bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-593 Sex-Specific Modifications in MicroRNAs Contained in Exosomes of Astrocytes in Response to Palmitic Acid
Authors: Chowen Julie Ann , Guerra-Cantera Santiago , Collado-Perez Roberto , Argente Jesús , Frago Laura M 
Published: May 2020

Abstract
Communication between astrocytes and neurons is fundamental for correct functioning of the brain, in both physiological and pathophysiological situations. It is clear that astrocytes play an active role in metabolic control, but much is yet to be learned regarding how these glial cells and the neurons involved in energy intake/expenditure communicate to regulate energy homeostasis. We hypothesized that miRNAs contained in exosomes are an important means of cross-talk between these cells. Our objectives here were to determine whether the miRNA content of exosomes released by hypothalamic astrocytes changes in function of nutrient signals and if these signals are similar between males and females. To this end, primary hypothalamic astrocyte cultures were prepared from 2-day old male and female mice, using a standard protocol, and treated with palmitic acid (PA, 0.5 mM) or vehicle for 24 hours. The exosomes secreted into the culture media were purified and next generation sequencing analysis of the miRNAs contained in these microvesicles performed. Over 200 known miRNAs were identified in the samples. Heat map analysis of the 50 miRNAs most highly expressed across all samples showed significant differences based on sex and PA exposure, as well as differential changes between sexes in response to PA. Of the 25 most highly expressed miRNAs, 24 were significantly different between males and females (Benjamini-Hochberg FDR corrected p-values, between p&lt;0.05 and p&lt;0.0001). In response to PA, 190 miRNAs changed significantly in female astrocytes, but only 92 in male astrocytes; hence, after exposure to PA, 59 miRNAs were identified to be differentially expressed in exosomes of male and female astrocytes. Gene ontology enrichment analysis indicated that modifications in the miRNAs identified here could be related to biological processes such as response to cell injury, as might be expected, but also protein polymerization, receptor trafficking, intracellular signaling, microtubule polymerization, vasodilation, and cytoskeleton organization. Our results suggest that astrocytes communicate changes in nutrient availability to other cell types through miRNAs. Verification and determination of the specific responses to the modification in these miRNAs are now necessary.
SAT-174 Adrenal Incidentalomas: Prevalence and Referral Patterns in a UK University Hospital Using Real-Life Data
Authors: Hanna Fahmy W F , Hancock Sarah , George Cherian , Issa Basil George , Powner Gillian , Waldron Julian , Golash Anurag , Fryer Anthony 
Published: May 2020

Abstract
The estimated prevalence of adrenal incidentaloma at abdominal CT scan is 0.5-2% (1). However, from clinical practice, we noticed that incidentalomas are referred from other imaging modalities (eg MRI) and of other sites (eg thorax, spine). We therefore explored the relationship between prevalence rates and (i) imaging modality and (ii) its change over time, in a real world clinical setting from a large UK teaching hospital/trauma centre. We also examined the referral pattern of potential lesions to endocrinology. We extracted data from all radiology reports for all CT and MRI scans from Jan 2018-Oct 2019. We utilised a key phrase search strategy (eg adrenal adenoma/lesion/mass/nodule/incidentaloma, incidental adrenal, indeterminate adrenal). Where possible we excluded false hits (eg no adrenal lesion). These were linked to the referral patterns as identified by a referral logged or an attendance (new or follow-up) to endocrine clinic 3 months post index scan. Preliminary data showed that, from a total of 127878 scans performed, 2604 potential lesions were reported (prevalence 2.0%), comprising 2496/88838 (2.8%) CT scans and 108/39040 (0.3%) MRI scans. The number of scans/month increased in 2019 vs 2018 (6.9% for CT and 12.6% for MRI). Only 9.0% and 15.7% of reported potential lesions detected by CT and MRI, respectively, were referred for endocrine review. Hence, MRI patients were more likely to be referred than those with CT scans (p=0.018). Referral rates were lower in 2019 than 2018 (8.6% vs 14.4%; p less than 0.001). This approach has its limitations but allows efficiently review of large cohorts. Adrenal incidentalomas pose a rising challenge in view of increasing reliance on scanning. Despite a dedicated adrenal multidisciplinary team with a national track record in improving management of incidentalomas (2), the referral rate of potential lesions is worryingly low and not improving, with &gt;90% of cases overlooked. This work is part of on-going innovation to enhance the pick-up rate for these cases whilst addressing the increased endocrine workload in a cost-effective manner. 1. Barzon L, Sonino N, Fallo F, Palu G, Boscaro M. Prevalence and natural history of adrenal incidentalomas. Eur J Endocrinol. 2003;149:273-285. 2. Hanna FWF, Issa BG, Lea SC, George C, Golash A, Firn M, Ogunmekan S, Maddock E, Sim J, Xydopoulos G, Fordham R, Fryer AA. Adrenal lesions found incidentally: how to improve clinical and cost-effectiveness. BMJ Open Quality. 2019;In press.
SUN-186 Case Report: Mifepristone Taper in an Individual with Equivocal Cushing’s Syndrome Screening Tests
Authors: Martin Christopher , Perez-Molinar David , Drake Tyler C 
Published: May 2020

