Publications by authors named "Gabrielle Winston-McPherson"

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.

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  • The study examines the effects of gender-affirming hormone therapy (estrogen and testosterone) on various clinical chemistry analytes in healthy transgender and nonbinary individuals.
  • Key findings indicate that while most measures like electrolytes and urea nitrogen remained stable, certain enzymes and lipid levels shifted toward those typical for their affirmed gender, particularly in the testosterone group.
  • The research highlights the need for more tailored reference intervals for transgender patients, as hormone therapy may significantly alter some lab values that differ by biological sex in cisgender individuals.
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  • Many eGFR equations use a Black race modifier (BRM) that could lead to inflated kidney function estimates for Black individuals, raising questions about its validity in clinical settings.
  • Research aims to systematically evaluate the impact of including or excluding the BRM on diagnosing chronic kidney disease (CKD).
  • The study found limited evidence supporting the necessity of the BRM in eGFR equations, suggesting it may not be beneficial to clinical practice.
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Background: 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).

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  • The COVID-19 pandemic significantly reduced in-person ambulatory care, leading to a substantial decline in HbA1c testing volume during early 2020 compared to pre-pandemic levels.
  • Testing volumes dropped by up to 70%, particularly in March to May, with decreases of 23%, 61%, and 40% in those specific months.
  • As testing decreased, there was a notable increase in abnormal HbA1c levels, indicating a 0.31% rise in abnormal results for every 1% drop in testing volume, highlighting potential health impacts of reduced access to care.
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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.

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Background: 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.

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  • Gender-affirming therapy with testosterone helps transgender men masculinize, but understanding hormone levels can be challenging due to limited reference data.
  • A study of 82 healthy transgender individuals on testosterone examined various hormone levels and found that testosterone and SHBG reference intervals from cisgender men are applicable, while others like estradiol and AMH need transmasculine-specific intervals.
  • Clinicians and labs should use these tailored reference intervals to accurately interpret hormone tests, as masculinizing hormones significantly affect endocrine profiles.
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Proprotein 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.

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Background: 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.

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The 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.

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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.

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Background: 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.

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Background: 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.

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Background: 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.

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Mass 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.

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  • Digoxin is a crucial medication for heart conditions, but its measurement can be affected by substances in the blood, notably bilirubin, which can lead to inaccurate results in tests.
  • A study examined how three different immunoassays (Beckman Coulter® Unicel DxI 800, Vitros® 4600, and Roche Cobas® 8000) performed in the presence of high bilirubin levels, showing that the DxI 800 was most affected.
  • Findings indicated that the DxI 800 reported higher digoxin levels in bilirubin-rich samples, while the other two platforms showed more reliable results, suggesting that caution is needed when interpreting test results from icteric samples on the DxI
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  • Beckman Coulter reformulated their TSH assay to align with the World Health Organization's 3rd international standard, completing a thorough evaluation of its performance.
  • The evaluation included tests for precision, linearity, reportable range, and accuracy using patient specimens, showing intra-day and inter-day variability below 10% and established limits of detection.
  • Results indicated that the new TSH3 assay demonstrates high sensitivity and comparable performance to previous assays, making it suitable for clinical use.
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Background: Cancer antigens 125, 27.29, and 15-3 (CA125, CA27.29, and CA15-3) are markers of ovarian and breast cancer.

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Notch1-3 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.

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Various 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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