Digital Commons Network^™

Heritable Vaginal Bacteria Influence Immune Tolerance And Relate To Early-Life Markers Of Allergic Sensitization In Infancy, Kathryn E. Mccauley, Elze Rackaityte, Brandon Lamere, Douglas W. Fadrosh, Kei E. Fujimura, Ariane R. Panzer, Din L. Lin, Kole V. Lynch, Joanna Halkias, Ventura F. Mendoza, Trevor D. Burt, Casper Bendixsen, Kathrine Barnes, Haejin Kim, Kyra Jones, Dennis R. Ownby, Christine C. Johnson, Christine M. Seroogy, James E. Gern, Homer A. Boushey, Susan V. Lynch

Allergy & Immunology Articles

Maternal asthma status, prenatal exposures, and infant gut microbiota perturbation are associated with heightened risk of atopy and asthma risk in childhood, observations hypothetically linked by intergenerational microbial transmission. Using maternal vaginal (n = 184) and paired infant stool (n = 172) samples, we identify four compositionally and functionally distinct Lactobacillus-dominated vaginal microbiota clusters (VCs) that relate to prenatal maternal health and exposures and infant serum immunoglobulin E (IgE) status at 1 year. Variance in bacteria shared between mother and infant pairs relate to VCs, maternal allergy/asthma status, and infant IgE levels. Heritable bacterial gene pathways associated with infant IgE …

Poziotinib Inhibits Her2-Mutant-Driven Therapeutic Resistance And Multiorgan Metastasis In Breast Cancer, Rashi Kalra, Ching Hui Chen, Junkai Wang, Ahmad Bin Salam, Lacey E Dobrolecki, Alaina Lewis, Christina Sallas, Clayton C Yates, Carolina Gutierrez, Balasubramanyam Karanam, Meenakshi Anurag, Bora Lim, Matthew J Ellis, Shyam M Kavuri

Faculty, Staff and Student Publications

The pan-HER tyrosine kinase inhibitor (TKI) neratinib is therapeutically active against metastatic breast cancers harboring activating HER2 mutations, but responses are variable and often not durable. Here we demonstrate that recurrent HER2 mutations have differential effects on endocrine therapy responsiveness, metastasis, and pan-HER TKI therapeutic sensitivity. The prevalence and prognostic significance may also depend on whether the HER2 mutant has arisen in the context of lobular versus ductal histology. The most highly recurrent HER2 mutant, L755S, was particularly resistant to neratinib but sensitive to the pan-HER TKI poziotinib, alone or in combination with fulvestrant. Poziotinib reduced tumor growth, diminished multiorgan …

A Multi-Institutional Prediction Model To Estimate The Risk Of Recurrence And Mortality After Mastectomy For T1-2n1 Breast Cancer, Sarah M C Sittenfeld, Emily C Zabor, Sarah N Hamilton, Henry M Kuerer, Mahmoud El-Tamer, George E Naoum, Pauline T Truong, Alan Nichol, Benjamin D Smith, Wendy A Woodward, Tracy-Ann Moo, Simon N Powell, Chirag S Shah, Alphonse G Taghian, Ibrahim Abu-Gheida, Rahul D Tendulkar

Faculty, Staff and Student Publications

Background: Post-mastectomy radiation therapy (PMRT) in women with pathologic stage T1-2N1M0 breast cancer is controversial.

Methods: Data from five North American institutions including women undergoing mastectomy without neoadjuvant therapy with pT1-2N1M0 breast cancer treated from 2006 to 2015 were pooled for analysis. Competing-risks regression was performed to identify factors associated with locoregional recurrence (LRR), distant metastasis (DM), overall recurrence (OR), and breast cancer mortality (BCM).

