bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-134 Incorporating Transgender Competent Care into the Medical School Curriculum
Authors: Lamos Elizabeth M , Quezada Sandra , Malek Rana 
Published: May 2020

Abstract
BACKGROUND: According to recent estimates, the US transgender population has doubled in the last decade. Incorporating transgender competent care into medical education is a growing need, and a focus of the AAMC. Care of the transgender individual is multifaceted, and medical school curriculae on transgender care are limited and lack standardization. Similarly, strategies for measuring effectiveness and impact of these curriculae remain limited.
Methods: Over 3 years, the use of a transgender clinical correlation in the endocrine section of the second-year medical student pre-clerkship curriculum progressed to the use of a triple modality intervention. This included (1) a self-directed written handout with terminology and the basic tenants of medical transition therapy with an optional podcast, (2) a traditional presentation covering social, ethical and multi-disciplinary transgender care, and (3) an interactive session with a transfemale and transmale patient. An anonymous 8 question pre-and post-intervention survey using an electronic clicker system was performed. Questions included interest level, comfort level with various aspects of transgender-competent care and resource awareness.
Results: Prior to the intervention, 74% of students were interested in learning more about transgender competent care. After the learning intervention, in all questions focusing on knowledge and skills of transgender care, students reported a significant increase in their comfort level (Figure 1, p&lt;0.5, all). This included reporting now higher comfort levels regarding goals of hormone therapy (8 to 63%), use of transgender affirming medications (19 to 44%), barriers to care (30 to 79%), and long term and multi-disciplinary care (8 to 63% and 13 to 71%, pre- and post-intervention respectively). At the end of the intervention, students felt they had more resources to access information about transgender-competent care (pre-23% to post-94% p= &lt;0.05).
Conclusion: Knowledge and skills in the care of transgender individuals is poor in the pre-clerkship medical school years. The interest to learn about transgender care is positive. This multi-modality intervention was successful in increasing medical student comfort and knowledge about comprehensive transgender care, and increased student awareness of available resources. Introduction of transgender care should be implemented early in medical student training.
1. Hembree WC et al. Endocrine Treatment of Gender-Dysphoric/ Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline. Endocr Pract. 2017 Dec;23(12):1437.
2. Harris M, Johnson C. Only Human. Trans Kids Update: Dating, PMS, And, Yeah, Bathrooms. NYPR WNYC Studios, 2017.
Figure 1. Change in student comfort across transgender competent care.
* p &lt; 0.05
SUN-559 Involvement of Sarco/Endoplasmic Reticulum Ca- ATPase (SERCA) in Membrane Progesterone Receptor Alpha (PAQR7)-Mediated Progesterone Induction of Vascular Smooth Muscle Relaxation
Authors: Pang Yefei , Thomas Peter 
Published: May 2020

Abstract
Progesterone (P4) exerts multiple beneficial effects on the human cardiovascular system through its actions on vascular endothelial cells and also by acting directly on vascular smooth muscle cells (VSMCs). Membrane progesterone receptor alpha (mPRα) has been shown to mediate the rapid P4-induction of human VSMC relaxation through activation of MAPK, Akt/Pi3k and RhoA/ROCK signaling pathways and the resulting reduction of calcium influx through calcium channels. In this study, we demonstrate that treatment of cultured human VSMCs with P4 for 1-2 hours increases both the mRNA and protein expression of sarco/endoplasmic reticulum Ca- ATPase (SERCA), the major transporter of calcium from the cytosol into the sarcoplasmic reticulum (SR) during muscle relaxation. Knockdown of mPRα with siRNA completely blocked this stimulatory effect of P4 as well as that of OD 02-0, a mPR selective agonist, on SERCA protein expression. In contrast, expression levels of phospholamban (PLB), a SR protein that reversibly inhibits SERCA were downregulated by this P4 treatment, and mRNA expression of a channel that releases calcium from the SR, inositol trisphosphate receptor (IP3R), was unaltered after treatment with P4. Moreover, treatments with P4 and OD 02-0, but not with R5020, a nuclear PR agonist, increased PLB phosphorylation, which would result in disinhibition of SERCA function. P4 and OD 02-0 significantly increased calcium levels in the SR detected with Fluo-5N, a specific SR calcium indicator, and caused VSMC relaxation. These effects were blocked by cyclopiazonic acid (CPA, a SERCA inhibitor), suggesting that SERCA plays a critical role in P4 induction of VSMC relaxation. Similarly, the effects of P4 and OD 02-0 on relaxation of umbilical artery rings measured with a myograph were significantly attenuated by CPA, which confirms the critical role of SERCA in the rapid action of P4 and 02-0 on vascular muscle relaxation. P4 has previously been shown to activate MAPK and Akt signaling pathways to induce VSMC relaxation. The P4- and OD 02-0-induced increases in calcium in the SR were blocked by MAPK and Akt/Pi3k signaling inhibitors, AZD6244 and wortmannin. Taken together, these results suggest that the direct, rapid effects of P4 on relaxation of VSMCs through mPRα involves regulation of the expression and function of the SR proteins SERCA and PLB through MAPK and Akt signaling pathways.
