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Articles 31 - 60 of 60
Full-Text Articles in Pharmaceutics and Drug Design
Nih Funding For Research Underlying New Cancer Therapies, Ekaterina Galkina Cleary, Fred D. Ledley
Nih Funding For Research Underlying New Cancer Therapies, Ekaterina Galkina Cleary, Fred D. Ledley
Natural & Applied Sciences Faculty Publications
Contemporary discovery and development of cancer drugs are based on the model that investments in basic biomedical science will provide insights that can be translated into new cures. In the USA, basic research is primarily funded by the National Institutes of Health (NIH),1 which allocates half of its research budget to basic science,2 with smaller amounts contributed by philanthropy, academics, or industry.1 Basic science is formally defined as the “systematic study directed toward fuller knowledge or understanding of the fundamental aspects of phenomena and observable facts without specific application towards processes or products in mind”.3 However, science is often useinspired,4 …
Vaccines In Current Culture: The Hpv Vaccine Controversy, Alyssa Johnston
Vaccines In Current Culture: The Hpv Vaccine Controversy, Alyssa Johnston
Senior Honors Theses
The use of vaccinations has drastically decreased mortality and morbidity rates related to infectious disease and has become an intrinsic part of modern health care. However, the fear of risks related to vaccines has been partially responsible for the decisions of many parents to delay or avoid vaccinating their children. The human papilloma virus (HPV) vaccine specifically is one of the most controversial vaccines in current culture due to reports of new onset or exacerbation of autoimmune diseases, infertility, and even death following its administration. This review synthesizes information regarding the relevance and safety of the HPV vaccine, as well …
Coronavirus Disease 2019 (Covid-19), Matthew Dunbar
Coronavirus Disease 2019 (Covid-19), Matthew Dunbar
Pharmacy Student Scholarship
No abstract provided.
After-Action Report: Tabletop Exercise On Opioid Crisis Response And Resilience, Alexander Siedschlag, Tiangeng Lu
After-Action Report: Tabletop Exercise On Opioid Crisis Response And Resilience, Alexander Siedschlag, Tiangeng Lu
Publications
AGENCY BRIEFINGS The opioid overdose epidemic has been characterized as the worst public health crisis in Pennsylvania, and the nation. Not only practitioners but also institutions of higher education with high research capacity, such as Penn State, are applying existing and developing new instruments to address opioid the crisis. Identifying best practices of preventing, protecting from, mitigating against, responding to, and recovering from opioid overdose outbreak is necessary for public health and safety and important for the overall homeland security enterprise, in consistency with the objectives of the Quadrennial Homeland Security Reviews (QHSR), the National Preparedness Goal (NPG), and the …
Polycystic Ovarian Syndrome And Hyperinsulinemia: Overview And Treatment, Amanda M. Meyer, Lauren D. Bajbus, Sarah E. Drake, Kristen M. Quertinmont, Ashley Overy, Anne Gentry
Polycystic Ovarian Syndrome And Hyperinsulinemia: Overview And Treatment, Amanda M. Meyer, Lauren D. Bajbus, Sarah E. Drake, Kristen M. Quertinmont, Ashley Overy, Anne Gentry
Pharmacy and Wellness Review
Polycystic ovary syndrome is a prevalent issue in women's health that is associated with hyperinsulinemia and insulin resistance and can lead to long-term health problems. The most highly recommended treatments are diet and lifestyle changes. If these changes alone are not enough, pharmacologic treatments may be employed which include metformin, spironolactone or thiazolidinediones, although more research is needed to fully realize their role. The role of the pharmacist in this disease state includes counseling patients on healthy lifestyle changes, consulting with the physician about prescribing the best medication for each patient, and monitoring therapy adherence in the patient.
