Associations between anxiety, body mass index, and sex hormones in women

Background: Several studies have shown a positive association between anxiety and obesity, particularly in women. We aimed to study whether sex hormone alterations related to obesity might play a role in this association. Patients and methods: Data for this study were obtained from a population-based cohort study (the LIFE-Adult-Study). A total of 3,124 adult women (970 premenopausal and 2,154 postmenopausal) were included into the analyses. The anxiety symptomatology was assessed using the GAD-7 questionnaire (cut-off ≥ 10 points). Sex hormones were measured from fasting serum samples. Results: We did not find significant differences in anxiety prevalence in premenopausal obese women compared with normal-weight controls (4.8% vs. 5.5%). Both obesity and anxiety symptomatology were separately associated with the same sex hormone alteration in premenopausal women: higher total testosterone level (0.97 ± 0.50 in obese vs. 0.86 ± 0.49 nmol/L in normal-weight women, p = 0.026 and 1.04 ± 0.59 in women with vs. 0.88 ± 0.49 nmol/L in women without anxiety symptomatology, p = 0.023). However, women with anxiety symptomatology had non-significantly higher estradiol levels than women without anxiety symptomatology (548.0 ± 507.6 vs. 426.2 ± 474.0 pmol/L), whereas obesity was associated with lower estradiol levels compared with those in normal-weight group (332.7 ± 386.5 vs. 470.8 ± 616.0 pmol/L). Women with anxiety symptomatology had also significantly higher testosterone and estradiol composition (p = 0.006). No associations of sex hormone levels and BMI with anxiety symptomatology in postmenopausal women were found. Conclusions: Although both obesity and anxiety symptomatology were separately associated with higher testosterone level, there was an opposite impact of anxiety and obesity on estradiol levels in premenopausal women. We did not find an evidence that the sex hormone alterations related to obesity are playing a significant role in anxiety symptomatology in premenopausal women. This could be the explanation why we did not find an association between obesity and anxiety. In postmenopausal women, other mechanisms seem to work than in the premenopausal group

High power neon seeded JET discharges: Experiments and simulations

A series of neon seeded JET ELMy H-mode pulses is considered from the modeling as well as from the experimental point of view. For two different Ne seeding rates and two different D puffing gas levels the heating power, P heat , is in the range 22–29.5 MW. The main focus is on the numerical reconstruction of the total radiated power (which mostly depends on the W concentration) and its distribution between core and divertor and of Z eff(which mostly depends on the Ne concentration). To model self-consistently the core and the SOL two input parameters had to be adjusted case by case: the SOL diffusivity, D SOL , and the core impurity inward pinch, v pinch . D SOL had to be increased with increasing Ne and the level of v pinch had to be changed, for any given Ne , according to the level of P heat : it decreases with increasing P heat . Since the ELM frequency, f ELM , is experimentally correlated with P heat , (it increases with P heat ) the impurity inward pinch can be seen as to depend on f ELM . Therefore, to maintain a low v pinch level (i.e. high f ELM ) Ne / P heat should not exceed a certain threshold, which slightly increases with the D puffing rate. This might lead to a limitation in the viability of reducing the target heat load by Ne seeding at moderate D , while keeping Z effat acceptably low level.EURATOM 63305

Application of the VUV and the soft x-ray systems on JET for the study of intrinsic impurity behavior in neon seeded hybrid discharges

This paper reports on impurity behavior in a set of hybrid discharges with Ne seeding—one of the techniques considered to reduce the power load on reactor walls. A series of experiments carried out with light gas injection on JET with the ITER-Like-Wall (ILW) suggests increased tungsten release and impurity accumulation [C. Challis et al., Europhysics Conference Abstracts 41F, 2.153 (2017)]. The presented method relies mainly on the measurements collected by vacuum-ultra-violet and soft X-ray (SXR) diagnostics including the “SOXMOS” spectrometer and the SXR camera system. Both diagnostics have some limitations. Consequently, only a combination of measurements from these systems is able to provide comprehensive information about high-Z [e.g., tungsten (W)] and mid-Z [nickel (Ni), iron (Fe), copper (Cu), and molybdenum (Mo)] impurities for their further quantitative diagnosis. Moreover, thanks to the large number of the SXR lines of sight, determination of a 2D radiation profile was also possible. Additionally, the experimental results were compared with numerical modeling based on integrated simulations with COREDIV. Detailed analysis confirmed that during seeding experiments, higher tungsten release is observed, which was also found in the past. Additionally, it was noticed that besides W, the contribution of molybdenum to SXR radiation was greater, which can be explained by the place of its origin.This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014-2018 under Grant Agreement No. 633053. The views and opinions expressed herein do not necessarily reflect those of the European Commission. This scientific work was partly supported by the Polish Ministry of Science and Higher Education within the framework of the scientific financial resources in the years 2014-2018 allocated for the realization of the international co-financed project.Postprint (author's final draft

