Selective Theca Cell Dysfunction in Autoimmune Oophoritis Results in Multifollicular Development, Decreased Estradiol, and Elevated Inhibin B Levels

We describe the clinical course of three women with presumptive autoimmune oophoritis who developed multiple follicles but very low to undetectable estradiol levels. Multiple follicles developed spontaneously in all subjects and during pulsatile GnRH treatment for ovulation induction in subject 1. The development of multiple dominant follicles was accompanied by LH levels in the postmenopausal range and FSH levels at the upper limit for premenopausal women. Serum inhibin B levels were elevated appropriately in the setting of multifollicular development, but estradiol levels remained low. Measurement of estradiol precursors demonstrated androstenedione and estrone levels below the 95th percentile in normal women. Adrenal cortical antibodies, and antibodies to 21-hydroxylase and P450 side chain cleavage enzymes were identified in all subjects. All subjects met the criteria for premature ovarian failure during follow-up. Subject 1 later developed adrenal failure, whereas subject 3 had adrenal failure at the time of the study. These subjects elucidate the hormonal pattern in autoimmune oophoritis, before the full criteria for premature ovarian failure are met. The elevated inhibin A and B levels, which accompany the development of multiple small and dominant follicles in these women, suppress FSH relative to LH levels, virtually independent of estradiol. These data provide further evidence for an important role of inhibin B and inhibin A in the negative feedback control of FSH. In addition, the normal inhibin A and inhibin B production in the absence of estradiol precursors and estradiol provide insight into the selective dysfunction of the theca cells in autoimmune oophoritis

Female Library Science Students and the Occupational Stereotype: Fact or Fiction?

published or submitted for publicatio

The epiphytic bryophyte community of Atlantic oak woodlands shows clear signs of recovery following the removal of invasive Rhododendron ponticum

Peer reviewedPostprin

Development of a Root Caries Prediction Model in a Population of Dental Attenders

Acknowledgement This study was conducted as part of the doctoral thesis of P.A.F. We would like to thank the participating dental practice teams and patients without whose valuable contribution this study could not have taken place. We would like to thank our colleagues in the INTERVAL Trial team Funding INTERVAL was funded by the NIHR HTA programme [project numbers 06/35/05 (Phase I) and 06/35/99 (Phase II)]. No additional funding was obtained to conduct the prediction study presented in this paper. The views expressed are those of the author(s) and not necessarily those of NIHR, the NHS or the Department of Health and Social Care.Peer reviewedPublisher PD

Depot Medroxyprogesterone Acetate Use and Blood Lead Levels in a Cohort of Young Women

BACKGROUND: Injectable contraceptive use is common, with 74 million users worldwide. Use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) is associated with bone mineral density loss. We hypothesize that increased bone resorption with DMPA use allows for mobilization of the toxic metal lead stored in bone to blood, presenting users with increased systemic exposure to lead. OBJECTIVE: The objective of our study was to investigate the association between current DMPA use and blood lead concentrations. METHODS: We conducted a cross-sectional analysis using enrollment data from the Study of Environment, Lifestyle & Fibroids (SELF), a cohort of 1,693 African-American women who were 23-35 years of age. Data on DMPA use were collected by computer-assisted telephone interview. Blood lead concentrations were measured in whole blood samples among 1,548 participants (91% of cohort). We estimated the adjusted percent difference in blood lead concentrations and 95% confidence intervals (CI) between current DMPA users and nonusers using multivariable linear regression. RESULTS: Geometric mean blood lead concentration was 0.69 μg/dL (95% CI: 0.67, 0.71). After adjustment, current DMPA users (7% of cohort) had blood lead concentrations that were 18% higher than those of nonusers (95% CI: 8%, 29%). Similar associations were observed with additional analyses to assess for potential bias from smoking, DMPA-induced amenorrhea, use of estrogen-containing contraceptives, having given birth in the prior year, and history of medical conditions or current medication use associated with bone loss./ DISCUSSION: Our results indicate that current DMPA use is associated with increased blood lead concentrations. Further research, particularly in populations highly exposed to lead, is warranted to consider tradeoffs between the adverse effects of lead on human health and the importance of DMPA as a contraceptive option to prevent unintended pregnancy. https://doi.org/10.1289/EHP7017

Preliminary Evaluation of the AFWA-NASA (ANSA) Blended Snow-Cover Product over the Lower Great Lakes Region

The Air Force Weather Agency (AFWA) - NASA (ANSA) blended-snow product utilizes EOS standard snow products from the Moderate-Resolution Imaging Spectroradiometer (MODIS) and the Advanced Microwave Scanning Radiometer for EOS (AMSR-E) to map daily snow cover and snow-water equivalent (SWE) globally. We have compared ANSA-derived SWE. with SWE values calculated from snow depths reported at approx.1500 National Climatic Data Center (NCDC) coop stations in the Lower Great Lakes basin. Our preliminary results show that conversion of snow depth to SWE is very sensitive to the choice of snow density (we used either 0.2 or 03 as conversion factors). We found overall better agreement between the ANSA-derived SWE and the co-op station data when we use a snow density of 0.3 to convert the snow depths to SWE. In addition, we show that the ANSA underestimates SWE in densely-forested areas, using January and February 2008 ANSA and co-op data. Furthermore, apparent large SWE changes from one day to the next may be caused by thaw-re-freeze events, and do not always represent a real change in SWE. In the near future we will continue the analysis in the 2006-07 and 2007-08 snow seasons

