Purpose: The goal of this preliminary study is to describe the vaginal microbiome of transgender and gender nonbinary (TGNB) individuals using nonculture-based techniques. TGNB individuals may undergo gender-affirming surgical procedures, which can include the creation of a neovagina. Little is known about microbial species that comprise this environment in states of health or disease.
View Article and Find Full Text PDFBackground: Racial disparities in SARS-CoV-2 prevalence are apparent. Race is a sociocultural construct, necessitating investigation into how sociocultural factors contribute.
Methods: This cross-sectional study linked laboratory data of adult patients between February 29 and May 15, 2020 with socio-demographics variables from the 2018 American Community Survey (ACS).
Serum hormone profiles among different feminizing gender-affirming hormone therapies (GAHT) are poorly characterized. To address this gap, we described the serum estrogen profiles of three 17β-estradiol preparations, taken with or without an antiandrogen, using a novel liquid chromatography-mass spectrometry (LC-MS/MS) assay in adults taking feminizing GAHT. This was a secondary analysis of 93 healthy transgender women and gender nonbinary adults taking feminizing GAHT in a prospective cross-sectional study.
View Article and Find Full Text PDFBackground: Inequitable use of next-generation sequencing (NGS) testing for cancer risk and treatment can contribute to heath disparity. Consequently, it is important to assess the population receiving this testing. In this article, we characterize the population receiving both germline and somatic NGS testing for cancer predisposition and precision oncology at the Genetics and Solid Tumors Laboratory of the University of Washington Medical Center.
View Article and Find Full Text PDFProprotein convertase subtilisin/kexin type 9 (PCSK9) is a recently validated therapeutic target for lowering low-density lipoprotein cholesterol (LDL-C). Through phenotypic screening, we previously discovered a class of small-molecules with a 2,3'-diindolymethane (DIM) skeleton that can decrease the expression of PCSK9. But these compounds have low potency and low metabolically stability.
View Article and Find Full Text PDFBackground: Transgender women and nonbinary people seeking feminizing therapy are often prescribed estrogen as a gender-affirming hormone, which will alter their reproductive hormone axis. Testosterone, estradiol, and other reproductive hormones are commonly evaluated to assess therapy, but reference intervals specific to transgender women have not been established. The objective of this study was to derive reference intervals for commonly measured analytes related to reproductive endocrinology in a cohort of healthy gender nonconforming individuals on stable feminizing hormone therapy.
View Article and Find Full Text PDFThe aryl hydrocarbon receptor (AhR) is a ligand activated transcription factor involved in multiple biological processes including immune cell differentiation, intestinal function and inflammation. Based on the scaffold of naturally occurring AhR ligand 6-formylindolo (3,2-b) carbazole (FICZ, 2), a series of analogues has been designed, synthesized and evaluated by cell-based assays. The structure-activity relationships study has successfully led to the discovery of compound 11e with extremely potent activity.
View Article and Find Full Text PDFBioorg Med Chem Lett
August 2019
Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of low density lipoprotein receptor (LDLR). Anti-PCSK9 agents have been approved for the treatment of hypercholesterolemia. We recently discovered a series of small-molecule PCSK9 modulators that contains a relatively small pharmacophore of 2,3'-diindolylmethane with molecular weights around only 250.
View Article and Find Full Text PDFBackground: The complete blood count (CBC) is a cornerstone of patient care. Several of the normal values for the components of the CBC differ by sex and, therefore, male-specific and female-specific reference intervals are required to interpret these laboratory results. Transgender individuals are often prescribed hormone therapy to affirm their gender, with resulting serum hormone concentrations similar to those of cisgender individuals.
View Article and Find Full Text PDFBackground: Hormonal changes influence the composition of vaginal flora, which is directly related to the health of an individual. Transgender men prescribed testosterone experience a vaginal hormone composition that differs from cisgender women. To the author's knowledge, there are no clinical studies evaluating the influence that testosterone administration has on the vaginal microbiome.
View Article and Find Full Text PDFBackground: Prescription opioid use and opioid related deaths continue to increase nationwide. Several states have adopted legislation allowing for recreational use of cannabis. Little is known about how recreational cannabis laws impact compliance in chronic pain patients who have been prescribed opioid therapy.
View Article and Find Full Text PDFMass spectrometry (MS) is a highly specific and sensitive technique that is used for the detection of many different analytes with diverse chemical characteristics. It has been adopted by clinical laboratories for the quantification of small molecules and, by extension, has been widely used for therapeutic drug monitoring. It is an attractive alternative to immunoassay methods, because it is not subject to the same interferences.
View Article and Find Full Text PDFBackground: Cancer antigens 125, 27.29, and 15-3 (CA125, CA27.29, and CA15-3) are markers of ovarian and breast cancer.
View Article and Find Full Text PDFNotch1-3 are transmembrane receptors that appear to be absent in medullary thyroid cancer (MTC). Previous research has shown that induction of Notch1 has a tumor-suppressor effect in MTC cell lines, but little is known about the biologic consequences of Notch3 activation for the progression of the disease. We elucidate the role of Notch3 in MTC by genetic (doxycycline-inducible Notch3 intracellular domain) and pharmacologic [AB3, novel histone deacetylase (HDAC) inhibitor] approaches.
View Article and Find Full Text PDFVarious highly substituted 2,3'-diindolylmethane heterocycles were prepared from propargylic alcohols and indole nucleophiles via a transition metal-catalyzed tandem indole annulation/arylation reaction for the first time. Among the metal catalysts we examined, the most economical copper(I) catalyst provided the highest efficiency. The indole nucleophiles could also be replaced by other electron-rich arenes or alcohols.
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