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  1. Home
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Browsing by Author "Essex, Amanda"

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    Endocannabinoids Regulate Cerebellar Granule Cell Differentiation
    (2017-09) Essex, Amanda; Black, Kylie; Baygani, Shawyon; Mier, Tristan; Martinez, Ricardo; Mackie, Ken; Kalinovsky, Anna
    The cerebellum plays a crucial role in learning and execution of complex automated behaviors, including fine motor skills, language, and emotional regulation. Cerebellar development continues throughout an extended postnatal period. The most numerous neurons in the cerebellum, as well as the entire brain, are the cerebellar granule cells (GCs), which are generated in a dedicated secondary proliferative zone, the external granule cell layer (EGL), during the first three postnatal weeks in mice, and over a year in humans. The robust expansion of granule cells during early development is responsible for the majority of cerebellar expansion. Morphological and molecular changes that drive GC proliferation and differentiation have been extensively characterized, starting from the developmental studies by Santiago Ramón y Cajal. GC progenitors (GCPs) proliferate in the outer EGL (oEGL). As they are pushed into the inner EGL (iEGL) by the newly generated GCPs, they exit the cell cycle and begin differentiation, first extending bipolar neurites, followed by tangential migration, and eventually radial migration to the inner granule cell layer (IGL), their target territory. Deregulation of GCPs expansion, proliferation to differentiation switch, or the rate of migration could contribute to abnormal cerebellar size and compartmentalization and disrupt cerebellar circuits’ wiring and function. Endocannabinoids (eCBs) have been identified as key players regulating neuron proliferation and migration in the fore- and mid-brain development, however their role in cerebellar development has not yet been explored in detail. Our preliminary results show robust expression of cannabinoid receptor 1 (CB1) in iEGL GCs, concomitant with expression diacylglycerol lipase α (DGLα) a major enzyme required for the synthesis of eCB 2-arachidonoylglycerol (2-AG), in PCs. Furthermore, our preliminary results show that cerebellar size is reduced in CB1 KOs. In this study we investigate the mechanisms through which eCB signaling may regulate GC proliferation and differentiation, focusing on the GCPs cycle length, rate of differentiation and migration.
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    Menorrhagia: The Importance of Treatment in Women with Disorders of Hemostasis
    (2021-03-25) Essex, Amanda; Sommers, Kit; Colomb, Elaine; Watters, Melissa
    Case A 37 yo female was admitted to the hospital for potential Immune Thrombocytopenic Purpura after laboratory findings noted a platelet count of 12k and mild anemia. Her history revealed new onset petechiae, gingival bleeding and recently worsening menorrhagia. Treatment began with IVIG, prednisone and iron and she was ultimately discharged with instructions to follow up. Within 2.5 months of her initial presentation of ITP, the patient had a recurrence of petechiae and a platelet count of 4k. Upon readmission, IVIG and steroids were restarted. At this time, she was also experiencing cramping, fatigue, and heavy menstrual bleeding that led to another drop in hemoglobin. Discussions about outpatient management of menorrhagia were started. After 5 days, she was discharged and began Tranexamic Acid to address excessive menstrual losses at home. In follow up, she expressed significant anxiety about her diagnosis of ITP and felt that her ongoing menorrhagia was causing her ITP to recur. Conclusions Finding the best treatment option for patients experiencing menorrhagia requires consideration of numerous factors including the patient’s medical history, cause and severity of menorrhagia, future childbearing plans, patient preference and more. Without proper management, menorrhagia has been linked to decreased quality of life in terms of physical, mental, and social health. Anxiety surrounding menorrhagia can be compounded when patients do not have a clear understanding of the etiology of their condition. Clinical Significance Managing disorders of hemostasis like ITP can be complex especially in cases of early relapse. Menorrhagia in the setting of a bleeding disorder can further complicate management and can lead to worsening physical and psychosocial consequences. While prompt recognition and treatment of menorrhagia in patients with disorders of hemostasis is important for improving physical outcomes, it also plays a critical role in improving quality of life for patients.
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    Neonatal Abstinence Syndrome Screening for Newborn Girl with Prenatal Maternal History of Substance Use Disorder
    (2020-03) Arnaudo, Camila; Chiu, Megan; Essex, Amanda; D'Arnaud, Lindsey
    Background: Neonatal Abstinence Syndrome (NAS) is a drug withdrawal syndrome of newborns with prenatal exposure to opioids and other substances. Incidence of NAS has increased significantly in the last decade and remains a current issue. Untreated NAS can lead to adverse outcomes including infant death. All newborns with known opioid exposure are screened for NAS using the Finnegan Scoring System or now more popular Eat Sleep Console (ESC) method. Treatment ranges from supportive care to pharmacological management, dependent on assessment scoring and clinical signs. Case: A 3.48kg female newborn was born at 40-week,2-day gestation from spontaneous vaginal delivery with no meconium and Apgar scores of 8 and 9. Prenatal maternal history was significant for hepatitis C, heroin use and buprenorphine (BUP) mono-product as medication assisted treatment (MAT) and maternal urine drug screen positive for BUP and benzodiazepines at delivery. The newborn’s urine drug screen was positive only for BUP. During her 4-day hospital course, she was eating and voiding well with some need for caregiver support for consoling and no need for pharmacological intervention per ESC. She was discharged home with mother and supportive extended family and has been developing well without major complications. Clinical Significance: Several barriers (social stigma, provider bias and legal policies) discourage mothers from seeking prenatal care and MAT, thus precluding NAS screening and treatment. Studies show that increased access and earlier initiation to maternal MAT improves outcomes for both mother and baby. Decreasing stigma and bias, implementing non-punitive policies and using ESC have also been shown to improve outcomes. This case provides a positive example of early initiation maternal MAT and use of ESC for a newborn with concern for NAS. We hope these cases will continue to help decrease stigma and help us advocate for non-punitive state policies regarding substance use during pregnancy.
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    “Women Never Use Drugs Alone” Assessing Stigma & Access to Care among Women who use Drugs.
    (2019-07) Essex, Amanda; Lawrence, Carrie; Turner, Brooklyne
    Increased rates of opioid misuse among pregnant women has become a significant public health issue in Indiana. Nation-wide the rate of opioid use among pregnant women has quadrupled since 2005, and Indiana is following the same trend. As this issue grows it becomes increasingly important to understand the unique needs of this vulnerable population. Mothers who use illicit drugs during pregnancy often have fewer prenatal care visits than non-using mothers. The issue of prenatal care access is intensified among women of color who systematically experience greater health disparities and inequities. Without access to adequate prenatal care both mothers and their children risk various health consequences. In Indiana, a state that is ranked among the 10 worst states for infant and maternal mortality, addressing stigma and factors that contribute to prenatal care barriers is critical. This qualitative study sought to assess the current role of stigma and identify other barriers to health and healthcare services among women of childbearing age in Indiana who use or have used illicit drugs and identify ways to improve their experiences with and access to these services.
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