debated and questioned. We aimed to identify plasma biomarkers indicating mesenteric ischemia in patients with CMI and MALS. Methods: Plasma α-glutathione S-transferase (α-GST), intestinal fatty acid-binding protein (I-FABP), citrulline, and ischemia modified albumin (IMA) were analyzed in fifty-eight patients with CMI (Group A, n=44) and MALS (Group B, n=14) before and after revascularization. The plasma levels of these potential biomarkers were compared with those of healthy individuals (Group C, n=16). Group comparison was performed with the Mann-Whitney U-test. Cross-tabulation and its derivatives were obtained. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were calculated. Results: Plasma levels of α-GST were significantly raised in the patients with CMI (7.8 ng/mL, p<0.001) and MALS (8.4 ng/mL, p<0.001), as compared with the control Group C (3.3 ng/mL). The threshold for normal median plasma α-GST levels of 4 ng/mL yielded a sensitivity of 93% and 86%, specificity of 86% and 88%, respectively, for the diagnosis of CMI due to atherosclerosis and MALS. AUC of ROC curves was 0.96 (p<0.0001) for CMI and 0.85 (p<0.002) for MALS. The patient groups did not differ from the healthy controls in any other biomarkers. Conclusion: Plasma α-GST levels are elevated in CMI and MALS patients. Elevated plasma levels of α-GST suggest ischemia as the etiology of MALS.

Stress responses to repeated captures in a wild ungulate.

While capture-mark-recapture studies provide essential individual-level data in ecology, repeated captures and handling may impact animal welfare and cause scientific bias. Evaluating the consequences of invasive methodologies should be an integral part of any study involving capture of live animals. We investigated short- and long-term stress responses to repeated captures within a winter on the physiology, behaviour, and reproductive success of female Svalbard reindeer (Rangifer tarandus platyrhynchus). Short-term responses were evaluated using serum concentrations of glucocorticoids and catecholamines during handling, and post-release recovery times in heart rate and activity levels. Repeated captures were associated with an increase in measured catecholamines and glucocorticoids, except cortisone, and delayed recovery in heart rate but not activity. Four months later, in summer, individuals captured repeatedly in winter exhibited a small increase in behavioural response to human disturbance and had a lower probability of being observed with a calf, compared to animals not captured, or captured only once. Our findings imply that single annual capture events have no significant negative consequences for Svalbard reindeer, but repeated captures within a season may impact offspring survival in the same year. Such unanticipated side effects highlight the importance of addressing multiple indicators of animal responses to repeated captures.