bluuebunny/crossref_metadata_2025_split huggingface dataset:
ODP409 Exercise Increases Microbiota Diversity in Women with Polycystic Ovary Syndrome: A Secondary Analysis of a Pilot Randomized Controlled Trial
Authors: Benham Jamie , Ramay Hena , Reimer Raylene , Booth Jane , Friedenreich Christine , Rabi Doreen , Sigal Ronald 
Published: November 2022

Abstract

Background
Women with polycystic ovary syndrome (PCOS) have reduced diversity and altered composition of gut microbiota (all microorganisms in the intestine) compared with healthy women. Shifts in gut microbiota with exercise may mediate some of the beneficial (e. g. anti-inflammatory) effects of exercise.

Objective
To evaluate the effect of exercise training on gut microbiota diversity (number of different species) and composition in women with PCOS.

Methods
18–40-year-old women with PCOS were randomly assigned to six months of thrice-weekly high-intensity interval training (HIIT), continuous aerobic exercise training (CAET) or no-exercise control. Stool samples were collected pre- and post-intervention. Bacterial DNA was extracted from stool samples and microbial sequencing performed on the MiSeq Illumina platform with amplification of the V3 and V4 regions of the 16S rRNA gene. The IDTAXA classifier was used to classify reads with the Silva rRNA database. Alpha diversity (within sample diversity) was measured using Shannon and Simpson indices. Changes in bacterial community structure (beta diversity) were based on Bray-Curtis dissimilarity and visualized using principal coordinates analysis.

Results
Data were available for 19 women pre- and post-intervention: control (n=8), CAET (n=6) and HIIT (n=5). In all samples, Firmicutes were the most abundant bacterial phylum followed by Bacteroidetes. The abundance of Actinobacteria, Verrucomicrobia and Proteobacteria decreased with exercise training in both exercise groups. Alpha diversity increased for all HIIT participants, but the effect was inconsistent in CAET participants with an increase in 3 (50%) participants. There were no statistically significant changes in beta diversity.

Conclusion
Exercise training may change the relative abundance of bacteria taxa of gut microbiota, and increase alpha diversity but not beta diversity in women living with PCOS. Further larger studies are needed to determine the effect of exercise training on gut microbiota in this population.
Presentation: No date and time listed
ODP413 Impact of Gestational Weight Gain according to 2009 IOM Recommendations on Neonatal Anthropometrics in Asians: A Pilot Study from Malaysia
Authors: Tai Yong Ting , Lim Quan Hziung , Ratnasingam Jeyakantha , Paramasivam Sharmila Sunita , Tan Peng Chiong , Omar Siti Zawiah , Chinna Karuthan , Lim Lee-Ling , Vethakkan Shireene Ratna 
Published: November 2022

Abstract

Introduction
Gestational Weight Gain (GWG) modulates pregnancy outcomes and long-term offspring metabolic health [1,2]. Thus far, the widely used 2009 Institute of Medicine (IOM) recommendations on GWG have largely been evaluated in Caucasian populations and some monoethnic East Asian cohorts. We designed this study to determine if IOM GWG thresholds are applicable in a multi-ethnic Asian cohort of Malaysian mothers.

Methods
In this prospective observational study, 875 mothers were recruited from a Malaysian tertiary urban center during screening for gestational diabetes. Amongst data collected were Total GWG (maternal weight at delivery – self-reported pre-gravid weight) and neonatal anthropometrics. BMI was stratified by Caucasian (overweight ≥25kg/m 2, obese ≥30 kg/m 2) and Asian (overweight ≥23kg/m 2, obese ≥27.5kg/m 2) thresholds, and patients categorized by 2009 IOM GWG recommendations.

Results
This study included 67% Malay, 23% Chinese and 10% Indian mothers. There was a high prevalence of overweight/obesity regardless of cut-offs used (Asian 56.9% vs Caucasian 44%). When Asian BMI cut-offs were used, excessive GWG prevalence increased (34.1% → 40.6%) whilst inadequate GWG declined (30% → 24.9%). Prevalence of LGA, macrosomia, Birth Weight(BW)/Neonatal Fat Mass(NFM)/Sum of Skinfold Thickness(SSFT) &gt;90th centile was highest (p&lt;0. 05) in those with excess GWG whether stratified by Caucasian or Asian BMI cut-offs. Upon multivariate analysis adjusting for age, parity, race, GDM, Ln HOMA2%S and baby gender, excessive GWG (by Asian BMI categories) was associated only with increased risk of SSFT &gt;90th centile (aOR 5.7, 95% CI 2.33–14. 03). Excessive GWG (by Caucasian BMI categories) was associated with increased risk of macrosomia (aOR 8.65, 95% CI 1. 07–70. 01), NFM &gt;90th centile (aOR 2.14, 95% CI 1. 02–4.45) and SSFT &gt;90th centile (aOR 3.88, 95% CI 1.77–8.51). SGA status was associated with insufficient GWG by both Caucasian (aOR 4.26, 95% CI 2.46–7.38) and Asian BMI cut-offs (aOR 3.55, 95% CI 2. 07–6.10).

