Obstetrics and Gynecology Commons^™

Isolated Vaginal Recurrence In Women With Stage I Endometrial Cancer, Eric Rios-Doria, Han T Cun, Olga T Filippova, Jennifer J Mueller, Kaled M Alektiar, Lora H Ellenson, Vicky Makker, Yulia Lakhman, Mario M Leitao, Anuja Jhingran, Pamela T Soliman, Nadeem R Abu-Rustum

Faculty, Staff and Student Publications

Objective: To compare clinical and pathologic characteristics of women with surgical stage I endometrial carcinoma by location of first recurrence and describe characteristics of isolated vaginal recurrence.

Methods: Patients with 2009 International Federation of Obstetrics and Gynecology (FIGO) stage I endometrial carcinoma treated at two large cancer centers from 1/1/2009-12/31/2017 were identified. Sarcoma histology was excluded. Recurrences were grouped into isolated vaginal or extravaginal. Isolated vaginal recurrences were localized by anatomic location within the vaginal vault. Clinical and pathologic variables were compared with chi-square analysis, and Kaplan-Meier curves with log-rank tests.

Results: Of 2815 women identified, 278 (10%) experienced a …

Nad+ Rescues Aging-Induced Blood-Brain Barrier Damage Via The Cx43-Parp1 Axis, Rui Zhan, Xia Meng, Dongping Tian, Jie Xu, Hongtu Cui, Jialei Yang, Yangkai Xu, Mingming Shi, Jing Xue, Weiwei Yu, Gaofei Hu, Ke Li, Xiaoxiao Ge, Qi Zhang, Mingming Zhao, Jianyong Du, Xin Guo, Wenli Xu, Yang Gao, Changyu Yao, Fan Chen, Yue Chen, Wenxin Shan, Yujie Zhu, Liang Ji, Bing Pan, Yan Yu, Wenguang Li, Xuyang Zhao, Qihua He, Xiaohui Liu, Yue Huang, Shengyou Liao, Bin Zhou, Dehua Chui, Y Eugene Chen, Zheng Sun, Erdan Dong, Yongjun Wang, Lemin Zheng

Faculty, Staff and Students Publications

Blood-brain barrier (BBB) function deteriorates during aging, contributing to cognitive impairment and neurodegeneration. It is unclear what drives BBB leakage in aging and how it can be prevented. Using single-nucleus transcriptomics, we identified decreased connexin 43 (CX43) expression in cadherin-5

Transforming Ovarian Cancer Care By Targeting Minimal Residual Disease, Amir A Jazaeri, Rachel Grisham, Anne Knisely, Stefani Spranger, Dmitriy Zamarin, R Tyler Hillman, Barrett C Lawson, Kathleen H Burns, Sanghoon Lee, Shannon N Westin, Enrico Moiso, Marc J Williams, Neelkanth M Bardhan, Thomas Pisanic, Ursula Matulonis, Britta Weigelt, Ieming Shih, Panagiotis A Konstantinopoulos, Stephanie Gaillard, Linghua Wang, Carol Aghajanian, Alan D D'Andrea, Paula Hammond, Sohrab Shah, Kai W Wucherpfennig, Karen H Lu

Faculty, Staff and Student Publications

Frontline treatment and resultant cure rates in patients with advanced ovarian cancer have changed little over the past several decades. Here, we outline a multidisciplinary approach aimed at gaining novel therapeutic insights by focusing on the poorly understood minimal residual disease phase of ovarian cancer that leads to eventual incurable recurrences.

