ABSTRACT
The COVID-19 pandemic has exposed significant disparities within certain population subsets that manifest through greater disease burden and worse outcomes. In this commentary, we propose specific preventive interventions to address these disparities within the United States.
Subject(s)
COVID-19 , Cardiovascular Diseases , COVID-19/epidemiology , COVID-19/prevention & control , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Health Services Accessibility , Healthcare Disparities , Humans , Pandemics/prevention & control , SARS-CoV-2 , United States/epidemiologyABSTRACT
Xp11.2 translocation renal cell carcinoma (TRCC) is a rare and aggressive variant of renal cell carcinoma (RCC) when presenting in adults. We report a case of a man in his early 40s who was diagnosed with stage III Xp11.2 TRCC and underwent radical nephrectomy. Seven months following the surgery, an adrenal nodule and bilateral pulmonary nodules were discovered. He underwent cryoablation of the adrenal nodule and systemic treatment with daily pazopanib. He displayed stable disease for approximately 6 years. Following this period, multiple hospitalisations interrupted daily pazopanib therapy resulting in progression of disease. His regimen was then changed to ipilimumab and nivolumab, followed by current daily therapy with axitinib. The patient now shows stable disease in his 10th year after diagnosis. This case study demonstrates the efficacy of pazopanib for metastatic Xp11.2 TRCC and warrants further investigation to supplement the guidelines regarding the use of targeted therapy for TRCC.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Adult , Carcinoma, Renal Cell/genetics , Chromosomes, Human, X , Humans , Indazoles , Kidney Neoplasms/genetics , Male , Pyrimidines , Sulfonamides , Translocation, GeneticABSTRACT
A library of natural products and their derivatives was screened for inhibition of protein tyrosine phosphatase (PTP) 1B, which is a validated drug target for the treatment of obesity and type II diabetes. Of those active in the preliminary assay, the most promising was compound 2 containing a novel pyrrolopyrazoloisoquinolone scaffold derived by treating radicicol (1) with hydrazine. This nitrogen-atom augmented radicicol derivative was found to be PTP1B selective relative to other highly homologous nonreceptor PTPs. Biochemical evaluation, molecular docking, and mutagenesis revealed 2 to be an allosteric inhibitor of PTP1B with a submicromolar Ki. Cellular analyses using C2C12 myoblasts indicated that 2 restored insulin signaling and increased glucose uptake.
Subject(s)
Enzyme Inhibitors/chemistry , Macrolides/chemistry , Nitrogen/chemistry , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , Protein Tyrosine Phosphatase, Non-Receptor Type 1/chemistry , Animals , Enzyme Inhibitors/metabolism , Macrolides/metabolism , Mice , Nitrogen/metabolism , Protein Binding/physiology , Protein Isoforms/chemistry , Protein Isoforms/metabolism , Protein Structure, Tertiary , Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolismABSTRACT
El objetivo del presente estudio fue analizar la estructura interna del cuestionario AWARE 3.0 en drogodependentientes. Fueron evaluados 240 sujetos en tratamiento residencial (hombres n=205 y mujeres n=35) entre 18 y 61 años con la escala de señales de alerta a recaída AWARE. Los análisis confirmaron la existencia de un solo factor, además se probaron cinco modelos confirmatorios incluyendo el factor de método que demostró influir en el modelo original. El análisis de confiabilidad obtuvo puntuaciones adecuadas tanto para variables observadas como variables latentes que representaron igualdad a nivel conceptual y de unidades (modelo congenérico y tau-equivalente). Los resultados indican un mejor ajuste solo con el modelo de ítems directos además de plantearse una versión breve. Estos hallazgos brindan una nueva perspectiva sobre la estructura del instrumento y una nueva versión que ayude a complementar la evaluación en el proceso de evaluación y detección de señales de alerta a recaídas.
The objective of the present study was to analyze the internal structure of the AWARE 3.0 questionnaire in drug addicts. A total of 240 subjects undergoing residential treatment (males n = 205 and females n = 35) between 18 and 61 years with the AWARE relapse alert scale were evaluated. The analyzes confirmed the existence of a single factor, in addition five confirmatory models were tested including the factor of method that demonstrated to influence in the original model. The reliability analysis obtained adequate scores for both observed and latent variables that represented equality at the conceptual and unit level (congeneric and tau-equivalent models). The results indicate a better fit only with the direct item model in addition to a short version. These findings provide a new perspective on the structure of the instrument and a new version that helps complement the evaluation in the process of evaluation and detection of relapse alert signals