Abstract
We present a 75-year-old male evaluated by the inpatient endocrine service during an admission for hemorrhagic stroke. Approximately 1 year prior to this admission he was started on mifepristone therapy for presumed Cushing’s Syndrome. Initial Cushing’s work-up was equivocal: 1 mg dexamethasone suppression cortisol level of 1.9 and midnight salivary cortisol 167 ng/dl. Random ACTH measurement was not obtained as part of this initial evaluation. Review of prior imaging studies did not demonstrate obvious culprit pituitary nor adrenal lesions. Mifepristone induced hyperaldosteronism, thyroid dysfunction and adrenal insufficiency were demonstrated presumably secondary to cortisol receptor antagonist induced up-regulation of adrenocorticotropic hormone and cortisol. We describe our experience stopping mifepristone and performing re-evaluation. We propose a tapering protocol in the setting of potentially untreated Cushing’s Syndrome and suggest use as a bridge therapy to surgical intervention rather than destination therapy.
SAT-161 Adrenal Incidentalomas: Pattern of Referral According to Clinical Specialty
Authors: Hanna Fahmy W F , Hancock Sarah , George Cherian , Issa Basil George , Lea Simon , Powner Gillian , Waldron Julian , Golash Anurag , Fryer Anthony 
Published: May 2020

Abstract
Whilst the estimated prevalence of adrenal incidentaloma is 0.5-2% following abdominal CT scan (1), little is known about subsequent endocrine referral patterns according to clinical specialty. We therefore examined the range of specialties that were responsible for requesting CT and MRI scans that led to reporting potential adrenal lesions. We also explored the referral pattern to endocrinology following identification. We extracted data from all radiology reports for all CT and MRI scans from Jan 2018-Oct 2019. We utilised a key phrase search strategy (eg adrenal adenoma/lesion/mass/nodule/incidentaloma, incidental adrenal, indeterminate adrenal). Where possible we excluded false hits (eg no adrenal lesion). These were lined to the referral patterns as identified by a referral logged or an attendance (new or follow-up) to endocrine clinic 3 months post index scan. These data were stratified by requesting specialty. Preliminary data showed that, out of 127878 scans, 2021 patients were identified to have a potential adrenal incidentaloma. These requests came from a total of 45 different clinical specialities (medical and surgical). The top 12 specialties accounted from 82.8% of these referrals. Medical specialties (renal, gastroenterology, respiratory, general medicine, acute medicine and geriatric medicine) accounted for 50.2%. The remaining 32.6% were via surgical specialities. The overall referral pattern in these cases was 8.5% with no difference between medical (8.6%) and surgical (8.4%) specialties. In conclusion, adrenal incidentalomas are potentially identifiable across a wide range of specialties. Currently, despite a dedicated adrenal multidisciplinary team and nationally-acknowledged quality improvement programme for the management of adrenal incidentalomas (2), the majority of cases are overlooked and not referred for endocrine review as suggested in current guidelines. We expect the findings in our centre to be reproducible elsewhere. We are considering innovative approaches to improve the process and cope with the additional workload cost-effectively. 1. Barzon L, Sonino N, Fallo F, Palu G, Boscaro M. Prevalence and natural history of adrenal incidentalomas. Eur J Endocrinol. 2003;149:273-285. Hanna FWF, Issa BG, Lea SC, George C, Golash A, Firn M, Ogunmekan S, Maddock E, Sim J, Xydopoulos G, Fordham R, Fryer AA. Adrenal lesions found incidentally: how to improve clinical and cost-effectiveness. BMJ Open Quality. 2019;In press.
SAT-168 Adrenal Incidentalomas: Impact of Patient Age on Referral Rates for Endocrine Evaluation
Authors: Fryer Anthony , Hancock Sarah , George Cherian , Issa Basil George , Lea Simon , Powner Gillian , Waldron Julian , Golash Anurag , Hanna Fahmy W F 
Published: May 2020