MON-681 Dulaglutide Commonly Known as Trulicity; An Anti-Diabetic Medication Causing Small Bowel Obstruction
Authors: Gandhi Ankita , Khanam Verisha , Peterson Daymon , Patel Fenil , Kulairi Zain 
Published: May 2020

Abstract
Introduction Small bowel obstruction is a common and life threatening surgical emergency. The general causes are intra and extra-intestinal mechanical obstruction, such as from post-operative adhesions, malignancy, hernias, Crohn’s disease, and volvulus. Less frequently neurologic, metabolic, and medications interfere with intestinal motility and lead to obstructive features. Here, we present a rare case of small intestinal obstruction caused by the anti-diabetic glucagon-like peptide 1 (GLP-1) agonist, Dulaglutide (Trulicity). Case A 52-year-old male with Diabetes Mellitus, presented with two weeks of severe nausea and vomiting, accompanied by four days of diffused abdominal pain. CT scan of the abdomen showed multiple mildly distended dilated loops of the proximal jejunum. The results lead to suspect the presence of fecal stasis with an apparent transition zone of a normal caliber bowel. This is strongly indicative of partial or evolving small bowel obstruction. The patient was treated with conservative management of bowel rest and NG tube per the surgery on board. However, patient deteriorated too quickly and the partial bowel obstruction lead to full obstruction and eventually taken for an emergent surgery. With careful investigation to identify underlying causes of small bowel obstruction revealed no mechanical, structural, or metabolic explanation. However, a review of patient’s medication list disclosed a daily consumption of Dulaglutide (Trulicity). The medication was started 3 weeks prior to admission. He started developing partial bowel obstruction symptoms within one week of starting the medications. Unfortunately, surgeon ended up performing a partial resection a small bowel due to severe ischemia. Patient improved clinically in four to five days and was discharged home with an alternative anti-diabatic medications. He follows up with us in the clinic and has no signs of bowel obstructions with the other anti-diabatic medications. Discussion: Dulaglutide (Trulicity) is associated with small bowel obstruction. The side effect is more common in males and in patients who are using the medication for less than one month. A total of 8 cases were reported in 2017 with majority of them requiring surgical intervention for the small bowel obstruction. In our patient, it also required a surgical intervention and was life threatening. Unfortunately, the actual mechanism Trulicity causing the small bowel obstruction is unknown; however the moderate side effect of Trulicity is constipation. In this case, our patient was not constipated. He had normal bowel movements on a regular basis. Also, he never had any history of abdominal surgeries which can cause adhesion and lead to small bowel obstruction. All the other caused of small bowel obstructions had been ruled out and finally concluded Trulicity was the culprit of this unfortunate case.