Aptamers As Potential Therapeutic Tools For Ovarian Cancer: Advancements And Challenges, Wojciech Szymanowski, Anna Szymanowska, Anna Bielawska, Gabriel Lopez-Berestein, Cristian Rodriguez-Aguayo, Paola Amero

Faculty, Staff and Student Publications

Ovarian cancer (OC) is the most common lethal gynecologic cause of death in women worldwide, with a high mortality rate and increasing incidence. Despite advancements in the treatment, most OC patients still die from their disease due to late-stage diagnosis, the lack of effective diagnostic methods, and relapses. Aptamers, synthetic, short single-stranded oligonucleotides, have emerged as promising anticancer therapeutics. Their ability to selectively bind to target molecules, including cancer-related proteins and receptors, has revolutionized drug discovery and biomarker identification. Aptamers offer unique insights into the molecular pathways involved in cancer development and progression. Moreover, they show immense potential as drug …

Ischemic Bowel Associated With Newly Diagnosed Patent Foramen Ovale, Hannah Hong, Deanna Glassman, Shannon Neville Westin

Faculty, Staff and Student Publications

No abstract provided.

Machine Learning Methods For Endocrine Disrupting Potential Identification Based On Single-Cell Data, Zahir Aghayev, Adam T Szafran, Anh Tran, Hari S Ganesh, Fabio Stossi, Lan Zhou, Michael A Mancini, Efstratios N Pistikopoulos, Burcu Beykal

Faculty, Staff and Students Publications

Humans are continuously exposed to a variety of toxicants and chemicals which is exacerbated during and after environmental catastrophes such as floods, earthquakes, and hurricanes. The hazardous chemical mixtures generated during these events threaten the health and safety of humans and other living organisms. This necessitates the development of rapid decision-making tools to facilitate mitigating the adverse effects of exposure on the key modulators of the endocrine system, such as the estrogen receptor alpha (ERα), for example. The mechanistic stages of the estrogenic transcriptional activity can be measured with high content/high throughput microscopy-based biosensor assays at the single-cell level, which …

Epidural Catheters For Cervical Epidural Steroid Injections To Target Higher Cervical Pathology: Clinical Images In Practice, Peter D Vu, Christopher L Robinson, Grant H Chen, Jamal J Hasoon

Faculty, Staff and Student Publications

Cervical radicular pain is commonly treated with cervical epidural steroid injections. The transforaminal approach allows for direct treatment of the steroid at a particular nerve root or level. Still, it carries a significant risk of morbidity and mortality with thromboembolism or injury to cervical vasculature. The interlaminar approach is commonly utilized as it avoids vascular structures. However, the epidural space becomes narrower at higher levels, limiting the ability to perform this approach at higher cervical levels. Cervical epidural catheters can be used and advanced to target higher cervical pathology through the interlaminar approach. We present clinical images demonstrating the utility …

Surface Charge Effects For The Hydrogen Evolution Reaction On Pt(111) Using A Modified Grand-Canonical Potential Kinetics Method, Mihir Patel, Matthias Franzen, Camille D Hawkins, Matthew Brown, Samir Patel

Faculty, Staff and Student Publications

Supraventricular tachycardia (SVT) is the most common tachyarrhythmia of pregnancy. Catecholamine surges, the use of vasoactive agents during delivery, and increased cardiac output during pregnancy are the most common contributing factors to developing SVT. SVT is usually benign in presentation but can lead to more serious arrhythmias in patients with a history of mitral stenosis secondary to rheumatic heart disease. When an SVT is detected, organic heart causes should be ruled out first. Symptoms of SVT include shortness of breath, palpitations, syncope, sweating, chest pain, and dizziness. In patients who are refractory to pharmacologic management and hemodynamically unstable, electrical cardioversion …

P2y2 Purinergic Receptor Gene Deletion Protects Mice From Bacterial Endotoxin And Sepsis-Associated Liver Injury And Mortality, Athis R Arunachalam, Sanju S Samuel, Arunmani Mani, Janielle P Maynard, Kelsey M Stayer, Eric Dybbro, Subapradha Narayanan, Aalekhya Biswas, Saliha Pathan, Krishnakant Soni, Abu Hena Mostafa Kamal, Chandra Shekar R Ambati, Nagireddy Putluri, Moreshwar S Desai, Sundararajah Thevananther