Options For Breast Cancer Prevention In High-Risk Patients, Ashley M. Overy, Lacey A. Shumate, Sarah M. Webb, Ashley E. Lehnert, Monica A. Weisenberger, Whitney N. Detillion, Andrew M. Roecker
Options For Breast Cancer Prevention In High-Risk Patients, Ashley M. Overy, Lacey A. Shumate, Sarah M. Webb, Ashley E. Lehnert, Monica A. Weisenberger, Whitney N. Detillion, Andrew M. Roecker
Pharmacy and Wellness Review
Breast cancer is the most frequently diagnosed non-skin cancer in women, and one in eight women will develop breast cancer within their Iifetimes. Unfortunately, the strongest risk factors for breast cancer (i.e. age, family history, hormonal factors) are not easily modified. There is some evidence that chemopreventative drugs may be able to prevent breast cancer in high-risk patients. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer in high-risk women but may be associated with several serious adverse events. Clinical trials are currently in progress to determine if aromatase inhibitors are a viable alternative for breast …
Combatting The Opioid Epidemic In Texas By Holding Big Pharma Manufacturers Liable, Katherine Spiser
Combatting The Opioid Epidemic In Texas By Holding Big Pharma Manufacturers Liable, Katherine Spiser
St. Mary's Law Journal
Abstract forthcoming
Health Risks And Emerging Trends With The Use Of Electronic Cigarettes, Lucy Wagala, Austin Hopkins, Natalie Lennartz, Brian Heilbronner, Brittany L. Long, Natalie Dipietro Mager
Health Risks And Emerging Trends With The Use Of Electronic Cigarettes, Lucy Wagala, Austin Hopkins, Natalie Lennartz, Brian Heilbronner, Brittany L. Long, Natalie Dipietro Mager
Pharmacy and Wellness Review
Cigarette smoking is associated with many health risks and complications. Despite smokers' strong desire to quit, most battle with nicotine withdrawal and relapse. Because electronic cigarettes (e-cigarettes) do not contain tobacco, some believe them to be safer than traditional cigarettes and have used them as a replacement or adjunct nicotine source to prevent withdrawal symptoms. Electronic cigarettes are designed to mimic traditional cigarettes and expel a vapor composed of nicotine, water, glycerol, propylene glycol and other flavorings. Many e-cigarette companies use appealing platforms, which promise smoking cessation and harm reduction, to attract consumers; however, several studies have found e-cigarettes actually …
Neonatal Abstinence Syndrome From Selective Serotonin Reuptake Inhibitor Use During Pregnancy, Elizabeth Kramer, Maria Patnella, Rachel Bulko, Allie Harrison, Hannah Lamb, Manoranjan D'Souza
Neonatal Abstinence Syndrome From Selective Serotonin Reuptake Inhibitor Use During Pregnancy, Elizabeth Kramer, Maria Patnella, Rachel Bulko, Allie Harrison, Hannah Lamb, Manoranjan D'Souza
Pharmacy and Wellness Review
Neonatal abstinence syndrome (NAS) is a concern for infants born to mothers receiving treatment with a selective serotonin reuptake inhibitor (SSRI) throughout the pregnancy. The risk of NAS associated with SSRI use during pregnancy varies with the specific SSRI that is used by the patient during pregnancy. Common symptoms of NAS include premature delivery, gastrointestinal disturbances, irritability, low birth weight, short length and lack of response to various stimuli. Neonates that present with these symptoms can be scored using either the Finnegan or Lipsitz scoring tools. Neonates experiencing NAS can be calmed or treated using nonpharmacologic methods such as swaddling, …
Emergency Contraception: A Comparison Of Levonorgestrel And Ulipristal Acetate, Tara Tokar, Rachel Muhlenkamp, Kelsey Lindsley, Alison Steinbrunner, Michelle Musser
Emergency Contraception: A Comparison Of Levonorgestrel And Ulipristal Acetate, Tara Tokar, Rachel Muhlenkamp, Kelsey Lindsley, Alison Steinbrunner, Michelle Musser
Pharmacy and Wellness Review
Emergency contraceptives (EC) are a birth control method that is available to minimize unintended pregnancies that might result from unprotected intercourse. Several products are on the market and largely contain levonorgestrel as the active component, including Plan B One-Step®, Next Choice®, Next Choice One Dose™ and My Way®. These are labeled as effective up to 72 hours after intercourse and are available without a prescription. Another product, Ella™, contains ulipristal acetate and can be effective up to 120 hours after intercourse, but does require a prescription. Legislative issues have surrounded these products. At this point in time only Plan B …