Abstract
It is estimated that the prevalence of adrenal incidentaloma increases with age: ~3% of those aged 50 years, rising to 10% in those &gt;70 years (1). Given the aging population together with increased utilisation of cross-sectional imaging in the UK (eg CT urogram, MR angiogram), we explored the proportion of patients with adrenal incidentaloma by age based on current imaging trends. Furthermore, there is no information currently available on the relationship between age and pattern of endocrine referrals. We extracted data for all CT and MRI scans from Jan 2018-Oct 2019 and used key phrases in radiology reports (eg adrenal adenoma/lesion/mass/nodule/incidentaloma, incidental adrenal, indeterminate adrenal) to identify potential lesions. We also extracted data on patient age and referral patterns as identified by a logged referral or an attendance (new or follow-up) to endocrine clinic 3 months post index scan, stratified by 10 year age groups. Where possible, we excluded false hits (eg no adrenal lesion). Preliminary data showed that, of the 2604 potential lesions identified by CT and MRI scans, 78.7% were on patients aged over 60 years. The numbers of identified lesions gradually increased with age to a peak in the 71-80 year age group after which these declined. Whilst patients younger that 60 years had fewer potential lesions identified, they were more likely to be referred to endocrine services (73 out of 55 patients; 13.2%) than those in the older age group (168 out of 2049; 8.2%; p&lt;0.001). Indeed there was a statistically significant trend towards decreasing referral with age group (Chi-squared test for trend; p&lt;0.001). In conclusion, patients over 60 years have a higher number of potential adrenal incidentalomas. However, this group is less likely to be referred for endocrine evaluation. This is particularly concerning given the large number of scans requested and the higher prevalence of incidentalomas in this age group. This study represents preparatory work on innovations to enhance case detection, particularly in the older age groups (2). 1. Fassnacht M, Arlt W, Bancos I, et al. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline. Eur J Endocrinol. 2016;175:G1-G34 2. Hanna FWF, Issa BG, Lea SC, George C, Golash A, Firn M, Ogunmekan S, Maddock E, Sim J, Xydopoulos G, Fordham R, Fryer AA. Adrenal lesions found incidentally: how to improve clinical and cost-effectiveness. BMJ Open Quality. 2019;In press.
MON-724 Crude Protein Extract of Pyropia Yezoensis Protects Against Tumor Necrosis Factor-á-Induced Apoptosis and Atrophy in C2C12 Myotubes
Authors: Lee Min-Kyeong , Nam Taek-Jeong , Choi Youn Hee 
Published: May 2020

Abstract
Proinflammatory cytokines such as tumor necrosis factor (TNF)-α play an important role in the development of skeletal muscle atrophy, and TNF-α-induced apoptosis may mediate skeletal muscle atrophy. Therefore, we evaluated the effect of Pyropia yezoensis crude protein (PYCP) on TNF-α-induced apoptosis and identified the involved signaling pathways. For this purpose, C2C12 myotubes were treated with 20 ng/mL TNF-α in the presence or absence of 25-100 μg/mL PYCP for 48 h. Treatment with TNF-α markedly increased the protein level of TNF-receptor 1 (TNF-R1). In contrast, treatment with PYCP downregulated the TNF-α-induced increase in the TNF-R1 protein level. Also, the expression of Bax, Bcl-2, cytochrome C, and apoptosis-inducing factor, markers of apoptosis in myofibers, was increased by TNF-α, but this effect was inhibited by PYCP in a concentration-dependent manner. In addition, exposure of C2C12 myotubes to TNF-α for 48 h enhanced the activity of caspase-3, which was significantly inhibited by PYCP. Furthermore, poly[ADP-ribose] polymerase cleavage and histone-associated DNA fragmentation were markedly increased by TNF-α and attenuated by PYCP in a concentration-dependent manner. In conclusion, the ability of PYCP to inhibit the apoptosis induced by TNF-α suggests that it has therapeutic potential for skeletal muscle atrophy.
OR20-06 Kisspeptin as a Biomarker for Pregnancy Complications
Authors: Phylactou Maria , Abbara Ali , Al-Memar Maya , Eng Pei Chia , Comninos Alexander N , Izzi-Engbeaya Chioma , Clarke Sophie A , Mills Edouard , Nadir Rans , Sykes Mark , Ewa Pacuszka , Yang Lisa , Fourie Hanine , Bech Paul , Kelsey Tom , Bourne Tom , Dhillo Waljit Singh 
Published: May 2020