Faculty, Staff and Students Publications

Prostate cancer (PCa) remains a leading cause of mortality among American men, with metastatic and recurrent disease posing significant therapeutic challenges due to a limited comprehension of the underlying biological processes governing disease initiation, dormancy, and progression. The conventional use of PCa cell lines has proven inadequate in elucidating the intricate molecular mechanisms driving PCa carcinogenesis, hindering the development of effective treatments. To address this gap, patient-derived primary cell cultures have been developed and play a pivotal role in unraveling the pathophysiological intricacies unique to PCa in each individual, offering valuable insights for translational research. This review explores the applications …

Oral Follicle-Stimulating Hormone Receptor Agonist Affects Granulosa Cells Differently Than Recombinant Human Fsh, Joie Z Guner, Diana Monsivais, Henry Yu, Fabio Stossi, Hannah L Johnson, William E Gibbons, Martin M Matzuk, Stephen Palmer

Faculty, Staff and Students Publications

Objective:

To determine whether TOP5300, a novel oral follicle stimulating hormone receptor (FSHR) allosteric agonist, elicits a different cellular response than recombinant human FSH (rh-FSH) in human granulosa cells from in vitro fertilization patients.

Design:

Basic science research with a preclinical allosteric FSHR agonist.

Subjects:

Infertility patients at a single academic fertility clinic were recruited under an IRB-approved protocol. Primary granulosa cell cultures were established for 41 patients, of which 8 had normal ovarian reserve (NOR), 17 were of advanced reproductive age (ARA), 12 had a diagnosis of polycystic ovarian syndrome (PCOS), and 4 had a combination of diagnoses, such …

Geographic Variation In Late-Stage Cervical Cancer Diagnosis, Itunu O Sokale, Aaron P Thrift, Jane Montealegre, Victor Adekanmbi, Onyema G Chido-Amajuoyi, Ann Amuta, Lorraine R Reitzel, Abiodun O Oluyomi

Faculty, Staff and Students Publications

IMPORTANCE: There are stark disparities in cervical cancer burden in the United States, notably by race and ethnicity and geography. Late-stage diagnosis is an indicator of inadequate access to and utilization of screening.

OBJECTIVE: To identify geospatial clusters of late-stage cervical cancer at time of diagnosis in Texas.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cross-sectional study used incident cervical cancer data from the Texas Cancer Registry from 2014 to 2018 of female patients aged 18 years or older. Late-stage cervical cancer cases were geocoded at the census tract level (n = 5265) using their residential coordinates (latitude and longitude) at …

Benefits Of The Enhanced Recovery After Surgery (Eras) Pathway With Quadratus Lumborum Blocks For Minimally Invasive Gynecologic Surgery Patients: A Retrospective Cohort Study, Paul S Lee, Laurie L Brunette, Intira Sriprasert, Mohamed Eloustaz, Rasika Deshpande, Crystal Adams, Laila Muderspach, Lynda Roman, Shane Dickerson, Michael P Kim

Faculty, Staff and Student Publications

STUDY OBJECTIVE: This study aimed to determine the effect of the implementation of the Enhanced Recovery After Surgery (ERAS) protocol among patients receiving minimally invasive gynecologic surgery.

DESIGN AND SETTING: This retrospective cohort study was performed in a tertiary care hospital.

PATIENTS: A total of 328 females who underwent minimally invasive gynecologic surgeries requiring at least one overnight stay at Keck Hospital of University of Southern California (USC), California, USA, from 2016 to 2020 were included in this study.

INTERVENTIONS: The institutional ERAS protocol was implemented in late 2018. A total of 186 patients from 2016 to 2018 prior to …

Care After Premenopausal Risk-Reducing Salpingo-Oophorectomy In High-Risk Women: Scoping Review And International Consensus Recommendations, Denise R Nebgen, Susan M Domchek, Joanne Kotsopoulos, Joanne A De Hullu, Emma J Crosbie, Vincent Singh Paramanandam, Monique M A Brood-Van Zanten, Barbara M Norquist, Theresa Guise, Serge Rozenberg, Allison W Kurian, Holly J Pederson, Nese Yuksel, Rachel Michaelson-Cohen, Sharon L Bober, Agnaldo Lopes Da Silva Filho, Nora Johansen, F Guidozzi, D Gareth Evans, Usha Menon, Sheryl A Kingsberg, C Bethan Powell, Giovanni Grandi, Claudia Marchetti, Michelle Jacobson, Donal J Brennan, Martha Hickey

Faculty, Staff and Student Publications

Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease.