Results: A total of 3532 patients were included for analysis with a median follow-up time among survivors of 6.8 years (interquartile range [IQR], 4.5-9.5 years). The 2154 (61%) patients who received PMRT had significantly more …

Exploring Intersectionality In School Disciplinary Decisions: A Phenomenology Of The Experiences Of African American Female Administrators, Jennifer M. Anthony

Doctoral Dissertations and Projects

The purpose of this transcendental phenomenological study was to explore how African American female school administrators experience and understand intersectionality regarding discipline outcomes. The theories used to guide this study are critical race theory, first introduced by Bell in 1977, and intersectionality theory coined by Crenshaw in 1989 as they seek to analyze how racism and the intersection of marginalized identities impact school discipline outcomes. The central question that guided this research is how do African American female school administrators experience and understand intersectionality and discipline outcomes? This study used purposeful and criterion sampling to acquire 10 African American female …

Insomnia Complaints And Perceived Immune Fitness In Young Adults With And Without Self-Reported Impaired Wound Healing, Jessica Balikji, Maarten M. Hoogbergen, Johan Garssen, Thomas Roth, Joris C. Verster

Sleep Medicine Articles

Background and Objectives: Adequate sleep and an effective immune system are both essential to maintain a good health status. The current study aimed to determine the nature of insomnia complaints and perceived immune fitness among Dutch young adults with and without self-reported impaired wound healing.

Materials and Methods: A total of (n = 2033) Dutch students (83.8% women) completed an online survey. Perceived immune fitness was assessed with a single-item scale and insomnia complaints with the SLEEP-50 insomnia subscale. The sample comprised a control group without self-reported impaired wound healing (n = 1622), a wound infection (WI) group (n = …

Left Sided Breast Cancer Is Associated With Aggressive Biology And Worse Outcomes Than Right Sided Breast Cancer, Yara Abdou, Medhavi Gupta, Mariko Asaoka, Kristopher Attwood, Opyrchal Mateusz, Shipra Gandhi, Kazuaki Takabe

2020-Current year OA Pubs

Breast cancer is more common on the left side than the right side. We aim to evaluate differences in clinicopathological and genomic characteristics based on laterality. We analyzed survival outcomes and clinical characteristics of 881,320 patients recorded by the Surveillance, Epidemiology, and End Results (SEER) program. The Cancer Genome Atlas (TCGA) was used to explore genomic and clinical features from 1,062 patients. Gene expression data was used to quantitate cytolytic activity and hallmark gene-sets were used for gene set enrichment analysis. An institutional retrospective review was conducted on 155 patients treated with neoadjuvant chemotherapy (NACT). Patient characteristics were summarized by …

Enhancing Interprofessional Collaboration And Interprofessional Education In Women's Health, Laura Baecher-Lind, Angela C Fleming, Rashmi Bhargava, Susan M Cox, Elise N Everett, David A Forstein, Shireen Madani Sims, Helen K Morgan, Christopher M Morosky, Celeste S Royce, Tammy S Sonn, Jill M Sutton, Scott C Graziano

2020-Current year OA Pubs

This article is from the 'To The Point' series from the Association of Professors of Gynecology and Obstetrics Undergraduate Medical Education Committee. The purpose of this review is to provide an understanding of the differing yet complementary nature of interprofessional collaboration and interprofessional education as well as their importance to the specialty of Obstetrics and Gynecology. We provide a historical perspective of how interprofessional collaboration and interprofessional education have become key aspects of clinical and educational programs, enhancing both patient care and learner development. Opportunities to incorporate interprofessional education within women's health educational programs across organizations are suggested. This is …

Online Randomised Factorial Trial Of Electronic Screening And Brief Intervention For Alcohol Use In Pregnancy: A Study Protocol, Steven J. Ondersma, Lisa Todd, Samantha Jablonski, Chaarushi Ahuja, Kathryn Gilstad-Hayden, Gregory Goyert, Amy M. Loree, Jaimee Heffner, Kimberly A. Yonkers

Center for Health Policy and Health Services Research Articles

INTRODUCTION: Approximately 1 in 7 pregnant women in the USA report past-month alcohol use. Strong evidence connects prenatal alcohol exposure with a range of adverse perinatal outcomes, including the spectrum of conditions known as fetal alcohol spectrum disorders. Screening and Brief Intervention (SBI) has been recommended for pregnant women but has proven difficult to implement. This study will test the efficacy of single-session technology-delivered SBI (electronic SBI) for alcohol use in pregnancy, while simultaneously evaluating the possible additional benefit of tailored text messages and/or booster sessions in a 3×2 factorial trial.