SAT-392 The Role of β-arrestin2 in Bone Catabolic Response to Hyperparathyroidism In Vivo
Authors: Feng Gilberto Li , Grynpas Marc , Mitchell Jane 
Published: May 2020

Abstract
Primary hyperparathyroidism (PHPT) is an endocrine disorder characterized by elevated parathyroid hormone (PTH) levels and hypercalcemia caused by the overactive parathyroid glands, resulting in negative impacts on the skeleton including bone loss and increased bone fragility1. PTH binds and activates parathyroid hormone type 1 receptor (PTH1R) which primary couples to Gαs, stimulating the downstream effectors that mediate bone remodeling processes2. PTH1R activity is regulated by arrestins, specially β-arrestin2 (β-arr2), through signal termination and receptor internalization2. Previously, we have seen anabolic effects of hyperparathyroidism (cPTH) on trabecular bone in mice overexpressing Gαs3. We hypothesized that increased Gαs protein levels in osteoblasts outcompete β-arr binding to PTH1R, leading to reduced signal termination and increased bone formation. To test this hypothesis, we are testing if the deletion of β-arr2 will also result in an anabolic response to cPTH in this study. The response of β-arr2 knockout (KO) mice to cPTH have yet to be documented. The hypothesis of this study is that β-arr2 KO mice treated with cPTH will exhibit anabolic effects on the trabecular bone. Nine-week-old wild-type (WT) C57BL/6 and β-arr2 KO mice were treated for 14 days with either rPTH1-34 (80ng/g/day) or saline (PBS) using micro-osmotic pumps to simulate hyperparathyroidism. There are 8 groups (n=10 per group) including both sexes, 2 genotypes (WT and KO), and 2 treatment groups (PTH and PBS). Two 30 mg/kg doses of 0.6% calcein green were administered subcutaneously to mice at 7 and 2 days prior to euthanasia to label bones. Decalcified tibiae were embedded in paraffin for histological analysis. Undecalcified tibiae were embedded in plastic for dynamic histomorphometry. Micro-computed tomography (μCT) was used to access bone microarchitecture of femurs and vertebrae followed by biomechanical testing of bone strength. The μCT data of distal femurs show that cPTH treatment increased bone volume in female KO mice (6.864 ± 2.318 vs 4.690 ± 1.555 %; P= 0.0328; n=9 per group) and maintained bone in male KO mice (13.37 ± 2.860 vs 13.38 ± 3.135; P= 0.9968, n= 10) compared to control. Histological analysis show higher osteoclastic activity in both sexes and genotypes when treated with cPTH, suggesting that the anabolic response may be at the level of osteoblasts and osteocytes. These promising results support our hypothesis that arrestin-mediated PTH receptor downregulation plays an importance role in bone weakness associated with hyperparathyroidism. These studies are important for understanding the clinical phenotype of PHPT patients and suggest that inhibition of β-arr2 in PHPT could be a path for drug therapy.
References: (1) Mosekilde L. Clin Endocrinol 2008;69:1-9. (2) Ferrari SL et al., J Biol Chem 1999; 274:29968–29975 (3) Zhang L. PhD thesis University of Toronto, 2018.
SAT-232 Pheochromocytoma Presenting Rare Skin Findings: Livedoid Vasculopathy and Raynaud’s Phenomenon
Authors: Kyo Chika , Usui Takeshi , Yamada Kanako , Torii-Hanakita Mizuki , Kosugi Rieko , Yonemoto Takako , Ogawa Tatuo , Kotani Masato , Tamura Naohisa , Inoue Tatsuhide 
Published: May 2020

Abstract
BACKGROUND: Oversecreted catecholamines from pheochromocytoma (PCC) is responsible for a large variety of clinical signs and symptoms, including skin lesions, due to their effects on hemodynamics and metabolism, as well as the putative effects on the blood coagulation system. Livedo reticularis had been reported as the skin complications of PCC, but there was no pathological evidence. Livedoid vasculopathy, a subtype of livedo reticularis is a noninflammatory thrombotic condition. Here we firstly showed that livedo reticularis accompanying PCC.
Case: A 36-year-old female with hypertension, hyperglycemia, and right adrenal mass had referred to our hospital. She had violaceous reticular lesions on bilateral lower limbs, a three-year history of recurrent ulcers around her right ankle with severe pain. She also had frequent Raynaud’s phenomenon. On admission, the blood examination showed that her hemoglobin concentration was 16.3g/dl and her platelet count was 408,000/ml. Plasma catecholamines and the metabolite levels were elevated. The abdominal CT scan showed the right adrenal mass, approximately 6.5cm in diameter, and MRI showed a heterogeneous mass with high signal intensity on T2-weighted images. MIBG scintigraphy showed uptake in the mass. We diagnosed her as PCC. A skin biopsy revealed occlusions of the lumen of small vessels in the mid dermis without vasculitis. Administration of doxazosin revealed the improvement of the clinical parameters including the pain and the ulcer of the right ankle. The laparoscopic right adrenalectomy was performed. Histopathological study of the adrenal tumor was consistent with PCC. Genetic testing and MLPA analysis for RET, VHL, SDHx, SDH-AF2, MAX, and TMEM127 showed no mutations or copy number alterations. Postoperatively, hypertension and hyperglycemia improved, and Raynaud’s phenomenon and reticular macules disappeared.
Discussion: Among the various clinical signs of PCC, skin disorders are relatively rare. Limited reports showed that the livedo reticularis was a complication of PCC, but its mechanism had not been elucidated. Livedoid vasculopathy is a rare cutaneous disease manifesting as recurrent ulcers on the lower extremities, which is a noninflammatory thrombotic condition associated with hypercoagulation. The catecholamine excess could induce arterial vasospasm in addition to relative hypercoagulation tendency, which could result in livedoid vasculopathy.