Trio-Based Gwas Identifies Novel Associations And Subtype-Specific Risk Factors For Cleft Palate, Kelsey Robinson, Trenell J Mosley, Kenneth S Rivera-González, Christopher R Jabbarpour, Sarah W Curtis, Wasiu Lanre Adeyemo, Terri H Beaty, Azeez Butali, Carmen J Buxó, David J Cutler, Michael P Epstein, Lord J J Gowans, Jacqueline T Hecht, Jeffrey C Murray, Gary M Shaw, Lina Moreno Uribe, Seth M Weinberg, Harrison Brand, Mary L Marazita, Robert J Lipinski, Elizabeth J Leslie

Faculty, Staff and Student Publications

Cleft palate (CP) is one of the most common craniofacial birth defects; however, there are relatively few established genetic risk factors associated with its occurrence despite high heritability. Historically, CP has been studied as a single phenotype, although it manifests across a spectrum of defects involving the hard and/or soft palate. We performed a genome-wide association study using transmission disequilibrium tests of 435 case-parent trios to evaluate broad risks for any cleft palate (ACP) (n = 435), and subtype-specific risks for any cleft soft palate (CSP), (n = 259) and any cleft hard palate (CHP) (n = 125). We identified …

Project Inclusive Genetics: Protecting Reproductive Autonomy From Bias Via Prenatal Patient-Centered Counseling, Apolline Jungels, Lindsay Demers, Eric Ford, Blair K Stevens, Maya Sabatello, Shoumita Dasgupta

Faculty, Staff and Student Publications

Clinician bias negatively impacts the healthcare received by marginalized communities. In this study, we explored factors that influence clinician and trainee bias against individuals with intellectual disabilities and its impact on clinical judgment in prenatal genetic testing settings. Specifically, we examined bias toward a fetus with a higher chance of developing a disability. We compared genetics specialists with their non-expert counterparts. This web-based study included clinical vignettes, implicit association tests (IATs), and an educational module. 595 participants were recruited via their institution or professional society. We conducted statistical analyses, including regression models controlling for key demographic characteristics, to analyze recommendation …

Functional Analysis Reveals Driver Cooperativity And Novel Mechanisms In Endometrial Carcinogenesis, Matthew Brown, Alicia Leon, Katarzyna Kedzierska, Charlotte Moore, Hayley L Belnoue-Davis, Susanne Flach, John P Lydon, Francesco J Demayo, Annabelle Lewis, Tjalling Bosse, Ian Tomlinson, David N Church

Faculty, Staff and Students Publications

High-risk endometrial cancer has poor prognosis and is increasing in incidence. However, understanding of the molecular mechanisms which drive this disease is limited. We used genetically engineered mouse models (GEMM) to determine the functional consequences of missense and loss of function mutations in Fbxw7, Pten and Tp53, which collectively occur in nearly 90% of high-risk endometrial cancers. We show that Trp53 deletion and missense mutation cause different phenotypes, with the latter a substantially stronger driver of endometrial carcinogenesis. We also show that Fbxw7 missense mutation does not cause endometrial neoplasia on its own, but potently accelerates carcinogenesis caused by Pten …

Influence Of Macrophages On Vascular Invasion Of Inflammatory Breast Cancer Emboli Measured Using An In Vitro Microfluidic Multi-Cellular Platform, Manasa Gadde, Melika Mehrabi-Dehdezi, Bisrat G Debeb, Wendy A Woodward, Marissa Nichole Rylander

