REPRODUCTIVE HEALTH IN TRANS AND GENDER-DIVERSE PATIENTS: Trauma-informed reproductive care for transgender and nonbinary people.

In Brief: There are some unique aspects to providing trauma-informed reproductive care to transgender and nonbinary people, who are affected by minority stress, stigma, and particular forms of trauma; we review the evidence and suggest strategies for the provision of trauma-informed reproductive care to gender minorities.

Abstract: Stigma and minority stress affect the health of transgender and nonbinary (TGNB) people, leading to disparities across a range of outcomes. Barriers to accessing care, including reproductive care, further complicate these health disparities.

A Review of Animal Models Investigating the Reproductive Effects of Gender-Affirming Hormone Therapy.

Gender-affirming hormone therapy (GAHT) is an important component in the process of transitioning for many transgender and gender-diverse (TGD) individuals. Multiple medical organizations recommend fertility preservation counseling prior to initiation of GAHT; however, there remains little high-quality data regarding the impact of GAHT on fertility and reproductive function. A PubMed literature review was performed using Boolean search operators linking keywords or phrases such as "mouse", "rat", "primate", "animal model", "transgender", "gender", "estrogen", "testosterone", "fertility", and "fertility preservation".

Assisted reproductive technology: considerations for the nonheterosexual population and single parents.

This study aimed to discuss fertility concerns unique to the lesbian, gay, bisexual, transgender, queer, plus and single-parent-to-be populations and review special considerations regarding the evaluation and treatment of these patients relevant to the practicing reproductive medicine provider. The use of assisted reproductive technology has rapidly increased over the past 50 years. Given these trends, providers can expect a greater diversity of patients making use of these technologies.

A review of fertility preservation in patients with breast cancer.

Breast cancer remains the most common cancer diagnosed in women and causes more lost disability-adjusted life years (DALYs) than any other cancer worldwide; however, improvements in therapies have led to increased survival and therefore a new focus on quality of life following treatment. Fertility is an important concern among cancer survivors of reproductive age. The purpose of this article is to contextualize the importance of oncofertility services for women with breast cancer and review options for fertility preservation, including oocyte/embryo cryopreservation, GnRH agonist therapy, and ovarian tissue cryopreservation.

Outcomes of Fertility Preservation Consults for Women at Risk for Primary Ovarian Insufficiency Due to History of Cancer Treatment or Mosaic Turner Syndrome.

Adolescents and young adults (AYAs) at risk of primary ovarian insufficiency (POI) often request fertility preservation consultation. We report consult/treatment outcomes for 21 cancer survivors and 3 mosaic Turner syndrome (TS) patients (mean age 21.6 at consult, 3 with POI).

Establishing a reproductive biorepository for basic and translational research: experience developing the reproductive subjects registry and sample repository.

Purpose: To report experience designing and establishing a reproductive registry and sample biorepository and to describe initial subject characteristics and biospecimens.

Methods: Beginning in December 2017, patients presenting for reproductive care at the University of Michigan were approached for study enrollment. Following consent, subjects completed detailed reproductive and health questionnaires.

Surgery Residents' Experiences With Seriously-Ill and Dying Patients: An Opportunity to Improve Palliative and End-of-Life Care.

Objective: To describe how and when surgery residents provided primary palliative care and engaged specialty palliative care services.

Design: Phase I consisted of a previously validated survey instrument supplemented with additional questions. We then conducted semistructured interviews with a subset of the survey respondents (Phase II).

Urinary markers aiding in the detection and risk stratification of prostate cancer.

The purpose of this review is to highlight the role of existing and promising urinary biomarkers for the detection and prognostication of prostate cancer (PCa). A number of novel urinary biomarkers have been introduced into the clinical space, which in combination with clinical variables, have demonstrated an increased ability to select patients for biopsy and identify men at risk of harboring clinically significant PCa. Though a number of assays require further validation, initial data is promising and forthcoming results will ultimately determine their clinical utility and commercial availability.

Localized Inflammatory Myofibroblastic Tumor Involving the Genitourinary System: Adolescent Case Series and Review.

We describe four adolescent cases of inflammatory myofibroblastic tumor involving the genitourinary system. Two patients with masses of the urinary bladder presented with gross hematuria. The third patient presented with left flank pain and a mass encasing the left ureter causing hydronephrosis.

Immunosuppressive Myeloid Cells' Blockade in the Glioma Microenvironment Enhances the Efficacy of Immune-Stimulatory Gene Therapy.

Survival of glioma (GBM) patients treated with the current standard of care remains dismal. Immunotherapeutic approaches that harness the cytotoxic and memory potential of the host immune system have shown great benefit in other cancers. GBMs have developed multiple strategies, including the accumulation of myeloid-derived suppressor cells (MDSCs) to induce immunosuppression.

Preclinical Efficacy and Safety Profile of Allometrically Scaled Doses of Doxycycline Used to Turn "On" Therapeutic Transgene Expression from High-Capacity Adenoviral Vectors in a Glioma Model.