METHOD AND ANALYSIS: This full factorial trial will use …

Polygenic Risk, Midlife Life's Simple 7, And Lifetime Risk Of Stroke, Emy A Thomas, Nitesh Enduru, Adrienne Tin, Eric Boerwinkle, Michael E Griswold, Thomas H Mosley, Rebecca F Gottesman, Myriam Fornage

Faculty, Staff and Student Publications

Background

Recent genetic discoveries in stroke have unleashed the potential of using genetic information for risk prediction and health interventions aimed at disease prevention. We sought to estimate the lifetime risk of stroke (LTRS) by levels of genetic risk and to investigate whether optimal cardiovascular health can offset the negative impact of high genetic risk on lifetime risk of stroke.

Methods and Results

Study participants were 11 568 middle‐aged adults (56% women, 23% Black adults), who were free of stroke at baseline and were followed up for a median of 28 years. The remaining LTRS was estimated according to levels …

Gonadal Sex Patterns P21-Induced Cellular Senescence In Mouse And Human Glioblastoma, Lauren Broestl, Nicole M Warrington, Lucia Grandison, Tamara Abou-Antoun, Olivia Tung, Saraswati Shenoy, Miranda M Tallman, Gina Rhee, Wei Yang, Jasmin Sponagel, Lihua Yang, Najla Kfoury-Beaumont, Cameron M Hill, Sulaiman A Qanni, Diane D Mao, Albert H Kim, Sheila A Stewart, Monica Venere, Jingqin Luo, Joshua B Rubin

2020-Current year OA Pubs

Males exhibit higher incidence and worse prognosis for the majority of cancers, including glioblastoma (GBM). Disparate survival may be related to sex-biased responses to treatment, including radiation. Using a mouse model of GBM, we show that female cells are more sensitive to radiation, and that senescence represents a major component of the radiation therapeutic response in both sexes. Correlation analyses revealed that the CDK inhibitor p21 and irradiation induced senescence were differentially regulated between male and female cells. Indeed, female cellular senescence was more sensitive to changes in p21 levels, a finding that was observed in wildtype and transformed murine …

Sex And Gender Differences In Symptoms Of Early Psychosis: A Systematic Review And Meta-Analysis, Brooke Carter, Jared Wootten, Suzanne Archie, Amanda L Terry, Kelly K. Anderson

Epidemiology and Biostatistics Publications

First-episode psychosis (FEP) can be quite variable in clinical presentation, and both sex and gender may account for some of this variability. Prior literature on sex or gender differences in symptoms of psychosis have been inconclusive, and a comprehensive summary of evidence on the early course of illness is lacking. The objective of this study was to conduct a systematic review and meta-analysis of the literature to summarize prior evidence on the sex and gender differences in the symptoms of early psychosis. We conducted an electronic database search (MEDLINE, Scopus, PsycINFO, and CINAHL) from 1990 to present to identify quantitative …

The Intersections Of Sex And Inequality In A Mixed Status Industrial London Sample, Anna Green

Boise State University Theses and Dissertations

Saint Pancras Burial Ground and its inhumated priests, paupers, aristocrats, and migrants provide a unique perspective into the interactions between sex and inequality in 18th and 19th century industrial London. Frequencies of caries, dental calculus, periodontal disease, linear enamel hypoplasia, periapical lesions, tuberculosis, treponematosis, rickets, and trauma among 224 females from St. Pancras were compared to 27 low-status females from Crossbones Burial Ground and 74 primarily high-status females from Chelsea Old Church Cemetery. Based on the information known about those buried at St. Pancras, it was hypothesized that the frequencies of health indicators in St. Pancras should fall between the …

