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Patient perspective: Is intensive screening of women at high risk of breast cancer evidence-based medicine or ?
Womens Health (Lond)
January 2025
Department of Pharmacy Practice, Midwestern University College of Pharmacy, Glendale Campus, Glendale, AZ, USA.
In 2023, a breast cancer risk assessment and a subsequent positive test for the BRCA-2 genetic mutation brought me to the uncomfortable intersection of a longstanding career as an advocate for high-quality medical evidence to support shared patient-provider decision making and a new role as a high-risk patient. My search for studies of available risk-management options revealed that the most commonly recommended approach for women with a ⩾20% lifetime breast cancer risk, intensive screening including annual mammography and/or magnetic resonance imaging beginning at age 25-40 years, was supported only by cancer-detection statistics, with almost no evidence on patient-centered outcomes-mortality, physical and psychological morbidity, or quality of life-compared with standard screening or a surgical alternative, bilateral risk-reducing mastectomy. In this commentary, I explore parallels between the use of the intensive screening protocol and another longstanding women's health recommendation based on limited evidence, the use of hormone therapy (HT) for postmenopausal chronic disease prevention, which was sharply curtailed after the publication of the groundbreaking Women's Health Initiative trial in 2002.
View Article and Find Full Text PDFCombination therapies and other therapeutic approaches targeting the NLRP3 inflammasome and neuroinflammatory pathways: a promising approach for traumatic brain injury.
Immunopharmacol Immunotoxicol
January 2025
Tobacco and Health Research Center, Endocrinology and Metabolism Research Center, Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Traumatic brain injury (TBI) precipitates a neuroinflammatory cascade, with the NLRP3 inflammasome emerging as a critical mediator. This review scrutinizes the complex activation pathways of the NLRP3 inflammasome by underscoring the intricate interplay between calcium signaling, mitochondrial disturbances, redox imbalances, lysosomal integrity, and autophagy. It is hypothesized that a combination therapy approach-integrating NF-κB pathway inhibitors with NLRP3 inflammasome antagonists-holds the potential to synergistically dampen the inflammatory storm associated with TBI.
View Article and Find Full Text PDFCan criminology sway the public? How empirical findings about deterrence affect public punishment preferences.
Crime Sci
December 2024
Center for Law and Behavior, Amsterdam Law School, University of Amsterdam, Amsterdam, The Netherlands.
Background Setting: Punitive approaches to deter offending remain popular despite limited evidence of their effectiveness. This study investigated what effect presenting empirical criminological findings about the effectiveness of deterrence to a general public has on their punishment preferences. It builds on earlier research showing that such presentation reduces the public's inclination towards strict punishment.
View Article and Find Full Text PDFCharacterizing selection on complex traits through conditional frequency spectra.
Genetics
December 2024
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Natural selection on complex traits is difficult to study in part due to the ascertainment inherent to genome-wide association studies (GWAS). The power to detect a trait-associated variant in GWAS is a function of frequency and effect size - but for traits under selection, the effect size of a variant determines the strength of selection against it, constraining its frequency. Recognizing the biases inherent to GWAS ascertainment, we propose studying the joint distribution of allele frequencies across populations, conditional on the frequencies in the GWAS cohort.
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