Faculty, Staff and Student Publications

Inflammatory breast cancer (IBC) is an aggressive disease with a poor prognosis and a lack of effective treatments. It is widely established that understanding the interactions between tumor-associated macrophages (TAMs) and the tumor microenvironment is essential for identifying distinct targeting markers that help with prognosis and subsequent development of effective treatments. In this study, we present a 3D in vitro microfluidic IBC platform consisting of THP1 M0, M1, or M2 macrophages, IBC cells, and endothelial cells. The platform comprises a collagen matrix that includes an endothelialized vessel, creating a physiologically relevant environment for cellular interactions. Through the utilization of this …

Delivery Outcomes In A Cohort Of Pregnant Patients With Covid-19 With And Without Viral Pneumonia, Brianna Dubose, Yazmeen Tembunde, Katherine E Goodman, Lisa Pineles, Gita Nadimpalli, Jonathan D Baghdadi, Jacqueline G Parchem, Anthony D Harris, Beth L Pineles

Faculty, Staff and Student Publications

Background: Among pregnant people, COVID-19 can lead to adverse outcomes, but the specific pregnancy outcomes that are affected by the disease are unclear. In addition, the effect of the severity of COVID-19 on pregnancy outcomes has not been clearly identified.

Objective: This study aimed to evaluate the associations between COVID-19 with and without viral pneumonia and cesarean delivery, preterm delivery, preeclampsia, and stillbirth.

Study design: We conducted a retrospective cohort study (April 2020-May 2021) of deliveries between 20 and 42 weeks of gestation from US hospitals in the Premier Healthcare Database. The primary outcomes were cesarean delivery, preterm delivery, preeclampsia, …

New Insights Into The Neuraminidase-Mediated Hemagglutination Activity Of Influenza A(H3n2) Viruses, Rongyuan Gao, Philippe Noriel Q Pascua, Ha T Nguyen, Anton Chesnokov, Chloe Champion, Vasiliy P Mishin, Dave E Wentworth, Larisa V Gubareva

Faculty, Staff and Student Publications

Influenza virus neuraminidase (NA) can act as a receptor-binding protein, a role commonly attributed to hemagglutinin (HA). In influenza A(H3N2) viruses, three NA amino acid residues have previously been associated with NA-mediated hemagglutination: T148, D151, and more recently, H150. These residues are part of the 150-loop of the NA monomer. Substitutions at 148 and 151 arise from virus propagation in laboratory cell cultures, whereas changes at 150 occurred during virus evolution in the human host. In this study, we examined the effect of natural amino acid polymorphism at position 150 on NA-mediated hemagglutination. Using the A/Puerto Rico/8/34 backbone, we generated …

A Retrospective Review Of Social Deprivation Index And Maternal Outcomes With Placenta Accreta Spectrum From A Single Referral Center, Alison N Goulding, Karin A Fox, Christina C Reed, Bahram Salmanian, Alireza A Shamshirsaz, Kjersti M Aagaard

Faculty, Staff and Students Publications

Objective

Little is known about how community characteristics influence placenta accreta spectrum (PAS) outcomes. Our objective was to evaluate whether adverse maternal outcomes among pregnant people (gravidae) with PAS delivering at a single referral center differ by community-level measures of social deprivation.

Study Design

We conducted a retrospective cohort study of singleton gravidae with histopathology confirmed PAS delivering from January 2011 to June 2021 at a referral center. Data abstraction collected relevant patient information, including resident zip code, which was linked to Social Deprivation Index (SDI) score (a measure of area-level social deprivation). SDI scores were divided into quartiles for …

Cutaneous Dermal Metastasis Of Inflammatory Breast Carcinoma Mimicking Granuloma Annulare, Vikram Shaw, Jay Patel, Hanna Siatecka, Omid Jalali

Faculty, Staff and Students Publications

Breast cancer can present as a wide range of cutaneous lesions at the time of diagnosis or months to years after a known diagnosis of breast cancer. Cutaneous sequela of breast cancer, including metastasis, have a diverse range of clinical appearances. Here, we describe the case of a 59-year-old female with stage IV metastatic inflammatory breast carcinoma presenting with a chronic worsening rash on her anterior chest wall. Biopsy results demonstrated metastatic carcinoma cells within the dermal lymphatics, consistent with primary breast cancer. To our knowledge, based on a thorough review of the literature, no previous case reports detailing cutaneous …