Conclusion
The 2009 IOM recommendations, using either Caucasian or regional Asian BMI thresholds, are applicable in our multi-ethnic Asian cohort in terms of predicting increased neonatal adiposity and SGA status.
References: 1. Rasmussen K, Yaktine AL, eds; Institute of Medicine; National Research Council. Weight Gain During Pregnancy: Reexamining the Guidelines. Washington, DC: National Academies Press; National Academy of Sciences; 2009.2. He Y, Tam CH, et al. Optimal gestational weight gain for Chinese women - analysis from a longitudinal cohort with childhood follow-up. Lancet Reg Health West Pac. 2021 Jul 6;13: 100190.
Presentation: No date and time listed
OR06-1 Cyclophosphamide Depletes Primordial Follicles via the p63 Apoptotic Pathway
Authors: Dong Rosemary , Elesh Ibrahim , Kim So-Youn , Xu Pauline , Yu Seok-Yeong , Luan Yi 
Published: November 2022

Abstract
Cancer therapies often cause serious side effects, affecting the quality of life for cancer survivors. The ovary can be affected by cancer therapies, causing premature ovarian insufficiency, leading to endocrine dysfunction and infertility. Thus, maintaining ovarian function against cancer treatment is an unmet need for female cancer patients. Cyclophosphamide (CPA), a common chemotherapeutic agent, is metabolized in vivo and forms DNA crosslinks, inducing apoptosis in rapidly proliferating tumor cells. However, the underlying mechanism of the CPA-induced oocyte death in ovarian reserve remains unclear. This study aims to investigate the mechanism of oocyte death in primordial follicles by generating oocyte-specific Abl1 and p63 knockout and Pik3ca* knockin mouse models using Gdf9-iCre+. Postnatal day 7 female mice were i.p. injected w/wo CPA. Notably, we found CPA drastically reduced the number of primordial follicles without increasing the number of growing follicles. The quantification of surviving follicles validated that 90% of the primordial follicles from oocyte-specific Abl1 knockout mice were lost following CPA treatment in vivo and in vitro. Concurrently, high expression of CHK2 was detected in the oocytes of the ovary cultured with CPA metabolite in vitro. This implied CHK2 rather than ABL is a possible tyrosine kinase for CPA-induced oocyte death. Most of all, p63 was a key player for CPA-induced oocyte death, supported by the result that p63 knockout oocytes were rescued after CPA treatment. To clarify whether the ovaries lose follicles via activation or apoptosis pathway, PIK3CA* mice were examined with CPA. As expected, primordial follicles and primordial follicles with activated oocytes in the ovary of PIK3CA* mice survived against CPA due to constitutive PI3K activity in them. This indicates activated follicles resist gonadotoxic reagents, although p63 is expressed inside their oocytes. Accordingly, the apoptosis markers, BAX and cleaved PARP were highly induced with CPA injection in a time-dependent manner in the ovaries from wild-type female mice but not from the p63 knockout. The double-strand break also occurred in the nucleus of oocytes post CPA administration as γH2AX was detected. Interestingly, OPA1, a protein required for mitochondrial fusion, was highly induced inside the oocyte cytoplasm of p63 knockout, while oocytes in wild-type mice time-dependently lost the OPA1 expression by CPA treatment. This indicates that oocytes without p63 in the nucleus survive and induce mitochondrial fusion to escape apoptosis by mitochondrial damages. In conclusion, CPA induces depletion of oocytes of primordial follicles through the CHK2-TAp63 apoptotic pathway.
Presentation: Saturday, June 11, 2022 11:30 a.m. - 11:45 a.m.
ODP061 When cortisol and catecholamines combine in a severe endocrine condition
Authors: Webster John , Mortensen Michael , Alsayed Mahmoud , Guo Rong , Correa Ricardo 
Published: November 2022

