Objective: Communicating genetic research results to participants presents ethical challenges. Our objectives were to examine participants’ preferences in receiving future genetic research results and to compare preferences reported by veteran and nonveterans participants. Methods: Secondary analysis was performed on data collected in 2000–2004 from 1,575 consent forms signed by Mexican-American participants enrolled in 2 genetic family studies (GFS) in San Antonio: The Family Investigation of Nephropathy and Diabetes (FIND) and the Extended FIND (EFIND). The consent forms for these studies contained multiple-choice questions to examine participants’ preferences about receiving their (1) clinical lab results and (2) future genetic research results. The FIND and EFIND databases had information on subjects’ demographic characteristics and some selected clinical variables. We identified veterans using the Veterans Health Administration’s (VHA’s) centralized data repository. We compared veterans’ and nonveterans’ preferences using Student’s t test for continuous variables and χ2 test for discrete variables. A logistic regression analyzed subjects’ preference for receiving their research results, controlling for other socio-demographic and clinical variables. Results: The sample included 275 (18%) veterans and 1,247 (82%) nonveterans. Our results indicated a strong desire among the majority of participants 1,445 (95%) in getting their clinical lab research results. Likewise, 93% expressed interest in being informed about their future genetic results. There was no significant difference in veterans’ and nonveterans’ preference to disclosure of the research results (χ2 test; p > 0.05). Regression analysis showed no significant relationship (p = 0.449) between the outcome (receiving research results) and veterans’ responses after controlling for demographics and educational levels. Conclusion: Participants believed they would prefer receiving their genetic research results. Veterans are similar to nonveterans in their preferences. Offering genetic research results to participants should be based on well defined and structured plans to enhance interpretation of genetic data.
In the majority of studies using primary cultures of myoblasts, the cells are maintained at ambient oxygen tension (21% O2), despite the fact that physiological O2 at the tissue level in vivo is much lower (~1–5% O2). We hypothesized that the cellular response in presence of high oxygen concentration might be particularly important in studies comparing energetic function or oxidative stress in cells isolated from young versus old animals. To test this, we asked whether oxygen tension plays a role in mitochondrial bioenergetics (oxygen consumption, glycolysis and fatty acid oxidation) or oxidative damage to proteins (protein disulfides, carbonyls and aggregates) in myoblast precursor cells (MPCs) isolated from young (3–4 m) and old (29–30 m) C57BL/6 mice. MPCs were grown under physiological (3%) or ambient (21%) O2 for two weeks prior to exposure to an acute oxidative insult (H2O2). Our results show significantly higher basal mitochondrial respiration in young versus old MPCs, an increase in basal respiration in young MPCs maintained at 3% O2 compared to cells maintained at 21% O2, and a shift toward glycolytic metabolism in old MPCs grown at 21% O2. H2O2 treatment significantly reduced respiration in old MPCs grown at 3% O2 but did not further repress respiration at 21% O2 in old MPCs. Oxidative damage to protein was higher in cells maintained at 21% O2 and increased in response to H2O2 in old MPCs. These data underscore the importance of understanding the effect of ambient oxygen tension in cell culture studies, in particular studies measuring oxidative damage and mitochondrial function.
intestine, and bone marrow for each group (nZ4-5 each data point) at serial time points at day 0 (prior to irradiation), 1, 2, 3, 4, 5, 6, or 7 after TBI. We measured 33 proteins known to be associated with response of tissues to ionizing irradiation. Data was used to generate "heat maps" of all 33 proteins to compare each experimental group with radiation only control. Survival studies were carried out for each radiation mitigator combination to determine the best time point for sequential administration of the second radiation mitigator (nZ15 for each group). Results: Administration of JP4-039 at 24 hrs post-irradiation (I.V. 20 mg/ kg in 100 ml F14 emulsion) delayed the elevation of plasma IL-6 to Day 3 which correlated with the time of increased bone marrow IL-1a signature for the onset of necroptosis. Increased survival was observed after JP4-039 at 24 hrs and when Necrostatin-1 was delayed until 72 hrs post-irradiation. This increased survival correlated with an increase in levels of plasma proteins including G-CSF, IL-6, KC, and eotaxin, which are indicators of stimulated cell proliferation and chemotaxis. Plasma levels of proteins did not always match changes in the bone marrow or intestine. Conclusion: Sequential administration of JP4-039 at 24 hrs and Necrostatin-1 at 72 hrs post-irradiation increased survival, and correlated with increased levels of plasma inflammatory proteins. Elevations in levels of some plasma proteins may reflect irradiation effects on organs other than bone marrow or intestine.
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