Improving Maternal And Fetal Health: A Look At Thyroid Function During Pregnancy, Sarah Ginty, Jessica Beck, Taylor Gauthier, Amanda Meyer, Michelle R. Musser
Improving Maternal And Fetal Health: A Look At Thyroid Function During Pregnancy, Sarah Ginty, Jessica Beck, Taylor Gauthier, Amanda Meyer, Michelle R. Musser
Pharmacy and Wellness Review
Maintenance of thyroid function during pregnancy is critical for both maternal and fetal health and development; therefore, knowledge regarding the relationship between thyroid hormones and pregnancy is essential. The American Thyroid Association task force has developed clinical guidelines on the diagnosis and treatment of thyroid disease during pregnancy. Gestational thyroid diseases are divided into two classifications, hypothyroidism and hyperthyroidism, which are further divided into more specific classifications based on clinical presentation. Differentiation, diagnosis, and monitoring of thyroid diseases throughout pregnancy require assessing symptoms, as well as obtaining levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) concentration by a simple …
Lysteda® For Heavy Menstrual Bleeding, Erica B. Schoenberger, Todd A. Tucker Jr., Justin W. Steele, Amanda Meyer, Sandra L. Hrometz
Lysteda® For Heavy Menstrual Bleeding, Erica B. Schoenberger, Todd A. Tucker Jr., Justin W. Steele, Amanda Meyer, Sandra L. Hrometz
Pharmacy and Wellness Review
Lysteda®, a novel formulation of tranexamic acid, is an antifibrinolytic medication recently approved by the Food and Drug Administration (FDA) for the treatment of heavy menstrual bleeding. Tranexamic acid has been shown to significantly reduce menstrual blood loss while simultaneously allowing a woman to safely become pregnant. The major advantage of Lysteda® (an oral modified-release formulation of tranexamic acid) compared to oral immediate-release tranexamic acid, is the decreased occurrence of gastrointestinal side effects. As there are no therapeutic equivalents to Lysteda® for heavy menstrual bleeding, it is important for pharmacists to be able to counsel patients appropriately on the specific …
Effects Of Hormone Therapy On Cognition In Post-Menopausal Women, Jessica Langhals, Megan Meyer, Erica Schoenberger, Amanda Meyer, Kristen Finley Sobota
Effects Of Hormone Therapy On Cognition In Post-Menopausal Women, Jessica Langhals, Megan Meyer, Erica Schoenberger, Amanda Meyer, Kristen Finley Sobota
Pharmacy and Wellness Review
Menopause occurs as a result of decreased natural estrogen production by the body. A variety of short-term and long-term symptoms can occur during menopause, which may significantly impact a woman's daily life. Hormone therapy (HT) is commonly employed to alleviate these unwanted symptoms and to regain balance of hormone levels. Options include estrogen-only or estrogen-progestin combination therapy. While HT may help relieve symptoms such as cognitive decline caused by menopause, it also carries potential side effects. Although HT has shown a potential benefit in women with Alzheimer's disease (AD), overall outcomes measuring cognitive function improvement are inconclusive. Therefore, HT should …
Safety Constraint Optimization Of Combination Drug Therapy In Hypertension Clinical Trials, Victor Chukwu
Safety Constraint Optimization Of Combination Drug Therapy In Hypertension Clinical Trials, Victor Chukwu
College of Graduate Studies: Theses & Dissertations
In Clinical Practice, combination drug therapy has become common in treating many disease conditions. The purpose of these combinations is often to ensure optimal efficacy and to reduce adverse effects that may arise from monotherapy. Clinical trials have also been conducted to ensure efficacy and safety of these combinations before they are introduced into the market. However, adverse effects still occur with combination therapies. The objective of this study is to (1) To determine a region of optimum doses of Drug A and Drug B in combination while focusing on efficacy alone (2) To determine a region of optimum doses …
Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender
Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender
Student Theses 2015-Present
This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim …
The Morality Of Compulsory Licensing As An Access To Medicines Tool, Margo A. Bagley
The Morality Of Compulsory Licensing As An Access To Medicines Tool, Margo A. Bagley
Faculty Articles
This Article contemplates the validity of theft rhetoric in relation to the right of countries to grant compulsory licenses from an unconventional perspective; that of biblical teachings on what it means to steal.