A Genome-Wide Association Study Of Obstructive Heart Defects Among Participants In The National Birth Defects Prevention Study, Sara R Rashkin, Mario Cleves, Gary M Shaw, Wendy N Nembhard, Eirini Nestoridi, Mary M Jenkins, Paul A Romitti, Xiang-Yang Lou, Marilyn L Browne, Laura E Mitchell, Andrew F Olshan, Kevin Lomangino, Sudeepa Bhattacharyya, John S Witte, Charlotte A Hobbs

Faculty, Staff and Student Publications

Obstructive heart defects (OHDs) share common structural lesions in arteries and cardiac valves, accounting for ~25% of all congenital heart defects. OHDs are highly heritable, resulting from interplay among maternal exposures, genetic susceptibilities, and epigenetic phenomena. A genome-wide association study was conducted in National Birth Defects Prevention Study participants (N

Electrophysiological Alterations Driving Pain-Associated Spontaneous Activity In Human Sensory Neuron Somata Parallel Alterations Described In Spontaneously Active Rodent Nociceptors, Robert Y North, Max A Odem, Yan Li, Claudio Esteves Tatsui, Ryan M Cassidy, Patrick M Dougherty, Edgar T Walters

Faculty, Staff and Student Publications

Neuropathic pain in rodents can be driven by ectopic spontaneous activity (SA) generated by sensory neurons in dorsal root ganglia (DRG). The recent demonstration that SA in dissociated human DRG neurons is associated with reported neuropathic pain in patients enables a detailed comparison of pain-linked electrophysiological alterations driving SA in human DRG neurons to alterations that distinguish SA in nociceptors from SA in low-threshold mechanoreceptors (LTMRs) in rodent neuropathy models. Analysis of recordings from dissociated somata of patient-derived DRG neurons showed that SA and corresponding pain in both sexes were significantly associated with the three functional electrophysiological alterations sufficient to …

Clinical Research In Ovarian Cancer: Consensus Recommendations From The Gynecologic Cancer Intergroup, Ignace Vergote, Antonio Gonzalez-Martin, Domenica Lorusso, Charlie Gourley, Mansoor Raza Mirza, Jean-Emmanuel Kurtz, Aikou Okamoto, Kathleen Moore, Frédéric Kridelka, Iain Mcneish, Alexander Reuss, Bénédicte Votan, Andreas Du Bois, Sven Mahner, Isabelle Ray-Coquard, Elise C Kohn, Jonathan S Berek, David S P Tan, Nicoletta Colombo, Rongyu Zang, Nicole Concin, Dearbhaile O'Donnell, Alejandro Rauh-Hain, C Simon Herrington, Christian Marth, Andres Poveda, Keiichi Fujiwara, Gavin C E Stuart, Amit M Oza, Michael A Bookman, Participants Of The 6th Gynecologic Cancer Intergroup (Gcig) Ovarian Cancer Consensus Conference On Clinical Research

Faculty, Staff and Student Publications

The Gynecologic Cancer InterGroup (GCIG) sixth Ovarian Cancer Conference on Clinical Research was held virtually in October, 2021, following published consensus guidelines. The goal of the consensus meeting was to achieve harmonisation on the design elements of upcoming trials in ovarian cancer, to select important questions for future study, and to identify unmet needs. All 33 GCIG member groups participated in the development, refinement, and adoption of 20 statements within four topic groups on clinical research in ovarian cancer including first line treatment, recurrent disease, disease subgroups, and future trials. Unanimous consensus was obtained for 14 of 20 statements, with …

Advances In Head And Neck Cancer Pain, Y Ye, D D Jensen, C T Viet, H L Pan, W M Campana, M Amit, M D Boada

Faculty, Staff and Student Publications

Head and neck cancer (HNC) affects over 890,000 people annually worldwide and has a mortality rate of 50%. Aside from poor survival, HNC pain impairs eating, drinking, and talking in patients, severely reducing quality of life. Different pain phenotype in patients (allodynia, hyperalgesia, and spontaneous pain) results from a combination of anatomical, histopathological, and molecular differences between cancers. Poor pathologic features (e.g., perineural invasion, lymph node metastasis) are associated with increased pain. The use of syngeneic/immunocompetent animal models, as well as a new mouse model of perineural invasion, provides novel insights into the pathobiology of HNC pain. Glial and immune …