Abstract
Background:
Placentation (invasion of the placenta into the maternal endometrium) is hypothesised to be critical for healthy placental function and is abnormal in two thirds of miscarriage. Kisspeptin has emerged as a putative regulator of physiological placentation; it is highly expressed in placental syncitio-trophoblasts, whereas its receptor is expressed in both syncitio- and cyto-trophoblasts, such that kisspeptin is hypothesized to play an important paracrine role to regulate placentation. Circulating kisspeptin levels are considerably raised during healthy pregnancy and are reduced in women with miscarriage.
Aim:
We aimed to investigate the utility of circulating kisspeptin concentrations in the assessment of pregnancy complications and assess whether kisspeptin provides additional diagnostic information compared to beta human chorionic gonadotropin (βhCG) alone.
Methods:
This study was performed in collaboration with the Early Pregnancy Outcome Study (EPOS), which aims to identify novel pregnancy biomarkers. Women were invited to attend every fortnight for blood-sampling, clinical and ultrasound assessment during the first trimester, and repeated during the second and third trimesters. Asymptomatic women with healthy pregnancy (n=265) provided 960 blood-samples. Women with pregnancy complications including miscarriage (n=95), pre-eclampsia (PET; n=24), pregnancy induced hypertension (PIH; n=14), gestational diabetes (GDM; n=41), preterm birth (PTB; n=14) and intrauterine growth restriction (IUGR; n=24) provided 569 blood-samples.
Results:
Gestation-adjusted circulating kisspeptin and βhCG levels were lower, by 66% and 57%, respectively, in women with miscarriage compared to healthy pregnant controls (p&lt;0.0001). Area under ROC curve for diagnosis of miscarriage was greater for the combination of both kisspeptin and βhCG together (0.92) than for either measure alone (βhCG 0.859, kisspeptin 0.874). An adjusted logistic regression model revealed that an 100pmol/L increase in plasma kisspeptin reduced the odds of miscarriage by 42%. Gestation-adjusted kisspeptin levels were lower in women with GDM (P=0.002), or IUGR (P&lt;0.0001), and higher in women with PTB (P=0.004). Kisspeptin increased with gestation greater in PET (P=0.008) and PIH (P&lt;0.0001) than in healthy controls.
Conclusions:
Plasma kisspeptin is a promising biomarker for pregnancy complications and provides additional diagnostic capability over that provided by βhCG alone.
SAT-017 Relationship Between Vitamin D Levels and Signs of Polycystic Ovary Syndrome
Authors: Smykalova Anastasia , Kalinchenko Svetlana , Safi Aigul , Orazov Mekan , Nizhnik Alexander 
Published: May 2020