Testosterone imbalance may link depression and increased body weight in premenopausal women

Accumulating evidence supports a link between depression and being overweight in women. Given previously reported sex differences in fat accumulation and depression prevalence, as well as the likely role of sex hormones in both overweight and mood disorders, we hypothesised that the depression-overweight association may be mediated by sex hormones. To this end, we investigated the association of being overweight with depression, and then considered the role of sex hormones in relation to being overweight and depression in a large population-based cohort. We included a total of 3124 women, 970 premenopausal and 2154 postmenopausal from the LIFE-Adult cohort study in our analyses. We evaluated associations between being overweight (BMI >25 kg/m2), sex hormone levels, and depressive symptomatology according to Centre for Epidemiologic Studies Depression (CES-D) scores, and explored mediation of depression in a mediation model. Being overweight was significantly associated with depressive symptoms in premenopausal but not postmenopausal women. Both premenopausal and postmenopausal overweight women had higher free testosterone levels compared with normal weight women. Premenopausal women with depressive symptomatology had higher free testosterone levels compared to women without. We found a significant mediation effect of depressive symptomatology in overweight premenopausal women through free testosterone level. These findings highlight the association between being overweight and depressed, and suggest that high free testosterone levels may play a significant role in depression of overweight premenopausal women. Based on this, pharmacological approaches targeting androgen levels in overweight depressed females, in particular when standard anti-depressive treatments fail, could be of specific clinical relevance

Referral rates for diagnostic testing support an incidence of permanent neonatal diabetes in three European countries of at least 1 in 260,000 live births

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Impact of plasma-wall interaction and exhaust on the EU-DEMO design

In the present work, the role of plasma facing components protection in driving the EU-DEMO design will be reviewed, focusing on steady-state and, especially, on transients. This work encompasses both the first wall (FW) as well as the divertor. In fact, while the ITER divertor heat removal technology has been adopted, the ITER FW concept has been shown in the past years to be inadequate for EU-DEMO. This is due to the higher foreseen irradiation damage level, which requires structural materials (like Eurofer) able to withstand more than 5 dpa of neutron damage. This solution, however, limits the tolerable steady-state heat flux to ~1 MW/m2, i.e. a factor 3–4 below the ITER specifications. For this reason, poloidally and toroidally discontinuous protection limiters are implemented in EU-DEMO. Their role consists in reducing the heat load on the FW due to charged particles, during steady state and, more importantly, during planned and off-normal plasma transients. Concerning the divertor configuration, EU-DEMO currently assumes an ITER-like, lower single null (LSN) divertor, with seeded impurities for the dissipation of the power. However, this concept has been shown by numerous simulations in the past years to be marginal during steady-state (where a detached divertor is necessary to maintain the heat flux below the technological limit and to avoid excessive erosion) and unable to withstand some relevant transients, such as large ELMs and accidental loss of detachment. Various concepts, deviating from the ITER design, are currently under investigation to mitigate such risks, for example in-vessel coils for strike point sweeping in case of reattachment, as well as alternative divertor configurations. Finally, a broader discussion on the impact of divertor protection on the overall machine design is presented

A Kir6.2 mutation causing severe functional effects in vitro produces neonatal diabetes without the expected neurological complications