Strategy For Generating Blinded Evidence For Single-Arm Trials With External Controls Using Expert Review Of Home Video, Bharti Manwani, Carson Finger, Lynda Lisabeth

Faculty, Staff and Student Publications

Stroke risk and prevalence increase with advanced age and women tend to be older than men at the time of their first stroke. Advanced age in women confers unique stroke risks that are beyond reproductive factors. Previous reviews and guidelines have largely focused on risk factors specific to women, with a predominant focus on reproductive factors and, therefore, younger to middle-aged women. This review aims to specifically describe stroke risk factors in elderly women, the population of women where the majority of strokes occur, with a focus on atrial fibrillation, hormone therapy, psychosocial risk factors, and cognitive impairment. Our review …

Microbiome Dynamics During Chemoradiation Therapy For Anal Cancer, Daniel Lin, Molly B El Alam, Joseph Abi Jaoude, Ramez Kouzy, Jae L Phan, Jacob H Elnaggar, Brianna Resendiz, Andrea Y Delgado Medrano, Erica J Lynn, Nicholas D Nguyen, Sonal S Noticewala, Geena G Mathew, Emma B Holliday, Bruce D Minsky, Prajnan Das, Van K Morris, Cathy Eng, Melissa P Mezzari, Joseph F Petrosino, Nadim J Ajami, Ann H Klopp, Cullen M Taniguchi, Lauren E Colbert

Faculty, Staff and Student Publications

Purpose: Patients with localized squamous cell carcinoma of the anus (SCCA) who experience treatment toxicity or recurrences have few therapeutic options. Investigation into the microbiome's influence on treatment toxicity and its potential use as a predictive biomarker could improve these patients' outcomes. Our study presents the first longitudinal characterization of the SCCA tumor microbiome and its associations with treatment-related toxicities.

Methods and materials: This prospective cohort study included patients with nonmetastatic SCCA receiving standard-of-care chemoradiation therapy. Anorectal swabs of the tumor site were collected before, during, and after treatment. Patient-reported quality-of-life metrics were collected at similar time points. 16S rRNA …

Immune Phenotype Of The Cd4+ T Cells In The Aged Lymphoid Organs And Lacrimal Glands, Claudia M Trujillo-Vargas, Kelsey E Mauk, Humberto Hernandez, Rodrigo G De Souza, Zhiyuan Yu, Jeremias G Galletti, Jana Dietrich, Friedrich Paulsen, Cintia S De Paiva

Faculty, Staff and Students Publications

Aging is associated with a massive infiltration of T lymphocytes in the lacrimal gland. Here, we aimed to characterize the immune phenotype of aged CD4+ T cells in this tissue as compared with lymphoid organs. To perform this, we sorted regulatory T cells (Tregs, CD4+CD25+GITR+) and non-Tregs (CD4+CD25negGITRneg) in lymphoid organs from female C57BL/6J mice and subjected these cells to an immunology NanoString® panel. These results were confirmed by flow cytometry, live imaging, and tissue immunostaining in the lacrimal gland. Importantly, effector T helper 1 (Th1) genes were highly upregulated on aged Tregs, including the master regulator Tbx21. Among …

Identifying Bone Matrix Impairments In A Mouse Model Of Neurofibromatosis Type 1 (Nf1) By Clinically Translatable Techniques, Rafay Ahmed, Sasidhar Uppuganti, Shrey Derasari, Joshua Meyer, Jacquelyn S Pennings, Florent Elefteriou, Jeffry S Nyman