The role of microRNA-binding site polymorphisms in DNA repair genes as risk factors for bladder cancer and breast cancer and their impact on radiotherapy outcomes

MicroRNAs (miRNAs) are involved in post-transcriptional regulation of gene expression through binding to messenger RNAs (mRNA) thereby promoting mRNA degradation or altered translation. A single-nucleotide polymorphism (SNP) located within a miRNA-binding site could thus alter mRNA translation and influence cancer risk and treatment response. The common SNPs located within the 3′-untranslated regions of 20 DNA repair genes were analysed for putative miRNA-binding sites using bioinformatics algorithms, calculating the difference in Gibbs free binding energy (ΔΔG) for each wild-type versus variant allele. Seven SNPs were selected to be genotyped in germ line DNAs both from a bladder cancer case–control series (752 cases and 704 controls) and 202 muscle-invasive bladder cancer radiotherapy cases. The PARP-1 SNP rs8679 was also genotyped in a breast cancer case–control series (257 cases and 512 controls). Without adjustment for multiple testing, multivariate analysis demonstrated an association with increased bladder cancer risk with PARP1 rs8679 (Ptrend = 0.05) while variant homozygotes of PARP1 rs8679 were also noted to have an increased breast cancer risk (P = 0.03). In the radiotherapy cases, carriers of the RAD51 rs7180135 minor allele had improved cancer-specific survival (hazard ratio 0.52, 95% confidence interval 0.31–0.87, P = 0.01). This is the first report of associations between DNA repair gene miRNA-binding site SNPs with bladder and breast cancer risk and radiotherapy outcomes. If validated, these findings may give further insight into the biology of bladder carcinogenesis, allow testing of the RAD51 SNP as a potential predictive biomarker and also reveal potential targets for new cancer treatments

Impact of estradiol variability and progesterone on mood in perimenopausal women with depressive symptoms

OBJECTIVE: To determine whether estradiol variability, ovulatory levels of progesterone, and VMS burden are independently associated with perimenopausal depressive symptomatology. DESIGN AND INTERVENTION: Depressive symptoms, serum levels of estradiol and progesterone, and VMS frequency were assessed weekly in an 8-week observational study. Association of mood with estradiol variability, ovulatory levels of progesterone, and VMS frequency were estimated using generalized estimating equation models. SETTING: Academic medical center. PATIENTS: Fifty unmedicated perimenopausal women with mild-to-moderate depressive symptoms (mean Montgomery-Asberg Depression Rating Scale [MADRS] score 15.5 +/- 5.3). RESULTS: During the study, 90.0% of participants had varying estradiol levels, 51.1% had ovulatory progesterone levels, and 90% had VMS. Greater estradiol variability and absence of progesterone levels consistent with ovulation, but not VMS frequency, are associated with higher levels of depressive symptoms (beta= 0.11, 95% confidence interval [95%CI] [0.04 to 0.18, p=0.001]; beta= -2.62 [95%CI -4.52 to -0.71, p=0.007], respectively), after accounting for higher BMI, lifetime history of depression, and stressful life events. CONCLUSIONS: Increasing dysregulation of ovarian hormones, but not VMS, associates with more depressive symptom burden during perimenopause. These results suggest that perimenopausal mood instability is driven by the underlying hormonal dysregulation of the menopause transition involving changes in both estradiol and progesterone

Dynamic expression of genes associated with schizophrenia and bipolar disorder across development

Common genetic variation contributes a substantial proportion of risk for both schizophrenia and bipolar disorder. Furthermore, there is evidence of significant, but not complete, overlap in genetic risk between the two disorders. It has been hypothesised that genetic variants conferring risk for these disorders do so by influencing brain development, leading to the later emergence of symptoms. The comparative profile of risk gene expression for schizophrenia and bipolar disorder across development over different brain regions however remains unclear. Using genotypes derived from genome-wide associations studies of the largest available cohorts of patients and control subjects, we investigated whether genes enriched for schizophrenia and bipolar disorder association show a bias for expression across any of 13 developmental stages in prefrontal cortical and subcortical brain regions. We show that genetic association with schizophrenia is positively correlated with expression in the prefrontal cortex during early midfetal development and early infancy, and negatively correlated with expression during late childhood, which stabilises in adolescence. In contrast, risk-associated genes for bipolar disorder did not exhibit a bias towards expression at any prenatal stage, although the pattern of postnatal expression was similar to that of schizophrenia. These results highlight the dynamic expression of genes harbouring risk for schizophrenia and bipolar disorder across prefrontal cortex development and support the hypothesis that prenatal neurodevelopmental events are more strongly associated with schizophrenia than bipolar disorder