Recent work in human glioblastoma (GBM) has documented recurrent mutations in the histone chaperone protein ATRX. We developed an animal model of ATRX-deficient GBM and show that loss of ATRX reduces median survival and increases genetic instability. Further, analysis of genome-wide data for human gliomas showed that ATRX mutation is associated with increased mutation rate at the single nucleotide variant (SNV) level. In mouse tumors, ATRX deficiency impairs non-homologous end joining (NHEJ) and increases sensitivity to DNA-damaging agents that induce double-stranded DNA breaks. We propose that ATRX loss results in a genetically unstable tumor, which is more aggressive when left untreated, but is more responsive to double-stranded DNA-damaging agents, resulting in improved overall survival.
Purpose of reviewThere is a rising interest in the impact of diet on the pathogenesis of common ophthalmic conditions. The purpose of this review is to summarize the potential preventive and therapeutic power of dietary interventions described in recent basic science and epidemiological literature.
Recent findingsBasic science investigations have elucidated a variety of mechanisms by which diet may impact ophthalmic disease, particularly through its action on chronic oxidative stress, inflammation and macular pigmentation. Epidemiologic investigations have shown the real-world influence of diet on the incidence and progression of a number of ophthalmic diseases, particularly cataract, age-related macular degeneration (AMD) and diabetic retinopathy. A large observational cohort study found a 20% reduction in the incidence of cataract among vegetarians compared with nonvegetarians. Two recent systematic reviews found that higher adherence to Mediterranean dietary patterns was associated with a decreased risk of progression of AMD to later stages. Finally, large meta-analyses found that patients following plant-based and Mediterranean diets had significant reductions of mean haemoglobin A1c scores and incidence of diabetic retinopathy as compared with controls.
SummaryThere is a significant and growing body of evidence that Mediterranean diet and plant-based diets --those that maximize fruits, vegetables, legumes, whole grains and nuts; and that minimize animal products and processed foods --help prevent vision loss from cataract, AMD and diabetic retinopathy. These diets may hold benefits for other ophthalmic conditions, as well. Nevertheless, there is a need for further randomized, controlled and longitudinal studies in this area.
Advances in preventive medicine have demonstrated the crucial role of whole-food unprocessed plant-based nutrition in reducing disease burden. Nutrition education and plant-based nutrition is seldom included in medical curriculum and is thus seldom incorporated into clinical care. Additionally, personal exposure to lifestyle modifications, including nutrition and diet, is associated with a provider’s willingness to recommend lifestyle modifications in clinical encounters. We offer this editorial to our fellow health professions’ students, practicing healthcare providers, and those community leaders intending to advocate for the patient population via evidence-based curricular enhancement. Our primary effort, Rooting for Wellness, consisted of a mandatory four-week segment within Wayne State University School of Medicine’s (WSUSOM’s) Patient, Population, Physician and Professional (P4) curriculum, which culminated in a required half-day event consisting of patient/provider panels and an interactive cooking demonstration. Prior to the curriculum, we provided several voluntary extracurricularopportunities for plant-based engagement including a 4-week plant-based kickstart program, cooking demonstration, journal club, and guest speaker events. To our knowledge, this is the first exclusively mandatory plant-based nutritional intervention undertaken at a medical institution in the United States. The strategy presented here may serve as a model for similar initiatives at a variety of institutions and settings.
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