Faculty, Staff and Students Publications

Three-to-four percent of children with neurofibromatosis type 1 (NF1) present with unilateral tibia bowing, fracture, and recalcitrant healing. Alkaline phosphatase enzyme therapy prevented poor bone mineralization and poor mechanical properties in mouse models of NF1 skeletal dysplasia; but transition to clinical trials is hampered by the lack of a technique that i) identifies NF1 patients at risk of tibia bowing and fracture making them eligible for trial enrollment and ii) monitors treatment effects on matrix characteristics related to bone strength. Therefore, we assessed the ability of matrix-sensitive techniques to provide characteristics that differentiate between cortical bone from mice characterized by …

Randomized Placebo-Controlled Trial Of Losartan For Pediatric Nafld, Miriam B Vos, Mark L Van Natta, Niviann M Blondet, Srinivasan Dasarathy, Mark Fishbein, Paula Hertel, Ajay K Jain, Saul J Karpen, Joel E Lavine, Saeed Mohammad, Laura A Miriel, Jean P Molleston, Marialena Mouzaki, Arun Sanyal, Emily P Sharkey, Jeffrey B Schwimmer, James Tonascia, Laura A Wilson, Stavra A Xanthakos, Nash Clinical Research Network

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: To date, no pharmacotherapy exists for pediatric NAFLD. Losartan, an angiotensin II receptor blocker, has been proposed as a treatment due to its antifibrotic effects.

APPROACH AND RESULTS: The Nonalcoholic Steatohepatitis Clinical Research Network conducted a multicenter, double-masked, placebo-controlled, randomized clinical trial in children with histologically confirmed NAFLD at 10 sites (September 2018 to April 2020). Inclusion criteria were age 8-17 years, histologic NAFLD activity score ≥ 3, and serum alanine aminotransferase (ALT) ≥ 50 U/l. Children received 100 mg of losartan or placebo orally once daily for 24 weeks. The primary outcome was change in ALT …

Chronic Granulomatous Disease-Like Presentation Of A Child With Autosomal Recessive Pkcδ Deficiency, Anna-Lena Neehus, Karen Tuano, Tom Le Voyer, Sarada L Nandiwada, Kruthi Murthy, Anne Puel, Jean-Laurent Casanova, Javier Chinen, Jacinta Bustamante

Faculty, Staff and Students Publications

BACKGROUND: Autosomal recessive (AR) PKCδ deficiency is a rare inborn error of immunity (IEI) characterized by autoimmunity and susceptibility to bacterial, fungal, and viral infections. PKCδ is involved in the intracellular production of reactive oxidative species (ROS).

MATERIAL AND METHODS: We studied a 5-year old girl presenting with a history of Burkholderia cepacia infection. She had no history of autoimmunity, lymphocyte counts were normal, and no auto-antibodies were detected in her plasma. We performed a targeted panel analysis of 407 immunity-related genes and immunological investigations of the underlying genetic condition in this patient.

RESULTS: Consistent with a history suggestive of …

Early Growth Response 1 Transcription Factor Is Essential For The Pathogenic Properties Of Human Endometriotic Epithelial Cells, Vineet K Maurya, Maria M Szwarc, Rodrigo Fernandez-Valdivia, David M Lonard, Song Yong, Niraj Joshi, Asgerally T Fazleabas, John P Lydon

Faculty, Staff and Students Publications

Although a non-malignant gynecological disorder, endometriosis displays some pathogenic features of malignancy, such as cell proliferation, migration, invasion and adaptation to hypoxia. Current treatments of endometriosis include pharmacotherapy and/or surgery, which are of limited efficacy and often associated with adverse side effects. Therefore, to develop more effective therapies to treat this disease, a broader understanding of the underlying molecular mechanisms that underpin endometriosis needs to be attained. Using immortalized human endometriotic epithelial and stromal cell lines, we demonstrate that the early growth response 1 (EGR1) transcription factor is essential for cell proliferation, migration and invasion, which represent some of the …

Sex-Specific Phenotypes In The Aging Mouse Heart And Consequences For Chronic Fibrosis, Aude Angelini, Jesus Ortiz-Urbina, Joann Trial, Anilkumar K Reddy, Anna Malovannaya, Antrix Jain, Mark L Entman, George E Taffet, Katarzyna A Cieslik

