Impact of perioperative myocardial infarction on angiographic and clinical outcomes following coronary artery bypass grafting (from PRoject of Ex-vivo Vein graft ENgineering via Transfection [PREVENT] IV)

Myocardial infarction (MI) after coronary artery bypass grafting (CABG) is associated with significant morbidity and mortality. Frequency, management, mechanisms, and angiographic and clinical outcomes associated with perioperative MI remain poorly understood. PREVENT IV was a multicenter, randomized, placebo-controlled trial of edifoligide in 3,014 patients undergoing CABG. Angiographic and 2-year clinical follow-up were complete for 1,920 and 2,956 patients, respectively. Perioperative MI was defined as creatinine kinase-MB increase >or=10 times the upper limit of normal or >or=5 times the upper limit of normal with new 30-ms Q waves within 24 hours of surgery. Baseline characteristics, in-hospital management, and angiographic and clinical outcomes of patients with and without perioperative MI were compared. Perioperative MI occurred in 294 patients (9.8%). Patients with perioperative MI had longer surgery (250 vs 230 minutes; p <0.001), more on-pump surgery (83% vs 78%; p = 0.048), and worse target-artery quality (p <0.001). Patients with perioperative MI more frequently underwent angiography within 30 days of enrollment (1.7% vs 0.6%; p = 0.021). One-year angiographic vein graft failure occurred in 62.4% of patients with and 43.8% of patients without perioperative MI (p <0.001). Two-year composite clinical outcome (death, MI, or revascularization) was worse in patients with perioperative MI before (19.4% vs 15.2%; p = 0.039) and after (hazard ratio 1.33, 95% confidence interval 1.00 to 1.76, p = 0.046) adjusting for differences in significant predictors. In conclusion, perioperative MI was relatively common, was associated with worse outcomes, and mechanisms other than vein graft failure accounted for a substantial proportion of these MIs. Further research is needed into the prevention and treatment of perioperative MI in patients undergoing CABG.     

Dynamic changes in cellular and microenvironmental composition can be controlled to elicit in vitro human hematopoietic stem cell expansion

OBJECTIVE: The absence of effective strategies for the ex vivo expansion of human hematopoietic stem cells (HSCs) limits the development of many cell-based therapies. Prior attempts to stimulate HSC expansion have focused on media supplementation using cytokines and growth factors. In these cultures, cellular and microenvironmental compositions change with time. In this study, the impact of controlling these dynamic changes on HSC output is determined. MATERIALS AND METHODS: Cord blood-derived lin(-) cells were cultured for 8 days in serum-free medium supplemented with stem cell factor, Flt3 ligand, and thrombopoietin. Functional, phenotypic, and molecular (gene and protein) analyses were used to characterize dynamic changes in cellular and microenvironmental composition. The effects of these changes and the mechanism behind their effects on HSC expansion were assessed using a selection/media exchange-based global culture manipulation (GCM) technique. RESULTS: We show that the direct secretion of negative regulators by culture-generated lin(+) cells, and the indirect stimulation of cells to secrete negative regulators by culture-conditioned media, limits in vitro HSC generation. The GCM strategy was able to abrogate these effects to produce elevated numbers of LTC-ICs (14.6-fold relative to input), migrating rapid NOD/SCID repopulating cells (12.1-fold), and long-term NOD/SCID repopulating cells (5.2-fold). CONCLUSIONS: Cellular and microenvironmental changes that occur during all in vitro HSC cultures can significantly affect HSC output through the direct or indirect secretion of negative regulators. This study provides insight into the mechanisms regulating HSC fate in vitro and describes a novel methodology to regulate overall in vitro microenvironmental dynamics to enable the generation of clinically relevant numbers of HSCs.     

