Background: An estimated 1.4 million persons in the United States identify as transgender or nonbinary, signifying that their gender identity does not correspond with their assigned sex at birth. Individuals assigned female at birth may seek gender-affirming hormone therapy with testosterone.
View Article and Find Full Text PDFObjectives: Cervical mucus varies in response to both natural and artificial hormonal changes. It is commonly believed that cervical mucus thinning is associated with normal fertility and that progestogen-induced thickening is an essential contraceptive mechanism. This review aims to broadly summarize our current knowledge about cervical mucus from both a clinical and basic research perspective.
View Article and Find Full Text PDFshort interval repeat pregnancy increases maternal and neonatal morbidity, and provision of postpartum contraception provides primary protection against these adverse outcomes. Confusion regarding effects on breast feeding and thrombosis risk delaying initiation of contraception in the immediate post-partum interval. Delaying contraception provision until the 6-week postpartum visit misses many women who either do not attend or have resumed ovulation and/or intercourse prior to this visit.
View Article and Find Full Text PDFObjective: Arachidonate 5-lipoxygenase (5-LO) is a key enzyme in the synthesis of leukotrienes. VIA-2291 is a potent 5-LO inhibitor, which has been shown to reduce hsCRP and noncalcified coronary plaque volume following an acute coronary syndrome (ACS). We aim to evaluate the effect of VIA-2291 on vascular inflammation compared to placebo using FDG-PET.
View Article and Find Full Text PDFAm J Physiol Gastrointest Liver Physiol
January 2015
Protein tyrosine phosphatase of liver regeneration-1 (Prl-1) is an immediate-early gene that is significantly induced during liver regeneration. Several in vitro studies have suggested that Prl-1 is important for the regulation of cell cycle progression. To evaluate its function in liver regeneration, we ablated the Prl-1 gene specifically in mouse hepatocytes using the Cre-loxP system.
View Article and Find Full Text PDFStarting from screening hit, (4S,7R)-1,7,8,8-tetramethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (7), we optimized the potency and pharmacokinetic properties. This led to the identification of compounds with good in vivo activity in a mouse pharmacodynamic model of inhibition of 11βHSD1.
View Article and Find Full Text PDFJ Med Chem
May 2014
In a discovery effort to find safe and effective DGAT-1 inhibitors, we have identified 2-phenyloxazole 4-carboxamide 1 as a conformationally constrained analog of a hydrazide hit, which was previously identified from high-throughput screening. Further optimization of this series has led to chemically more stable 2-phenyloxazole-based DGAT-1 inhibitor 25 with improved solubility, cell-based activity, and pharmacokinetic properties. Compound 25 also demonstrated in vivo efficacy in a diet-induced obesity (DIO) rat model.
View Article and Find Full Text PDFLittle is known about how sociodemographic factors relate to children's chronic pain. This paper describes the pain, health, and sociodemographic characteristics of a cohort of children presenting to an urban tertiary chronic pain clinic and documents the role of age, sex and minority status on pain-related characteristics. A multidisciplinary, tertiary clinic specializing in pediatric chronic pain.
View Article and Find Full Text PDFAtherosclerosis is the primary cause of heart disease and stroke and is thus the underlying pathology of the leading causes of death in the western world. Although risk can be reduced by lowering lipid levels, the equally important contribution of inflammation to the development of cardiovascular disease is not adequately addressed by existing therapies. Here, we summarize the evidence supporting a role for inflammation in the pathogenesis of atherosclerosis, discuss agents that are currently in the clinic and provide a perspective on the challenges faced in the development of drugs that target vascular inflammation.
View Article and Find Full Text PDFJ Med Chem
April 2011
Diacylglycerol acyltransferase-1 (DGAT-1) is the enzyme that catalyzes the final and committed step of triglyceride formation, namely, the acylation of diacylglycerol with acyl coenzyme A. DGAT-1 deficient mice demonstrate resistance to weight gain on high fat diet, improved insulin sensitivity, and reduced liver triglyceride content. Inhibition of DGAT-1 thus represents a potential novel approach for the treatment of obesity, dyslipidemia, and metabolic syndrome.
View Article and Find Full Text PDFContext: Rheumatoid arthritis (RA) is a chronic disease that often impacts patient's quality of life. For young people with RA, there is a need for rehabilitative approaches that have been shown to be safe and to lead to improved functioning.
Objectives: This pilot study investigated the feasibility of a single-arm, group-administered, six-week, biweekly Iyengar yoga (IY) program for eight young adults with RA.
Background: Production of leukotrienes by 5-lipoxygenase (5-LO) has been linked to unstable atherosclerotic plaques and cardiovascular events. VIA-2291 is a potent 5-LO inhibitor.
Methods And Results: In a double-blinded study, 191 patients were randomly assigned 3 weeks after an acute coronary syndrome to receive 25, 50, or 100 mg VIA-2291 or placebo daily for 12 weeks.
Objective: Heterozygous activating mutations of glucokinase have been reported to cause hypoglycemia attributable to hyperinsulinism in a limited number of families. We report three children with de novo glucokinase hyperinsulinism mutations who displayed a spectrum of clinical phenotypes corresponding to marked differences in enzyme kinetics.
Research Design And Methods: Mutations were directly sequenced, and mutants were expressed as glutathionyl S-transferase-glucokinase fusion proteins.
Tryptophan fluorescence was used to study GK (glucokinase), an enzyme that plays a prominent role in glucose homoeostasis which, when inactivated or activated by mutations, causes diabetes mellitus or hypoglycaemia in humans. GK has three tryptophan residues, and binding of D-glucose increases their fluorescence. To assess the contribution of individual tryptophan residues to this effect, we generated GST-GK [GK conjugated to GST (glutathione transferase)] and also pure GK with one, two or three of the tryptophan residues of GK replaced with other amino acids (i.
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