Faculty, Staff and Students Publications

The incidence of diastolic dysfunction increases with age in both humans and mice. This is characterized by increased passive stiffness and slower relaxation of the left ventricle. The stiffness arises at least partially from progressively increased interstitial collagen deposition because of highly secretory fibroblasts. In the past, we demonstrated that AMPK activation via the drug 5-aminoimidazole-4-carboxamide riboside (AICAR) in middle-aged mice reduced adverse remodeling after myocardial infarction. Therefore, as an attempt to normalize the fibroblast phenotype, we used 21-mo-old male and female mice and treated them with AICAR (0.166 mg/g body wt) where each mouse was followed in a functional …

Circulating Trophoblast Numbers As A Potential Marker For Pregnancy Complications, Brielle Crovetti, Mohamad Ali Maktabi, Hadi Erfani, Tachjaree Panchalee, Qun Wang, Liesbeth Vossaert, Ignatia Van Den Veyver

Center for Medical Ethics and Health Policy Staff Publications

Objective: To explore the potential of circulating trophoblasts (TBs) as a non-invasive tool to assess placental health and predict obstetric complications.

Methods: We retrospectively reviewed maternal characteristics and pregnancy outcomes of 369 women who enrolled in our original cell-based NIPT (cbNIPT) study. The number of circulating TBs recovered from the maternal blood samples was recorded and expressed as fetal cell concentration (FCC). We evaluated if FCC can be used to predict pregnancy outcomes such as hypertensive disorders of pregnancy (HDP), fetal growth restriction, placental abruption, preterm labor, and pregnancy loss.

Results: Receiver operating characteristic (ROC) analysis was performed to find …

De Novo Heterozygous Variants In Slc30a7 Are A Candidate Cause For Joubert Syndrome, Monica Penon-Portmann, Mohammad K Eldomery, Lorraine Potocki, Dana Marafi, Jennifer E Posey, Zeynep Coban-Akdemir, Tamar Harel, Christopher M Grochowski, Hailey Loucks, Walter Patrick Devine, Jessica Van Ziffle, Dan Doherty, James R Lupski, Joseph T Shieh

Center for Medical Ethics and Health Policy Staff Publications

Joubert syndrome (JS), a well-established ciliopathy, is characterized by the distinctive molar tooth sign on brain MRI, ataxia, and neurodevelopmental features. Other manifestations can include polydactyly, accessory frenula, renal, or liver disease. Here, we report individuals meeting criteria for JS with de novo heterozygous variants in SLC30A7 (Chr1p21.2). The first individual is a female with history of unilateral postaxial polydactyly, classic molar tooth sign on MRI, macrocephaly, ataxia, ocular motor apraxia, neurodevelopmental delay, and precocious puberty. Exome sequencing detected a de novo heterozygous missense variant in SLC30A7: NM_133496.5: c.407 T > C, (p.Val136Ala). The second individual had bilateral postaxial polydactyly, molar …

Reoperative Brachial Plexus Neurolysis After Previous Anatomically Complete Supraclavicular Decompression For Neurogenic Thoracic Outlet Syndrome: A 10-Year Single-Center Case Series, Momodou L Jammeh, Alexander Yang, Ahmmad A Abuirqeba, J Westley Ohman, Robert W Thompson

2020-Current year OA Pubs

BACKGROUND: Optimal management of recurrent neurogenic thoracic outlet syndrome (NTOS) remains a considerable challenge.

OBJECTIVE: To assess the safety and effectiveness of reoperative brachial plexus neurolysis in patients with recurrent NTOS.

METHODS: From 2009 to 2019, 85 patients underwent reoperative supraclavicular brachial plexus neurolysis for recurrent NTOS after a previous anatomically complete supraclavicular decompression. Data from a prospectively maintained database were analyzed retrospectively.