Abstract

Introduction
While the majority of ACTH dependent Cushing's Syndrome cases are the result of over secretion of ACTH from the pituitary gland, ectopic ACTH production can occur. Pheochromocytoma, a tumor originating from the adrenal chromaffin cells and classically associated with catecholamine excess, has also been very rarely shown to secrete ACTH. A 54 year old male with a history of obesity, type 2 diabetes, and resistant HTN presented to ED with a tonic clonic seizure, hypoxia and altered mental status. Labs were notable for thrombocytopenia and hypokalemia. His thrombocytopenia was treated with IVIG and solumedrol. Renin activity and renal doppler were normal. He was discharged on additional blood pressure medication, antipsychotics and Keppra. After 2 weeks he was readmitted with hypertensive urgency, anemia and worsening thrombocytopenia. Bone marrow biopsy did not elucidate the etiology of thrombocytopenia. CT abdomen showed a 5.4 cm, 54 Hounsfield unit, right adrenal mass. MRI brain showed no intracranial pathology. MRI abdomen/pelvis showed bilateral adrenal thickening. The right adrenal mass had characteristics of hematoma as well. Additional labs showed urine metanephrines 1412mcg/24Hr and normetanephrines 978mcg/24Hr, Urine free cortisol was 4494 mcg/24h, random serum cortisol was 207mg/dl, and ACTH was 1091 pg/ml. Dexamethasone suppression test cortisol was 151 ug/dL. Interesting the patient lacked cushingoid phenotypical characteristicsexcept for truncal obesity. The patient was placed on doxazosin for alpha blockadeand etomidate drip to control cortisol. The diagnosis of ACTH secreting pheochromocytoma was reaffirmed after both octreoscan and dotatate PET CT showed the presence of somatostatin receptors in the rightadrenal mass. After 14 days with controlling treatment, the patient underwent successful right adrenalectomy. Pathology was notable for a well circumscribed dark brown mass that had replaced the adrenal medulla that stained patchy positive for ACTH and was positive for synaptophysin and chromogranin. Post surgical labs demonstrated cortisol of 26.3ug/dLand ACTH of 7pg/ml. The patient was discharged 14 days after surgery.

Discussion and conclusion
Pheochromocytomas are rare tumors for which classical features are often absent. Symptoms of palpitations, headache and sweating are only present in 17% of patients. ACTH secreting pheochromocytomas represent 5% of ectopic ACTH syndrome with less than 100 documented cases worldwide. While obesity, hypertension and diabetes are common in our society, this patient's rapid clinical deterioration was the key clue to this rare diagnosis. This case highlights how the decisive actions of a well-coordinated, multidisciplinary team can result in a good outcome for a very challenging and critically ill patient.
Presentation: No date and time listed
OR25-1 Bilateral and Unilateral Malformations of Male Reproductive Tracts in Mice with Androgen Receptor Gene Deletion in the Mesenchyme
Authors: Jia Shuai , Zhao Fei , Wilbourne Jillian 
Published: November 2022

Abstract
Congenital unilateral defects of male reproductive tracts have been documented in men, suggesting the potential left-right asymmetry in male reproductive tract development. However, classic textbooks of endocrinology have been teaching us that the development of the paired male reproductive tract is governed by the universal action of the androgen receptor (Ar). During sexual differentiation, testis-derived androgens activate the Ar to promote the stabilization of the bilateral Wolffian ducts, the progenitor for the male reproductive tract. The Wolffian ducts then differentiate into the paired male reproductive tract organs, which include the epididymes, vas deferentes, and seminal vesicles. The Ar is expressed both in the epithelium and mesenchyme of the male reproductive tract during fetal development. Landmark tissue recombinant studies and the observation of normal morphology in the epithelium-specific Ar knockout mouse all support the notion that Ar action in the mesenchyme dictates the morphogenesis of the male reproductive tract. However, no genetic study has been performed to investigate the consequence of the loss of mesenchymal Ar on male reproductive tract development. To test the functional significance of the mesenchymal Ar, we designed a mesenchyme-specific Ar knockout mouse model (ARcKO) to ablate Ar specifically in the mesenchyme prior to the initiation of sexual differentiation. We performed immunohistochemistry of AR to confirm that Ar expression was absent in the mesenchyme while epithelial Ar remained intact in this ARcKO model. Based on the widely accepted notion that mesenchymal Ar regulates epithelial morphogenesis of the male reproductive tract, we expected to see abnormal patterning of the male reproductive tract. Indeed, the epididymis lost its characteristic coiling and became cystic. However, 40% of the 23 collected ARcKO males displayed these abnormalities on both horns; 43% and 17% displayed these abnormal phenotype solely on the left and right horn, respectively. This surprising observation might result from asynchronous activities of Cre on the left and right horns. However, when the Cre was crossed with a reporter (tdTomato), we observed comparable reporter expression on both horns at the onset of sexual differentiation of reproductive tracts. These observations suggest that the developmental programs in the morphogenesis of the left and right male reproductive tracts are asymmetrical and there could be a compensation mechanism for the loss of mesenchymal AR. We are currently in the process of comparing the left and the right horns in Ar knockout male mice to determine any biased signaling. Taken together, our study provides a unique model for not only studying congenital defects of male reproductive tracts but also for investigating the potential asymmetry in the masculinization program.
Presentation: Monday, June 13, 2022 11:00 a.m. - 11:15 a.m.
PMON201 The Impact of Menopause on Poor Outcomes in Hospitalized Patients with COVID-19 Infection
Authors: Toure Tonslyn , Ravindra Lakshmi , Monteiro Filipe , Gopalakrishnan Geetha 
Published: November 2022