Neuromodulation For Adjunctive Treatment In Postmastectomy Pain Syndrome, Kennedy Kirkpatrick, Jay D Shah, Krishna Shah

Faculty, Staff and Students Publications

Postmastectomy pain syndrome (PMPS) affects nearly half of patients who undergo mastectomy to treat breast cancer. As the survival rate of breast cancer increases with advancements in treatment, the incidence of PMPS is also increasing. Patients with PMPS can experience unrelenting, chronic pain refractory to traditional management with oral pharmacotherapy in conjunction with nonpharmacologic treatment (physical therapy, transcutaneous electrical nerve stimulation (TENS)). Neuromodulation is an emerging treatment modality for numerous chronic pain conditions. This case report highlights the tremendous success of spinal cord stimulator placement for a patient with PMPS.

Proteogenomic Insights Suggest Druggable Pathways In Endometrial Carcinoma, Yongchao Dou, Lizabeth Katsnelson, Marina A Gritsenko, Yingwei Hu, Boris Reva, Runyu Hong, Yi-Ting Wang, Iga Kolodziejczak, Rita Jui-Hsien Lu, Chia-Feng Tsai, Wen Bu, Wenke Liu, Xiaofang Guo, Eunkyung An, Rebecca C Arend, Jasmin Bavarva, Lijun Chen, Rosalie K Chu, Andrzej Czekański, Teresa Davoli, Elizabeth G Demicco, Deborah Delair, Kelly Devereaux, Saravana M Dhanasekaran, Peter Dottino, Bailee Dover, Thomas L Fillmore, Mckenzie Foxall, Catherine E Hermann, Tara Hiltke, Galen Hostetter, Marcin Jędryka, Scott D Jewell, Isabelle Johnson, Andrea G Kahn, Amy T Ku, Chandan Kumar-Sinha, Paweł Kurzawa, Alexander J Lazar, Rossana Lazcano, Jonathan T Lei, Yi Li, Yuxing Liao, Tung-Shing M Lih, Tai-Tu Lin, John A Martignetti, Ramya P Masand, Rafał Matkowski, Wilson Mckerrow, Mehdi Mesri, Matthew E Monroe, Jamie Moon, Ronald J Moore, Michael D Nestor, Chelsea Newton, Tatiana Omelchenko, Gilbert S Omenn, Samuel H Payne, Vladislav A Petyuk, Ana I Robles, Henry Rodriguez, Kelly V Ruggles, Dmitry Rykunov, Sara R Savage, Athena A Schepmoes, Tujin Shi, Zhiao Shi, Jimin Tan, Mason Taylor, Mathangi Thiagarajan, Joshua M Wang, Karl K Weitz, Bo Wen, C M Williams, Yige Wu, Matthew A Wyczalkowski, Xinpei Yi, Xu Zhang, Rui Zhao, David Mutch, Arul M Chinnaiyan, Richard D Smith, Alexey I Nesvizhskii, Pei Wang, Maciej Wiznerowicz, Li Ding, D R Mani, Hui Zhang, Matthew L Anderson, Karin D Rodland, Bing Zhang, Tao Liu, David Fenyö

Faculty, Staff and Students Publications

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of β-catenin, which may render …

Sars-Cov-2 Niches In Human Placenta Revealed By Spatial Transcriptomics, Enrico R Barrozo, Maxim D Seferovic, Eumenia C C Castro, Angela M Major, David N Moorshead, Michael D Jochum, Ricardo Ferral Rojas, Cynthia D Shope, Kjersti M Aagaard

Faculty, Staff and Students Publications

BACKGROUND: Functional placental niches are presumed to spatially separate maternal-fetal antigens and restrict the vertical transmission of pathogens. We hypothesized a high-resolution map of placental transcription could provide direct evidence for niche microenvironments with unique functions and transcription profiles.