RESULTS: The mean patient age at reoperation was 36.9 ± 1.3 (range 15-64) years, 75% were female, and the interval after previous primary operation was 2.5 ± 0.2 years. Intervening injury had precipitated recurrent NTOS in 14 …

Patient With Multiple Genetically Distinct Thyroid Nodules Including Papillary Thyroid Carcinoma Harboring Novel Ywhag-Braf Fusion, Ruihe Lin, Zi-Xuan Wang, Elizabeth Cottrill, Nitika Badjatia, Stacey Gargano

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Next-generation sequencing (NGS) analysis of thyroid samples aids in risk stratification of cytologically indeterminate nodules and contributes to our understanding of molecular mechanisms in thyroid neoplasia. Several genes, including BRAF, RAS, and EIF1AX, are known to play a role in thyroid tumorigenesis. Here we report a case of papillary thyroid carcinoma (PTC) in which a single lesion harbored a novel YWHAG-BRAF fusion and EIF1AX mutation and displayed mixed morphological findings. The patient is a 74-year-old female with multiple incidentally discovered thyroid nodules, two of which were sampled by ultrasound-guided fine needle aspiration (FNA). Cytologic diagnosis for both nodules was suspicious …

Experiences With Menses In Transgender And Gender Nonbinary Adolescents., Beth I. Schwartz, Arielle Effron, Benjamin Bear, Vanessa L Short, Julia Eisenberg, Sarah Felleman, Anne E Kazak

Department of Obstetrics and Gynecology Faculty Papers

STUDY OBJECTIVE: To describe menstrual history, associated dysphoria, and desire for menstrual management in transgender male and gender diverse adolescents who were assigned female at birth

DESIGN: Retrospective chart review

SETTING: Tertiary care children's hospital

PARTICIPANTS: All patients seen in a multidisciplinary pediatric gender program from March 2015 through December 2020 who were assigned female at birth, identified as transgender male or gender nonbinary, and had achieved menarche

INTERVENTION: None

MAIN OUTCOME MEASURES: Patient demographics, menstrual history, interest in and prior experiences with menstrual management, parental support, and concerns about menstrual management

RESULTS: Of the 129 included patients, 116 (90%) …

Sex Differences In The Genetic Architecture Of Cognitive Resilience To Alzheimer's Disease., Jaclyn M Eissman, Logan Dumitrescu, Emily R Mahoney, Alexandra N Smith, Shubhabrata Mukherjee, Michael L Lee, Phoebe Scollard, Seo Eun Choi, William S Bush, Corinne D Engelman, Qiongshi Lu, David W Fardo, Emily H Trittschuh, Jesse Mez, Catherine C Kaczorowski, Hector Hernandez Saucedo, Keith F Widaman, Rachel F Buckley, Michael J Properzi, Elizabeth C Mormino, Hyun Sik Yang, Theresa M Harrison, Trey Hedden, Kwangsik Nho, Shea J Andrews, Douglas Tommet, Niran Hadad, R Elizabeth Sanders, Douglas M Ruderfer, Katherine A Gifford, Xiaoyuan Zhong, Neha S Raghavan, Badri N Vardarajan, Margaret A Pericak-Vance, Lindsay A Farrer, Li San Wang, Carlos Cruchaga, Gerard D Schellenberg, Nancy J Cox, Jonathan L Haines, C Dirk Keene, Andrew J Saykin, Eric B Larson, Reisa A Sperling, Richard Mayeux, Michael L Cuccaro, David A Bennett, Julie A Schneider, Paul K Crane, Angela L Jefferson, Timothy J Hohman

Faculty Research 2022

Approximately 30% of elderly adults are cognitively unimpaired at time of death despite the presence of Alzheimer's disease neuropathology at autopsy. Studying individuals who are resilient to the cognitive consequences of Alzheimer's disease neuropathology may uncover novel therapeutic targets to treat Alzheimer's disease. It is well established that there are sex differences in response to Alzheimer's disease pathology, and growing evidence suggests that genetic factors may contribute to these differences. Taken together, we sought to elucidate sex-specific genetic drivers of resilience. We extended our recent large scale genomic analysis of resilience in which we harmonized cognitive data across four cohorts …