Abstract

Background
Studies evaluating risk factors for poor outcomes with COVID-19 infection report gender variation. Impact of estrogen on immune regulation may be one factor contributing to better outcomes in women. This study evaluates the impact of menopausal status and other risk factors on health outcomes in women hospitalized with COVID-19 infection.

Methods
Data from 1863 non-pregnant women admitted to the Lifespan Hospital System in Rhode Island with COVID-19 infection during the first wave (March 1 - June 30, 2020) and second wave (July 1, 2020 - February 28, 2021) were analyzed. Subjects were categorized as pre-menopausal (age less than 45 years), perimenopausal (age 45 to 55 years), and post-menopausal (age greater than 55 years). Multivariate models to look for risk factors associated with severe illness (i.e. intensive care unit admissions, mechanical ventilation and death) controlled for menopause status, race/ethnicity, insurance type, wave of COVID-19, body mass index, diabetes (DM), hyperglycemia, hypertension (HTN), pulmonary disease, cardiovascular disease (CVD) and chronic kidney disease (CKD).

Results
In our cohort, pre-, peri- and pre, peri and post- menopausal status represented 12.8, 10.4 and 76.8% of the study population, respectively. The mean (± SD) age was 67.57 ±18.0 with 61.4% White/Caucasian, 20% Hispanic/Latino and 1.7% Black. 98.4% had commercial or government-sponsored health insurance. Hyperglycemia (Blood glucose &gt; 180mg/dL on two occurrences) was noted in 26.8% of hospitalized women. Compared to pre- and peri- menopausal status, post- menopausal status was associated with a higher prevalence of Hyperglycemia (OR 1.59 [1.23-2.07]), DM 1.90 (1.50-2.42), HTN 5.06 (4.02-6.37), Pulmonary disease 1.35 (1.07-1.70) and CKD 3.7 (2.58-5.42). Post-menopausal status was also associated with higher mortality (OR 8.6 [2.7-27.6]), severe illness (OR 5.7 [1.3-23.9]), readmission (OR 1.5 [1.04-2.2]) and longer length of hospital stay (OR 1.6 [1.2-2.2]). Adjusted model identified, hyperglycemia (OR 14.8 [4.5-48.8]) and first wave (OR 2.7 [1.1-6.4]) to be independent risk factors for severe illness in post-menopausal women admitted to the hospital with COVID -19 infection.

Conclusion
While patients with comorbidities are known to be at greater risk for complications related to COVID-19 infection, menopausal status has rarely been considered a risk factor. Recognizing underlying risk factors in females, particularly menopausal females with COVID-19, can help clinicians attempt to identify patients at a higher risk of COVID-19 complications and drive early, more aggressive interventions to mitigate risk in this population.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON224 Newly Observed Interference of Oral Biotin with the Free Testosterone Assay? In a Woman with Postmenopausal Virilization.
Authors: Caputi Rafael , Ayala Alejandro 
Published: November 2022

Abstract

Introduction
Approximately 15-20% of US adults take supraphysiologic doses of biotin-containing supplements for common hair and skin problems. When consumed in high doses, competitive and non-competitive immunoassays which use the streptavidin-biotin binding complex can skew results to be either falsely high or falsely low.