Part I describes the use of theft rhetoric in relation to IP infringement broadly and drug-patent compulsory licenses in particular.
Part II challenges the contention, suggested by theft rhetoric, that compulsory licenses are morally wrong as a form of stealing, by considering the meaning of theft in the context of its Judeo-Christian origins.
Part III considers the cogency of the accusation that the issuance of compulsory licenses …
Development And Validation Of Triticum Phytobiological Method As An Alternative Procedure For Investigating In Vivo Acute Toxicity On Mice, Emil Ştefănescu, Aurelia N. Cristea, Cornel Chiriță, Octavian Olaru, Adriana Anghel, Mihaela Dinu
Development And Validation Of Triticum Phytobiological Method As An Alternative Procedure For Investigating In Vivo Acute Toxicity On Mice, Emil Ştefănescu, Aurelia N. Cristea, Cornel Chiriță, Octavian Olaru, Adriana Anghel, Mihaela Dinu
Journal of Mind and Medical Sciences
The goal of this study was to validate an alternative method for determining in vivo acute toxicity using vegetal material instead of laboratory animals, starting from the phytobiological method known also as the Triticum technique. We set out to demonstrate that vegetal cells have similar sensitivity to some toxic agents as animal cells, in which case a statistical correlation could be established. A series of new compounds synthesized by the Romanian National Institute for Chemical Pharmaceutical Research and Development as potential β3 adrenergic receptors agonists were tested for their acute toxicity using classic animal exposure models, before investigating possible anti-diabetic …
Calcium Phosphate As A Key Material For Socially Responsible Tissue Engineering, Vuk Uskoković, Victoria M. Wu
Calcium Phosphate As A Key Material For Socially Responsible Tissue Engineering, Vuk Uskoković, Victoria M. Wu
Pharmacy Faculty Articles and Research
Socially responsible technologies are designed while taking into consideration the socioeconomic, geopolitical and environmental limitations of regions in which they will be implemented. In the medical context, this involves making therapeutic platforms more accessible and affordable to patients in poor regions of the world wherein a given disease is endemic. This often necessitates going against the reigning trend of making therapeutic nanoparticles ever more structurally complex and expensive. However, studies aimed at simplifying materials and formulations while maintaining the functionality and therapeutic response of their more complex counterparts seldom provoke a significant interest in the scientific community. In this review …
Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez
Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez
Biology: Student Scholarship & Creative Works
ABSTRACT: The HIV-1 pandemic continues to thrive due to ineffective HIV-1 vaccines. Historically, the world’s most infectious diseases, such as polio and smallpox, have been eradicated or have come close to eradication due to the advent of effective vaccines. Highly active antiretroviral therapy is able to delay the onset of AIDS but can neither rid the body of HIV-1 proviral DNA nor prevent further transmission. A prophylactic vaccine that prevents the various mechanisms HIV-1 has to evade and attack our immune system is needed to end the HIV-1 pandemic. Recent advances in engineered nuclease systems, like the CRISPR/Cas9 system, have …
Stabilization Of Gp120 Outer Domain For Hiv-1-1 Vaccine Immunogen Design, Duoyi Hu
Stabilization Of Gp120 Outer Domain For Hiv-1-1 Vaccine Immunogen Design, Duoyi Hu
School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research
The sole envelope glycoprotein spike on the surface of Human Immunodeficiency Virus (HIV-1) is composed of two subunits: gp120 and gp41. The gp120 consists of three domains: the inner domain, outer domain and bridging sheet, to which the viral primary receptor CD4 binds and induces a conformational change in gp120 to expose the co-receptor binding site. Previous studies have found that the outer domain of gp120 is relatively more stable than the inner domain and bridging sheet. When superimposed, the co-crystal structures of CD4-gp120 complex and VRC01-gp120 complex revealed that the CD4-binding site (CD4-BS) antibody VRC01 actually mainly bound to …
Wake Me When It's Over- Bacterial Toxin-Antitoxin Proteins And Induced Dormancy, Nathan P. Coussens, Dayle A. Daines
Wake Me When It's Over- Bacterial Toxin-Antitoxin Proteins And Induced Dormancy, Nathan P. Coussens, Dayle A. Daines
Biological Sciences Faculty Publications
Toxin-antitoxin systems are encoded by bacteria and archaea to enable an immediate response to environmental stresses, including antibiotics and the host immune response. During normal conditions, the antitoxin components prevent toxins from interfering with metabolism and arresting growth; however, toxin activation enables microbes to remain dormant through unfavorable conditions that might continue over millions of years. Intense investigations have revealed a multitude of mechanisms for both regulation and activation of toxin-antitoxin systems, which are abundant in pathogenic microorganisms. This minireview provides an overview of the current knowledge regarding type II toxin-antitoxin systems along with their clinical and environmental implications.