Arcuate nucleus lesions reduce opioid stress-induced analgesia (SIA) and enhance non-opioid SIA in rats

When rats were tested more than two weeks following surgery, lesions of the medial basal hypothalamus centered on the arcuate nucleus enhanced a form of foot-shock stress-induced analgesia (SIA) that was not blocked by injections of the opiate receptor blocker, naltrexone (6 mg/kg;). These arcuate nucleus lesions reduced the SIA produced by the same stressor when similar rats were tested 3-4 days following surgery. Finally, when similar rats were tested more than 2 weeks following surgery these lesions reduced a different form of SIA that was blocked by naltrexone. There were no effects of the lesions or naltrexone on baseline pain reactivity in any of the experiments. We suggest that arcuate nucleus lesions disrupt a system important for the elaboration of opiate-mediated SIA (Expt. 4), perhaps by damaging the brain's beta-endorphin system. In response to damage to this opioid analgesic system, we hypothesize that the damaged brain initiates time-dependent compensatory changes in an undamaged non-opioid analgesic system, resulting in enhanced non-opiate-mediated SIA.     

Effects of variety and repeated in-home consumption on product acceptance

The present study was designed to investigate the effect of variety on long-term product acceptance and consumption in a home-use situation. Subjects (N= 105) consumed a meat sauce once a week at dinner at home for a period of 10 weeks. Three variety groups were designed. The monotony group (N= 45) consistently received the same flavour of meat sauce across all 10 weeks; the imposed variation group (N= 30) received one from three different flavours of the meat sauce in random order, and the free choice (N= 30) in variation group was allowed to choose among three flavours of the meat sauce. Results showed a substantial increase in boredom and decline in acceptance ratings after repeated consumption. As hypothesized, this effect was the largest for the monotony group and was least pronounced in the free-choice group, with the imposed variation group in between. Consumption data were in line with these acceptance ratings; the monotony group consumed less of the food than the free-choice group over that time. In conclusion, repeated consumption of a food product only once a week at home resulted in a remarkable increase of boredom over time. The boredom effect was the largest for subjects who consistently received the same food, and was least pronounced for subjects who were allowed to choose among three different flavours of the food.     

Parametric analysis of thermal preference following sleep deprivation in the rat

A thermal preference task was used to assess the effects of sleep deprivation on nociceptive behavior using hot and cool stimuli. The thermal preference apparatus allowed male rats to move freely from a hot thermal plate (44.7 °C) to an adjacent plate at neutral (33.5 °C) or cold temperatures (1.3–11 °C). Investigators recorded occupancy on the colder side, frequency of movements between the 2 compartments, and first escape latency from the cold side. Parametric analysis of thermal preference indicated that behavioral allocation was related to temperature ranges previously associated with activation of thermal nociceptors. A 50% occupancy rate was determined from a stimulus–response function identifying 1.3 °C vs. 44.7 °C as optimal temperatures. This temperature combination was then used to test the effects of sleep deprivation for 48 h using the pedestal-over-water method on response allocation to the 2 temperature zones. Sleep deprivation decreased time spent on the cooled plate. Cumulative occupancy indicated differential effects for sleep deprivation with the rats preferring to remain on the hot side vs. the cold side, suggesting that sleep deprivation increased the nociceptive properties of the cold stimulus.     

Confirmatory Factor Analysis of the Perceived Stress Scale‐4 in a Community Sample

Although the Perceived Stress Scale (PSS) is among the most widely used measures of perceived stress, it has only recently begun to be tested in independent psychometric validation studies, and the four‐item version of the PSS (PSS‐4) (the briefest version of this measure) has never undergone testing to examine and confirm the originally proposed structure. To address this paucity of research, the present study (a) tested the structure of the PSS‐4 in the first confirmatory factor analysis of the instrument and (b) tested for item‐level gender differences in the PSS that have been demonstrated in other versions of this scale. Results indicated that the PSS four‐item measure does not fit its proposed model. Additionally, score differences were observed for one item across genders. Copyright © 2014 John Wiley & Sons, Ltd.