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Genetically heterogeneous UM-HET3 mice born in 2020 were used to test possible lifespan effects of alpha-ketoglutarate (AKG), 2,4-dinitrophenol (DNP), hydralazine (HYD), nebivolol (NEBI), 16α-hydroxyestriol (OH_Est), and sodium thiosulfate (THIO), and to evaluate the effects of canagliflozin (Cana) when started at 16 months of age. OH_Est produced a 15% increase (p = 0.0001) in median lifespan in males but led to a significant (7%) decline in female lifespan. Cana, started at 16 months, also led to a significant increase (14%, p = 0.004) in males and a significant decline (6%, p = 0.03) in females. Cana given to mice at 6 months led, as in our previous study, to an increase in male lifespan without any change in female lifespan, suggesting that this agent may lead to female-specific late-life harm. We found that blood levels of Cana were approximately 20-fold higher in aged females than in young males, suggesting a possible mechanism for the sex-specific disparities in its effects. NEBI was also found to produce a female-specific decline (4%, p = 0.03) in lifespan. None of the other tested drugs provided a lifespan benefit in either sex. These data bring to 7 the list of ITP-tested drugs that induce at least a 10% lifespan increase in one or both sexes, add a fourth drug with demonstrated mid-life benefits on lifespan, and provide a testable hypothesis that might explain the sexual dimorphism in lifespan effects of the SGLT2 inhibitor Cana.

In genetically heterogeneous (UM-HET3) mice produced by the CByB6F1 × C3D2F1 cross, the Nrf2 activator astaxanthin (Asta) extended the median male lifespan by 12% (p = 0.003, log-rank test), while meclizine (Mec), an mTORC1 inhibitor, extended the male lifespan by 8% (p = 0.03). Asta was fed at 1840 ± 520 (9) ppm and Mec at 544 ± 48 (9) ppm, stated as mean ± SE (n) of independent diet preparations. Both were started at 12 months of age. The 90th percentile lifespan for both treatments was extended in absolute value by 6% in males, but neither was significant by the Wang-Allison test. Five other new agents were also tested as follows: fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate. None of these increased lifespan significantly at the dose and method of administration tested in either sex. Amounts of dimethyl fumarate in the diet averaged 35% of the target dose, which may explain the absence of lifespan effects. Body weight was not significantly affected in males by any of the test agents. Late life weights were lower in females fed Asta and Mec, but lifespan was not significantly affected in these females. The male-specific lifespan benefits from Asta and Mec may provide insights into sex-specific aspects of aging.

This article summarizes the emergency department approach to diagnosing cerebellar infarction in the patient presenting with vertigo. Vertigo is defined and identification of a vertigo syndrome is discussed. The differentiation of common vertigo syndromes such as benign paroxysmal positional vertigo, Meniere’s disease, migrainous vertigo, and vestibular neuritis is summarized. Confirmation of a peripheral vertigo syndrome substantially lowers the likelihood of cerebellar infarction, as do indicators of a peripheral disorder such as an abnormal head impulse test. Approximately 10% of patients with cerebellar infarction present with vertigo and no localizing neurologic deficits. The majority of these may have other signs of central vertigo, specifically direction-changing nystagmus and severe ataxia.[West J Emerg Med. 2009;10(4):273-277.]

The present work empirically examines the validity of Student Self-Assessment (SSA) as an educational assessment in higher education. We briefly review the principle methodological factors that could affect SSA validity, as well as the main findings identified in the literature. One empirical study is presented that compares student-self evaluations on a test with the evaluation made by the course instructor while controlling for students' experience with SSA, criteria, rubric, and scales used by the student and teacher, and that the teacher was blind. Results show a strong correlation overall between the SSA and the instructor's evaluation and show that lower-performing students tend to over-estimate their performance while higher-performing students under-estimate their performance. The results support that SSA is valid for the average student, but less so for those that deviate above and below average in the absence of measurements of potentially mediating variables. The need to consider metacognitive factors in SSA is proposed.