Early postnatal nutrition is a vital determinant of adult health; this is particularly true for the infant born prematurely and cared for in a hospital setting such as the neonatal intensive care unit. Human and animal studies support the contribution of postnatal dietary composition and the rate of extrauterine growth to long-term metabolic outcomes. One mechanism by which postnatal nutrition affects long-term outcome is via developmental programming. Programming, or the modulation of gene expression to impart a short-term advantage accompanied by a long-term cost, may be achieved by epigenetic modifications to chromatin. This review summarizes the details of postnatal nutritional content and rate of growth on the development of metabolic disease. The role of epigenetics in developmental programming of the preterm infant is also discussed, with an emphasis on animal models of dietary manipulation and directions in which the field must move in order to formulate effective feeding strategies for the preterm infant.
Purpose Physician–scientists have long been considered an endangered species, and their extended training pathway is vulnerable to disruptions. This study investigated the effects of COVID-19-related challenges on the personal lives, career activities, stress levels, and research productivity of physician–scientist trainees and faculty. Method The authors surveyed medical students (MS), graduate students (GS), residents/fellows (R/F), and faculty (F) using a tool distributed to 120 U.S. institutions with MD–PhD programs in April–June 2020. Chi-square and Fisher’s exact tests were used to compare differences between groups. Machine learning was employed to select variables for multivariate logistic regression analyses aimed at identifying factors associated with stress and impaired productivity. Results The analyses included 1,929 respondents (MS: n = 679, 35%; GS: n = 676, 35%; R/F: n = 274, 14%; F: n = 300, 16%). All cohorts reported high levels of social isolation, stress from effects of the pandemic, and negative impacts on productivity. R/F and F respondents were more likely than MS and GS respondents to report financial difficulties due to COVID-19. R/F and F respondents with a dual degree expressed more impaired productivity compared with those without a dual degree. Multivariate regression analyses identified impacted research/scholarly activities, financial difficulties, and social isolation as predictors of stress and impaired productivity for both MS and GS cohorts. For both R/F and F cohorts, impacted personal life and research productivity were associated with stress, while dual-degree status, impacted research/scholarly activities, and impacted personal life were predictors of impaired productivity. More female than male respondents reported increased demands at home. Conclusions This national survey of physician–scientist trainees and faculty found a high incidence of stress and impaired productivity related to the COVID-19 pandemic. Understanding the challenges faced and their consequences may improve efforts to support the physician–scientist workforce in the postpandemic period.
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BRCA1 plays an important role in preventing breast cancer and is often silenced or repressed in sporadic cancer. The BRCA1 promoter is bidirectional: it drives transcription of the long non-coding (lnc) NBR2 transcript in the opposite orientation relative to the BRCA1 transcript. Hypoxic conditions repress BRCA1 transcription, but their effect on expression of the NBR2 transcript has not been reported. We used quantitative RT-PCR to measure BRCA1 and NBR2 transcript levels in 0% and 1% oxygen in MCF-7 breast cancer cells and found that NBR2 transcript levels increased as a function of time under hypoxic conditions, whereas BRCA1 mRNA levels were repressed. Hypoxic conditions were ineffective in reducing BRCA1 mRNA in the UACC-3199 breast cancer cell line, which is reported to have an epigenetically silenced BRCA1 promoter, even though appreciable levels of BRCA1 and NBR2 mRNA were detected. Significant recovery back to baseline RNA levels occurred within 48h after the MCF-7 cells were restored to normoxic conditions. We used a construct with the 218bp minimal BRCA1 promoter linked to marker genes to show that this minimal promoter repressed expression bidirectionally under hypoxic conditions, which suggests that the elements necessary for induction of NBR2 are located elsewhere.
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