Conclusion: The present study showed first pathological evidence of that the livedo reticularis accompanying PCC was livedoid vasculopathy.
SAT-444 Long-Term Effect of Neutering on Plasma Luteinizing Hormone Concentrations in Cats: A Potential Role in the Pathogenesis of Feline Hyperthyroidism
Authors: Aguiar Joana , Crossley Victoria , Davison Lucy , Fowkes Robert C , Syme Harriet Merlin 
Published: May 2020

Abstract
Feline hyperthyroidism remains a major area of interest within the veterinary field given its high prevalence, affecting nearly 10% of geriatric cats, and that causal factors leading to this disease are not completely understood.1,2 Feline hyperthyroidism shares clinical and histopathological similarities with Toxic Multinodular Goitre in humans and therefore the discovery of driving cellular mechanisms behind the pathogenesis of this feline disease may bring translational insight into the pathogenesis of the later.3,4 Gonadotropin hormones such as LH are structurally related to other glycoproteins including TSH and cross-reactivity between these and their receptors has been demonstrated.5 It is hypothesized that increased concentrations of gonadotropins in neutered cats might be implicated in the pathogenesis of hyperthyroidism. This study aimed to determine the long-term effect of neutering on plasma LH concentrations in cats. Stored plasma samples from client-owned cats were used for measurement of LH and TSH concentrations. Clinical data, including age, sex, neutering age and medical history were reviewed. Two study populations were included in this study: (1) a geriatric cat population (≥ 9 years old): 18 entire and 18 neutered cats matched for age, sex and date of sample collection; (2) an adult cat population (2-8 years old): 45 neutered cats. LH concentrations were measured using a feline ELISA and TSH concentrations were measured by the Immulite canine TSH assay. Geriatric neutered cats have higher plasma LH concentrations (median, 0.25 ng/ml [25th percentile, 0.25; 75th percentile, 2.1]) than age matched entire cats (0.25 ng/ml [0.25, 0.25], P &lt; 0 .001). Cats neutered between 6-9 months of age have higher LH concentrations than cats neutered before or after that period (P = 0.004). No correlation was found between plasma LH and TSH concentrations (P = 0.422). In conclusion, neutering causes significant long-term increase in LH concentrations in cats. Further research to determine whether this results in activation of the TSH receptor and ultimately in thyrocyte hyperplasia and/or hyperfunction is warranted.
References:
1. Mooney CT. Pathogenesis of feline hyperthyroidism. J Feline Med Surg 2002;4:167-169.
2. Peterson M. Hyperthyroidism in cats: what’s causing this epidemic of thyroid disease and can we prevent it? J Feline Med Surg 2012;14:804-818.
3. Krohn K, Fuhrer D, Bayer Y, et al. Molecular pathogenesis of euthyroid and toxic multinodular goiter. Endocr Rev 2005;26:504-524.
4. Gunn-Moore D. Feline endocrinopathies. Vet Clin North Am Small Anim Pract 2005;35:171-210, vii.
5. Jiang X, Dias JA, He X. Structural biology of glycoprotein hormones and their receptors: insights to signaling. Mol Cell Endocrinol 2014;382:424-451.
MON-715 How Heterogeneous Are Pituitary Thyrotropes?
Authors: Dudley Lindsey Anne , Daley Alexandre Zacharie , Mortensen Amanda Helen , Sridhar Rachna , Brinkmeier Michelle , Cheung Leonard , Camper Sally Ann 
Published: May 2020

Abstract
Many transcription factors have been identified that are important for specification and differentiation of the hormone-producing cells of the pituitary gland. For example, POU1F1 is essential for differentiation of thyrotropes, somatotropes, and lactotropes. GATA2 is important for differentiation of both thyrotropes and gonadotropes, and NR5A1 drives gonadotrope differentiation. It is not known whether additional transcription factors are involved in thyrotrope specification. A few POU1F1-independent thyrotropes arise during development at the rostral tip of the pituitary gland, but the majority of thyrotropes are POU1F1-dependent and arise in the caudo-medial area of the anterior pituitary gland. Pou1f1-deficient mice lack this major, critical type of thyrotropes and are severely hypothyroid. Several pieces of evidence suggest that the caudo-medial population of thyrotropes is heterogeneous. First, NR5A1-positive cells exist that express both TSH and FSH during pituitary development. Second, Pou1f1 mRNA is detected in only about half of pituitary cells immuno-positive for TSH. Third, the transcription factor ISL1 is only detected in a fraction of developing thyrotropes. The Helix-Loop-Helix transcription factor ASCL1 is critical for zebrafish pituitary development, but there are conflicting data about its role in pituitary thyrotrope specification in mice. To quantify the role of ASCL1 in thyrotrope development we carried out immunostaining for TSH in pituitaries of Ascl1 deficient mice in late gestation. We did not detect any reduction in TSH immuno-reactive cells at this time, suggesting there are species-specific differences in the requirement of ASCL1 in the developing pituitary. To systematically assess and quantify the heterogeneity of thyrotropes for transcription factor expression, we performed co-immunostaining for TSH and various transcription factors in pituitaries of newborn mice. We found that approximately 75% of TSH-positive cells in the caudo-medial region of the pituitary express POU1F1, and the majority express GATA2. We detected a small portion of cells co-expressing NR5A1 and TSH at this time. To confirm our immunostaining results, we analyzed data from single cell RNA sequencing of postnatal thyrotropes. Three robust clusters of thyrotropes were identified. Approximately 80% expressed Gata2, 85% expressed Pou1f1, and roughly 15% expressed Nr5a1. Taken together, the protein and RNA analysis support that thyrotrope heterogeneity exists during development. The functional significance of this heterogeneity and its variation during development will be the subject of future investigation.