Research Fatigue Among Injecting Drug Users In Karachi, Pakistan, Aysha Zahidie, Arshad Altaf, Adeel Ahsan, Tanzil Jamali
Research Fatigue Among Injecting Drug Users In Karachi, Pakistan, Aysha Zahidie, Arshad Altaf, Adeel Ahsan, Tanzil Jamali
Community Health Sciences
Background
Karachi is the largest metropolis of Pakistan and its economic hub attracting domestic migrants for economic opportunities. It is also the epicenter of HIV epidemic in the country. Since 2004, one pilot study and four behavioral and biological surveillance rounds have been conducted in Karachi. In addition many student research projects have also focused on key risk groups including injection drug users (IDUs). As a result of this extra ordinary exposure of same kind of questions, IDUs know how to respond to high value questions related to sharing of needles or unsafe sexual practices. The purpose of the study …
In Vitro Characterization Of Avian Influenza Virus Isolates With A Truncated Ns1 Gene Segment, Aaron Dick
In Vitro Characterization Of Avian Influenza Virus Isolates With A Truncated Ns1 Gene Segment, Aaron Dick
Honors Scholar Theses
Avian Influenza Virus represents a significant threat to the world poultry population, and is a potential threat to humans due to the possibility of cross-species AIV infection. Our approach is to characterize a number of avian virus populations with respect to their content of biologically active particles that include hemagglutinating particles (HAP), plaque forming particles (PFP), interferon inducing particles (IFP), interferon induction-suppressing particles (ISP), defective-interfering particles (DIP), cell-killing particles (CKP) and non-infectious cell killing particles (niCKP) using unique in vitro assays developed for avian influenza virus in the Marcus-Sekellick Laboratory. Specifically, we will use a strain of Avian influenza virus, …
Intellectual Property And Public Health – A White Paper, Ryan G. Vacca, James Ming Chen, Jay Dratler Jr., Thomas Folsom, Timothy S. Hall, Yaniv Heled, Frank A. Pasquale, Elizabeth A. Reilly, Jeffery Samuels, Katherine J. Strandburg, Kara W. Swanson, Andrew W. Torrance, Katharine A. Van Tassel
Intellectual Property And Public Health – A White Paper, Ryan G. Vacca, James Ming Chen, Jay Dratler Jr., Thomas Folsom, Timothy S. Hall, Yaniv Heled, Frank A. Pasquale, Elizabeth A. Reilly, Jeffery Samuels, Katherine J. Strandburg, Kara W. Swanson, Andrew W. Torrance, Katharine A. Van Tassel
Faculty Scholarship
On October 26, 2012, the University of Akron School of Law’s Center for Intellectual Property and Technology hosted its Sixth Annual IP Scholars Forum. In attendance were thirteen legal scholars with expertise and an interest in IP and public health who met to discuss problems and potential solutions at the intersection of these fields. This report summarizes this discussion by describing the problems raised, areas of agreement and disagreement between the participants, suggestions and solutions made by participants and the subsequent evaluations of these suggestions and solutions. Led by the moderator, participants at the Forum focused generally on three broad …
Nonclinical Development Needs And Regulatory Requirements For Multipurpose Prevention Technologies: A Primer, Joseph W. Romano, Martha Brady, Judy Manning
Nonclinical Development Needs And Regulatory Requirements For Multipurpose Prevention Technologies: A Primer, Joseph W. Romano, Martha Brady, Judy Manning
HIV and AIDS
This summary outlines key development elements that will be necessary for various configurations of multipurpose prevention products for the simultaneous prevention of HIV, sexually transmitted infections, and/or pregnancy.