Abstract
An analysis of the structure of the causes of infertility shows that up to almost 25% of women of reproductive age ovulation disorders are observed. Hormonal disorders leading to the absence of ovulation, began to play a leading role in the etiology of infertility, special vitamin D deficiency, while today it has been established that its D receptors (VDR) are localized in most organs, including reproductive ones. VDR affect the expression of 1000 genes and play a crucial role in the implementation of sex hormones function.
The aim of the study was to assess the vitamin D level in women of reproductive age, depending on the presence of signs of PCOS and waist circumference (WC).
71 women from 19 to 44 years old were examined of these, 41 patients were diagnosed with PCOS and impaired ovulatory function, in 30 patients the ovulatory cycle was preserved, and signs of PCOS were not detected. The level of vitamin 25 (OH) D3 in the serum of the subjects was evaluated by tandem chromato-mass spectrometry at the ArchiMed clinic of new medical technologies, Moscow.
In the recommendations of the Canadian “The Vitamin D society”, 40-60 ng/ml the optimal level of serum vitamin D, a concentration of 20-40 ng/ml insufficiency, &lt;20 ng/ml as a deficiency.
Vitamin D deficiency was detected in 57% of women in both groups, with a pronounced deficiency (&lt;10 ng/ml) in 17%, insufficiency was observed in 43% of cases, a sufficient level was not detected in any of the subjects. The average level of vitamin D in patients with PCOS was 18.2 (2 to 32.3) ng/ml, the value in patients without signs of PCOS was 18.5 (6.8 to 31) ng/ml.
Comparison of the vitamin D value with WC showed that in women with PCOS with an WC &lt;80 cm the value of this indicator was 18.8 ng/ml, and for WC ≥ 80 cm it was statistically significantly lower - 13.3 ng/ml (p&lt;0.05).
Conclusion. High prevalence of vitamin D deficiency among patients of reproductive age, with no differences in the magnitude of this indicator depending on the presence of signs of PCOS and persistent ovulation.
Difference was established between the levels of vitamin D in patients with PCOS depending on the waist circumference - its insufficiency increases with an increase in WC.
The results of the study suggest that the deficiency of vitamin D in the body increases with the aggravation of hormonal dysfunction in PCOS, which should be taken into account by specialists during the management of this category of patients and the treatment of infertility.
SUN-134 Estrogen Induces Granulocytic Myeloid Derived Suppressor Cell Production to Potentially Modulate Lymphangioleiomyomatosis (LAM) Tumor Progression
Authors: Minor Briaunna , Hammes Stephen R 
Published: May 2020

Abstract
Affecting almost exclusively women, lymphangioleiomyomatosis (LAM) is a rare lung disease characterized by estrogen-sensitive metastatic smooth muscle cell-like adenomas that grow slowly, resulting in cystic lung change and loss of pulmonary function. LAM tumors are caused by mutations in tuberous sclerosis complex 1 or 2 genes (TSC1 or TSC2). Mutations in TSC1 or TSC2 genes results in deficient inhibitory regulation of the mammalian target of rapamycin complex 1 (mTORC1), which in turn leads to increased mTORC1 activity and cell proliferation. There is no consensus amongst LAM researchers regarding the origin of these estrogen receptor-positive smooth muscle like LAM cells; however, we previously reported inactivation of TSC2 in the mouse uterus results in notable LAM features in the setting of primary myometrial tumors. Approximately 50% of the TSC2-null mice had metastatic myometrial tumors present in the lung, suggesting that LAM tumor cells might in fact originate from the uterus, thus explaining the female sexual dimorphism, the estrogen sensitivity, and the metastatic nature of the LAM tumors.
Interestingly, flow cytometry revealed large numbers of granulocytic myeloid derived suppressors cells (G-MDSCs) in the blood and myometrial tumors of uterine-specific Tsc2 null mice. MDSCs are known to accumulate in the setting of chronic inflammation caused by trauma, infection, and various cancers. This granulocytic subtype not only has the capacity to suppress anti-tumor immune cells of the tumor microenvironment, but also directly promotes tumor cell malignant neoplasicity. We found that Tsc2-null myometrial tumors required MDSCs for normal progression, as MDSC depletion or inhibition of MDSC recruitment reduced tumor growth. We have showed that these tumors expressed estrogen receptors and were exquisitely sensitive to estrogen, while other studies demonstrate that G-MDSCs are also positively influenced by estradiol. Therefore, we hypothesized that, in addition to direct effects of estrogen on tumor cells, estrogen also stimulates tumor growth by promoting MDSC production in the bone marrow. We have developed a technique to stimulate MDSC production from mouse bone marrow. Using this strategy, we found that estradiol is indeed a potent promotor of G-MDSC production. These effects occurred in both male and female bone marrow. Employing both pharmacologic agents and bone marrow from ERα; knockout mice, we showed that ERα; is necessary for promoting a G-MDSC fate for immature myeloid cells and precursors. Thus, estradiol may have duel effects in LAM, both directly promoting tumor growth and indirectly upregulating MDSC production, which in turn promotes tumor growth. We propose that these estrogen effects on MDSC production are not limited to LAM and may be important regulators of tumor growth in many tissues.