METHODS: We utilized Visium Spatial Transcriptomics paired with H&E staining to generate 17,927 spatial transcriptomes. By integrating these spatial transcriptomes with 273,944 placental single-cell and single-nuclei transcriptomes, we generated an atlas composed of at least 22 subpopulations in the maternal decidua, fetal chorionic villi, and chorioamniotic membranes.

FINDINGS: Comparisons of placentae from uninfected healthy controls (n = 4) with COVID-19 asymptomatic …

Effects Of In Utero Etoh Exposure On 18s Ribosomal Rna Processing: Contribution To Fetal Alcohol Spectrum Disorder, Nune Darbinian, Gary L Gallia, Armine Darbinyan, Ekaterina Vadachkoria, Nana Merabova, Amos Moore, Laura Goetzl, Shohreh Amini, Michael E Selzer

Faculty, Staff and Student Publications

Fetal alcohol spectrum disorders (FASD) are leading causes of neurodevelopmental disability. The mechanisms by which alcohol (EtOH) disrupts fetal brain development are incompletely understood, as are the genetic factors that modify individual vulnerability. Because the phenotype abnormalities of FASD are so varied and widespread, we investigated whether fetal exposure to EtOH disrupts ribosome biogenesis and the processing of pre-ribosomal RNAs and ribosome assembly, by determining the effect of exposure to EtOH on the developmental expression of 18S rRNA and its cleaved forms, members of a novel class of short non-coding RNAs (srRNAs). In vitro neuronal cultures and fetal brains (11–22 …

Low-Grade Serous Ovarian Cancer: Expert Consensus Report On The State Of The Science, Rachel N Grisham, Brian M Slomovitz, Nicole Andrews, Susana Banerjee, Jubilee Brown, Mark S Carey, Herman Chui, Robert L Coleman, Amanda N Fader, Stephanie Gaillard, Charlie Gourley, Anil K Sood, Bradley J Monk, Kathleen N Moore, Isabelle Ray-Coquard, Ie-Ming Shih, Shannon N Westin, Kwong-Kwok Wong, David M Gershenson

Faculty, Staff and Student Publications

Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly sensitive to chemotherapy and affects younger women, many of whom endure years of ineffective treatments and poor quality of life. The pathogenesis of this disease and its management remain incompletely understood. However, recent advances in the molecular characterization of the disease and identification of novel targeted therapies with activity in low-grade serous carcinoma offer the promise of improved outcomes. To update clinicians regarding recent scientific and clinical trial advancements and discuss unanswered questions related to low-grade …

Antiviral Susceptibility Of Clade 2344b Highly Pathogenic Avian Influenza A(H5n1) Viruses Isolated From Birds And Mammals In The United States, 2022, Ha T Nguyen, Anton Chesnokov, Juan De La Cruz, Philippe Noriel Q Pascua, Vasiliy P Mishin, Yunho Jang, Joyce Jones, Han Di, Andrei A Ivashchenko, Mary Lea Killian, Mia K Torchetti, Kristina Lantz, David E Wentworth, Charles T Davis, Alexandre V Ivachtchenko, Larisa V Gubareva

Faculty, Staff and Student Publications

Clade 2.3.4.4b highly pathogenic avian influenza (HPAI) A(H5N1) viruses that are responsible for devastating outbreaks in birds and mammals pose a potential threat to public health. Here, we evaluated their susceptibility to influenza antivirals. Of 1,015 sequences of HPAI A(H5N1) viruses collected in the United States during 2022, eight viruses (∼0.8%) had a molecular marker of drug resistance to an FDA-approved antiviral: three adamantane-resistant (M2-V27A), four oseltamivir-resistant (NA-H275Y), and one baloxavir-resistant (PA-I38T). Additionally, 31 viruses contained mutations that may reduce susceptibility to inhibitors of neuraminidase (NA) (n = 20) or cap-dependent endonuclease (CEN) (n = 11). A panel of 22 …

