Metformin is safe and effective for therapy-induced hyperglycemia. Initially, insulin may be required for significant hyperglycemia or metabolic abnormalities. We are unaware of any prior studies using metformin in this population.
Mutations accumulate within somatic cells and have been proposed to contribute to aging. It is unclear what level of mutation burden may be required to consistently reduce cellular lifespan. Human cancers driven by a mutator phenotype represent an intriguing model to test this hypothesis, since they carry the highest mutation burdens of any human cell. However, it remains technically challenging to measure the replicative lifespan of individual mammalian cells. Here, we modeled the consequences of cancer-related mutator phenotypes on lifespan using yeast defective for mismatch repair (MMR) and/or leading strand (Polε) or lagging strand (Polδ) DNA polymerase proofreading. Only haploid mutator cells with significant lifetime mutation accumulation (MA) exhibited shorter lifespans. Diploid strains, derived by mating haploids of various genotypes, carried variable numbers of fixed mutations and a range of mutator phenotypes. Some diploid strains with fewer than two mutations per megabase displayed a 25% decrease in lifespan, suggesting that moderate numbers of random heterozygous mutations can increase mortality rate. As mutation rates and burdens climbed, lifespan steadily eroded. Strong diploid mutator phenotypes produced a form of genetic anticipation with regard to aging, where the longer a lineage persisted, the shorter lived cells became. Using MA lines, we established a relationship between mutation burden and lifespan, as well as population doubling time. Our observations define a threshold of random mutation burden that consistently decreases cellular longevity in diploid yeast cells. Many human cancers carry comparable mutation burdens, suggesting that while cancers appear immortal, individual cancer cells may suffer diminished lifespan due to accrued mutation burden.
Objectives/Hypothesis Diversity in medicine positively influences healthcare delivery. As we aim to make otolaryngology more diverse, it is essential to analyze our current leadership. Study Design Observational study. Methods A total of 262 department chairs and chiefs, residency program directors, and assistant and associate directors from 117 otolaryngology residency programs as well as 92 society leaders from nine otolaryngology national societies from 2010 to 2020 in the United States are included in this study. The position, academic rank, name, gender, inferred race (based on name and image), and h‐index are collected and recorded from publicly available data. Fisher's exact test, unpaired t tests, and analysis of variance tests are used. Results The ethno‐racial breakdown of all otolaryngology residency leaders is as follows: 78.63% non‐Hispanic (NH) White, 16.03% NH Asian, 2.29% Middle Eastern, 1.91% NH Black, and 1.15% Latinx. Male gender is found to be a predictor of full professorship title (P < .0001) with an odds ratio (OR) of 4.066. NH White male is also a predictor of full professorship (P < .0001) with an OR 3.05. When comparing h‐index, males and females differ (P < .0001) across all residency leadership positions. There is a higher h‐index among full professors compared to non‐full professors (P < .0001). The ethno‐racial breakdown of society leaders is 84% NH White, 11% NH Asian, 2% NH Black, 2% Latinx, and 1% Middle Eastern. Conclusions In conclusion, otolaryngology leadership has an under‐representation of women and certain ethno‐racial groups. Continued efforts should be made to diversify our specialty's leadership. Level of Evidence NA Laryngoscope, 132:1729–1737, 2022
Background: Diversity within the medical profession with respect to sex and racial minorities has been shown to have a positive effect on health and healthcare. Characterization of a field is key to evaluating trends and the advancement of diversity in an otolaryngology subspecialty.Study Design: Observational study. Methods: A comprehensive list of all the academic laryngologists was compiled from the Accreditation Council for Graduate Medical Education accredited otolaryngology residency programs in 2020. The last 20 past presidents of the American Laryngological Association (ALA) and American Broncho-Esophogological Association (ABEA) were analyzed. Academic rank and years in practice were determined from departmental websites, with online search tools used as secondary resources. The h-index was utilized as a measure of research productivity. Regression analysis was performed to analyze these variables.Results: There are 184 academic laryngologists in the 124 programs. The majority of the population is Caucasian 76.6% (141/184), followed by Asian 16.3% (30/184), African American 4.34% (8/184), and then Hispanic 1% (2/184). There are 47 full professors with 83% Caucasian, 14.1% Asian, and 2.1% African American and 91.5% male and only 8.5% female. Past ALA presidents were 90% male and for the ABEA 75% male. H-index revealed a statistically significant difference between Caucasian and African American colleagues [P value (<.0005)].Conclusions: Minorities are disproportionately underrepresented in laryngology. Women are less likely to be in leadership roles in laryngology and become full professors. Laryngology lags behind other surgical specialties in the representation of minorities and women. Continued efforts should be made to increase diversity in the field of laryngology, especially in regard to underrepresented minorities.
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