Shaping The Operations Research Agenda For Antiretroviral-Based Prevention Products For Women: Gels And Rings, Martha Brady, C. Elizabeth Mcgrory
Shaping The Operations Research Agenda For Antiretroviral-Based Prevention Products For Women: Gels And Rings, Martha Brady, C. Elizabeth Mcgrory
HIV and AIDS
This report summarizes discussions from a two-day international experts consultation meeting in 2012 on preparing for the successful introduction of women-centered antiretroviral-based HIV prevention methods. It examines the limits and expectations of operations research in antiretroviral health technologies.
Constructing A Critical Path For Product Development, Commercialization, And Access, Martha Brady
Constructing A Critical Path For Product Development, Commercialization, And Access, Martha Brady
HIV and AIDS
This brief discusses the Council's health technologies development and the product development path from conceptualization to market. It defines the steps in the Critical Path Framework, and examines activities at the preclinical and clinical stage.
Day Of Dialogue On Multipurpose Prevention Technologies: Toward Clarity In Nomenclature, Martha Brady, C. Elizabeth Mcgrory
Day Of Dialogue On Multipurpose Prevention Technologies: Toward Clarity In Nomenclature, Martha Brady, C. Elizabeth Mcgrory
Poverty, Gender, and Youth
The report summarizes a half-day meeting convened by the Population Council to clarify the wide variety of nomenclature and concepts associated with multipurpose prevention technologies (MPTs). The first section outlines where different types of products are reviewed within the FDA and existing processes that could be applied to MPTs. This is followed by a section that reviews what guidance exists and what else may be needed for review of products like MPTs that address two (or more) indications, including those with a single active, two actives, and multiple components. This meeting identified some of the specific opportunities and challenges for …
Legal Movements In Intellectual Property: Trips, Unilateral Action, Bilateral Agreements, And Hiv/Aids, Margo A. Bagley
Legal Movements In Intellectual Property: Trips, Unilateral Action, Bilateral Agreements, And Hiv/Aids, Margo A. Bagley
Faculty Articles
This Article begins with an overview of the relationship between the Agreement on Trade-Related Aspects of Intellectual Property Rights (the "TRIPS Agreement") and the HIV/AIDS pandemic which created the need for the Doha Declaration. It then discusses two trade-related movements, unilateral action and TRIPS-plus bilateral agreements, that call into question the long-term effectiveness of the TRIPS Agreement process, generally, and the benefits of the Doha Declaration, in particular, in addressing multiple facets of the access to essential medicines problem. This Article concludes that a consideration of these issues should be included in the development of any further TRIPS-related solutions to …
What Is The Risk Of Teratogenicity With The Use Of Selective Serotonin Reuptake Inhibitors During Pregnancy?, Michael Z. Wincor, Mary Gutierrez, Ann Nguyen
What Is The Risk Of Teratogenicity With The Use Of Selective Serotonin Reuptake Inhibitors During Pregnancy?, Michael Z. Wincor, Mary Gutierrez, Ann Nguyen
Pharmacy Faculty Articles and Research
"The lifetime prevalence of major depressive disorder in women is 10 to 25%, with an average age of onset in the mid-20s.1 Over the nine years that the selective serotonin reuptake inhibitors (SSRis) have been available, for many prescribers, they have become first-line agents in the treatment of depression. In addition, sorne of them are also being used in the treatment of obsessive- compulsive disorder and panic disorder. In light of these facts, itis not unlikely that women of childbearing age would be treated with one of the SSRis. In considering the risks of exposing a fetus to an SSRI, …