Case Presentation
A 74 y/o Caucasian female who initially presented to her primary care physician concerned for alopecia with frontal balding, acne and moderate hirsutism. Her total testosterone was elevated with 146 ng/dL (7.0–40 ng/dL) with a perplexing normal free testosterone of 4.2 pg/mL (&lt;4.2 pg/mL) in the context of a normal SHBG of 48 nmol/L (14–73 nmol/L). Androstenedione was elevated with 161 ng/dL (17–99 ng/dL) with a normal CMP, prolactin, DHEA-s and 17-hydroxyprogesterone. Transvaginal US was normal. The size of the ovaries was consistent with menopause. Abdominal and pelvic MRI showed normal adrenal glands and ovaries. She was taking between 1 to 3mg of biotin per day. Biotin was discontinued. Repeat testing revealed an elevated free testosterone of 12.7 pg/mL (0.2 - 3.7 pg/mL) along with an elevated total testosterone of 120 ng/dL (2 - 45 ng/dL) and a normal SHBG of 39 nmol/L (14–73 nmol/L) which was now consistent with her clinical picture of postmenopausal hyperandrogenism. Bilateral laparoscopic salpingo-oophorectomy was recommended to exclude an androgen-secreting ovarian tumor or hyperthecosis. Testing was then repeated while taking biotin which again manifested a normal free testosterone of 2.8 pg/mL (&lt;4.2 pg/mL) with an elevated total testosterone of 121.4 ng/dL (7.0–40 ng/dL) and a normal SHBG of 45 nmol/L (14–73 nmol/L).

Discussion
Biotin may interfere with the total testosterone levels, but little is known of its effects on free testosterone. We report the first case of biotin interference on the free testosterone assay, resulting in falsely low values demonstrated in two different occasions, that improved following withdrawal of this widely used vitamin supplement. Laboratories use a direct analog enzyme immunoassay to calculate the free testosterone however its calibration and specificity has been debatable, and it is still unclear how biotin can affect it. It is critical that laboratorians and clinicians are aware of this biotin interference so that misdiagnosis and inappropriate treatment can be prevented. References: 1. Macarena Alpañés, José M. González-Casbas, Juan Sánchez, Héctor Pián, Héctor F. Escobar-Morreale, Management of Postmenopausal Virilization, The Journal of Clinical Endocrinology & Metabolism, Volume 97, Issue 8, 1 August 2012, Pages 2584–2588.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON225 Androgen excess in pre-menopausal women due to Granulosa Cell tumor: A case report.
Authors: Kaval Roopitha , Moll Teresa , Shenoy Veena , Alhussain Aljunaid , Ridway Mildred , Crews James , Cardozo Licy Yanes 
Published: November 2022

Abstract
A 23-year-old nulliparous female without any significant past medical history presented for irregular menstrual cycles, amenorrhea, hirsutism and 25-pound weight loss in one year. Excessive hair growth was found on the face and chest. Prior to endocrinology visit she was started on oral contraceptives without any improvements. Of importance, she had a negative progesterone challenge test (no withdrawal bleeding). On examination in the Endocrinology clinic, she was a class II morbidly obese female, with coarse terminal hair on her chin and chest and no cushingoid features. Intra-vaginal ultrasound revealed large bilateral multi cystic masses in the ovaries. Her laboratory work up was significant for elevated DHEA-S at 826.6 ng/dl (134-407), Total testosterone 144 ng/dl(0-60) and free testosterone 4.75 ng/dl (0.06-1.08). Her 17-OH pregnenolone was also elevated at 539 ng/dl (31- 455), Inhibin B was elevated at 374 pg/ml (&lt;139 premenopausal). 17 - OH progesterone was normal. Estradiol, inhibin A and FSH/LH were normal. ACTH, AM cortisol, TSH and prolactin were normal. Beta HCG and Cancer markers CA 19-9, CA 125, and CEA were negative. CT scan of the abdomen showed a right ovarian mass measuring 10.7×9.6×9.2 cm. Adrenal glands were normal. Patient subsequently underwent a laparoscopic diagnostic right salpingo-oophorectomy. Pathology was reported as an adult granulosa cell tumor (9.5 cm) of the ovary with an intact capsule. After surgery Inhibin B level decreased from 374 to 10 (normal &lt;139), Total testosterone decreased from 144 to 36 ng/dl (0-60), Free testosterone decreased from 4.75 to 1.22 ng/dl (0.06-1.08) and DHEA-S from 826.60 to 687.40 ng/dl (134-407) however remained elevated. Moreover, after surgery irregular menses resolved and she noted some improvement in hirsutism.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.