Glioblastoma multiforme (GBM) is the most commonly occurring primary brain cancer in adults, in whom its highly infiltrative cells prevent total surgical resection, often leading to tumor recurrence and patient death. Our group has discovered a gene therapy approach for GBM that utilizes high-capacity "gutless" adenoviral vectors encoding regulatable therapeutic transgenes. The herpes simplex type 1-thymidine kinase (TK) actively kills dividing tumor cells in the brain when in the presence of the prodrug, ganciclovir (GCV), whereas the FMS-like tyrosine kinase 3 ligand (Flt3L) is an immune-stimulatory molecule under tight regulation by a tetracycline-inducible "Tet-On" activation system that induces anti-GBM immunity.

INX-08189, a phosphoramidate prodrug of 6-O-methyl-2'-C-methyl guanosine, is a potent inhibitor of hepatitis C virus replication with excellent pharmacokinetic and pharmacodynamic properties.

INX-08189 is an aryl-phosphoramidate of 6-O-methyl-2'-C-methyl guanosine. INX-08189 was highly potent in replicon assays, with a 50% effective concentration of 10±6 nM against hepatitis C genotype 1b at 72 h. The inhibitory effect on viral replication was rapid, with a 50% effective concentration (EC50) of 35±8 nM at 24 h.

Phosphoramidate ProTides of 2'-C-methylguanosine as highly potent inhibitors of hepatitis C virus. Study of their in vitro and in vivo properties.

Hepatitis C virus infection constitutes a serious health problem in need of more effective therapies. Nucleoside analogues with improved exposure, efficacy, and selectivity are recognized as likely key components of future HCV therapy. 2'-C-Methylguanosine triphosphate has been known as a potent inhibitor of HCV RNA polymerase for some time, but the parent nucleoside is only moderately active due to poor intracellular phosphorylation.

Multi-antigen vaccines based on complex adenovirus vectors induce protective immune responses against H5N1 avian influenza viruses.

There are legitimate concerns that the highly pathogenic H5N1 avian influenza virus could adapt for human-to-human transmission and cause a pandemic similar to the 1918 "Spanish flu" that killed 50 million people worldwide. We have developed pandemic influenza vaccines by incorporating multiple antigens from both avian and Spanish influenza viruses into complex recombinant adenovirus vectors. In vaccinated mice, these vaccines induced strong humoral and cellular immune responses against pandemic influenza virus antigens, and protected vaccinated mice against lethal H5N1 virus challenge.

Complex adenovirus-mediated expression of West Nile virus C, PreM, E, and NS1 proteins induces both humoral and cellular immune responses.

West Nile Virus (WNV), a member of the family Flaviviridae, was first identified in Africa in 1937. In recent years, it has spread into Europe and North America. The clinical manifestations of WNV infection range from mild febrile symptoms to fatal encephalitis.

Induction of bivalent immune responses by expression of dengue virus type 1 and type 2 antigens from a single complex adenoviral vector.

There are approximately 100 million new cases of dengue (DEN) virus infection each year. Infection can result in illness ranging from a mild fever to hemorrhaging, shock, or even death. There are four serotypes of dengue virus (DEN1-4), and immunity to one serotype does not cross protect from infection with other serotypes.

Two complex, adenovirus-based vaccines that together induce immune responses to all four dengue virus serotypes.

Dengue virus infections can cause hemorrhagic fever, shock, encephalitis, and even death. Worldwide, approximately 2.5 billion people live in dengue-infested regions with about 100 million new cases each year, although many of these infections are believed to be silent.

Complex adenovirus-vectored vaccine protects guinea pigs from three strains of Marburg virus challenges.

The Marburg virus (MARV), an African filovirus closely related to the Ebola virus, causes a deadly hemorrhagic fever in humans, with up to 90% mortality. Currently, treatment of disease is only supportive, and no vaccines are available to prevent spread of MARV infections. In order to address this need, we have developed and characterized a novel recombinant vaccine that utilizes a single complex adenovirus-vectored vaccine (cAdVax) to overexpress a MARV glycoprotein (GP) fusion protein derived from the Musoke and Ci67 strains of MARV.

De novo syntheses of Marburg virus antigens from adenovirus vectors induce potent humoral and cellular immune responses.

Marburg virus (MARV) is an African filovirus that causes a deadly hemorrhagic fever in humans, with up to 90% mortality. Currently, there are no MARV vaccines or therapies approved for human use. We hypothesized that developing a vaccine that induces a de novo synthesis of MARV antigens in vivo will lead to strong induction of both a humoral and cell-mediated immune response against MARV.

Development of a cAdVax-based bivalent ebola virus vaccine that induces immune responses against both the Sudan and Zaire species of Ebola virus.

Ebola virus (EBOV) causes a severe hemorrhagic fever for which there are currently no vaccines or effective treatments. While lethal human outbreaks have so far been restricted to sub-Saharan Africa, the potential exploitation of EBOV as a biological weapon cannot be ignored. Two species of EBOV, Sudan ebolavirus (SEBOV) and Zaire ebolavirus (ZEBOV), have been responsible for all of the deadly human outbreaks resulting from this virus.