Breastfeeding Initiation And Duration Among People With Mild Chronic Hypertension: A Secondary Analysis Of The Chronic Hypertension And Pregnancy Trial, Alison N Goulding, Leah Antoniewicz, Justin M Leach, Kim Boggess, Lorraine Dugoff, Baha Sibai, Kirsten Lawrence, Brenna L Hughes, Joseph Bell, Rodney K Edwards, Kelly Gibson, David M Haas, Lauren Plante, Torri D Metz, Brian Casey, Sean Esplin, Sherri Longo, Matthew Hoffman, George R Saade, Kara K Hoppe, Janelle Foroutan, Methodius Tuuli, Michelle Y Owens, Hyagriv N Simhan, Heather Frey, Todd Rosen, Anna Palatnik, Susan Baker, Uma M Reddy, Wendy Kinzler, Emily Su, Iris Krishna, Nicki Nguyen, Mary E Norton, Daniel Skupski, Yasser Y El-Sayed, Dotun Ogunyemi, Lorie M Harper, Namasivayam Ambalavanan, Suzanne Oparil, Jeff M Szychowski, Alan T Tita

Faculty, Staff and Students Publications

BACKGROUND: Increased duration of breastfeeding improves maternal cardiovascular health and may be especially beneficial in high-risk populations, such as those with chronic hypertension. Others have shown that individuals with hypertension are less likely to breastfeed, and there has been limited research aimed at supporting breastfeeding goals in this population. The impact of perinatal blood pressure control on breastfeeding outcomes among people with chronic hypertension is unknown.

OBJECTIVE: This study aimed to evaluate whether breastfeeding initiation and short-term duration assessed at the postpartum clinic visit differed according to perinatal blood pressure treatment strategy (targeting blood pressure <140/90 mm Hg vs reserving antihypertensive treatment for blood pressure ≥160/105 mm Hg).

STUDY DESIGN: We performed a …

Lipid Dysfunction And Adrenomedullin Expression In Omental Versus Subcutaneous Adipose Tissues In Diabetic Pregnancies, Mary Duarte Thibault, Luyun Chen, Markus Huebner, John O Delancey, Carolyn W Swenson

Faculty, Staff and Students Publications

INTRODUCTION AND HYPOTHESIS: We sought to 1) test the hypothesis that young women (≤45 years) with pelvic organ prolapse have a higher prevalence of major levator ani muscle (LAM) defects than old women (≥70 years) with prolapse and 2) compare level II/III measurements between young and old women with prolapse and age-matched controls to evaluate age-related mechanistic differences in the disease process.

METHODS: A secondary analysis examined four groups of parous women: young prolapse (YPOP, n = 17); old prolapse (OPOP, n = 17); young controls (YC, n = 15); old controls, (OC, n = 13). Prolapse was defined as …

Loss Of The Maternal Effect Gene Nlrp2 Alters The Transcriptome Of Ovulated Mouse Oocytes And Impacts Expression Of Histone Demethylase Kdm1b, Zahra Anvar, Imen Chakchouk, Momal Sharif, Sangeetha Mahadevan, Eleni Theodora Nasiotis, Li Su, Zhandong Liu, Ying-Wooi Wan, Ignatia B Van Den Veyver

Faculty, Staff and Students Publications

The subcortical maternal complex (SCMC) is a multiprotein complex in oocytes and preimplantation embryos that is encoded by maternal effect genes. The SCMC is essential for zygote-to-embryo transition, early embryogenesis, and critical zygotic cellular processes, including spindle positioning and symmetric division. Maternal deletion of Nlrp2, which encodes an SCMC protein, results in increased early embryonic loss and abnormal DNA methylation in embryos. We performed RNA sequencing on pools of meiosis II (MII) oocytes from wild-type and Nlrp2-null female mice that were isolated from cumulus-oocyte complexes (COCs) after ovarian stimulation. Using a mouse reference genome-based analysis, we found 231 …