SAT-128 An Uncommon Case of Squamous Cell Carcinoma of the Vulva with Metastasis to the Thyroid Gland
Authors: Munshi Laishiya , Pulipati Vishnu Priya , Mascarell Susana 
Published: May 2020

Abstract
Background: Distant metastasis from Squamous Cell Carcinoma (SCC) of the Vulva is very rare and typically associated with poor outcomes. In the literature, there have been no reported cases of vulvar SCC with metastasis to the thyroid, which augments the uniqueness of the case we are presenting.
Clinical Case: A 29-year-old female was hospitalized for abdominal pain & altered mental status. Labs showed calcium 21 (RR 8.5-10.5 mg/dL) with iPTH 4.3 (RR 12-88 pg/mL). Imaging revealed an 8.6 x 7.2 cm right thyroid mass (solid with cystic internal components, hyperechoic to isoechoic, wider than tall, lobulated margins, punctate echogenic foci occupying nearly the entire right lobe, minimal vascularity), mildly effacing the trachea. There were also extensive lesions consistent with systemic metastasis involving the left hilar lymph nodes, pre-tracheal lymph nodes, right hepatic lobe, head of pancreas, retroperitoneal lymph nodes, right inferior pubic ramus, proximal right humerus, left humerus, proximal femur & frontal lobe of the brain. Hypercalcemia of malignancy from an unknown cancer was diagnosed. FNA biopsy of the thyroid mass was consistent with atypia of undetermined significance. Liver biopsy showed evidence of high grade carcinoma with non-calcitonin producing neuroendocrine differentiation. Labs showed serum serotonin 11 (RR 56-244 ng/mL), CA 19-9 &lt; 0.8 (RR 0-35 U/mL), alpha-fetoprotein 2.12 (RR 0-9 ng/mL), CEA 20.97 (RR 0-2.9 ng/mL), PTHrP 33 (RR 14-27 pg/mL), 1,25OH Vit D 18 (RR 18-72 pg/mL), chromogranin A 189 (RR 25-140 pg/mL), & calcitonin &lt; 2 (RR &lt; 5 pg/mL). A vaginal lesion was discovered on exam & biopsy showed squamous cells with cytopathic effect of Herpes Simplex Virus (confirmed with immunohistochemical stain). Subsequent biopsy of the brain & core needle biopsy of the thyroid showed morphology similar to a concurrent biopsy of a vulvar lesion also found on exam: poorly differentiated SCC. The patient was diagnosed with vulvar SCC with extensive metastasis. Her hospital course was complicated by atrial fibrillation, acute respiratory failure, & sepsis. She, unfortunately, passed away from her severe morbidities.
Discussion: Metastasis to the thyroid is an infrequent occurrence. It is commonly encountered in breast, lung & renal cell carcinomas. It can occur due to direct spread from adjacent tissues or by lymphatic or hematogenous spread. Thyroid gland metastasis is more commonly seen in patients with aggressive or widespread carcinomas, especially by hematogenous route, due to the thyroid’s extensive vascularity.
Conclusion: Thyroid gland metastasis, particularly due to vulvar SCC, is a rare entity with a poor prognosis. In patients with extensive poorly differentiated carcinoma such as our patient, it is of utmost importance to identify suspicious thyroid nodules and perform comprehensive diagnostic testing to facilitate timely intervention for improved outcomes.