AIMS/HYPOTHESIS: Heterozygous activating mutations in the pancreatic ATP-sensitive K+ channel cause permanent neonatal diabetes mellitus (PNDM). This results from a decrease in the ability of ATP to close the channel, which thereby suppresses insulin secretion. PNDM mutations that cause a severe reduction in ATP inhibition may produce additional symptoms such as developmental delay and epilepsy. We identified a heterozygous mutation (L164P) in the pore-forming (Kir6.2) subunit of the channel in three unrelated patients and examined its functional effects. METHODS: The patients (currently aged 2, 8 and 20 years) developed diabetes shortly after birth. The two younger patients attempted transfer to sulfonylurea therapy but were unsuccessful (up to 1.1 mg kg(-1) day(-1)). They remain insulin dependent. None of the patients displayed neurological symptoms. Functional properties of wild-type and mutant channels were examined by electrophysiology in Xenopus oocytes. RESULTS: Heterozygous (het) and homozygous L164P K(ATP) channels showed a marked reduction in channel inhibition by ATP. Consistent with its predicted location within the pore, L164P enhanced the channel open state, which explains the reduction in ATP sensitivity. HetL164P currents exhibited greatly increased whole-cell currents that were unaffected by sulfonylureas. This explains the inability of sulfonylureas to ameliorate the diabetes of affected patients. CONCLUSIONS/INTERPRETATION: Our results provide the first demonstration that mutations such as L164P, which produce a severe reduction in ATP sensitivity, do not inevitably cause developmental delay or neurological problems. However, the neonatal diabetes of these patients is unresponsive to sulfonylurea therapy. Functional analysis of PNDM mutations can predict the sulfonylurea response

EIF2S3 Mutations Associated with Severe X-Linked Intellectual Disability Syndrome MEHMO

Impairment of translation initiation and its regulation within the integrated stress response (ISR) and related unfolded-protein response has been identified as a cause of several multisystemic syndromes. Here, we link MEHMO syndrome, whose genetic etiology was unknown, to this group of disorders. MEHMO is a rare X-linked syndrome characterized by profound intellectual disability, epilepsy, hypogonadism and hypogenitalism, microcephaly, and obesity. We have identified a C-terminal frameshift mutation (Ile465Serfs) in the EIF2S3 gene in three families with MEHMO syndrome and a novel maternally inherited missense EIF2S3 variant (c.324T>A; p.Ser108Arg) in another male patient with less severe clinical symptoms. The EIF2S3 gene encodes the gamma subunit of eukaryotic translation initiation factor 2 (eIF2), crucial for initiation of protein synthesis and regulation of the ISR. Studies in patient fibroblasts confirm increased ISR activation due to the Ile465Serfs mutation and functional assays in yeast demonstrate that the Ile465Serfs mutation impairs eIF2gamma function to a greater extent than tested missense mutations, consistent with the more severe clinical phenotype of the Ile465Serfs male mutation carriers. Thus, we propose that more severe EIF2S3 mutations cause the full MEHMO phenotype, while less deleterious mutations cause a milder form of the syndrome with only a subset of the symptoms

Identification of a Novel β-Cell Glucokinase (GCK) Promoter Mutation (−71G>C) That Modulates GCK Gene Expression Through Loss of Allele-Specific Sp1 Binding Causing Mild Fasting Hyperglycemia in Humans

OBJECTIVE: Inactivating mutations in glucokinase (GCK) cause mild fasting hyperglycemia. Identification of a GCK mutation has implications for treatment and prognosis; therefore, it is important to identify these individuals. A significant number of patients have a phenotype suggesting a defect in glucokinase but no abnormality of GCK. We hypothesized that the GCK beta-cell promoter region, which currently is not routinely screened, could contain pathogenic mutations; therefore, we sequenced this region in 60 such probands. RESEARCH DESIGN AND METHODS: The beta-cell GCK promoter was sequenced in patient DNA. The effect of the identified novel mutation on GCK promoter activity was assessed using a luciferase reporter gene expression system. Electrophoretic mobility shift assays (EMSAs) were used to determine the impact of the mutation on Sp1 binding. RESULTS: A novel -71G>C mutation was identified in a nonconserved region of the human promoter sequence in six apparently unrelated probands. Family testing established cosegregation with fasting hyperglycemia (> or = 5.5 mmol/l) in 39 affected individuals. Haplotype analysis in the U.K. family and four of the Slovakian families demonstrated that the mutation had arisen independently. The mutation maps to a potential transcriptional activator binding site for Sp1. Reporter assays demonstrated that the mutation reduces promoter activity by up to fourfold. EMSAs demonstrated a dramatic reduction in Sp1 binding to the promoter sequence corresponding to the mutant allele. CONCLUSIONS: A novel beta-cell GCK promoter mutation was identified that significantly reduces gene expression in vitro through loss of regulation by Sp1. To ensure correct diagnosis of potential GCK-MODY (maturity-onset diabetes of the young) cases, analysis of the beta-cell GCK promoter should be included