Stress can influence the secretion of neuroendocrine mediators, thereby exposing immune cells to altered signaling and interactions. Here we investigated the synergetic effect of stress and environmental enrichment on the immune response of Long-Evans rats. Subjects (n = 46) were assigned to 5 treatment groups: acute compared with chronic stress with or without environmental enrichment, plus an unmanipulated control group. Animals also were classified as active, passive, and flexible copers according to back-test assessment. Rats were exposed to enrichment in an open-field containing objects in different areas for 30 min 3 times each week, thus modeling the effects of a temporary increase in environmental stimuli. Animals assigned to chronic stress groups were exposed to predator sound stressors for 30 min daily, whereas animals assigned to acute stress groups were exposed once each week. After 7 wk, a dermal punch biopsy was administered to activate the immune response, after which rats were challenged through a forced swim test. Biologic samples were collected to measure corticosterone, dehydroepiandrosterone (DHEA), oxytocin, testosterone, and the cytokines IL6 and IL10. Rats exposed to chronic stress had lower DHEA:corticosterone ratios, suggesting increased allostatic load. Enrichment exposure modulated these effects, lowering overall corticosterone and testosterone levels and increasing DHEA and oxytocin levels in animals exposed to the predator sound. The immune response was decreased in rats exposed to chronic stress, but the effect of environmental enrichment helped to mitigate the negative influence on cells producing IL6. Combining acute stress and exposure to an enriched environment returned a healthier profile in terms of both immune activation and stress regulation. By using a multidimensional scaling model, we found that a combination of 'good' stress and exposure to brief sessions of enriching stimuli can reliably predict health in Long-Evans rats.
BackgroundNational Institutes of Health (NIH) funding is a key driver of orthopaedic research, but it has become increasingly difficult to obtain in recent years. An understanding of the types of grants that are commonly funded, how productive they are, and the factors associated with obtaining funding may help orthopaedic surgeons better understand how to earn grants.Questions/purposesIn this study, we sought to determine (1) the proportion of current academic orthopaedic surgeons who have obtained NIH grant funding, (2) the productivity of these grants by calculating grant productivity metrics, and (3) the factors (such as gender, subspecialty, and additional degrees) that are associated with obtaining grant funding.MethodsCurrent academic orthopaedic surgeons at the top 140 NIH-funded institutions were identified via faculty webpages; 3829 surgeons were identified. Demographic information including gender (men constituted 88% of the group [3364 of 3829]), academic rank (full professors constituted 22% [856 of 3829]), additional degrees (those with MD-PhD degrees constituted 3% [121 of 3829]), leadership positions, and orthopaedic subspecialty was collected. Funding histories from 1985 through 2021 were collected using the NIH Research Portfolio Online Reporting Tools Expenditures and Results. Grant type, funding, publications, and citations of each article were collected. A previously used grant impact metric (total citations per USD 0.1 million) was calculated to assess grant productivity. Multivariable binomial logistic regression was used to evaluate factors associated with obtaining funding.ResultsFour percent (150 of 3829) of academic orthopaedic surgeons obtained USD 338.3 million in funding across 301 grants, resulting in 2887 publications over the entire study period. The R01 was the most commonly awarded grant in terms of the total number awarded, at 36% (108 of 301), as well as by funding, publications, and citations, although other grant types including T32, F32, R03, R13, and R21 had higher mean grant impact metrics. There was no difference between men and women in the by-gender percentage of academic orthopaedic surgeons who obtained funding (4% [135 of 3229] versus 3% [15 of 450]; odds ratio 0.9 [95% confidence interval 0.5 to 1.7]; p = 0.80). A department having a single funded PhD researcher may be associated with surgeon-scientists obtaining grant funding, but with the numbers available, we could not demonstrate this was the case (OR 1.4 [95% CI 0.9 to 2.2]; p = 0.12).ConclusionFewer than one in 20 academic orthopaedic surgeons have received NIH funding. R01s are the most commonly awarded grant, although others demonstrate increased productivity metrics. Future studies should investigate the role of co–principal investigators on productivity and the role of different funding sources.Clinical RelevanceIndividuals should pursue both R01 and non-R01 grants, and departments should consider cultivating relationships with funded PhDs. The specific research infrastructure and departmental poli...
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